Science.gov

Sample records for abacavir hypersensitivity reactions

  1. Clinical Abacavir Hypersensitivity Reaction among Children in India.

    PubMed

    Chakravarty, Jaya; Sharma, Saurabh; Johri, Anuradha; Chourasia, Ankita; Sundar, Shyam

    2016-08-01

    Abacavir is currently recommended as a part of first line regimen by National AIDS Control Organization. The objective of this study was to observe the incidence of clinically diagnosed abacavir Hypersensitivity reaction (HSR) among children on abacavir based therapy in the National program. In this observational study, all children started on abacavir were included and HSR reaction was diagnosed clinically as per National guidelines. HLA- B*5701 testing was done in children diagnosed with clinical abacavir HSR. Among 101 children started on abacavir during the study period, 8 [7.9 % (95 % CI 3.5-15.0 %)] children developed clinically diagnosed abacavir HSR. All children with concomitant illness (4/8) were HLA-B*5701 negative. Only 2 (25 %, 2/8) carried HLA-B*5701 allele. Fever with abdominal symptoms as compared to respiratory symptoms were more common in HLA-B*5701 positive cases. Overdiagnosis of clinically diagnosed abacavir HSR is common and could be decreased by treating concomitant illness before starting abacavir.

  2. A severe hypersensitivity reaction to abacavir following re-challenge.

    PubMed

    Todd, Sej; Emerson, C R

    2017-03-01

    We report this case to highlight the possibility of a severe hypersensitivity reaction as an important potential consequence of couples, living with HIV, sharing anti-retroviral treatment. An HIV-1 positive and carrier of HLA-B*57:01 allele, treatment experienced man was commenced one pill Regimen Stribild (tenofovir, emtricitabine, elvitegravir and cobicistat) in July 2015. On running short of medication, he admitted to sharing his partner's treatment (Triumeq; abacavir, lamivudine and dolutegravir). On the second occasion, re-introduction resulted in whole body rash 4 h post dose and was associated with fever, respiratory symptoms, headache and vomiting. On examination, he was pyrexic, tachyponeic, tachycardiac and hypotensive. Hypersensitivity to abacavir can cause significant morbidity. Re-challenge can result in a more rapid, severe and potentially life-threatening reaction. This potentially could become an increasing problem with more couples, living with HIV, sharing medication.

  3. Low incidence of abacavir hypersensitivity reaction among African children initiating antiretroviral therapy.

    PubMed

    Nahirya-Ntege, Patricia; Musiime, Victor; Naidoo, Bethany; Bakeera-Kitaka, Sabrina; Nathoo, Kusum; Munderi, Paula; Mugyenyi, Peter; Kekitiinwa, Adeodata; Bwakura-Dangarembizi, Mutsa F; Crawley, Jane

    2011-06-01

    Hypersensitivity reactions are reported in approximately 5% of adults receiving abacavir, but there are few published data in children. Among 1150 African children receiving antiretroviral therapy in a randomized trial, suspected hypersensitivity reactions to abacavir were rare (0.3%; 95% CI, 0.01-0.9). Patients were managed successfully through the provision of clear guidelines and education of clinical staff, children, and their caregivers.

  4. Use of patch testing for the diagnosis of abacavir-related hypersensitivity reaction in HIV patients.

    PubMed

    Giorgini, S; Martinelli, C; Tognetti, L; Carocci, A; Giuntini, R; Mastronardi, V; Torricelli, F; Leoncini, F; Lotti, T

    2011-01-01

    The use of antiretroviral drug abacavir (ABC) has been often associated with cutaneous hypersensitivity reactions, the majority being severe. The present study discusses the issues of patch testing associated with pharmacogenetic screening in light of the development of abacavir hypersensitivity reactions (HSRs). The present authors classified 100 patients into three groups: 20 patients (group A) had experienced a hypersensitivity reaction when treated with highly active antiretroviral therapy (HAART) including ABC; 60 HIV-positive patients (group B) were receiving HAART scheme including ABC; 20 HIV-negative patients acted as control group (group C). Patients of group A and B were patch tested with ABC as such, then with an ABC extract diluted to 1 and 10% in petrolatum. Group C patients underwent patches with petrolatum only. A biopsy of the lesion was performed in those patients who showed a positive skin reaction. All patients had been tested for HLA-B5701. A correlation between positive ABC-patch testing and HLA-B5701 was found in 50% of patients enrolled in group A, while in group B and C, all patients tested negative for both genetic marker and ABC-patch testing. Histopathology findings confirmed a vigorous CD4+ and CD8+ cellular response that is compatible with HSR. Patch testing is a safe and sensitive method that can be used for to confirm or exclude any correlation between abacavir and hypersensitivity skin reactions in patients who have been previously treated with abacavir during HAART. Correlation between patch test, immunohistochimical, and genetic tests results shows that genetic testing increases the possibility to identify patients with a true reaction. © 2012 Wiley Periodicals, Inc.

  5. Detection of abacavir hypersensitivity by ELISpot method.

    PubMed

    Esser, Stefan; Jablonka, Robert; Heinemann, Falko M; Reuter, Stefan; Jaeger, Hans; von Krosigk, Ariane; Schenk-Westkamp, Pia; Schadendorf, Dirk; Horn, Peter A; Lindemann, Monika

    2012-06-01

    The antiretroviral agent abacavir can cause hypersensitivity reaction (HSR) and the presence of HLA-B*57:01 is predictive of abacavir-HSR in Caucasian HIV-infected patients. However, abacavir-HSR also occurs in HLA-B*57:01 negative patients. In these patients, a safe diagnostic tool to dissect clinically suspected HSR against abacavir from adverse reactions against co-administered drugs is mandatory, and abacavir-ELISpot was evaluated. Peripheral blood mononuclear cells from 87 HIV patients were stimulated by abacavir and the production of interferon-γ to the ELISpot was determined. Abacavir treated patients with HSR [confirmed (n=5) or suspected (n=12)] vs without HSR (n=42) displayed significantly higher numbers of abacavir-specific cells (82.3±23.0 or 10.5±4.5 vs -0.5±1.0 spot forming cells per million PBMC, p < .005 each). In conclusion, we established the first abacavir-specific ELISpot. According to our preliminary data, a negative abacavir-ELISpot nearly excludes HSR against abacavir. Thereby the ELISpot may facilitate the decision to continue or withdraw abacavir treatment.

  6. Hypersensitivity Reaction Associated with Abacavir Therapy in an Indian HIV Patient - A Case Report.

    PubMed

    Janardhanan, Manju; Amberkar V, Mohan Babu; Vidyasagar, Sudha; Kumari K, Meena; Holla, Sadhana N

    2014-09-01

    The most important and unique adverse effect of abacavir (ABC) is fatal hypersensitivity reaction (HSR). The objective of this report is to describe a case of ABC induced HSR that occurred in an Indian HIV patient during treatment. Although this adverse effect is not uncommon, it is perhaps underreported or has never been reported so far in an Indian case scenario. A 44-year-old known case of HIV-1 was admitted in view of his worsening condition and very low CD4 cell counts 3 cells/μL. He was on anti-retroviral therapy since three years but not regular. On the basis of treatment failure, non-compliance and progressive low CD4 counts, the anti HIV regime was switched over to abacavir 600 mg+ atazanavir/ ritonavir 300mg/100mg Two weeks after ABC therapy he presented with maculopapular rash, headache and signs of hepatic damage (serum AST, ALP and ALT increased to 3-4 fold) suggestive of hypersensitivity reaction. As we know discontinuation of the drug is the ultimate litmus test to confirm diagnosis of drug induced adverse reaction. We did confirm ABC induced HSR by de-challenge wherein, rash disappeared within 2-3 days and LFT came back to normal within 5 days. However, no rechallenge was done. HSR was more in favour of ABC because atazanavir failed to produce any similar reaction after re-challenge.

  7. Studies on abacavir-induced hypersensitivity reaction: a successful example of translation of pharmacogenetics to personalized medicine.

    PubMed

    Guo, Yongli; Shi, Leming; Hong, Huixiao; Su, Zhenqiang; Fuscoe, James; Ning, Baitang

    2013-02-01

    Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus (HIV) infected patients. Its main side effect is hypersensitivity reaction (HSR). The incidence of the HSR is associated with ethnicity among patients exposed to abacavir, and retrospective and prospective studies show a significantly increased risk of abacavir-induced HSR in human leukocyte antigen (HLA)-B*57:01-carrying patients. Immunological studies indicated that abacavir interacts specifically with HLA-B*57:01 and changed the binding specificity between the HLA molecule and the HLA-presented endogenous peptide repertoire, leading to a systemic autoimmune reaction. HLA-B*57:01 screening, combined with patch testing, had clinically predictive value and cost-effective impact in reducing the incidence of abacavir-induced HSR regardless of the HLA-B*57:01 prevalence in the population. Therefore, the US Food and Drug Administration (FDA) and international HIV treatment guidelines recommend a routine HLA-B*57:01 screening prior to abacavir treatment to decrease false positive diagnosis and prevent abacavir-induced HSR. The studies of abacavir-induced HSR and the implementation of the HLA-B*57:01 screening in the clinic represent a successful example of the use of pharmacogenetics for personalized diagnosis and therapy.

  8. HLA- B*5701 Allele in HIV-infected Indian Children and its Association with Abacavir Hypersensitivity.

    PubMed

    Manglani, Mamta V; Gabhale, Yashwant R; Lala, Mamatha M; Sekhar, Rohini; More, Dipti

    2018-02-15

    To determine the prevalence of HLA-B*5701 allele in HIV-infected children, and to find its association with Abacavir hypersensitivity. Children (2 to 18 y) already on, or to be initiated on Abacavir were included for PCR sequencing to detect HLA-B*5701. proportion with HLA B*5701 allele and hypersensitivity with Abacavir. Abacavir was stopped if patient tested positive for HLA-B*5701 allele. 100 children (median age 11 y) were enrolled; 10 were already on Abacavir. HLA-B*5701 positivity was observed in 11 (11%) children. Two of these 11 children developed hypersensitivity after initiation of Abacavir. Abacavir was thereafter stopped in all who tested HLA-B*5701 positive, irrespective of the development of hypersensitivity reaction. HLA-B*5701 allele was present in 11 (11%) of HIV-infected children, of which two developed Abacavir hypersensitivity. None of the patients without the allele developed hypersensitivity.

  9. Reducing hypersensitivity reactions with HLA-B*5701 genotyping before abacavir prescription: clinically useful but is it cost-effective in Singapore?

    PubMed

    Kapoor, Ritika; Martinez-Vega, Rosario; Dong, Di; Tan, Sharlene Yanying; Leo, Yee-Sin; Lee, Cheng-Chuan; Sung, Cynthia; Ng, Oon-Tek; Archuleta, Sophia; Teo, Yik-Ying

    2015-02-01

    Abacavir (ABC) is one of the more affordable antiretroviral drugs used for controlling HIV. Although with similar efficacy to current first-line drugs, its limited usage in Singapore can be attributed to its possible side effect of adverse hypersensitivity reactions (HSRs). HLA-B*5701 genotyping is a clinically relevant procedure for avoiding abacavir-induced HSRs. As patients who do not carry the risk allele are unlikely to develop HSRs, a simple rule can be developed to allow abacavir prescription for patients who are B*5701 negative. Here, we carry out a cost-effectiveness analysis of HLA-B*5701 genotyping before abacavir prescription in the context of the Singapore healthcare system, which caters predominantly to Han Chinese, Southeast-asian Malays, and South-asian Indians. In addition, we aim to identify the most cost-effective treatment regimen for HIV patients. A decision tree model was developed in TreeAge. The model considers medical treatment and genotyping costs, genotyping test characteristics, the prevalence of the risk allele, reduction in the quality of life, and increased expenditure due to side effects and other factors, evaluating independently over early-stage and late-stage HIV patients segmented by drug contraindications. The study indicates that genotyping is not cost-effective for any ethnicity irrespective of the disease stage, except for Indian patients with early-stage HIV who are contraindicated to tenofovir. Abacavir (as first-line) without genotyping is the cheapest and most cost-effective treatment for all ethnicities except for early-stage Indian HIV patients contraindicated to tenofovir. The HLA-B*5701 frequency, the mortality rate from abacavir-induced HSRs, and genotyping costs are among the major factors influencing the cost-effectiveness.

  10. Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity.

    PubMed

    Hughes, Dyfrig A; Vilar, F Javier; Ward, Charlotte C; Alfirevic, Ana; Park, B Kevin; Pirmohamed, Munir

    2004-06-01

    Abacavir, a human immunodeficiency virus-1 (HIV-1) nucleoside-analogue reverse transcriptase inhibitor, causes severe hypersensitivity in 4-8% of patients. HLA B*5701 is a known genetic risk factor for abacavir hypersensitivity in Caucasians. Our aim was to confirm the presence of this genetic factor in our patients, and to determine whether genotyping for HLA B*5701 would be a cost-effective use of healthcare resources. Patients with and without abacavir hypersensitivity were identified from a UK HIV clinic. Patients were genotyped for HLA B*5701, and pooled data used for calculation of test characteristics. The cost-effectiveness analysis incorporated the cost of testing, cost of treating abacavir hypersensitivity, and the cost and selection of alternative antiretroviral regimens. A probabilistic decision analytic model (comparing testing versus no testing) was formulated and Monte Carlo simulations performed. Of the abacavir hypersensitive patients, six (46%) were HLA B*5701 positive, compared to five (10%) of the non-hypersensitive patients (odds ratio 7.9 [95% confidence intervals 1.5-41.4], P = 0.006). Pooling of our data on HLA B*5701 with published data resulted in a pooled odds ratio of 29 (95% CI 6.4-132.3; P < 0.0001). The cost-effectiveness model demonstrated that depending on the choice of comparator, routine testing for HLA B*5701 ranged from being a dominant strategy (less expensive and more beneficial than not testing) to an incremental cost-effectiveness ratio (versus no testing) of Euro 22,811 per hypersensitivity reaction avoided. Abacavir hypersensitivity is associated with HLA B*5701, and pre-prescription pharmacogenetic testing for this appears to be a cost-effective use of healthcare resources.

  11. The frequency of HLA-B(∗)57:01 and the risk of abacavir hypersensitivity reactions in the majority population of Costa Rica.

    PubMed

    Arrieta-Bolaños, Esteban; Madrigal, J Alejandro; Marsh, Steven G E; Shaw, Bronwen E; Salazar-Sánchez, Lizbeth

    2014-11-01

    HLA-B(∗)57:01 is a well-known and cost-effective pharmacogenetic marker for abacavir hypersensitivity. As with other HLA alleles, there is widespread variation in its frequency across populations. The Costa Rica Central Valley Population (CCVP) is the major population in this country. The frequency of HLA-B(∗)57:01 in this population has not been described yet. Thus, our aim was to determine the frequency of this allele in the CCVP. 200 unrelated healthy volunteer donors born in the CCVP were typed. HLA-B(∗)57-positive samples identified by HLA intermediate resolution typing methods were further typed by SBT to high resolution. An HLA-B(∗)57:01 carrier frequency of 5.00% was determined in this sample. This frequency is relatively high in comparison to reports from other populations in Latin America. These results suggest that there is a considerable frequency of HLA-B(∗)57:01 in the CCVP and that pharmacogenetic testing for HIV+ patients who are going to receive abacavir-based treatment should be considered in this country. Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  12. HLA-B*57:01 allele prevalence in HIV-infected North American subjects and the impact of allele testing on the incidence of abacavir-associated hypersensitivity reaction in HLA-B*57:01-negative subjects.

    PubMed

    Small, Catherine Butkus; Margolis, David A; Shaefer, Mark S; Ross, Lisa L

    2017-04-11

    The presence of the HLA-B*57:01 allele in HIV-infected subjects is associated with a higher risk of abacavir-associated hypersensitivity reaction (ABC HSR). HLA-B*57:01 allele prevalence varies in different populations, but HLA-B*57:01 testing with immunological confirmation has had a negative predictive value for ABC HSR between 97 and 100%. In the ASSURE study (EPZ113734), the HLA-B*57:01 prevalence in virologically suppressed, antiretroviral treatment-experienced, HIV-infected subjects from the United States, including Puerto Rico, was assessed. Three hundred eighty-five subjects were screened; 13 were HLA-B*57:01 positive and 372 were negative. Only HLA-B*57:01-negative, abacavir-naive subjects were eligible to enroll into the ASSURE trial. Eleven of the 13 subjects who possessed the HLA-B*57:01 allele were white, the other 2 were African-American. There was no geographic clustering of HLA-B*57:01-positive subjects, and the incidence correlated roughly with those states with the greatest numbers of subjects screened. Similarly, there was no statistically significant correlation between subjects who possessed or lacked the allele and age, gender, ethnicity or CD4+ T-cell numbers. The incidence of ABC HSR following abacavir initiation was also evaluated. Only 1 of 199 HLA-B*57:01-negative subjects (an African-American male) randomized to receive abacavir-containing treatment developed symptoms consistent with suspected ABC HSR; ABC HSR was not immunologically confirmed. These findings confirm the utility of HLA-B*57:01 allele testing to reduce the frequency of ABC HSR. The prevalence of HLA-B*57:01 positivity was higher in white than in African-American subjects. In HLA-B*57:01-negative subjects, suspected ABC HSR is very rare, but should lead to discontinuation of abacavir when ABC HSR cannot be definitively excluded from the differential diagnosis. The ASSURE (EPZ113734) study was registered on ClinicalTrials.gov registration on April 8th 2010 and the

  13. Hypersensitivity reactions to HIV therapy

    PubMed Central

    Chaponda, Mas; Pirmohamed, Munir

    2011-01-01

    Many drugs used for the treatment of HIV disease (including the associated opportunistic infections) can cause drug hypersensitivity reactions, which vary in severity, clinical manifestations and frequency. These reactions are not only seen with the older compounds, but also with the newer more recently introduced drugs. The pathogenesis is unclear in most cases, but there is increasing evidence to support that many of these are mediated through a combination of immunologic and genetic factors through the major histocompatibility complex (MHC). Genetic predisposition to the occurrence of these allergic reactions has been shown for some of the drugs, notably abacavir hypersensitivity which is strongly associated with the class I MHC allele, HLA-B*5701. Testing before the prescription of abacavir has been shown to be of clinical utility, has resulted in a change in the drug label, is now recommended in clinical guidelines and is practiced in most Western countries. For most other drugs, however, there are no good methods of prevention, and clinical monitoring with appropriate (usually supportive and symptomatic) treatment is required. There is a need to undertake further research in this area to increase our understanding of the mechanisms, which may lead to better preventive strategies through the development of predictive genetic biomarkers or through guiding the design of drugs less likely to cause these types of adverse drug reactions. PMID:21480946

  14. Abacavir

    MedlinePlus

    ... HIV in the blood. Although abacavir does not cure HIV, it may decrease your chance of developing acquired ... prescribed by your doctor.Abacavir helps to control HIV infection but does not cure it. Continue to take abacavir even if you ...

  15. Hypersensitivity reactions to etoposide.

    PubMed

    Hoetelmans, R M; Schornagel, J H; ten Bokkel Huinink, W W; Beijnen, J H

    1996-04-01

    To report a hypersensitivity reaction to etoposide occurring in a patient after 2 months of drug therapy. A 20-year-old man with a diagnosis of testicular carcinoma was treated with bleomycin, etoposide, and cisplatin (BEP regimen). After dose 20 of etoposide, an exanthema was noted, which was attributed to etoposide. The patient had received 19 doses of etoposide during the previous 2 months without any sign of an allergic reaction. Rechallenging the patient with etoposide from another batch resulted in recurrence of the exanthema. Both etoposide and its excipient (polysorbate 80) are suspected of causing hypersensitivity reactions. Although the exact mechanism of the hypersensitivity reaction is not known, it is believed to be of nonimmunogenic origin. With a lower rate of infusion of etoposide and/or by premedication with antihistamines and/or corticosteroids, hypersensitivity reactions to etoposide might be prevented in patients with a history of hypersensitivity to this drug.

  16. Abacavir induces loading of novel self-peptides into HLA-B*57:01: an autoimmune model for HLA-associated drug hypersensitivity

    PubMed Central

    Norcross, Michael A.; Luo, Shen; Lu, Li; Boyne, Michael T.; Gomarteli, Mary; Rennels, Aaron D.; Woodcock, Janet; Margulies, David H.; McMurtrey, Curtis; Vernon, Stephen; Hildebrand, William H.; Buchli, Rico

    2014-01-01

    Background Abacavir drug hypersensitivity in HIV-treated patients is associated with HLA-B*57:01 expression. To understand the immunochemistry of abacavir drug reactions, we investigated the effects of abacavir on HLA-B*57:01 epitope-binding in vitro and the quality and quantity of self-peptides presented by HLA-B*57:01 from abacavir-treated cells. Design and methods An HLA-B*57:01-specific epitope-binding assay was developed to test for effects of abacavir, didanosine or flucloxacillin on self-peptide binding. To examine whether abacavir alters the peptide repertoire in HLA-B*57:01, a B-cell line secreting soluble human leucocyte antigen (sHLA) was cultured in the presence or absence of abacavir, peptides were eluted from purified human leucocyte antigen (HLA), and the peptide epitopes comparatively mapped by mass spectroscopy to identify drug-unique peptides. Results Abacavir, but not didansosine or flucloxacillin, enhanced binding of the FITC-labeled self-peptide LF9 to HLA-B*57:01 in a dose-dependent manner. Endogenous peptides isolated from abacavir-treated HLA-B*57:01 B cells showed amino acid sequence differences compared with peptides from untreated cells. Novel drug-induced peptides lacked typical carboxyl (C) terminal amino acids characteristic of the HLA-B*57:01 peptide motif and instead contained predominantly isoleucine or leucine residues. Drug-induced peptides bind to soluble HLA-B*57:01 with high affinity that was not altered by abacavir addition. Conclusion Our results support a model of drug-induced autoimmunity in which abacavir alters the quantity and quality of self-peptide loading into HLA-B*57:01. Drug-induced loading of novel self-peptides into HLA, possibly by abacavir either altering the binding cleft or modifying the peptide-loading complex, generates an array of neo-antigen peptides that drive polyclonal T-cell autoimmune responses and multiorgan systemic toxicity. PMID:22617051

  17. Abacavir induces loading of novel self-peptides into HLA-B*57: 01: an autoimmune model for HLA-associated drug hypersensitivity.

    PubMed

    Norcross, Michael A; Luo, Shen; Lu, Li; Boyne, Michael T; Gomarteli, Mary; Rennels, Aaron D; Woodcock, Janet; Margulies, David H; McMurtrey, Curtis; Vernon, Stephen; Hildebrand, William H; Buchli, Rico

    2012-07-17

    Abacavir drug hypersensitivity in HIV-treated patients is associated with HLA-B57:01 expression. To understand the immunochemistry of abacavir drug reactions, we investigated the effects of abacavir on HLA-B57:01 epitope-binding in vitro and the quality and quantity of self-peptides presented by HLA-B57:01 from abacavir-treated cells. An HLA-B57:01-specific epitope-binding assay was developed to test for effects of abacavir, didanosine or flucloxacillin on self-peptide binding. To examine whether abacavir alters the peptide repertoire in HLA-B57:01, a B-cell line secreting soluble human leucocyte antigen (sHLA) was cultured in the presence or absence of abacavir, peptides were eluted from purified human leucocyte antigen (HLA), and the peptide epitopes comparatively mapped by mass spectroscopy to identify drug-unique peptides. Abacavir, but not didansosine or flucloxacillin, enhanced binding of the FITC-labeled self-peptide LF9 to HLA-B57:01 in a dose-dependent manner. Endogenous peptides isolated from abacavir-treated HLA-B57:01 B cells showed amino acid sequence differences compared with peptides from untreated cells. Novel drug-induced peptides lacked typical carboxyl (C) terminal amino acids characteristic of the HLA-B57:01 peptide motif and instead contained predominantly isoleucine or leucine residues. Drug-induced peptides bind to soluble HLA-B57:01 with high affinity that was not altered by abacavir addition. Our results support a model of drug-induced autoimmunity in which abacavir alters the quantity and quality of self-peptide loading into HLA-B57:01. Drug-induced loading of novel self-peptides into HLA, possibly by abacavir either altering the binding cleft or modifying the peptide-loading complex, generates an array of neo-antigen peptides that drive polyclonal T-cell autoimmune responses and multiorgan systemic toxicity.

  18. Oral Hypersensitivity Reactions

    MedlinePlus

    ... of substances. The most common causes are food, food additives, drugs, oral hygiene products, and dental materials. Q: Are there any specific foods that are more commonly implicated in intraoral hypersensitivity ...

  19. Leucovorin-induced hypersensitivity reaction.

    PubMed

    Damaske, Avni; Ma, Nichole; Williams, Reba

    2012-03-01

    Leucovorin is a reduced form of folic acid, which has multiple uses.(1) In this case report, it is used in combination with fluorouracil in the treatment of colon cancer. We describe a 53-year-old male, who was started on FOLFOX 6 + bevacizumab who experienced a hypersensitivity reaction to leucovorin. There have been very few cases of leucovorin hypersensitivity reactions reported in the literature. In this case, symptoms include flushing, hives, body pain, headaches, elevated blood pressures, and general discomfort. Although leucovorin reactions are considered rare, one should be aware of the types of reactions that can occur with leucovorin.

  20. Diagnostic accuracy of HLA-B*57:01 screening for the prediction of abacavir hypersensitivity and clinical utility of the test: a meta-analytic review.

    PubMed

    Cargnin, Sarah; Jommi, Claudio; Canonico, Pier Luigi; Genazzani, Armando A; Terrazzino, Salvatore

    2014-05-01

    To determine diagnostic accuracy of HLA-B*57:01 testing for prediction of abacavir-induced hypersensitivity and to quantify the clinical benefit of pretreatment screening through a meta-analytic review of published studies. A comprehensive search was performed up to June 2013. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. The pooled diagnostic estimates were calculated using a random effect model. Despite the presence of heterogeneity in sensitivity or specificity estimates, the pooled diagnostic odds ratio to detect abacavir-induced hypersensitivity on the basis of clinical criteria was 33.07 (95% CI: 22.33-48.97, I(2): 13.9%), while diagnostic odds ratio for detection of immunologically confirmed abacavir hypersensitivity was 1141 (95% CI: 409-3181, I(2): 0%). Pooled analysis of risk ratio showed that prospective HLA-B*57:01 testing significantly reduced the incidence of abacavir-induced hypersensitivity. This meta-analysis demonstrates an excellent diagnostic accuracy of HLA-B*57:01 testing to detect immunologically confirmed abacavir hypersensitivity and corroborates existing recommendations.

  1. Comparison of methods for in-house screening of HLA-B*57:01 to prevent abacavir hypersensitivity in HIV-1 care.

    PubMed

    De Spiegelaere, Ward; Philippé, Jan; Vervisch, Karen; Verhofstede, Chris; Malatinkova, Eva; Kiselinova, Maja; Trypsteen, Wim; Bonczkowski, Pawel; Vogelaers, Dirk; Callens, Steven; Ruelle, Jean; Kabeya, Kabamba; De Wit, Stephane; Van Acker, Petra; Van Sandt, Vicky; Emonds, Marie-Paule; Coucke, Paul; Sermijn, Erica; Vandekerckhove, Linos

    2015-01-01

    Abacavir is a nucleoside reverse transcriptase inhibitor used as part of combination antiretroviral therapy in HIV-1-infected patients. Because this drug can cause a hypersensitivity reaction that is correlated with the presence of the HLA-B*57:01 allotype, screening for the presence of HLA-B*57:01 is recommended before abacavir initiation. Different genetic assays have been developed for HLA-B*57:01 screening, each with specific sensitivity, turnaround time and assay costs. Here, a new real-time PCR (qPCR) based analysis is described and compared to sequence specific primer PCR with capillary electrophoresis (SSP PCR CE) on 149 patient-derived samples, using sequence specific oligonucleotide hybridization combined with high resolution SSP PCR as gold standard. In addition to these PCR based methods, a complementary approach was developed using flow cytometry with an HLA-B17 specific monoclonal antibody as a pre-screening assay to diminish the number of samples for genetic testing. All three assays had a maximum sensitivity of >99. However, differences in specificity were recorded, i.e. 84.3%, 97.2% and >99% for flow cytometry, qPCR and SSP PCR CE respectively. Our data indicate that the most specific and sensitive of the compared methods is the SSP PCR CE. Flow cytometry pre-screening can substantially decrease the number of genetic tests for HLA-B*57:01 typing in a clinical setting.

  2. Hypersensitivity reaction with deferasirox

    PubMed Central

    Sharma, Atul; Arora, Ekta; Singh, Harmanjit

    2015-01-01

    Thalassemias comprise a group of hereditary blood disorders. Thalassemia major presents with anemia within the first 2 years of life requiring frequent blood transfusions for sustaining life. Regular blood transfusions lead to iron overload-related complications. Prognosis of thalassemia has improved because of the availability of iron-chelating agents. Oral iron chelators are the mainstay of chelation therapy. Deferasirox is a new-generation oral iron chelator for once daily usage. We herein describe a patient of beta thalassemia major who developed an allergic manifestation in the form of erythematous pruritic skin rashes to the oral iron chelator deferasirox. This is a rare adverse reaction reported with deferasirox that led to a therapeutic dilemma in this particular case. PMID:25969661

  3. Monitoring abacavir bioactivation in humans: screening for an aldehyde metabolite.

    PubMed

    Grilo, Nádia M; Antunes, Alexandra M M; Caixas, Umbelina; Marinho, Aline T; Charneira, Catarina; Conceição Oliveira, M; Monteiro, Emília C; Matilde Marques, M; Pereira, Sofia A

    2013-05-10

    The anti-HIV drug abacavir is associated with idiosyncratic hypersensitivity reactions and cardiotoxicity. Although the mechanism underlying abacavir-toxicity is not fully understood, drug bioactivation to reactive metabolites may be involved. This work was aimed at identifying abacavir-protein adducts in the hemoglobin of HIV patients as biomarkers of abacavir bioactivation and protein modification. The protocol received prior approval from the Hospital Ethics Committee, patients gave their written informed consent and adherence was controlled through a questionnaire. Abacavir-derived Edman adducts with the N-terminal valine of hemoglobin were analyzed by an established liquid chromatography-electrospray ionization-tandem mass spectrometry method. Abacavir-valine adducts were detected in three out of ten patients. This work represents the first evidence of abacavir-protein adduct formation in humans. The data confirm the ability of abacavir to modify self-proteins and suggest that the molecular mechanism(s) of some abacavir-induced adverse reactions may require bioactivation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Hypersensitivity reactions in patients receiving hemodialysis.

    PubMed

    Butani, Lavjay; Calogiuri, Gianfranco

    2017-06-01

    To describe hypersensitivity reactions in patients receiving maintenance hemodialysis. PubMed search of articles published during the past 30 years with an emphasis on publications in the past decade. Case reports and review articles describing hypersensitivity reactions in the context of hemodialysis. Pharmacologic agents are the most common identifiable cause of hypersensitivity reactions in patients receiving hemodialysis. These include iron, erythropoietin, and heparin, which can cause anaphylactic or pseudoallergic reactions, and topical antibiotics and anesthetics, which lead to delayed-type hypersensitivity reactions. Many hypersensitivity reactions are triggered by complement activation and increased bradykinin resulting from contact system activation, especially in the context of angiotensin-converting enzyme inhibitor use. Several alternative pharmacologic preparations and dialyzer membranes are available, such that once an etiology for the reaction is established, recurrences can be prevented without affecting the quality of care provided to patients. Although hypersensitivity reactions are uncommon in patients receiving hemodialysis, they can be life-threatening. Moreover, considering the large prevalence of the end-stage renal disease population, the implications of such reactions are enormous. Most reactions are pseudoallergic and not mediated by immunoglobulin E. The multiplicity of potential exposures and the complexity of the environment to which patients on dialysis are exposed make it challenging to identify the precise cause of these reactions. Great diligence is needed to investigate hypersensitivity reactions to avoid recurrence in this high-risk population. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Abacavir Pharmacogenetics – From Initial Reports to Standard of Care

    PubMed Central

    Martin, Michael A.; Kroetz, Deanna L.

    2013-01-01

    Abacavir is a nucleoside analogue reverse transcriptase inhibitor (NRTI) indicated for the treatment of human immunodeficiency virus (HIV) infection as part of a multidrug, highly active antiretroviral therapy (HAART) regimen. Despite its efficacy in treating HIV, approximately 5% of individuals that receive abacavir develop an immune-mediated hypersensitivity reaction (HSR) that warrants immediate discontinuation of abacavir and switching to an alternative antiretroviral regimen. Abacavir HSR is associated with individuals that carry the *57:01 variant in the human leukocyte antigen B (HLA-B) gene. There is a large volume of evidence to show that those who carry HLA-B*57:01 are at significantly increased risk of developing HSR and should not receive abacavir. Using pharmacogenetic screening to ensure individuals who carry y HLA-B*57:01 do not receive abacavir can reduce the incidence of abacavir HSR and is now considered the standard of care before prescribing abacavir. Genetic testing for abacavir HSR is currently one of the best examples of integrating pharmacogenetic testing into clinical practice. PMID:23649914

  6. Alopecia areata associated with abacavir therapy.

    PubMed

    Kim, Hee-Sung; Shin, Hyoung-Shik

    2014-06-01

    Abacavir is a nucleoside reverse-transcriptase inhibitor that has been approved for use in combination with other retroviral agents in the treatment of HIV infection. Common adverse reactions include headache, fatigue, nausea, and rash. A fatal hypersensitivity reaction may occur in 5% of patients receiving abacavir; therefore, screening for HLA-B5701 should be performed before starting abacavir. Alopecia areata (AA) is infrequently reported in HIV-infected patients. Certain underlying conditions have been associated with AA, including a decreased CD4:CD8 ratio related to the progression of HIV infection, some opportunistic infections, and syphilis. Several antiretroviral drugs, such as zidovudine, indinavir, indinavir/ritonavir, lopinavir/ritonavir, and atazanavir/ritonavir have been implicated in the development of AA. At present, the occurrence of AA has not been associated with abacavir use. We cannot exclude that the use of abacavir and the development of AA could be coincidental. Nevertheless, patients given abacavir should be monitored for hair loss and the drug discontinued promptly if such signs appear.

  7. Abacavir pharmacogenetics--from initial reports to standard of care.

    PubMed

    Martin, Michael A; Kroetz, Deanna L

    2013-07-01

    Abacavir is a nucleoside analogue reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus infection as part of a multidrug, highly active antiretroviral therapy regimen. Despite its efficacy, approximately 5% of individuals who receive abacavir develop an immune-mediated hypersensitivity reaction (HSR) that warrants immediate discontinuation of abacavir and switching to an alternative antiretroviral regimen. Abacavir HSR is associated with individuals who carry the *57:01 variant in the human leukocyte antigen B (HLA-B) gene. There is a large volume of evidence to show that those who carry HLA-B*57:01 are at significantly increased risk of developing HSR and should not receive abacavir. Pharmacogenetic screening to ensure individuals who carry HLA-B*57:01 do not receive abacavir can reduce the incidence of HSR and is now considered the standard of care before prescribing abacavir. Genetic testing to prevent abacavir HSR is currently one of the best examples of integrating pharmacogenetic testing into clinical practice. © 2013 Pharmacotherapy Publications, Inc.

  8. Drug metabolism and hypersensitivity reactions to drugs.

    PubMed

    Agúndez, José A G; Mayorga, Cristobalina; García-Martin, Elena

    2015-08-01

    The aim of the present review was to discuss recent advances supporting a role of drug metabolism, and particularly of the generation of reactive metabolites, in hypersensitivity reactions to drugs. The development of novel mass-spectrometry procedures has allowed the identification of reactive metabolites from drugs known to be involved in hypersensitivity reactions, including amoxicillin and nonsteroidal antiinflammatory drugs such as aspirin, diclofenac or metamizole. Recent studies demonstrated that reactive metabolites may efficiently bind plasma proteins, thus suggesting that drug metabolites, rather than - or in addition to - parent drugs, may elicit an immune response. As drug metabolic profiles are often determined by variability in the genes coding for drug-metabolizing enzymes, it is conceivable that an altered drug metabolism may predispose to the generation of reactive drug metabolites and hence to hypersensitivity reactions. These findings support the potential for the use of pharmacogenomics tests in hypersensitivity (type B) adverse reactions, in addition to the well known utility of these tests in type A adverse reactions. Growing evidence supports a link between genetically determined drug metabolism, altered metabolic profiles, generation of highly reactive metabolites and haptenization. Additional research is required to developing robust biomarkers for drug-induced hypersensitivity reactions.

  9. A Prospective Screening of HLA-B*57.01 Allelic Variant for Preventing the Hypersensivity Reaction to Abacavir: Experience from the Laboratory of Molecular Biology of the Infectious Diseases Division at the University Hospital of Salerno.

    PubMed

    Senatore, C; Charlier, B; Truono, A; Punzi, R; D'Aniello, F; Boffa, N; Izzo, V; Conti, V; Russomanno, G; Manzo, V; Filippelli, A; Mazzeo, M

    2015-01-01

    Abacavir is a nucleoside reverse transcriptase inhibitor largely used as part of the antiretroviral therapy in Human Immunodeficiency Virus (HIV)-infected patients. Some individuals (2-9%) who start an abacavir treatment show an immunologic reaction indicated as hypersensitivity reaction syndrome (HSR) that is often responsible for therapy discontinuation and could represent a life-threatening event. Some studies demonstrated a correlation between this adverse reaction and the class I of the major histocompatibility complex (MHC) allele, HLA-B*57.01, in several populations, including Caucasians. Nowadays, International HIV treatment guidelines recommend the HLA-B*57.01 genotyping before abacavir administration to reduce the incidence of HSR. Both male and female HIV-infected patients were enrolled at the Infectious Diseases Division at the University Hospital of Salerno, and admitted to a prospective HLAB*57.01 screening. Genetic analysis was carried out through two sequential Real-Time PCR reactions in which Sybr-Green was used. Out of 248 patients, 215 were Italians from Southern Italy and 33 were coming from several non-EU members countries. All were genotyped: 6 Italians (2.8%) and 1 of the non-EU group (3%) were identified as HLAB*57.01 carriers. In this paper we present our experience in the field of abacavir pharmacogenetic and confirm the importance of Real Time PCR as a valid and cost-effective HLA-B*57.01 typing methodology.

  10. Immediate-type hypersensitivity drug reactions.

    PubMed

    Stone, Shelley F; Phillips, Elizabeth J; Wiese, Michael D; Heddle, Robert J; Brown, Simon G A

    2014-07-01

    Hypersensitivity reactions including anaphylaxis have been reported for nearly all classes of therapeutic reagents and these reactions can occur within minutes to hours of exposure. These reactions are unpredictable, not directly related to dose or the pharmacological action of the drug and have a relatively high mortality risk. This review will focus on the clinical presentation, immune mechanisms, diagnosis and prevention of the most serious form of immediate onset drug hypersensitivity reaction, anaphylaxis. The incidence of drug-induced anaphylaxis deaths appears to be increasing and our understanding of the multiple and complex reasons for the unpredictable nature of anaphylaxis to drugs is also expanding. This review highlights the importance of enhancing our understanding of the biology of the patient (i.e. immune response, genetics) as well as the pharmacology and chemistry of the drug when investigating, diagnosing and treating drug hypersensitivity. Misdiagnosis of drug hypersensitivity leads to substantial patient risk and cost. Although oral provocation is often considered the gold standard of diagnosis, it can pose a potential risk to the patient. There is an urgent need to improve and standardize diagnostic testing and desensitization protocols as other diagnostic tests currently available for assessment of immediate drug allergy are not highly predictive. © 2013 The British Pharmacological Society.

  11. Immediate-type hypersensitivity drug reactions

    PubMed Central

    Stone, Shelley F; Phillips, Elizabeth J; Wiese, Michael D; Heddle, Robert J; Brown, Simon G A

    2014-01-01

    Hypersensitivity reactions including anaphylaxis have been reported for nearly all classes of therapeutic reagents and these reactions can occur within minutes to hours of exposure. These reactions are unpredictable, not directly related to dose or the pharmacological action of the drug and have a relatively high mortality risk. This review will focus on the clinical presentation, immune mechanisms, diagnosis and prevention of the most serious form of immediate onset drug hypersensitivity reaction, anaphylaxis. The incidence of drug-induced anaphylaxis deaths appears to be increasing and our understanding of the multiple and complex reasons for the unpredictable nature of anaphylaxis to drugs is also expanding. This review highlights the importance of enhancing our understanding of the biology of the patient (i.e. immune response, genetics) as well as the pharmacology and chemistry of the drug when investigating, diagnosing and treating drug hypersensitivity. Misdiagnosis of drug hypersensitivity leads to substantial patient risk and cost. Although oral provocation is often considered the gold standard of diagnosis, it can pose a potential risk to the patient. There is an urgent need to improve and standardize diagnostic testing and desensitization protocols as other diagnostic tests currently available for assessment of immediate drug allergy are not highly predictive. PMID:24286446

  12. Abacavir induced T cell reactivity from drug naïve individuals shares features of allo-immune responses.

    PubMed

    Adam, Jacqueline; Wuillemin, Natascha; Watkins, Stephan; Jamin, Heidi; Eriksson, Klara K; Villiger, Peter; Fontana, Stefano; Pichler, Werner J; Yerly, Daniel

    2014-01-01

    Abacavir hypersensitivity is a severe hypersensitivity reaction which occurs exclusively in carriers of the HLA-B*57∶01 allele. In vitro culture of PBMC with abacavir results in the outgrowth of abacavir-reacting CD8+ T cells, which release IFNγ and are cytotoxic. How this immune response is induced and what is recognized by these T cells is still a matter of debate. We analyzed the conditions required to develop an abacavir-dependent T cell response in vitro. The abacavir reactivity was independent of co-stimulatory signals, as neither DC maturation nor release of inflammatory cytokines were observed upon abacavir exposure. Abacavir induced T cells arose in the absence of professional APC and stemmed from naïve and memory compartments. These features are reminiscent of allo-reactivity. Screening for allo-reactivity revealed that about 5% of generated T cell clones (n = 136) from three donors were allo-reactive exclusively to the related HLA-B*58∶01. The addition of peptides which can bind to the HLA-B*57∶01-abacavir complex and to HLA-B*58∶01 during the induction phase increased the proportion of HLA-B*58∶01 allo-reactive T cell clones from 5% to 42%. In conclusion, abacavir can alter the HLA-B*57∶01-peptide complex in a way that mimics an allo-allele ('altered self-allele') and create the potential for robust T cell responses.

  13. Investigation of Seminal Plasma Hypersensitivity Reactions

    DTIC Science & Technology

    1998-10-01

    the same questionnaire which has been used to screen civilian populations of women with localized and/or systemic seminal plasma hypersensitivity. This...3. If not, how many times have you experienced a reaction with other sexual partners? 4. Did you have the reaction on your first intercourse? A...YES B. NO 5. 6. If the answer above is no, how many years after your first intercourse did the firstreaction occur? Prior to the

  14. Abacavir-Reactive Memory T Cells Are Present in Drug Naïve Individuals

    PubMed Central

    Lucas, Andrew; Lucas, Michaela; Strhyn, Anette; Keane, Niamh M.; McKinnon, Elizabeth; Pavlos, Rebecca; Moran, Ellen M.; Meyer-Pannwitt, Viola; Gaudieri, Silvana; D’Orsogna, Lloyd; Kalams, Spyros; Ostrov, David A.; Buus, Søren; Peters, Bjoern; Mallal, Simon; Phillips, Elizabeth

    2015-01-01

    Background Fifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR) that has been attributed to naïve T-cell responses to neo-antigen generated by the drug. Immunologically confirmed abacavir HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least in some cases, abacavir HSR is due to re-stimulation of a pre-existing memory T-cell population rather than priming of a high frequency naïve T-cell population. Methods To determine whether a pre-existing abacavir reactive memory T-cell population contributes to early abacavir HSR symptoms, we studied the abacavir specific naïve or memory T-cell response using HLA-B*57:01 positive HSR patients or healthy controls using ELISpot assay, intra-cellular cytokine staining and tetramer labelling. Results Abacavir reactive CD8+ T-cell responses were detected in vitro in one hundred percent of abacavir unexposed HLA-B*57:01 positive healthy donors. Abacavir-specific CD8+ T cells from such donors can be expanded from sorted memory, and sorted naïve, CD8+ T cells without need for autologous CD4+ T cells. Conclusions We propose that these pre-existing abacavir-reactive memory CD8+ T-cell responses must have been primed by earlier exposure to another foreign antigen and that these T cells cross-react with an abacavir-HLA-B*57:01-endogenous peptide ligand complex, in keeping with the model of heterologous immunity proposed in transplant rejection. PMID:25674793

  15. Abacavir-reactive memory T cells are present in drug naïve individuals.

    PubMed

    Lucas, Andrew; Lucas, Michaela; Strhyn, Anette; Keane, Niamh M; McKinnon, Elizabeth; Pavlos, Rebecca; Moran, Ellen M; Meyer-Pannwitt, Viola; Gaudieri, Silvana; D'Orsogna, Lloyd; Kalams, Spyros; Ostrov, David A; Buus, Søren; Peters, Bjoern; Mallal, Simon; Phillips, Elizabeth

    2015-01-01

    Fifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR) that has been attributed to naïve T-cell responses to neo-antigen generated by the drug. Immunologically confirmed abacavir HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least in some cases, abacavir HSR is due to re-stimulation of a pre-existing memory T-cell population rather than priming of a high frequency naïve T-cell population. To determine whether a pre-existing abacavir reactive memory T-cell population contributes to early abacavir HSR symptoms, we studied the abacavir specific naïve or memory T-cell response using HLA-B*57:01 positive HSR patients or healthy controls using ELISpot assay, intra-cellular cytokine staining and tetramer labelling. Abacavir reactive CD8+ T-cell responses were detected in vitro in one hundred percent of abacavir unexposed HLA-B*57:01 positive healthy donors. Abacavir-specific CD8+ T cells from such donors can be expanded from sorted memory, and sorted naïve, CD8+ T cells without need for autologous CD4+ T cells. We propose that these pre-existing abacavir-reactive memory CD8+ T-cell responses must have been primed by earlier exposure to another foreign antigen and that these T cells cross-react with an abacavir-HLA-B*57:01-endogenous peptide ligand complex, in keeping with the model of heterologous immunity proposed in transplant rejection.

  16. Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing

    PubMed Central

    Martin, MA; Klein, TE; Dong, BJ; Pirmohamed, M; Haas, DW; Kroetz, DL

    2012-01-01

    Human leukocyte antigen B (HLA-B) is responsible for presenting peptides to immune cells and plays a critical role in normal immune recognition of pathogens. A variant allele, HLA-B★57:01, is associated with increased risk of a hypersensitivity reaction to the anti-HIV drug abacavir. In the absence of genetic prescreening, hypersensitivity affects ∼6% of patients and can be life-threatening with repeated dosing. We provide recommendations (updated periodically at http://www.pharmkgb.org) for the use of abacavir based on HLA-B genotype. PMID:22378157

  17. Active suppression rather than ignorance: tolerance to abacavir-induced HLA-B*57:01 peptide repertoire alteration.

    PubMed

    Phillips, Elizabeth J; Mallal, Simon A

    2018-05-21

    The discovery of HLA-B*57:01-associated abacavir hypersensitivity is a translational success story that eliminated adverse reactions to abacavir through pretreatment screening and defined a mechanistic model of an altered peptide repertoire. In this issue of the JCI, Cardone et al. have developed an HLA-B*57:01-transgenic mouse model and demonstrated that CD4+ T cells play a key role in mediating tolerance to the dramatically altered endogenous peptide repertoire induced by abacavir and postulate a known mechanism by which CD4+ T cells suppress DC maturation. This report potentially explains why 45% of HLA-B*57:01 carriers tolerate abacavir and provides a framework for future studies of HLA-restricted, T cell-mediated drug tolerance and hypersensitivity.

  18. [Hypersensitivity reaction to radio contrast media: diagnosis, prevention and treatment].

    PubMed

    Mahlab-Guri, Keren; Herskovitz, Pearl; Sthoeger, Zev

    2012-07-01

    More than 70 million radiographic examinations with radio contrast media are performed worldwide each year. The incidence of adverse reactions to radio contrast media is 5-13%. Adverse reactions include hypersensitivity reactions, chemotoxic reactions and renal toxicity. Hypersensitivity reactions to radio contrast media range from mild pruritus to life-threatening emergency. The differential diagnosis between hypersensitivity reaction to radio contrast media and chemotoxic reaction is challenging. The incidence of chemotoxic reactions is mainly affected by the chemical structure of the radio contrast media and the rate of infusion. The incidence of hypersensitivity radio contrast media reaction is affected by age and by the presence of asthma and other atopic diseases. The diagnosis of hypersensitivity reaction to radio contrast media is based on clinical manifestations. The additional value of laboratory tests is limited and questionable. In case of hypersensitivity radio contrast reaction, the infusion should be stopped immediately, airways should be protected and fluids, oxygen and drugs should be given. Prophylactic treatment before its administration may prevent hypersensitivity reactions to radio contrast media.

  19. Nonimmediate hypersensitivity reactions to iodinated contrast media.

    PubMed

    Gómez, Enrique; Ariza, Adriana; Blanca-López, Natalia; Torres, Maria J

    2013-08-01

    To provide a detailed analysis of the latest findings on the mechanisms underlying the nonimmediate reactions to iodinated contrast media and comment on the recent advances in diagnosis, focusing on the roles of the skin test, drug provocation test (DPT), and lymphocyte transformation test (LTT). Several studies have reported new findings supporting an important role for T-lymphocytes in the nonimmediate reactions to iodinated contrast media. The LTT has been used as an in-vitro tool for diagnosis, but with variable results. However, the inclusion of autologous monocyte-derived dendritic cells as professional antigen-presenting cells has improved the sensitivity of this test. Regarding in-vivo diagnosis, although skin testing has been routine, it has now been shown that its sensitivity and negative predictive value are low. Recent studies have demonstrated that the DPT is a well tolerated and useful procedure that is necessary to confirm the diagnosis of nonimmediate hypersensitivity reactions to iodinated contrast media. Nonimmediate reactions to contrast media are usually T-cell mediated. Diagnosis is based on skin testing, although its sensitivity and negative predictive value are not optimal. Consequently, drug provocation testing is often needed to confirm the diagnosis and also to seek alternative contrast media that can be tolerated.

  20. Towards depersonalized abacavir therapy: chemical modification eliminates HLA-B*57 : 01-restricted CD8+ T-cell activation.

    PubMed

    Naisbitt, Dean J; Yang, Emma L; Alhaidari, Mohammad; Berry, Neil G; Lawrenson, Alexandre S; Farrell, John; Martin, Philip; Strebel, Klaus; Owen, Andrew; Pye, Matthew; French, Neil S; Clarke, Stephen E; O'Neill, Paul M; Park, B Kevin

    2015-11-28

    Exposure to abacavir is associated with T-cell-mediated hypersensitivity reactions in individuals carrying human leukocyte antigen (HLA)-B57 : 01. To activate T cells, abacavir interacts directly with endogenous HLA-B57 : 01 and HLA-B57 : 01 expressed on the surface of antigen presenting cells. We have investigated whether chemical modification of abacavir can produce a molecule with antiviral activity that does not bind to HLA-B57 : 01 and activate T cells. An interdisciplinary laboratory study using samples from human donors expressing HLA-B57 : 01. Researchers were blinded to the analogue structures and modelling data. Sixteen 6-amino substituted abacavir analogues were synthesized. Computational docking studies were completed to predict capacity for analogue binding within HLA-B57 : 01. Abacavir-responsive CD8 clones were generated to study the association between HLA-B57 : 01 analogue binding and T-cell activation. Antiviral activity and the direct inhibitory effect of analogues on proliferation were assessed. Major histocompatibility complex class I-restricted CD8 clones proliferated and secreted IFNγ following abacavir binding to surface and endogenous HLA-B57 : 01. Several analogues retained antiviral activity and showed no overt inhibitory effect on proliferation, but displayed highly divergent antigen-driven T-cell responses. For example, abacavir and N-propyl abacavir were equally potent at activating clones, whereas the closely related analogues N-isopropyl and N-methyl isopropyl abacavir were devoid of T-cell activity. Docking abacavir analogues to HLA-B57 : 01 revealed a quantitative relationship between drug-protein binding and the T-cell response. These studies demonstrate that the unwanted T-cell activity of abacavir can be eliminated whilst maintaining the favourable antiviral profile. The in-silico model provides a tool to aid the design of safer antiviral agents that may not require a personalized medicines approach to therapy.

  1. Structural Elements Recognized by Abacavir-Induced T Cells.

    PubMed

    Yerly, Daniel; Pompeu, Yuri Andreiw; Schutte, Ryan J; Eriksson, Klara K; Strhyn, Anette; Bracey, Austin W; Buus, Soren; Ostrov, David A

    2017-07-07

    Adverse drug reactions are one of the leading causes of morbidity and mortality in health care worldwide. Human leukocyte antigen (HLA) alleles have been strongly associated with drug hypersensitivities, and the causative drugs have been shown to stimulate specific T cells at the sites of autoimmune destruction. The structural elements recognized by drug-specific T cell receptors (TCRs) in vivo are poorly defined. Drug-stimulated T cells express TCRs specific for peptide/HLA complexes, but the characteristics of peptides (sequence, or endogenous or exogenous origin) presented in the context of small molecule drugs are not well studied. Using HLA-B*57:01 mediated hypersensitivity to abacavir as a model system, this study examines structural similarities of HLA presented peptides recognized by drug-specific TCRs. Using the crystal structure of HLA-B*57:01 complexed with abacavir and an immunogenic self peptide, VTTDIQVKV SPT5a 976-984, peptide side chains exhibiting flexibility and solvent exposure were identified as potential drug-specific T cell recognition motifs. Viral sequences with structural motifs similar to the immunogenic self peptide were identified. Abacavir-specific T cell clones were used to determine if virus peptides presented in the context of abacavir stimulate T cell responsiveness. An abacavir-specific T cell clone was stimulated by VTQQAQVRL, corresponding to HSV1/2 230-238, in the context of HLA-B*57:01. These data suggest the T cell polyclonal response to abacavir consists of multiple subsets, including T cells that recognize self peptide/HLA-B*57:01 complexes and crossreact with viral peptide/HLA-B*57:01 complexes due to similarity in TCR contact residues.

  2. Structural Elements Recognized by Abacavir-Induced T Cells

    PubMed Central

    Yerly, Daniel; Pompeu, Yuri Andreiw; Schutte, Ryan J.; Eriksson, Klara. K.; Strhyn, Anette; Bracey, Austin. W.; Buus, Soren; Ostrov, David A.

    2017-01-01

    Adverse drug reactions are one of the leading causes of morbidity and mortality in health care worldwide. Human leukocyte antigen (HLA) alleles have been strongly associated with drug hypersensitivities, and the causative drugs have been shown to stimulate specific T cells at the sites of autoimmune destruction. The structural elements recognized by drug-specific T cell receptors (TCRs) in vivo are poorly defined. Drug-stimulated T cells express TCRs specific for peptide/HLA complexes, but the characteristics of peptides (sequence, or endogenous or exogenous origin) presented in the context of small molecule drugs are not well studied. Using HLA-B*57:01 mediated hypersensitivity to abacavir as a model system, this study examines structural similarities of HLA presented peptides recognized by drug-specific TCRs. Using the crystal structure of HLA-B*57:01 complexed with abacavir and an immunogenic self peptide, VTTDIQVKV SPT5a 976–984, peptide side chains exhibiting flexibility and solvent exposure were identified as potential drug-specific T cell recognition motifs. Viral sequences with structural motifs similar to the immunogenic self peptide were identified. Abacavir-specific T cell clones were used to determine if virus peptides presented in the context of abacavir stimulate T cell responsiveness. An abacavir-specific T cell clone was stimulated by VTQQAQVRL, corresponding to HSV1/2 230–238, in the context of HLA-B*57:01. These data suggest the T cell polyclonal response to abacavir consists of multiple subsets, including T cells that recognize self peptide/HLA-B*57:01 complexes and crossreact with viral peptide/HLA-B*57:01 complexes due to similarity in TCR contact residues. PMID:28686208

  3. Outpatient desensitization in selected patients with platinum hypersensitivity reactions.

    PubMed

    O'Malley, David M; Vetter, Monica Hagan; Cohn, David E; Khan, Ambar; Hays, John L

    2017-06-01

    Platinum-based chemotherapies are a standard treatment for both initial and recurrent gynecologic cancers. Given this widespread use, it is important to be aware of the features of platinum hypersensitivity reactions and the subsequent treatment of these reactions. There is also increasing interest in the development of desensitization protocols to allow patients with a history of platinum hypersensitivity to receive further platinum based therapy. In this review, we describe the management of platinum hypersensitivity reactions and the desensitization protocols utilized at our institution. We also describe the clinical categorizations utilized to triage patients to appropriate desensitization protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Potent NLRP3 Inflammasome Activation by the HIV Reverse Transcriptase Inhibitor Abacavir.

    PubMed

    Toksoy, Atiye; Sennefelder, Helga; Adam, Christian; Hofmann, Sonja; Trautmann, Axel; Goebeler, Matthias; Schmidt, Marc

    2017-02-17

    There is experimental and clinical evidence that some exanthematous allergic drug hypersensitivity reactions are mediated by drug-specific T cells. We hypothesized that the capacity of certain drugs to directly stimulate the innate immune system may contribute to generate drug-specific T cells. Here we analyzed whether abacavir, an HIV-1 reverse transcriptase inhibitor often inducing severe delayed-type drug hypersensitivity, can trigger innate immune activation that may contribute to its allergic potential. We show that abacavir fails to generate direct innate immune activation in human monocytes but potently triggers IL-1β release upon pro-inflammatory priming with phorbol ester or Toll-like receptor stimulation. IL-1β processing and secretion were sensitive to Caspase-1 inhibition, NLRP3 knockdown, and K + efflux inhibition and were not observed with other non-allergenic nucleoside reverse transcriptase inhibitors, identifying abacavir as a specific inflammasome activator. It further correlated with dose-dependent mitochondrial reactive oxygen species production and cytotoxicity, indicating that inflammasome activation resulted from mitochondrial damage. However, both NLRP3 depletion and inhibition of K + efflux mitigated abacavir-induced mitochondrial reactive oxygen species production and cytotoxicity, suggesting that these processes were secondary to NLRP3 activation. Instead, depletion of cardiolipin synthase 1 abolished abacavir-induced IL-1β secretion, suggesting that mitochondrial cardiolipin release may trigger abacavir-induced inflammasome activation. Our data identify abacavir as a novel inflammasome-stimulating drug allergen. They implicate a potential contribution of innate immune activation to medication-induced delayed-type hypersensitivity, which may stimulate new concepts for treatment and prevention of drug allergies. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Hypersensitivity reactions to metal implants: laboratory options.

    PubMed

    Carossino, Anna Maria; Carulli, Christian; Ciuffi, Simone; Carossino, Roberto; Zappoli Thyrion, Giorgia Donata; Zonefrati, Roberto; Innocenti, Massimo; Brandi, Maria Luisa

    2016-11-23

    All implant compounds undergo an electrochemical process when in contact with biological fluids, as well as mechanical corrosion due to abrasive wear, with production of metal debris that may inhibit repair processes. None of the commonly-used methods can diagnose implant allergies when used singly, therefore a panel of tests should be performed on allergic patients as pre-operative screening, or when a postoperative metal sensitisation is suspected. We analysed patients with painful prostheses and subjects prone to allergies using the Patch Test in comparison with the Lymphocyte Transformation Test. Cytokine production was evaluated to identify prognostic markers for early diagnosis of aseptic loosening. Metal debris endocytosis and cytoskeletal rearrangement was visualised by confocal microscopy. Our results demonstrate that the Lymphocyte Transformation Test can identify patients who have a predisposition to develop allergic reactions and can confirm the diagnosis of hypersensitivity in patients with painful prostheses. The prevalence of a Th2-cytokine pattern may be used to identify predisposition to the development of allergic diseases, while the selective presence of osteoclastogenic cytokines may be used as predictor of a negative outcome in patients with painful prosthesis. The hypothesis of the prognostic value of these cytokines as early markers of aseptic loosening is attractive, but its confirmation would require extensive testing. The Lymphocyte Transformation Test is the most suitable method for testing systemic allergies. We suggest that the combined use of the Patch Test and the Lymphocyte Transformation Test, associated with cytokine detection in selected patients, could provide a useful tool for preventive evaluation of immune reactivity in patients undergoing primary joint replacement surgery, and for clinical monitoring of the possible onset of a metal sensitization in patients with implanted devices.

  6. Abacavir Induced T Cell Reactivity from Drug Naïve Individuals Shares Features of Allo-Immune Responses

    PubMed Central

    Adam, Jacqueline; Wuillemin, Natascha; Watkins, Stephan; Jamin, Heidi; Eriksson, Klara K.; Villiger, Peter; Fontana, Stefano; Pichler, Werner J.; Yerly, Daniel

    2014-01-01

    Abacavir hypersensitivity is a severe hypersensitivity reaction which occurs exclusively in carriers of the HLA-B*57∶01 allele. In vitro culture of PBMC with abacavir results in the outgrowth of abacavir-reacting CD8+ T cells, which release IFNγ and are cytotoxic. How this immune response is induced and what is recognized by these T cells is still a matter of debate. We analyzed the conditions required to develop an abacavir-dependent T cell response in vitro. The abacavir reactivity was independent of co-stimulatory signals, as neither DC maturation nor release of inflammatory cytokines were observed upon abacavir exposure. Abacavir induced T cells arose in the absence of professional APC and stemmed from naïve and memory compartments. These features are reminiscent of allo-reactivity. Screening for allo-reactivity revealed that about 5% of generated T cell clones (n = 136) from three donors were allo-reactive exclusively to the related HLA-B*58∶01. The addition of peptides which can bind to the HLA-B*57∶01-abacavir complex and to HLA-B*58∶01 during the induction phase increased the proportion of HLA-B*58∶01 allo-reactive T cell clones from 5% to 42%. In conclusion, abacavir can alter the HLA-B*57∶01-peptide complex in a way that mimics an allo-allele (‘altered self-allele’) and create the potential for robust T cell responses. PMID:24751900

  7. Adverse events associated with abacavir use in HIV-infected children and adolescents: a systematic review and meta-analysis.

    PubMed

    Jesson, Julie; Dahourou, Désiré L; Renaud, Françoise; Penazzato, Martina; Leroy, Valériane

    2016-02-01

    Concerns exist about the toxicity of drugs used in the implementation of large-scale antiretroviral programmes, and documentation of antiretroviral toxicity is essential. We did a systematic review and meta-analysis of adverse events among children and adolescents receiving regimens that contain abacavir, a widely used antiretroviral drug. We searched bibliographic databases and abstracts from relevant conferences from Jan 1, 2000, to March 1, 2015. All experimental and observational studies of HIV-infected patients aged 0-18 years who used abacavir, were eligible. Incidence of adverse outcomes in patients taking abacavir (number of new events in a period divided by population at risk at the beginning of the study) and relative risks (RR) compared with non-abacavir regimens were pooled with random effects models. Of 337 records and 21 conference abstracts identified, nine studies (eight full-text articles and one abstract) collected information about 2546 children, of whom 1769 (69%) were on abacavir regimens. Among children and adolescents taking abacavir, hypersensitivity reactions (eight studies) had a pooled incidence of 2·2% (95% CI 0·4-5·2); treatment switching or discontinuation (seven studies) pooled incidence was 10·9% (2·1-24·3); of grade 3-4 adverse events (six studies) pooled incidence was 9·9% (2·4-20·9); and adverse events other than hypersensitivity reaction (six studies) pooled incidence was 21·5% (2·8-48·4). Between-study inconsistency was significant for all outcomes (p<0·0001 for all inconsistencies). Incidence of death (four studies) was 3·3% (95% CI 1·5-5·6). In the three randomised clinical trials with comparative data, no increased risk of hypersensitivity reaction (pooled RR 1·08; 95% CI 0·19-6·15), grade 3 or 4 events (0·79 [0·44-1·42]), or death (1·72 [0·77-3·82]) was noted for abacavir relative to non-abacavir regimens. None of the reported deaths were related to abacavir. Abacavir-related toxicity occurs early

  8. Hypersensitivity reaction to mizolastine: study of cross reactions.

    PubMed

    Gonzalo-Garijo, M A; Jiménez-Ferrera, G; Bobadilla-González, P; Cordobés-Durán, C

    2006-01-01

    A 26-year-old male suffering from acute rhinitis took the first dose of Zolistan (mizolastine, 10 mg), orally, and 15 minutes later he developed intense generalized pruritus, cutaneous rash, oropharyngeal pruritus, edema on his face, difficulty in swallowing, and mild dyspnea. He was treated with methylprednisolone and epinephrine and improved within 30 minutes. The patient had not taken mizolastine before and he has avoided it since the reaction. Cutaneous tests with Zolistan and its excipients proved negative. Simple-blind oral challenge tests with the excipients and then with Zolistan were positive only with Zolistan. In order to confirm the absence of cross-reactivity between mizolastine and other benzimidazoles, we tested omeprazole, domperidone and mebendazole, all of which yielded negative results. To our knowledge, this is the second case of immediate hypersensitivity to mizolastine documented to date. In our case, the clinical history, physical examination and provocation tests allow us to establish the diagnosis of hypersensitivity to mizolastine and exclude the cross reactivity with other benzimidazole derivatives.

  9. Pharmacogenetics of drug hypersensitivity

    PubMed Central

    Phillips, Elizabeth J; Mallal, Simon A

    2010-01-01

    Drug hypersensitivity reactions and severe cutaneous adverse drug reactions, such as Stevens–Johnson syndrome and toxic epidermal necrolysis, are examples of serious adverse drug reactions mediated through a combination of metabolic and immunological mechanisms that could traditionally not have been predicted based on the pharmacological characteristics of the drug alone. The discovery of new associations between these syndromes and specific HLA has created the promise that risk for these reactions could be predicted through pharmacogenetic screening, thereby avoiding serious morbidity and mortality associated with these types of drug reactions. Despite this, several hurdles exist in the translation of these associations into pharmacogenetic tests that could be routinely used in the clinical setting. HLA-B*5701 screening to prevent abacavir hypersensitivity syndrome is an example of a test now in widespread routine clinical use in the developed world. PMID:20602616

  10. Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions.

    PubMed

    Böhm, Ruwen; Cascorbi, Ingolf

    2016-01-01

    Adverse drug reactions adverse drug reaction (ADR) occur in approximately 17% of patients. Avoiding ADR is thus mandatory from both an ethical and an economic point of view. Whereas, pharmacogenetics changes of the pharmacokinetics may contribute to the explanation of some type A reactions, strong relationships of genetic markers has also been shown for drug hypersensitivity belonging to type B reactions. We present the classifications of ADR, discuss genetic influences and focus on delayed-onset hypersensitivity reactions, i.e., drug-induced liver injury, drug-induced agranulocytosis, and severe cutaneous ADR. A guidance how to read and interpret the contingency table is provided as well as an algorithm whether and how a test for a pharmacogenetic biomarker should be conducted.

  11. Bioactivation to an aldehyde metabolite--possible role in the onset of toxicity induced by the anti-HIV drug abacavir.

    PubMed

    Grilo, Nádia M; Charneira, Catarina; Pereira, Sofia A; Monteiro, Emília C; Marques, M Matilde; Antunes, Alexandra M M

    2014-01-30

    Aldehydes are highly reactive molecules, which can be generated during numerous physiological processes, including the biotransformation of drugs. Several non-P450 enzymes participate in their metabolism albeit alcohol dehydrogenase and aldehyde dehydrogenase are the ones most frequently involved in this process. Endogenous and exogenous aldehydes have been strongly implicated in multiple human pathologies. Their ability to react with biomacromolecules (e.g. proteins) yielding covalent adducts is suggested to be the common primary mechanism underlying the toxicity of these reactive species. Abacavir is one of the options for combined anti-HIV therapy. Although individual susceptibilities to adverse effects differ among patients, abacavir is associated with idiosyncratic hypersensitivity drug reactions and an increased risk of cardiac dysfunction. This review highlights the current knowledge on abacavir metabolism and discusses the potential role of bioactivation to an aldehyde metabolite, capable of forming protein adducts, in the onset of abacavir-induced toxic outcomes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. In vitro analysis of metabolic predisposition to drug hypersensitivity reactions.

    PubMed Central

    Riley, R J; Leeder, J S

    1995-01-01

    Idiosyncratic hypersensitivity reactions may account for up to 25% of all adverse reactions, and pose a constant problem to physicians because of their unpredictable nature, potentially fatal outcome and resemblance to other disease processes. Current understanding of how drug allergy arises is based largely on the hapten hypothesis: since most drugs are not chemically reactive per se, they must be activated metabolically to reactive species which may become immunogenic through interactions with cellular macromolecules. The role of drug metabolism is thus pivotal to the hapten hypothesis both in activation of the parent compound and detoxification of the reactive species. Although conjugation reactions may occasionally produce potential immunogens (for example, the generation of acylglucuronides from non-steroidal anti-inflammatory drugs such as diclofenac), bioactivation is catalysed most frequently by cytochrome P450 (P450) enzymes. The multifactorial nature of hypersensitivity reactions, particularly the role of often unidentified, reactive drug metabolites in antigen generation, has hampered the routine diagnosis of these disorders by classical immunological methods designed to detect circulating antibodies or sensitized T cells. Similarly, species differences in drug metabolism and immune system regulation have largely precluded the establishment of appropriate animal models with which to examine the immunopathological mechanisms of these toxicities. However, the combined use of in vitro toxicity assays incorporating human tissues and in vivo phenotyping (or, ultimately, in vitro genotyping) methods for drug detoxification pathways may provide the metabolic basis for hypersensitivity reactions to several drugs. This brief review highlights recent efforts to unravel the bases for hypersensitivity reactions to these therapeutic agents (which include anticonvulsants and sulphonamides) using drug metabolism and immunochemical approaches. In particular, examples

  13. Linezolid desensitization for a patient with multiple medication hypersensitivity reactions.

    PubMed

    Bagwell, Autumn D; Stollings, Joanna L; White, Katie D; Fadugba, Olajumoke O; Choi, Jane J

    2013-01-01

    To describe a case in which a linezolid desensitization protocol was successfully used for a polymicrobial surgical wound infection in a patient with multiple drug hypersensitivity reactions. A 24-year-old woman with vocal cord dysfunction requiring tracheostomy was admitted for a surgical wound infection following a tracheostomy fistula closure procedure. The patient reported multiple antibiotic allergies including penicillins (rash), sulfonamides (rash), vancomycin (anaphylaxis), azithromycin (rash), cephalosporins (anaphylaxis), levofloxacin (unspecified), clindamycin (unspecified), and carbapenems (unspecified). Gram stain of the purulent wound drainage demonstrated mixed gram-negative and gram-positive flora, and bacterial cultures were overgrown with Proteus mirabilis, which precluded identification of other pathogens. Following failed test doses of linezolid, tigecycline, and daptomycin, all of which resulted in hypersensitivity reactions, a 16-step linezolid desensitization protocol was developed and successfully implemented without adverse reactions. The patient completed a 2-week course of antibiotic therapy that included linezolid upon finishing the desensitization protocol. Linezolid is useful in treating complicated and uncomplicated skin and soft tissue infections caused by gram-positive bacteria. With precautions, including premedication, a monitored nursing unit, and immediate availability of an emergency anaphylaxis kit, drug desensitization allows patients the ability to safely use medications to which they may have an immediate hypersensitivity reaction. Minimal data exist on linezolid desensitization protocols. Linezolid desensitization can be a viable option in patients requiring antimicrobial therapy for complicated gram-positive skin infections.

  14. [Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].

    PubMed

    Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P

    2016-06-01

    Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  15. Studies of the quenching phenomenon in delayed contact hypersensitivity reactions.

    PubMed

    Basketter, D A; Allenby, C F

    1991-09-01

    Studies in guinea pig and man have shown that eugenol can quench non-specifically contact urticarial responses, whereas limonene seems largely ineffective. In a comprehensive series of studies, there was little evidence of quenching of delayed contact hypersensitivity reactions to cinnamic aldehyde or citral, including in 'pre-quenched' material supplied by a perfume/flavour company, and in a similar mixture prepared in this laboratory, in the guinea pig model. In addition, there was no evidence of the quenching by eugenol of allergic reactions to cinnamic aldehyde in a panel of human subjects with a proven history of cinnamic-aldehyde-induced allergic contact dermatitis. Overall, the results lend little credibility to earlier literature reports of quenching phenomena in delayed contact hypersensitivity responses.

  16. Cutaneous and systemic hypersensitivity reactions to metallic implants.

    PubMed

    Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C

    2011-01-01

    Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous, and vasculitic eruptions may occur. Also, more complex immune reactions may develop around the implants, resulting in pain, inflammation, and loosening. Nickel, cobalt, and chromium are the three most common metals that elicit both cutaneous and extracutaneous allergic reactions from chronic internal exposure. However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis) following the insertion of intravascular stents, dental implants, cardiac pacemakers, or implanted gynecologic devices. Despite repeated attempts by researchers and clinicians to further understand this difficult area of medicine, the association between metal sensitivity and cutaneous allergic reactions remains to be fully understood. This review provides an update of the current knowledge in this field and should be valuable to health care providers who manage patients with conditions related to this field.

  17. Induction of Hypozincemia and Hepatic Metallothionein Synthesis in Hypersensitivity Reactions.

    DTIC Science & Technology

    1978-06-19

    cells to produce endogenous pyrogen (EP), the mediator of febrile response. Controversial evidence exists, however , concerning the differentiation of LEM...hypersensitivity reactions, Kampschmid t and Pulliam (1) proposed that leukocytic endogenous mediator (LEN) is released from phagocytic cells after... endogenous mediator(s) such as LEN, no conclusive evidence is available to indicate a mRNA requirement for the production of potential mediator(s

  18. Persistent Skin Reactions and Aluminium Hypersensitivity Induced by Childhood Vaccines.

    PubMed

    Salik, Elaha; Løvik, Ida; Andersen, Klaus E; Bygum, Anette

    2016-11-02

    There is increasing awareness of reactions to vaccination that include persistent skin reactions. We present here a retrospective investigation of long-lasting skin reactions and aluminium hypersensitivity in children, based on medical records and questionnaires sent to the parents. In the 10-year period 2003 to 2013 we identified 47 children with persistent skin reactions caused by childhood vaccinations. Most patients had a typical presentation of persisting pruritic subcutaneous nodules. Five children had a complex diagnostic process involving paediatricians, orthopaedics and plastic surgeons. Two patients had skin biopsies performed from their skin lesions, and 2 patients had the nodules surgically removed. Forty-two children had a patch-test performed with 2% aluminium chloride hexahydrate in petrolatum and 39 of them (92%) had a positive reaction. The persistent skin reactions were treated with potent topical corticosteroids and disappeared slowly. Although we advised families to continue vaccination of their children, one-third of parents omitted or postponed further vaccinations.

  19. Multinational experience with hypersensitivity drug reactions in Latin America.

    PubMed

    Jares, Edgardo José; Sánchez-Borges, Mario; Cardona-Villa, Ricardo; Ensina, Luis Felipe; Arias-Cruz, Alfredo; Gómez, Maximiliano; Barayazarra, Susana; Bernstein, Jonathan A; Serrano, Carlos D; Cuello, Mabel Noemi; Morfin-Maciel, Blanca María; De Falco, Alicia; Cherrez-Ojeda, Iván

    2014-09-01

    Epidemiologic drug allergy data from Latin America are scarce, and there are no studies on specific procedures focusing on this topic in Latin America. To assess the clinical characteristics and management of hypersensitivity drug reactions in different Latin American countries. An European Network of Drug Allergy questionnaire survey was implemented in 22 allergy units in 11 Latin American countries to report on consecutive patients who presented with a suspected hypersensitivity drug reaction. Each unit used its own protocols to investigate patients. Included were 868 hypersensitivity drug reactions in 862 patients (71% of adults and elderly patients were women and 51% of children were girls, P = .0001). Children presented with less severe reactions than adults and elderly patients (P < .0001). Urticaria and angioedema accounted for the most frequent clinical presentations (71%), whereas anaphylaxis was present in 27.3% of cases. There were no deaths reported. Nonsteroidal anti-inflammatory drugs (52.3%), β-lactam antibiotics (13.8%), and other antibiotics (10.1%) were the drugs used most frequently. Skin prick tests (16.7%) and provocation tests (34.2%) were the study procedures most commonly used. A large proportion of patients were treated in the emergency department (62%) with antihistamines (68%) and/or corticosteroids (53%). Only 22.8% of patients presenting with anaphylaxis received epinephrine. Nonsteroidal anti-inflammatory drugs and antibiotics were the drugs used in at least 75% of patients. More than half the reactions were treated in the emergency department, whereas epinephrine was administered in fewer than 25% of patients with anaphylaxis. Dissemination of guidelines for anaphylaxis among primary and emergency department physicians should be encouraged. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  20. Hypersensitivity reactions to non-steroidal anti-inflammatory drugs.

    PubMed

    Cornejo-Garcia, José Antonio; Blanca-López, Natalia; Doña, Inmaculada; Andreu, Inmaculada; Agúndez, José A G; Carballo, Miguel; Blanca, Miguel; Canto, María Gabriela

    2009-11-01

    NSAIDs are the most important group of drugs involved in hypersensitivity drug reactions, and include heterogeneous compounds with very different chemical structures. These reactions can be IgE dependent (immediate reactions), T cell-mediated (non-immediate), or induced by a non-specific immunological mechanism related with the blocking of the COX-1 enzyme and the shunting to the lipooxygenase pathway (cross-intolerant reactions). Cutaneous symptoms are the most frequent, with ibuprofen, naproxen and diclofenac being common culprit drugs worldwide, although others can be involved because patterns of consumption and exposure rates vary between countries. A very important proportion of immunological reactions are immediate, with urticaria and anaphylaxis being the typical clinical manifestations. Non-immediate reactions comprise a number of heterogeneous entities ranging from mild exanthema to severe TEN or DRESS syndrome, as well as organ-specific reactions such as hepatitis or pneumonitis. Cross-intolerant reactions appear to non-chemically related drugs, and involve respiratory airways, skin or both. In vivo diagnostic tests are based on the capacity of the skin to respond to the culprit drug, but their sensitivity is in many instances rather low. The approach for in vitro testing consists of either detecting specific IgE antibodies or studying the proliferation of T lymphocytes toward the eliciting drug. No appropriate tests are yet available for the in vitro validation of cross-intolerance reactions, although techniques based on the stimulation of basophils have been proposed. Based on these findings, the diagnostic approach is often based on the controlled administration of the drug to assess tolerance. In this work we review current knowledge on hypersensitivity reactions to NSAIDs, including diagnostic approach and genetic studies.

  1. Cutaneous hypersensitivity reactions to freshwater cyanobacteria – human volunteer studies

    PubMed Central

    Stewart, Ian; Robertson, Ivan M; Webb, Penelope M; Schluter, Philip J; Shaw, Glen R

    2006-01-01

    Background Pruritic skin rashes associated with exposure to freshwater cyanobacteria are infrequently reported in the medical and scientific literature, mostly as anecdotal and case reports. Diagnostic dermatological investigations in humans are also infrequently described. We sought to conduct a pilot volunteer study to explore the potential for cyanobacteria to elicit hypersensitivity reactions. Methods A consecutive series of adult patients presenting for diagnostic skin patch testing at a hospital outpatient clinic were invited to participate. A convenience sample of volunteers matched for age and sex was also enrolled. Patches containing aqueous suspensions of various cyanobacteria at three concentrations were applied for 48 hours; dermatological assessment was made 48 hours and 96 hours after application. Results 20 outpatients and 19 reference subjects were recruited into the study. A single outpatient produced unequivocal reactions to several cyanobacteria suspensions; this subject was also the only one of the outpatient group with a diagnosis of atopic dermatitis. No subjects in the reference group developed clinically detectable skin reactions to cyanobacteria. Conclusion This preliminary clinical study demonstrates that hypersensitivity reactions to cyanobacteria appear to be infrequent in both the general and dermatological outpatient populations. As cyanobacteria are widely distributed in aquatic environments, a better appreciation of risk factors, particularly with respect to allergic predisposition, may help to refine health advice given to people engaging in recreational activities where nuisance cyanobacteria are a problem. PMID:16584576

  2. Methotrexate Hypersensitivity Reactions in Pediatrics: Evaluation and Management

    PubMed Central

    Dilley, Meredith A.; Lee, Joyce P.; Broyles, Ana Dioun

    2017-01-01

    Reports of hypersensitivity reactions (HSRs) to MTX are limited to single case studies. We retrospectively reviewed HSRs to MTX during a 12-year period in our tertiary care pediatric center. Seven patients were evaluated for HSRs to MTX. Skin testing was positive in one of the 4 patients tested. One patient underwent successful graded challenge to MTX. Seventeen desensitizations to MTX were successfully performed in the other 6 patients. Skin testing, graded challenge, and desensitization were safe and effective procedures in the evaluation and management of patients with HSRs to MTX in our pediatric population. PMID:27786403

  3. Biophoton distress flares signal the onset of the hypersensitive reaction.

    PubMed

    Mansfield, John W

    2005-07-01

    Detection of biophoton emission, a natural bioluminescence, has emerged as a non-destructive method to mark the onset of the hypersensitive resistance reaction in Arabidopsis, bean and tomato. Rapid biophoton emission in Arabidopsis requires an intact R-gene signalling network and increased levels of cytosolic calcium and nitric oxide. The burst of biophotons precedes macroscopic symptoms by several hours and its timing is characteristic for specific gene-for-gene interactions. The ability to monitor biophoton emission from whole plants in real time should allow detailed dissection of plant defence responses.

  4. Genotyping for Severe Drug Hypersensitivity

    PubMed Central

    Karlin, Eric; Phillips, Elizabeth

    2014-01-01

    Over the past decade, there have been significant advances in our understanding of the immunopathogenesis and pharmacogenomics of severe immunologically-mediated adverse drug reactions. Such T-cell-mediated adverse drug reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced liver disease (DILI) and other drug hypersensitivity syndromes have more recently been shown to be mediated through interactions with various class I and II HLA alleles. Key examples have included the associations of HLA-B*15:02 and carbamazepine induced SJS/TEN in Southeast Asian populations and HLA-B*57:01 and abacavir hypersensitivity. HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation. Ultimately, our increased understanding of the interaction between drugs and the MHC could be used to inform drug design and drive pre-clinical toxicity programs to improve drug safety. PMID:24429903

  5. Abacavir-induced fulminant hepatic failure in a HIV/HCV co-infected patient

    PubMed Central

    Haas, Christopher; Ziccardi, Mary Rodriguez; Borgman, Jody

    2015-01-01

    Abacavir hypersensitivity is a rare, yet significant adverse reaction that results in a spectrum of physical and laboratory abnormalities, and has been postulated to stem from a variety of aetiological factors. The major histocompatibility complex haplotype human leucocyte antigen (HLA)-B5701 is a significant risk factor in development of hypersensitivity reactions, yet only 55% of HLA-B5701+ individuals develop such reactions, suggesting a multifactorial aetiology. Nevertheless, prospective screening and avoidance of abacavir in these patients has limited adverse events. Within this spectrum of adverse events, abacavir-induced liver toxicity is exceedingly rare and reported events have ranged from mild elevations of aminotransferases to fulminant hepatic failure. We report the case of a 50-year-old Caucasian woman with a history significant for HIV, hepatitis C virus and a HLA-B5701+ status, transferred to our emergency department in a hypotensive state and found to have acute liver failure, acute renal failure and significant rhabdomyolysis following a change of highly active antiretroviral therapy regimen. PMID:26670894

  6. Abacavir-induced fulminant hepatic failure in a HIV/HCV co-infected patient.

    PubMed

    Haas, Christopher; Ziccardi, Mary Rodriguez; Borgman, Jody

    2015-12-15

    Abacavir hypersensitivity is a rare, yet significant adverse reaction that results in a spectrum of physical and laboratory abnormalities, and has been postulated to stem from a variety of aetiological factors. The major histocompatibility complex haplotype human leucocyte antigen (HLA)-B5701 is a significant risk factor in development of hypersensitivity reactions, yet only 55% of HLA-B5701+ individuals develop such reactions, suggesting a multifactorial aetiology. Nevertheless, prospective screening and avoidance of abacavir in these patients has limited adverse events. Within this spectrum of adverse events, abacavir-induced liver toxicity is exceedingly rare and reported events have ranged from mild elevations of aminotransferases to fulminant hepatic failure. We report the case of a 50-year-old Caucasian woman with a history significant for HIV, hepatitis C virus and a HLA-B5701+ status, transferred to our emergency department in a hypotensive state and found to have acute liver failure, acute renal failure and significant rhabdomyolysis following a change of highly active antiretroviral therapy regimen. 2015 BMJ Publishing Group Ltd.

  7. Hypersensitive Reaction to Tattoos: A Growing Menace in Rural India

    PubMed Central

    Shashikumar, B M; Harish, M R; Shwetha, B; Kavya, M; Deepadarshan, K; Phani, H N

    2017-01-01

    Background: Increased enthusiasm toward newer fashion trends among rural India along with the lack of government regulation has led to increased tattoo reactions. Objective: The objective of this study is to describe various clinical manifestations of hypersensitive reactions to tattoo ink reported at a tertiary care hospital in Mandya district. Materials and Methods: An observational study was carried out over a period of 1 year from June 2014 to May 2015 at Mandya Institute of Medical Sciences, Mandya. All the patients reporting with allergic reaction due to tattooing were included in the present study after obtaining informed consent. Transient acute inflammatory reaction, infections, and skin diseases localized on tattooed area were excluded from this study. A detailed history regarding the onset, duration and color used for tattooing were collected. Cutaneous examination and biopsy was to done to know the type of reaction. Results: Fifty cutaneous allergic reactions were diagnosed among 39 patients. Mean age of subjects was 22 years and mean duration before the appearance of lesion was 7 months. Common colors associated with reactions were red (53.9%), black (33.3%), green (5.1%), and multicolor (7.7%). Itching was the predominant symptom. Skin lesions mainly consisted of lichenoid papules and plaques, eczematous lesions, and verrucous lesions. Lichenoid histopathology reaction was the most common tissue allergic reaction. Conclusion: Increasing popularity of tattooing among young people has predisposed to parallel increase in adverse reactions. Red pigment is most common cause of allergic reaction in the present study, and lichenoid reaction is the most common reaction. PMID:28584372

  8. Safety analysis of Ziagen® (abacavir sulfate) in postmarketing surveillance in Japan†

    PubMed Central

    Kurita, Tomoko; Kitaichi, Tomomi; Nagao, Takako; Miura, Toshiyuki; Kitazono, Yoshifumi

    2014-01-01

    Purpose Abacavir is a nucleoside reverse transcriptase inhibitor indicated for human immunodeficiency virus (HIV) infection. In Japan, Ziagen® (300-mg abacavir sulfate) has been marketed since 1999. To obtain safety data on Ziagen, a mandatory postmarketing surveillance was conducted between September 1999 and September 2009. Methods A joint survey [HIV-related Drug Surveys (HRD)] has been conducted involving manufacturers of drugs for HIV treatment in Japan. Safety data from total 643 cases (1345.7 person-years) registered to the HRD surveys and received Ziagen were obtained. Adverse drug reaction (ADR) was defined as adverse event of which association with abacavir could not be “ruled out.” Results It was found that the overall frequency of ADR was 47.6% (306/643); the common ADRs were “hyperlipidemia,” “nausea,” “increased γ-glutamyltransferase level,” “increased blood triglycerides,” “abnormal hepatic function,” and so on. Serious adverse events were reported in 65 subjects; however, none of the three fatal cases were clearly associated with Ziagen use. The survey-defined hypersensitivity has been infrequently reported in 15 subjects (2.3%). Although some studies had indicated of the association between abacavir and myocardial infarction, no ischemic heart diseases were reported in the present survey. Two of the three pregnant cases delivered normal neonates (one induced abortion). Conclusions During the mandatory postmarketing survey of Ziagen, there were no cases of ischemic heart diseases, and the incidence of hypersensitivity was considerably low. These indicated that abacavir can be safely used in Japanese HIV+ population. However, the safety profile of Ziagen should be continued to be monitored through pharmacovigilance. PMID:24585486

  9. Safety analysis of Ziagen® (abacavir sulfate) in postmarketing surveillance in Japan.

    PubMed

    Kurita, Tomoko; Kitaichi, Tomomi; Nagao, Takako; Miura, Toshiyuki; Kitazono, Yoshifumi

    2014-04-01

    Abacavir is a nucleoside reverse transcriptase inhibitor indicated for human immunodeficiency virus (HIV) infection. In Japan, Ziagen® (300-mg abacavir sulfate) has been marketed since 1999. To obtain safety data on Ziagen, a mandatory postmarketing surveillance was conducted between September 1999 and September 2009. A joint survey [HIV-related Drug Surveys (HRD)] has been conducted involving manufacturers of drugs for HIV treatment in Japan. Safety data from total 643 cases (1345.7 person-years) registered to the HRD surveys and received Ziagen were obtained. Adverse drug reaction (ADR) was defined as adverse event of which association with abacavir could not be "ruled out." It was found that the overall frequency of ADR was 47.6% (306/643); the common ADRs were "hyperlipidemia," "nausea," "increased γ-glutamyltransferase level," "increased blood triglycerides," "abnormal hepatic function," and so on. Serious adverse events were reported in 65 subjects; however, none of the three fatal cases were clearly associated with Ziagen use. The survey-defined hypersensitivity has been infrequently reported in 15 subjects (2.3%). Although some studies had indicated of the association between abacavir and myocardial infarction, no ischemic heart diseases were reported in the present survey. Two of the three pregnant cases delivered normal neonates (one induced abortion). During the mandatory postmarketing survey of Ziagen, there were no cases of ischemic heart diseases, and the incidence of hypersensitivity was considerably low. These indicated that abacavir can be safely used in Japanese HIV+ population. However, the safety profile of Ziagen should be continued to be monitored through pharmacovigilance. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

  10. Abacavir, Lamivudine, and Zidovudine

    MedlinePlus

    ... combination of abacavir, lamivudine and zidovudine does not cure HIV, it may decrease your chance of developing acquired ... doctor.Abacavir, lamivudine, and zidovudine helps to control HIV infection but does not cure it. Continue to take abacavir, lamivudine, and zidovudine ...

  11. Safety and Efficacy of Ziagen (Abacavir Sulfate) in HIV-Infected Korean Patients.

    PubMed

    Ann, Heawon; Kim, Ki Hyon; Choi, Hyun Young; Chang, Hyun Ha; Han, Sang Hoon; Kim, Kye Hyung; Lee, Jin Soo; Kim, Yeon Sook; Park, Kyung Hwa; Kim, Young Keun; Sohn, Jang Wook; Yun, Na Ra; Lee, Chang Seop; Choi, Young Wha; Lee, Yil Seob; Kim, Shin Woo

    2017-09-01

    Abacavir is a widely-used nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) infection. Mandatory postmarketing surveillance was conducted in Korea to monitor the safety and evaluate the effectiveness of Ziagen® (abacavir sulfate 300 mg; ViiV Healthcare, Middlesex, UK). An open-label, multi-center, non-interventional postmarketing surveillance study was conducted from June 2010 to June 2016 to monitor the safety and effectiveness of Ziagen across 12 hospitals in Korea. Subjects older than 18 years taking Ziagen according to prescribing information were enrolled. The primary outcome was defined as the occurrence of any adverse events after Ziagen administration. Secondary outcomes included the occurrence of adverse drug reactions, occurrence of serious adverse events, and effectiveness of Ziagen administration. A total of 669 patients were enrolled in this study, with a total observation period of 1047.8 person-years. Of these, 90.7% of patients were male. The mean age of patients was 45.8±11.9 years. One-hundred ninety-six (29.3%) patients reported 315 adverse events, and four patients reported seven serious adverse events, without any fatal events. There was one potential case of an abacavir hypersensitivity reaction. Among the 97 adverse drug reactions that were reported from 75 patients, the most frequent adverse drug reactions included diarrhea (12 events), dyspepsia (10 events), and rash (9 events). No ischemic heart disease was observed. In the effectiveness analysis, 91% of patients achieved HIV-1 RNA under 50 copies/mL after 24 months of observation with abacavir administration. Our data showed the safety and effectiveness of Ziagen in a real-world setting. During the study period, Ziagen was well-tolerated, with one incident of a clinically suspected abacavir hypersensitivity reaction. The postmarketing surveillance of Ziagen did not highlight any new safety information. These data may be helpful in

  12. Successful desensitization protocol for hypersensitivity reaction probably caused by dabrafenib in a patient with metastatic melanoma.

    PubMed

    Bar-Sela, Gil; Abu-Amna, Mahmoud; Hadad, Salim; Haim, Nissim; Shahar, Eduardo

    2015-09-01

    Vemurafenib and dabrafenib are both orally bioavailable small molecule agents that block mitogen activated protein kinase signalling in patients with melanoma and BRAF(V600E) mutation. Generalized hypersensitivity reactions to vemurafenib or dabrafenib have not been described. Continuing vemurafenib or dabrafenib therapy despite hypersensitivity reaction is especially important in patients with melanoma and BRAF(V600E) mutation, in whom this mutation plays a critical role in tumour growth. Desensitization protocols to overcome hypersensitivity reactions by gradual reintroduction of small amounts of the offending drug up to full therapeutic doses are available for many anti-cancer agents, including vemurafenib but, to the best of our knowledge, have not been reported for dabrafenib. We describe a patient with metastatic melanoma who developed Type I hypersensitivity reaction to vemurafenib and to subsequent treatment with dabrafenib, and who was successfully treated by drug desensitization which allowed safe prolonged continuation of dabrafenib. The development of hypersensitivity reactions for both dabrafenib and vemurafinib in the current case could be because these drugs have a similar chemical structure and cause a cross-reactivity. However, hypersensitivity reaction to a non-medicinal ingredient shared by the two drugs is also possible. Oral desensitization appears to be an option for patients with hypersensitivity Type I to dabrafenib. This approach may permit clinicians to safely administer dabrafenib to patients who experience hypersensitivity reactions to this life-prolonging medication. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Immediate-type hypersensitivity reaction to Mannitol as drug excipient (E421): a case report.

    PubMed

    Calogiuri, G F; Muratore, L; Nettis, E; Casto, A M; Di Leo, E; Vacca, A

    2015-05-01

    Allergic reactions to mannitol have been reported rarely, despite its widespread use as a drug and as a food excipient. This is the first case report in which oral mannitol induces an immediate type hypersensitivity as a drug excipient, in a 42 year old man affected by rhinitis to olive tree pollen. Unusual and undervalued risk factors for mannitol hypersensitivity are examined.

  14. Virological efficacy of abacavir: systematic review and meta-analysis.

    PubMed

    Cruciani, Mario; Mengoli, Carlo; Malena, Marina; Serpelloni, Giovanni; Parisi, Saverio G; Moyle, Graeme; Bosco, Oliviero

    2014-12-01

    The efficacy of abacavir/lamivudine has been reported to be inferior to tenofovir/emtricitabine. Several randomized clinical trials (RCTs) investigated the effectiveness and safety of abacavir/lamivudine and tenofovir/emtricitabine combined antiretroviral treatment (cART) and we have reviewed the available evidence. Systematic review and meta-analysis of RCTs using standard Cochrane Collaboration methodologies. We calculated risk ratios (RRs) with 95% CIs. The primary outcome was the rate of patients with viral load (VL) below the pre-defined cut-off at 48 weeks and/or at 96 weeks. Where available, results were analysed according to VL screening levels (<100,000 or >100,000 copies/mL) with conventional meta-analytical pooling by subgroups and meta-regression. Meta-analytical pooling of RCTs with a direct comparison of abacavir/lamivudine and tenofovir/emtricitabine according to baseline VL at 48 weeks (six trials, 4118 patients) showed that the proportions of subjects with VL <50 copies/mL were similar in the overall comparison (RR 0.98; 95% CI 0.94-1.03), in the low baseline VL strata (RR 1.01; 95% CI 0.99-1.03) and in the high baseline VL strata (RR 0.96; 95% CI 0.90-1.03). Meta-regression analysis at 48 weeks confirms the results of subgroup analysis. Similar virological results were found at 96 weeks (four trials, 2003 patients). Differences in the occurrence of adverse events requiring discontinuation of treatment favoured tenofovir recipients (RR 1.26; 95% CI 0.99-1.61), but this difference, mostly related to suspected abacavir hypersensitivity reaction, was not statistically significant. Our cumulative, cross-sectional data suggest a similar virological efficacy of abacavir/lamivudine and tenofovir/emtricitabine regardless of the baseline VL. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Drug Hypersensitivity: Pharmacogenetics and Clinical Syndromes

    PubMed Central

    Phillips, Elizabeth J.; Chung, Wen-Hung; Mockenhaupt, Maja; Roujeau, Jean-Claude; Mallal, Simon A.

    2011-01-01

    Severe cutaneous adverse reactions (SCARs) include syndromes such as drug reaction, eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) and Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN). An important advance has been the discovery of associations between HLA alleles and many of these syndromes including abacavir hypersensitivity reaction, allopurinol DRESS/DIHS and SJS/TEN and SJS/TEN associated with aromatic amine anticonvulsants. These HLA associations have created the promise for prevention through screening and have additionally shed further light on the immunopathogenesis of SCARs. The roll-out of HLA-B*5701 into routine clinical practice as a genetic screening test to prevent abacavir hypersensitivity provides a translational roadmap for other drugs. Numerous hurdles exist in the widespread translation of several other drugs such as carbamazepine where the positive predictive value of HLA-B*1502 is low and the negative predictive value of HLA-B*1502 for SJS/TEN may not be 100% in all ethnic groups. International collaborative consortia have been formed with the goal of developing phenotype standardization and undertaking HLA and genome-wide analyses in diverse populations with these syndromes. PMID:21354501

  16. An unexpected cause of an acute hypersensitivity reaction during recovery from anaesthesia.

    PubMed

    Thong, C L; Lambros, M; Stewart, M G; Kam, P C A

    2005-08-01

    Acute hypersensitivity reactions to chlorhexidine in the operating room are probably more likely to occur during the early phases of anaesthesia because chlorhexidine is often used for cleaning the surgical field or during placement of indwelling catheters. We report a case of an acute hypersensitivity reaction that occurred in the post anaesthetic care unit. Subsequent skin testing suggested sensitivity to chlorhexidine, which had been applied over the vaginal mucosa at the end of surgery. Relevant issues in the investigation of acute hypersensitivity reactions in the post anaesthetic period are discussed.

  17. Utility of Risk Stratification for Paclitaxel Hypersensitivity Reactions.

    PubMed

    Otani, Iris M; Lax, Timothy; Long, Aidan A; Slawski, Benjamin R; Camargo, Carlos A; Banerji, Aleena

    2017-10-03

    Hypersensitivity reactions (HSRs) are a common impediment to paclitaxel therapy. Management strategies to guide care after a paclitaxel-induced HSR are needed. The objective was to evaluate the utility and safety of risk stratification on the basis of severity of the initial HSR. A risk stratification pathway was developed on the basis of a retrospective review of the management and outcome of 130 patients with paclitaxel-induced HSRs at Massachusetts General Hospital. This pathway was then studied prospectively in patients referred to Allergy/Immunology with paclitaxel-induced HSRs. The study population (n = 35) had a mean age of 56.1 ± 12 years and most were women (n = 33 [94%]). All 5 patients (15%) with grade 1 initial HSRs were successfully reexposed to paclitaxel, 1 patient at the standard infusion rate and 4 patients at 50% of the standard infusion rate. Thirty patients (85%) with grade 2 to 4 initial HSRs underwent initial paclitaxel desensitization based on the risk stratification pathway. No patients developed severe HSRs using the pathway. Eleven (31%) patients had HSRs that were mild to moderate in nature (grade 1, n = 4 [11%]; grade 2, n = 6 [17%]; grade 3, n = 1 [3%]) during their first desensitization. Sixteen (46%) of the 35 patients safely returned to the outpatient infusion setting for paclitaxel treatment at 50% of the standard infusion rate. Seven (20%) discontinued paclitaxel before the completion of the risk stratification pathway because of disease progression, completion of therapy, or death. A management strategy using the initial HSR severity for risk stratification allowed patients to receive paclitaxel safely. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. Hypersensitivity reactions to vaccine constituents: a case series and review of the literature.

    PubMed

    Leventhal, Jonathan S; Berger, Emily M; Brauer, Jeremy A; Cohen, David E

    2012-01-01

    Vaccines are composed of immunogens, preservatives, adjuvants, antibiotics, and manufacturing by-products. Components of vaccines may rarely elicit adverse reactions in susceptible individuals, thus raising concerns regarding vaccine safety. In this report, we add to the medical literature 3 cases of cutaneous delayed-type hypersensitivity to the vaccine preservative aluminum. We provide a review of major constituents in vaccines that have elicited immediate-type or delayed-type hypersensitivity reactions and describe their clinical manifestations. We include a table of the Food and Drug Administration-approved vaccines, which lists the quantities of major components including ovalbumin (egg protein), gelatin, aluminum, neomycin, 2-phenoxyethanol, thimerosal, and formaldehyde. Our goals were to inform physicians on the variety of hypersensitivity reactions to common vaccines and to provide information on the choice of vaccines in patients with suspected hypersensitivity.

  19. The Effectiveness of Automatic Recommending System for Premedication in Reducing Recurrent Radiocontrast Media Hypersensitivity Reactions

    PubMed Central

    Bae, Yun-Jeong; Hwang, Ye Won; Yoon, Sun-young; Kim, Sujeong; Lee, Taehoon; Lee, Yoon Su; Kwon, Hyouk-Soo; Cho, You Sook; Shin, Myung Jin; Moon, Hee-Bom; Kim, Tae-Bum

    2013-01-01

    Background Non-ionic radiocontrast media (RCM) is rarely associated with hypersensitivity reactions. Premedication of patients who reacted previously to RCM with systemic corticosteroids and/or antihistamines can help reduce recurrent hypersensitivity reactions. However, premedication is still not prescribed in many cases for various reasons. This study aimed to determine the effectiveness of our novel RCM hypersensitivity surveillance and automatic recommending system for premedication. Methods and Results Hospitalized patients with a history of RCM hypersensitivity were identified in an electronic medical record system that included a mandatory reporting system for past adverse drug reactions. In 2009, a novel automatic prescription system was added that classified index RCM reactions by severity and dispensed appropriate corticosteroid and/or antihistamine pretreatment prior to new RCM exposures. The data from 12 months under the previous system and 12 months under the current system were compared. The two systems had similar overall premedication rates (91% and 95%) but the current system was associated with a significantly higher corticosteroid premedication rate (65% vs. 14%), which significantly reduced the breakthrough reaction rate (6.7% vs. 15.2%). The current system was also associated with increased corticosteroid and antihistamine premedication of patients with a mild index reaction (61% vs. 7%) and a reduction in their breakthrough reaction rate (6% vs. 15%). Conclusions Premedication with corticosteroid and/or antihistamine, which was increased by our novel automatic prescription system, significantly reduced breakthrough reactions in patients with a history of RCM hypersensitivity. PMID:23840391

  20. Involvement of Histamine and RhoA/ROCK in Penicillin Immediate Hypersensitivity Reactions.

    PubMed

    Han, Jiayin; Yi, Yan; Li, Chunying; Zhang, Yushi; Wang, Lianmei; Zhao, Yong; Pan, Chen; Liang, Aihua

    2016-09-13

    The mechanism of penicillin immediate hypersensitivity reactions has not been completely elucidated. These reactions are generally considered to be mediated by IgE, but penicillin-specific IgE could not be detected in most cases. This study demonstrated that penicillin was able to cause vascular hyperpermeability in a mouse model mimicking clinical symptoms of penicillin immediate hypersensitivity reactions. The first exposure to penicillin also induced immediate edema and exudative reactions in ears and lungs of mice in a dose-dependent manner. Vasodilation was noted in microvessels in ears. These reactions were unlikely to be immune-mediated reactions, because no penicillin-specific IgE was produced. Furthermore, penicillin treatment directly elicited rapid histamine release. Penicillin also led to F-actin reorganization in human umbilical vein endothelial cells and increased the permeability of the endothelial monolayer. Activation of the RhoA/ROCK signaling pathway was observed in ears and lungs of mice and in endothelial cells after treatment with penicillin. Both an anti-histamine agent and a ROCK inhibitor attenuated penicillin immediate hypersensitivity reactions in mice. This study presents a novel mechanism of penicillin immediate hypersensitivity reactions and suggests a potential preventive approach against these reactions.

  1. Involvement of Histamine and RhoA/ROCK in Penicillin Immediate Hypersensitivity Reactions

    PubMed Central

    Han, Jiayin; Yi, Yan; Li, Chunying; Zhang, Yushi; Wang, Lianmei; Zhao, Yong; Pan, Chen; Liang, Aihua

    2016-01-01

    The mechanism of penicillin immediate hypersensitivity reactions has not been completely elucidated. These reactions are generally considered to be mediated by IgE, but penicillin-specific IgE could not be detected in most cases. This study demonstrated that penicillin was able to cause vascular hyperpermeability in a mouse model mimicking clinical symptoms of penicillin immediate hypersensitivity reactions. The first exposure to penicillin also induced immediate edema and exudative reactions in ears and lungs of mice in a dose-dependent manner. Vasodilation was noted in microvessels in ears. These reactions were unlikely to be immune-mediated reactions, because no penicillin-specific IgE was produced. Furthermore, penicillin treatment directly elicited rapid histamine release. Penicillin also led to F-actin reorganization in human umbilical vein endothelial cells and increased the permeability of the endothelial monolayer. Activation of the RhoA/ROCK signaling pathway was observed in ears and lungs of mice and in endothelial cells after treatment with penicillin. Both an anti-histamine agent and a ROCK inhibitor attenuated penicillin immediate hypersensitivity reactions in mice. This study presents a novel mechanism of penicillin immediate hypersensitivity reactions and suggests a potential preventive approach against these reactions. PMID:27619816

  2. Acute hypersensitivity reactions associated with administration of crotalidae polyvalent immune Fab antivenom.

    PubMed

    Cannon, Robert; Ruha, Anne-Michelle; Kashani, John

    2008-04-01

    Acute hypersensitivity reactions are well known to occur with the administration of the Antivenin (Crotalidae) Polyvalent (Wyeth Laboratories, Marietta, PA). Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV, Protherics, Inc., Brentwood, TN) was introduced in 2001, and early studies reported a hypersensitivity reaction rate up to 19%. We describe the incidence of acute hypersensitivity reactions to FabAV in patients bitten by rattlesnakes. This was a nonconcurrent observational cohort study, with data obtained by chart review of all patients admitted to our service for rattlesnake bites from July 2000 to June 2004. The study was conducted at an urban Level I trauma center and urban children's hospital. All patients treated with FabAV were included. Those who received no antivenom or who were treated with Antivenin (Crotalidae) Polyvalent were excluded. The main outcome variable was whether an acute hypersensitivity reaction developed. Ninety-three patients were included in the review (72 male and 21 female patients). The mean age was 34.5 years (range 16 months to 91 years), and the mean dose of antivenom was 12 vials (range 4 to 32 vials). The incidence of acute hypersensitivity reactions was 5 of 93, or 5.4%. Four patients developed a mild reaction that was easily treated and were able to finish the full course of antivenom. Only 1 patient developed a reaction that prevented further antivenom administration. FabAV appears to be associated with a lower incidence of acute hypersensitivity than initially reported. Most reactions are mild and easily treated and do not preclude further dosing of antivenom.

  3. Risk Factors for Oxaliplatin-Induced Hypersensitivity Reactions in Japanese Patients with Advanced Colorectal Cancer

    PubMed Central

    Seki, Kyoko; Senzaki, Kenzou; Tsuduki, Yasuo; Ioroi, Takeshi; Fujii, Michiko; Yamauchi, Hiroko; Shiraishi, Yukinari; Nakata, Izumi; Nishiguchi, Kohshi; Matsubayashi, Teruhisa; Takakubo, Yoshihide; Okamura, Noboru; Yamamori, Motohiro; Tamura, Takao; Sakaeda, Toshiyuki

    2011-01-01

    Objective: Previously, we suggested that oxaliplatin (L-OHP)-related grade 3/4 hypersensitivity reactions occurred immediately after the initiation, but grade 1/2 reactions did not. This study was conducted to clarify the risk factors for L-OHP-related hypersensitivity reactions. Methods: Clinical data from 108 Japanese patients with colorectal cancer were analyzed, who were treated with L-OHP-containing regimens, FOLFOX4 and/or mFOLFOX6. The risk factors examined included demographic data, preexisting allergies, laboratory test data, treatment regimen, treatment line of therapy, pretreatment with steroids, total number of cycles and cumulative amount of L-OHP. Results: The incidence of grade 1/2 and grade 3/4 hypersensitivity reactions were found at 13.0% (14/108) and 9.3% (10/108), respectively. Female (P=0.037), preexisting allergies (P=0.004) and lower level of lactate dehydrogenase (P=0.003) were risk factors for grade 1/2 hypersensitivity reactions, and higher neutrophil count (P=0.043) and lower monocyte count (P=0.007) were for grade 3/4 reactions. Total number of cycles were larger in the patients with grade 3/4 reactions than those without reactions (P=0.049). Conclusions: Further extensive examination with a large number of patients is needed to establish a patient management strategy. PMID:21448307

  4. Desensitization in delayed drug hypersensitivity reactions -- an EAACI position paper of the Drug Allergy Interest Group.

    PubMed

    Scherer, K; Brockow, K; Aberer, W; Gooi, J H C; Demoly, P; Romano, A; Schnyder, B; Whitaker, P; Cernadas, J S R; Bircher, A J

    2013-07-01

    Drug hypersensitivity may deprive patients of drug therapy, and occasionally no effective alternative treatment is available. Successful desensitization has been well documented in delayed drug hypersensitivity reactions. In certain situations, such as sulfonamide hypersensitivity in HIV-positive patients or hypersensitivity to antibiotics in patients with cystic fibrosis, published success rates reach 80%, and this procedure appears helpful for the patient management. A state of clinical tolerance may be achieved by the administration of increasing doses of the previously offending drug. However, in most cases, a pre-existent sensitization has not been proven by positive skin tests. Successful re-administration may have occurred in nonsensitized patients. A better understanding of the underlying mechanisms of desensitization is needed. Currently, desensitization in delayed hypersensitivity reactions is restricted to mild, uncomplicated exanthems and fixed drug eruptions. The published success rates vary depending on clinical manifestations, drugs, and applied protocols. Slower protocols tend to be more effective than rush protocols; however, underreporting of unsuccessful procedures is very probable. The decision to desensitize a patient must always be made on an individual basis, balancing risks and benefits. This paper reviews the literature and presents the expert experience of the Drug Hypersensitivity Interest Group of the European Academy of Allergy and Clinical Immunology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Carboplatin Hypersensitivity Reactions in Pediatric Low Grade Glioma Are Protocol Specific and Desensitization Shows Poor Efficacy.

    PubMed

    Dodgshun, Andrew J; Hansford, Jordan R; Cole, Theresa; Choo, Sharon; Sullivan, Michael J

    2016-01-01

    The use of carboplatin for the treatment of pediatric low grade gliomas (PLGG) is often limited by the development of carboplatin hypersensitivity. Reported rates of carboplatin hypersensitivity reactions vary between 6% and 32% in these patients. Here we report the frequency of carboplatin hypersensitivity reactions depending on the treatment regimen used, and outcomes of carboplatin desensitization. The records of all patients in a single institution who were treated with carboplatin for PLGG were accessed and all patients receiving more than one dose of carboplatin are reported. Thirty four patients with PLGG were treated with carboplatin according to one of the two different regimens. Carboplatin hypersensitivity was documented in 47% of patients, but the frequency differed by treatment protocol. Those patients treated with 4-weekly single agent carboplatin had carboplatin allergy in 8% of cases whereas 68% of those treated with combined carboplatin and vincristine (every three weeks, according to the SIOP 2004 low grade glioma protocol) had carboplatin reactions (OR 23.6, P < 0.01). Desensitization was only successful in two out of 10 patients in whom it was attempted. Hypersensitivity reactions to carboplatin are more common in this cohort than previously reported and rates are protocol-dependent. Desensitization showed limited effectiveness in this cohort. © 2015 Wiley Periodicals, Inc.

  6. Rice hypersensitive induced reaction protein 1 (OsHIR1) associates with plasma membrane and triggers hypersensitive cell death.

    PubMed

    Zhou, Liang; Cheung, Ming-Yan; Li, Man-Wah; Fu, Yaping; Sun, Zongxiu; Sun, Sai-Ming; Lam, Hon-Ming

    2010-12-30

    In plants, HIR (Hypersensitive Induced Reaction) proteins, members of the PID (Proliferation, Ion and Death) superfamily, have been shown to play a part in the development of spontaneous hypersensitive response lesions in leaves, in reaction to pathogen attacks. The levels of HIR proteins were shown to correlate with localized host cell deaths and defense responses in maize and barley. However, not much was known about the HIR proteins in rice. Since rice is an important cereal crop consumed by more than 50% of the populations in Asia and Africa, it is crucial to understand the mechanisms of disease responses in this plant. We previously identified the rice HIR1 (OsHIR1) as an interacting partner of the OsLRR1 (rice Leucine-Rich Repeat protein 1). Here we show that OsHIR1 triggers hypersensitive cell death and its localization to the plasma membrane is enhanced by OsLRR1. Through electron microscopy studies using wild type rice plants, OsHIR1 was found to mainly localize to the plasma membrane, with a minor portion localized to the tonoplast. Moreover, the plasma membrane localization of OsHIR1 was enhanced in transgenic rice plants overexpressing its interacting protein partner, OsLRR1. Co-localization of OsHIR1 and OsLRR1 to the plasma membrane was confirmed by double-labeling electron microscopy. Pathogen inoculation studies using transgenic Arabidopsis thaliana expressing either OsHIR1 or OsLRR1 showed that both transgenic lines exhibited increased resistance toward the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. However, OsHIR1 transgenic plants produced more extensive spontaneous hypersensitive response lesions and contained lower titers of the invading pathogen, when compared to OsLRR1 transgenic plants. The OsHIR1 protein is mainly localized to the plasma membrane, and its subcellular localization in that compartment is enhanced by OsLRR1. The expression of OsHIR1 may sensitize the plant so that it is more prone to HR and hence can react more

  7. Abacavir, Dolutegravir, and Lamivudine

    MedlinePlus

    ... If you have HCV and are taking interferon alfa with or without ribavirin (Copegus, Rebetol, Ribasphere) and ... are taking abacavir, dolutegravir, and lamivudine and interferon alfa with or without ribavirin, tell your doctor if ...

  8. Common allergies do not influence the prevalence of cutaneous hypersensitivity reactions to antiepileptic drugs.

    PubMed

    Bosak, Magdalena; Porębski, Grzegorz; Słowik, Agnieszka; Turaj, Wojciech

    2017-09-01

    The aim of the study was to establish whether the presence of common allergies increases the risk of drug-related hypersensitivity reactions among patients with epilepsy treated with antiepileptic drugs (AEDs). We studied 753 patients with epilepsy seen in tertiary outpatient epilepsy clinic. We obtained data related to epilepsy type, past and ongoing treatment with AEDs, occurrence of maculopapular exanthema or more serious cutaneous adverse reactions (Stevens-Johnson syndrome - SJS) and their characteristics. We noted an occurrence of allergic reactions unrelated to treatment with AED, including rash unrelated to AED, bronchial asthma, persistent or seasonal allergic rhinitis, atopic dermatitis, rash after specific food and other allergic reactions. There were 61 cases of AED-related cutaneous hypersensitivity reaction (including 3 cases of SJS) noted in association with 2319 exposures to AEDs (2.63%) among 55 out of 753 patients (7.3%). Cutaneous hypersensitivity reaction to AED was most commonly noted after lamotrigine (12.1%), carbamazepine (5.4%) and oxcarbazepine (4.1%). Prevalence of allergic reactions unrelated to AED was similar between patients with and without AED-related cutaneous hypersensitivity reaction (rash unrelated to AED: 16.4% vs. 10.2%; bronchial asthma: 1.8% vs. 0.1%; persistent allergic rhinitis: 7.3% vs. 10.2%; seasonal allergic rhinitis: 7.3% vs. 11.7%; atopic dermatitis: 0 vs. 0.7%; rash after specific food: 5.4% vs. 6.4%; other allergic reactions: 5.4% vs. 5.2%, respectively; P>0.1 for each difference). Presence of common allergies is not a significant risk factor for AED-related cutaneous hypersensitivity reaction among patients with epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Immediate hypersensitivity reaction following liposomal amphotericin-B (AmBisome) infusion

    PubMed Central

    Nath, Proggananda; Harada, Michiyo; Sarkar, Santana; Selim, Shahjada; Maude, Richard J; Noiri, Eisei; Faiz, Abul

    2014-01-01

    Liposomal amphotericin-B (AmBisome) is now becoming first choice for the treatment of visceral leishmaniasis (kala-azar) patients due to high efficacy and less toxicity. The reported incidence of hypersensitivity reactions to liposomal amphotericin-B (AmBisome), especially during therapy, is very rare. We report two patients with kala-azar: one developed breathing difficulties and hypotension followed by shock and the other had facial angioedema with chest tightness during treatment. Both patients were managed with immediate action of injection: adrenaline, diphenhydramine and hydrocortisone. In our experience, AmBisome can cause severe hypersensitivity reactions that warrant proper support and close supervision. PMID:25139411

  10. Current use of Australian snake antivenoms and frequency of immediate-type hypersensitivity reactions and anaphylaxis.

    PubMed

    Isbister, Geoffrey K; Brown, Simon G; MacDonald, Ellen; White, Julian; Currie, Bart J

    2008-04-21

    To investigate current use of Australian snake antivenoms and the frequency and severity of immediate-type hypersensitivity reactions. Nested prospective cohort study as part of the Australian Snakebite Project. Patients receiving snake antivenom in Australian hospitals between 1 January 2002 and 30 November 2007. The use of CSL Limited antivenom; frequency and severity of hypersensitivity reactions to antivenom; premedication and treatment of these reactions. Snake antivenom was administered to 195 patients, mostly for venom-induced consumption coagulopathy (145 patients, 74%), followed by non-specific systemic effects (12%), neurotoxicity (5%) and myotoxicity (4%). Antivenom was given to nine patients (5%) without evidence of envenoming or who were bitten by a species of snake for which antivenom is not required. The commonest antivenoms used were brown snake (46%), tiger snake (30%) and polyvalent (11%). The median dose was four vials (interquartile range, 2-5 vials), and 24 patients received two different types of antivenom. Immediate-type hypersensitivity reactions occurred in 48 patients (25%); 21 satisfied our definition of anaphylaxis, with 11 moderate and 10 severe cases, including nine in which patients were hypotensive. The remaining 27 reactions were mild (skin only). Adrenaline was used in 26 cases with good effect. The frequency of reactions to tiger snake (41%) and polyvalent (41%) antivenoms was higher than that to brown snake antivenom (10%). Hypersensitivity reactions occurred in 11 of 40 patients receiving any form of premedication (28%) and in 2 of 11 given adrenaline for premedication (18%) versus 20 of 86 not receiving premedication (23%). Antivenom was used appropriately, and most commonly for coagulopathy. Hypersensitivity reactions were common, but most were not severe. The discretionary use of premedication was not associated with any reduction in reactions.

  11. Surveillance of contrast-media-induced hypersensitivity reactions using signals from an electronic medical recording system.

    PubMed

    Kim, Min-Hye; Park, Chang-Han; Kim, Duk-In; Kim, Kyung-Mook; Kim, Hui-Kyu; Lim, Kyu-Hyoung; Song, Woo-Jung; Lee, Sang-Min; Kim, Sae-Hoon; Kwon, Hyouk-Soo; Park, Heung-Woo; Yoon, Chang-Jin; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young; Chang, Yoon-Seok

    2012-03-01

    Contrast-media (CM) hypersensitivity is a well-known adverse drug reaction. Surveillance of adverse drug reactions usually depends on spontaneous reports. However, the rate of spontaneous reports is low. Recent progress in information technology enables the electronic search on signals of adverse drug reactions from electronic medical recording (EMR) systems. To analyze the incidence and clinical characteristics of CM hypersensitivity using an EMR-based surveillance system. The surveillance system used signals from standardized terms within the international classification of nursing practice terms that can indicate symptoms of CM hypersensitivity and from the order codes for procedures that used contrast media, antihistamine, and epinephrine. The search strategy was validated by allergists comparing the electronic search strategy versus manually reviewing medical charts over one month. The main study covered for one year period. Detection rate of the electronic search method was 0.9% (7/759), while that of the manual search method was 0.8% (6/759). EMR-based electronic search method was highly efficient: reduced the charts that needed to be reviewed by 96% (28/759). The sensitivity of electronic screening was 66.7%, specificity was 99.6%, and the negative predictive value was 99.7%. CM hypersensitivity reactions were noted in 266 among 12,483 cases (2.1%). Urticaria was the most frequent symptom (74.4%). CT was the most frequent procedure (3.6%) that induced CM hypersensitivity. A surveillance system using EMR may be a useful tool in the study of drug hypersensitivity epidemiology and may be used in an adverse drug reaction alarm system and as a clinical, decision making support system. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. An algorithm for treatment of patients with hypersensitivity reactions after vaccines.

    PubMed

    Wood, Robert A; Berger, Melvin; Dreskin, Stephen C; Setse, Rosanna; Engler, Renata J M; Dekker, Cornelia L; Halsey, Neal A

    2008-09-01

    Concerns about possible allergic reactions to immunizations are raised frequently by both patients/parents and primary care providers. Estimates of true allergic, or immediate hypersensitivity, reactions to routine vaccines range from 1 per 50000 doses for diphtheria-tetanus-pertussis to approximately 1 per 500000 to 1000000 doses for most other vaccines. In a large study from New Zealand, data were collected during a 5-year period on 15 marketed vaccines and revealed an estimated rate of 1 immediate hypersensitivity reaction per 450000 doses of vaccine administered. Another large study, conducted within the Vaccine Safety Datalink, described a range of reaction rates to >7.5 million doses. Depending on the study design and the time after the immunization event, reaction rates varied from 0.65 cases per million doses to 1.53 cases per million doses when additional allergy codes were included. For some vaccines, particularly when allergens such as gelatin are part of the formulation (eg, Japanese encephalitis), higher rates of serious allergic reactions may occur. Although these per-dose estimates suggest that true hypersensitivity reactions are quite rare, the large number of doses that are administered, especially for the commonly used vaccines, makes this a relatively common clinical problem. In this review, we present background information on vaccine hypersensitivity, followed by a detailed algorithm that provides a rational and organized approach for the evaluation and treatment of patients with suspected hypersensitivity. We then include 3 cases of suspected allergic reactions to vaccines that have been referred to the Clinical Immunization Safety Assessment network to demonstrate the practical application of the algorithm.

  13. Leukemoid reaction secondary to hypersensitivity syndrome to phenobarbital: a case report.

    PubMed

    Zeng, Qinghai; Wu, Yuanqiang; Zhan, Yi; Tang, Ling; Zhou, Yangmei; Yin, Jun; Fan, Fan; Zhang, Guiying; Lu, Qianjin; Xiao, Rong

    2013-01-01

    The most important adverse effects of phenobarbital, an anticonvulsant drug, are behavior and cognitive alterations. Hypersensitivity syndrome caused by phenobarbital presenting with a leukemoid reaction is a rare side effect, which is rarely ever reported and needs to be known. We report on a 27-year-old Chinese woman who experienced hypersensitivity syndrome three weeks after the initiation of phenobarbital. The patient developed fever, skin rash, face swelling, lymphadenopathy, myalgia, hepatitis, eosinophilia, atypical lymphocytes and leukocytosis. Along with the pathological progress of the disease, the patient noticed a gradual exacerbation of her symptoms. And the highest leukocyte count was up to 127.2 x 10(9)/L. After discontinuing of phenobarbital and administration of methylprednisolone combined with the intravenous immunoglobulin shock therapy, all initial symptoms improved and the leukocyte count normalized. This case is reported because of its rarity of the leukemoid reaction secondary to hypersensitivity syndrome to phenobarbital.

  14. HLA-A★3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans

    PubMed Central

    McCormack, Mark; Alfirevic, Ana; Bourgeois, Stephane; Farrell, John J.; Kasperavičiūtė, Dalia; Carrington, Mary; Sills, Graeme J.; Marson, Tony; Jia, Xiaoming; de Bakker, Paul I.W.; Chinthapalli, Krishna; Molokhia, Mariam; Johnson, Michael R.; O’Connor, Gerard D.; Chaila, Elijah; Alhusaini, Saud; Shianna, Kevin V.; Radtke, Rodney A.; Heinzen, Erin L.; Walley, Nicole; Pandolfo, Massimo; Pichler, Werner; Park, B. Kevin; Depondt, Chantal; Sisodiya, Sanjay M.; Goldstein, David B.; Deloukas, Panos; Delanty, Norman; Cavalleri, Gianpiero L.; Pirmohamed, Munir

    2011-01-01

    BACKGROUND Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B★1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS–TEN) in the Han Chinese and other Asian populations but not in European populations. METHODS We performed a genomewide association study of samples obtained from 22 subjects with carbamazepine-induced hypersensitivity syndrome, 43 subjects with carbamazepine-induced maculopapular exanthema, and 3987 control subjects, all of European descent. We tested for an association between disease and HLA alleles through proxy single-nucleotide polymorphisms and imputation, confirming associations by high-resolution sequence-based HLA typing. We replicated the associations in samples from 145 subjects with carbamazepine-induced hypersensitivity reactions. RESULTS The HLA-A★3101 allele, which has a prevalence of 2 to 5% in Northern European populations, was significantly associated with the hypersensitivity syndrome (P = 3.5×10−8). An independent genomewide association study of samples from subjects with maculopapular exanthema also showed an association with the HLA-A★3101 allele (P = 1.1×10−6). Follow-up genotyping confirmed the variant as a risk factor for the hypersensitivity syndrome (odds ratio, 12.41; 95% confidence interval [CI], 1.27 to 121.03), maculopapular exanthema (odds ratio, 8.33; 95% CI, 3.59 to 19.36), and SJS–TEN (odds ratio, 25.93; 95% CI, 4.93 to 116.18). CONCLUSIONS The presence of the HLA-A★3101 allele was associated with carbamazepine-induced hypersensitivity reactions among subjects of Northern European ancestry. The presence of the allele increased the risk from 5.0% to 26.0%, whereas its absence reduced the risk from 5.0% to 3.8%. (Funded by the U.K. Department of Health and others.) PMID:21428769

  15. Fatal hypersensitivity reaction to an oral spray of flurbiprofen: a case report.

    PubMed

    Calapai, G; Imbesi, S; Cafeo, V; Ventura Spagnolo, E; Minciullo, P L; Caputi, A P; Gangemi, S; Milone, L

    2013-08-01

    Safety of the anti-inflammatory drug flurbiprofen is comparable with that of other non-steroidal anti-inflammatory drugs of the propionic acid class, which are commonly associated with gastrointestinal and renal side effects. Here we report a case of a fatal hypersensitivity reaction to an oral spray of flurbiprofen taken for sore throat. A 29-year-old man came to the emergency care unit reporting sore throat with an intense burning sensation associated with fever. Pharyngotonsillitis was diagnosed, and local treatment with oral flurbiprofen spray was prescribed. Immediately after using the spray, the patient experienced a severe reaction characterized by serious dyspnoea, followed by death. The cause of death was heart failure with acute asphyxia from oedema of the glottis. The cause of death was concluded to be hypersensitivity to flurbiprofen spray. Oral propionic acid derivatives have been associated with a relatively high frequency of allergic reactions. However, allergy to flurbiprofen has rarely been documented. Scientific literature reports two relevant cases of hypersensitivity reaction to flurbiprofen: in one case, a patient presented with a maculopapular rash 48 h after having taken oral flurbiprofen followed by angio-oedema and hypotension. In another case, a single oral dose of flurbiprofen caused itching and swelling around the eyes, redness and increased lacrimation. We describe, for the first time, a fatal case of hypersensitivity reaction to flurbiprofen oral spray. Hypersensitivity reactions to flurbiprofen are infrequent; however, health professionals should be aware of potential adverse reactions, even during topical administration as oral spray. © 2013 John Wiley & Sons Ltd.

  16. Anaesthesia-associated hypersensitivity reactions: seven years' data from a British bi-specialty clinic.

    PubMed

    Low, A E; McEwan, J C; Karanam, S; North, J; Kong, K-L

    2016-01-01

    Our bi-specialty clinic was established to systematically investigate patients with suspected peri-operative hypersensitivity reactions. Four hundred and ten patients were studied; 316 following an intra-operative reaction ('postoperative' group) and 94 with a previous history of reaction, referred before undergoing anaesthesia ('pre-operative' group). In the postoperative group, 173 (54.7%) were diagnosed with IgE-mediated reactions: 65 (37.6%) to neuromuscular blocking drugs; 54 (31.2%) antibiotics; 15 (8.7%) chlorhexidine and 12 (6.9%) patent blue dye. Reactions were severe in 114 patients (65.9%). All reactions to patent blue dye were severe. We identified IgE sensitisation in 22 (13.2%) cases with isolated mucocutaneous reactions. Only 173 (54.7%) patients had serum tryptase samples taken. Referrers' suspected causal agent was confirmed in only 37.2% of patients. Of 94 patients reviewed 'pre-operatively', 29 (30.8%) were diagnosed with IgE-mediated hypersensitivity reactions, reinforcing the importance of investigating this group of patients. Knowledge of the range of causative agents identified in our study should guide the investigation of suspected peri-operative hypersensitivity reactions. © 2015 The Association of Anaesthetists of Great Britain and Ireland.

  17. Hypersensitivity reaction to ranitidine: description of a case and review of the literature.

    PubMed

    Foti, Caterina; Cassano, Nicoletta; Panebianco, Rosanna; Calogiuri, Gian Franco; Vena, Gino A

    2009-01-01

    Ranitidine is an H2-receptor antagonist which is usually well tolerated. Hypersensitivity reactions to ranitidine, as well as other H2 antihistamines, have been rarely described. We report the case of a 47-year-old woman who developed an anaphylactic reaction to ranitidine used as intravenous premedication before anesthesia induction. The patient's history revealed that previous use of oral ranitidine for a peptic ulcer disease did not cause any adverse reaction. Intradermal test with ranitidine at a dilution of 1:100 gave an intense positive reaction. The protective role of H2-receptor antagonists as premedication is still unclear and should be carefully reconsidered on the basis of the available controversial evidence and the possible risk of hypersensitivity reactions.

  18. Drug desensitization in the management of hypersensitivity reactions to monoclonal antibodies and chemotherapy.

    PubMed

    Mezzano, Veronica; Giavina-Bianchi, Pedro; Picard, Matthieu; Caiado, Joana; Castells, Mariana

    2014-04-01

    Hypersensitivity reactions to monoclonal antibodies and chemotherapy, which may vary in severity from mild to life-threatening, can lead to their discontinuation and replacement by alternative agents that are often less effective, more toxic, and/or more expensive. Drug desensitization has emerged as the best treatment modality capable of allowing re-introduction of the hypersensitivity reaction-inducing medication in highly sensitized patients in need of first line therapies. In recent years, the availability of new anti-neoplastic drugs and therapeutic monoclonal antibodies has increased, as has the potential for hypersensitivity reactions. Development of desensitization protocols for these new medications requires a careful assessment of the potential risks and benefits. The purposes of this review are to provide an overview of the presentation of hypersensitivity reactions amenable to desensitization and to increase awareness of the indications for and outcomes of desensitization protocols. Rapid drug desensitization has proven to be a safe and effective way of administering first line therapy to patients with hypersensitivity reactions, providing an extremely powerful treatment modality for patients for whom alternative drugs are deemed unacceptable. Rapid drug desensitization protocols should be administered only by highly trained allergists and nurses who have experience in determining which reactions are amenable to desensitization, and can identify high risk patients and provide them with appropriate care. Efforts should be made to increase awareness of the remarkable safety and efficacy of rapid drug desensitization among non-allergists, especially in the fields of oncology and rheumatology, so as to favor its universal application. Development of desensitization units to provide state-of-the-art care is possible only through coordinated teamwork.

  19. Delayed Cutaneous Hypersensitivity Reactions to Antibiotics: Management with Desensitization.

    PubMed

    McNulty, Caitlin M G; Park, Miguel A

    2017-11-01

    Successful desensitization to mild to moderate delayed cutaneous adverse reaction to antibiotics has been described in a limited number of antibiotics and found to be safe. However, there are ample opportunities to standardize protocols for delayed cutaneous adverse reactions to antibiotics. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Pilot study of once-daily simplification therapy with abacavir/lamivudine/zidovudine and efavirenz for treatment of HIV-1 infection.

    PubMed

    Ruane, Peter; Lang, Joseph; DeJesus, Edwin; Berger, Daniel S; Dretler, Robin; Rodriguez, Allan; Ward, Douglas J; Lim, Michael L; Liao, Qiming; Reddy, Sunila; Clair, Marty St; Vila, Tania; Shaefer, Mark S

    2006-01-01

    ). No patients withdrew due to adverse events, and no abacavir hypersensitivity reactions were reported. In this pilot study of patients suppressed on abacavir/lamivudine/zidovudine bid plus EFV, 94% of participants switching to abacavir/lamivudine/zidovudine qd plus EFV maintained virologic suppression, compared to 89% of participants continuing abacavir/lamivudine/zidovudine bid plus EFV.

  1. Efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV infected children and adolescents: a systematic review and meta-analysis.

    PubMed

    Adetokunboh, Olatunji O; Schoonees, Anel; Balogun, Tolulope A; Wiysonge, Charles S

    2015-10-26

    Abacavir is one of the recommended nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infections among children and adolescents. However, there are concerns that the antiviral efficacy of abacavir might be low when compared to other NRTIs especially among children. There are also concerns that abacavir use may lead to serious adverse events such as hypersensitivity reactions and has potential predisposition to developing cardiovascular diseases We searched four electronic databases, four conference proceedings and two clinical trial registries in August 2014, without language restrictions. Experimental and observational studies with control groups that examined the efficacy and safety of abacavir-containing regimens in comparison with other NRTIs as first-line treatment for HIV-infected children and adolescents aged between one month and eighteen years were eligible. Two authors independently screened search results, extracted data and assessed the risk of bias of included studies using a pre-specified, standardised data extraction form and validated risk of bias tools. We also assessed the quality of evidence per outcome with the GRADE tool. We included two randomised controlled trials (RCTs) and two analytical cohort studies with a total of 10,595 participants. Among the RCTs we detected no difference in virologic suppression after a mean duration of 48 weeks between abacavir- and stavudine-containing regimens (2 trials; n = 326: RR 1.28; 95 % CI 0.67-2.42) with significant heterogeneity (P = 0.02; I(2) = 81 %). We also found no significant differences between the two groups for adverse events and death. After five years of follow-up, virologic suppression improved with abacavir (1 trial; n = 69: RR 1.96; 95 % CI 1.11-3.44). For cohort studies, we detected that the virologic suppression activity of abacavir was less effective than stavudine in both the lopinavir/ritonavir (1 study, n = 2165: RR 0.79, 95 % CI 0.67-0.92) and efavirenz sub

  2. In Vivo Cysteinyl Leukotriene Release in Allergic and Nonallergic Immediate Hypersensitivity Reactions during Anesthesia.

    PubMed

    Laroche, Dominique; Léturgie, Pierre; Mariotte, Delphine; Ollivier, Yann; Hanouz, Jean-Luc; Le Mauff, Brigitte; Parienti, Jean-Jacques

    2017-05-01

    Immediate hypersensitivity reactions occurring during anesthesia are classified as allergic when skin tests and mast cell tryptase are positive and as nonallergic when negative results are obtained. Cysteinyl leukotrienes (cysLTs) are potent mediators synthesized by mast cell and eosinophil that induce bronchial constriction. They could play a role in hypersensitivity reactions. cysLT C4, D4, and E4 concentrations were measured by a competition immunoassay in serial plasma samples obtained prospectively from 21 anesthetized controls and retrospectively from 34 patients who reacted at induction of anesthesia (24 with allergic and 10 with nonallergic reactions). In controls, the median (interquartile range) cysLT concentration was 0.83 (0.69 to 1.02) μg/l before anesthesia and was unchanged 30 min, 6 h, and 24 h afterward. In the patients with allergic reactions, the values were highly increased 30 to 60 min after the reaction (17.9 [7.8 to 36.0] μg/l), while the patients with nonallergic reactions had less increased values (7.3 [3.0 to 11.5] μg/l). The difference between the three groups was significant (P < 0.0001). Increased values persisted during the 24 h of observation. Concentrations were significantly higher in patients with bronchospasm (P = 0.016). cysLTs appear to be an important mediator of allergic and nonallergic immediate hypersensitivity reactions. These findings might open a new field for management of patients with hypersensitivity reactions, especially nonallergic ones.

  3. Immediate-type hypersensitivity reactions and hypnosis: problems in methodology.

    PubMed

    Laidlaw, T M; Richardson, D H; Booth, R J; Large, R G

    1994-08-01

    Hypnosis has been used to ameliorate skin test reactivity in studies dating back to the 1930s. This study using modern methodology and statistical analyses sets out to test the hypothesis that it was possible to decrease reactions to histamine by hypnotic suggestion. Five subjects, all asthmatic and untrained in hypnosis, were given three hypnotic sessions where they were asked to control their reactions to histamine administered by the Pepys technique to forearm skin. These sessions were to be compared with three non-hypnotic sessions. The flare sizes but not wheal sizes were found to be significantly reduced after the hypnosis sessions, compared to sessions without hypnosis. Skin temperature was correlated with the size of reactions. The day upon which the sessions took place contributed significant amounts of the remaining unexplained variance, giving rise to questions about what could cause these day to day changes.

  4. Identification of risk factors of severe hypersensitivity reactions in general anaesthesia.

    PubMed

    Mirone, Corrado; Preziosi, Donatella; Mascheri, Ambra; Micarelli, Gianluigi; Farioli, Laura; Balossi, Luca G; Scibilia, Joseph; Schroeder, Jan; Losappio, Laura M; Aversano, Maria G; Stafylaraki, Chrysi; Nichelatti, Michele; Pastorello, Elide A

    2015-01-01

    Hypersensitivity reactions to anaesthetic agents are rare but often severe, with a mortality ranging from 4 to 9% in IgE-mediated events. Identification of the risk factors may contribute to limit the incidence of these reactions. The aim of our study was to search for possible risk factors of severe perioperative hypersensitivity reactions in our study population. For this study we retrospectively reviewed data from 193 patients who experienced drug hypersensitivity reactions during general anaesthesia. The diagnostic protocol consisted of 1) history of the reaction, 2) measurement of serum baseline tryptase and specific IgE-assays for latex, beta-lactams and succinylcholine, 3) skin tests for the agents listed in the anaesthesia chart and for others likely to be safe for future use, latex, and others medications administered during the perioperative period (i.e. antibiotics), 4) subdivision of our patients on the basis of two criteria: a) grade of severity of clinical reactions according to the Ring and Messmer classification; b) results of skin tests and/or serum specific IgE-assays. One hundred of 193 patients had reactions of grade I, 32/193 patients had reactions of grade II, 55/193 patients had reactions of grade III and 6/193 patients had reactions of grade IV. A diagnosis of IgE-mediated reaction was established in 55 cases (28.50%); the most common causes were neuromuscular blocking agents, followed by latex and beta-lactams. Severe reactions were associated with older age (p = 0.025), asthma (p = 0.042), history of hypertension (p = 0.001), intake of serum angiotensin converting enzyme inhibitor medication (p = 0.012) or serum angiotensin II antagonist (p = 0.033), higher levels of basal tryptase (p = 0.0211). Cardiovascular symptoms (p = 0.006) and history of hypersensitivity to antibiotics (p = 0.029) were more frequently reported in IgE-mediated reactions. We confirmed the relevance of several clinical features as risk

  5. Testing for Drug Hypersensitivity Syndromes

    PubMed Central

    Rive, Craig M; Bourke, Jack; Phillips, Elizabeth J

    2013-01-01

    Adverse drug reactions are a common cause of patient morbidity and mortality. Type B drug reactions comprise only 20% of all drug reactions but they tend to be primarily immunologically mediated and less dependent on the drug’s pharmacological action and dose. Common Type B reactions seen in clinical practice are those of the immediate, IgE, Gell-Coombs Type I reactions, and the delayed, T-cell mediated, Type IV reactions. Management of these types of reactions, once they have occurred, requires careful consideration and recognition of the utility of routine diagnostic tests followed by ancillary specialised diagnostic testing. For Type I, IgE mediated reactions this includes prick/intradermal skin testing and oral provocation. For Type IV, T-cell mediated reactions this includes a variety of in vivo (patch testing) and ex vivo tests, many of which are currently mainly used in highly specialised research laboratories. The recent association of many serious delayed (Type IV) hypersensitivity reactions to specific drugs with HLA class I and II alleles has created the opportunity for HLA screening to exclude high risk populations from exposure to the implicated drug and hence prevent clinical reactions. For example, the 100% negative predictive value of HLA-B*5701 for true immunologically mediated abacavir hypersensitivity and the development of feasible, inexpensive DNA-based molecular tests has led to incorporation of HLA-B*5701 screening in routine HIV clinical practice. The mechanism by which drugs specifically interact with HLA has been recently characterised and promises to lead to strategies for pre-clinical screening to inform drug development and design. PMID:23592889

  6. Desensitization to ceftaroline in a patient with multiple medication hypersensitivity reactions.

    PubMed

    Jones, Justin M; Richter, Lisa M; Alonto, Augusto; Leedahl, David D

    2015-02-01

    The case of a patient with multiple medication hypersensitivity reactions and a methicillin-resistant Staphylococcus aureus (MRSA) infection who underwent desensitization to ceftaroline is reported. A 32-year-old Caucasian woman with asthma, gastroesophageal reflux disease, heart murmur, and major depression was admitted for MRSA cellulitis with a subcutaneous abscess along the left sternomanubrial joint and clavicular osteomyelitis secondary to port placement after gastric bypass surgery. The patient had an extensive history of hypersensitivity reactions. Pertinent documented allergies were as follows: penicillin (anaphylaxis), daptomycin (anaphylaxis), vancomycin (hives), linezolid (hives), ertapenem (rash), ciprofloxacin (rash), and tigecycline (rash). The patient also reported previous reactions to aztreonam (unknown) and gentamicin (hives). The pharmacy was consulted to develop a desensitization protocol for ceftaroline. The desensitization protocol used three serial dilutions of ceftaroline to make 14 sequential infusions with escalating doses. Intramuscular epinephrine, i.v. diphenhydramine, and i.v. methylprednisolone were ordered as needed for the development of immediate hypersensitivity reactions during or after administration of ceftaroline. The cumulative dose (574.94 mg) was administered intravenously over 225 minutes with no breakthrough symptoms reported during or after the desensitization protocol. Ceftaroline fosamil 600 mg i.v. every 12 hours was continued for six weeks. Desensitization to ceftaroline was conducted for a patient with extensive history of hypersensitivity reactions to other drugs, including penicillin-induced anaphylaxis. Desensitization and subsequent treatment with full doses of ceftaroline were accomplished without apparent adverse effects. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  7. Delayed hypersensitivity reaction of the knee after injection of arthroscopy portals with bupivacaine (marcaine)

    PubMed

    Craft, D V; Good, R P

    1994-06-01

    The number of arthroscopic procedures performed annually for the management of intraarticular injuries has grown at an exponential rate. Whether done with the patient under general anesthesia or local anesthesia supplemented with intravenous sedation, it is common practice to postoperatively inject each portal as well as the joint with a local anesthetic to provide pain relief in the transition to the recovery room and discharge after outpatient surgery. To our knowledge, no previous reports of localized urticaria and delayed hypersensitivity reaction have been reported in the postarthroscopy setting. We are reporting a case of delayed hypersensitivity reaction and urticaria of the knee that presented after bupivacaine (Marcaine) injection of arthroscopic portals after routine meniscectomy.

  8. Immediate hypersensitivity reaction following liposomal amphotericin-B (AmBisome) infusion.

    PubMed

    Nath, Proggananda; Basher, Ariful; Harada, Michiyo; Sarkar, Santana; Selim, Shahjada; Maude, Richard J; Noiri, Eisei; Faiz, Abul

    2014-10-01

    Liposomal amphotericin-B (AmBisome) is now becoming first choice for the treatment of visceral leishmaniasis (kala-azar) patients due to high efficacy and less toxicity. The reported incidence of hypersensitivity reactions to liposomal amphotericin-B (AmBisome), especially during therapy, is very rare. We report two patients with kala-azar: one developed breathing difficulties and hypotension followed by shock and the other had facial angioedema with chest tightness during treatment. Both patients were managed with immediate action of injection: adrenaline, diphenhydramine and hydrocortisone. In our experience, AmBisome can cause severe hypersensitivity reactions that warrant proper support and close supervision. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  9. Minocycline successfully treats exaggerated granulomatous hypersensitivity reaction to Mw immunotherapy.

    PubMed

    Vinay, Keshavamurthy; Narang, Tarun; Saikia, Uma N; Kumaran, Muthu Sendhil; Dogra, Sunil

    2017-03-01

    Mycobacterium W (Mw) vaccine has been found to be effective in the treatment of leprosy and warts. Despite increasing use of Mw immunotherapy, data on its safety is limited. We report a series of eight patients who developed persisting injection site granulomatous reaction following Mw immunotherapy and were successfully treated with minocycline. Eight patients with persistent nodular swelling at the site of Mw injections were identified. Seven of them had received Mw immunotherapy for cutaneous warts and one for verrucous epidermal nevus. The lesions were firm, erythematous, succulent, non-tender nodules confined to the sites of Mw vaccine injections. In 6 of these patients nodules also involved the previously injected areas. Skin biopsy from all patients showed eosinophil rich inflammation admixed with histiocytes and lymphocytes. In addition granulomas were seen in all with septal and nodular panniculitis in four patients. Broken and granular acid-fast bacilli were identified in two cases. All patients were treated with oral minocycline 100 mg/day for a mean of 9 weeks and showed good clinical response. Granulomatous reaction is a rare but significant adverse effect of Mw immunotherapy at cosmetically and functionally imperative sites. Oral minocycline appears to be effective therapy in this situation. © 2016 Wiley Periodicals, Inc.

  10. A perspective of nanotechnology in hypersensitivity reactions including drug allergy.

    PubMed

    Montañez, Maria Isabel; Ruiz-Sanchez, Antonio J; Perez-Inestrosa, Ezequiel

    2010-08-01

    We provide an overview of the application of the concepts of nanoscience and nanotechnology as a novel scientific approach to the area of nanomedicine related to the domain of the immune system. Particular emphasis will be paid to studies on drug allergy reactions. Several well defined chemical structures arranged in the dimension of the nanoscale are currently being studied for biomedical purposes. By interacting with the immune system, some of these show promising applications as vaccines, diagnostic tools and activators/effectors of the immune response. Even a brief listing of some key applications of nanostructured materials shows how broad and intense this area of nanomedicine is. As a result of the development of nanoscience and nanotechnology applied to medicine, new approaches can be envisioned for problems related to the modulation of the immune response, as well as in immunodiagnosis, and to design new tools to solve related medical challenges. Nanoparticles offer unique advantages with which to exploit new properties and for materials to play a major role in new diagnostic techniques and therapies. Fullerene-C60 and multivalent functionalized gold nanoparticles of various sizes have led to new tools and opened up new ways to study and interact with the immune system. Some of the most versatile nanostructures are dendrimers. In their interaction with the immune system they can naturally occurring macromolecules, taking advantage of the fact that dendrimers can be synthesized into nanosized structures. Their multivalence can be successfully exploited in vaccines and diagnostic tests for allergic reactions.

  11. Hypersensitivity reaction to human papillomavirus vaccine due to polysorbate 80.

    PubMed

    Badiu, Iuliana; Geuna, Massimo; Heffler, Enrico; Rolla, Giovanni

    2012-05-08

    A 17-year-old girl reported generalised urticaria, eyelid angioedema, rhino-conjunctivitis, dyspnoea and wheezing 1 h after third intramuscular administration of quadrivalent human papilloma virus vaccine (Gardasil). She was treated with antihistamine, and corticosteroids with prompt relief of rhinitis and dyspnoea, while urticaria and angioedema lasted 24 h. Intradermal test with Gardasil, which contains polysorbate 80 (PS80), resulted positive, while skin tests with the bivalent vaccine were negative. Prick test performed with PS80 resulted positive in the patient and negative in ten healthy controls. The CD203 basophil activation test result was negative for PS80 at all the tested dilutions and specific IgE was not found. As flu vaccine was recommended, the authors skin tested two flu vaccine, one containing PS80 (Fluarix, GSK), which resulted positive and another flu vaccine with no adjuvant or preservative (Vaxigrip, Sanofi Pasteur MSD), which gave negative results. The patient then received Vaxigrip without adverse reactions.

  12. Patch testers' opinions regarding diagnostic criteria for metal hypersensitivity reactions to metallic implants.

    PubMed

    Schalock, Peter C; Thyssen, Jacob P

    2013-01-01

    Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated. Diagnostic criteria for hypersensitivity reactions after metallic device implantation are evaluated in this study by a multinational group of patch testers using Thyssen's previously published criteria. A total of 119 dermatologists at the 2012 European Contact Dermatitis Society and 2013 American Contact Dermatitis Society meetings answered a survey regarding their opinions on topics relating to metal hypersensitivity. Four major and 5 minor diagnostic criteria emerged. Approximately 80% of respondents found the following criteria useful (major criteria): chronic dermatitis beginning weeks to months after metallic implantation, eruption overlying the metal implant, positive patch test to a metal component of the implant, and complete clearing after removal of the potentially allergenic implant. Minor criteria (<61% of respondents) were as follows: systemic allergic dermatitis reaction, therapy-resistant dermatitis, morphology consistent with dermatitis, histology consistent with allergic contact dermatitis, and a positive in vitro test to metals (eg, lymphocyte transformation test). In the challenging situation such as a symptomatic or failing orthopedic device, applying these 4 major criteria and the 5 supportive minor criteria may be useful for guiding decision making.

  13. Cross-protection against Salmonella enteritidis infection in mice. III. Delayed hypersensitivity reaction and clearance of the challenge organism.

    PubMed

    Padmanaban, V D; Mittal, K R

    1979-01-01

    Mice were immunized with live vaccines and with live vaccines with complete adjuvant incorporating Salmonella enteritidis, Salmonella typhi-murium, Salmonella gallinarum or Salmonella pullorum. On the 21st day after vacination, the hypersensitivity reactions elicited by the mice to extracts of the challenge organism (S. enteritidis 5694 SMR) were assessed. The degree of delayed hypersensitivity reaction was compared with the level of protection induced by the vaccine. The role in protection of delayed hypersensitivity is discussed. Clearance of the challenge organism from the liver of previously vaccinated and unvaccinated mice was assessed quantitatively.

  14. Abacavir-induced liver toxicity.

    PubMed

    Pezzani, Maria Diletta; Resnati, Chiara; Di Cristo, Valentina; Riva, Agostino; Gervasoni, Cristina

    2016-01-01

    Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests occurring in a young HLA B*5701-negative woman on a stable nevirapine-based regimen with no history of liver problems or alcohol abuse after switching to abacavir from tenofovir. We also investigated the reasons for abacavir discontinuation in a cohort of patients treated with abacavir-lamivudine-nevirapine. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  15. [The use of the macrophage disappearance reaction for detecting delayed hypersensitivity to Yersinia pestis antigens].

    PubMed

    Vasil'eva, G I; Doroshenko, E P; Kiseleva, A K; Pustovalov, V L

    1990-12-01

    The possibility of using the reaction of macrophage disappearance (RMD) for the detection of delayed hypersensitivity (DH) to Y. pestis has been studied. As the result of these studies, RMD has been found suitable, in principle, for use in the quantitative evaluation of DH to Y. pestis. High sensitivity and specificity of this reaction have been established. The presence of DH in the process of the formation of immunity after immunization with Y. pestis antigen FIA has been shown. RMD can be observed during 28 days after immunization (the term of observation).

  16. Immediate hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines: reports to VAERS.

    PubMed

    Halsey, Neal A; Griffioen, Mari; Dreskin, Stephen C; Dekker, Cornelia L; Wood, Robert; Sharma, Devindra; Jones, James F; LaRussa, Philip S; Garner, Jenny; Berger, Melvin; Proveaux, Tina; Vellozzi, Claudia; Broder, Karen; Setse, Rosanna; Pahud, Barbara; Hrncir, David; Choi, Howard; Sparks, Robert; Williams, Sarah Elizabeth; Engler, Renata J; Gidudu, Jane; Baxter, Roger; Klein, Nicola; Edwards, Kathryn; Cano, Maria; Kelso, John M

    2013-12-09

    Hypersensitivity disorders following vaccinations are a cause for concern. To determine the type and rate by age, gender, and vaccine received for reported hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines. A systematic review of reports to the Vaccine Adverse Event Reporting System (VAERS) following monovalent 2009 pandemic influenza A (H1N1) vaccines. US Civilian reports following vaccine received from October 1, 2009 through May 31, 2010. Age, gender, vaccines received, diagnoses, clinical signs, and treatment were reviewed by nurses and physicians with expertise in vaccine adverse events. A panel of experts, including seven allergists reviewed complex illnesses and those with conflicting evidence for classification of the event. Of 1984 reports, 1286 were consistent with immediate hypersensitivity disorders and 698 were attributed to anxiety reactions, syncope, or other illnesses. The female-to-male ratio was ≥4:1 for persons 20-to-59 years of age, but approximately equal for children under 10. One hundred eleven reports met Brighton Collaboration criteria for anaphylaxis; only one-half received epinephrine for initial therapy. The overall rate of reported hypersensitivity reactions was 10.7 per million vaccine doses distributed, with a 2-fold higher rate for live vaccine. Underreporting, especially of mild events, would result in an underestimate of the true rate of immediate hypersensitivity reactions. Selective reporting of events in adult females could have resulted in higher rates than reported for males. Adult females may be at higher risk of hypersensitivity reactions after influenza vaccination than men. Although the risk of hypersensitivity reactions following 2009 pandemic influenza A (H1N1) vaccines was low, all clinics administering vaccines should be familiar with treatment guidelines for these adverse events, including the use of intramuscular epinephrine early in the course of serious hypersensitivity

  17. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial.

    PubMed

    Mulenga, Veronica; Musiime, Victor; Kekitiinwa, Adeodata; Cook, Adrian D; Abongomera, George; Kenny, Julia; Chabala, Chisala; Mirembe, Grace; Asiimwe, Alice; Owen-Powell, Ellen; Burger, David; McIlleron, Helen; Klein, Nigel; Chintu, Chifumbe; Thomason, Margaret J; Kityo, Cissy; Walker, A Sarah; Gibb, Diana M

    2016-02-01

    NRTIs had low toxicity and good clinical, immunological, and virological responses. Clinical and subclinical lipodystrophy was not noted in those younger than 5 years and anaemia was no more frequent with zidovudine than with the other drugs. Absence of hypersensitivity reactions, superior resistance profile and once-daily dosing favours abacavir for African children, supporting WHO 2013 guidelines. European Developing Countries Clinical Trials Partnership. Copyright © 2016 Walker et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

  18. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial

    PubMed Central

    Mulenga, Veronica; Musiime, Victor; Kekitiinwa, Adeodata; Cook, Adrian D; Abongomera, George; Kenny, Julia; Chabala, Chisala; Mirembe, Grace; Asiimwe, Alice; Owen-Powell, Ellen; Burger, David; McIlleron, Helen; Klein, Nigel; Chintu, Chifumbe; Thomason, Margaret J; Kityo, Cissy; Walker, A Sarah; Gibb, Diana M

    2016-01-01

    -experienced children maintained suppression (p=1·00). Interpretation All NRTIs had low toxicity and good clinical, immunological, and virological responses. Clinical and subclinical lipodystrophy was not noted in those younger than 5 years and anaemia was no more frequent with zidovudine than with the other drugs. Absence of hypersensitivity reactions, superior resistance profile and once-daily dosing favours abacavir for African children, supporting WHO 2013 guidelines. Funding European Developing Countries Clinical Trials Partnership. PMID:26481928

  19. Azithromycin is more allergenic than clarithromycin in children with suspected hypersensitivity reaction to macrolides.

    PubMed

    Barni, S; Butti, D; Mori, F; Pucci, N; Rossi, M E; Cianferoni, A; Novembre, E

    2015-01-01

    Macrolides are considered safe antibiotics with reduced allergenic activity. However, studies on the safety of macrolides are scarce, particularly in children. The aim of this study was to assess the frequency of hypersensitivity reactions to clarithromycin and azithromycin in a group of children referred to our allergy unit for suspected macrolide allergy. We retrospectively reviewed the charts of 90 children aged 1-17 years with symptoms suggestive of hypersensitivity reaction to clarithromycin or azithromycin between December 31, 2008 and December 31, 2013. The allergy workup included skin tests (ie, skin prick tests and/or intradermal tests), determination of serum specific IgE (sIgE) to clarithromycin and azithromycin, and, if necessary to reach a diagnosis, oral provocation tests. Seventy-seven children completed the allergy workup. A reaction to clarithromycin was recorded in 58 children (75.3%): 21 (36.2%) had a history of immediate reactions, and 37 (63.8%) had a history of nonimmediate reactions. A reaction to azithromycin was recorded in 19 children (24.6%): 6 (31.5%) had a history of immediate reaction, and 13 (68.42%) had a history of nonimmediate reaction. Positive results in skin tests and oral provocation tests with the suspect drug confirmed the diagnosis in 15.5% of reactions to clarithromycin (9 of 58) and in 47.3% of reactions to azithromycin (9 of 19) (P = .004). A complete allergy workup enabled us to confirm a diagnosis of clarithromycin and azithromycin allergy in 15.5% and 47.3% of cases, respectively. Azithromycin was more allergenic than clarithromycin in children.

  20. Immediate hypersensitivity reaction associated with the rapid infusion of Crotalidae polyvalent immune Fab (ovine).

    PubMed

    Holstege, Christopher P; Wu, Jeffrey; Baer, Alexander B

    2002-06-01

    A 16-year-old boy presented to the emergency department with rapidly progressing extremity pain, edema, and ecchymosis after envenomation by a copperhead. Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) was infused. Six vials were placed in 250 mL of normal saline solution, and the infusion was gradually increased. Fifty minutes after beginning, the infusion was increased to 640 mL/h. Within minutes of the rate increase, the patient experienced full-body urticaria, facial edema, voice change, and tachycardia. The infusion was stopped. Hydroxyzine pamoate, famotidine, methylprednisolone, and a 1-L bolus of normal saline solution were administered intravenously. The symptoms abated, and the remaining FabAV was infused at a slower rate without return of this reaction. This immediate hypersensitivity reaction was most likely a rate-related anaphylactoid reaction that has not been previously reported with FabAV.[Holstege CP, Wu J, Baer AB. Immediate hypersensitivity reaction associated with the rapid infusion of Crotalidae polyvalent immune Fab (ovine). Ann Emerg Med. June 2002;39:677-679.

  1. Implications of HLA-allele associations for the study of type IV drug hypersensitivity reactions.

    PubMed

    Sullivan, A; Watkinson, J; Waddington, J; Park, B K; Naisbitt, D J

    2018-03-01

    Type IV drug hypersensitivity remains an important clinical problem and an obstacle to the development of new drugs. Several forms of drug hypersensitivity are associated with expression of specific HLA alleles. Furthermore, drug-specific T-lymphocytes have been isolated from patients with reactions. Despite this, controversy remains as to how drugs interact with immune receptors to stimulate a T-cell response. Areas covered: This article reviews the pathways of T-cell activation by drugs and how the ever increasing number of associations between expression of HLA alleles and susceptibility to hypersensitivity is impacting on our research effort to understanding this form of iatrogenic disease. Expert opinion: For a drug to activate a T-cell, a complex is formed between HLA molecules, an HLA binding peptide, the drug and the T-cell receptor. T-cell responses can involve drugs and stable or reactive metabolites bound covalently or non-covalently to any component of this complex. Recent research has linked the HLA associations to the disease through the characterization of drug-specific T-cell responses restricted to specific alleles. However, there is now a need to identify the additional genetic or environment factors that determine susceptibility and use our increased knowledge to develop predictive immunogenicity tests that offer benefit to Pharma developing new drugs.

  2. A practical and successful desensitization protocol for immediate hypersensitivity reactions to iron salts.

    PubMed

    Demir, Semra; Olgac, Muge; Unal, Derya; Gelincik, Asli; Colakoglu, Bahauddin; Buyukozturk, Suna

    2014-01-01

    Orally administered iron salts (OAS) are widely used in the management of iron deficiency anemia and hypersensitivity reactions to OAS are not common. If an offending drug is the sole option or is significantly more effective than its alternatives, it can be readministered by desensitization. The oral desensitization protocols for iron published so far concern either desensitization that was completed only over a long period or did not attain the recommended therapeutic dose. We aimed to develop a more effective protocol. We report here on 2 patients who experienced hypersensitivity reactions to OAS. After confirming the diagnosis, both patients were desensitized to oral ferrous (II) glycine sulfate complex according to a 2-day desensitization protocol. A commercial suspension of oral ferrous glycine sulfate, which contains 4 mg of elemental iron in 1 ml, was preferred. We started with a dose as low as 0.1 ml from a 1/100 dilution (0.004 mg elemental iron) of the original suspension and reached the maximum effective dose in 2 days. Both patients were successfully desensitized and they went on to complete the 6-month iron treatment without any adverse effects. Although hypersensitvity reactions to iron are not common, there is no alternative for iron administration. Therefore, desensitization has to be the choice. This easy desensitization protocol seems to be a promising option. © 2014 S. Karger AG, Basel.

  3. Impact of Prophylactic Conversion to an Extended Infusion Schedule to Prevent Hypersensitivity Reactions in Ovarian Cancer Patients during Carboplatin Retreatment

    PubMed Central

    O’Cearbhaill, Roisin; Zhou, Qin; Iasonos, Alexia; Hensley, Martee L.; Tew, William P.; Aghajanian, Carol; Spriggs, David R.; Lichtman, Stuart M.; Sabbatini, Paul J.

    2015-01-01

    Objective Repeated exposure to carboplatin can lead to hypersensitivity reactions during retreatment with carboplatin. This may prevent its further use in platinum-sensitive ovarian cancer patients. At our institution, an increasing proportion of patients are prophylactically converted to an extended schedule of infusion after 8 cycles of carboplatin. We sought to determine whether an incrementally increasing, extended 3-hour infusion of carboplatin was associated with a lower rate of hypersensitivity reactions compared to the standard 30-minute schedule in sequentially treated patients. Methods We performed a retrospective electronic medical record review of patients with recurrent ovarian cancer retreated with carboplatin at our institution from 01/98–12/08. Results Seven hundred seventy-seven patients with relapsed ovarian, fallopian tube, or primary peritoneal cancer were retreated with carboplatin and met study inclusion criteria. Of these, 117 (17%) developed hypersensitivity reactions during second-line or greater carboplatin-based treatment for recurrent disease. Only 6 (3.4%) of the 174 patients who received the extended schedule developed hypersensitivity reactions (0% grade 4; 1.7% grade 3) compared to 111 (21%) of 533 patients in the standard schedule group (12% grade 4; 77% grade 3). The first hypersensitivity episode occurred after a median of 16 platinum (carboplatin and cisplatin) treatments in the extended group compared to 9 in the standard group. Using the Fisher-exact test, there was an association with a reduced incidence of hypersensitivity reactions with the extended infusion schedule (P<0.001). Conclusion Our data suggest appropriate premedication and prophylactic conversion to an extended infusion during carboplatin retreatment may reduce hypersensitivity reactions. PMID:19944454

  4. Reactive aldehyde metabolites from the anti-HIV drug abacavir: amino acid adducts as possible factors in abacavir toxicity.

    PubMed

    Charneira, Catarina; Godinho, Ana L A; Oliveira, M Conceição; Pereira, Sofia A; Monteiro, Emília C; Marques, M Matilde; Antunes, Alexandra M M

    2011-12-19

    Abacavir is a nucleoside reverse transcriptase inhibitor marketed since 1999 for the treatment of infection with the human immunodeficiency virus type 1 (HIV). Despite its clinical efficacy, abacavir administration has been associated with serious and sometimes fatal toxic events. Abacavir has been reported to undergo bioactivation in vitro, yielding reactive species that bind covalently to human serum albumin, but the haptenation mechanism and its significance to the toxic events induced by this anti-HIV drug have yet to be elucidated. Abacavir is extensively metabolized in the liver, resulting in inactive glucuronide and carboxylate metabolites. The metabolism of abacavir to the carboxylate involves a two-step oxidation via an unconjugated aldehyde, which under dehydrogenase activity isomerizes to a conjugated aldehyde. Concurrently with metabolic oxidation, the two putative aldehyde metabolites may be trapped by nucleophilic side groups in proteins yielding covalent adducts, which can be at the onset of the toxic events associated with abacavir. To gain insight into the role of aldehyde metabolites in abacavir-induced toxicity and with the ultimate goal of preparing reliable and fully characterized prospective biomarkers of exposure to the drug, we synthesized the two putative abacavir aldehyde metabolites and investigated their reaction with the α-amino group of valine. The resulting adducts were subsequently stabilized by reduction with sodium cyanoborohydride and derivatized with phenyl isothiocyanate, leading in both instances to the formation of the same phenylthiohydantoin, which was fully characterized by NMR and MS. These results suggest that the unconjugated aldehyde, initially formed in vivo, rapidly isomerizes to the thermodynamically more stable conjugated aldehyde, which is the electrophilic intermediate mainly involved in reaction with bionucleophiles. Moreover, we demonstrated that the reaction of the conjugated aldehyde with nitrogen

  5. Hypersensitivity reactions to penicillins: studies in a group of patients with negative benzylpenicillin G skin test.

    PubMed

    Qiao, H-L; Li, Z; Yang, J; Tian, X; Gao, N; Jia, L-J

    2009-06-01

    Although skin tests are usually employed to evaluate current penicillin allergy status, a negative result does not exclude hypersensitivity. There is a need for accurate in vitro tests to exclude hypersensitivity. A radioallergosorbent test (RAST) is a potentially good supplementary approach, but there is little information on the suitability of this method to diagnose penicillin hypersensitivity in subjects with a negative skin test to benzylpenicillin. A total of 133 patients with a negative skin test to benzylpenicillin G (PG) and all of whom developed allergic reactions to PG were studied. RAST was used to detect eight kinds of specific IgE antibodies to penicillins in serum, which included four kinds of major and minor antigenic determinants to four penicillin drugs. The combination sites for the specific IgE antibodies were studied by RAST inhibition test. The rate of positive reactions for the specific IgE antibodies was 59.40% (79/133). Of the eight kinds of antigenic determinants, the positive rates for specific IgE against the major and minor determinants were 39.10% (52) and 42.86% (57) respectively. Of the four drugs, positive cases only to PG were 10 (7.5%), were significantly fewer than the cross-reacting positive cases (36) to PG (P < 0.01). In the RAST inhibition studies all drugs exhibited good inhibitory potencies, and in some instances the side-chain of the penicillins could induce specific responses with a variable degree of cross-reactivity among the different penicillins. Radioallergosorbent test is a good complementary test in persons who are skin-test negative with PG, and the sensitivity of RAST increases with increasing specificity of IgE antibodies to be detected. 6-APA and the groups, making part of the different side-chains on penicillins, all contributed to the cross-reactivity.

  6. Hypersensitivity reactions to food colours with special reference to the natural colour annatto extract (butter colour).

    PubMed

    Mikkelsen, H; Larsen, J C; Tarding, F

    1978-01-01

    It is well known that synthetic food colours especially some azo dyes can provoke hypersensitivity reactions such as urticaria, angioneurotic oedema, and astma (Michaëlsson and Juhlin, 1973, Granholt and Thune, 1975). Natural food colours are scarcely investigated with respect to potential allergic properties. Annatto extract, a commonly used food colour in edible fats e.g. butter, has been tested in patients. Among 61 consecutive patients suffereing from chornic urticaria and/or angioneurotic oedema 56 patients were orally provoked by annatto extract during elimination diet. Challenge was performed with a dose equivalent to the amount used in 25 grammes of butter. Twentysix per cent of the patients reacted to this colour 4 hours (SD: 2,6) after intake. Similar challenges with synthetic dyes showed the following results: Tartrazine 11%, Sunset Yellow FCF 17%, Food Red 17 16%, Amaranth 9%, Ponceau 4 R 15%, Erythrosine 12% and Brillant Blue FCF 14%. The present study indicates that natural food colours may induce hypersensitivity reactions as frequent as synthetic dyes.

  7. Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century.

    PubMed

    Castells Guitart, M C

    2014-01-01

    The frequency of hypersensitivity reactions (HSR) to drugs has risen in the last 10 years owing to increased exposure to better and more allergenic medications including monoclonal antibodies. HSRs prevent patients from using their first-line therapy, leading to decreased quality of life and life expectancy. Although premedication with antihistamines, leukotriene blockers, and corticosteroids can protect against mild-to-moderate HSR, none of these medications has provided protection against anaphylaxis. Rapid drug desensitization is a treatment option for patients with HSR to their first-line medication that protects against anaphylaxis.Although the mechanisms of drug desensitization are not completely understood, in vitro mast cell models of IgE antigen desensitization have led to the design of safe and effective in vivo protocols aimed at protecting highly sensitized patients from hypersensitivity reactions and anaphylaxis. This review provides an insight into the mechanisms of IgE/mast cell desensitization, the principles and practice of drug desensitization, and an overview of the different desensitization protocols and their safety and efficacy profiles. Drug desensitization should only be performed by allergists, trained nurses, and experienced pharmacists, since this high-risk procedure involves reintroducing allergenic medication to highly sensitized patients, with the consequent potential for severe or fatal HSRs.

  8. Self-reported prevalence of hypersensitivity reactions against drugs among medical students: does awareness cause any difference?

    PubMed

    Bavbek, Sevim; Erkekol, Ferda Öner; Celik, Gülfem Elif; Gönüllü, Ipek; Misirligil, Zeynep

    2011-02-01

    True epidemiologic data on hypersensitivity reactions to drugs are scarce. More accurate data may be obtained in more specific clinical settings. Considering their educational background, medical students may be an appropriate target audience for evaluating prevalence of drug hypersensitivity. This study is designed to determine the prevalence of self-reported drug hypersensitivity alongside related factors among young adults. A structured questionnaire was administered to the students. A total of 1267 students (mean age: 21.71+1.90 years, F/M: 648/619) from all grades responded to the survey. The mean prevalence of self-reported drug hypersensitivity was 4.7% (60/1267). The most frequently involved drugs were beta-lactam antibiotics (55%) followed by non-steroidal anti-inflammatory drugs (28%). The most commonly reported clinical presentations were cutaneous (43.3%), followed by systemic (36.8%), cardiovascular (8.3%) and respiratory (8.3%) symptoms. Factors related with reported reactions were higher grades (p=0.015, OR: 2.09), female gender (p=0.006, OR: 2.13), personal history of allergic diseases (p=0.001, OR: 2.64), and family history of drug hypersensitivity (p<0.001, OR: 5.78). Half of the students sought medical help during the acute stage of their reaction. Only 3.2% of the cases have been referred to an allergist for further evaluation. This study, the first of its kind in Turkey, with medical students showed that self-reported hypersensitivity reactions to drugs is highly prevalent and its prevalence seems to be affected by awareness of the individuals in addition to previously reported risk factors. The education of both patients and physicians on the management of drug hypersensitivity seems to be necessary. Copyright © 2010 John Wiley & Sons, Ltd.

  9. Nevirapine patch testing in Thai human immunodeficiency virus infected patients with nevirapine drug hypersensitivity.

    PubMed

    Prasertvit, Piyatida; Chareonyingwattana, Angkana; Wattanakrai, Penpun

    2017-12-01

    Antiretroviral drug hypersensitivity in HIV patients is common. Publications have shown that Abacavir (ABC) patch testing is useful in confirming ABC hypersensitivity in 24-50% of cases with a 100% sensitivity of HLA-B*5701 in patch test positive cases. However, Nevirapine (NVP) patch testing has not been reported. (1) To evaluate the usefulness and safety of NVP patch testing in Thai HIV patients with NVP hypersensitivity. (2) To assess the correlation of positive patch tests with HLA-B*3505. Patients were classified into two groups: (1) study group of 20 HIV NVP hypersensitivity patients and (2) control group of 15 volunteers without NVP hypersensitivity. Both groups were patch tested with purified and commercialized form of NVP in various vehicles. Two HIV patients with NVP hypersensitivity were patch test positive. All controls tested negative. Three HIV patients were positive for HLA-B*3505 and the two patients with positive patch testing were both HLA-B*3505 positive. NVP patch testing in Thai HIV patients is safe and can be used to help confirm the association between NVP and hypersensitivity skin reactions. NVP patch test results significantly correlated with HLA-B*3505. The sensitivity of HLA-B*3505 for positive patch test was 100%. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Co-formulated abacavir-lamivudine-zidovudine for initial treatment of HIV infection and AIDS.

    PubMed

    Shey, Muki S; Kongnyuy, Eugene J; Alobwede, Samuel M; Wiysonge, Charles Shey

    2013-03-28

    . Overall, there was no significant difference in virological suppression between co-formulated abacavir-lamivudine-zidovudine and NNRTI- or PI-based therapy (4 trials; 2247 participants: RR 0.73, 95% CI 0.39 to 1.36). However, the results showed significant heterogeneity (I(2)=79%); with co-formulated abacavir-lamivudine-zidovudine inferior to NNRTI (1 trial, 1147 participants: RR 0.35, 95%CI 0.26 to 0.49) but with a trend towards co-formulated abacavir-lamivudine-zidovudine being superior to PI (3 trials, 1110 participants: RR 1.07, 95%CI 1.00 to 1.16; I(2)=0%). We found no significant differences between co-formulated abacavir-lamivudine-zidovudine and either PI or NNRTI on CD4+ cell counts (3 trials, 1687 participants: MD -0.01, 95%CI -0.11 to 0.09; I(2)=0%), severe adverse events (4 trials: RR 1.22, 95%CI 0.78 to 1.92; I(2)=62%) and hypersensitivity reactions (4 trials: RR 4.04, 95% CI 0.41 to 40.02; I(2)=72%). Only two studies involving PIs reported data on the lipid profile. One study found that the mean increase in total cholesterol from baseline to 96 weeks was significantly lower with co-formulated abacavir-lamivudine-zidovudine than with nelfinavir, but there were no differences with triglyceride levels. The second study found the fasting lipid profile to be comparable in both co-formulated abacavir-lamivudine-zidovudine and atazanavir arms at 48 weeks.The significant heterogeneity of effects for most outcomes evaluated was largely due to differences in the control therapy used in the included trials (i.e. NNRTIs or PIs). Using the GRADE approach, we rated the overall quality of the evidence on the relative effects of co-formulated abacavir-lamivudine-zidovudine for initial treatment of HIV infection as moderate. The main reason for downgrading the quality of the evidence was imprecision of the findings. The estimate of the treatment effect for each outcome has wide confidence intervals, which extend from the fixed-dose NRTI combination regimen being appreciably

  11. Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Contrast Media.

    PubMed

    Rosado Ingelmo, A; Doña Diaz, I; Cabañas Moreno, R; Moya Quesada, M C; García-Avilés, C; García Nuñez, I; Martínez Tadeo, J I; Mielgo Ballesteros, R; Ortega-Rodríguez, N; Padial Vilchez, M A; Sánchez-Morillas, L; Vila Albelda, C; Moreno Rodilla, E; Torres Jaén, M J

    2016-01-01

    The objective of these guidelines is to ensure efficient and effective clinical practice. The panel of experts who produced this consensus document developed a research protocol based on a review of the literature. The prevalence of allergic reactions to iodinated contrast media (ICM) is estimated to be 1:170 000, that is, 0.05%-0.1% of patients undergoing radiologic studies with ICM (more than 75 million examinations per year worldwide). Hypersensitivity reactions can appear within the first hour after administration (immediate reactions) or from more than 1 hour to several days after administration (nonimmediate or delayed reactions). The risk factors for immediate reactions include poorly controlled bronchial asthma, concomitant medication (eg, angiotensin-converting enzyme inhibitors, ß-blockers, and proton-pump inhibitors), rapid administration of the ICM, mastocytosis, autoimmune diseases, and viral infections. The most common symptoms of immediate reactions are erythema and urticaria with or without angioedema, which appear in more than 70% of patients. Maculopapular rash is the most common skin feature of nonimmediate reactions (30%-90%). Skin and in vitro tests should be performed for diagnosis of both immediate and nonimmediate reactions. The ICM to be administered will therefore be chosen depending on the results of these tests, the ICM that induced the reaction (when known), the severity of the reaction, the availability of alternative ICM, and the information available on potential ICM cross-reactivity. Another type of contrast media, gadolinium derivatives, is used used for magnetic resonance imaging. Although rare, IgE-mediated reactions to gadolinium derivatives have been reported.

  12. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2012-01-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  13. Hypersensitivity reactions to the Sabin vaccine in children with cow's milk allergy.

    PubMed

    Parisi, C A S; Smaldini, P L; Gervasoni, M E; Maspero, J F; Docena, G H

    2013-02-01

    The Sabin vaccine is used world-wide, and most children with food allergies receive it without incident. However, in the 2009 vaccination campaign conducted in Argentina, four children experienced immediate-type hypersensitivity reactions following vaccination. We aimed to review the medical history of the affected children, study their allergic condition after the episodes and analyse the presence of allergenic vaccine components. Patients were selected based on their immediate allergic reactions following vaccination. They were assessed for allergies to cow's milk and hen's egg. The presence of cow's milk proteins in the vaccine was tested by various immunoassays involving cow's milk- or α-lactalbumin-specific polyclonal rabbit antiserum and patient sera. All of the patients had a history of milk allergy, and no history or current evidence of egg hypersensitivity was found. Levels of cow's milk- and Sabin vaccine-specific IgE were increased, and the result of a skin prick test with cow's milk proteins or the Sabin vaccine was positive in each patient. In addition, an ELISA using specific rabbit antiserum detected α-lactalbumin in the Sabin vaccine. When α-lactalbumin was employed as a soluble inhibitor in a competitive ELISA, binding to vaccine-coated plates by cow's milk- or α-lactalbumin-specific rabbit antiserum or by patient serum containing IgE was inhibited. We have demonstrated that these patients were allergic to cow's milk, and had circulating and mast cell-bound IgE antibodies specific to cow's milk proteins. We found that the Sabin vaccine contained α-lactalbumin, which may have been responsible for the reactions elicited following vaccination with the Sabin and dual viral vaccines in combination. © 2012 Blackwell Publishing Ltd.

  14. IgE-mediated hypersensitivity reactions to cannabis in laboratory personnel.

    PubMed

    Herzinger, T; Schöpf, P; Przybilla, B; Ruëff, F

    2011-01-01

    There have been sporadic reports of hypersensitivity reactions to plants of the Cannabinaceae family (hemp and hops), but it has remained unclear whether these reactions are immunologic or nonimmunologic in nature. We examined the IgE-binding and histamine-releasing properties of hashish and marijuana extracts by CAP-FEIA and a basophil histamine release test. Two workers at a forensic laboratory suffered from nasal congestion, rhinitis, sneezing and asthmatic symptoms upon occupational contact with hashish or marijuana, which they had handled frequently for 25 and 16 years, respectively. Neither patient had a history of atopic disease. Serum was analyzed for specific IgE antibodies to hashish or marijuana extract by research prototype ImmunoCAP, and histamine release from basophils upon exposure to hashish or marijuana extracts was assessed. Results were matched to those of 4 nonatopic and 10 atopic control subjects with no known history of recreational or occupational exposure to marijuana or hashish. Patient 1 had specific IgE to both hashish and marijuana (CAP class 2), and patient 2 to marijuana only (CAP class 2). Controls proved negative for specific IgE except for 2 atopic individuals with CAP class 1 to marijuana and 1 other atopic individual with CAP class 1 to hashish. Stimulation of basophils with hashish or marijuana extracts elicited histamine release from basophils of both patients and 4 atopic control subjects. Our results suggest an IgE-related pathomechanism for hypersensitivity reactions to marijuana or hashish. Copyright © 2011 S. Karger AG, Basel.

  15. Antiviral efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV-infected children and adolescents: a systematic review protocol

    PubMed Central

    2014-01-01

    Background Abacavir is one of the recommended nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infections among children and adolescents. However, there are concerns that the antiviral efficacy of abacavir might be low when compared to other NRTIs especially among children. There are also concerns that abacavir use may lead to serious adverse events such as hypersensitivity reactions and has potential predisposition to developing cardiovascular diseases. Methods We plan to do a systematic review to evaluate the antiviral efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV-infected children aged between 3 months and 18 years, compared with other NRTIs. We will search Scopus, Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science databases for eligible studies regardless of language or publication status. We will check the reference lists of included studies, search relevant conference proceedings, email the authors of included studies and also look for unpublished and ongoing trials in prospective clinical trial registries. Two authors will independently screen search outputs, select studies, extract data and assess the risk of bias in included studies. All disagreements will be resolved by discussion and consensus. Where data allow, we will conduct meta-analysis for similar types of participants, study designs, interventions, and outcome measures. If the results are statistically homogeneous, we will use the fixed-effect model; otherwise, we will use the random-effects model and explore the reasons for heterogeneity using subgroup analyses. Heterogeneity will be assessed with the Chi-squared test and quantified with the I-squared statistic. Discussion The findings will be useful to policy makers and programme managers to inform treatment and management of HIV in children and adolescents and to point out research gaps for future research. Trial registration

  16. Antiviral efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV-infected children and adolescents: a systematic review protocol.

    PubMed

    Adetokunboh, Olatunji O; Schoonees, Anel; Wiysonge, Charles S

    2014-08-12

    Abacavir is one of the recommended nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infections among children and adolescents. However, there are concerns that the antiviral efficacy of abacavir might be low when compared to other NRTIs especially among children. There are also concerns that abacavir use may lead to serious adverse events such as hypersensitivity reactions and has potential predisposition to developing cardiovascular diseases. We plan to do a systematic review to evaluate the antiviral efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV-infected children aged between 3 months and 18 years, compared with other NRTIs. We will search Scopus, Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science databases for eligible studies regardless of language or publication status. We will check the reference lists of included studies, search relevant conference proceedings, email the authors of included studies and also look for unpublished and ongoing trials in prospective clinical trial registries. Two authors will independently screen search outputs, select studies, extract data and assess the risk of bias in included studies. All disagreements will be resolved by discussion and consensus. Where data allow, we will conduct meta-analysis for similar types of participants, study designs, interventions, and outcome measures. If the results are statistically homogeneous, we will use the fixed-effect model; otherwise, we will use the random-effects model and explore the reasons for heterogeneity using subgroup analyses. Heterogeneity will be assessed with the Chi-squared test and quantified with the I-squared statistic. The findings will be useful to policy makers and programme managers to inform treatment and management of HIV in children and adolescents and to point out research gaps for future research. This review is registered with PROSPERO

  17. Delayed-type hypersensitivity reactions induced by proton pump inhibitors: A clinical and in vitro T-cell reactivity study.

    PubMed

    Lin, C-Y; Wang, C-W; Hui, C-Y R; Chang, Y-C; Yang, C-H; Cheng, C-Y; Chen, W-W; Ke, W-M; Chung, W-H

    2018-01-01

    Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed-type hypersensitivity reactions (DHR) induced by PPI, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI-related DHR, followed up their tolerability to alternative anti-ulcer agents, and investigated the T-cell reactivity to PPI in PPI-related DHR patients. We retrospectively analyzed patients with PPI-related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross-hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon-γ to confirm the causalities. There were 69 cases of PPI-related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI-related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross-hypersensitivity reactions, whereas three patients developed cross-hypersensitivity reactions to alternative structurally similar PPI. The cross-reactivity to structurally similar PPI was also observed in LAT assay. PPIs have the potential to induce life-threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  18. STUDIES ON THE TUBERCULIN REACTION AND ON SPECIFIC HYPERSENSITIVENESS IN BACTERIAL INFECTION

    PubMed Central

    Zinsser, Hans

    1921-01-01

    The work reported in the preceding sections justifies, we think, a number of definite conclusions. In addition to this, some of the experiments indicate a line of thought which may lead to considerable alteration in our conceptions, both of phenomena of bacterial hypersensitiveness and of infection. 1. In guinea pigs two fundamentally different types of intradermal reactions may be observed. One of these is the immediate, transitory reaction which develops in animals sensitized against proteins (horse serum, etc.) and may be regarded as one of the manifestations of general protein hypersensitiveness, or anaphylaxis; the other is the tuberculin type of skin reaction which develops more slowly, leads to a more profound injury of the tissues and is independent of anaphylaxis as ordinarily conceived. 2. The tuberculin type of hypersensitiveness (as well as probably the typhoidin, mallein, abortin reactions, etc.) does not develop at all in guinea pigs sensitized with proteins, like horse serum, etc. While this form of hypersensitiveness may eventually be induced with materials not bacterial in origin, it has been observed up to date only as a reaction of bacterial infection. 3. Methods of treatment with protein material from bacterial cultures which sensitize guinea pigs to anaphylactic reactions with the bacterial extracts, do not sensitize them to the tuberculin type of reaction. Such sensitization is easily accomplished only by infecting the animals with living organisms. No reliable method of sensitizing guinea pigs to such reactions with dead bacterial material has as yet been worked out, though a few hopeful experiments have been obtained with massive injections of large amounts of the acid-precipitable substances (nucleoproteins?) from bacterial extracts. 4. In animals made hypersensitive to the tuberculin type of reaction by infection with living bacteria, the reaction may be elicited by intradermal injections of bacterial extracts from which all coagulable

  19. Characterization of hypersensitivity reactions reported among Andrographis paniculata users in Thailand using Health Product Vigilance Center (HPVC) database.

    PubMed

    Suwankesawong, Wimon; Saokaew, Surasak; Permsuwan, Unchalee; Chaiyakunapruk, Nathorn

    2014-12-24

    Andrographis paniculata (andrographis) is one of the herbal products that are widely used for various indications. Hypersensitivity reactions have been reported among subjects receiving Andrographis paniculata in Thailand. Understanding of characteristics of patients, adverse events, and clinical outcomes is essential for ensuring population safety.This study aimed to describe the characteristics of hypersensitivity reactions reported in patients receiving andrographis containing products in Thailand using national pharmacovigilance database. Thai Vigibase data from February 2001 to December 2012 involving andrographis products were used. This database includes the reports submitted through the spontaneous reporting system and intensive monitoring programmes. The database contained patient characteristic, adverse events associated with andrographis products, and details on seriousness, causality, and clinical outcomes. Case reports were included for final analysis if they met the inclusion criteria; 1) reports with andrographis being the only suspected cause, 2) reports with terms consistent with the constellation of hypersensitivity reactions, and 3) reports with terms considered critical terms according to WHO criteria. Descriptive statistics were used. A total of 248 case reports of andrographis-associated adverse events were identified. Only 106 case reports specified andrographis herbal product as the only suspected drug and reported at least one term consistent with constellation of hypersensitivity reactions. Most case reports (89%) came from spontaneous reporting system with no previously documented history of drug allergy (88%). Of these, 18 case reports were classified as serious with 16 cases requiring hospitalization. For final assessment, the case reports with terms consistent with constellation of hypersensitivity reactions and critical terms were included. Thirteen case reports met such criteria including anaphylactic shock (n = 5), anaphylactic

  20. HLA Association with Drug-Induced Adverse Reactions

    PubMed Central

    Fan, Wen-Lang; Shiao, Meng-Shin; Hui, Rosaline Chung-Yee; Wang, Chuang-Wei; Chang, Ya-Ching

    2017-01-01

    Adverse drug reactions (ADRs) remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs), such as Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA) genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV) infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01). The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- ) induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI). In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs. PMID:29333460

  1. Effects of relaxation on the delayed-type hypersensitivity (DTH) reaction to diphenylcyclopropenone (DCP).

    PubMed

    Zachariae, R; Jørgensen, M M; Christensen, S; Bjerring, P

    1997-07-01

    Delayed-type hypersensitivity (DTH) reactions to the experimental allergen diphenylcyclopropenone (DCP) were measured in four groups, which either trained (+) or did not train in relaxation (-) during the sensitization and/or the challenge phase. All groups consisted of high and low hypnotic susceptible subjects. While there were no differences in erythema, the mean induration of the group which trained in relaxation in both the sensitization and the challenge phase (+/+) was significantly greater than that of the group which trained in relaxation in the challenge phase only (-/+). Significant correlations were found between induration and hypnotic susceptibility scores, and between induration and degree of perceived relaxation during challenge. High hypnotic susceptible subjects experienced a higher degree of perceived relaxation and exhibited greater indurative and erythematous DTH reactions to DCP than low hypnotic susceptible subjects in all four experimental conditions. Though the mediating mechanisms remain unclear, our results suggest that relaxation may affect the DTH reaction, and support previous findings of higher psychophysiologic reactivity of high hypnotic susceptible subjects.

  2. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2009.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2010-01-01

    This review highlights some of the research advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insects, as well as advances in allergic skin disease that were reported in the Journal in 2009. Among key epidemiologic observations, several westernized countries report that more than 1% of children have peanut allergy, and there is some evidence that environmental exposure to peanut is a risk factor. The role of regulatory T cells, complement, platelet-activating factor, and effector cells in the development and expression of food allergy were explored in several murine models and human studies. Delayed anaphylaxis to mammalian meats appears to be related to IgE binding to the carbohydrate moiety galactose-alpha-1,3-galactose, which also has implications for hypersensitivity to murine mAb therapeutics containing this oligosaccharide. Oral immunotherapy studies continue to show promise for the treatment of food allergy, but determining whether the treatment causes tolerance (cure) or temporary desensitization remains to be explored. Increased baseline serum tryptase levels might inform the risk of venom anaphylaxis and might indicate a risk for mast cell disorders in persons who have experienced such episodes. Reduced structural and immune barrier function contribute to local and systemic allergen sensitization in patients with atopic dermatitis, as well as increased propensity of skin infections in these patients. The use of increased doses of nonsedating antihistamines and potential usefulness of omalizumab for chronic urticaria was highlighted. These exciting advances reported in the Journal can improve patient care today and provide insights on how we can improve the diagnosis and treatment of these allergic diseases in the future. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  3. Immediate Reactions to More Than 1 NSAID Must Not Be Considered Cross-Hypersensitivity Unless Tolerance to ASA Is Verified.

    PubMed

    Pérez-Alzate, D; Cornejo-García, J A; Pérez-Sánchez, N; Andreu, I; García-Moral, A; Agúndez, J A; Bartra, J; Doña, I; Torres, M J; Blanca, M; Blanca-López, N; Canto, G

    Individuals who develop drug hypersensitivity reactions (DHRs) to chemically unrelated nonsteroidal anti-inflammatory drugs (NSAIDs) are considered cross-hypersensitive. The hallmark for this classification is that the patient presents a reaction after intake of or challenge with acetylsalicylic acid (ASA). Whether patients react to 2 or more NSAIDs while tolerating ASA remains to be studied (selective reactions, SRs). Objective: To identify patients with SRs to 2 or more NSAIDs including strong COX-1 inhibitors. Patients who attended the Allergy Service of Hospital Infanta Leonor, Madrid, Spain with DHRs to NSAIDs between January 2011 and December 2014 were evaluated. Those with 2 or more immediate reactions occurring in less than 1 hour after intake were included. After confirming tolerance to ASA, the selectivity of the response to 2 or more NSAIDs was demonstrated by in vivo and/or in vitro testing or by controlled administration. From a total of 203 patients with immediate DHRs to NSAIDs, 16 (7.9%) met the inclusion criteria. The patients presented a total of 68 anaphylactic or cutaneous reactions (mean [SD], 4.2 [2.1]). Most reactions were to ibuprofen and other arylpropionic acid derivatives and to metamizole. Two different NSAIDs were involved in 11 patients and 3 in 5 patients. Patients with NSAID-induced anaphylaxis or urticaria/angioedema should not be considered cross-hypersensitive unless tolerance to ASA is verified.

  4. Cutaneous basophil anaphylaxis. Immediate vasopermeability increases and anaphylactic degranulation of basophils at delayed hypersensitivity reactions challenged with additional antigen.

    PubMed Central

    Askenase, P W; Debernardo, R; Tauben, D; Kashgarian, M

    1978-01-01

    Many delayed-type reactions contain large infiltrates of basophils whose function is unknown. We have studied these cutaneous basophil hypersensitivity (CBH) reactions in guinea-pigs to ascertain whether basophils that are recruited to delayed reaction sites could be triggered for immediate reactivity. We compared 24 h CBH reactions with nearby skin for immediate hypersensitivity by challenging each site with small amounts of antigen. CBH sites had augmented immediate increases in vascular permeability detected by extravasation of Evan's blue dye. The ability to elicit this augmented anaphylactic phenomenon correlated with the local presence of basophils, and light microscopy at CBH reactions 15 min after antigen challenge showed a 50% decline in basophil counts. Electron microscopy showed that progressive anaphylactic-type degranulation of local basophils occurred within minutes following reintroduction of antigen. There was fusion of vacuoles containing granules, exocytosis of granules, and dissolution of granules, without ultrastructural disruption of cellular integrity. These results establish that basophils in CBH reactions can be triggered with soluble antigen to undergo anaphylactic degranulation, with the immediate release of vasoactive mediators. We have termed this phenomenon 'cutaneous basophil anaphylaxis'. Thus, one function of basophils at sites of delayed hypersensitivity may be to provide the potential for augmented, local, immediate anaphylactic reactivity. Images Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:721140

  5. A systematic review of validated methods for identifying hypersensitivity reactions other than anaphylaxis (fever, rash, and lymphadenopathy), using administrative and claims data.

    PubMed

    Schneider, Gary; Kachroo, Sumesh; Jones, Natalie; Crean, Sheila; Rotella, Philip; Avetisyan, Ruzan; Reynolds, Matthew W

    2012-01-01

    The Food and Drug Administration's Mini-Sentinel pilot program aims to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest from administrative and claims data. This article summarizes the process and findings of the algorithm review of hypersensitivity reactions. PubMed and Iowa Drug Information Service searches were conducted to identify citations applicable to the hypersensitivity reactions of health outcomes of interest. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles using administrative and claims data to identify hypersensitivity reactions and including validation estimates of the coding algorithms. We identified five studies that provided validated hypersensitivity-reaction algorithms. Algorithm positive predictive values (PPVs) for various definitions of hypersensitivity reactions ranged from 3% to 95%. PPVs were high (i.e. 90%-95%) when both exposures and diagnoses were very specific. PPV generally decreased when the definition of hypersensitivity was expanded, except in one study that used data mining methodology for algorithm development. The ability of coding algorithms to identify hypersensitivity reactions varied, with decreasing performance occurring with expanded outcome definitions. This examination of hypersensitivity-reaction coding algorithms provides an example of surveillance bias resulting from outcome definitions that include mild cases. Data mining may provide tools for algorithm development for hypersensitivity and other health outcomes. Research needs to be conducted on designing validation studies to test hypersensitivity-reaction algorithms and estimating their predictive power, sensitivity, and specificity. Copyright © 2012 John Wiley & Sons, Ltd.

  6. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2006-07-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported primarily in the Journal in 2005. Although studies documented deficiencies in community management of anaphylaxis, guidelines and National Institutes of Health summary reports provide direction toward improved research and education. At least 9% of young children "outgrow" a tree nut allergy. Advances in food allergy diagnosis include reports of probability of reactions to peanut at various peanut-specific IgE concentrations and skin test response size and the utility of evaluating IgE binding to specific epitopes. Future food allergy treatments might include selection of "less allergenic" fruit cultivars, genetic silencing of major allergens, and treatment of allergic patients with Chinese herbal remedies. Osteopontin might be a useful biomarker for success of venom immunotherapy. Progress in our understanding of the immunology of atopic dermatitis and autoimmune urticaria has also been made. These observations will likely contribute toward optimizing management of these common allergic disorders.

  7. Patch-testing for the management of hypersensitivity reactions to second-line anti-tuberculosis drugs: a case report.

    PubMed

    Khan, Samsuddin; Andries, Aristomo; Pherwani, Asha; Saranchuk, Peter; Isaakidis, Petros

    2014-08-15

    The second-line anti-tuberculosis drugs used in the treatment of multidrug-resistant tuberculosis often cause adverse events, especially in patients co-infected with the human immunodeficiency virus. Severe hypersensitivity reactions due to these drugs are rare and there is little published experience to guide their management. A 17-year old Indian female multidrug-resistant tuberculosis patient co-infected with human immunodeficiency virus developed a hypersensitivity reaction after starting second-line anti-tuberculosis treatment in Mumbai, India. The patient was being treated with kanamycin, moxifloxacin, para-aminosalicylic acid, cycloserine, clofazimine, and amoxicillin-clavulanic acid. Twenty-four hours later, the patient developed generalized urticaria, morbilliform rash and fever. All drugs were suspended and the patient was hospitalised for acute management. Skin patch-testing was used to identify drugs that potentially caused the hypersensitivity reaction; results showed a strong reaction to clofazimine, moderate reaction to kanamycin and mild reaction to cycloserine. An interim second-line anti-tuberculosis regimen was prescribed; cycloserine and kanamycin were then re-challenged one-by-one using incremental dosing, an approach that allowed clinicians to re-introduce these drugs promptly and safely. The patient is currently doing well. This is the first case-report of a multidrug-resistant tuberculosis patient co-infected with the human immunodeficiency virus with hypersensitivity reaction to multiple second-line anti-tuberculosis drugs. Skin patch-testing and controlled re-challenge can be a useful management strategy in such patients. There is an urgent need for second-line anti-tuberculosis regimens that are more effective, safe and better tolerated.

  8. Incidence of immediate hypersensitivity reaction and serum sickness following administration of Crotalidae polyvalent immune Fab antivenom: a meta-analysis.

    PubMed

    Schaeffer, Tammi H; Khatri, Vaishali; Reifler, Liza M; Lavonas, Eric J

    2012-02-01

      Crotalidae polyvalent immune Fab (ovine) (FabAV) is commonly used in the treatment of symptomatic North American crotaline snake envenomation. When approved by the U.S. Food and Drug Administration in 2000, the incidences of immediate hypersensitivity reactions and serum sickness were reported as 0.14 and 0.18, respectively. The objective of this meta-analysis was to evaluate the incidence of immediate hypersensitivity reactions and serum sickness reported in studies of patients treated with FabAV therapy after North American crotaline envenomation.   The authors searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to September 20, 2010, for English-language medical literature and cross-referenced bibliographies of reviewed articles. The published abstracts of the major toxicology conferences were also searched. All prospective and retrospective cohort studies with patients receiving FabAV therapy for North American crotaline envenomations were eligible for data abstraction. Two content experts reviewed full-text articles and extracted relevant study design and outcome data. Proportions of immediate hypersensitivity and serum sickness for each study were analyzed in a random-effects model to produce an overall estimate of immediate hypersensitivity and serum sickness incidence associated with FabAV administration.   The literature search revealed 11 unique studies of patients who received FabAV that contained information on immediate hypersensitivity reactions and serum sickness. The meta-analysis produced a combined estimate of the incidence of immediate hypersensitivity of 0.08 (95% confidence interval [CI] = 0.05 to 0.11) and a combined estimate of the incidence of serum sickness of 0.13 (95% CI = 0.07 to 0.21).   In this systematic literature review and meta-analysis, the combined estimates of the incidence of immediate hypersensitivity reactions and serum sickness from FabAV in the treatment of symptomatic North American crotaline

  9. Proposal of a skin tests based approach for the prevention of recurrent hypersensitivity reactions to iodinated contrast media.

    PubMed

    Della-Torre, E; Berti, A; Yacoub, M R; Guglielmi, B; Tombetti, E; Sabbadini, M G; Voltolini, S; Colombo, G

    2015-05-01

    The purpose of the present work is to evaluate the efficacy of an approach that combines clinical history, skin tests results, and premedication, in preventing recurrent hypersensitivity reactions to iodinated contrast media (ICM). Skin Prick tests, Intradermal tests, and Patch tests were performed in 36 patients with a previous reaction to ICM. All patients underwent a second contrast enhanced radiological procedure with an alternative ICM selected on the basis of the proposed approach. After alternative ICM re-injection, only one patient presented a mild NIR. The proposed algorithm, validated in clinical settings where repeated radiological exams are needed, offers a safe and practical approach for protecting patients from recurrent hypersensitivity reactions to ICM.

  10. T-cells from HLA-B*57:01+ human subjects are activated with abacavir through two independent pathways and induce cell death by multiple mechanisms.

    PubMed

    Bell, Catherine C; Faulkner, Lee; Martinsson, Klara; Farrell, John; Alfirevic, Ana; Tugwood, Jonathan; Pirmohamed, Munir; Naisbitt, Dean J; Park, B Kevin

    2013-05-20

    Susceptibility to abacavir hypersensitivity has been attributed to possession of the specific human leukocyte antigen allele HLA-B*57:01. HLA-B*57:01-restricted activation of CD8+ T-cells provides a link between the genetic association and the iatrogenic disease. The objectives of this study were to characterize the functionality of drug-responsive CD8+ T-cell clones generated from HLA-B*57:01+ drug-naive subjects and to explore the relationship between abacavir accumulation in antigen presenting cells and the T-cell response. Seventy-four CD8+ clones expressing different Vβ receptors were shown to proliferate and kill target cells via different mechanisms when exposed to abacavir. Certain clones were activated with abacavir in the absence of antigen presenting cells. Analysis of the remaining clones revealed two pathways of drug-dependent T-cell activation. Overnight incubation of antigen presenting cells with abacavir, followed by repeated washing to remove soluble drug, activated approximately 50% of the clones, and the response was blocked by glutaraldehyde fixation. In contrast, a 1 h antigen presenting cell pulse did not activate any of the clones. Accumulation of abacavir in antigen presenting cells was rapid (less than 1 h), and the intracellular concentrations were maintained for 16 h. However, intracellular abacavir was not detectable by mass spectrometry after pulsing. These data suggest that T-cells can be activated by abacavir through a direct interaction with surface and intracellular major histocompatibility complex (MHC) molecules. With the former, abacavir seemingly participates in the MHC T-cell receptor binding interaction. In contrast, the latter pathway likely involves MHC binding peptides displayed as a consequence of abacavir exposure, but not abacavir itself.

  11. Oxidative bioactivation of abacavir in subcellular fractions of human antigen presenting cells.

    PubMed

    Bell, Catherine C; Santoyo Castelazo, Anahi; Yang, Emma L; Maggs, James L; Jenkins, Rosalind E; Tugwood, Jonathan; O'Neill, Paul M; Naisbitt, Dean J; Park, B Kevin

    2013-07-15

    Human exposure to abacavir, a primary alcohol antiretroviral, is associated with the development of immunological drug reactions in individuals carrying the HLA risk allele B*57:01. Interaction of abacavir with antigen presenting cells results in cell activation through an Hsp70-mediated Toll-like receptor pathway and the provision of T-cell antigenic determinants. Abacavir's electrophilic aldehyde metabolites are potential precursors of neoantigens. Herein, we have used mass spectrometry to study the oxidative metabolism of abacavir in EBV-transformed human B-cells. RNA and protein were isolated from the cells and subjected to transcriptomic and mass spectrometric analyses to identify the redox enzymes expressed. Low levels of isomeric abacavir carboxylic acids were detected in subcellular fractions of EBV-transformed human B-cells incubated with abacavir. Metabolite formation was time-dependent but was not reduced by an inhibitor of Class I alcohol dehydrogenases. Relatively high levels of mRNA were detected for several redox enzymes, including alcohol dehydrogenase 5 (Class III), aldehyde dehydrogenases (ALDH3A2, ALDH6A1, and ALDH9A1), CYP1B1, CYP2R1, CYP7B1, and hydroxysteroid dehydrogenase 10. Over 2600 proteins were identified by mass spectrometry. More than 1000 of these proteins exhibited catalytic activity, and 80 were oxido-reductases. This is the first proteomic inventory of enzymes in antigen presenting cells. However, neither of the hepatic alcohol dehydrogenases of Class I which metabolize abacavir in vitro was expressed at the protein level. Nevertheless the metabolic production of abacavir carboxylic acids by B-cell fractions implies abacavir-treated immune cells might be exposed to the drug's protein-reactive aldehyde metabolites in vivo.

  12. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2005-07-01

    This review highlights some of the research advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects that were reported primarily in the Journal in 2004. Clinical observations included that gastrointestinal symptoms during anaphylaxis are associated with an increased risk for hypotension; recurrence of peanut allergy can occur for about 8% of children who pass an oral food challenge and is associated with continued avoidance of the food after the challenge; seafood allergy is reported by 2.3% of the US population; and determination of the time to resolution of childhood egg and milk allergy might be predictable by means of serial determination of food-specific IgE levels. The comorbid effects of atopic dermatitis (AD) on asthma and the role of topical calcineurin inhibitors in the therapy of AD were also addressed. Basic and translational research observations indicate that improved diagnosis and therapy might become possible on the basis of reported identification or characterization of allergens such as: lipid transfer proteins and birch pollen-related cross-reactive allergens in plant foods; proteins in scorpion venom that cross-react with proteins from imported fire ant; mosquito saliva proteins responsible for systemic anaphylaxis; and IgE binding to quinolones detectable with an in vitro immunoassay. In addition, advances in understanding immune regulation associated with abrogation of oral tolerance in food allergy and of dendritic cell function, modulation of regulatory T cells, and chemokine expression in AD have elucidated possible targets for future intervention.

  13. Potential immediate hypersensitivity reactions following immunization in preschool aged children in Victoria, Australia.

    PubMed

    Baxter, C-M; Clothier, H J; Perrett, K P

    2018-04-06

    Immediate hypersensitivity reactions (IHR) are rare but potentially serious adverse events following immunization (AEFI). Surveillance of Adverse Events following Vaccination in the Community (SAEFVIC) is an enhanced passive surveillance system that collects, analyses and reports information about AEFI in Victoria, Australia. We describe the incidence, timing and type of potential IHR following vaccination in preschool children reported over an 8-year period. A total of 2110 AEFI were reported in 1620 children, of which 23.5% (496) were classified as potential IHR. Of these, 37.1% (184) were suspected to be IgE-mediated, (including anaphylaxis, angioedema and/or urticaria) and 83.5% (414) occurred within 15 minutes of vaccination. The incidence of potential IHR was 5.4 per 100,000 doses, with that of suspected IgE-mediated IHR being 2.0 per 100,000 doses. The incidence of anaphylaxis was extremely low (0.13 per 100,000 doses) and is consistent with other published studies. Potential IHR following immunization should be reported to appropriate local pharmacovigilance systems and patients reviewed by specialists able to evaluate, investigate and manage future vaccinations.

  14. Enhancement of the contact hypersensitivity reaction by acute morphine administration at the elicitation phase.

    PubMed

    Nelson, C J; How, T; Lysle, D T

    1999-11-01

    The present study investigated the effects of morphine on the irritant contact sensitivity (ICS) and contact hypersensitivity (CHS) reaction. ICS was induced by croton oil application on the pinnae of naïve rats. Morphine injected prior to croton oil application did not affect the ICS response when assessed by measurements of pinnae thickness. CHS was induced by applying the antigen 2,4-dinitro-1-fluorobenzene (DNFB) to the pinnae of rats sensitized to DNFB. Rats received an injection of morphine prior to either initial antigen exposure (sensitization) or antigen reexposure (challenge). Morphine prior to challenge, but not sensitization, resulted in a pronounced enhancement of the CHS response as measured by pinna thickness. Quantitative PCR also showed increased IFN-gamma mRNA levels in the inflamed tissue of morphine-treated rats. Naltrexone blocked the morphine-induced enhancement of the CHS response. The differential effects of morphine suggest that opioids have a more pronounced effect on in vivo immune responses that involve immunological memory. Copyright 1999 Academic Press.

  15. Frequencies of immune hypersensitivity reaction-associated HLA class I alleles in healthy South African Indian and mixed ancestry populations determined by a novel real-time PCR assay.

    PubMed

    Loubser, S; Paximadis, M; Gentle, N; Puren, A; Gray, C M; Tiemessen, C T

    2014-10-01

    We have determined the frequencies of human leucocyte antigen (HLA)-B*57:01, HLA-B*35:05, HLA-C*04 and HLA-C*08 in healthy individuals of South African Indian (SAI) ethnicity (n = 50) and South African mixed (SAM) ancestry (n = 50) using real-time allele-specific polymerase chain reaction (AS-PCR) assay. HLA-B*57:01 associates with immune hypersensitivity reaction (IHR) in individuals exposed to abacavir (ABC), while nevirapine (NVP) IHR associates with HLA-B*35:05, HLA-C*04 and HLA-C*08. Real-time AS-PCR assays typically use less DNA, are more cost-effective and rapid compared with conventional genotyping methods, such as sequence-based typing (SBT). The assay was developed using samples of known HLA class I genotype and subsequently applied to the SAI and SAM samples. HLA-B*57:01 was detected in SAM and SAI populations at frequencies of 8.0% and 12.0%, respectively, while HLA-B*35:05 was not found in SAI individuals, but was present in 6.0% of SAM individuals. HLA-C*04 was detected in 22.0% and 24.0% of SAM and SAI individuals, respectively, while 10.0% and 8.0% of SAM and SAI individuals, respectively, were HLA-C*08 positive. This study reports the development of a novel real-time AS-PCR assay to identify HLA class I alleles associated with ABC and NVP IHR and has established the frequencies of these alleles present in healthy SAI and SAM populations. Using South African demographic data, our hypothetical analysis suggests that a substantial number of individuals would benefit from the assay. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Metronidazole hypersensitivity.

    PubMed

    Knowles, S; Choudhury, T; Shear, N H

    1994-03-01

    To report a case of a possible hypersensitivity reaction induced by metronidazole. An Asian woman with a history of recurrent vaginitis had previously developed localized erythema while on intravaginal metronidazole and nystatin. While receiving oral metronidazole for treatment of a current bacterial vaginosis, she developed chills, fever, generalized erythema, and a rash within 60 minutes of the first dose. Treatment with diphenhydramine was instituted. The following day while in the hospital, the patient's condition worsened; she experienced shortness of breath and increased edema of the extremities. Methylprednisolone was administered with diphenhydramine and her condition improved over the next 5 days. The patient's vaginitis was treated with gentian violet and she was discharged on a tapering dosage of prednisone. Metronidazole-induced cutaneous reactions and systemic hypersensitivity reactions are reviewed. Alternatives to metronidazole and other potential cross-reactive drugs are suggested for the treatment of recurrent vaginitis. Although the patient's initial reaction to metronidazole represented a rare event, written documentation and communication in the patient's native language may have prevented the subsequent severe hypersensitivity reaction.

  17. Generalized reactions during skin testing with clindamycin in drug hypersensitivity: a report of 3 cases and review of the literature.

    PubMed

    Papakonstantinou, Eleni; Müller, Sabine; Röhrbein, Jan H; Wieczorek, Dorothea; Kapp, Alexander; Jakob, Thilo; Wedi, Bettina

    2018-04-01

    The diagnostic approach to drug hypersensitivity includes a detailed medical history, clinical examination, and skin testing and/or oral challenge with a culprit or alternative drug, depending on the type of reaction and the suspected drugs. Although skin testing is considered to be rather safe, cutaneous and systemic, including fatal, reactions have been described. To report 3 cases with generalized delayed reactions after skin testing with clindamycin, and to review the existing literature. Thorough clinical examination, blood tests and prick, intradermal and patch tests were performed in 3 patients. All patients experienced generalized maculopapular exanthema after intradermal and patch testing with clindamycin and amoxicillin in the first patient, and clindamycin alone in the second and third patient. None of the patients showed immediate reactions to skin tests, while positive intradermal reactions after 24 h to amoxicillin and clindamycin were observed in the first patient, and positive intradermal reactions after 24 h to clindamycin were observed in the second and third patients. Skin testing with clindamycin in the diagnosis of drug hypersensitivity carries some risk of adverse reactions. A stepwise and individual diagnostic work-up, considering potential risk factors, and testing in a specialized centre with emergency equipment available is highly recommended. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Herbex-kid Inhibits Immediate Hypersensitivity Reactions in Mice and Rats

    PubMed Central

    Prasad, Rawal; Jogge, Nanjan Mulla; Bhojraj, Suresh; Emerson, Solomon F.; Prabakar, S.

    2008-01-01

    Herbex-kid (HK), a polyherbal formulation was evaluated in various experimental allergic models of Type I hypersensitivity reactions. Compound 48/80 (C 48/80) has been shown to induce rat mesentery mast cell degranulation and HK (1.07, 10.75 and 107.5 mg ml−1) inhibited the mast cell degranulation in a dose dependent manner. HK (1.07, 10.75 and 107.5 mg kg−1; p.o.) showed dose-dependent protection against C 48/80 induced systemic anaphylaxis in male Balb/C mice. In active anaphylaxis model, male Wistar rats orally administered with 10.75 and 107.5 mg kg−1 of HK showed significant (P < 0.01) protection against mast cell degranulation, while in passive anaphylaxis model, only at 107.5 mg kg−1 showed significant (P < 0.01) reduction in mast cell degranulation. HK at all dose levels was able to significantly decrease the time spent in nasal rubbing in Wistar rats sensitized to ovalbumin, while only at 107.5 mg kg−1 it showed significant (P < 0.01) reduction in number of sneezes. In C 48/80-induced skin itch model, all dose levels of HK significantly (P < 0.001) decreased the time spent in itching and the number of itches. HK did not produce any significant inhibition in histamine induced contraction in guinea pig ileum. From the above findings we conclude that the HK possesses antiallergic activity mediated by reducing of the release mediators from mast cells and also by 5-HT antagonism without the involvement of histamine (H1) receptors. PMID:18830458

  19. Cercarial dermatitis caused by bird schistosomes comprises both immediate and late phase cutaneous hypersensitivity reactions.

    PubMed

    Kourilová, Pavlína; Hogg, Karen G; Kolárová, Libuse; Mountford, Adrian P

    2004-03-15

    Avian schistosomes are the primary causative agent of cercarial dermatitis in humans, but despite its worldwide occurrence, little is known of the immune mechanism of this disease. Using a murine model, hosts were exposed to primary (1x) and multiple (4x) infections of Trichobilharzia regenti via the pinna. Penetration of larvae into the skin evoked immediate edema, thickening of the exposure site, and an influx of leukocytes, including neutrophils, macrophages, CD4+ lymphocytes, and mast cells. A large proportion of the latter were in the process of degranulating. After 1x infection, inflammation was accompanied by the release of IL-1beta, IL-6, and IL-12p40. In contrast, in 4x reinfected animals the production of histamine, IL-4, and IL-10 was dramatically elevated within 1 h of infection. Analysis of Ag-stimulated lymphocytes from the skin-draining lymph nodes revealed that cells from 1x infected mice produced a mixed Th1/Th2 cytokine response, including abundant IFN-gamma, whereas cells from 4x reinfected mice were Th2 polarized, dominated by IL-4 and IL-5. Serum Abs confirmed this polarization, with elevated levels of IgG1 and IgE after multiple infections. Infection with radiolabeled cercariae revealed that almost 90% of larvae remained in the skin, and the majority died within 8 days after infection, although parasites were cleared more rapidly in 4x reinfected mice. Our results are the first demonstration that cercarial dermatitis, caused by bird schistosomes, is characterized by an early type I hypersensitivity reaction and a late phase of cutaneous inflammation, both associated with a polarized Th2-type acquired immune response.

  20. Antibiotics Are the Most Commonly Identified Cause of Perioperative Hypersensitivity Reactions.

    PubMed

    Kuhlen, James L; Camargo, Carlos A; Balekian, Diana S; Blumenthal, Kimberly G; Guyer, Autumn; Morris, Theresa; Long, Aidan; Banerji, Aleena

    2016-01-01

    Hypersensitivity reactions (HSRs) during the perioperative period are unpredictable and can be life threatening. Prospective studies for the evaluation of perioperative HSRs are lacking, and data on causative agents vary between different studies. The objective of this study was to prospectively determine the success of a comprehensive allergy evaluation plan for patients with HSRs during anesthesia, including identification of a causative agent and outcomes during subsequent anesthesia exposure. All patients referred for a perioperative HSR between November 2013 and March 2015, from a Boston teaching hospital, were evaluated using a standardized protocol with skin testing (ST) within 6 months of HSR. Comprehensive allergy evaluation included collection of patient information, including characteristics of HSR during anesthesia. We reviewed the results of ST and/or test doses for all potential causative medications Event-related tryptase levels were reviewed when available. Over 17 months, 25 patients completed the comprehensive allergy evaluation. Fifty-two percent (13 of 25) were female with a median age of 52 (interquartile range 43-66) years. The most frequently observed HSR systems were cutaneous (68%), cardiovascular (64%), and pulmonary (24%). A culprit drug, defined as a positive ST, was identified in 36% (9 of 25) of patients. The most common agent identified was cefazolin (6 of 9). After our comprehensive evaluation and management plan, 7 (7 of 8, 88%) patients tolerated subsequent anesthesia. Cefazolin was the most commonly identified cause of a perioperative HSR in our study population. Skin testing patients within 6 months of a perioperative HSR may improve the odds of finding a positive result. Tolerance of subsequent anesthesia is generally achieved in patients undergoing our comprehensive evaluation. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Peripheral Blood Eosinophilia and Hypersensitivity Reactions among Patients Receiving Outpatient Parenteral Antibiotics

    PubMed Central

    Blumenthal, Kimberly G.; Youngster, Ilan; Rabideau, Dustin J.; Parker, Robert A.; Manning, Karen S.; Walensky, Rochelle P.; Nelson, Sandra B.

    2015-01-01

    Background While drug-induced peripheral eosinophilia complicates antimicrobial therapy, little is known about its frequency and implications. Objective We aimed to determine the frequency and predictors of antibiotic-induced eosinophilia and subsequent hypersensitivity reactions (HSRs). Methods We evaluated a prospective cohort of former inpatients receiving intravenous antibiotic therapy as outpatients with at least one differential blood count. We used multivariate Cox proportional hazards models, with time-varying antibiotic treatment indicators, to assess the impact of demographic data and antibiotic exposures on eosinophilia and subsequent HSR, including documented rash, renal injury, and liver injury. Possible Drug Rash Eosinophilia and Systemic Symptoms (DRESS) syndrome cases were identified and manually validated. Results Of 824 patients (60% male, median age 60 years, median therapy duration 41 days), 210 (25%) developed eosinophilia with median peak absolute eosinophil count of 726/mL [IQR: 594–990/mL]. Use of vancomycin, penicillin, rifampin, and linezolid were associated with a higher hazard of developing eosinophilia. There was subsequent HSR in 64/210 (30%) patients with eosinophilia, including rash (N=32), renal injury (N=31), and liver injury (N=13). Patients with eosinophilia were significantly more likely to develop rash (HR = 4.16 [2.54, 6.83]; p<0.0001) and renal injury (HR = 2.13 [1.36, 3.33]; p=0.0009), but not liver injury (HR = 1.75 [0.92, 3.33]; p=0.09). Possible DRESS syndrome occurred in 7/824 (0.8%) patients; 4 (57%) were on vancomycin. Conclusions Drug-induced eosinophilia is common with parenteral antibiotics. While most patients with eosinophilia do not develop an HSR, eosinophilia increases the hazard rate of developing rash and renal injury. DRESS syndrome was more common than previously described. PMID:25981739

  2. Drug‐specific hypophosphatemia and hypersensitivity reactions following different intravenous iron infusions

    PubMed Central

    Hvas, Christian L.; Dahlerup, Jens F.

    2017-01-01

    Aims Intravenous (IV) iron infusions have been associated with hypophosphataemia (HP) and hypersensitivity reactions (HSRs). No studies have compared the side effects of ferric carboxymaltose (FCM) with those of isomaltoside 1000 (ISM). This study aimed to describe the occurrence of HP and HSRs following the administration of either FCM or ISM. Methods Data on 231 outpatients treated with IV iron infusions, between November 2011 and April 2014, were collected. During that period, the department made a switch from FCM to ISM and then back to FCM. Of the 231 patients, 39 received both FCM and ISM during the period. The prevalences of HP and HSRs were compared between the two drugs. Results We found more HP events when FCM was given (64 vs. 9; P < 0.01). In contrast, more patients had mild HSRs when ISM was given (2.5% vs. 10.7%; P < 0.01). A comparison of the two drugs in the subpopulation who received both drug types (n = 39) revealed a difference in phosphate decrease (P < 0.01), with the most marked decrease occurring with FCM. Nine patients who had HSRs were exposed to both drugs. No potential HSR crossover between the two drugs was found. Conclusion We found a higher risk of HP with FCM administration when compared to ISM administration. Conversely, we found a higher risk of mild HSRs with ISM administration when compared to FCM administration. The impacts of the two types of side effects should be considered when choosing an IV iron drug. PMID:27859495

  3. Drug-specific hypophosphatemia and hypersensitivity reactions following different intravenous iron infusions.

    PubMed

    Bager, Palle; Hvas, Christian L; Dahlerup, Jens F

    2017-05-01

    Intravenous (IV) iron infusions have been associated with hypophosphataemia (HP) and hypersensitivity reactions (HSRs). No studies have compared the side effects of ferric carboxymaltose (FCM) with those of isomaltoside 1000 (ISM). This study aimed to describe the occurrence of HP and HSRs following the administration of either FCM or ISM. Data on 231 outpatients treated with IV iron infusions, between November 2011 and April 2014, were collected. During that period, the department made a switch from FCM to ISM and then back to FCM. Of the 231 patients, 39 received both FCM and ISM during the period. The prevalences of HP and HSRs were compared between the two drugs. We found more HP events when FCM was given (64 vs. 9; P < 0.01). In contrast, more patients had mild HSRs when ISM was given (2.5% vs. 10.7%; P < 0.01). A comparison of the two drugs in the subpopulation who received both drug types (n = 39) revealed a difference in phosphate decrease (P < 0.01), with the most marked decrease occurring with FCM. Nine patients who had HSRs were exposed to both drugs. No potential HSR crossover between the two drugs was found. We found a higher risk of HP with FCM administration when compared to ISM administration. Conversely, we found a higher risk of mild HSRs with ISM administration when compared to FCM administration. The impacts of the two types of side effects should be considered when choosing an IV iron drug. © 2016 The British Pharmacological Society.

  4. Antibiotics are the Most Commonly Identified Cause of Perioperative Hypersensitivity Reactions

    PubMed Central

    Kuhlen, James L.; Camargo, Carlos A.; Balekian, Diana S.; Blumenthal, Kimberly G.; Guyer, Autumn; Morris, Theresa; Long, Aidan; Banerji, Aleena

    2016-01-01

    Background Hypersensitivity reactions (HSR) during the perioperative period are unpredictable and can be life threatening. Prospective studies for evaluation of perioperative HSR are lacking and data on causative agents varies between different studies. Objective To prospectively determine the success of a comprehensive allergy evaluation plan for patients with HSR during anesthesia, including identification of causative agent and outcomes during subsequent anesthesia exposure. Methods All patients referred for perioperative HSR between November 2013 and March 2015, from a Boston teaching hospital, were evaluated using a standardized protocol with skin testing (ST) within 6 months of HSR. Comprehensive allergy evaluation included collection of patient information, including characteristics of HSR during anesthesia. We reviewed results of ST and/or test doses for all potential causative medications Event-related tryptase levels were reviewed when available. Results Over 17 months, 25 patients completed the comprehensive allergy evaluation. Fifty-two percent (13/25) were female with a median age of 52 (IQR 43–66) years. The most frequently observed HSR systems were cutaneous (68%), cardiovascular (64%), and pulmonary (24%). A culprit drug, defined as a positive ST, was identified in 36% (9/25) of patients. The most common agent identified was cefazolin (6/9). Following our comprehensive evaluation and management plan, seven (7/8, 88%) patients tolerated subsequent anesthesia. Conclusions Cefazolin was the most commonly identified cause of perioperative HSR in our study population. Skin testing patients within 6 months of a perioperative HSR may improve the odds of finding a positive result. Tolerance of subsequent anesthesia is generally achieved in patients undergoing our comprehensive evaluation. PMID:27039234

  5. Hypersensitivity Reactions to Oxaliplatin: Identifying the Risk Factors and Judging the Efficacy of a Desensitization Protocol.

    PubMed

    Okayama, Tetsuya; Ishikawa, Takeshi; Sugatani, Kazuko; Yoshida, Naohisa; Kokura, Satoshi; Matsuda, Kiyomi; Tsukamoto, Shigeru; Ihara, Norihiko; Kuriu, Yoshiaki; Nakanishi, Masayoshi; Nakamura, Terukazu; Kamada, Kazuhiro; Katada, Kazuhiro; Uchiyama, Kazuhiko; Takagi, Tomohisa; Handa, Osamu; Konishi, Hideyuki; Yagi, Nobuaki; Naito, Yuji; Otsuji, Eigo; Hosoi, Hajime; Miki, Tsuneharu; Itoh, Yoshito

    2015-06-01

    We examined the clinical data of patients treated with oxaliplatin to determine the risk factors of oxaliplatin-related hypersensitivity reaction (HSR). In addition, we evaluated the efficacy of rechallenging patients with HSRs with oxaliplatin using prophylactic agents or desensitization procedures. This study consisted of 162 patients with colorectal cancer (88 men and 74 women) who were treated consecutively at the outpatient chemotherapy department at University Hospital, Kyoto Prefectural University of Medicine. Patients underwent chemotherapy, including oxaliplatin, between March 2006 and June 2012. We analyzed the patients' clinical backgrounds (eg, age, sex, performance status, disease stage, and allergic history) to uncover any connections to the development of HSR to oxaliplatin. In addition, we rechallenged 10 patients who had oxaliplatin-related HSR using prophylactic agents or desensitization procedures. Of 162 patients, 28 (17.2%) developed oxaliplatin-related HSRs (16, 2, 9 and 1 patient had grade 1, 2, 3, and 4 HSRs, respectively). The total cumulative dose of oxaliplatin at the onset of the HSR was 301 to 1126 mg/m(2) (median, 582 mg/m(2)), and the first reactions developed in these patients after 5 to 17 infusions of oxaliplatin (median, 8 infusions). Logistic regression analysis indicated that sex (male: odds ratio = 3.624; 95% CI, 1.181-11.122; P = 0.024) and eosinophil count in peripheral blood (odds ratio = 35.118; 95% CI, 1.058-1166.007; P = 0.046) were independent variables for oxaliplatin-related HSRs. Rechallenging patients with prophylactic agents was successful in 2 (28.6%) of 7 patients who successfully completed their treatment. On the other hand, all 3 patients rechallenged with oxaliplatin using a desensitization protocol successfully completed their treatment without new HSRs. In this retrospective study, we observed that being male and having higher counts of peripheral eosinophil could be predictors for HSR to oxaliplatin. In

  6. Respiratory hypersensitivity reactions to NSAIDs in Europe: the global allergy and asthma network (GA2 LEN) survey.

    PubMed

    Makowska, J S; Burney, P; Jarvis, D; Keil, T; Tomassen, P; Bislimovska, J; Brozek, G; Bachert, C; Baelum, J; Bindslev-Jensen, C; Bousquet, J; Bousquet, P J; Kai-Håkon, C; Dahlen, S E; Dahlen, B; Fokkens, W J; Forsberg, B; Gjomarkaj, M; Howarth, P; Salagean, E; Janson, C; Kasper, L; Kraemer, U; Louiro, C; Lundback, B; Minov, J; Nizankowska-Mogilnicka, E; Papadopoulos, N; Sakellariou, A G; Todo-Bom, A; Toskala, E; Zejda, J E; Zuberbier, T; Kowalski, M L

    2016-11-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders. The GA 2 LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID-induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires. The mean prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants with chronic rhinosinusitis symptoms (Odds Ratio 2.12; 95%CI 1.78-2.74), asthma symptoms in last 12 months (2.7; 2.18-3.35), hospitalization due to asthma (1.53; 1.22-1.99), and adults vs children (1.53; 1.24-1.89), but was not associated with allergic rhinitis. Our study documented significant variation between European countries in the prevalence of NSAID-induced respiratory hypersensitivity reactions, and association with chronic airway diseases, but also with environmental factors. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. New genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity.

    PubMed

    Pirmohamed, Munir; Ostrov, David A; Park, B Kevin

    2015-08-01

    Drug hypersensitivity reactions are an important clinical problem for both health care and industry. Recent advances in genetics have identified a number of HLA alleles associated with a range of these adverse reactions predominantly affecting the skin but also other organs, such as the liver. The associations between abacavir hypersensitivity and HLA-B*57:01 and carbamazepine-induced Stevens-Johnson syndrome and HLA-B*15:02 have been implemented in clinical practice. There are many different mechanisms proposed in the pathogenesis of drug hypersensitivity reactions, including the hapten hypothesis, direct binding to T-cell receptors (the pharmacologic interaction hypothesis), and peptide-binding displacement. A problem with all the hypotheses is that they are largely based on in vitro findings, with little direct in vivo evidence. Although most studies have focused on individual mechanisms, it is perhaps more important to consider them all as being complementary, potentially occurring at the same time with the same drug in the same patient. This might at least partly account for the heterogeneity of the immune response seen in different patients. There is a need to develop novel methodologies to evaluate how the in vitro mechanisms relate to the in vivo situation and how the highly consistent genetic findings with different HLA alleles can be more consistently used for both prediction and prevention of these serious adverse reactions. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. New genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity

    PubMed Central

    Pirmohamed, Munir; Ostrov, David A.; Park, B. Kevin

    2015-01-01

    Drug hypersensitivity reactions are an important clinical problem for both health care and industry. Recent advances in genetics have identified a number of HLA alleles associated with a range of these adverse reactions predominantly affecting the skin but also other organs, such as the liver. The associations between abacavir hypersensitivity and HLA-B*57:01 and carbamazepine-induced Stevens-Johnson syndrome and HLA-B*15:02 have been implemented in clinical practice. There are many different mechanisms proposed in the pathogenesis of drug hypersensitivity reactions, including the hapten hypothesis, direct binding to T-cell receptors (the pharmacologic interaction hypothesis), and peptide-binding displacement. A problem with all the hypotheses is that they are largely based on in vitro findings, with little direct in vivo evidence. Although most studies have focused on individual mechanisms, it is perhaps more important to consider them all as being complementary, potentially occurring at the same time with the same drug in the same patient. This might at least partly account for the heterogeneity of the immune response seen in different patients. There is a need to develop novel methodologies to evaluate how the in vitro mechanisms relate to the in vivo situation and how the highly consistent genetic findings with different HLA alleles can be more consistently used for both prediction and prevention of these serious adverse reactions. PMID:26254050

  9. Effect of Prophylactic Extended-Infusion Carboplatin on Incidence of Hypersensitivity Reactions in Patients with Ovarian, Fallopian Tube, or Peritoneal Carcinomas.

    PubMed

    Pasternak, Amy L; Link, Nicholas A; Richardson, Carolyn M; Rose, Peter G

    2016-07-01

    To determine whether extended-infusion carboplatin, initiated at approximately the eighth cumulative carboplatin cycle and prior to development of carboplatin hypersensitivity, reduces the incidence of carboplatin hypersensitivity reactions in patients with ovarian, fallopian tube, or peritoneal cancer. Retrospective chart review. Large integrated health system. A total of 326 patients with ovarian, fallopian tube, or primary peritoneal cancer who received at least eight cumulative cycles of carboplatin between January 2007 and September 2014 were included. Of these, 161 patients received all doses of carboplatin infused over 30 or 60 minutes (standard-infusion group [total of 1317 carboplatin cycles]), and 165 patients received the 3-hour extended infusion of carboplatin administered at approximately the eighth cumulative cycle and prior to development of a hypersensitivity reaction (extended-infusion group [total of 1527 carboplatin cycles]). Baseline characteristics were similar between the groups, except significantly more patients in the extended-infusion group received triple premedication therapy prior to infusion (p<0.001). Hypersensitivity reactions occurred in 64 patients (40%) who received standard-infusion carboplatin and 40 patients (24.2%) who received extended-infusion carboplatin (p=0.0027). The median cycle of hypersensitivity reaction development did not differ significantly between the groups: 9 cycles in patients who received standard-infusion versus 11 cycles in patients who received extended-infusion carboplatin (p=0.06). Through regression analysis, the premedication regimen received prior to carboplatin infusion was the only variable significantly associated with hypersensitivity reactions (odds ratio 0.59, 95% confidence interval 0.36-0.97, p=0.038). Patients who received extended-infusion carboplatin experienced a lower incidence of hypersensitivity reactions than patients who received standard-infusion carboplatin, which may be attributed

  10. Hypersensitivity reaction to β-lactam antibiotics in patients with adult T-cell leukemia/lymphoma treated with mogamulizumab
.

    PubMed

    Yasu, Takeo; Imai, Yoichi; Ohno, Nobuhiro; Uchimaru, Kaoru; Kurokawa, Yosuke; Tojo, Arinobu

    2017-10-01

    Mogamulizumab (MOG) is a humanized anti-CCR4 monoclonal antibody that is highly cytotoxic for adult T-cell leukemia/lymphoma (ATL) cells. Most non-hematological adverse events are cutaneous adverse reactions in ATL patients. We reviewed the medical records of 24 patients with CCR4-positive aggressive ATL who had received MOG treatment. The incidence of MOG-induced cutaneous adverse reactions (MCARs) was 25% (6 patients). Four patients with MCAR had an interesting clinical course, compared with MCARs reported in previous reports. The factors causing MCAR were suspected to be cefepime, cefozopran, and piperacillin/tazobactam. We consider that hypersensitivity reaction to β-lactam antibiotics is involved in a significant proportion of MCARs.
.

  11. An Animal Model of Abacavir-Induced HLA-Mediated Liver Injury.

    PubMed

    Song, Binbin; Aoki, Shigeki; Liu, Cong; Susukida, Takeshi; Ito, Kousei

    2018-04-01

    Genome-wide association studies indicate that several idiosyncratic adverse drug reactions are highly associated with specific human leukocyte antigen (HLA) alleles. For instance, abacavir, a human immunodeficiency virus reverse transcriptase inhibitor, induces multiorgan toxicity exclusively in patients carrying the HLA-B*57:01 allele. However, the underlying mechanism is unclear due to a lack of appropriate animal models. Previously, we developed HLA-B*57:01 transgenic mice and found that topical application of abacavir to the ears induced proliferation of CD8+ lymphocytes in local lymph nodes. Here, we attempted to reproduce abacavir-induced liver injury in these mice. However, oral administration of abacavir alone to HLA-B*57:01 transgenic mice did not increase levels of the liver injury marker alanine aminotransferase. Considering the importance of innate immune activation in mouse liver, we treated mice with CpG oligodeoxynucleotide, a toll-like receptor 9 agonist, plus abacavir. This resulted in a marked increase in alanine aminotransferase, pathological changes in liver, increased numbers of activated CD8+ T cells, and tissue infiltration by immune cells exclusively in HLA-B*57:01 transgenic mice. These results indicate that CpG oligodeoxynucleotide-induced inflammatory reactions and/or innate immune activation are necessary for abacavir-induced HLA-mediated liver injury characterized by infiltration of CD8+ T cells. Thus, we developed the first mouse model of HLA-mediated abacavir-induced idiosyncratic liver injury. Further investigation will show that the proposed HLA-mediated liver injury model can be applied to other combinations of drugs and HLA types, thereby improving drug development and contributing to the development of personalized medicine.

  12. Reduced Levels of Chloroplast FtsH Protein in Tobacco Mosaic Virus–Infected Tobacco Leaves Accelerate the Hypersensitive Reaction

    PubMed Central

    Seo, Shigemi; Okamoto, Masaji; Iwai, Takayoshi; Iwano, Megumi; Fukui, Kiichi; Isogai, Akira; Nakajima, Nobuyoshi; Ohashi, Yuko

    2000-01-01

    In tobacco cultivars resistant to tobacco mosaic virus (TMV), infection results in the death of the infected cells accompanying the formation of necrotic lesions. To identify the genes involved in this hypersensitive reaction, we isolated the cDNA of tobacco DS9, the transcript of which decreases before the appearance of necrotic lesions. The DS9 gene encodes a chloroplastic homolog of bacterial FtsH protein, which serves to maintain quality control of some cytoplasmic and membrane proteins. A large quantity of DS9 protein was found in healthy leaves, whereas the quantity of DS9 protein in infected leaves decreased before the lesions appeared. In transgenic tobacco plants containing less and more DS9 protein than wild-type plants, the necrotic lesions induced by TMV were smaller and larger, respectively, than those on wild-type plants. These results suggest that a decrease in the level of DS9 protein in TMV-infected cells, resulting in a subsequent loss of function of the chloroplasts, accelerates the hypersensitive reaction. PMID:10852937

  13. Hypersensitivity reactions associated with L-asparaginase administration in 142 dogs and 68 cats with lymphoid malignancies: 2007-2012.

    PubMed

    Blake, Mary Kay; Carr, Brittany J; Mauldin, Glenna E

    2016-02-01

    Clinically significant hypersensitivity reactions (HSRs) to the chemotherapy drug L-asparaginase are reported in humans and dogs, but frequency in small animals is not well-defined. This study retrospectively evaluated the frequency of HSR to L-asparaginase given by IM injection to dogs and cats with lymphoid malignancies. The medical records of all dogs and cats treated with at least 1 dose of L-asparaginase chemotherapy over a 5-year period were reviewed. A total of 370 doses of L-asparaginase were administered to the dogs, with 88 of 142 dogs receiving multiple doses, and 6 dogs experiencing an HSR. A total of 197 doses were administered to the cats, with 33 of 68 cats receiving multiple doses, and no cats experiencing an HSR. Hypersensitivity reactions were documented in 4.2% of dogs, and in association with 1.6% of L-asparaginase doses administered. These results show that HSRs occur uncommonly among dogs and cats, even with repeated dosing.

  14. Hypersensitivity reactions associated with L-asparaginase administration in 142 dogs and 68 cats with lymphoid malignancies: 2007–2012

    PubMed Central

    Blake, Mary Kay; Carr, Brittany J.; Mauldin, Glenna E.

    2016-01-01

    Clinically significant hypersensitivity reactions (HSRs) to the chemotherapy drug L-asparaginase are reported in humans and dogs, but frequency in small animals is not well-defined. This study retrospectively evaluated the frequency of HSR to L-asparaginase given by IM injection to dogs and cats with lymphoid malignancies. The medical records of all dogs and cats treated with at least 1 dose of L-asparaginase chemotherapy over a 5-year period were reviewed. A total of 370 doses of L-asparaginase were administered to the dogs, with 88 of 142 dogs receiving multiple doses, and 6 dogs experiencing an HSR. A total of 197 doses were administered to the cats, with 33 of 68 cats receiving multiple doses, and no cats experiencing an HSR. Hypersensitivity reactions were documented in 4.2% of dogs, and in association with 1.6% of L-asparaginase doses administered. These results show that HSRs occur uncommonly among dogs and cats, even with repeated dosing. PMID:26834270

  15. From the Children’s Oncology Group: Evidence-based recommendations for PEG-asparaginase nurse monitoring, hypersensitivity reaction management, and patient/family education

    PubMed Central

    Woods, Deborah; Winchester, Kari; Towerman, Alison; Gettinger, Katie; Carey, Christina; Timmermann, Karen; Langley, Rachel; Browne, Emily

    2017-01-01

    PEG-aspariginase is a backbone chemotherapy agent in pediatric acute lymphoblastic leukemia and in some non-Hodgkin lymphoma therapies. Nurses lack standardized guidelines for monitoring patients receiving PEG-asparaginase and for educating patients/families about hypersensitivity reaction risks. An electronic search of six databases using publication years 2000–2015 and multiple professional organizations and clinical resources was conducted. Evidence sources were reviewed for topic applicability. Each of the final 23 sources was appraised by two team members. The GRADE system was used to assign a quality and strength rating for each recommendation. Multiple recommendations were developed: four relating to nurse monitoring of patients during and after drug administration, eight guiding hypersensitivity reaction management, and four concerning patient/family educational content. These strong recommendations were based on moderate, low, or very-low quality evidence. Several recommendations relied upon generalized drug hypersensitivity guidelines. Additional research is needed to safely guide PEG-asparaginase monitoring, hypersensitivity reaction management and patient/family education. Nurses administering PEG-asparaginase play a critical role in the early identification and management of hypersensitivity reactions. PMID:28602129

  16. Quantitation of cytokine mRNA expression as an endpoint for prediction and diagnosis of xenobiotic-induced hypersensitivity reactions.

    PubMed

    Gaspard, I; Kerdine, S; Pallardy, M; Lebrec, H

    1999-09-01

    Xenobiotic-induced hypersensitivity reactions are immune-mediated effects that involve specific antibodies and/or effector and regulatory T lymphocytes. Cytokines are key mediators of such responses and must be considered as possible endpoints for predicting sensitizing potency of drugs and chemicals, as well as for helping diagnosis of allergy. Detecting cytokine production at the protein level has been shown to not be always sensitive enough. This paper describes three examples of the utilization of semiquantitative or competitive reverse transcription polymerase chain reaction analysis of interleukin-4, interferon gamma, and interleukin-1beta mRNAs as endpoints for assessing T-cell or dendritic cell responses to sensitizing drugs (beta-lactam antibiotics) or chemicals (dinitrochlorobenzene). Copyright 1999 Academic Press.

  17. Primary irritant and delayed-contact hypersensitivity reactions to the freshwater cyanobacterium Cylindrospermopsis raciborskii and its associated toxin cylindrospermopsin

    PubMed Central

    Stewart, Ian; Seawright, Alan A; Schluter, Philip J; Shaw, Glen R

    2006-01-01

    Background Freshwater cyanobacteria are common inhabitants of recreational waterbodies throughout the world; some cyanobacteria can dominate the phytoplankton and form blooms, many of which are toxic. Numerous reports in the literature describe pruritic skin rashes after recreational or occupational exposure to cyanobacteria, but there has been little research conducted on the cutaneous effects of cyanobacteria. Using the mouse ear swelling test (MEST), we sought to determine whether three toxin-producing cyanobacteria isolates and the purified cyanotoxin cylindrospermopsin produced delayed-contact hypersensitivity reactions. Methods Between 8 and 10 female Balb/c mice in each experiment had test material applied to depilated abdominal skin during the induction phase and 10 or 11 control mice had vehicle only applied to abdominal skin. For challenge (day 10) and rechallenge (day 17), test material was applied to a randomly-allocated test ear; vehicle was applied to the other ear as a control. Ear thickness in anaesthetised mice was measured with a micrometer gauge at 24 and 48 hours after challenge and rechallenge. Ear swelling greater than 20% in one or more test mice is considered a positive response. Histopathology examination of ear tissues was conducted by independent examiners. Results Purified cylindrospermopsin (2 of 9 test mice vs. 0 of 5 control mice; p = 0.51) and the cylindrospermopsin-producing cyanobacterium C. raciborskii (8 of 10 test mice vs. 0 of 10 control mice; p = 0.001) were both shown to produce hypersensitivity reactions. Irritant reactions were seen on abdominal skin at induction. Two other toxic cyanobacteria (Microcystis aeruginosa and Anabaena circinalis) did not generate any responses using this model. Histopathology examinations to determine positive and negative reactions in ear tissues showed excellent agreement beyond chance between both examiners (κ = 0.83). Conclusion The irritant properties and cutaneous sensitising potential of

  18. The risk for cross-reactions after a cutaneous delayed-type hypersensitivity reaction to heparin preparations is independent of their molecular weight: a systematic review.

    PubMed

    Weberschock, Tobias; Meister, Anna Christina; Bohrt, Kevin; Schmitt, Jochen; Boehncke, Wolf-Henning; Ludwig, Ralf J

    2011-10-01

    Heparins are a widely used class of drugs known to cause delayed-type hypersensitivity (DTH) reactions. Recent publications indicate that the incidence of these may be higher than previously thought. To date, patient-related but no drug-related risk factors for the development of DTH reactions to heparins have been identified, although molecular weight is discussed as a potentially relevant parameter. To address this, a systematic review was conducted on the frequency of cross-reactions after DTH reactions to heparin preparations. We electronically searched MEDLINE and EMBASE, hand-searched selected journals and references, and contacted experts for unpublished data. Sixty-six publications and unpublished data of 14 patients resulted in 198 patients with 1084 tests for cross-reactivity. The primary causative agents were mostly unfractionated heparin (50%) and low molecular weight heparins (49.5%). Cross-reactions were more likely after an initial DTH reaction to unfractionated heparin than after an initial DTH reaction to low molecular weight heparin. Our findings also indicate that molecular weight does not correlate with the risk for cross-reactivity, which is in line with recent observations, indicating that different heparins have to be individually considered. The available data demonstrated the lowest overall risk for cross-reactions for pentosan polysulfate (36.4%) and fondaparinux (10.4%). In the clinical context, fondaparinux is recommended as the current best alternative when a DTH reaction occurs. © 2011 John Wiley & Sons A/S.

  19. A Review on Dapsone Hypersensitivity Syndrome Among Chinese Patients with an Emphasis on Preventing Adverse Drug Reactions with Genetic Testing.

    PubMed

    Wang, Na; Parimi, Leela; Liu, Hong; Zhang, Furen

    2017-05-01

    AbstractDapsone is a bactericidal and bacteriostatic against Mycobacterium leprae , a causative agent of leprosy. Dapsone is also applied in a range of medical fields because of its anti-inflammatory and immunomodulatory effects. Dapsone hypersensitivity syndrome (DHS) is a rare yet serious adverse drug reaction (ADR) caused by dapsone involving multiple organs. We performed a systematic review of published articles describing dapsone-induced hypersensitivity syndrome, including all Chinese articles and the latest literature available in online databases published between October 2009 and October 2015. We determined the prevalence, clinical characteristics, and mortality rate of DHS. Importantly, we also summarized the recent advances in genetic testing allowing prediction of ADRs. In an initial systematic electronic search, we retrieved 191 articles. Subsequently, these articles were further filtered and ultimately 84 articles (60 Chinese case reports, 21 non-Chinese articles, and three epidemiological studies) were selected, which included 877 patients. The prevalence of DHS among Chinese patients was 1.5% with a fatality rate of 9.6%. Early withdrawal of dapsone and appropriate treatment reduced the fatality rate. Most importantly, genetic screening for the HLA-B*13:01 allele among high-risk populations showed a significant utility as a useful genetic marker to DHS. In conclusion, this review discusses the epidemiological and clinical characteristics of DHS among Chinese patients, which may help physicians to understand this syndrome.

  20. Drug Hypersensitivity: How Drugs Stimulate T Cells via Pharmacological Interaction with Immune Receptors.

    PubMed

    Pichler, Werner J; Adam, Jacqueline; Watkins, Stephen; Wuillemin, Natascha; Yun, James; Yerly, Daniel

    2015-01-01

    Small chemicals like drugs tend to bind to proteins via noncovalent bonds, e.g. hydrogen bonds, salt bridges or electrostatic interactions. Some chemicals interact with other molecules than the actual target ligand, representing so-called 'off-target' activities of drugs. Such interactions are a main cause of adverse side effects to drugs and are normally classified as predictable type A reactions. Detailed analysis of drug-induced immune reactions revealed that off-target activities also affect immune receptors, such as highly polymorphic human leukocyte antigens (HLA) or T cell receptors (TCR). Such drug interactions with immune receptors may lead to T cell stimulation, resulting in clinical symptoms of delayed-type hypersensitivity. They are assigned the 'pharmacological interaction with immune receptors' (p-i) concept. Analysis of p-i has revealed that drugs bind preferentially or exclusively to distinct HLA molecules (p-i HLA) or to distinct TCR (p-i TCR). P-i reactions differ from 'conventional' off-target drug reactions as the outcome is not due to the effect on the drug-modified cells themselves, but is the consequence of reactive T cells. Hence, the complex and diverse clinical manifestations of delayed-type hypersensitivity are caused by the functional heterogeneity of T cells. In the abacavir model of p-i HLA, the drug binding to HLA may result in alteration of the presenting peptides. More importantly, the drug binding to HLA generates a drug-modified HLA, which stimulates T cells directly, like an allo-HLA. In the sulfamethoxazole model of p-i TCR, responsive T cells likely require costimulation for full T cell activation. These findings may explain the similarity of delayed-type hypersensitivity reactions to graft-versus-host disease, and how systemic viral infections increase the risk of delayed-type hypersensitivity reactions. © 2015 The Author(s) Published by S. Karger AG, Basel.

  1. Tracking Silent Hypersensitivity Reactions to Asparaginase during Leukemia Therapy Using Single-Chip Indirect Plasmonic and Fluorescence Immunosensing.

    PubMed

    Charbonneau, David M; Breault-Turcot, Julien; Sinnett, Daniel; Krajinovic, Maja; Leclerc, Jean-Marie; Masson, Jean-François; Pelletier, Joelle N

    2017-12-22

    Microbial asparaginase is an essential component of chemotherapy for the treatment of childhood acute lymphoblastic leukemia (cALL). Silent hypersensitivity reactions to this microbial enzyme need to be monitored accurately during treatment to avoid adverse effects of the drug and its silent inactivation. Here, we present a dual-response anti-asparaginase sensor that combines indirect SPR and fluorescence on a single chip to perform ELISA-type immunosensing, and correlate measurements with classical ELISA. Analysis of serum samples from children undergoing cALL therapy revealed a clear correlation between single-chip indirect SPR/fluorescence immunosensing and ELISA used in clinical settings (R 2 > 0.9). We also report that the portable SPR/fluorescence system had a better sensitivity than classical ELISA to detect antibodies in clinical samples with low antigenicity. This work demonstrates the reliability of dual sensing for monitoring clinically relevant antibody titers in clinical serum samples.

  2. Randomized, Controlled Trial of Dexamethasone Versus Dexamethasone Plus Hydrocortisone as Prophylaxis for Hypersensitivity Reactions Due to Paclitaxel Treatment for Gynecologic Cancer.

    PubMed

    Jeerakornpassawat, Dhammapoj; Suprasert, Prapaporn

    2017-10-01

    The aim of this study was to assess intravenous hydrocortisone (HCT) added to standard dexamethasone (DXM) prophylaxis for paclitaxel-associated hypersensitivity reactions (HSRs). Paclitaxel naives scheduled for 6 cycles of paclitaxel (plus platinum) were randomized to DXM alone (20 mg intravenously [IV]) versus DXM plus HCT (100 mg IV) as premedication including chlorpheniramine (10 mg IV), diphenhydramine (25 mg orally), and ranitidine (50 mg IV) 30 minutes before infusion. Clinic nurses observed for HSRs. Groups were well balanced for cancer type, stage, drug allergy, chemotherapy naivete, mean age, body mass index, and paclitaxel dose. The 44 DXM controls underwent 213 cycles and the 42 investigational DXM plus HCT group 192 per protocol cycles. Hypersensitivity reactions were observed among 9 (4.2%) DXM only cycles compared with 1 (0.5%) among DXM plus HCT cycles (P = 0.022). Hypersensitivity reactions occurred in 8 (18%) DXM only patients and in 1 (2.4%) among those correctly receiving DXM plus HCT (P = 0.030). All HSRs occurred in cycles 1 to 3, within 10 to 40 minutes after infusion initiation, and peaked in cycle 2 (5/39) for DXM recipients and in cycle 3 (1/30) for DXM plus HCT. Hypersensitivity reaction severity was grade 1 in 3 DXM only recipients and grade 2 in 6 DXM and 1 DXM plus HCT. A sole grade 3 HSR was in an intention-to-treat DXM-HCT patient, who erroneously received no HCT. Hypersensitivity reaction symptoms were facial flushing (8 episodes), dyspnea (7), palmar rash (1), and transient hypotension (1). Paclitaxel infusion was suspended for treatment of HSRs; in all cases, symptoms mitigated and infusion successfully restarted for the remaining dose. Adding HCT to routine DXM prophylaxis significantly decreased paclitaxel HSR frequency.

  3. Immediate-type hypersensitivity reactions to proton pump inhibitors: usefulness of skin tests in the diagnosis and assessment of cross-reactivity.

    PubMed

    Kepil Özdemir, S; Yılmaz, I; Aydin, Ö; Büyüköztürk, S; Gelincik, A; Demirtürk, M; Erdoğdu, D; Cömert, S; Erdoğan, T; Karakaya, G; Kalyoncu, A F; Oner Erkekol, F; Dursun, A B; Misirligil, Z; Bavbek, S

    2013-08-01

    Data are limited about the value of skin tests in the diagnosis of proton pump inhibitor (PPI)-induced hypersensitivity reactions and the cross-reactivity between PPIs. We aimed to assess the role of skin testing in the diagnosis of PPI-related immediate hypersensitivity reactions and the cross-reactivity patterns among PPIs. The study was designed in a prospective, national, multicentre nature. Sixty-five patients with a suggestive history of a PPI-induced immediate hypersensitivity reaction and 30 control subjects were included. Standardized skin prick and intradermal tests were carried out with a panel of PPIs. Single-blind, placebo-controlled oral provocation tests (OPTs) with the PPIs other than the culprit PPI that displayed negative results in skin tests (n = 61) and diagnostic OPTs with the suspected PPI (n = 12) were performed. The suspected PPIs were lansoprazole (n = 52), esomeprazole (n = 11), pantoprazole (n = 9), rabeprazole (n = 2), and omeprazole (n = 1). The sensitivity, specificity, and negative and positive predictive values of the skin tests with PPIs were 58.8%, 100%, 70.8%, and 100%, respectively. Fifteen of the 31 patients with a hypersensitivity reaction to lansoprazole had a positive OPT or skin test result with at least one of the alternative PPIs (8/52 pantoprazole, 6/52 omeprazole, 5/52 esomeprazole, 3/52 rabeprazole). Considering the high specificity, skin testing seems to be a useful method for the diagnosis of immediate-type hypersensitivity reactions to PPIs and for the evaluation of cross-reactivity among PPIs. However, OPT should be performed in case of negativity on skin tests. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Long-term follow-up of re-sting reactions in children with moderate to severe venom hypersensitivity.

    PubMed

    Ertoy Karagol, Hacer Ilbilge; Bakirtas, Arzu; Yilmaz, Ozlem; Topal, Erdem; Arga, Mustafa; Demirsoy, Mehmet Sadik; Turktas, Ipek

    2015-07-01

    Few data exists about re-sting reactions and their prognosis in children with moderate to severe venom hypersensitivity. The reasons behind not consenting to or prematurely ending venom immunotherapy (VIT) and the preparedness of children who refused or quit VIT for future moderate-severe systemic reaction (SR) to re-stings have not been studied. Data on children with moderate to severe SR after Hymenoptera stings was collected for a 17-year period using our database. A standardized questionnaire was administered to patients who accepted to be interviewed at the clinic. These patients were evaluated in terms of their preparedness for future moderate-severe SR to re-stings. A total of 55 children, 75 % of whom commenced on VIT, were included in the analysis. Different reasons exist for not consenting to VIT; the most common of which is living at a distance from the allergy center. There were no differences in terms of the number of re-stung patients (27.7 and 27.2 %, respectively) and moderate-severe SR (60 and 16.6 %, respectively) between children who prematurely ended or who did not consent to VIT and children who completed VIT. Sixty-four percent of the children who refused or discontinued VIT were not prepared for future moderate-severe SR to re-stings. Long-term prognosis for re-sting reactions is good in children with moderate to severe SR to venoms. Some of the reasons behind refusing or discontinuing VIT may be related to quality of life issues. Preparedness of children who refused or discontinue VIT in emergencies is very low.

  5. MIP-1 alpha contributes to the anticryptococcal delayed-type hypersensitivity reaction and protection against Cryptococcus neoformans.

    PubMed

    Doyle, H A; Murphy, J W

    1997-02-01

    Leukocyte infiltration into infected tissues is essential for the clearance of microorganisms. In animals with a cell-mediated immune (CMI) response to the infectious agent, as opposed to naive animals, leukocyte migration is greatly enhanced into sites of the organism or antigen. The role of the,chemotactic cytokine or chemokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha), in the expression phase of the CMI response and in protection against Cryptococcus neoformans was assessed. With the use of a gelatin sponge model in mice as a means of detecting an anti-cryptococcal delayed-type hypersensitivity (DTH) reaction, we found that MIP-1 alpha levels in fluids from cryptococcal antigen (CneF)-injected sponges in immunized mice (DTH-reactive sponges) were significantly increased over levels of MIP-1 alpha in fluids from saline-injected control sponges at 12 and 24-30 h after injection. MIP-1 alpha levels peaked before increases in neutrophils and lymphocytes in the DTH-reactive sponges, suggesting that MIP-1 alpha was responsible, at least in part, for attracting these leukocyte types. Immunized mice treated with neutralizing antibody to MIP-1 alpha before sponge injection with CneF had reduced numbers of neutrophils and lymphocytes in the DTH-reactive sponges and showed reduced clearance of C. neoformans from the lungs, spleens, livers, and brains when compared with controls. Furthermore, injection of rmMIP-1 alpha into sponges in naive mice resulted in an increase in the influx of neutrophils and lymphocytes into the sponges compared with saline-injected sponges. Together our findings provide solid evidence that MIP-1 alpha is a component of the anticryptococcal DTH reaction. In addition, MIP-1 alpha influences neutrophil influx and attracts lymphocytes into the DTH reaction site. Finally, we showed that MIP-1 alpha plays a role in protection against C. neoformans.

  6. Evaluation of colonoscopic allergen provocation as a diagnostic tool in dogs with proven food hypersensitivity reactions.

    PubMed

    Allenspach, K; Vaden, S L; Harris, T S; Gröne, A; Doherr, M G; Griot-Wenk, M E; Bischoff, S C; Gaschen, F

    2006-01-01

    To evaluate the colonoscopic allergen provocation (COLAP) test as a new tool for the diagnosis of IgE-mediated food allergy. Oral food challenges as well as COLAP testing were performed in a colony of nine research dogs with proven immediate-type food allergic reactions. In addition, COLAP was performed in five healthy dogs. When compared with the oral challenge test, COLAP accurately determined 18 of 23 (73 per cent) positive oral challenge reactions (73 per cent) in dogs with food allergies and was negative in the healthy dogs. The accuracy of this new test may be higher than that for gastric sensitivity testing. Therefore, COLAP holds promise as a new test to confirm the diagnosis of suspect IgE-mediated food allergy in dogs.

  7. Relaxation effect of abacavir on rat basilar arteries.

    PubMed

    Li, Rachel Wai Sum; Yang, Cui; Chan, Shun Wan; Hoi, Maggie Pui Man; Lee, Simon Ming Yuen; Kwan, Yiu Wa; Leung, George Pak Heng

    2015-01-01

    The use of abacavir has been linked with increased cardiovascular risk in patients with human immunodeficiency virus infection; however, the mechanism involved remains unclear. We hypothesize that abacavir may impair endothelial function. In addition, based on the structural similarity between abacavir and adenosine, we propose that abacavir may affect vascular contractility through endogenous adenosine release or adenosine receptors in blood vessels. The relaxation effect of abacavir on rat basilar arteries was studied using the myograph technique. Cyclic GMP and AMP levels were measured by immunoassay. The effects of abacavir on nucleoside transporters were studied using radiolabeled nucleoside uptake experiments. Ecto-5' nucleotidase activity was determined by measuring the generation of inorganic phosphate using adenosine monophosphate as the substrate. Abacavir induced the relaxation of rat basilar arteries in a concentration-dependent manner. This relaxation was abolished when endothelium was removed. In addition, the relaxation was diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was also abolished by adenosine A2 receptor blockers. However, abacavir had no effect on ecto-5' nucleotidase and nucleoside transporters. Short-term and long-term treatment of abacavir did not affect acetylcholine-induced relaxation in rat basilar arteries. Abacavir induces acute endothelium-dependent relaxation of rat basilar arteries, probably through the activation of adenosine A2 receptors in endothelial cells, which subsequently leads to the release of nitric oxide, resulting in activation of the cyclic guanosine monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells. It is speculated that abacavir-induced cardiovascular risk may not be related to endothelial dysfunction

  8. Relaxation Effect of Abacavir on Rat Basilar Arteries

    PubMed Central

    Li, Rachel Wai Sum; Yang, Cui; Chan, Shun Wan; Hoi, Maggie Pui Man; Lee, Simon Ming Yuen; Kwan, Yiu Wa; Leung, George Pak Heng

    2015-01-01

    Background The use of abacavir has been linked with increased cardiovascular risk in patients with human immunodeficiency virus infection; however, the mechanism involved remains unclear. We hypothesize that abacavir may impair endothelial function. In addition, based on the structural similarity between abacavir and adenosine, we propose that abacavir may affect vascular contractility through endogenous adenosine release or adenosine receptors in blood vessels. Methods The relaxation effect of abacavir on rat basilar arteries was studied using the myograph technique. Cyclic GMP and AMP levels were measured by immunoassay. The effects of abacavir on nucleoside transporters were studied using radiolabeled nucleoside uptake experiments. Ecto-5′ nucleotidase activity was determined by measuring the generation of inorganic phosphate using adenosine monophosphate as the substrate. Results Abacavir induced the relaxation of rat basilar arteries in a concentration-dependent manner. This relaxation was abolished when endothelium was removed. In addition, the relaxation was diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was also abolished by adenosine A2 receptor blockers. However, abacavir had no effect on ecto-5’ nucleotidase and nucleoside transporters. Short-term and long-term treatment of abacavir did not affect acetylcholine-induced relaxation in rat basilar arteries. Conclusion Abacavir induces acute endothelium-dependent relaxation of rat basilar arteries, probably through the activation of adenosine A2 receptors in endothelial cells, which subsequently leads to the release of nitric oxide, resulting in activation of the cyclic guanosine monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells. It is speculated that abacavir-induced cardiovascular risk may

  9. Single-tree nut immunotherapy attenuates allergic reactions in mice with hypersensitivity to multiple tree nuts.

    PubMed

    Kulis, Mike; Li, Yifan; Lane, Hannah; Pons, Laurent; Burks, Wesley

    2011-01-01

    Allergic reactions to tree nuts are often severe and are outgrown in less than 10% of diagnosed patients. To determine whether treatment of underlying tree nut sensitization will prevent allergic reactions to cross-reacting tree nuts and to determine the effects of single-tree nut immunotherapy on true multi-tree nut sensitization. Cross-reactivity model: Cashew-sensitized mice underwent immunotherapy with cashew and were subsequently challenged with cashew and pistachio. Multisensitization model: Cashew plus walnut-sensitized mice were treated with cashew alone, walnut alone, or both cashew and walnut and then underwent challenges to cashew and walnut. Challenges were assessed on the basis of symptoms, changes in body temperature, and mouse mast cell protease-1 release. In the cross-reactivity model, cashew immunotherapy completely prevented allergic reactions on challenges with cashew or the cross-reactive pistachio. In the multisensitization model, mice with cashew plus walnut allergy were significantly protected from anaphylactic reactions on cashew challenge in both the cashew-alone and walnut-alone immunotherapy groups. Results from the walnut challenge demonstrated significantly decreased allergic responses in the walnut immunotherapy group, whereas mice in the cashew immunotherapy group experienced significantly lower symptoms. In the cross-reactivity model, immunotherapy effectively decreased IL-4 and IL-5 production and increased IL-12 relative to placebo while also inducing a 5-fold increase in specific IgG(1). Single-tree nut immunotherapy can effectively decrease allergic responses in both the cross-reactivity and multisensitization mouse models. Further studies are needed to determine which single-tree nut immunotherapies will be most effective for specific multi-tree nut allergy profiles. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  10. The Major Soybean Allergen Gly m Bd 28K Induces Hypersensitivity Reactions in Mice Sensitized to Cow's Milk Proteins.

    PubMed

    Candreva, Ángela María; Smaldini, Paola Lorena; Curciarello, Renata; Fossati, Carlos Alberto; Docena, Guillermo Horacio; Petruccelli, Silvana

    2016-02-24

    Reactions to soy have been reported in a proportion of patients with IgE-mediated cow's milk allergy (CMA). In this work, we analyzed if Gly m Bd 28K/P28, one of the major soybean allergens, is a cross-reactive allergen with cow milk proteins (CMP). We showed that P28 was recognized by IgE sera from CMA patients and activated human peripheral basophils degranulation. Moreover, IgE sera of mice exclusively sensitized to CMP recognized P28. Splenocytes from sensitized animals secreted IL-5 and IL-13 when incubated with CMP or soy proteins, but only IL-13 when treated with P28. In addition, a skin test was strongly positive for CMP and weakly positive for P28. Remarkably, milk-sensitized mice showed hypersensitivity symptoms following sublingual challenge with P28 or CMP. With the use of bioinformatics' tools seven putative cross-reactive epitopes were identified. In conclusion, using in vitro and in vivo tests we demonstrated that P28 is a novel cross-reactive allergen with CMP.

  11. Nab-paclitaxel after docetaxel hypersensitivity reaction: case report and literature review.

    PubMed

    Pellegrino, Benedetta; Boggiani, Daniela; Tommasi, Chiara; Palli, Dante; Musolino, Antonino

    2017-10-23

    Taxanes, including paclitaxel and docetaxel, are one of the most active cytotoxic agents in breast cancer  treatment  including  Her-2  positive  subtype characterized  by  aggressive  clinical  and pathological features since the early stage. However, their use is sometimes limited by the occurrence of hypersensivity reactions (HSRs) characterized by erythematous rashes, bronchospasm, respiratory distress, hypotension, and pulmonary edema. Cross-reactions between paclitaxel and docetaxel are described in literature with a rate ranging from 49% to 90%. Abraxane (nab-paclitaxel), an albumin-bound form of paclitaxel, has a different toxicity profile from solvent-based paclitaxel and a lower rate of HSRs. Interestingly, several authors have recently reported cases of patients who developed HSRs to taxanes, principally paclitaxel, and were then safety treated with Abraxane, suggesting the absence of cross-reactivity between these drugs. Based on these considerations, we report our clinical experience and perform a literature review on this topic with the aim to investigate the cross-reactivity between nab-paclitaxel and other taxanes, in particular with docetaxel.

  12. In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper.

    PubMed

    Mayorga, C; Celik, G; Rouzaire, P; Whitaker, P; Bonadonna, P; Rodrigues-Cernadas, J; Vultaggio, A; Brockow, K; Caubet, J C; Makowska, J; Nakonechna, A; Romano, A; Montañez, M I; Laguna, J J; Zanoni, G; Gueant, J L; Oude Elberink, H; Fernandez, J; Viel, S; Demoly, P; Torres, M J

    2016-08-01

    Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well-controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well-characterized patients with DHR and to develop new tests for diagnosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. CD32a antibodies induce thrombocytopenia and type II hypersensitivity reactions in FCGR2A mice

    PubMed Central

    Robles-Carrillo, Liza; Davila, Monica; Brodie, Meghan; Desai, Hina; Rivera-Amaya, Mildred; Francis, John L.; Amirkhosravi, Ali

    2015-01-01

    The CD32a immunoglobulin G (IgG) receptor (Fcγ receptor IIa) is a potential therapeutic target for diseases in which IgG immune complexes (ICs) mediate inflammation, such as heparin-induced thrombocytopenia, rheumatoid arthritis, and systemic lupus erythematosus. Monoclonal antibodies (mAbs) are a promising strategy for treating such diseases. However, IV.3, perhaps the best characterized CD32a-blocking mAb, was recently shown to induce anaphylaxis in immunocompromised “3KO” mice. This anaphylactic reaction required a human CD32a transgene because mice lack an equivalent of this gene. The finding that IV.3 induces anaphylaxis in CD32a-transgenic mice was surprising because IV.3 had long been thought to lack the intrinsic capacity to trigger cellular activation via CD32a. Such an anaphylactic reaction would also limit potential therapeutic applications of IV.3. In the present study, we examine the molecular mechanisms by which IV.3 induces anaphylaxis. We now report that IV.3 induces anaphylaxis in immunocompetent CD32a-transgenic “FCGR2A” mice, along with the novel finding that IV.3 and 2 other well-characterized CD32a-blocking mAbs, AT-10 and MDE-8, also induce severe thrombocytopenia in FCGR2A mice. Using recombinant variants of these same mAbs, we show that IgG “Fc” effector function is necessary for the induction of anaphylaxis and thrombocytopenia in FCGR2A mice. Variants of these mAbs lacking the capacity to activate mouse IgG receptors not only failed to induce anaphylaxis or thrombocytopenia, but also very potently protected FCGR2A mice from near lethal doses of IgG ICs. Our findings show that effector-deficient IV.3, AT-10, and MDE-8 are promising candidates for developing therapeutic mAbs to treat CD32a-mediated diseases. PMID:26396093

  14. Acute cutaneous graft-vs.-host disease compared to drug hypersensitivity reaction with vacuolar interface changes: a blinded study of microscopic and immunohistochemical features.

    PubMed

    Lehman, Julia S; Gibson, Lawrence E; el-Azhary, Rokea A; Chavan, Rahul N; Hashmi, Shahrukh K; Lohse, Christine M; Flotte, Thomas J

    2015-01-01

    Complications from graft-vs.-host disease (GVHD), a major contributor to morbidity and mortality following hematopoietic cell transplantation, may be mitigated by early diagnosis and intervention. However, differentiation between acute cutaneous GVHD and other common skin eruptions that develop in the post-transplantation period, such as drug hypersensitivity reaction, can be challenging clinically and microscopically. Because recent evidence indicates that CD123, a marker of plasmacytoid dendritic cells, can help to distinguish gastrointestinal GVHD from the clinicopathologic mimic cytomegalovirus colitis, we aimed to determine whether CD123 could aid in the diagnosis of acute cutaneous GVHD. We studied 12 skin specimens of patients with grades I-II cutaneous GVHD and 12 from patients who had drug hypersensitivity reaction with vacuolar interface changes on biopsy. No differences were seen between the two groups with regards to density or distribution of CD123 expression. Specimens representing GVHD showed significantly less spongiosis (P < 0.001) and fewer dermal eosinophils (P = 0.03) compared to those representing drug hypersensitivity reaction. We conclude that CD123 does not appear to be a useful ancillary test in the diagnosis of acute cutaneous GVHD. Careful correlation between clinical findings and features with microscopy remains the cornerstone of accurate diagnosis of acute cutaneous GVHD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Hypersensitivity lo local anesthetics.

    PubMed

    Grzanka, Alicja; Wasilewska, Iwona; Śliwczyńska, Magdalena; Misiołek, Hanna

    2016-01-01

    Using local anaesthetics in daily practice, particularly by anaesthetists and dentists, is connected with the risk of side effects. Therefore, the observation of side effects, carrying out detailed research (according to the chart proposed in this study) and conducting specialist examinations is of the highest importance. There is a variety of side effects that could occur during local anaesthesia procedures, with the intensity ranging from clinically unimportant to life threatening. Clinicians' major concerns are the appearance of various hypersensitivity reactions, including anaphylaxis. Healthcare providers responsible for the administration of local anaesthetics should be able to detect hypersensitivity reactions to implement appropriate treatment and then choose highly selected diagnostic procedures. The final diagnosis should be based on specific medical history; documentation, including a description of the case and measurement of tryptase activity; skin tests; and provocation trials. Screening tests are not recommended in populations without hypersensitivity to local anaesthestics in their medical history.

  16. Detection of feline herpes virus 1 via polymerase chain reaction and immunohistochemistry in cats with ulcerative facial dermatitis, eosinophilic granuloma complex reaction patterns and mosquito bite hypersensitivity.

    PubMed

    Persico, Paola; Roccabianca, Paola; Corona, Antonio; Vercelli, Antonella; Cornegliani, Luisa

    2011-12-01

    Ulcerative dermatitis caused by feline herpes virus 1 (FHV-1) is an uncommon disease characterized by cutaneous ulcers secondary to epidermal, adnexal and dermal necrosis. Differential diagnoses for FHV-1 lesions include, but are not limited to, mosquito bite hypersensitivity and eosinophilic granuloma complex. Histopathological diagnosis of FHV-1 dermatitis is based on the detection of the intranuclear inclusion bodies. In cases where intranuclear inclusions are missing but clinical and histological findings are compatible with FHV-1 dermatitis, immunohistochemistry (IHC) and PCRs have been used. In this retrospective study, we evaluated the presence of FHV-1 by IHC and PCR in skin biopsies and compared the results of the two tests. Sixty-four skin biopsy specimens from cats with compatible lesions were reviewed and tested via PCR and IHC for evidence of FHV-1. Polymerase chain reaction was positive in 12 of 64 biopsies; PCR and IHC were positive only in two of 64 biopsies, and these cases were considered true positive cases. The higher number of PCR-positive cases was possibly attributed to amplification of viral DNA from a live attenuated vaccination, but a previous FHV-1 infection with subsequent amplification of latently inserted FHV-1 could not be excluded. If clinical signs and histopathology suggest FHV-1 infection in the absence of typical inclusion bodies, IHC is the preferred diagnostic test; PCR may be useful for initial screening, but due to false positives is not sufficient for a definitive diagnosis. © 2011 The Authors. Veterinary Dermatology. © 2011 ESVD and ACVD.

  17. Hypersensitivity pneumonitis

    MedlinePlus

    Hypersensitivity pneumonitis usually occurs in people who work in places where there are high levels of organic dusts, fungus, or molds. Long-term exposure can lead to lung inflammation and acute lung disease . ...

  18. Reclassifying Anaphylaxis to Neuromuscular Blocking Agents Based on the Presumed Patho-Mechanism: IgE-Mediated, Pharmacological Adverse Reaction or "Innate Hypersensitivity"?

    PubMed

    Spoerl, David; Nigolian, Haig; Czarnetzki, Christoph; Harr, Thomas

    2017-06-07

    Approximately 60% of perioperative anaphylactic reactions are thought to be immunoglobulin IgE mediated, whereas 40% are thought to be non-IgE mediated hypersensitivity reactions (both considered non-dose-related type B adverse drug reactions). In both cases, symptoms are elicited by mast cell degranulation. Also, pharmacological reactions to drugs (type A, dose-related) may sometimes mimic symptoms triggered by mast cell degranulation. In case of hypotension, bronchospasm, or urticarial rash due to mast cell degranulation, identification of the responsible mechanism is complicated. However, determination of the type of the underlying adverse drug reaction is of paramount interest for the decision of whether the culprit drug may be re-administered. Neuromuscular blocking agents (NMBA) are among the most frequent cause of perioperative anaphylaxis. Recently, it has been shown that NMBA may activate mast cells independently from IgE antibodies via the human Mas-related G-protein-coupled receptor member X2 (MRGPRX2). In light of this new insight into the patho-mechanism of pseudo-allergic adverse drug reactions, in which as drug-receptor interaction results in anaphylaxis like symptoms, we critically reviewed the literature on NMBA-induced perioperative anaphylaxis. We challenge the dogma that NMBA mainly cause IgE-mediated anaphylaxis via an IgE-mediated mechanism, which is based on studies that consider positive skin test to be specific for IgE-mediated hypersensitivity. Finally, we discuss the question whether MRGPRX2 mediated pseudo-allergic reactions should be re-classified as type A adverse reactions.

  19. Arthritis as a hypersensitivity reaction in a case of sporotrichosis transmitted by a sick cat: clinical and serological follow up of 13 months.

    PubMed

    Orofino-Costa, R; Bóia, M N; Magalhães, G A P; Damasco, P S; Bernardes-Engemann, A R; Benvenuto, F; Silva, I C; Lopes-Bezerra, L M

    2010-01-01

    Sporotrichosis is a subacute or chronic fungal infection caused by Sporothrix schenckii, which is commonly acquired by traumatic inoculation of the fungus carried in a contaminated material into the skin. Joint involvement is the most frequent extracutaneous manifestation in immunosuppressed patients. We report the case of an immunocompetent woman who acquired sporotrichosis through the scratch of a sick cat. She presented skin lesions and arthritis possibly because of a hypersensitivity reaction. Treatment resulted in complete cure up to 13 months of clinical and serological follow-up.

  20. Lymphomatoid hypersensitivity reaction to levofloxacin during autologous stem cell transplantation: a potential diagnostic pitfall in patients treated for lymphoma or leukemia.

    PubMed

    Esparza, Edward M; Takeshita, Junko; George, Evan

    2011-01-01

    Drug-associated cutaneous lymphomatoid hypersensitivity reactions are rare eruptions that can clinically and microscopically mimic a bona fide lymphomatous process. Clinically, the appearance ranges from papulosquamous to purpuric. Histopathologically, these reactions simulate a wide variety of lymphoma subtypes; the most frequently reported examples resemble mycosis fungoides. We report a 61-year-old female who developed a purpuric eruption prior to engraftment of an autologous hematopoietic stem cell transplant for stage IV mantle cell lymphoma. Skin biopsies showed a superficial perivascular and interstitial infiltrate of large, immature-appearing mononuclear cells associated with spongiosis, papillary dermal edema and erythrocyte extravasation. The cells were immunoreactive for T-cell markers and lacked B-cell marker expression, excluding recurrence of the underlying mantle cell lymphoma as a diagnostic possibility. The cutaneous eruption was temporally linked to levofloxacin administration and resolved after discontinuation of this medication. This is the first report of a lymphomatoid hypersensitivity reaction associated with fluoroquinolone use. The histopathologic features presented in this paper underscore the potential for misdiagnosis of such lesions as lymphoma or acute myeloid leukemia, particularly in the setting of hematopoietic stem cell transplantation for underlying lymphoma or leukemia. Clinical correlation, morphologic comparison to the original malignancy and immunohistochemical studies aid the dermatopathologist in rendering the correct diagnosis. Copyright © 2010 John Wiley & Sons A/S.

  1. DELAYED HYPERSENSITIVITY

    PubMed Central

    Uhr, Jonathan W.; Salvin, S. B.; Pappenheimer, A. M.

    1957-01-01

    A general method for induction of the delayed hypersensitive state directed against single protein antigens is described. The method consists of intradermal injection of minute amounts of washed immune precipitates containing the antigen in question. Provided the specific precipitates are formed in the region of antibody excess, maximal sensitivity develops at least 2 to 3 weeks before detectable circulating antibody is formed in guinea pigs against the sensitizing antigen. Neither adjuvant nor killed acid-fast bacteria are required for induction of the delayed hypersensitive state although the degree of sensitization is considerably increased when the sensitizing material is incorporated in Freund's complete adjuvant. Characteristics of the "delayed" as opposed to the "immediate" hypersensitive states in the guinea pig are described and implications of the findings are discussed. PMID:13385403

  2. Abacavir induces arterial thrombosis in a murine model.

    PubMed

    Collado-Diaz, Victor; Andujar, Isabel; Sanchez-Lopez, Ainhoa; Orden, Samuel; Blanch-Ruiz, María Amparo; Martinez-Cuesta, María Angeles; Blas-García, Ana; Esplugues, Juan V; Álvarez, Ángeles

    2018-01-16

    The effects of abacavir were evaluated in a validated model of arterial thrombosis. The role of ATP-P2X7-receptors and the actions of two vascular-damaging agents (diclofenac or rofecoxib) and other NRTIs were also analysed. Abacavir dose-dependently promoted thrombus formation. This effect was reversed by a P2X7-receptor antagonist and was non-existent in P2X7 KO mice. The effects of abacavir were similar to those of diclofenac and rofecoxib. Other NRTIs had no thrombosis-related effects. Abacavir promotes arterial thrombosis through interference with purinergic signalling, suggesting a possible biological mechanism for the clinical association of abacavir with cardiovascular diseases. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  3. Sulfite hypersensitivity. A critical review

    SciTech Connect

    Gunnison, A.F.; Jacobsen, D.W.

    Sulfiting agents (sulfur dioxide and the sodium and potassium salts of bisulfite, sulfite, and metabisulfite) are widely used as preservatives in foods, beverages, and pharmaceuticals. Within the past 5 years, there have been numerous reports of adverse reactions to sulfiting agents. This review presents a comprehensive compilation and discussion of reports describing reactions to ingested, inhaled, and parenterally administered sulfite. Sulfite hypersensitivity is usually, but not exclusively, found within the chronic asthmatic population. Although there is some disagreement on its prevalence, a number of studies have indicated that 5 to 10% of all chronic asthmatics are sulfite hypersensitive. This reviewmore » also describes respiratory sulfur dioxide sensitivity which essentially all asthmatics experience. Possible mechanisms of sulfite hypersensitivity and sulfur dioxide sensitivity are discussed in detail. Sulfite metabolism and the role of sulfite oxidase in the detoxification of exogenous sulfite are reviewed in relationship to the etiology of sulfite hypersensitivity. 147 references.« less

  4. Acute hypersensitivity reaction to Crotalidae polyvalent immune Fab (CroFab) as initial presentation of galactose-α-1,3-galactose (α-gal) allergy.

    PubMed

    Rizer, Justin; Brill, Kaitlin; Charlton, Nathan; King, Joshua

    2017-08-01

    Crotalidae polyvalent immune Fab antivenom (CroFab), commonly used for the treatment of clinically significant North American crotalinae envenomation, is generally well-tolerated. A novel form of anaphylaxis due to an IgE antibody response to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) has been established following red-meat consumption as well as IV administration of cetuximab, which contain the α-gal epitope. We present a case of α-gal allergy discovered after acute hypersensitivity reaction to FabAV. A 61-year-old healthy female was bitten on her left ankle by Agkistrodon contortrix. Given the patient's rapid progression of pain and swelling, she was given FabAV. During infusion of FabAV, she developed diffuse hives over her entire body and itching, but denied respiratory or gastrointestinal symptoms and her vital signs remained stable. The FabAV was immediately discontinued and she received intravenous diphenhydramine and famotidine with gradual resolution of symptoms. On further discussion, she denied a history of α-gal or papaya allergy but rarely ate red meat and endorsed sustaining frequent tick bites. Subsequent antibody testing was significant for an α-1,3-galactose IgE concentration of 45,000 U/L (normal <3500 U/L), confirming α-gal allergy. To our knowledge, this is the first report of FabAV hypersensitivity associated with an underlying α-gal allergy.

  5. Usefulness of In Vivo and In Vitro Diagnostic Tests in the Diagnosis of Hypersensitivity Reactions to Quinolones and in the Evaluation of Cross-Reactivity: A Comprehensive Study Including the Latest Quinolone Gemifloxacin

    PubMed Central

    Gelincik, Asli; Akdeniz, Nilgun; Aktas-Cetin, Esin; Olgac, Muge; Unal, Derya; Ertek, Belkis; Coskun, Raif; Colakoğlu, Bahattin; Deniz, Gunnur; Buyukozturk, Suna

    2017-01-01

    Purpose Reports evaluating diagnosis and cross reactivity of quinolone hypersensitivity have revealed contradictory results. Furthermore, there are no reports investigating the cross-reactivity between gemifloxacin (GFX) and the others. We aimed to detect the usefulness of diagnostic tests of hypersensitivity reactions to quinolones and to evaluate the cross reactivity between different quinolones including the latest quinolone GFX. Methods We studied 54 patients (mean age 42.31±10.39 years; 47 female) with 57 hypersensitivity reactions due to different quinolones and 10 nonatopic quinolone tolerable control subjects. A detailed clinical history, skin test (ST), and single-blind placebo-controlled drug provocation test (SBPCDPT), as well as basophil activation test (BAT) and lymphocyte transformation test (LTT) were performed with the culprit and alternative quinolones including ciprofloxacin (CFX), moxifloxacin (MFX), levofloxacin (LFX), ofloxacin (OFX), and GFX. Results The majority (75.9%) of the patients reported immediate type reactions to various quinolones. The most common culprit drug was CFX (52.6%) and the most common reaction type was urticaria (26.3%). A quarter of the patients (24.1%) reacted to SBPCDPTs, although their STs were negative; while false ST positivity was 3.5% and ST/SBPCDPTs concordance was only 1.8%. Both BAT and LTT were not found useful in quinolone hypersensitivity. Cross-reactivity was primarily observed between LFX and OFX (50.0%), whereas it was the least between MFX and the others, and in GFX hypersensitive patients the degree of cross-reactivity to the other quinolones was 16.7%. Conclusions These results suggest that STs, BAT, and LTT are not supportive in the diagnosis of a hypersensitivity reaction to quinolone as well as in the prediction of cross-reactivity. Drug provocation tests (DPTs) are necessary to identify both culprit and alternative quinolones. PMID:28497922

  6. Expression of CD73 slows down migration of skin dendritic cells, affecting the sensitization phase of contact hypersensitivity reactions in mice.

    PubMed

    Neuberger, A; Ring, S; Silva-Vilches, C; Schrader, J; Enk, A; Mahnke, K

    2017-09-01

    Application of haptens to the skin induces release of immune stimulatory ATP into the extracellular space. This "danger" signal can be converted to immunosuppressive adenosine (ADO) by the action of the ectonucleotidases CD39 and CD73, expressed by skin and immune cells. Thus, the expression and regulation of CD73 by skin derived cells may have crucial influence on the outcome of contact hypersensitivity (CHS) reactions. To investigate the role of CD73 expression during 2,4,6-trinitrochlorobenzene (TNCB) induced CHS reactions. Wild type (wt) and CD73 deficient mice were subjected to TNCB induced CHS. In the different mouse strains the resulting ear swelling reaction was recorded along with a detailed phenotypic analysis of the skin migrating subsets of dendritic cells (DC). In CD73 deficient animals the motility of DC was higher as compared to wt animals and in particular after sensitization we found increased migration of Langerin + DC from skin to draining lymph nodes (LN). In the TNCB model this led to a stronger sensitization as indicated by increased frequency of interferon-γ producing T cells in the LN and an increased ear thickness after challenge. CD73 derived ADO production slows down migration of Langerin + DC from skin to LN. This may be a crucial mechanism to avoid over boarding immune reactions against haptens. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  7. Tuberculin-induced delayed-type hypersensitivity reaction in a model of hu-PBMC-SCID mice grafted with autologous skin.

    PubMed Central

    Tsicopoulos, A.; Pestel, J.; Fahy, O.; Vorng, H.; Vandenbusche, F.; Porte, H.; Eraldi, L.; Wurtz, A.; Akoum, H.; Hamid, Q.; Wallaert, B.; Tonnel, A. B.

    1998-01-01

    We have developed an animal model to study human delayed-type hypersensitivity reactions. Previous studies in humans have shown after tuberculin injection the presence of a mononuclear cell infiltration, with almost no eosinophils, associated with a preferential Th-1-type cytokine profile. Human skin graft obtained from tuberculin-reactive donors was grafted onto the back of severe combined immunodeficient mice. After healing, mice were reconstituted intraperitoneally with peripheral mononuclear cells. Tuberculin and diluent were injected intradermally, and skin biopsies were performed 72 hours later. Skin grafts were divided into two parts, one for immunohistochemistry and one for in situ hybridization studies. Immunohistochemistry was performed on cryostat sections using the alkaline phosphatase anti-alkaline phosphatase technique. In the tuberculin-injected sites as compared with the diluent-injected sites, there were significant increases in the number of CD45+ pan leukocytes and CD4+, CD8+, CD45RO+ T cells but not in CD68+ monocytes/macrophages and EG2 or MBP+ eosinophils. The activation markers CD25 and HLA-DR were up-regulated in the tuberculin-injected sites. In situ hybridization was performed using 35S-labeled riboprobes for interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-5. After tuberculin injection, a preferential Th-1-type cytokine profile was observed with significant increases in the numbers of IL-2 and IFN-gamma mRNA-expressing cells. These results are similar to those reported after tuberculin-induced delayed-type hypersensitivity in humans, suggesting that this model might be useful to study cutaneous inflammatory reaction. Images Figure 4 PMID:9626072

  8. Tuberculin-induced delayed-type hypersensitivity reaction in a model of hu-PBMC-SCID mice grafted with autologous skin.

    PubMed

    Tsicopoulos, A; Pestel, J; Fahy, O; Vorng, H; Vandenbusche, F; Porte, H; Eraldi, L; Wurtz, A; Akoum, H; Hamid, Q; Wallaert, B; Tonnel, A B

    1998-06-01

    We have developed an animal model to study human delayed-type hypersensitivity reactions. Previous studies in humans have shown after tuberculin injection the presence of a mononuclear cell infiltration, with almost no eosinophils, associated with a preferential Th-1-type cytokine profile. Human skin graft obtained from tuberculin-reactive donors was grafted onto the back of severe combined immunodeficient mice. After healing, mice were reconstituted intraperitoneally with peripheral mononuclear cells. Tuberculin and diluent were injected intradermally, and skin biopsies were performed 72 hours later. Skin grafts were divided into two parts, one for immunohistochemistry and one for in situ hybridization studies. Immunohistochemistry was performed on cryostat sections using the alkaline phosphatase anti-alkaline phosphatase technique. In the tuberculin-injected sites as compared with the diluent-injected sites, there were significant increases in the number of CD45+ pan leukocytes and CD4+, CD8+, CD45RO+ T cells but not in CD68+ monocytes/macrophages and EG2 or MBP+ eosinophils. The activation markers CD25 and HLA-DR were up-regulated in the tuberculin-injected sites. In situ hybridization was performed using 35S-labeled riboprobes for interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-5. After tuberculin injection, a preferential Th-1-type cytokine profile was observed with significant increases in the numbers of IL-2 and IFN-gamma mRNA-expressing cells. These results are similar to those reported after tuberculin-induced delayed-type hypersensitivity in humans, suggesting that this model might be useful to study cutaneous inflammatory reaction.

  9. The Absence of CYP3A5*3 Is a Protective Factor to Anticonvulsants Hypersensitivity Reactions: A Case-Control Study in Brazilian Subjects

    PubMed Central

    dos Santos, Bernardo; Talib, Leda Leme; Yamaguti, Célia; Rodrigues, Helcio; Gattaz, Wagner Farid; Kalil, Jorge

    2015-01-01

    Although aromatic anticonvulsants are usually well tolerated, they can cause cutaneous adverse drug reactions in up to 10% of patients. The clinical manifestations of the antiepileptics-induced hypersensitivity reactions (AHR) vary from mild skin rashes to severe cutaneous drug adverse reactions which are related to high mortality and significant morbidity. Genetic polymorphisms in cytochrome P450 genes are associated with altered enzymatic activity and may contribute to the risk of AHR. Here we present a case-control study in which we genotyped SNPs of CYP2C19, 2C9 and 3A5 of 55 individuals with varying severities of AHR, 83 tolerant, and 366 healthy control subjects from São Paulo, Brazil. Clinical characterization was based on standardized scoring systems and drug patch test. All in vivo investigation followed the ENDA (European Network of Drug Allergy) recommendations. Genotype was determined by real time PCR using peripheral blood DNA as a template. Of all 504 subjects, 65% were females, 45% self-identified as Afro-American, 38% as Caucasian and 17% as having non-African mixed ascendancy. Amongst 55 subjects with AHR, 44 had severe cutaneous drug adverse reactions. Of the 46 drug patch tests performed, 29 (63%) were positive. We found a strong association between the absence of CYP3A5*3 and tolerant subjects when compared to AHR (p = 0.0002, OR = 5.28 [CI95% 2.09–14.84]). None of our groups presented positive association with CYP2C19 and 2C9 polymorphisms, however, both SNPs contributed to separation of cases and tolerants in a Classification and Regression Tree. Our findings indicate that drug metabolism genes can contribute in the tolerability of antiepileptics. CYP3A5*3 is the most prevalent CYP3A5 allele associated with reduced enzymatic function. The current study provides evidence that normal CYP3A5 activity might be a protective factor to aromatic antiepileptics-induced hypersensitivity reactions in Brazilian subjects. PMID:26291084

  10. The Absence of CYP3A5*3 Is a Protective Factor to Anticonvulsants Hypersensitivity Reactions: A Case-Control Study in Brazilian Subjects.

    PubMed

    Tanno, Luciana Kase; Kerr, Daniel Shikanai; dos Santos, Bernardo; Talib, Leda Leme; Yamaguti, Célia; Rodrigues, Helcio; Gattaz, Wagner Farid; Kalil, Jorge

    2015-01-01

    Although aromatic anticonvulsants are usually well tolerated, they can cause cutaneous adverse drug reactions in up to 10% of patients. The clinical manifestations of the antiepileptics-induced hypersensitivity reactions (AHR) vary from mild skin rashes to severe cutaneous drug adverse reactions which are related to high mortality and significant morbidity. Genetic polymorphisms in cytochrome P450 genes are associated with altered enzymatic activity and may contribute to the risk of AHR. Here we present a case-control study in which we genotyped SNPs of CYP2C19, 2C9 and 3A5 of 55 individuals with varying severities of AHR, 83 tolerant, and 366 healthy control subjects from São Paulo, Brazil. Clinical characterization was based on standardized scoring systems and drug patch test. All in vivo investigation followed the ENDA (European Network of Drug Allergy) recommendations. Genotype was determined by real time PCR using peripheral blood DNA as a template. Of all 504 subjects, 65% were females, 45% self-identified as Afro-American, 38% as Caucasian and 17% as having non-African mixed ascendancy. Amongst 55 subjects with AHR, 44 had severe cutaneous drug adverse reactions. Of the 46 drug patch tests performed, 29 (63%) were positive. We found a strong association between the absence of CYP3A5*3 and tolerant subjects when compared to AHR (p = 0.0002, OR = 5.28 [CI95% 2.09-14.84]). None of our groups presented positive association with CYP2C19 and 2C9 polymorphisms, however, both SNPs contributed to separation of cases and tolerants in a Classification and Regression Tree. Our findings indicate that drug metabolism genes can contribute in the tolerability of antiepileptics. CYP3A5*3 is the most prevalent CYP3A5 allele associated with reduced enzymatic function. The current study provides evidence that normal CYP3A5 activity might be a protective factor to aromatic antiepileptics-induced hypersensitivity reactions in Brazilian subjects.

  11. Acute hypersensitivity to mannitol: a case report

    NASA Astrophysics Data System (ADS)

    Siahaan, A. M.; Fithrie, A.

    2018-03-01

    Mannitol is an osmotic diuretic agent that has been considered a main therapeutic option in cerebral edema for the past several decades. The most common adverse effect reported is acute kidney injury and electrolyte imbalance. Hypersensitivity associated with mannitol is not a usual finding. Here we describe a case of a traumatic brain injury patient who had a hypersensitivity reaction to mannitol. It is the first reported case report about hypersensitivity to Mannitol in Indonesia.

  12. Hypersensitivity to contrast media and dyes.

    PubMed

    Brockow, Knut; Sánchez-Borges, Mario

    2014-08-01

    This article updates current knowledge on hypersensitivity reactions to diagnostic contrast media and dyes. After application of a single iodinated radiocontrast medium (RCM), gadolinium-based contrast medium, fluorescein, or a blue dye, a hypersensitivity reaction is not a common finding; however, because of the high and still increasing frequency of those procedures, patients who have experienced severe reactions are nevertheless frequently encountered in allergy departments. Evidence on allergologic testing and management is best for iodinated RCM, limited for blue dyes, and insufficient for fluorescein. Skin tests can be helpful in the diagnosis of patients with hypersensitivity reactions to these compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Immediate-type hypersensitivity reaction to ingestion of mycoprotein (Quorn) in a patient allergic to molds caused by acidic ribosomal protein P2.

    PubMed

    Hoff, Michael; Trüeb, Ralph M; Ballmer-Weber, Barbara K; Vieths, Stefan; Wuethrich, Brunello

    2003-05-01

    Quorn is the brand name for a line of foods made with so-called "mycoprotein," which springs from the mold Fusarium venenatum. Since the introduction on the food market, there have been complaints from consumers reporting adverse gastrointestinal reactions after ingestion of mycoprotein. To date, it is not clear whether the reported symptoms are IgE-mediated. The aim of the study was to describe for the first time a case history of an asthmatic patient with severe hypersensitivity reactions to ingested mycoprotein and to identify and characterize the potential allergen that might be responsible for this. The sensitization pattern of the asthmatic subject was characterized, and food allergy to mycoprotein was assessed by double-blinded placebo-controlled food challenge. Afterward, specific IgE antibodies of the serum of this patient were used to screen a Fusarium culmorum cDNA expression library. The coding sequence of one enriched cDNA-clone was expressed in Escherichia coli to produce a recombinant protein that was further purified and immunologically characterized. The patient showed high sensitization to many known aeroallergens but apart from Quorn not to any other tested food samples. The deduced amino acid sequence of the enriched cDNA-clone (Fus c 1) showed large identity to the 60S acidic ribosomal protein P2 which is highly conserved among several species and also described as minor allergen in other mold species. The frequency of IgE reactivity of sera from F culmorum -sensitized subjects to rFus c 1 was approximately 35%. By enzyme allergosorbent test inhibition, we found 65% inhibition of mycoprotein IgE reactivity by rFus c 1. On the opposite we found reduced IgE reactivity of rFus c 1 of 68% by using mycoprotein as inhibitor. Sensitization to mold allergens by the respiratory tract and subsequent oral ingestion of cross-reactive proteins may lead to severe food-allergic reactions. Thus, the 60S acidic ribosomal protein P2 of F venenatum probably is

  14. Outcomes of corticosteroid prophylaxis for hypersensitivity reactions to low osmolar contrast media in high-risk patients.

    PubMed

    Jung, Jae-Woo; Choi, Young Hun; Park, Chang Min; Park, Heung Woo; Cho, Sang-Heon; Kang, Hye-Ryun

    2016-09-01

    Corticosteroid prophylaxis has been widely adopted for the prevention of acute allergic-like reactions to iodinated contrast media, but its use is still controversial because there is no strong evidence supporting its efficacy before administration of nonionic low osmolar contrast media (LOCM). To assess the outcomes of premedication in patients with previous acute allergic-like reactions to LOCM in clinical practice. A retrospective study was performed on 322 high-risk patients who were reexposed to LOCM after premedication composed of antihistamines and/or systemic corticosteroids because of a previous history of acute allergic-like reactions to LOCM. After premedication, 275 patients (85.4%) did not experience any reaction, but 47 patients (14.6%) still experienced a breakthrough reaction. The premedication rate and amount of corticosteroid administered were significantly higher in the nonrecurrence group than in the recurrence group (P = .04 and P = .04, respectively), and a linear trend was observed in the use of corticosteroid premedication and the efficacy of prevention (P for trend = .02). Multivariate binary logistic regression revealed that corticosteroid premedication was effective in preventing recurrence (odds ratio, 0.284; 95% confidence interval, 0.103-0.784). Nonetheless, despite corticosteroid premedication, 3.4% of high-risk patients still experienced moderate to severe reactions, and 14.3% of patients with a severe index reaction again had a severe reaction. Premedication with corticosteroids seems to be helpful in reducing the overall rate of recurrence of acute allergic-like reactions to LOCM in high-risk patients, but patients with severe index reactions are still at risk of developing severe reactions despite corticosteroid premedication. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  15. Differences in components at delayed-type hypersensitivity reaction sites in mice immunized with either a protective or a nonprotective immunogen of Cryptococcus neoformans.

    PubMed

    Nichols, Kasie L; Bauman, Sean K; Schafer, Fredda B; Murphy, Juneann W

    2002-02-01

    Cell-mediated immunity is the major protective mechanism against Cryptococcus neoformans. Delayed swelling reactions, i.e., delayed-type hypersensitivity (DTH), in response to an intradermal injection of specific antigen are used as a means of detecting a cell-mediated immune (CMI) response to the antigen. We have found previously that the presence of an anticryptococcal DTH response in mice is not always indicative of protection against a cryptococcal infection. Using one immunogen that induces a protective anticryptococcal CMI response and one that induces a nonprotective response, we have shown that mice immunized with the protective immunogen undergo a classical DTH response characterized by mononuclear cell and neutrophil infiltrates and the presence of gamma interferon and NO. In contrast, immunization with the nonprotective immunogen results in an influx of primarily neutrophils and production of tumor necrosis factor alpha (TNF-alpha) at the DTH reaction site. Even when the anticryptococcal DTH response was augmented by blocking the down-regulator, CTLA-4 (CD152), on T cells in the mice given the nonprotective immunogen, the main leukocyte population infiltrating the DTH reaction site is the neutrophil. Although TNF-alpha is increased at the DTH reaction site in mice immunized with the nonprotective immunogen, it is unlikely that TNF-alpha activates the neutrophils, because the density of TNF receptors on the neutrophils is reduced below control levels. Uncoupling of DTH reactivity and protection has been demonstrated in other infectious-disease models; however, the mechanisms differ from our model. These findings stress the importance of defining the cascade of events occurring in response to various immunogens and establishing the relationships between protection and DTH reactions.

  16. Dietary hypersensitivity in cats and dogs.

    PubMed

    Mandigers, Paul; German, Alexander J

    2010-10-01

    Adverse reactions to food or dietary hypersensitivity are frequently seen problems in companion animal medicine and may be difficult to differentiate from inflammatory bowel disease (IBD). Dietary hypersensitivity can be divided into two subgroups: immunological and nonimmunological problems. Non-immunological problems can be subdivided into food intolerance, food poisoning, and dietary indiscretion. The immunological group can be subdivided into true food allergy (IgE mediated) and anaphylaxis (non-IgE mediated). This article gives an outline of what dietary hypersensitivity is, and more specifically food allergy and how to deal with patients with possible dietary hypersensitivity.

  17. Abacavir has no prothrombotic effect on platelets in vitro.

    PubMed

    Diallo, Yacouba L; Ollivier, Véronique; Joly, Véronique; Faille, Dorothée; Catalano, Giovanna; Jandrot-Perrus, Martine; Rauch, Antoine; Yeni, Patrick; Ajzenberg, Nadine

    2016-12-01

    HIV patients exposed to abacavir have an increased risk of myocardial infarction, with contradictory results in the literature. The aim of our study was to determine whether abacavir has a direct effect on platelet activation and aggregation using platelets from healthy donors and from HIV-infected patients under therapy with an undetectable viral load. Platelet-rich plasma (PRP) or whole blood from healthy donors was treated with abacavir (5 or 10 μg/mL) or its active metabolite carbovir diphosphate. Experiments were also performed using blood of HIV-infected patients (n = 10) with an undetectable viral load. Platelet aggregation was performed on PRP by turbidimetry and under high shear conditions at 4000 s -1 . Platelet procoagulant potential was analysed by measuring thrombin generation by thrombinography. Abacavir and carbovir diphosphate significantly increased the aggregation of platelets from healthy donors induced by collagen at 2 μg/mL (P = 0.002), but not at 0.5 μg/mL. No effect of abacavir or carbovir diphosphate was observed on platelet aggregation induced by other physiological agonists or by high shear stress, or on thrombin generation. Pretreatment of blood from HIV-infected patients with abacavir produced similar results. Our results suggest that abacavir does not significantly influence platelet activation in vitro when incubated with platelets from healthy donors or from HIV-infected patients. It is, however, not excluded that a synergistic effect with other drugs could promote platelet activation and thereby play a role in the pathogenesis of myocardial infarction. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Type I allergic hypersensitivity reactions due to ethylene oxide sterilised leucocyte filters in patients with thalassaemia: report of four cases.

    PubMed

    Belen, Burcu; Polat, Meltem

    2015-02-27

    Ethylene oxide (EO) is a highly reactive gas used in sterilisation of heat sensitive medical devices, such as infusion sets, cannulae, intubation materials, ventriculoperitoneal shunts, dialysis catheters and stents. Allergic reactions due to EO have been reported in haemodialysis patients, patients undergoing extracorporeal photopheresis and donors of plasmapheresis. Clinical manifestations vary considerably and generally do not allow differentiation between IgE-mediated anaphylaxis and anaphylactoid reactions. We report four patients with thalassaemia who experienced anaphylaxis during transfusion due to ethylene oxide sterilised leucocyte filters. The aim of this report is to highlight the fact that frequently transfused patients can have allergic reactions due to EO particles left in leucocyte filters. 2015 BMJ Publishing Group Ltd.

  19. Abacavir and cardiovascular disease: A critical look at the data.

    PubMed

    Llibre, Josep M; Hill, Andrew

    2016-08-01

    Most HIV-infected subjects will receive a treatment regimen including abacavir or tenofovir. Therefore, clarifying if there is an increased risk of acute myocardial infarction (AMI) among those exposed to abacavir is of the utmost importance. Due to the low frequency of AMI in this young population (2-5 per 1000 patients/year), efforts to clarify this have been quite controversial. While some observational cohorts have found a statistically significant association, others have not. Meta-analysis of randomized clinical trials offering the highest scientific evidence found no association at all, but with a limited statistical power to definitely rule out a small effect. A channelling or selection bias has been demonstrated in cohort studies, favouring the prescription of abacavir to subjects with or at risk for chronic kidney disease, and therefore, with an intrinsic increased cardiovascular risk. The recent NA-ACCORD cohort study does not identify an increased risk for AMI associated with recent abacavir use in a fully adjusted model (HR 1.33; 95%CI:0.96, 1.88). However, it does find an association in a second analysis restricted to treatment-naïve persons, with higher differences in baseline characteristics among compared arms. A critical review of the compiled available evidence is therefore mandatory, particularly in light of the first single-tablet regimen to receive approval that does contain abacavir. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Comparative safety of intravenous Ferumoxytol versus Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia: rationale and study design of a randomized double-blind study with a focus on acute hypersensitivity reactions.

    PubMed

    Adkinson, N Franklin; Strauss, William E; Bernard, Kristine; Kaper, Robert F; Macdougall, Iain C; Krop, Julie S

    2017-01-01

    Intravenous (IV) iron is often used to treat iron deficiency anemia in patients who are unable to tolerate or are inadequately managed with oral iron. However, IV iron treatment has been associated with acute hypersensitivity reactions. The comparative risk of adverse events (AEs) with IV iron preparations has been assessed by a few randomized controlled trials, which are most often limited by small patient numbers, which lack statistical power to identify differences in low-frequency AE such as hypersensitivity reactions. Ferumoxytol versus Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia (FIRM) is a randomized, double-blind, international, multicenter, Phase III study designed to compare the safety of ferumoxytol and ferric carboxymaltose (FCM). The study includes adults with hemoglobin <12.0 g/dL (females) or <14.0 g/dL (males), transferrin saturation ≤20% or ferritin ≤100 ng/mL within 60 days of dosing, and a history of unsatisfactory or nontolerated oral iron therapy or in whom oral iron therapy is inappropriate. Patients are randomized (1:1) to ferumoxytol 510 mg or FCM 750 mg, each given intravenously on days 1 and 8. Primary end points are the incidence of moderate-to-severe hypersensitivity reactions, including anaphylaxis, and moderate-to-severe hypotension. All potential hypersensitivity and hypotensive reactions will be adjudicated by a blinded, independent Clinical Events Committee. A secondary safety end point is the composite frequency of moderate-to-severe hypersensitivity reactions, including anaphylaxis, serious cardiovascular events, and death. Secondary efficacy end points include mean change in hemoglobin and mean change in hemoglobin per milligram of iron administered from baseline to week 5. Urinary excretion of phosphorus and the occurrence of hypophosphatemia after IV iron administration will be examined as well as the mechanisms of such hypophosphatemia in a substudy. FIRM will provide data on the comparative safety of

  1. Outpatient rapid 4-step desensitization for gynecologic oncology patients with mild to low-risk, moderate hypersensitivity reactions to carboplatin/cisplatin.

    PubMed

    Li, Quan; Cohn, David; Waller, Allyson; Backes, Floor; Copeland, Larry; Fowler, Jeffrey; Salani, Ritu; O'Malley, David

    2014-10-01

    The primary objective of this study is to assess the efficacy and safety of an outpatient, 4-step, one-solution desensitization protocol in gynecologic oncology patients with history of mild to low-risk, moderate hypersensitivity reactions (HSRs) to platinums (carboplatin and cisplatin). This was a single institutional retrospective review. Gynecologic oncology patients with a documented history of mild or low-risk, moderate immediate HSRs to carboplatin/cisplatin and continued treatment with 4-step, one-solution desensitization protocols in the outpatient infusion center were included. Patients with delayed HSRs or immediate high-risk, moderate or severe HSRs were excluded. The primary end point was the rate of successful administrations of each course of platinums. From January 2011 to June 2013, eighteen eligible patients were evaluated for outpatient 4-step, one-solution desensitization. Thirteen patients had a history of HSRs to carboplatin and 5 with HSRs to cisplatin. All of 18 patients successfully completed 94 (98.9%) of 95 desensitization courses in the outpatient infusion center. Eight of 8 (100%) patients with initial mild HSRs completed 29/29 (100%) desensitization courses, and 9 of 10 (90%) of patients with initial moderate HSRs completed 65/66 (94%) desensitization courses. In total, 65/95 (68%) desensitizations resulted in no breakthrough reactions, and mild, moderate and severe breakthrough reactions were seen in 19%, 12% and 1% desensitizations, respectively. No patients were hospitalized during desensitization. The outpatient rapid, 4-step, one-solution desensitization protocol was effective and appeared safe among gynecologic oncology patients who experienced mild to low-risk, moderate HSRs to carboplatin/cisplatin. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. CD22 expression mediates the regulatory functions of peritoneal B-1a cells during the remission phase of contact hypersensitivity reactions.

    PubMed

    Nakashima, Hiroko; Hamaguchi, Yasuhito; Watanabe, Rei; Ishiura, Nobuko; Kuwano, Yoshihiro; Okochi, Hitoshi; Takahashi, Yoshimasa; Tamaki, Kunihiko; Sato, Shinichi; Tedder, Thomas F; Fujimoto, Manabu

    2010-05-01

    Although contact hypersensitivity (CHS) has been considered a prototype of T cell-mediated immune reactions, recently a significant contribution of regulatory B cell subsets in the suppression of CHS has been demonstrated. CD22, one of the sialic acid-binding immunoglobulin-like lectins, is a B cell-specific molecule that negatively regulates BCR signaling. To clarify the roles of B cells in CHS, CHS in CD22(-/-) mice was investigated. CD22(-/-) mice showed delayed recovery from CHS reactions compared with that of wild-type mice. Transfer of wild-type peritoneal B-1a cells reversed the prolonged CHS reaction seen in CD22(-/-) mice, and this was blocked by the simultaneous injection with IL-10 receptor Ab. Although CD22(-/-) peritoneal B-1a cells were capable of producing IL-10 at wild-type levels, i.p. injection of differentially labeled wild-type/CD22(-/-) B cells demonstrated that a smaller number of CD22(-/-) B cells resided in lymphoid organs 5 d after CHS elicitation, suggesting a defect in survival or retention in activated CD22(-/-) peritoneal B-1 cells. Thus, our study reveals a regulatory role for peritoneal B-1a cells in CHS. Two distinct regulatory B cell subsets cooperatively inhibit CHS responses. Although splenic CD1d(hi)CD5(+) B cells have a crucial role in suppressing the acute exacerbating phase of CHS, peritoneal B-1a cells are likely to suppress the late remission phase as "regulatory B cells." CD22 deficiency results in disturbed CHS remission by impaired retention or survival of peritoneal B-1a cells that migrate into lymphoid organs.

  3. Switching to lopinavir/ritonavir with or without abacavir/lamivudine in lipoatrophic patients treated with zidovudine/abacavir/lamivudine.

    PubMed

    Bernardino, J I; Pulido, F; Martinez, E; Arrizabalaga, J; Domingo, P; Portilla, J; Ocampo, A; Muñoz, J; Torres, R; Arribas, J R

    2013-06-01

    Discontinuation of thymidine nucleoside reverse transcriptase inhibitors (tNRTIs) is the only proven strategy for improving lipoatrophy. It is unclear whether switching to NRTI-sparing or to non-thymidine NRTI-containing therapy has differential effects on body fat recovery. This was a 96 week, open-label, randomized study in suppressed patients with moderate/severe lipoatrophy and no prior virological failure while receiving a protease inhibitor and who had their triple NRTI regimen (zidovudine/lamivudine/abacavir) switched to lopinavir/ritonavir plus abacavir/lamivudine for a 1 month run-in period and then randomized to lopinavir/ritonavir plus abacavir/lamivudine versus lopinavir/ritonavir monotherapy. The KRETA trial is registered with ClinicalTrials.gov (number NCT00865007). Of 95 patients included, 88 were randomized to lopinavir/ritonavir plus abacavir/lamivudine (n = 44) or lopinavir/ritonavir monotherapy (n = 44). Median (IQR) baseline limb fat was 2.5 (1.6-3.7) kg in the lopinavir/ritonavir plus abacavir/lamivudine group and 2.5 (2.0-5.4) kg in the lopinavir/ritonavir monotherapy group. Six patients in the triple therapy group and 13 in the monotherapy group had discontinued study drugs by week 96. Although there were limb fat gains in each group at weeks 48/96 (+324/+358 g in lopinavir/ritonavir plus abacavir/lamivudine, P = 0.09/0.07, versus +215/+416 g in the lopinavir/ritonavir monotherapy group, P = 0.28/0.16), differences between groups were not significant [difference +109 g (95% CI -442, +660)/-57 g (95% CI -740, +625)]. In lipoatrophic patients treated with zidovudine/lamivudine/abacavir, switching to lopinavir/ritonavir monotherapy had no additional benefit in limb fat recovery relative to switching to lopinavir/ritonavir with abacavir/lamivudine. These data suggest that non-thymidine nucleosides such as abacavir/lamivudine are not an obstacle to limb fat recovery.

  4. Immunization against an IL-6 peptide induces anti-IL-6 antibodies and modulates the Delayed-Type Hypersensitivity reaction in cynomolgus monkeys.

    PubMed

    Desallais, Lucille; Bouchez, Caroline; Mouhsine, Hadley; Moreau, Gabriel; Ratsimandresy, Rojo; Montes, Matthieu; Do, Hervé; Quintin-Colonna, Françoise; Zagury, Jean-François

    2016-01-19

    Interleukin-6 (IL-6) overproduction has been involved in the pathogenesis of several chronic inflammatory diseases and the administration of an anti-IL-6 receptor monoclonal antibody has been proven clinically efficient to treat them. However, the drawbacks of monoclonal antibodies have led our group to develop an innovative anti-IL-6 strategy using a peptide-based active immunization. This approach has previously shown its efficacy in a mouse model of systemic sclerosis. Here the safety, immunogenicity, and efficacy of this strategy was assessed in non human primates. No unscheduled death and clinical signs of toxicity was observed during the study. Furthermore, the cynomolgus monkeys immunized against the IL-6 peptide produced high levels of anti-IL-6 antibodies as well as neutralizing antibodies compared to control groups. They also showed an important decrease of the cumulative inflammatory score following a delayed-type hypersensitivity reaction induced by the Tetanus vaccine compared to control groups (minus 57,9%, P = 0.014). These findings are highly significant because the immunizing IL-6 peptide used in this study is identical in humans and in monkeys and this novel anti-IL-6 strategy could thus represent a promising alternative to monoclonal antibodies.

  5. Classification and pathophysiology of radiocontrast media hypersensitivity.

    PubMed

    Brockow, Knut; Ring, Johannes

    2010-01-01

    Hypersensitivity reactions to radiocontrast media (RCM) are unpredictable and are a concern for radiologists and cardiologists. Immediate hypersensitivity reactions manifest as anaphylaxis, and an allergic IgE-mediated mechanism has been continuously discussed for decades. Non-immediate reactions clinically are exanthemas resembling other drug-induced non-immediate hypersensitivities. During the past years, evidence is increasing that some of these reactions may be immunological. Repeated reactions after re-exposure, positive skin tests, and presence of specific IgE antibodies as well as positive basophil activation tests in some cases, and positive lymphocyte transformation or lymphocyte activation tests in others, indicate that a subgroup of both immediate and non-immediate reactions are of an allergic origin, although many questions remain unanswered. Recently reported cases highlight that pharmacological premedication is not safe to prevent RCM hypersensitivity in patients with previous severe reactions. These insights may have important consequences. A large multicenter study on the value of skin tests in RCM hypersensitivity concluded that skin testing is a useful tool for diagnosis of RCM allergy. It may have a role for the selection of a safe product in previous reactors, although confirmatory validation data is still scarce. In vitro tests to search for RCM-specific cell activation still are in development. In conclusion, recent data indicate that RCM hypersensitivity may have an allergic mechanism and that allergological testing is useful and may indicate tolerability. Copyright 2010 S. Karger AG, Basel.

  6. Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions.

    PubMed

    Amstutz, Ursula; Shear, Neil H; Rieder, Michael J; Hwang, Soomi; Fung, Vincent; Nakamura, Hidefumi; Connolly, Mary B; Ito, Shinya; Carleton, Bruce C

    2014-04-01

    To systematically review evidence on genetic risk factors for carbamazepine (CBZ)-induced hypersensitivity reactions (HSRs) and provide practice recommendations addressing the key questions: (1) Should genetic testing for HLA-B*15:02 and HLA-A*31:01 be performed in patients with an indication for CBZ therapy to reduce the occurrence of CBZ-induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLA-B*15:02 or HLA-A*31:01 compared to others? (3) How should patients with an indication for CBZ therapy be managed based on their genetic test results? A systematic literature search was performed for HLA-B*15:02 and HLA-A*31:01 and their association with CBZ-induced HSRs. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus. Patients carrying HLA-B*15:02 are at strongly increased risk for CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in populations where HLA-B*15:02 is common, but not CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE). HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported from Asian countries only, including China, Thailand, Malaysia, and India. HLA-B*15:02 is rare among Caucasians or Japanese; no HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported so far in these groups. HLA-A*31:01-positive patients are at increased risk for CBZ-induced HSS and MPE, and possibly SJS/TEN and acute generalized exanthematous pustulosis (AGEP). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however, HLA-A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop an HSR, resulting in a relatively low positive predictive value of the genetic tests. This review provides the latest update on genetic markers for CBZ HSRs, clinical practice recommendations as a basis for informed decision making regarding

  7. N-terminal valine adduct from the anti-HIV drug abacavir in rat haemoglobin as evidence for abacavir metabolism to a reactive aldehyde in vivo

    PubMed Central

    Charneira, C; Grilo, NM; Pereira, SA; Godinho, ALA; Monteiro, EC; Marques, MM; Antunes, AMM

    2012-01-01

    BACKGROUND AND PURPOSE The aim of this study was to obtain evidence for the activation of the nucleoside reverse transcriptase inhibitor abacavir to reactive aldehyde metabolites in vivo. Protein haptenation by these reactive metabolites may be a factor in abacavir-induced toxic events. EXPERIMENTAL APPROACH The formation of N-terminal valine adducts from the abacavir-derived aldehydes was investigated in the haemoglobin of Wistar rats treated with eight daily doses (120 mg·kg−1) of abacavir. The analyses were conducted by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry upon comparison with synthetic standards. KEY RESULTS An N-terminal valine haemoglobin adduct derived from an α,β-unsaturated aldehyde metabolite of abacavir was identified in vivo for the first time. CONCLUSIONS AND IMPLICATIONS This preliminary work on abacavir metabolism provides the first unequivocal evidence for the formation of an α,β-unsaturated aldehyde metabolite in vivo and of its ability to form haptens with proteins. The methodology described herein can be used to assess the formation of this metabolite in human samples and has the potential to become a valuable pharmacological tool for mechanistic studies of abacavir toxicity. In fact, the simplicity of the method suggests that the abacavir adduct with the N-terminal valine of haemoglobin could be used to investigate abacavir-induced toxicity for accurate risk/benefit estimations. PMID:22725138

  8. N-terminal valine adduct from the anti-HIV drug abacavir in rat haemoglobin as evidence for abacavir metabolism to a reactive aldehyde in vivo.

    PubMed

    Charneira, C; Grilo, N M; Pereira, S A; Godinho, A L A; Monteiro, E C; Marques, M M; Antunes, A M M

    2012-11-01

    The aim of this study was to obtain evidence for the activation of the nucleoside reverse transcriptase inhibitor abacavir to reactive aldehyde metabolites in vivo. Protein haptenation by these reactive metabolites may be a factor in abacavir-induced toxic events. The formation of N-terminal valine adducts from the abacavir-derived aldehydes was investigated in the haemoglobin of Wistar rats treated with eight daily doses (120 mg·kg(-1)) of abacavir. The analyses were conducted by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry upon comparison with synthetic standards. An N-terminal valine haemoglobin adduct derived from an α,β-unsaturated aldehyde metabolite of abacavir was identified in vivo for the first time. This preliminary work on abacavir metabolism provides the first unequivocal evidence for the formation of an α,β-unsaturated aldehyde metabolite in vivo and of its ability to form haptens with proteins. The methodology described herein can be used to assess the formation of this metabolite in human samples and has the potential to become a valuable pharmacological tool for mechanistic studies of abacavir toxicity. In fact, the simplicity of the method suggests that the abacavir adduct with the N-terminal valine of haemoglobin could be used to investigate abacavir-induced toxicity for accurate risk/benefit estimations. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  9. Compact quadruple therapy with the lamivudine/zidovudine combination tablet plus abacavir and efavirenz, followed by the lamivudine/zidovudine/abacavir triple nucleoside tablet plus efavirenz in treatment-naïve HIV-infected adults.

    PubMed

    Ruane, Peter J; Parenti, David M; Margolis, David M; Shepp, David H; Babinchak, Timothy J; Van Kempen, Amy S; Kauf, Teresa L; Danehower, Susan A; Yau, Linda; Hessenthaler, Siegrid M; Goodwin, Diane; Hernandez, Jaime E

    2003-01-01

    To assess efficacy, safety, and adherence with compact quadruple therapy comprising one lamivudine 150-mg/zidovudine 300-mg tablet (COM) twice daily + one abacavir (ABC) 300-mg tablet twice daily + three efavirenz (EFV) 200-mg capsules at bedtime for 24 weeks, followed by one lamivudine 150-mg/zidovudine 300-mg/ABC 300-mg triple nucleoside tablet (TZV) twice daily + three EFV 200-mg capsules at bedtime for 24 weeks. A pilot 48-week, prospective, open-label trial in which 38 antiretroviral-naïve HIV-infected adults (baseline median HIV-1 RNA 5.1 log(10) copies/mL, CD4+ cell count 285/microL) received the above treatment and were monitored regularly with respect to plasma HIV-1 RNA levels, CD4+ cell counts, T-cell receptor excision circles (TRECs), adherence, and adverse events. At Week 48, intent-to-treat, switch-included analysis showed plasma HIV-1 RNA levels <400 copies/mL in 100% (29/29) of patients and <50 copies/mL in 93% (27/29); 59% of patients who achieved <50 copies/mL had <3 copies/mL (16/27). Similar virologic suppression was observed in patients with baseline HIV-1 RNA above or below 100000 copies/mL. HIV-1 RNA and CD4+ cell counts changed from baseline by a median of -3.4 log(10) copies/mL and +172 cells/microL, respectively. One virologic failure occurred at Week 16. Median TRECs/100000 peripheral blood lymphocytes increased 6-fold between baseline and Week 48. Median adherence rates were consistently 100% by self-report and 94% by pill count. Grade 2-4 treatment-related adverse events included dreams (16%), nausea (13%), decreased white cells (8%), dizziness (8%), sleep disorders (8%), and malaise and fatigue (8%). A suspected ABC hypersensitivity reaction occurred in 8% (3/38) of patients. COM/ABC/EFV or TZV/EFV produced potent, durable virologic suppression and immunologic benefits, was associated with high adherence rates, and was generally well tolerated.

  10. The Multi-Resistant Reaction of Drought-Tolerant Coffee 'Conilon Clone 14' to Meloidogyne spp. and Late Hypersensitive-Like Response in Coffea canephora.

    PubMed

    Lima, Edriana A; Furlanetto, Cleber; Nicole, Michel; Gomes, Ana C M M; Almeida, Maria R A; Jorge-Júnior, Aldemiro; Correa, Valdir R; Salgado, Sônia Maria; Ferrão, Maria A G; Carneiro, Regina M D G

    2015-06-01

    Root-knot nematodes (RKN), Meloidogyne spp., have major economic impact on coffee production in Central and South America. Genetic control of RKN constitutes an essential part for integrated pest management strategy. The objective of this study was to evaluate the resistance of Coffea canephora genotypes (clones) to Meloidogyne spp. Sensitive and drought-tolerant coffee genotypes were used to infer their resistance using nematode reproduction factor and histopathology. Eight clonal genotypes were highly resistant to M. paranaensis. 'Clone 14' (drought-tolerant) and 'ESN2010-04' were the only genotypes highly resistant and moderately resistant, respectively, to both M. incognita races 3 and 1. Several clones were highly resistant to both avirulent and virulent M. exigua. Clone 14 and ESN2010-04 showed multiple resistance to major RKNs tested. Roots of 'clone 14' (resistant) and 'clone 22' (susceptible) were histologically studied against infection by M. incognita race 3 and M. paranaensis. Reduction of juvenile (J2) penetration in clone 14 was first seen at 2 to 6 days after inoculation (DAI). Apparent early hypersensitive reaction (HR) was seen in root cortex between 4 and 6 DAI, which led to cell death and prevention of some nematode development. At 12 to 20 DAI, giant cells formed in the vascular cylinder, besides normal development into J3/J4. From 32 to 45 DAI, giant cells were completely degenerated. Late, intense HR and cell death were frequently observed around young females and giant cells reported for the first time in coffee pathosystem. These results provide rational bases for future studies, including prospection, characterization, and expression profiling of genomic loci involved in both drought tolerance and resistance to multiple RKN species.

  11. Re-exposure to low osmolar iodinated contrast media in patients with prior moderate-to-severe hypersensitivity reactions: A multicentre retrospective cohort study.

    PubMed

    Park, Hye Jung; Park, Jung-Won; Yang, Min-Suk; Kim, Mi-Yeong; Kim, Sae-Hoon; Jang, Gwang Cheon; Nam, Young-Hee; Kim, Gun-Woo; Kim, Sujeong; Park, Hye-Kyung; Jung, Jae-Woo; Park, Jong-Sook; Kang, Hye-Ryun

    2017-07-01

    To evaluate the outcomes of re-exposure to low-osmolar iodinated contrast medium (LOCM) in patients with a history of moderate-to-severe hypersensitivity reaction (HSR). We retrospectively evaluated a cohort comprising all subjects satisfying the following conditions at 11 centres: (1) experienced a moderate-to-severe HSR to LOCM by December 2014, and (2) underwent contrast-enhanced computed tomography after the initial HSR between January 2014 and December 2014. A total of 150 patients with 328 instances of re-exposure were included; the recurrence rate of HSR was 19.5%. Patients with severe initial HSR exhibited a higher recurrence rate of severe HSR compared to patients with moderate initial HSR, despite more intensive premedication. In the multivariate analysis, the independent risk factors for recurrence of HSR were diabetes, chronic urticaria, drug allergy other than to iodinated contrast media (ICM) and severe initial HSR. The risk of recurrent HSR was 67.1% lower in cases where the implicated ICM was changed to another one (odds ratio: 0.329; P = 0.001). However, steroid premedication did not show protective effects against recurrent HSR. In high-risk patients who have previously experienced a moderate-to-severe initial HSR to LOCM, we should consider changing the implicated ICM to reduce recurrence risk. • In patients with moderate-to-severe HSR, steroid premedication only shows limited effectiveness. • Changing the implicated ICM can reduce the recurrence of HSR to ICM. • Diabetes, chronic urticaria and drug allergies increase the risk of ICM HSR.

  12. Population pharmacokinetics of abacavir in infants, toddlers and children.

    PubMed

    Zhao, Wei; Piana, Chiara; Danhof, Meindert; Burger, David; Della Pasqua, Oscar; Jacqz-Aigrain, Evelyne

    2013-06-01

    To characterize the pharmacokinetics of abacavir in infants, toddlers and children and to assess the influence of covariates on drug disposition across these populations. Abacavir concentration data from three clinical studies in human immunodeficiency virus-infected children (n = 69) were used for model building. The children received either a weight-normalized dose of 16 mg kg(-1) day(-1) or the World Health Organization recommended dose based on weight bands. A population pharmacokinetic analysis was performed using nonlinear mixed effects modelling VI. The influence of age, gender, bodyweight and formulation was evaluated. The final model was selected according to graphical and statistical criteria. A two-compartmental model with first-order absorption and first-order elimination best described the pharmacokinetics of abacavir. Bodyweight was identified as significant covariate influencing the apparent oral clearance and volume of distribution. Predicted steady-state maximal plasma concentration and area under the concentration-time curve from 0 to 12 h of the standard twice daily regimen were 2.5 mg l(-1) and 6.1 mg h l(-1) for toddlers and infants, and 3.6 mg l(-1) and 8.7 mg h l(-1) for children, respectively. Model-based predictions showed that equivalent systemic exposure was achieved after once and twice daily dosing regimens. There were no pharmacokinetic differences between the two formulations (tablet and solution). The model demonstrated good predictive performance for dosing prediction in individual patients and, as such, can be used to support therapeutic drug monitoring in conjunction with sparse sampling. The disposition of abacavir in children appears to be affected only by differences in size, irrespective of the patient's age. Maturation processes of abacavir metabolism in younger infants should be evaluated in further studies to demonstrate the potential impact of ontogeny. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012

  13. Population pharmacokinetics of abacavir in infants, toddlers and children

    PubMed Central

    Zhao, Wei; Piana, Chiara; Danhof, Meindert; Burger, David; Della Pasqua, Oscar; Jacqz-Aigrain, Evelyne

    2013-01-01

    Aims To characterize the pharmacokinetics of abacavir in infants, toddlers and children and to assess the influence of covariates on drug disposition across these populations. Methods Abacavir concentration data from three clinical studies in human immunodeficiency virus-infected children (n = 69) were used for model building. The children received either a weight-normalized dose of 16 mg kg−1 day−1 or the World Health Organization recommended dose based on weight bands. A population pharmacokinetic analysis was performed using nonlinear mixed effects modelling VI. The influence of age, gender, bodyweight and formulation was evaluated. The final model was selected according to graphical and statistical criteria. Results A two-compartmental model with first-order absorption and first-order elimination best described the pharmacokinetics of abacavir. Bodyweight was identified as significant covariate influencing the apparent oral clearance and volume of distribution. Predicted steady-state maximal plasma concentration and area under the concentration–time curve from 0 to 12 h of the standard twice daily regimen were 2.5 mg l−1 and 6.1 mg h l−1 for toddlers and infants, and 3.6 mg l−1 and 8.7 mg h l−1 for children, respectively. Model-based predictions showed that equivalent systemic exposure was achieved after once and twice daily dosing regimens. There were no pharmacokinetic differences between the two formulations (tablet and solution). The model demonstrated good predictive performance for dosing prediction in individual patients and, as such, can be used to support therapeutic drug monitoring in conjunction with sparse sampling. Conclusions The disposition of abacavir in children appears to be affected only by differences in size, irrespective of the patient's age. Maturation processes of abacavir metabolism in younger infants should be evaluated in further studies to demonstrate the potential impact of ontogeny. PMID:23126277

  14. Targeting a Cross-Reactive Gly m 5 Soy Peptide as Responsible for Hypersensitivity Reactions in a Milk Allergy Mouse Model

    PubMed Central

    Curciarello, Renata; Smaldini, Paola L.; Candreva, Angela M.; González, Virginia; Parisi, Gustavo; Cauerhff, Ana; Barrios, Ivana; Blanch, Luis Bruno; Fossati, Carlos A.

    2014-01-01

    Background Cross-reactivity between soybean allergens and bovine caseins has been previously reported. In this study we aimed to map epitopes of the major soybean allergen Gly m 5 that are co-recognized by casein specific antibodies, and to identify a peptide responsible for the cross-reactivity. Methods Cow's milk protein (CMP)-specific antibodies were used in different immunoassays (immunoblotting, ELISA, ELISA inhibition test) to evaluate the in vitro recognition of soybean proteins (SP). Recombinant Gly m 5 (α), a truncated fragment containing the C-terminal domain (α-T) and peptides of α-T were obtained and epitope mapping was performed with an overlapping peptide assay. Bioinformatics tools were used for epitope prediction by sequence alignment, and for modelling the cross-recognized soy proteins and peptides. The binding of SP to a monoclonal antibody was studied by surface Plasmon resonance (SPR). Finally, the in vivo cross-recognition of SP was assessed in a mouse model of milk allergy. Results Both α and α-T reacted with the different CMP-specific antibodies. α-T contains IgG and IgE epitopes in several peptides, particularly in the peptide named PA. Besides, we found similar values of association and dissociation constants between the α-casein specific mAb and the different milk and soy components. The food allergy mouse model showed that SP and PA contain the cross-reactive B and T epitopes, which triggered hypersensitivity reactions and a Th2-mediated response on CMP-sensitized mice. Conclusions Gly m 5 is a cross-reactive soy allergen and the α-T portion of the molecule contains IgG and IgE immunodominant epitopes, confined to PA, a region with enough conformation to be bound by antibodies. These findings contribute to explain the intolerance to SP observed in IgE-mediated CMA patients, primarily not sensitised to SP, as well as it sets the basis to propose a mucosal immunotherapy for milk allergy using this soy peptide. PMID:24416141

  15. Targeting a cross-reactive Gly m 5 soy peptide as responsible for hypersensitivity reactions in a milk allergy mouse model.

    PubMed

    Curciarello, Renata; Smaldini, Paola L; Candreva, Angela M; González, Virginia; Parisi, Gustavo; Cauerhff, Ana; Barrios, Ivana; Blanch, Luis Bruno; Fossati, Carlos A; Petruccelli, Silvana; Docena, Guillermo H

    2014-01-01

    Cross-reactivity between soybean allergens and bovine caseins has been previously reported. In this study we aimed to map epitopes of the major soybean allergen Gly m 5 that are co-recognized by casein specific antibodies, and to identify a peptide responsible for the cross-reactivity. Cow's milk protein (CMP)-specific antibodies were used in different immunoassays (immunoblotting, ELISA, ELISA inhibition test) to evaluate the in vitro recognition of soybean proteins (SP). Recombinant Gly m 5 (α), a truncated fragment containing the C-terminal domain (α-T) and peptides of α-T were obtained and epitope mapping was performed with an overlapping peptide assay. Bioinformatics tools were used for epitope prediction by sequence alignment, and for modelling the cross-recognized soy proteins and peptides. The binding of SP to a monoclonal antibody was studied by surface Plasmon resonance (SPR). Finally, the in vivo cross-recognition of SP was assessed in a mouse model of milk allergy. Both α and α-T reacted with the different CMP-specific antibodies. α-T contains IgG and IgE epitopes in several peptides, particularly in the peptide named PA. Besides, we found similar values of association and dissociation constants between the α-casein specific mAb and the different milk and soy components. The food allergy mouse model showed that SP and PA contain the cross-reactive B and T epitopes, which triggered hypersensitivity reactions and a Th2-mediated response on CMP-sensitized mice. Gly m 5 is a cross-reactive soy allergen and the α-T portion of the molecule contains IgG and IgE immunodominant epitopes, confined to PA, a region with enough conformation to be bound by antibodies. These findings contribute to explain the intolerance to SP observed in IgE-mediated CMA patients, primarily not sensitised to SP, as well as it sets the basis to propose a mucosal immunotherapy for milk allergy using this soy peptide.

  16. Managing hypersensitivity to asparaginase in pediatrics, adolescents, and young adults.

    PubMed

    Shinnick, Sara E; Browning, Mary L; Koontz, Susannah E

    2013-01-01

    Hypersensitivity reactions to chemotherapeutic drugs have been documented for numerous cancer therapies. Clinical hypersensitivity to Escherichia coli asparaginase has been reported to range from 0% to 75%. Throughout the United States, nurses assume frontline responsibility for the assessment of asparaginase-related hypersensitivity reactions. It is essential that nurses educate themselves on the signs and symptoms of asparaginase-related hypersensitivity reactions as well as current supportive care approaches. The purpose of this review is to summarize acute lymphoblastic leukemia and the role of asparaginase and the pathology of allergic reactions. We will also update nurses on the differences in asparaginase preparations including dosing, half-life, rates of hypersensitivity, and routes of administration. A summary of current management and supportive care strategies will be provided as will a discussion of the relationship between allergy, antibodies, and asparaginase activity.

  17. [Anticonvulsant hypersensitivity syndrome and lamotrigine-associated anticonvulsant hypersensitivity syndrome].

    PubMed

    Taillia, H; Alla, P; Fournier, B; Bounolleau, P; Ouologem, M; Ricard, D; Sallansonnet-Froment, M; de Greslan, T; Renard, J-L

    2009-10-01

    Anticonvulsant hypersensitivity syndrome (AHS) is defined by the association of high fever, cutaneous rash and multiorgan-system abnormalities (incidence, one in 1000 to one in 10,000 exposures). Fatal complications are described in 10%. This reaction usually develops 1 to 12 weeks after initiation of an aromatic anticonvulsant. Drug rash with eosinophilia and systemic symptoms (DRESS) can be discussed as differential diagnosis. Several hypotheses have been put forward to explain the pathogenesis of AHS. These include accumulation of toxic metabolites, antibody production and viral infection. The one based on toxic metabolites has found the greatest acceptance due to the fact that it can be proven by an in vitro test, the lymphocyte toxicity assay. In vivo, skin biopsies show characteristic findings of erythema multiform or typical leucocytoclastic angitis. The patch-test is positive in 80% of the cases. Lamotrigine-associated anticonvulsant hypersensitivity syndrome (LASH) is rare and was described in 1998. We report two new cases demonstrating the two particular configurations of apparition of LASH found in the 14 cases from the review of literature (Pubmed: anticonvulsant hypersensitivity syndrome - lamotrigine): high doses of lamotrigine (or lamotrigine in very young or old patients), and lamotrigine associated with another anti-epileptic (phenobarbital or sodium valproate). We discuss the links between DRESS after lamotrigine and LASH as illustrated in a new case.

  18. Cerebrospinal fluid abacavir concentrations in HIV-positive patients following once-daily administration.

    PubMed

    Calcagno, A; Pinnetti, C; De Nicolò, A; Scarvaglieri, E; Gisslen, M; Tempestilli, M; D'Avolio, A; Fedele, V; Di Perri, G; Antinori, A; Bonora, S

    2018-06-01

    Abacavir is a widely used nucleotide reverse transcriptase inhibitor, for which cerebrospinal fluid (CSF) exposure has been previously assessed in twice-daily recipients. We studied abacavir CSF concentrations in 61 and nine HIV-positive patients taking abacavir once daily and twice daily, respectively. Patients on once-daily abacavir had higher plasma and CSF concentrations (96 vs. 22 ng ml -1 , P = 0.038 and 123 vs. 49 ng ml -1 , P = 0.038) but similar CSF-to-plasma ratios (0.8 vs. 0.5, P = 0.500). CSF abacavir concentrations were adequate in patients receiving once-daily treatment. © 2018 The British Pharmacological Society.

  19. Abacavir increases platelet reactivity via competitive inhibition of soluble guanylyl cyclase

    PubMed Central

    Baum, Paul D.; Sullam, Paul M.; Stoddart, Cheryl A.; McCune, Joseph M.

    2011-01-01

    Objective To provide a molecular mechanism that explains the association of the antiretroviral guanosine analogue, abacavir, with an increased risk of myocardial infarction. Design Drug effects were studied with biochemical and cellular assays. Methods Human platelets were incubated with nucleoside analogue drugs ex vivo. Platelet activation stimulated by ADP was studied by measuring surface P-selectin with flow cytometry. Inhibition of purified soluble guanylyl cyclase was quantified using an ELISA to measure cGMP production. Results Pre-incubation of platelets in abacavir significantly increased activation in response to ADP in a time and dose-dependent manner. The active anabolite of abacavir, carbovir triphosphate, competitively inhibited soluble guanylyl cyclase activity with a Ki of 55 μmol/l. Conclusion Abacavir competitively inhibits guanylyl cyclase, leading to platelet hyper-reactivity. This may explain the observed increased risk of myocardial infarction in HIV patients taking abacavir. PMID:21941165

  20. Open-label randomized multicenter selection study of once daily antiretroviral treatment regimen comparing ritonavir-boosted atazanavir to efavirenz with fixed-dose abacavir and lamivudine.

    PubMed

    Honda, Miwako; Ishisaka, Michiyo; Ishizuka, Naoki; Kimura, Satoshi; Oka, Shinichi

    2011-01-01

    The side-effects of anti-retroviral drugs are different between Japanese and Caucasian patients. Severe central nerve system (CNS) side-effects to efavirenz and low rate of hypersensitivity against abacavir characterize the Japanese. The objective of this study was to select a once daily regimen for further non-inferior study comparing the virological efficacy and safety of the first line once daily antiretroviral treatment regimens in the current HIV/AIDS guideline. The study design was a randomized, open label, multicenter, selection study. One arm was treated with efavirenz and the other with ritonavir-boosted atazanavir. A fixed-dose lamivudine plus abacavir were used in both arms. The primary endpoint was virologic success (viral load less than 50 copies/mL) rate at 48 weeks. Patients were followed-up to 96 weeks with safety as the secondary endpoint. Clinicaltrials.Gov (NCT00280969) and the University hospital Medical Information Network (UMIN000000243). A total of 71 participants were enrolled. Virologic success rates in both arms were similar at week 48 [efavirenz arm 28/36 (77.8%); atazanavir arm 27/35 (77.1%)], but were decreased at week 96 to 55.6% in the efavirenz arm and 68.8% in the atazanavir arm (p=0.33). At the 96-week follow-up, 52.8% of the EFV arm and 34.3% of the ATV/r arm reached total cholesterol more than 220 mg/dL and required treatment. None of the patients developed cardiovascular complications in this study by week 96. There was no significant difference in the efficacy of efavirenz and ritonavir-boosted atazanavir combined with lamivudine plus abacavir at 48 weeks. The evaluation of safety was extended to 96 weeks, which also showed no significant difference in both arms.

  1. Pharmacokinetic Interaction of Abacavir (1592U89) and Ethanol in Human Immunodeficiency Virus-Infected Adults

    PubMed Central

    McDowell, James A.; Chittick, Gregory E.; Stevens, Cristina Pilati; Edwards, Kathleen D.; Stein, Daniel S.

    2000-01-01

    While in vitro results at clinically relevant concentrations do not predict abacavir (1592U89) interactions with drugs highly metabolized by cytochrome P450, the potential does exist for a pharmacokinetic interaction between abacavir and ethanol, as both are metabolized by alcohol dehydrogenase. Twenty-five subjects were enrolled in an open-label, randomized, three-way-crossover, phase I study of human immunodeficiency virus-infected male subjects. The three treatments were administration of (i) 600 mg of abacavir, (ii) 0.7 g of ethanol per kg of body weight, and (iii) 600 mg of abacavir and 0.7 g of ethanol per kg. Twenty-four subjects completed the study with no unexpected adverse events reported. Ethanol pharmacokinetic parameters were unchanged with abacavir coadministration. The geometric least squares mean area under the concentration curve extrapolated to infinite time for abacavir increased 41% (from 11.07 to 15.62 μg · h/ml), and the half-life increased 26% (from 1.42 to 1.79 h) in the presence of ethanol (mean ethanol maximum concentration in plasma of 498 μg/ml). The percentages of abacavir dose recovered in urine as abacavir and its two major metabolites were each altered in the presence of ethanol, but there was no change in the total percentage (≈50%) of administered dose recovered in the 12-h collection interval. In conclusion, while a single 600-mg dose of abacavir does not alter blood ethanol concentration, ethanol does increase plasma abacavir concentrations. PMID:10817729

  2. Zidovudine/Lamivudine vs. Abacavir/Lamivudine vs. Tenofovir/Emtricitabine in fixed-dose combinations as initial treatment for HIV patients: a systematic review and network meta-analysis

    PubMed Central

    Duque Molina, Marcela María; García García, Héctor Iván

    2017-01-01

    Abstract Introduction: Initial treatment of the HIV is based on the use of three drugs, two of which are nucleoside analog reverse-transcriptase inhibitors. There are three combinations of these drugs which have been approved by different guidelines, each with divergent results in terms of efficacy and safety. Objective: To compare the efficacy and safety of these three combinations. Methods: Systematic review and network meta-analysis of randomized clinical trials comparing fixed doses of Tenofovir Disoproxil Fumarate / Emtricitabine (TDF/FTC), Abacavir / Lamivudine (ABC/3TC) and Zidovudine / Lamivudine (ZDV/3TC). Results: Seven clinical trials met the eligibility criteria. The results suggested higher efficacy with TDF/FTC vs. ABC/3TC at 96 weeks and vs. ZDV/3TC at 48 weeks. However, there is clinical and statistical heterogeneity. Subgroup analysis were performed by third drug and by level of viral load prior to treatment, and found no differences in virological control. Network meta-analysis could only be carried out with TDF/FTC vs. ZDV/3TC, and the proportion of patients with virological response, with no differences at 48 weeks nor at 96 weeks. Direct comparisons showed an increased risk of bone marrow suppression of ZDV/3TC vs. TDF/FTC and of ABC/3TC hypersensitivity reactions vs. ZDV/3TC Conclusions: The results did not show differences in effectiveness among the interventions. However, due to the heterogeneity of the third drug and the follow-up time between the included studies, this result is not definitive. The results raise the need for further studies to help improve treatment recommendations in patients infected with HIV. PMID:29021641

  3. The use of an electronic medical record system for mandatory reporting of drug hypersensitivity reactions has been shown to improve the management of patients in the university hospital in Korea.

    PubMed

    Park, Chan Sun; Kim, Tae-Bum; Kim, Seoung Lan; Kim, Jae Youn; Yang, Kyung Ai; Bae, Yun-Jeong; Cho, You Sook; Moon, Hee-Bom

    2008-09-01

    This study was conducted to evaluate the effectiveness of a computerized surveillance system for adverse drug events (ADEs) reinforced with mandatory reporting of all past drug hypersensitivity reactions (DHSRs) and supervision of the processes by allergy specialists in a university hospital. All information on both prior and newly developed DHSRs was collected via the surveillance system described above and compared with the data from previous system based on voluntary reporting of DHSRs by attending physicians. The report rate of past DHSRs was greatly increased and the estimated incidence of new events decreased under the new system. The occurrence rate of new DHSRs during hospitalization, which were caused by the repeated administration of the agents previously suspected as culprit drugs enormously, decreased from 15% of previous system to 1% of new system. The mandatory reporting system for past DHSRs and the supervision by allergy specialists appear to be important in improving the management of patients with drug hypersensitivity and in preventing the occurrence of DHSRs in a general hospital.

  4. Increased platelet reactivity in HIV-1-infected patients receiving abacavir-containing antiretroviral therapy.

    PubMed

    Satchell, Claudette S; O'Halloran, Jane A; Cotter, Aoife G; Peace, Aaron J; O'Connor, Eileen F; Tedesco, Anthony F; Feeney, Eoin R; Lambert, John S; Sheehan, Gerard J; Kenny, Dermot; Mallon, Patrick W G

    2011-10-15

    Current or recent use of abacavir for treating human immunodeficiency virus type 1 (HIV-1) infection has been associated with increased rates of myocardial infarction (MI). Given the role of platelet aggregation in thrombus formation in MI and the reversible nature of the abacavir association, we hypothesized that patients treated with abacavir would have increased platelet reactivity. In a prospective study in adult HIV-infected patients, we determined associations between antiretrovirals (ARVs), and in particular the nucleoside reverse transcriptase inhibitor abacavir, and platelet reactivity by measuring time-dependent platelet aggregation in response to agonists: adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), collagen, and epinephrine. Of 120 subjects, 40 were ARV-naive and 80 ARV-treated, 40 of whom were receiving abacavir. No consistent differences in platelet reactivity were observed between the ARV-naive and ARV-treated groups. In contrast, within the ARV-treated group, abacavir-treated subjects had consistently higher percentages of platelet aggregation upon exposure to ADP, collagen, and epinephrine (P = .037, P = .022, and P = .032, respectively) and had platelets that were more sensitive to aggregation upon exposure to TRAP (P = .025). The consistent increases in platelet reactivity observed in response to a range of agonists provides a plausible underlying mechanism to explain the reversible increased rates of MI observed in abacavir-treated patients.

  5. Rapid screening for the detection of HLA-B57 and HLA-B58 in prevention of drug hypersensitivity.

    PubMed

    Kostenko, L; Kjer-Nielsen, L; Nicholson, I; Hudson, F; Lucas, A; Foley, B; Chen, K; Lynch, K; Nguyen, J; Wu, A H B; Tait, B D; Holdsworth, R; Mallal, S; Rossjohn, J; Bharadwaj, M; McCluskey, J

    2011-07-01

    HLA-B57 and HLA-B58 are major histocompatibility class (MHC)-I allotypes that are potentially predictive of important clinical immune phenotypes. HLA-B*5701 is strongly associated with hypersensitivity to the HIV drug abacavir, liver toxicity from the antibiotic flucloxacillin and is a marker for slow progression of HIV AIDS. HLA-B*5801 is associated with hypersensitivity to allopurinol used to treat hyperuricaemia and recurrent gout. Here we describe a monoclonal antibody (mAb) specific for HLA-B57 and HLA-B58 that provides an inexpensive and sensitive screen for these MHC-I allotypes. The usefulness of HLA-B57 screening for prediction of abacavir hypersensitivity was shown in three independent laboratories, including confirmation of the mAb sensitivity and specificity in a cohort of patients enrolled in the PREDICT-1 trial. Our data show that patients who test negative by mAb screening comprise 90%-95% of all individuals in most human populations and require no further human leukocyte antigen (HLA) typing. Patients who test positive by mAb screening should proceed to high-resolution typing to ascertain the presence of HLA-B*5701 or HLA-B*5801. Hence, mAb screening provides a low-cost alternative to high-resolution typing of all patients and lends itself to point-of-care diagnostics and rapid ascertainment of low-risk patients who can begin immediate therapy with abacavir, flucloxacillin or allopurinol. © 2011 John Wiley & Sons A/S.

  6. Use of Abacavir and Risk of Cardiovascular Disease Among HIV-Infected Individuals.

    PubMed

    Marcus, Julia L; Neugebauer, Romain S; Leyden, Wendy A; Chao, Chun R; Xu, Lanfang; Quesenberry, Charles P; Klein, Daniel B; Towner, William J; Horberg, Michael A; Silverberg, Michael J

    2016-04-01

    Evidence is conflicting about the association of abacavir use and cardiovascular disease (CVD) among HIV-infected individuals. Previous studies may have been biased by the preferential initiation or continuation of abacavir in patients with renal dysfunction. We conducted a cohort study in Kaiser Permanente California during 1998-2011, following HIV-infected adults initiating antiretroviral therapy until the earliest of CVD (ie, coronary heart disease or ischemic stroke), health plan disenrollment, death, or end of study. We used inverse-probability weighting to fit marginal structural models to estimate hazard ratios (HRs) for CVD comparing regimens with and without abacavir. Propensity score models included demographics, HIV-specific factors, and CVD risk factors, including alcohol/drug use, smoking, overweight/obesity, diabetes, lipid-lowering and hypertension therapy, and renal dysfunction (ie, estimated glomerular filtration rate <60 mL·min·1.73 m). Among 8154 subjects, 178 had ≥1 CVD event, with 24/704 (3.4%) in the abacavir group and 154/7450 (2.1%) in the group initiating regimens without abacavir. Abacavir users had more renal dysfunction at antiretroviral therapy initiation (7.0% vs. 3.3%, P < 0.001). Compared with patients initiating regimens without abacavir, abacavir users had a 2.2-fold higher risk of CVD in intention-to-treat analysis [HR 2.2, 95% confidence interval (CI): 1.4 to 3.5], a 2.7-fold higher risk when remaining on their initial regimens for ≥1 year (HR 2.7, 95% CI: 1.5 to 5.0), and a 2.1-fold higher risk in per-protocol analysis (HR 2.1, 95% CI: 0.9 to 5.0). Abacavir was associated with an over 2-fold increased risk of CVD, which was not explained by renal dysfunction or other CVD risk factors.

  7. Association of Abacavir and Impaired Endothelial Function in Treated and Suppressed HIV-Infected Patients

    PubMed Central

    Hsue, Priscilla Y.; Hunt, Peter W.; Wu, Yuaner; Schnell, Amanda; Ho, Jennifer E.; Hatano, Hiroyu; Xie, Yu; Martin, Jeffrey N.; Ganz, Peter; Deeks, Steven G.

    2009-01-01

    Background HIV-infected patients have accelerated atherosclerosis. Abacavir has been associated with increased risk of cardiovascular events, for reasons that remain to be elucidated. As endothelial dysfunction is central to the pathogenesis of atherosclerosis, we tested the hypothesis that current treatment with abacavir is associated with impaired endothelial function. Methods We studied a cohort of 61 antiretroviral-treated patients who had undetectable plasma HIV RNA levels. Endothelial function was assessed by measuring flow-mediated vasodilation (FMD) of the brachial artery. We compared FMD in patients treated with or without abacavir, while adjusting for traditional risk factors and HIV-specific characteristics. Results The median age was 50 years (IQR 45–57). The median duration of HIV infection was 18 years, and the median CD4 cell count was 369 cells/mm3. Thirty subjects (49%) were receiving abacavir. Overall, the median FMD in the HIV-infected patients was low (3.5%; IQR 2.3–5.6%). The FMD was lower in the abacavir-treated patients than those not on abacavir (2.8% vs. 4.9%, p=0.01). After adjustment for traditional risk factors, HIV specific factors, and baseline brachial artery diameter, current abacavir use was independently associated with lower FMD (p=0.017). Duration of therapy and CD4 count were not associated with reduced FMD. Conclusions Endothelial function, a central mechanism in atherosclerosis and a marker of cardiovascular risk, is impaired among antiretroviral-treated patients with undetectable viral loads. Current use of abacavir was independently associated with impaired endothelial function. This finding suggests that abnormal endothelial function may underlie the clinically observed increased risk in myocardial infarction among abacavir-treated patients. PMID:19542863

  8. Incidence of hypersensitivity and anaphylaxis with sugammadex.

    PubMed

    Min, K Chris; Woo, Tiffany; Assaid, Christopher; McCrea, Jacqueline; Gurner, Deborah M; Sisk, Christine McCrary; Adkinson, Franklin; Herring, W Joseph

    2018-06-01

    To evaluate the incidence of hypersensitivity and anaphylaxis after administration of sugammadex. Retrospective analysis. Sugammadex clinical development program and post-marketing experience. Surgical patients and healthy volunteers who received sugammadex or placebo/comparator with anesthesia and/or neuromuscular blockade (NMB). Sugammadex administered as 2.0 mg/kg at reappearance of the second twitch, 4.0 mg/kg at 1-2 post-tetanic count, or 16.0 mg/kg at 3 min after rocuronium 1.2 mg/kg. Three analytical methods were used: 1) automated MedDRA queries; 2) searches of adverse events (AEs) consistent with treatment-related hypersensitivity reactions as diagnosed by the investigator; and 3) a retrospective adjudication of AEs suggestive of hypersensitivity by a blinded, independent adjudication committee (AC). In addition, a search of all post-marketing reports of events of hypersensitivity was performed, and events were retrospectively adjudicated by an independent AC. Anaphylaxis was determined according to Sampson Criterion 1. The pooled dataset included 3519 unique subjects who received sugammadex and 544 who received placebo. The automated MedDRA query method showed no apparent increase in hypersensitivity or anaphylaxis with sugammadex as compared to placebo or neostigmine. Similarly, there was a low overall incidence of AEs of treatment-related hypersensitivity (<1%), with no differences between sugammadex and placebo or neostigmine. Finally, the retrospective adjudication of AEs suggestive of hypersensitivity showed a low incidence of hypersensitivity (0.56% and 0.21% for sugammadex 2 mg/kg and 4 mg/kg, respectively), with an incidence similar to subjects who received placebo (0.55%). There were no confirmed cases of anaphylaxis in the pooled studies. During post-marketing use, spontaneous reports of anaphylaxis occurred with approximately 0.01% of sugammadex doses. Subjects who received sugammadex with general anesthesia and/or NMB had a low

  9. Bioequivalence of a dolutegravir, abacavir, and lamivudine fixed-dose combination tablet and the effect of food.

    PubMed

    Weller, Stephen; Chen, Shuguang; Borland, Julie; Savina, Paul; Wynne, Brian; Piscitelli, Stephen C

    2014-08-01

    The integrase inhibitor dolutegravir and nucleoside analogues abacavir and lamivudine are once-daily treatment options for HIV. This study (NCT01622790) evaluated, first, the bioequivalence (BE) of a fixed-dose combination (FDC) tablet containing dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg (dolutegravir/abacavir/lamivudine FDC) vs coadministered dolutegravir 50 mg and abacavir/lamivudine combination tablets (Epzicom) and, second, the effect of food on the dolutegravir/abacavir/lamivudine FDC tablet. Study part A (66 healthy subjects) was a single-dose, open-label, randomized, 2-period crossover study to evaluate the BE of the dolutegravir/abacavir/lamivudine FDC tablet and dolutegravir + abacavir/lamivudine tablets in the fasted state. In study part B, 12 subjects from part A received the dolutegravir/abacavir/lamivudine FDC tablet with a high-fat meal. BE and food effect were assessed by analysis of variance to determine the ratio of geometric least squares means and associated 90% confidence intervals for key pharmacokinetic parameters for each of dolutegravir, abacavir, and lamivudine. Sixty-two subjects completed part A. The dolutegravir/abacavir/lamivudine tablet was bioequivalent to the dolutegravir + abacavir/lamivudine tablets; 90% confidence intervals for the geometric least squares mean ratios fell within the 0.8-1.25 BE criteria. The effect of food on the dolutegravir/abacavir/lamivudine FDC tablet was similar to previous food effects observed with the separate formulations. The safety profile was comparable between treatments, with no observed serious or grade 3/4 adverse events. The BE of the dolutegravir/abacavir/lamivudine FDC tablet was demonstrated; it may be administered without regard to meals.

  10. Food hypersensitivity reactions in Soft Coated Wheaten Terriers with protein-losing enteropathy or protein-losing nephropathy or both: gastroscopic food sensitivity testing, dietary provocation, and fecal immunoglobulin E.

    PubMed

    Vaden, S L; Hammerberg, B; Davenport, D J; Orton, S M; Trogdon, M M; Melgarejo, L T; VanCamp, S D; Williams, D A

    2000-01-01

    The purpose of this study was to evaluate Soft Coated Wheaten Terriers (SCWTs) affected with protein-losing enteropathy (PLE) or protein-losing nephropathy (PLN) or both for allergy to food. We performed gastroscopic food-sensitivity testing, a provocative dietary trial, and measurement of fecal immunoglobulin E (IgE) in 6 SCWTs affected with PLE or PLN or both. Positive gastroscopic food-sensitivity test reactions were noted in 5 of 6 dogs. Positive reactions were found to milk in 4 dogs, to lamb in 2 dogs, and to wheat and chicken each in 1 dog. Adverse reactions to food (diarrhea, vomiting, or pruritus) were detected in all 6 dogs during the provocative dietary trial. Adverse reactions were found to corn in 5 dogs, to tofu in 3 dogs, to cottage cheese in 2 dogs, to milk in 2 dogs, to farina cream of wheat in 2 dogs, and to lamb in 2 dogs. Serum albumin concentrations significantly decreased and fecal alpha1-protease inhibitor concentration significantly increased 4 days after the provocative trial when compared with baseline values. Antigen-specific fecal IgE varied throughout the provocative trial, with peak levels following ingestion of test meals. We conclude that food hypersensitivities are present in SCWTs affected with the syndrome of PLE/PLN. Mild inflammatory bowel disease was already established in the 6 SCWTs of this report at the time of study, making it impossible to determine if food allergies were the cause or result of the enteric disease.

  11. Development of albumin-based nanoparticles for the delivery of abacavir.

    PubMed

    Wilson, Barnabas; Paladugu, Latishkumar; Priyadarshini, S R Brahmani; Jenita, J Josephine Leno

    2015-11-01

    The study was designed to prepare and evaluate albumin nanoparticles containing antiviral drug abacavir sulphate. Various batches of albumin nanoparticles containing abacavir sulphate were prepared by desolvation method. The abacavir loaded particles were characterized for their yield, percentage of drug loading, surface morphology, particle size, surface charge, pattern of in vitro drug release and release mechanism studies. Drug loading ranged from 1.2 to 5.9%w/w. The mean particle size and the surface charge were 418.2nm and -40.8mV respectively. The in vitro drug release varied between 38.73 and 51.36%w/w for 24h. The n value for Korsmeyer-Peppas was 0.425 indicating Fickian type drug release. The preliminary findings indicated that albumin nanoparticles of abacavir can be prepared by desolvation method with good yield, high drug loading and sustained release. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Desensitization for Drug Hypersensitivity to Chemotherapy and Monoclonal Antibodies.

    PubMed

    Bonamichi-Santos, Rafael; Castells, Mariana

    2016-01-01

    Chemotherapies drugs and monoclonal antibodies are key components of the treatment of cancer patients and patients with chronic inflammatory conditions to provide increase in life expectancy and quality of life. Their increased use has lead to an increase in drugs hypersensitivity reactions (DHR) worldwide. DHR to those agents prevented their use and promoted the use of second line therapies to protect patients' hypersensitive reactions and anaphylaxis. Second line medications may not fully address the patients' medical condition and it is desirable to keep patients on first line therapy. Drug hypersensitivity symptoms can range from mild cutaneous reactions to life-threatening anaphylaxis. Rapid drug desensitization (RDD) is a novel approach to the management of drug hypersensitivity reactions which are IgE and non-IgE mediated. Through the diferent desensitization protocols patients can receive the full dose of the medications that they have presented a hypersensitive reaction and been protected against anaphylaxis. This review looks at the current literature on hypersensitivity reactions (HSR) to chemotherapy drugs and monoclonal antibodies and the potential use of RDD for their management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. The antiretroviral nucleoside analogue Abacavir reduces cell growth and promotes differentiation of human medulloblastoma cells

    PubMed Central

    Rossi, Alessandra; Russo, Giuseppe; Puca, Andrew; La Montagna, Raffaele; Caputo, Mariella; Mattioli, Eliseo; Lopez, Massimo; Giordano, Antonio; Pentimalli, Francesca

    2009-01-01

    Abacavir is one of the most efficacious nucleoside analogues, with a well-characterized inhibitory activity on reverse transcriptase enzymes of retroviral origin, and has been clinically approved for the treatment of AIDS. Recently, Abacavir has been shown to inhibit also the human telomerase activity. Telomerase activity seems to be required in essentially all tumours for the immortalization of a subset of cells, including cancer stem cells. In fact, many cancer cells are dependent on telomerase for their continued replication and therefore telomerase is an attractive target for cancer therapy. Telomerase expression is upregulated in primary primitive neuroectodermal tumours and in the majority of medulloblastomas suggesting that its activation is associated with the development of these diseases. Therefore, we decided to test Abacavir activity on human medulloblastoma cell lines with high telomerase activity. We report that exposure to Abacavir induces a dose-dependent decrease in the proliferation rate of medulloblastoma cells. This is associated with a cell accumulation in the G2/M phase of the cell cycle in the Daoy cell line, and with increased cell death in the D283-MED cell line, and is likely to be dependent on the inhibition of telomerase activity. Interestingly, both cell lines showed features of senescence after Abacavir treatment. Moreover, following Abacavir exposure we detected, by immunofluorescence staining, increased protein expression of the glial marker glial fibrillary acidic protein (GFAP) and the neuronal marker synaptophysin (SYN) in both medulloblastoma cell lines. In conclusion, our results suggest that Abacavir reduces proliferation and induces differentiation of human medulloblastoma cells through the downregulation of telomerase activity. Thus, using Abacavir, alone or in combination with current therapies, might be an effective therapeutic strategy for the treatment of medulloblastoma. PMID:19358275

  14. Effect of drug efflux transporters on placental transport of antiretroviral agent abacavir.

    PubMed

    Neumanova, Zuzana; Cerveny, Lukas; Greenwood, Susan L; Ceckova, Martina; Staud, Frantisek

    2015-11-01

    Abacavir is as a frequent part of combination antiretroviral therapy used in pregnant women. The aim of this study was to investigate, using in vitro, in situ and ex vivo experimental approaches, whether the transplacental pharmacokinetics of abacavir is affected by ATP-binding cassette (ABC) efflux transporters functionally expressed in the placenta: P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), multidrug resistance-associated protein 2 (ABCC2) and multidrug resistance-associated protein 5 (ABCC5). In vitro transport assays revealed that abacavir is a substrate of human ABCB1 and ABCG2 transporters but not of ABCC2 or ABCC5. In addition, in situ experiments using dually perfused rat term placenta confirmed interactions of abacavir with placental Abcb1/Abcg2. In contrast, uptake studies in human placental villous fragments did not reveal any interaction of abacavir with efflux transporters suggesting a large contribution of passive diffusion and/or influx mechanisms to net transplacental abacavir transfer. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia.

    PubMed

    Tada, Kohei; Kobayashi, Masayuki; Takiuchi, Yoko; Iwai, Fumie; Sakamoto, Takashi; Nagata, Kayoko; Shinohara, Masanobu; Io, Katsuhiro; Shirakawa, Kotaro; Hishizawa, Masakatsu; Shindo, Keisuke; Kadowaki, Norimitsu; Hirota, Kouji; Yamamoto, Junpei; Iwai, Shigenori; Sasanuma, Hiroyuki; Takeda, Shunichi; Takaori-Kondo, Akifumi

    2015-04-01

    Adult T cell leukemia (ATL) is an aggressive T cell malignancy caused by human T cell leukemia virus type 1 (HTLV-1) and has a poor prognosis. We analyzed the cytotoxic effects of various nucleoside analog reverse transcriptase inhibitors (NRTIs) for HIV-1 on ATL cells and found that abacavir potently and selectively kills ATL cells. Although NRTIs have minimal genotoxicities on host cells, the therapeutic concentration of abacavir induced numerous DNA double-strand breaks (DSBs) in the chromosomal DNA of ATL cells. DSBs persisted over time in ATL cells but not in other cell lines, suggesting impaired DNA repair. We found that the reduced expression of tyrosyl-DNA phosphodiesterase 1 (TDP1), a repair enzyme, is attributable to the cytotoxic effect of abacavir on ATL cells. We also showed that TDP1 removes abacavir from DNA ends in vitro. These results suggest a model in which ATL cells with reduced TDP1 expression are unable to excise abacavir incorporated into genomic DNA, leading to irreparable DSBs. On the basis of the above mechanism, we propose abacavir as a promising chemotherapeutic agent for ATL.

  16. Management of trichomonas vaginalis in women with suspected metronidazole hypersensitivity.

    PubMed

    Helms, Donna J; Mosure, Debra J; Secor, W Evan; Workowski, Kimberly A

    2008-04-01

    Standard treatment for Trichomonas vaginalis is metronidazole or tinidazole. Hypersensitivity to these drugs has been documented but is poorly understood. Desensitization is an option described in limited reports of women with hypersensitivity to nitroimidazoles. The purpose of this analysis is to improve documentation of management for trichomonas infections among women with metronidazole hypersensitivity. Clinicians who consulted Centers for Disease Control and Prevention concerning patients with suspected hypersensitivity to metronidazole were provided with treatment options and asked to report outcomes. From September 2003-September 2006, complete information was obtained for 59 women. The most common reactions were urticaria (47%) and facial edema (11%). Fifteen of these women (25.4%) were treated with metronidazole desensitization and all had eradication of their infection. Seventeen women (28.8%) were treated with alternative intravaginal drugs, which were less successful; 5 of 17 infections (29.4%) were eradicated. Metronidazole desensitization was effective in the management of women with nitroimidazole hypersensitivity.

  17. Practical Management of Antibiotic Hypersensitivity in 2017.

    PubMed

    Macy, Eric; Romano, Antonino; Khan, David

    Antibiotics are the most common class of medications that individuals report allergy or intolerance to. Adverse reactions are reported at a predictable rate with all antibiotic use that vary by antibiotic. Antibiotic allergy incidence rates are sex dependent, higher in females than in males. Most of these events are not reproducible or immunologically mediated. Antibiotic allergy prevalence increases with increasing age and is more common in hospitalized populations and in populations that use more antibiotics. Determining potential mechanisms for the observed symptoms of the adverse reactions is the starting point for effective management of antibiotic hypersensitivity. Skin testing and direct challenges are the primary tools used to determine acute tolerance in 2017. Commercially available in vitro testing is not currently clinically useful in determining antibiotic hypersensitivity, with rare exceptions. Desensitization can be used when acute-onset immunologically mediated hypersensitivity is confirmed to safely administer a needed antibiotic. Desensitization is not possible when clinically significant T-cell-mediated delayed-type hypersensitivity is present. Effective management of antibiotic allergy is an important part of a comprehensive antibiotic stewardship program. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. Diagnostic testing of dogs for food hypersensitivity.

    PubMed

    Jeffers, J G; Shanley, K J; Meyer, E K

    1991-01-15

    Thirteen food-allergic dogs were studied to evaluate the efficacy of feeding a commercially available egg and rice diet, intradermal skin testing, and serologic testing by ELISA for diagnosing and/or characterizing food hypersensitivity. Feeding of a home-cooked whole lamb meat and rice diet for 3 weeks, followed by challenge with each dog's regular diet, served as the standard for diagnosing food hypersensitivity. Each dog underwent provocative testing with 6 individual ingredients to determine as many of its dietary allergens as possible. Prior to skin testing and serologic testing by ELISA, most dogs had been recently exposed to the offending diet and subsequently manifested clinical signs of allergy. All dogs that tolerated the aforementioned commercial diet were exposed to it for at least 7 weeks; 84.6% of food-hypersensitive dogs ate the commercial diet with impunity. Of the 2 reactors to the commercial diet, only 1 became pruritic in response to provocation testing with chicken eggs. Low sensitivity and high specificity were found for skin testing and the ELISA, indicating a lack of true- and false-positive reactions. Neither the positive nor negative predictive values adequately predicted positive and negative reactions, respectively, for either test. On the basis of these results, the commercial diet, skin testing, and anti-IgE ELISA cannot replace an owner-prepared food elimination diet for food hypersensitivity testing in dogs.

  19. Self-report prevalence and associated factors to drug hypersensitivity in Mexican young adults.

    PubMed

    Bedolla-Barajas, Martín; Puente-Fernández, Cecilia; Flores-Merino, Miriam V; Morales-Romero, Jaime; Domínguez-García, Ma Victoria

    2017-07-01

    Drug hypersensitivity is defined as any unfavorable reaction that occurs after the administration of any drug. It may or may not be mediated by the involvement of the immune system. Epidemiological data related to drug hypersensitivity reactions in our country are scarce. To determine the prevalence of drug hypersensitivity in a group of young adults, as well as to identify associated factors. A structured questionnaire was applied to young people aged 18 to 25 years. The instrument was oriented to identify reactions of drug hypersensitivity, as well as the most prevalent drugs involved. In addition, a personal and family history of atopic diseases was included. Analysis for associations between variables was been done through logistic regression. The prevalence of drug hypersensitivity reactions was 12% (144 of 1,200). The antibiotics were the agents most related to hypersensitivity reactions (9.8%) followed by nonsteroidal anti-inflammatory drugs (1.6%). Factors associated with drug hypersensitivity were a personal history of asthma, odds ratio (OR) 3.15 (95% confidence interval [CI], 1.44-6.91), maternal and paternal history of drug hypersensitivity, OR 2.33 (95% CI, 1.21-4.48) and OR 3.11 (95% CI, 1.22-7.92), respectively. The results of this research show that drug hypersensitivity in young adults is a highly prevalent event and it is associated with personal history of asthma and history of drug hypersensitivity in parents.

  20. Investigation of an outbreak of hypersensitivity-type reactions during the 2004 national measles-mumps-rubella vaccination campaign in Brazil.

    PubMed

    Freitas, Daniel R C; Moura, Evoide; Araújo, Gisele; Cardoso, Alessandra; Scheidt, Penelope; Ferraz, Elizabete; Madalosso, Geraldine; Chen, Robert T; Hatch, Douglas L

    2013-01-30

    During Brazil's national measles, mumps, and rubella (MMR) vaccination campaign in August 2004, an unexpectedly high rate of hypersensitivity-type adverse events (HAEs) was reported. We reviewed information about children with suspected HAEs reported by clinicians to Brazil's national passive surveillance system for adverse events following immunization (AEFI), compared attack rate of HAE by manufacturer of MMR vaccine used in the campaign, and conducted a case-control study to determine possible risk factors for HAEs. During the 2004 national campaign, the rate of HAEs following MMR vaccination was one log higher for manufacturer A (15.2/100,000 doses administered) compared to the other two manufacturers (1.2 and 0.6/100,000 doses; p<0.0001); a similar pattern was observed retrospectively in analysis of the 2000-2003 AEFI surveillance (0.95 vs. 0.07 per 100,000 doses administered; p<0.0001). In the case-control study, among the 49 case-patients with HAEs identified, reported symptoms included conjunctival injection (60%), urticaria (55%), fever (54%), and facial edema (53%); no deaths occurred. The median time interval between vaccination and symptom onset was 42min (range: 5min-24h). We did not identify any differences in the proportion of case-patients and control children with a history of known allergy to food (including egg, egg-containing products or gelatin), drugs, or environmental antigens. Our study highlights the importance of a well-functioning routine AEFI surveillance system linked with mass vaccination campaigns. Such a system in Brazil permitted timely detection of HAEs and validation of a safety signal associated with one vaccine manufacturer. Unlike earlier publications, this outbreak linked to a single manufacturer of MMR showed no association with a prior allergic history to eggs or other foods, including gelatin; subsequent studies implicate the dextran stabilizer in MMR from manufacturer A as the likely cause of HAEs. Copyright © 2012

  1. Ribavirin and abacavir drug interaction in HIV-HCV coinfected patients: fact or fiction?

    PubMed

    Solas, Caroline; Pambrun, Elodie; Winnock, Maria; Salmon, Dominique; Poizot-Martin, Isabelle; Dominguez, Stéphanie; Bani-Sadr, Firouzé; Izopet, Jacques; Garraffo, Rodolphe; Peytavin, Gilles

    2012-11-13

    To examine the impact of ribavirin and abacavir coadministration on hepatitis C virus (HCV) virological response and trough ribavirin plasma concentration (Cmin) in HIV-HCV coinfected patients. Pharmacokinetic substudy on patients from the ANRS CO-13 HEPAVIH cohort. Patients receiving ribavirin-pegylated interferon for whom a ribavirin steady state Cmin was prospectively determined were included. Rapid virological response (RVR), early virological response (EVR) and sustained virological response (SVR) as well as HCV-RNA decline were evaluated. Overall, 124 HIV-HCV coinfected patients (95% on antiretroviral therapy) were enrolled. Of these patients, 22% received abacavir. The overall median (interquartile range) ribavirin Cmin was 1.6 mg/l (1.2-2.2) with no statistical difference between abacavir users and nonusers [1.5 mg/l (0.99-2.1) and 1.7 (1.2-2.3), P = 0.15]. RVR and EVR were 52 and 72%, respectively. There was no difference observed in the proportion of abacavir users vs. nonusers achieving RVR (respectively 59 vs. 50%, P = 0.40) or EVR (72 vs. 73%, P = 0.94), or in the HCV-RNA decline at week 4 [-2.24 log(10) IU/ml, (-3.58; -0.81) and -1.27 (-2.8; -0.47) P = 0.28] or at week 12 [-1.76 log(10) IU/ml (-3.67; -0.35) and -1.85 (-3.13; -1.13) (P = 0.58)]. The SVR rate was 45% for abacavir users and 24% for abacavir nonusers, but the difference was not statistically significant (P = 0.059). In our study, there was no evidence that abacavir affected HCV treatment outcomes and the ribavirin Cmin was similar in abacavir users and nonusers, confirming the absence of pharmacokinetic interaction between abacavir and ribavirin. An abacavir-containing regimen is, therefore, a well tolerated treatment alternative for coinfected patients starting HCV treatment.

  2. [Food hypersensitivity dermatitis in the dog: diagnostic possibilities].

    PubMed

    Wilhelm, S; Favrot, C

    2005-04-01

    Dogs with food hypersensitivity usually develop chronic pruritic dermatoses virtually indistinguishable from atopic dermatitis. These reactions are often called food allergy but the pathogenesis is poorly characterized. Several studies have addressed the incidence of canine adverse reactions to food but the outcomes were conflicting. The gold standard for the diagnosis of such a condition is the restricted dietary trial and the subsequent provocation challenge. Some attempts have been made to develop serological tests but none of these tests accurately predicted canine food sensitivity. The aim of the present study was to determine the incidence of food hypersensitivity dermatitis and to evaluate a newly developed serological test for the diagnosis of food allergy in dogs. Only 9% of 55 dogs with dermatological signs compatible with food hypersensitivity or atopic dermatitis have been diagnosed as food hypersensitive dogs. The repeatability of the serological test has shown to be insufficient.

  3. Effects of abacavir administration on structural and functional markers of platelet activation.

    PubMed

    Trevillyan, Janine M; Arthur, Jane F; Jing, Jing; Andrews, Robert K; Gardiner, Elizabeth E; Hoy, Jennifer F

    2015-11-01

    Current abacavir exposure has been reported to be associated with cardiovascular disease. Changes in platelet reactivity could plausibly explain the clinically observed pattern of association. To determine if platelet reactivity changed following abacavir exposure and whether this effect was reversible on cessation of the drug. In an open-label, interventional study abacavir, 600 mg daily, was added to a suppressive antiretroviral regimen in 20 adult HIV-positive men. Platelet function, estimated by the phosphorylated vasodilator-stimulated phosphoprotein (P-VASP) assay and through measurement of the expression and shedding of platelet-specific receptors, was assessed at baseline, following 15 days of abacavir and at completion of a 28-day washout period. The VASP-index decreased significantly from 79.1% [interquartile range (IQR) 47.8-87.6] to 32.6% (IQR -11.5-51.0) following 15 days of abacavir administration (P = 0.010), and returned to baseline levels following the washout period (day 43 =76.3%; IQR 40.7-92.3). There was no change in resting (prostaglandin E1 alone) P-VASP but a slight increase in P-VASP within stimulated platelets (prostaglandin E1 and adenosine diphosphate). Integrin β3 levels decreased significantly [208.5 ng/ml (IQR 177.0-231.1) to 177.5 ng/ml (IQR 151.7-205) P < 0.001] and there was a nonsignificant trend towards decreased soluble glycoprotein VI levels [baseline; 72.5 ng/ml (95% CI 58.3-81.5) vs. day 15; 45.0 ng/ml (95% CI 33.0-98.2) P = 0.79]. Abacavir led to reversible changes in platelet function and structure. The clinical implications of these changes are uncertain; they may represent negative feedback mechanisms in response to an abacavir-associated prothrombotic state.

  4. Abacavir and didanosine induce the interaction between human leukocytes and endothelial cells through Mac-1 upregulation.

    PubMed

    De Pablo, Carmen; Orden, Samuel; Apostolova, Nadezda; Blanquer, Amando; Esplugues, Juan V; Alvarez, Angeles

    2010-06-01

    Abacavir and didanosine are nucleoside reverse transcriptase inhibitors (NRTI) widely used in therapy for HIV-infection but which have been linked to cardiovascular complications. The objective of this study was to analyze the effects of clinically relevant doses of abacavir and didanosine on human leukocyte-endothelium interactions and to compare them with those of other NRTIs. The interactions between human leukocytes - specifically peripheral blood polymorphonuclear (PMN) or mononuclear (PBMC) cells - and human umbilical vein endothelial cells were evaluated in a flow chamber system that reproduces conditions in vivo. The expression of adhesion molecules was analyzed by flow cytometry. Abacavir induced a dose-dependent increase in PMN and PBMC rolling and adhesion. This was reproduced by didanosine but not by lamivudine or zidovudine. Both abacavir and didanosine increased Mac-1 expression in neutrophils and monocytes, but produced no effects on either lymphocytes or the expression of endothelial adhesion molecules. The PMN/PBMC rolling and adhesion induced by abacavir or didanosine did not occur when antibodies against Mac-1 or its ligand ICAM-1 were blocked. Abacavir induces significant human leukocyte accumulation through the activation of Mac-1, which in turn interacts with its endothelial ligand ICAM-1. The fact that didanosine exhibits similar effects and that lamivudine and zidovudine do not points to a relationship between the chemical structure of NRTIs and the induction of leukocyte/endothelial cell interactions. This mechanism may be especially relevant to the progression of the vascular damage associated with atherosclerosis and myocardial infarction in abacavir and didanosine-treated patients.

  5. Cardiovascular risks associated with abacavir and tenofovir exposure in HIV-infected persons.

    PubMed

    Choi, Andy I; Vittinghoff, Eric; Deeks, Steven G; Weekley, Cristin C; Li, Yongmei; Shlipak, Michael G

    2011-06-19

    Abacavir use has been associated with cardiovascular risk, but it is unknown whether this association may be partly explained by patients with kidney disease being preferentially treated with abacavir to avoid tenofovir. Our objective was to compare associations of abacavir and tenofovir with cardiovascular risks in HIV-infected veterans. Cohort study of 10 931 HIV-infected patients initiating antiretroviral therapy in the Veterans Health Administration from 1997 to 2007, using proportional hazards survival regression. Primary predictors were exposure to abacavir or tenofovir within the past 6 months, compared with no exposure to these drugs, respectively. Outcomes were time to first atherosclerotic cardiovascular event, defined as coronary, cerebrovascular, or peripheral arterial disease; and time to incident heart failure. Over 60 588 person-years of observation, there were 501 cardiovascular and 194 heart failure events. Age-standardized event rates among abacavir and tenofovir users were 12.5 versus 8.2 per 1000 person-years for cardiovascular disease, and 3.9 and 3.7 per 1000 person-years for heart failure, respectively. In multivariate-adjusted models, including time-updated measurements of kidney function, recent abacavir use was significantly associated with incident cardiovascular disease [hazard ratio 1.48, 95% confidence interval (CI) 1.08-2.04]; the association was similar but nonsignificant for heart failure (1.45, 0.85-2.47). In contrast, recent tenofovir use was significantly associated with heart failure (1.82, 1.02-3.24), but not with cardiovascular events (0.78, 0.52-1.16). Recent abacavir exposure was independently associated with increased risk for cardiovascular events. We also observed an association between recent tenofovir exposure and heart failure, which needs to be confirmed in future studies.

  6. Cardiovascular risks associated with abacavir and tenofovir exposure in HIV-infected persons

    PubMed Central

    Choi, Andy I.; Vittinghoff, Eric; Deeks, Steven G.; Weekley, Cristin C.; Li, Yongmei; Shlipak, Michael G.

    2014-01-01

    Objective Abacavir use has been associated with cardiovascular risk, but it is unknown whether this association may be partly explained by patients with kidney disease being preferentially treated with abacavir to avoid tenofovir. Our objective was to compare associations of abacavir and tenofovir with cardiovascular risks in HIV-infected veterans. Design Cohort study of 10 931 HIV-infected patients initiating antiretroviral therapy in the Veterans Health Administration from 1997 to 2007, using proportional hazards survival regression. Methods Primary predictors were exposure to abacavir or tenofovir within the past 6 months, compared with no exposure to these drugs, respectively. Outcomes were time to first atherosclerotic cardiovascular event, defined as coronary, cerebrovascular, or peripheral arterial disease; and time to incident heart failure. Results Over 60 588 person-years of observation, there were 501 cardiovascular and 194 heart failure events. Age-standardized event rates among abacavir and tenofovir users were 12.5 versus 8.2 per 1000 person-years for cardiovascular disease, and 3.9 and 3.7 per 1000 person-years for heart failure, respectively. In multivariate-adjusted models, including time-updated measurements of kidney function, recent abacavir use was significantly associated with incident cardiovascular disease [hazard ratio 1.48, 95% confidence interval (CI) 1.08–2.04]; the association was similar but nonsignificant for heart failure (1.45, 0.85–2.47). In contrast, recent tenofovir use was significantly associated with heart failure (1.82, 1.02–3.24), but not with cardiovascular events (0.78, 0.52–1.16). Conclusion Recent abacavir exposure was independently associated with increased risk for cardiovascular events. We also observed an association between recent tenofovir exposure and heart failure, which needs to be confirmed in future studies. PMID:21516027

  7. Pharmacokinetic interactions between lersivirine and zidovudine, tenofovir disoproxil fumarate/emtricitabine and abacavir/lamivudine.

    PubMed

    Vourvahis, Manoli; Davis, John; Langdon, Grant; Layton, Gary; Fang, Juanzhi; Choo, Heng Wee; Hansson, Arne G; Tawadrous, Margaret

    2013-01-01

    To investigate pharmacokinetic interactions associated with coadministration of lersivirine with zidovudine, tenofovir disoproxil fumarate (DF)/emtricitabine (Truvada(®)) or abacavir/lamivudine (Epzicom(®)/Kivexa(®)). Three Phase I, open, crossover studies with two (studies 1 and 3) or three (study 2) treatment periods were conducted in healthy individuals. In study 1, individuals received zidovudine and placebo or zidovudine and lersivirine on days 1-14. In study 2, individuals received lersivirine and tenofovir DF/emtricitabine, lersivirine and placebo or tenofovir DF/emtricitabine and placebo on days 1-10. In study 3, individuals received abacavir/lamivudine only in period 1 (5 days) and abacavir/lamivudine and lersivirine in period 2 (10 days). Blood samples were taken on days 1-14 (study 1) or day of final dose (studies 2 and 3) and analysed using high performance liquid chromatography/dual mass spectrometry. Pharmacokinetic parameters were calculated by standard non-compartmental methods. When coadministered with lersivirine, zidovudine exposure increased by 35%, and exposure of its metabolite zidovudine-glucuronide decreased by 19%. Following coadministration of lersivirine and tenofovir DF/emtricitabine, tenofovir exposure increased by 30%, and lersivirine exposure decreased by 12%. Coadministration of lersivirine and abacavir/lamivudine increased abacavir exposure by 27% and decreased lamivudine exposure by 8%. Adverse events were predominantly mild in these Phase I studies. Coadministration of lersivirine with zidovudine, tenofovir DF/emtricitabine or abacavir/lamivudine influenced the systemic exposure of all nucleoside reverse transcriptase inhibitor agents investigated (except for lamivudine; emtricitabine pharmacokinetics were not assessed). Changes were not considered clinically meaningful for zidovudine and abacavir. The clinical relevance of the effect on tenofovir pharmacokinetics is currently unknown.

  8. An approach to natalizumab hypersensitivity: a case series of induction of tolerance.

    PubMed

    Camacho-Halili, Marie; George, Roxanne; Gottesman, Malcolm; Davis-Lorton, Mark

    2011-02-01

    Induction of tolerance protocols have been applied successfully to manage allergic reactions to many medications. Hypersensitivity reactions to natalizumab (TYSABRI®) have been recognized as a growing problem. In circumstances where a hypersensitivity reaction to a medication has occurred, but no suitable alternative exists, drug induction of tolerance protocols may be considered. Drug induction of tolerance protocols were performed in three patients with prior hypersensitivity reactions to natalizumab. All three patients tolerated the protocol without adverse reactions, allowing for the safe reintroduction of natalizumab. To conclude, this case series demonstrates success with an induction of tolerance procedure to a highly effective biological agent for multiple sclerosis, in patients with allergic reactions to natalizumab.

  9. An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity

    PubMed Central

    Abe, Riichiro; Pan, Ren-You; Wang, Chuang-Wei

    2018-01-01

    Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR) molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity. PMID:29651444

  10. A World Allergy Organization International Survey on Diagnostic Procedures and Therapies in Drug Allergy/Hypersensitivity

    PubMed Central

    Mirakian, Rita; Castells, Mariana; Pichler, Werner; Romano, Antonino; Bonadonna, Patrizia; Diana, Deleanu; Kowalski, Marek; Yanez, Anahi; Lleonart, Ramon; Sanchez-Borges, Mario; Demoly, Pascal

    2011-01-01

    Objective To study the diagnostic and treatment modalities used in drug allergy/hypersensitivity among members of the World Allergy Organization (WAO). Methods A questionnaire comprising 39 questions was circulated electronically to member societies, associate member societies, and regional and affiliate organizations of WAO between June 29, 2009, and August 9, 2009. Results Eighty-two responses were received. Skin testing was used by 74.7%, with only 71.4% having access to penicillin skin test reagents. In vitro–specific IgE tests were used by 67.4%, and basophil activation test was used by 54.4%. Lymphocyte transformation tests were used by 36.8% and patch tests by 54.7%. Drug provocation tests were used by 68.4%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (76.9%). Rapid desensitization for chemotherapy, antibiotics, or biologic agents was used by 69.6%. Systemic corticosteroid was used in the treatment of Stevens–Johnson syndrome by 72.3%, and high-dose intravenous immunoglobulins in toxic epidermal necrolysis by 50.8%. Human leukocyte antigen screening before prescription of abacavir was used by 92.9% and before prescription of carbamazepine by 21.4%. Conclusions Results of this survey form a useful framework for developing educational and training needs and for improving access to drug allergy diagnostic and treatment modalities across WAO member societies. PMID:23268453

  11. Chronic hypersensitivity pneumonitis

    PubMed Central

    Pereira, Carlos AC; Gimenez, Andréa; Kuranishi, Lilian; Storrer, Karin

    2016-01-01

    Hypersensitivity pneumonitis (HSP) is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary. PMID:27703382

  12. Abacavir coadministration does not interfere with the suppressive activity of ribavirin in an HCV replicon system.

    PubMed

    Van den Eynde, Eva; Quer, Josep; Cubero, María; Curran, Adriá; Homs, María; Garcia-Cehic, Damir; Falco, Vicenç; Ribera, Esteban; Esteban, Juan I; Pahissa, Albert; Crespo, Manuel

    2011-01-01

    HCV is a major cause of morbidity and mortality in HIV-coinfected patients. Several observational studies have suggested that HCV response to pegylated interferon and ribavirin is lower in HIV-coinfected patients treated with abacavir. It has been postulated that abacavir could compete with ribavirin to be phosphorylated, leading to a reduction in the active form of the drug (triphosphorylated ribavirin). Here, we studied the effect of abacavir, tenofovir or lamivudine addition on the suppressive activity of ribavirin in an HCV RNA replicon system. We used the human hepatoma HuH-7 cell clone 9B containing the HCV genotype 1b replicon I389/NS3-3'. Cells were treated for 24 h with ribavirin (0, 10 and 50 μM) plus abacavir, tenofovir or lamivudine at doses of 0, 10 and 50 μM and HCV RNA production was quantified by real-time PCR in triplicate assays. Results were expressed as mean±SD of the HCV RNA produced per cell (log(10) IU/cell). Means were compared using the Student's t-test. Ribavirin treatment produced a dose-dependent suppression of HCV RNA production by the replicon system. Combination of ribavirin and interferon resulted in an additive antiviral activity. The addition of abacavir did not modify the suppressive activity of ribavirin on the replicon HCV RNA expression. Similar results were obtained when ribavirin was used in combination with tenofovir or lamivudine. In a subgenomic HCV RNA replicon system, the antiviral effect of ribavirin was not modified by the addition of abacavir, tenofovir or lamivudine. © 2011 International Medical Press

  13. Abacavir + dolutegravir + lamivudine for the treatment of HIV.

    PubMed

    Comi, Laura; Maggiolo, Franco

    2016-10-01

    Since the last revision of both European and American guidelines (EACS and DHHS), new data from clinical trials and cohort studies, as well as experience in clinical practice, have prompted significant changes to the list of recommended/preferred options for the treatment of HIV infected patients, highlighted the role of INSTI-based regimens. Dolutegravir (DTG) in combination with abacavir/lamivudine (ABC/3TC) is one of these preferred regimens in multiple clinical scenarios, including treatment-naive and treatment-experienced patients. In this article we describe the coformulation of ABC/3TC/DTG in a fixed-dose combination (FDC) approved in September 2014 for the treatment of HIV infection. We focused our research on the efficacy and safety data resulting from phase 2 and 3 clinical study, particularly on the results of both SPRING (1 and 2) and SINGLE studies. Triple combination therapy with ABC/3TC/DTG should be considered among the initial options for treatment-naive patients, being effective, well tolerated, with a high genetic barrier to resistance along with a convenient once-daily administration. In treatment-experienced patients the single-tablet regimen (STR) based on ABC/3TC/DTG could be used as simplification strategy in subjects with sustained viral suppression, as the high genetic barrier of DTG should ensure a safe switch from both NNRTI or PI based regimens.

  14. Case of immediate hypersensitivity to beer.

    PubMed

    Inoue, Tomoko; Yagami, Akiko; Shimojo, Naoshi; Hara, Kazuhiro; Nakamura, Masashi; Matsunaga, Kayoko

    2016-06-01

    We report here a case of immediate hypersensitivity to beer, in which a female patient developed angioedema of the eyelids shortly after consuming beer. In skin prick tests, the patient showed positive reactions to the base ingredients of beer, particularly malt and barley. The specific serum immunoglobulin E antibodies against barley and malt displayed weakly positive reactivity. To identify the immunoreactive antigens, malt and barley proteins were separated by 2-D polyacrylamide gel electrophoresis and immunoreacted with the patient's serum. The results of mass spectrometric analysis revealed that the main antigen was a protein with similarity to protein z-type serpin. Notably, the identified antigen had a molecular weight of 20-25 kDa, which is markedly smaller than that previously reported for protein Z4 (44 kDa). Taken together, these analyses indicate that a possible new antigen which belongs to the protein Z family elicits immediate hypersensitivity to beer. © 2015 Japanese Dermatological Association.

  15. Intentional overdose of dolutegravir/abacavir/lamivudine (Triumeq) in a 26-year-old man.

    PubMed

    van Dam, Paul Mel; van Geffen, Mark Wl; Havenith, Thomas Ra; Posthouwer, Dirk

    2018-03-13

    Triumeq is a single-tablet regimen for patients with HIV infection comprising dolutegravir, abacavir and lamivudine. Overdoses with Triumeq have not been reported previously. We present a case of a 26-year-old man who presented to our hospital after intentionally ingesting 30 tablets of Triumeq. An intoxication with Triumeq can lead to several side effects. An overdose of abacavir and lamivudine can cause mitochondrial toxicity and lactic acidosis. An intoxication with dolutegravir appears to be relatively harmless. As Triumeq will be used on a regular basis as treatment for patients with HIV-1 infection, these intoxications are expected to be encountered more often.

  16. Carboplatin hypersensitivity: evaluation and successful desensitization protocol.

    PubMed

    Bruchim, Ilan; Goldberg, Arnon; Fishman, Ami; Confino-Cohen, Ronit

    2014-01-01

    Carboplatin-induced immediate hypersensitivity reactions are relatively common among patients with gynecological malignancies. Once this occurs, the patient might be at risk for future carboplatin-induced reactions. This study evaluated the efficacy of allergic consultation, carboplatin skin testing and desensitization as a single intervention strategy in this population. Patients with a well-documented immediate reaction to carboplatin were offered allergy consultation, carboplatin skin testing and a desensitization plan in a single visit between scheduled chemotherapy sessions. Fifty-five patients with an immediate reaction were evaluated. After allergist assessment, 44 (89%) of 49 patients skin tested had a positive result. A total of 207 carboplatin desensitization cycles were administered to 49 women. Among them, 10 patients had a mild immediate hypersensitivity reaction during desensitization. Five patients subsequently tolerated carboplatin administered in the prolonged desensitization protocol. In the data presented, we propose a strategy that is both cost effective and very convenient for the patient. The diagnostic procedure, including allergist consultation and skin test, can be completed in less than 2 h. In most cases where carboplatin is indispensable, desensitization can be administered without overnight hospitalization.

  17. Abacavir, didanosine and tenofovir do not induce inflammatory, apoptotic or oxidative stress genes in coronary endothelial cells.

    PubMed

    Kim, Chul; Gupta, Samir K; Green, Linden; Taylor, Brian M; Deuter-Reinhard, Maja; Desta, Zeruesenay; Clauss, Matthias

    2011-01-01

    The use of abacavir and didanosine in HAART has been associated with an increased risk of myocardial infarction in HIV-infected patients. The aim of this study was to address the development of endothelial dysfunction in cultivated coronary artery endothelial cells (HCAECs) in response to abacavir, didanosine and tenofovir. We examined the impact of these drugs on the expression levels of the proinflammatory, oxidative stress and apoptosis regulating genes in HCAECs. We tested gene and protein expression changes in HCAECs in response to abacavir, didanosine and tenofovir using quantitative real-time reverse transciptase PCR, FACS and ELISA. The assessed genes/proteins included the proinflammatory molecules VCAM-1, ICAM-1, MCP-1, RANTES and IL-6. In addition, we assessed the gene expression of the intracellular reactive oxygen producing NADPH oxidase subunit gp91(PHOX) and the apoptosis regulating molecules Bcl-2 and BAD. Exposure of HCAECs to abacavir, didanosine and tenofovir resulted in no statistically significant changes in any of the tested genes/proteins at any time point or at any concentration. We found no evidence that abacavir, didanosine or tenofovir had direct in vitro effects on coronary endothelial cell gene transcription and protein expression of the selected mediators. If abacavir or didanosine increase cardiovascular risk, it is likely not through the direct endothelial activation pathways tested in these experiments. However, further studies are needed to completely exclude the toxicity of abacavir or didanosine on endothelial cells.

  18. Xanthomonas filamentous hemagglutinin-like protein Fha1 interacts with pepper hypersensitive-induced reaction protein CaHIR1 and functions as a virulence factor in host plants.

    PubMed

    Choi, Hyong Woo; Kim, Dae Sung; Kim, Nak Hyun; Jung, Ho Won; Ham, Jong Hyun; Hwang, Byung Kook

    2013-12-01

    Pathogens have evolved a variety of virulence factors to infect host plants successfully. We previously identified the pepper plasma-membrane-resident hypersensitive-induced reaction protein (CaHIR1) as a regulator of plant disease- and immunity-associated cell death. Here, we identified the small filamentous hemagglutinin-like protein (Fha1) of Xanthomonas campestris pv. vesicatoria as an interacting partner of CaHIR1 using yeast two-hybrid screening. Coimmunoprecipitation and bimolecular fluorescence complementation experiments revealed that Fha1 specifically interacts with CaHIR1 in planta. The endocytic tracker FM4-64 staining showed that the CaHIR1-Fha1 complex localizes in the endocytic vesicle-like structure. The X. campestris pv. vesicatoria Δfha1 mutant strain exhibited significantly increased surface adherence but reduced swarming motility. Mutation of fha1 inhibited the growth of X. campestris pv. vesicatoria and X. campestris pv. vesicatoria ΔavrBsT in tomato and pepper leaves, respectively, suggesting that Fha1 acts as a virulence factor in host plants. Transient expression of fha1 and also infiltration with purified Fha1 proteins induced disease-associated cell death response through the interaction with CaHIR1 and suppressed the expression of pathogenesis-related (PR) genes. Silencing of CaHIR1 in pepper significantly reduced ΔavrBsT growth and Fha1-triggered susceptibility cell death. Overexpression of fha1 in Arabidopsis retarded plant growth and triggered disease-associated cell death, resulting in altered disease susceptibility. Taken together, these results suggest that the X. campestris pv. vesicatoria virulence factor Fha1 interacts with CaHIR1, induces susceptibility cell death, and suppresses PR gene expression in host plants.

  19. Abacavir/lamivudine versus tenofovir/emtricitabine in virologically suppressed patients switching from ritonavir-boosted protease inhibitors to raltegravir.

    PubMed

    Martínez, Esteban; d'Albuquerque, Polyana M; Pérez, Ignacio; Pich, Judit; Gatell, José M

    2013-02-01

    There are few clinical data on the combination abacavir/lamivudine plus raltegravir. We compared the outcomes of patients from the SPIRAL trial receiving either abacavir/lamivudine or tenofovir/emtricitabine at baseline who had taken at least one dose of either raltegravir or ritonavir-boosted protease inhibitors. For the purpose of this analysis, treatment failure was defined as virological failure (confirmed HIV-1 RNA ≥50 copies/ml) or discontinuation of abacavir/lamivudine or tenofovir/emtricitabine because of adverse events, consent withdrawal, or lost to follow-up. There were 143 (72.59%) patients with tenofovir/emtricitabine and 54 (27.41%) with abacavir/lamivudine. In the raltegravir group, there were three (11.11%) treatment failures with abacavir/lamivudine and eight (10.96%) with tenofovir/emtricitabine (estimated difference 0.15%; 95% CI -17.90 to 11.6). In the ritonavir-boosted protease inhibitor group, there were four (14.81%) treatment failures with abacavir/lamivudine and 12 (17.14%) with tenofovir/emtricitabine (estimated difference -2.33%; 95% CI -16.10 to 16.70). Triglycerides decreased and HDL cholesterol increased through the study more pronouncedly with abacavir/lamivudine than with tenofovir/emtricitabine and differences in the total-to-HDL cholesterol ratio between both combinations of nucleoside reverse transcriptase inhibitors (NRTIs) tended to be higher in the raltegravir group, although differences at 48 weeks were not significant. While no patient discontinued abacavir/lamivudine due to adverse events, four (2.80%) patients (all in the ritonavir-boosted protease inhibitor group) discontinued tenofovir/emtricitabine because of adverse events (p=0.2744). The results of this analysis do not suggest that outcomes of abacavir/lamivudine are worse than those of tenofovir/emtricitabine when combined with raltegravir in virologically suppressed HIV-infected adults.

  20. The pharmacokinetics of abacavir 600 mg once daily in HIV-1-positive pregnant women.

    PubMed

    Schalkwijk, Stein; Colbers, Angela; Konopnicki, Deborah; Weizsäcker, Katharina; Moltó, José; Tenorio, Carmen Hidalgo; Hawkins, David; Taylor, Graham; Wood, Chris; van der Ende, Marchina; Burger, David

    2016-05-15

    To describe the pharmacokinetics of abacavir 600 mg once daily (q.d.) in HIV-1-positive women during pregnancy and postpartum. A nonrandomized, open-label, multicentre, phase-IV study. HIV-positive pregnant women receiving abacavir 600 mg q.d. as part of clinical care were included. Intensive 24-h pharmacokinetic sampling was performed during the third trimester and at least 2 weeks after delivery. Pharmacokinetic parameters were calculated by noncompartmental analysis. Paired cord blood and maternal blood samples were taken at delivery when feasible. A total of 14 women were included in the analysis. Geometric mean ratios (90% confidence intervals) of third trimester versus postpartum were 1.05 (0.92-1.19) for AUC0-24h and 1.00 (0.83-1.21) for Cmax. The median (range) ratio of abacavir cord plasma to maternal plasma was 1.0 (0.7-1.0, n = 3). Viral load at the third trimester visit was less than 50 copies/ml in 13 participants (93%; one unknown). In total, 13 (93%; one unknown) children were tested HIV-negative. The pharmacokinetics of abacavir 600 mg q.d. during pregnancy are equivalent to postpartum. No dose adjustments are required during pregnancy and similar antiviral activity is expected.

  1. Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies

    PubMed Central

    Tai, Yu-Hsiao; Tai, Yi-Jou; Hsu, Heng-Cheng; Lee, Shu-Ping; Chen, Yun-Yuan; Chiang, Ying-Cheng; Chen, Yu-Li; Chen, Chi-An; Cheng, Wen-Fang

    2017-01-01

    We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease (P < 0.001, Kruskal-Wallis test), serous and mixed histological types (P = 0.003, Kruskal-Wallis test), malignant ascites (P = 0.009, chi-square test), and history of other drug allergy (P < 0.001, chi-square test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P < 0.001, independent sample t-test) and dose (6,816 vs. 3,844 mg, P < 0.001, independent sample t-test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications. PMID:29163180

  2. Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies.

    PubMed

    Tai, Yu-Hsiao; Tai, Yi-Jou; Hsu, Heng-Cheng; Lee, Shu-Ping; Chen, Yun-Yuan; Chiang, Ying-Cheng; Chen, Yu-Li; Chen, Chi-An; Cheng, Wen-Fang

    2017-01-01

    We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease ( P < 0.001, Kruskal-Wallis test), serous and mixed histological types ( P = 0.003, Kruskal-Wallis test), malignant ascites ( P = 0.009, chi-square test), and history of other drug allergy ( P < 0.001, chi-square test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P < 0.001, independent sample t -test) and dose (6,816 vs. 3,844 mg, P < 0.001, independent sample t -test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.

  3. Effect of abacavir on acute changes in biomarkers associated with cardiovascular dysfunction.

    PubMed

    Patel, Pragna; Bush, Tim; Overton, Turner; Baker, Jason; Hammer, John; Kojic, Erna; Conley, Lois; Henry, Keith; Brooks, John T

    2012-01-01

    This study examined the effect of abacavir on acute changes in biomarkers associated with cardiovascular dysfunction. Among the Study to Understand the Natural History of HIV/AIDS in the Era of Effective therapy (SUN) participants, we identified 25 individuals (cases) who were HLA-B5701-negative and who had ≥ 2 weeks without abacavir exposure at one visit and ≥ 2 weeks with abacavir exposure at the consecutive visit while maintaining viral suppression. We identified 43 individuals (controls) similarly unexposed and exposed to tenofovir. We assessed concentrations of prothrombin fragment F(1+2), D-dimer, high-sensitivity C-reactive protein, interleukin-8, intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin, P-selectin, serum amyloid A and serum amyloid P. We examined the median percentage change of these biomarkers from the unexposed to exposed state among cases and controls compared with the expected assay variability using a sign test, and compared changes among cases with controls using the Wilcoxon rank-sum test. Baseline characteristics were similar between cases and controls: median age 45 versus 46 years, 80% versus 81% male, 64% versus 63% non-Hispanic White and median CD4(+) T-cell count 538 versus 601 cells/mm(3), respectively. Mean exposure times were 65 and 15 weeks for abacavir and tenofovir, respectively. We observed no significant changes in biomarkers from the unexposed to exposed state among cases or controls compared with the expected assay variability. We found that no biomarkers were significantly increased among cases compared with controls; however, prothrombin fragment F(1+2) was significantly lower among controls (P=0.035). In virologically suppressed contemporary HIV-infected patients, abacavir exposure was not associated with increases in biomarkers associated with increased cardiovascular risk.

  4. Corticosteroid hypersensitivity studies in a skin allergy clinic.

    PubMed

    Berbegal, L; DeLeon, F J; Silvestre, J F

    2015-12-01

    Corticosteroids can cause hypersensitivity reactions, particularly delayed-type allergic reactions. A new classification system for testing hypersensitivity to corticosteroids distributes the drugs into 3 groups according to molecular structure; patients are classified according to whether they are allergic to agents in 1 or more of the groups. We aimed to describe the clinical characteristics of corticosteroid-allergic patients treated at our clinic and apply the new classification system to them; we also compared these patients' characteristics to those of others treated at our clinic. Retrospective study of cases of delayed-type corticosteroid hypersensitivity treated in the skin allergy clinic of a tertiary level hospital over an 11-year period. We reviewed the records of 2857 patients, finding 33 with at least one positive patch test result showing corticosteroid hypersensitivity. Atopic dermatitis and hand involvement were less common in our corticosteroid-allergic patients. All were allergic to a group 1 corticosteroid (most often, budesonide, the culprit in 87.9%). Testing with a specific corticosteroid series revealed that 14 (42.4%) were also allergic to corticosteroids in group 2 and/or group 3. None were allergic exclusively to group 2 or group 3 agents. Twenty-one patients were exposed to a corticosteroid cream from a group their patch test results indicated allergy to; 13 of them (61.9%) did not develop a hypersensitivity reaction. The Spanish standard series only contains group 1 corticosteroids. In the interest of improving allergy management, we recommend testing with a specific corticosteroid series and a patient's own creams whenever patch testing with a standard series reveals a hypersensitivity reaction to corticosteroids. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  5. Abacavir/dolutegravir/lamivudine single-tablet regimen: a review of its use in HIV-1 infection.

    PubMed

    Greig, Sarah L; Deeks, Emma D

    2015-04-01

    A fixed-dose, single-tablet regimen comprising the integrase strand transfer inhibitor (INSTI) dolutegravir and the nucleos(t)ide reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine (abacavir/dolutegravir/lamivudine; Triumeq®) is now available for the treatment of HIV-1 infection. In a randomized, double-blind, phase III trial in antiretroviral therapy (ART)-naive adults (SINGLE), once-daily dolutegravir plus abacavir/lamivudine had noninferior efficacy to once-daily efavirenz/tenofovir disoproxil fumarate (tenofovir DF)/emtricitabine with regard to establishing and sustaining virological suppression over 144 weeks, and subsequent superiority testing significantly favoured dolutegravir plus abacavir/lamivudine. This outcome was predominantly driven by more favourable rates of discontinuation due to adverse events versus the efavirenz/tenofovir DF/emtricitabine group. These data were generally supported by findings from other phase III trials in ART-naive adults receiving dolutegravir plus either abacavir/lamivudine or tenofovir DF/emtricitabine (SPRING-2 and FLAMINGO). Dolutegravir plus abacavir/lamivudine is generally well tolerated, with a tolerability profile that appears to be more favourable than efavirenz/tenofovir DF/emtricitabine. In the SINGLE trial, there were no major treatment-emergent INSTI or NRTI resistance-associated mutations in dolutegravir plus abacavir/lamivudine recipients with protocol-defined virological failure, indicating a high genetic barrier to resistance. Thus, triple combination therapy with abacavir, dolutegravir and lamivudine is an effective, generally well tolerated option for the management of HIV-1 infection, with the convenient once-daily fixed-dose tablet providing the first single-tablet regimen option without tenofovir DF.

  6. Aspirin and Nonsteroidal Antiinflammatory Drugs Hypersensitivity and Management.

    PubMed

    Modena, Brian; White, Andrew A; Woessner, Katharine M

    2017-11-01

    Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) are widely used in the United States and throughout the world for a variety of indications. Several unique hypersensitivity syndromes exist to this class of medications, making them one of the common reasons for consultation to the allergist. The lack of any laboratory-based diagnostic studies to assist in identifying the culprits in these reactions make evaluation of aspirin and NSAID hypersensitivity challenging. Identifying patients appropriate for oral challenge and/or desensitization protocols is the standard pragmatic approach to this issue when it arises. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. A study on the immunological basis of the dissociation between type I-hypersensitivity skin reactions to Blomia tropicalis antigens and serum anti-B. tropicalis IgE antibodies

    PubMed Central

    2011-01-01

    individuals), and differences in α-BtE IgE avidities (which would have high affinities for A. lumbricoides antigens in SPT- than in SPT+ individuals) may play a role in the down-modulation of type-I hypersensitivity reaction against aeroallergens described in helminth-infected individuals. PMID:21631925

  8. [Adaptive desensitization for acetylsalicylic acid hypersensitivity: A success story?].

    PubMed

    Mühlmeier, G; Hausch, R; Maier, H

    2015-10-01

    Adaptive desensitization still remains the only causative therapy for acetylsalicylic acid (ASA) hypersensitivity and is carried out nearly worldwide. To date there are hardly any data available on disease development under current desensitization therapy and longitudinal data in particular are missing. Out of a large collective of patients with proven hypersensitivity to ASA, 194 patients with initiated desensitization treatment were observed for periods up to 5 years (average 32 months). Patients with immediate reactions to systemic challenge tests revealed a response rate of 77% after 12 months of therapy. In this period 12% reached complete remission, 38% showed a clear reduction in symptoms, 32% reached partial remission, 13% remained unchanged and 5% suffered from disease progression. Adaptive desensitization therapy for hypersensitivity to ASA has been shown to be an effective causative therapy and chronic hyperplastic sinusitis as well as bronchial asthma could be improved. For the determination of maintenance dosages and required time periods more data are needed.

  9. Pro and Contra: Provocation Tests in Drug Hypersensitivity

    PubMed Central

    Soyer, Ozge; Sahiner, Umit Murat; Sekerel, Bulent Enis

    2017-01-01

    Drug provocation test (DPT) is the controlled administration of a drug to diagnose immune- or non-immune-mediated drug hypersensitivity and the last step for accurate recognition of drug hypersensitivity reactions when the previous diagnostic evaluations are negative or unavailable. A DPT is performed only if other conventional tests fail to yield conclusive results. In each clinical presentation, “to provoke or not to provoke” a patient should be decided after careful assessment of the risk–benefit ratio. Well-defined benefits of DPT include confirmative exclusion of diagnoses of drug hypersensitivity and provision of safe alternatives. However, disadvantages such as safety, difficulty in interpretations of results, lack of objective biomarkers, risks of resensitization, efficiency in daily practice, and lack of standardized protocols, are poorly debated. This review summarizes the current published research concerning DPT, with particular emphasis on the advantages and disadvantages of DPT in an evidence-based manner. PMID:28677662

  10. Effect of Premedications in a Murine Model of Asparaginase Hypersensitivity

    PubMed Central

    Fernandez, Christian A.; Smith, Colton; Karol, Seth E.; Ramsey, Laura B.; Liu, Chengcheng; Pui, Ching-Hon; Jeha, Sima; Evans, William E.; Finkelman, Fred D.

    2015-01-01

    A murine model was developed that recapitulates key features of clinical hypersensitivity to Escherichia coli asparaginase. Sensitized mice developed high levels of anti-asparaginase IgG antibodies and had immediate hypersensitivity reactions to asparaginase upon challenge. Sensitized mice had complete inhibition of plasma asparaginase activity (P = 4.2 × 10−13) and elevated levels of mouse mast cell protease 1 (P = 6.1 × 10−3) compared with nonsensitized mice. We investigated the influence of pretreatment with triprolidine, cimetidine, the platelet activating factor (PAF) receptor antagonist CV-6209 [2-(2-acetyl-6-methoxy-3,9-dioxo-4,8-dioxa-2,10-diazaoctacos-1-yl)-1-ethyl-pyridinium chloride], or dexamethasone on the severity of asparaginase-induced allergies. Combining triprolidine and CV-6209 was best for mitigating asparaginase-induced hypersensitivity compared with nonpretreated, sensitized mice (P = 1.2 × 10−5). However, pretreatment with oral dexamethasone was the only agent capable of mitigating the severity of the hypersensitivity (P = 0.03) and partially restoring asparaginase activity (P = 8.3 × 10−4). To rescue asparaginase activity in sensitized mice without requiring dexamethasone, a 5-fold greater dose of asparaginase was needed to restore enzyme activity to a similar concentration as in nonsensitized mice. Our results suggest a role of histamine and PAF in asparaginase-induced allergies and indicate that mast cell–derived proteases released during asparaginase allergy may be a useful marker of clinical hypersensitivity. PMID:25573198

  11. Short communication: initiation of an abacavir-containing regimen in HIV-infected adults is associated with a smaller decrease in inflammation and endothelial activation markers compared to non-abacavir-containing regimens.

    PubMed

    Hileman, Corrilynn O; Wohl, David A; Tisch, Daniel J; Debanne, Sara M; McComsey, Grace A

    2012-12-01

    Abacavir has been associated with myocardial infarction in several studies. This may be related to inflammation and endothelial cell activation. We compared changes in inflammation and endothelial activation markers between antiretroviral-naive adults initiating zidovudine, lamivudine, abacavir, and nonnucleoside reverse transcriptase inhibitor (NNRTI) or this regimen without abacavir. Changes in soluble tumor necrosis factor receptors-I, -II (sTNFR-I, -II), high sensitivity C-reactive protein, and soluble vascular cell adhesion molecule-1 (sVCAM-1) from baseline (pre-ART) to a second time point about 24 weeks after initiating antiretroviral therapy (ART) were compared between groups using multivariable linear regression. A total of 37 met eligibility criteria; 12 received abacavir. The median (interquartile range) age was 37 years (27-45). Most were men (32/37), African-American (15/37), or white (15/37). The median nadir CD4(+) and baseline HIV-1 RNA were 230 cells/mm(3) (180-301) and 82,642 copies/ml (34,400-204,703). In all, 15/30 smoked, 7/37 had hypertension, 1/37 had diabetes, and 1/37 had hyperlipidemia. None had coronary or renal disease. Changes in CD4(+) and HIV-1 RNA level and timing of stored samples with regard to ART initiation were not different between groups. In univariable analysis, log transformed percent change in sTNFR-I (p=0.05) and -II (p=0.04) showed significant between-group differences and trended toward significance for sVCAM-1 (p=0.08). These markers decreased less in the abacavir group. After adjustment for confounders, significantly less decrease for sTNFR-II and sVCAM-1 was seen for those receiving the abacavir-containing regimen. When taken with an NNRTI, abacavir induced a smaller decrease in inflammation biomarkers in this cohort, suggesting a possible proinflammatory effect of this nucleoside analogue.

  12. Biomaterial Hypersensitivity: Is It Real? Supportive Evidence and Approach Considerations for Metal Allergic Patients following Total Knee Arthroplasty

    PubMed Central

    Mihalko, William M.; Grupp, Thomas M.; Manning, Blaine T.; Dennis, Douglas A.; Goodman, Stuart B.; Saleh, Khaled J.

    2015-01-01

    The prospect of biomaterial hypersensitivity developing in response to joint implant materials was first presented more than 30 years ago. Many studies have established probable causation between first-generation metal-on-metal hip implants and hypersensitivity reactions. In a limited patient population, implant failure may ultimately be related to metal hypersensitivity. The examination of hypersensitivity reactions in current-generation metal-on-metal knee implants is comparatively limited. The purpose of this study is to summarize all available literature regarding biomaterial hypersensitivity after total knee arthroplasty, elucidate overall trends about this topic in the current literature, and provide a foundation for clinical approach considerations when biomaterial hypersensitivity is suspected. PMID:25883940

  13. Association of HLA genotypes with phenobarbital hypersensitivity in children.

    PubMed

    Manuyakorn, Wiparat; Mahasirimongkol, Surakameth; Likkasittipan, Plernpit; Kamchaisatian, Wasu; Wattanapokayakit, Sukanya; Inunchot, Wimala; Visudtibhan, Anannit; Wichukchinda, Nuanjun; Benjaponpitak, Suwat

    2016-10-01

    Phenobarbital hypersensitivity is one of the common drug hypersensitivity syndromes in children. Clinical symptoms of phenobarbital hypersensitivity vary from maculopapular rashes (MPs) to severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Drug hypersensitivity has been demonstrated to be associated with variations in the HLA genotypes. This study was to investigate the association between the variations of HLA genotypes and phenobarbital hypersensitivity in Thai children. The cases were Thai children, between 0 and 18 years of age, who were diagnosed with phenobarbital hypersensitivity, which included SCARs and MPs. The control patients were Thai children of a corresponding age who had taken phenobarbital for at least 12 weeks without any hypersensitivity reaction. Blood samples were collected for HLA genotyping by using a reverse-sequence-specific oligonucleotide (SSO) probes method. The carrier rates of HLA alleles were compared between 47 cases (27 SCARs and 20 MPs) and 54 controls. The carrier rates of HLA-A*01:01 and HLA-B*13:01 were significantly higher in the phenobarbital-induced SCARs than in the tolerant controls (18.5% vs. 1.85%, p = 0.01, odds ratio [OR] 11.66, 95% confidence interval [CI] 1.21-578.19; 37.04% vs. 11.11%, p = 0.009, OR 4.60, 95%CI 1.29-17.98). There was a trend of a higher carrier rate of HLA-C*06:02 in the phenobarbital-induced SCARs when compared with those in the tolerant controls (29.63% vs. 11.11%, p = 0.059, OR 3.31, 95% CI 0.88-13.31). In contrast to the phenobarbital-induced SCARs, only the HLA-A*01:01 carrier rate in the phenobarbital-induced MPs was significantly higher than those in the tolerant controls (20% vs. 1.85%, p = 0.017, OR 12.69, 95% CI 1.15-661.62). An association between phenobarbital hypersensitivity and HLA-A*01:01 and HLA-B*13:01 has been demonstrated in Thai children

  14. Anticonvulsant hypersensitivity syndrome. In vitro assessment of risk.

    PubMed Central

    Shear, N H; Spielberg, S P

    1988-01-01

    Arene oxide metabolites of aromatic anticonvulsants (phenytoin, phenobarbital, and carbamazepine) may be involved in the pathogenesis of hypersensitivity reactions. We investigated 53 patients with clinical sensitivity to anticonvulsants by exposing their lymphocytes in vitro to drug metabolites generated by a murine hepatic microsomal system. The diagnosis of a hypersensitivity reaction was corroborated by in vitro rechallenge for each drug (phenytoin, n = 34; phenobarbital, n = 22; carbamazepine, n = 25) when cytotoxicity (% dead cells) exceeded 3 SD above the mean result for controls. Cross-reactivity among the drugs was noted. 7 out of 10 patients who had received all three anticonvulsants had adverse reactions to each. 40 out of 50 patients tested to all three drugs in vitro were positive to each. Adverse reactions were indistinguishable among anti-convulsants. Skin rash (87%), fever (94%), hepatitis (51%), and hematologic abnormalities (51%) were common clinical features of each drug. 62% of reactions involved more than two organs. Cells from patients' parents exhibited in vitro toxicity that was intermediate between values for controls and patients. In vitro testing can help diagnose hypersensitivity to anticonvulsants. Cells from patients may also be used for prospective individualization of therapy to decrease risk of adverse reaction. Cross-reactivity among the major anticonvulsants is common and should be considered before deciding on alternative therapy. Images PMID:3198757

  15. Food hypersensitivity in patients over 14 years of age suffering from atopic dermatitis.

    PubMed

    Celakovská, Jarmila; Ettler, K; Ettlerová, K; Vaněčková, J

    2014-05-01

    Patients suffering from atopic dermatitis often describe food hypersensitivity. Rising prevalence of food hypersensitivity and severe allergic reactions to foods have been reported, but the data are scarce. Evaluation of food hypersensitivity reactions in patients suffering from atopic dermatitis. The dermatological examination was performed in patients of age 14 years and above and the detailed history was taken concerning the food hypersensitivity. A total of 228 patients were examined-72 men, 156 women, average age 26.2 (SD 9.5) years. The food hypersensitivity reactions were recorded in 196 patients from 228 (86%), no reactions were recorded in 32 patients (24%). Foods with the most often recorded reactions are: Nuts (in 35% of patients), tomatoes (in 20%), and kiwi (in 17, 5%), apples and spices (in 16%), tangerines and oranges (in 15%), capsicum (in 13%), fishes (in 12%), celery (in 9%), and chocolate (in 7%). Food hypersensitivity reactions are recorded in 86% of patients suffering from atopic dermatitis. Nuts, tomatoes, and pollen-associated foods play a role in the majority of patients suffering from atopic dermatitis.

  16. Early changes in inflammatory and pro-thrombotic biomarkers in patients initiating antiretroviral therapy with abacavir or tenofovir

    PubMed Central

    2011-01-01

    Background Abacavir has been associated with an increased risk of acute myocardial infarction, but the pathogenic mechanisms remain unknown. We evaluated longitudinal changes in pro-atherosclerotic biomarkers in patients initiating abacavir or tenofovir. Methods Consecutive patients initiating antiretroviral therapy (ART) with abacavir/lamivudine or tenofovir/emtricitabine were included. Plasma levels of high sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (sVCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and at different time points throughout 48 weeks. Comparisons were adjusted for age, sex, ART status at inclusion, viral load, lipodystrophy, Framingham score and hepatitis C virus co-infection status. Results 50 patients were analyzed, 28 initiating abacavir and 22 tenofovir. The endothelial biomarker sVCAM-1 declined significantly in both treatment groups. hsCRP tended to increase soon after starting therapy with abacavir, a trend that was not seen in those initiating tenofovir. IL-6 significantly increased only at week 24 from baseline in patients on abacavir (+225%, p < 0.01) although the differences were not significant between groups. The procoagulant biomarker PAI-1 plasma levels increased from baseline at week 12 (+57%; p = 0.017), week 24 (+72%; p = 0.008), and week 48 (+149%; p < 0.001) in patients on tenofovir, but differences between groups were not statistically significant. Conclusion Changes in biomarkers of inflammation, coagulation, and endothelial function are not different in viremic patients starting ART with abacavir/lamivudine or tenofovir/emtricitabine. These changes occur in the early phases of treatment and include anti- and pro-atherosclerotic effects with both drugs. PMID:21294867

  17. Substituting Abacavir for Stavudine in Children Who Are Virally Suppressed Without Lipodystrophy: Randomized Clinical Trial in Johannesburg, South Africa.

    PubMed

    Strehlau, Renate; Shiau, Stephanie; Arpadi, Stephen; Patel, Faeezah; Pinillos, Francoise; Tsai, Wei-Yann; Coovadia, Ashraf; Abrams, Elaine; Kuhn, Louise

    2018-01-24

    Abacavir has replaced stavudine in antiretroviral therapy (ART) regimens because it has largely been phased out as a result of toxicity concerns; this loss has reduced further the already-limited drug options for children. Few data regarding virologic and metabolic outcomes among children who undergo substitution of stavudine exist. We evaluated the effects of preemptive substitution of abacavir for stavudine in children initially without lipodystrophy and virally suppressed on a stavudine-containing regimen. At Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa, virally suppressed human immunodeficiency virus (HIV)-infected children ≥36 months of age without lipodystrophy were randomly assigned to continue taking stavudine as part of their ART regimen (n = 106) or to have abacavir substituted for stavudine (n = 107). The children were followed for 56 weeks after randomization in the context of a larger trial of treatment options for ART-experienced children. The mean age of the children was 4.3 years, and the mean duration of ART before random assignment was 3.5 years. No differences in virological outcomes, CD4 response, growth, or dyslipidemia were noted between the stavudine and abacavir groups. By 56 weeks, children in the abacavir group had less clinically detected lipodystrophy (4.7% vs 16%, respectively), a higher proportion of leg fat relative to total fat (0.243 vs 0.230, respectively; P = .006), and a lower trunk/leg-skinfold ratio (0.547 vs 0.569, respectively; P = .003) than the children in the stavudine group. Substituting abacavir for stavudine did not compromise virological response to treatment and was associated with significantly less lipodystrophy. These results support recommendations that favor abacavir in this population. © The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Early changes in inflammatory and pro-thrombotic biomarkers in patients initiating antiretroviral therapy with abacavir or tenofovir.

    PubMed

    Padilla, Sergio; Masiá, Mar; García, Natalia; Jarrin, Inmaculada; Tormo, Consuelo; Gutiérrez, Félix

    2011-02-04

    Abacavir has been associated with an increased risk of acute myocardial infarction, but the pathogenic mechanisms remain unknown. We evaluated longitudinal changes in pro-atherosclerotic biomarkers in patients initiating abacavir or tenofovir. Consecutive patients initiating antiretroviral therapy (ART) with abacavir/lamivudine or tenofovir/emtricitabine were included. Plasma levels of high sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (sVCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and at different time points throughout 48 weeks. Comparisons were adjusted for age, sex, ART status at inclusion, viral load, lipodystrophy, Framingham score and hepatitis C virus co-infection status. 50 patients were analyzed, 28 initiating abacavir and 22 tenofovir. The endothelial biomarker sVCAM-1 declined significantly in both treatment groups. hsCRP tended to increase soon after starting therapy with abacavir, a trend that was not seen in those initiating tenofovir. IL-6 significantly increased only at week 24 from baseline in patients on abacavir (+225%, p < 0.01) although the differences were not significant between groups. The procoagulant biomarker PAI-1 plasma levels increased from baseline at week 12 (+57%; p = 0.017), week 24 (+72%; p = 0.008), and week 48 (+149%; p < 0.001) in patients on tenofovir, but differences between groups were not statistically significant. Changes in biomarkers of inflammation, coagulation, and endothelial function are not different in viremic patients starting ART with abacavir/lamivudine or tenofovir/emtricitabine. These changes occur in the early phases of treatment and include anti- and pro-atherosclerotic effects with both drugs.

  19. LOCAL ORGAN HYPERSENSITIVENESS

    PubMed Central

    Seegal, David; Seegal, Beatrice Carrier

    1931-01-01

    1. Rabbit eyes sensitized with guinea pig red blood cells or fresh egg white respond with an inflammatory reaction following the intravenous injection of the homologous antigen, but not the heterologous. 2. Two-tenths of 1.0 cc. of a multiple antigen containing ten separate ingredients, or in other words, 0.02 cc. of each foreign protein, when introduced into the rabbit's anterior chamber, is sufficient to produce an altered ocular reactivity such that when 1 cc. of one of the ten antigens is introduced intravenously the eye shows hyperemia of the iris and conjunctiva with more or less edema and lacrimation during the next 24 hours. 3. For as long as 8 months after sensitization eyes will respond with an inflammatory reaction following the intravenous injection of fractions of the total antigen. 4. Repeated daily intravenous injections of a single antigen usually produce no reaction in the sensitized eye after the first few days. Injection of different antigens intravenously on succeeding days produces a continued sterile inflammatory process in the sensitized eye. After the total number of single antigens has been injected, repetition of these injections now fails to produce a similar response. Instead, the eye reaction is at a much lower level and the inflammatory response is manifested only to a few of the antigens injected intravenously. 5. Unless massive doses of antigen are used to desensitize, permanent desensitization of the eye has not occurred in animals which have been followed for at least 8 months. Animals may develop maximal eye responses following repeated intravenous injections of the same antigen, if sufficient time has elapsed between injections. Nevertheless, the eye reactions which can be elicited 6 or 7 months after sensitization are less intense than the initial responses. 6. The ability of the eye inflammation to light up following the intravenous injection of homologous antigen is not due to an initial tissue injury as proven by the fact

  20. Zidovudine, abacavir and lamivudine increase the radiosensitivity of human esophageal squamous cancer cell lines.

    PubMed

    Chen, Xuan; Wang, Cong; Guan, Shanghui; Liu, Yuan; Han, Lihui; Cheng, Yufeng

    2016-07-01

    Telomerase is a type of reverse transcriptase that is overexpressed in almost all human tumor cells, but not in normal tissues, which provides an opportunity for radiosensitization targeting telomerase. Zidovudine, abacavir and lamivudine are reverse transcriptase inhibitors that have been applied in clinical practice for several years. We sought to explore the radiosensitization effect of these three drugs on human esophageal cancer cell lines. Eca109 and Eca9706 cells were treated with zidovudine, abacavir and lamivudine for 48 h before irradiation was administered. Samples were collected 1 h after irradiation. Clonal efficiency assay was used to evaluate the effect of the combination of these drugs with radiation doses of 2, 4, 6 and 8 Gy. DNA damage was measured by comet assay. Telomerase activity (TA) and relative telomere length (TL) were detected and evaluated by real-time PCR. Apoptosis rates were assessed by flow cytometric analysis. The results showed that all the drugs tested sensitized the esophageal squamous cell carcinoma (ESCC) cell lines to radiation through an increase in radiation-induced DNA damage and cell apoptosis, deregulation of TA and decreasing the shortened TL caused by radiation. Each of the drugs investigated (zidovudine, abacavir and lamivudine) could be used for sensitizing human esophageal cancer cell lines to radiation. Consequently, the present study supports the potential of these three drugs as therapeutic agents for the radiosensitization of esophageal squamous cell cancer.

  1. Abacavir Pharmacokinetics During Chronic Therapy in HIV-1-Infected Adolescents and Young Adults

    PubMed Central

    Sleasman, JW; Robbins, BL; Cross, SJ; Lindsey, JC; Kraimer, JM; Heckman, BE; Sprenger, HL; Tustin, NB; Rose, CH; Poston, PA; Neal, EF; Pakes, GE; Nikanjam, M; Capparelli, EV

    2009-01-01

    The pharmacokinetics of abacavir and its metabolites were investigated in 30 human immunodeficiency virus (HIV)-infected adolescents and young adults 13-25 years of age, equally divided into two groups: <18 years of age and ≥18 years of age. All the subjects received the recommended adult dose of 300 mg twice daily. The area under the plasma concentration-time curve (AUC) and half-life of abacavir did not differ significantly between the age groups or by gender or race, and there were only modest associations of age with apparent abacavir clearance and with volume of distribution. There were no significant correlations of carboxylate or glucuronide metabolite levels with age or gender, although glucuronide AUC was higher in Hispanic subjects than in African-American subjects. Zidovudine and lamivudine concentration profiles were also similar in the two age groups. A novel aspect of the study included an assessment of intracellular carbovir, zidovudine, and lamivudine triphosphate levels, and these were found to be similar in the two age-based groups. Overall, these findings suggest that current recommendations relating to adult dosages are appropriate for adolescents and young adults. PMID:19118380

  2. [Anaphylaxis after vaccination due to hypersensitivity to gelatin].

    PubMed

    Kamin, W; Staubach, P; Klär-Hlawatsch, B; Erdnüss, F; Knuf, M

    2006-01-01

    Most allergic reactions after vaccination occur in patients sensitive to egg protein. Therefore this subject is well investigated, and the majority of common vaccines today contain only traces of egg protein. In contrast, there is little knowledge of hypersensitivities to other substances frequently contained in vaccines, e. g. antibiotics, phenol, gelatin and different preservatives. Here we report the case of a boy who had an anaphylactic reaction after being vaccinated against measles, mumps, rubella (MMR), and tick-born encephalitis (TBE) simultaneously. Different tests finally revealed a hypersensitivity to gelatin. This should be kept in mind especially during emergency care, since gelatin containing products like Haemaccel, Gelifundol or Gelofusin are widely used as colloid for resuscitation. If type 1 reactions after vaccination occur, gelatin should be taken into account as the causative agent. A medical alert card is recommended for such patients.

  3. Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity

    PubMed Central

    Ding, Hao; Liu, Xiao-Chang; Mei, Qiao; Xu, Jian-Ming; Hu, Xiang-Yang; Hu, Jing

    2014-01-01

    Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories. PMID:24707159

  4. Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.

    PubMed

    Ding, Hao; Liu, Xiao-Chang; Mei, Qiao; Xu, Jian-Ming; Hu, Xiang-Yang; Hu, Jing

    2014-04-07

    Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories.

  5. Occupational hypersensitivity pneumonitis: an EAACI position paper.

    PubMed

    Quirce, S; Vandenplas, O; Campo, P; Cruz, M J; de Blay, F; Koschel, D; Moscato, G; Pala, G; Raulf, M; Sastre, J; Siracusa, A; Tarlo, S M; Walusiak-Skorupa, J; Cormier, Y

    2016-06-01

    The aim of this document was to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the diagnosis and management of this condition. Occupational hypersensitivity pneumonitis (OHP) is an immunologic lung disease resulting from lymphocytic and frequently granulomatous inflammation of the peripheral airways, alveoli, and surrounding interstitial tissue which develops as the result of a non-IgE-mediated allergic reaction to a variety of organic materials or low molecular weight agents that are present in the workplace. The offending agents can be classified into six broad categories that include bacteria, fungi, animal proteins, plant proteins, low molecular weight chemicals, and metals. The diagnosis of OHP requires a multidisciplinary approach and relies on a combination of diagnostic tests to ascertain the work relatedness of the disease. Both the clinical and the occupational history are keys to the diagnosis and often will lead to the initial suspicion. Diagnostic criteria adapted to OHP are proposed. The cornerstone of treatment is early removal from exposure to the eliciting antigen, although the disease may show an adverse outcome even after avoidance of exposure to the causal agent. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era.

    PubMed

    Bedimo, Roger J; Westfall, Andrew O; Drechsler, Henning; Vidiella, Gabriela; Tebas, Pablo

    2011-07-01

    Some studies have suggested that exposure to antiretroviral therapy (ART) with abacavir is associated with an increased risk of acute myocardial infarction (AMI). Using the Veterans Health Administration's Clinical Case Registry we calculated the risk of AMI and cerebrovascular events (CVA) associated with the cumulative use of abacavir and other nucleoside combinations. We also evaluated the impact of pre-existing chronic kidney disease on the selection of abacavir versus tenofovir in the last recorded ART regimen, and on highly active antiretroviral therapy-associated AMI and CVA risks. A total of 19,424 human immunodeficiency virus-infected patients contributed 76,376 patient-years of follow. After adjusting for age, hypercholesterolemia, hypertension, type 2 diabetes, and smoking, the hazard ratio (HR) for each year of abacavir use was 1.18 (95% confidence interval [CI], .92-1.50; P=.191) for AMI and 1.16 (95% CI, .98-1.37; P=.096) for CVA. Abacavir use was more common among patients with prior chronic kidney disease than was tenofovir use (12.46% versus 7.15%; P=.0001), and chronic kidney disease was associated with a significantly higher risk of AMI (HR, 2.41; 95% CI, 1.73-3.36), and CVA (HR, 1.80; 95% CI, 1.44-2.24). Compared with patients who received neither tenofovir nor abacavir, patients who received tenofovir had lower risk of AMI (HR, 0.16; 95% CI, .08-.33; P=.0001) and CVA (HR, 0.22; 95% CI, .15-.32; P=.001). Use of abacavir was associated with lower risk of CVA (HR, 0.60; 95% CI, .45-.79). We observed no association between cumulative or current abacavir use and AMI or CVA. Abacavir use was more common than was tenofovir use among patients with prior chronic kidney disease, and chronic kidney disease independently predicted higher rates of AMI and CVA. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

  7. Contact hypersensitivity in hand dermatitis.

    PubMed

    Li, Lin-feng; Wang, Jing

    2002-10-01

    Contact hypersensitivity (CHS) in hand dermatitis (HD) was studied by patch testing (PT) 105 consecutive adult HD patients and 361 cases of suspected non-hand allergic contact dermatitis (NHD). The suspected offending agents were also investigated by a questionnaire. Age and sex distribution was no different between the 2 groups. The total positivity rate of PT in the HD group was much lower than in the control group (46.7% versus 63.2%, p < 0.01, chi2-test). The most common allergens in HD were rubber mix(17.1%), p-phenylenediamine (PPD) (14.3%), fragrance mix (9.5%), nickel (9.5%), colophonium (6.7%) and potassium dichromate (2.9%), while those in the control group, in sequence, were nickel (20.5%), rubber mix (16.9%), PPD (14.1%), fragrance mix (12.7%), potassium dichromate (5.5%) and colophonium (5.0%). The positivity rate to nickel was lower in the HD group (9.5% versus 20.5%, p < 0.05, chi2-test), while there was no significant difference for the other allergens. HD was divided arbitrarily into 5 groups: (1) vesicular form, in which fine papules and vesicles can be detected. 65.7% of the HD was vesicular form and 55.1% of them were PT positive; (2) fissured form, in which dry skin with fine fissures or desquamation is seen. 8.6% of the HD was fissured form and 30% of them were PT positive; (3) hyperkeratotic form, in which the lesions are thick, hyperkeratotic plaques - 6.7% of the HD was this form and no positive reaction was found; (4) hand and foot dermatitis (HFD) - 12.4% of HD was HFD and 53.8% of them were PT positive; (5) pompholyx - 6.7% of the patients had pompholyx and one positive result to nickel was detected. The suspected offending agents were reported in only 13 (12.4%) patients. These results suggest that CHS is less common in HD than in NHD and that other factors, such as skin irritation, may play more of a role in HD. Nickel allergy is less common in HD than in NHD. CHS may play a role in more than 1/2 of vesicular form HD, HFD and in some

  8. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM).

    PubMed

    Brockow, Knut; Przybilla, Bernhard; Aberer, Werner; Bircher, Andreas J; Brehler, Randolf; Dickel, Heinrich; Fuchs, Thomas; Jakob, Thilo; Lange, Lars; Pfützner, Wolfgang; Mockenhaupt, Maja; Ott, Hagen; Pfaar, Oliver; Ring, Johannes; Sachs, Bernhardt; Sitter, Helmut; Trautmann, Axel; Treudler, Regina; Wedi, Bettina; Worm, Margitta; Wurpts, Gerda; Zuberbier, Torsten; Merk, Hans F

    Drug hypersensitivity reactions are unpredictable adverse drug reactions. They manifest either within 1-6 h following drug intake (immediate reactions) with mild to life-threatening symptoms of anaphylaxis, or several hours to days later (delayed reactions), primarily as exanthematous eruptions. It is not always possible to detect involvement of the immune system (allergy). Waiving diagnostic tests can result in severe reactions on renewed exposure on the one hand, and to unjustified treatment restrictions on the other. With this guideline, experts from various specialist societies and institutions have formulated recommendations and an algorithm for the diagnosis of allergies. The key principles of diagnosing allergic/hypersensitivity drug reactions are presented. Where possible, the objective is to perform allergy diagnostics within 4 weeks-6 months following the reaction. A clinical classification of symptoms based on the morphology and time course of the reaction is required in order to plan a diagnostic work-up. In the case of typical symptoms of a drug hypersensitivity reaction and unequivocal findings from validated skin and/or laboratory tests, a reaction can be attributed to a trigger with sufficient confidence. However, skin and laboratory tests are often negative or insufficiently reliable. In such cases, controlled provocation testing is required to clarify drug reactions. This method is reliable and safe when attention is paid to indications and contraindications and performed under appropriate medical supervision. The results of the overall assessment are discussed with the patient and documented in an "allergy passport" in order to ensure targeted avoidance in the future and allow the use of alternative drugs where possible.

  9. Hypersensitivity to sub-Tenon's topotecan in fibrin adhesive in patients with retinoblastoma.

    PubMed

    Astudillo, Paulita Pamela P; Durairaj, Priya; Chan, Helen S L; Héon, Elise; Gallie, Brenda L

    2015-02-01

    Sub-Tenon's space delivery of topotecan in a fibrin sealant was used as an adjunct to laser therapy for small retinoblastoma tumors in 25 children (77 injections). We report serious hypersensitivity reactions in 2 children on their third sub-Tenon's injection of topotecan in fibrin sealant. One child subsequently had topotecan in an autologous blood clot with no allergic reaction. Although allergic reaction to topotecan has been reported in the literature, fibrin glue reactions are more common and are likely due to aprotinin hypersensitivity. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  10. Optimization of the strength of the efavirenz/lamivudine/abacavir fixed-dose combination for paediatric patients.

    PubMed

    Bouazza, Naïm; Cressey, Tim R; Foissac, Frantz; Bienczak, Andrzej; Denti, Paolo; McIlleron, Helen; Burger, David; Penazzato, Martina; Lallemant, Marc; Capparelli, Edmund V; Treluyer, Jean-Marc; Urien, Saïk

    2017-02-01

    Child-friendly, low-cost, solid, oral fixed-dose combinations (FDCs) of efavirenz with lamivudine and abacavir are urgently needed to improve clinical management and drug adherence for children. Data were pooled from several clinical trials and therapeutic drug monitoring datasets from different countries. The number of children/observations was 505/3667 for efavirenz. Population pharmacokinetic analyses were performed using a non-linear mixed-effects approach. For abacavir and lamivudine, data from 187 and 920 subjects were available (population pharmacokinetic models previously published). Efavirenz/lamivudine/abacavir FDC strength options assessed were (I) 150/75/150, (II) 120/60/120 and (III) 200/100/200 mg. Monte Carlo simulations of the different FDC strengths were performed to determine the optimal dose within each of the WHO weight bands based on drug efficacy/safety targets. The probability of being within the target efavirenz concentration range 12 h post-dose (1-4 mg/L) varied between 56% and 60%, regardless of FDC option. Option I provided a best possible balance between efavirenz treatment failure and toxicity risks. For abacavir and lamivudine, simulations showed that for option I >75% of subjects were above the efficacy target. According to simulations, a paediatric efavirenz/lamivudine/abacavir fixed-dose formulation of 150 mg efavirenz, 75 mg lamivudine and 150 mg abacavir provided the most effective and safe concentrations across WHO weight bands, with the flexibility of dosage required across the paediatric population. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Aripiprazole-induced hypersensitivity pneumonitis.

    PubMed

    Gunasekaran, Kulothungan; Murthi, Swetha; Jennings, Jeffrey; Lone, Nazir

    2017-05-09

    Aripiprazole is an atypical antipsychotic agent commonly used in the management of schizophrenia. Aripiprazole has not been reported to have an association with interstitial lung disease. We describe a case of a 36-year-old woman who began to experience respiratory issues shortly after starting aripiprazole and presented to us 4 years later with progressive exertional shortness of breath. High-resolution CT of the chest showed a bilateral ground glass pattern. Video-assisted thoracoscopy with biopsy revealed alveolar septal thickening and an inflammatory infiltrate composed mainly of lymphocytes, suggestive of chronic hypersensitivity pneumonitis. After discontinuing aripiprazole and initiating prednisolone therapy, the patient's pulmonary symptoms improved. This case highlights that aripiprazole can cause hypersensitivity pneumonitis in susceptible individuals. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Cracking the egg: An insight into egg hypersensitivity.

    PubMed

    Dhanapala, Pathum; De Silva, Chamika; Doran, Tim; Suphioglu, Cenk

    2015-08-01

    Hypersensitivity to the chicken egg is a widespread disorder mainly affecting 1-2% of children worldwide. It is the second most common food allergy in children, next to cow's milk allergy. Egg allergy is mainly caused by hypersensitivity to four allergens found in the egg white; ovomucoid, ovalbumin, ovotransferrin and lysozyme. However, some research suggests the involvement of allergens exclusively found in the egg yolk such as chicken serum albumin and YGP42, which may play a crucial role in the overall reaction. In egg allergic individuals, these allergens cause conditions such as itching, atopic dermatitis, bronchial asthma, vomiting, rhinitis, conjunctivitis, laryngeal oedema and chronic urticaria, and anaphylaxis. Currently there is no permanent cure for egg allergy. Upon positive diagnosis for egg allergy, strict dietary avoidance of eggs and products containing traces of eggs is the most effective way of avoiding future hypersensitivity reactions. However, it is difficult to fully avoid eggs since they are found in a range of processed food products. An understanding of the mechanisms of allergic reactions, egg allergens and their prevalence, egg allergy diagnosis and current treatment strategies are important for future studies. This review addresses these topics and discusses both egg white and egg yolk allergy as a whole. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Genome-wide Association Study of Virologic Response with Efavirenz- or Abacavir-containing Regimens in AIDS Clinical Trials Group Protocols

    PubMed Central

    Lehmann, David S.; Ribaudo, Heather J.; Daar, Eric S.; Gulick, Roy M.; Haubrich, Richard H.; Robbins, Gregory K.; de Bakker, Paul I.W.; Haas, David W.; McLaren, Paul J.

    2015-01-01

    Background Efavirenz and abacavir are components of recommended first-line regimens for human immunodeficiency virus (HIV)-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among subjects randomized to efavirenz- or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols. Methods Virologic response and genome-wide genotype data were available from treatment-naive subjects randomized to efavirenz-containing (n=1,596) or abacavir-containing (n=786) regimens in ACTG protocols 384, A5142, A5095, and A5202. Results Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (p<5×10−8) with virologic response for either efavirenz or abacavir. Our sample size provided 80% power to detect a genotype relative risk of 1.8 for efavirenz, and 2.4 for abacavir. Analyses focused on CYP2B genotypes that define the lowest plasma efavirenz exposure stratum did not reveal associations, nor did analysis limited to gene sets predicted to be relevant to efavirenz and abacavir disposition. Conclusions No single polymorphism is strongly associated with virologic failure with efavirenz- or abacavir-containing regimens. Analyses to better consider context, and that minimize confounding by non-genetic factors, may reveal associations not apparent herein. PMID:25461247

  14. Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols.

    PubMed

    Lehmann, David S; Ribaudo, Heather J; Daar, Eric S; Gulick, Roy M; Haubrich, Richard H; Robbins, Gregory K; de Bakker, Paul I W; Haas, David W; McLaren, Paul J

    2015-02-01

    Efavirenz and abacavir are components of recommended first-line regimens for HIV-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among patients randomized to efavirenz-containing or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols. Virologic response and genome-wide genotype data were available from treatment-naive patients randomized to efavirenz-containing (n=1596) or abacavir-containing (n = 786) regimens in ACTG protocols 384, A5142, A5095, and A5202. Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (P < 5 × 10) with virologic response for either efavirenz or abacavir. Our sample size provided 80% power to detect a genotype relative risk of 1.8 for efavirenz and 2.4 for abacavir. Analyses focused on CYP2B genotypes that define the lowest plasma efavirenz exposure stratum did not show associations nor did analysis limited to gene sets predicted to be relevant to efavirenz and abacavir disposition. No single polymorphism is associated strongly with virologic failure with efavirenz-containing or abacavir-containing regimens. Analyses to better consider context, and that minimize confounding by nongenetic factors, may show associations not apparent here.

  15. Management of hypersensitivity to platinum- and taxane-based chemotherapy: cepo review and clinical recommendations

    PubMed Central

    Boulanger, J.; Boursiquot, J.N.; Cournoyer, G.; Lemieux, J.; Masse, M.S.; Almanric, K.; Guay, M.P.

    2014-01-01

    Background Although antineoplastic agents are critical in the treatment of cancer, they can potentially cause hypersensitivity reactions that can have serious consequences. When such a reaction occurs, clinicians can either continue the treatment, at the risk of causing a severe or a potentially fatal anaphylactic reaction, or stop the treatment, although it might be the only one available. The objective of the present work was to evaluate the effectiveness of methods used to prevent and treat hypersensitivity reactions to platinum- or taxane-based chemotherapy and to develop evidence-based recommendations. Methods The scientific literature published to December 2013, inclusive, was reviewed. Results Premedication with antihistamines, H2 blockers, and corticosteroids is not effective in preventing hypersensitivity reactions to platinum salts. However, premedication significantly reduces the incidence of hypersensitivity to taxanes. A skin test can generally be performed to screen for patients at risk of developing a severe reaction to platinum salts in the presence of grade 1 or 2 reactions, but skin testing does not appear to be useful for taxanes. A desensitization protocol allows for re-administration of either platinum- or taxane-based chemotherapy to some patients without causing severe hypersensitivity reactions. Conclusions Several strategies such as premedication, skin testing, and desensitization protocols are available to potentially allow for administration of platinum- or taxane-based chemotherapy to patients who have had a hypersensitivity reaction and for whom no other treatment options are available. Considering the available evidence, the Comité de l’évolution des pratiques en oncologie made recommendations for clinical practice in Quebec. PMID:25089112

  16. A case of adverse drug reaction induced by dispensing error.

    PubMed

    Gallelli, L; Staltari, O; Palleria, C; Di Mizio, G; De Sarro, G; Caroleo, B

    2012-11-01

    To report about a case of acute renal failure due to absence of communication between physician and patient. A 78 year old man with human immunodeficiency virus (HIV) accessed our hospital and was brought to our attention in August 2011 for severe renal failure. Clinical history revealed that he had been taking highly active antiretroviral therapy with lamivudine/abacavir and fosamprenavir since 2006. In April 2011 due to an augmentation in creatinine plasma levels, a reduction in lamivudine dosage to 100 mg/day and the prescription of abacavir 300 mg/day became necessary. Unfortunately, the patient took both lamivudine and abacavir therefore the association of the two medications (lamivudine/abacavir) lead to asthenia and acute renal failure within a few days. This case emphasizes the importance about how physicians must pay very careful attention during drug prescription, most particularly, as far as elderly patients are concerned. In fact, communication improvement between physicians and patients can prevent increase of adverse drug reactions related to drug dispensing, with consequential reduction of costs in the healthcare system. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  17. Abacavir and warfarin modulate allosterically kinetics of NO dissociation from ferrous nitrosylated human serum heme-albumin

    SciTech Connect

    Ascenzi, Paolo; National Institute for Infectious Diseases I.R.C.C.S. 'Lazzaro Spallanzani', Via Portuense 292, I-00149 Roma; Imperi, Francesco

    Human serum albumin (HSA) participates to heme scavenging, in turn HSA-heme binds gaseous diatomic ligands at the heme-Fe-atom. Here, the effect of abacavir and warfarin on denitrosylation kinetics of HSA-heme-Fe(II)-NO (i.e., k{sub off}) is reported. In the absence of drugs, the value of k{sub off} is (1.3 {+-} 0.2) x 10{sup -4} s{sup -1}. Abacavir and warfarin facilitate NO dissociation from HSA-heme-Fe(II)-NO, the k{sub off} value increases to (8.6 {+-} 0.9) x 10{sup -4} s{sup -1}. From the dependence of k{sub off} on the drug concentration, values of the dissociation equilibrium constant for the abacavir and warfarin binding to HSA-heme-Fe(II)-NOmore » (i.e., K = (1.2 {+-} 0.2) x 10{sup -3} M and (6.2 {+-} 0.7) x 10{sup -5} M, respectively) were determined. The increase of k{sub off} values reflects the stabilization of the basic form of HSA-heme-Fe by ligands (e.g., abacavir and warfarin) that bind to Sudlow's site I. This event parallels the stabilization of the six-coordinate derivative of the HSA-heme-Fe(II)-NO atom. Present data highlight the allosteric modulation of HSA-heme-Fe(II) reactivity by heterotropic effectors.« less

  18. MDR1 and BCRP Transporter-Mediated Drug-Drug Interaction between Rilpivirine and Abacavir and Effect on Intestinal Absorption.

    PubMed

    Reznicek, Josef; Ceckova, Martina; Ptackova, Zuzana; Martinec, Ondrej; Tupova, Lenka; Cerveny, Lukas; Staud, Frantisek

    2017-09-01

    Rilpivirine (TMC278) is a highly potent nonnucleoside reverse transcriptase inhibitor (NNRTI) representing an effective component of combination antiretroviral therapy (cART) in the treatment of HIV-positive patients. Many antiretroviral drugs commonly used in cART are substrates of ATP-binding cassette (ABC) and/or solute carrier (SLC) drug transporters and, therefore, are prone to pharmacokinetic drug-drug interactions (DDIs). The aim of our study was to evaluate rilpivirine interactions with abacavir and lamivudine on selected ABC and SLC transporters in vitro and assess its importance for pharmacokinetics in vivo Using accumulation assays in MDCK cells overexpressing selected ABC or SLC drug transporters, we revealed rilpivirine as a potent inhibitor of MDR1 and BCRP, but not MRP2, OCT1, OCT2, or MATE1. Subsequent transport experiments across monolayers of MDCKII-MDR1, MDCKII-BCRP, and Caco-2 cells demonstrated that rilpivirine inhibits MDR1- and BCRP-mediated efflux of abacavir and increases its transmembrane transport. In vivo experiments in male Wistar rats confirmed inhibition of MDR1/BCRP in the small intestine, leading to a significant increase in oral bioavailability of abacavir. In conclusion, rilpivirine inhibits MDR1 and BCRP transporters and may affect pharmacokinetic behavior of concomitantly administered substrates of these transporters, such as abacavir. Copyright © 2017 American Society for Microbiology.

  19. MDR1 and BCRP Transporter-Mediated Drug-Drug Interaction between Rilpivirine and Abacavir and Effect on Intestinal Absorption

    PubMed Central

    Reznicek, Josef; Ceckova, Martina; Ptackova, Zuzana; Martinec, Ondrej; Tupova, Lenka; Cerveny, Lukas

    2017-01-01

    ABSTRACT Rilpivirine (TMC278) is a highly potent nonnucleoside reverse transcriptase inhibitor (NNRTI) representing an effective component of combination antiretroviral therapy (cART) in the treatment of HIV-positive patients. Many antiretroviral drugs commonly used in cART are substrates of ATP-binding cassette (ABC) and/or solute carrier (SLC) drug transporters and, therefore, are prone to pharmacokinetic drug-drug interactions (DDIs). The aim of our study was to evaluate rilpivirine interactions with abacavir and lamivudine on selected ABC and SLC transporters in vitro and assess its importance for pharmacokinetics in vivo. Using accumulation assays in MDCK cells overexpressing selected ABC or SLC drug transporters, we revealed rilpivirine as a potent inhibitor of MDR1 and BCRP, but not MRP2, OCT1, OCT2, or MATE1. Subsequent transport experiments across monolayers of MDCKII-MDR1, MDCKII-BCRP, and Caco-2 cells demonstrated that rilpivirine inhibits MDR1- and BCRP-mediated efflux of abacavir and increases its transmembrane transport. In vivo experiments in male Wistar rats confirmed inhibition of MDR1/BCRP in the small intestine, leading to a significant increase in oral bioavailability of abacavir. In conclusion, rilpivirine inhibits MDR1 and BCRP transporters and may affect pharmacokinetic behavior of concomitantly administered substrates of these transporters, such as abacavir. PMID:28696229

  20. Abacavir/Dolutegravir/Lamivudine (Triumeq)-Induced Liver Toxicity in a Human Immunodeficiency Virus-Infected Patient.

    PubMed

    Christensen, Erin S; Jain, Rupali; Roxby, Alison C

    2017-01-01

    Drug-induced liver injury related to Triumeq (abacavir/lamivudine/dolutegravir) has not been reported in clinical trials. We report a case of hepatotoxicity related to Triumeq exposure in a human immunodeficiency virus-infected patient. Clinicians should remain aware of the risk for acute and late-onset hepatitis with these agents. Close monitoring is recommended.

  1. Abacavir/Dolutegravir/Lamivudine (Triumeq)–Induced Liver Toxicity in a Human Immunodeficiency Virus–Infected Patient

    PubMed Central

    Jain, Rupali; Roxby, Alison C.

    2017-01-01

    Abstract Drug-induced liver injury related to Triumeq (abacavir/lamivudine/dolutegravir) has not been reported in clinical trials. We report a case of hepatotoxicity related to Triumeq exposure in a human immunodeficiency virus–infected patient. Clinicians should remain aware of the risk for acute and late-onset hepatitis with these agents. Close monitoring is recommended. PMID:28748198

  2. An outer membrane protein (porin) as an eliciting antigen for delayed-type hypersensitivity in murine salmonellosis.

    PubMed Central

    Udhayakumar, V; Muthukkaruppan, V R

    1987-01-01

    The porin, an outer membrane protein of Salmonella typhimurium, was found to be a suitable antigen for eliciting delayed-type hypersensitivity in mouse salmonellosis. Histological examination of the reaction site revealed that the porin was superior to other antigenic preparations in eliciting a typical delayed-type hypersensitivity reaction consisting of mononuclear cell infiltration without polymorphonuclear cell contamination. This study indicates the importance of using a suitable protein antigen from S. typhi for human application. Images PMID:3028963

  3. Stratified premedication strategy for the prevention of contrast media hypersensitivity in high-risk patients.

    PubMed

    Lee, Suh-Young; Yang, Min Suk; Choi, Young-Hoon; Park, Chang Min; Park, Heung-Woo; Cho, Sang Heon; Kang, Hye-Ryun

    2017-03-01

    Although the severity of hypersensitivity reactions to iodinated contrast media varies, it is well correlated with the severity of recurrent reactions; however, prophylaxis protocols are not severity-stratified. To assess the outcomes of tailored prophylaxis according to the severity of hypersensitivity reactions to iodinated contrast media. Our premedication protocols were stratified based on the severity of previous reactions: (1) 4 mg of chlorpheniramine for mild reactions, (2) adding 40 mg of methylprednisolone for moderate reactions, and (3) adding multiple doses of 40 mg of methylprednisolone for severe index reactions. Cases of reexposure in patients with a history of hypersensitivity reactions were routinely monitored and mandatorily recorded. Among a total of 850 patients who underwent enhanced computed tomography after severity-tailored prophylaxis, breakthrough reactions occurred in 17.1%, but most breakthrough reactions (89.0%) were mild and did not require medical treatment. Additional corticosteroid use did not reduce the breakthrough reaction rate in cases with a mild index reaction (16.8% vs 17.2%, P = .70). However, underpremedication with a single dose of corticosteroid revealed significantly higher rates of breakthrough reaction than did double doses of corticosteroid in cases with a severe index reaction (55.6% vs 17.4%, P = .02). Changing the iodinated contrast media resulted in an additional reduction of the breakthrough reaction rate overall (14.9% vs 32.1%, P = .001). In a total severity-based stratified prophylaxis regimens and changing iodinated contrast media can be considered in patients with a history of previous hypersensitivity reaction to iodinated contrast media to reduce the risk of breakthrough reactions. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Cervical dentin hypersensitivity: a cross-sectional investigation in Athens, Greece.

    PubMed

    Rahiotis, C; Polychronopoulou, A; Tsiklakis, K; Kakaboura, A

    2013-12-01

    The purpose of this study was to identify the prevalence of cervical dentin hypersensitivity in a cross-sectional investigation of Greek adults. Seven hundred and sixty-seven subjects were examined. Participants were patients processed for first examination in the Clinic of Oral Diagnosis and Radiology at the Faculty of Dentistry, University of Athens. The evaluation of hypersensitivity was performed using two methods: for each tooth, the response to a) tactile stimulus and b) air-blast stimulus was measured. Additional factors such as smoking habits, oral health behaviour, consumption of acidic foods, type of toothbrush, daily use of fluoride solution and of desensitising toothpaste, gingival recession and non-carious cervical lesions were recorded and evaluated as causative factors. Descriptive statistics on the demographics of the study sample, of oral health behaviour characteristics and of oral examination findings were performed. Comparisons of these characteristics in the presence or absence of hypersensitivity were conducted with the chi-square test. Data were further analysed using multiple logistic regression modelling. Among study participants, 21·3% had at least one cervical dentin hypersensitivity reaction to the tactile stimulus, and 38·6%, to the air-blast stimulus. Multivariate analysis detected association of the hypersensitivity in tactile or air-blast stimulus with the non-carious lesions and with the gingival recessions. Additionally, a relation between hypersensitivity and air-blast stimulus with gender (female) was found. There was no association between the hypersensitivity in both of the stimuli and the level of education, smoking, consumption of acidic foods, type of toothbrush and daily use of fluoride solution or desensitising toothpaste. The overall prevalence of cervical dentin hypersensitivity in the adult population in Athens ranged from 21·3% to 38·6% depending on the type of stimuli. Cervical non-carious lesions and gingival

  5. [Hypersensitivity to mosquito bite manifested as Skeeter síndrome].

    PubMed

    Pérez-Vanzzini, Rafael; González-Díaz, Sandra Nora; Arias-Cruz, Alfredo; Palma-Gómez, Samuel; Yong-Rodríguez, Adrián; Gutiérrez-Mujica, José Julio; García-Calderín, Diego; Ibarra, Jesús Arturo

    2015-01-01

    The reactions to mosquito bites are immunological reactions with involvement of IgE, IgG and T cells mediated hypersensitivity. These reactions are common and range from small local reactions, large local reactions to systemic allergic reactions. Skeeter syndrome is defined as a large local induced inflammatory reaction to mosquito bite and sometimes accompanied by systemic symptoms such as fever and vomiting. Diagnosis is based on clinical history and physical examination, supported by the identification of specific IgE by skin testing. Treatment includes prevention, antihistamines and steroids in some cases. Specific immunotherapy still requires further study. This paper reports two cases of patients with hypersensitivity reactions to mosquito bites, which were evaluated in our center presenting positive skin tests.

  6. Hypersensitivity Events, Including Potentially Hypersensitivity-Related Skin Events, with Dapagliflozin in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis.

    PubMed

    Mellander, Annika; Billger, Martin; Johnsson, Eva; Träff, Anna Karin; Yoshida, Shigeru; Johnsson, Kristina

    2016-11-01

    In patients with type 2 diabetes mellitus (T2DM), dapagliflozin improves glycemic control and has a safety profile typically related to its mechanism of action. Hypersensitivity adverse events (AEs) have been reported in some patients with sodium-glucose cotransporter 2 (SGLT2) inhibitors, including a recent report of dermatological AEs in Japan. We investigated the frequency and characteristics of hypersensitivity AEs, including potentially hypersensitivity-related skin AEs, across 21 phase IIb/III trials of dapagliflozin (N = 5936) versus active or placebo comparators (N = 3403), including the subpopulation of Asian patients (N = 1563). Overall, AEs and serious AEs (SAEs) of hypersensitivity were infrequent and were reported in a similar proportion of patients with dapagliflozin versus active or placebo comparators (AEs: 4.5 vs. 4.3 %; SAEs: 0.2 vs. 0.1 %, respectively). The most common events affected the skin or subcutaneous tissue: rash (dapagliflozin: 1.1 %, comparator: 1.1 %), eczema (0.6, 0.8 %), dermatitis (0.5, 0.4 %), and urticaria (0.5, 0.2 %). Few patients discontinued as a result of hypersensitivity AEs (≤0.2 %). In patients of Asian descent, a lower frequency of hypersensitivity AEs was observed with dapagliflozin versus comparators (2.0 vs. 4.5 %). In the subset of placebo-controlled trials, hypersensitivity AEs were slightly more frequent with dapagliflozin than with placebo across the overall population (4.7 vs. 3.8 %), and less frequent with dapagliflozin in Asian patients (1.5 vs. 5.0 %). The findings of this post hoc analysis indicate that dapagliflozin does not lead to an increased risk of serious hypersensitivity reactions or potentially hypersensitivity-related skin events among patients with T2DM, including Asian patients. Long-term outcome studies and postmarketing surveillance will provide further information on hypersensitivity reactions with SGLT2 inhibitors. CLINICALTRIALS. NCT01042977, NCT01031680, NCT00855166, NCT

  7. Electromagnetic hypersensitivity: fact or fiction?

    PubMed

    Genuis, Stephen J; Lipp, Christopher T

    2012-01-01

    As the prevalence of wireless telecommunication escalates throughout the world, health professionals are faced with the challenge of patients who report symptoms they claim are connected with exposure to some frequencies of electromagnetic radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of hypersensitivity to EMR resulting from common exposures such as wireless systems and electrical devices in the home or workplace; others suggest that electromagnetic hypersensitivity (EHS) is psychosomatic or fictitious. Various organizations including the World Health Organization as well as some nation states are carefully exploring this clinical phenomenon in order to better explain the rising prevalence of non-specific, multi-system, often debilitating symptoms associated with non-ionizing EMR exposure. As well as an assortment of physiological complaints, patients diagnosed with EHS also report profound social and personal challenges, impairing their ability to function normally in society. This paper offers a review of the sparse literature on this perplexing condition and a discussion of the controversy surrounding the legitimacy of the EHS diagnosis. Recommendations are provided to assist health professionals in caring for individuals complaining of EHS. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Pharmacovigilance of drug allergy and hypersensitivity using the ENDA-DAHD database and the GALEN platform. The Galenda project.

    PubMed

    Bousquet, P-J; Demoly, P; Romano, A; Aberer, W; Bircher, A; Blanca, M; Brockow, K; Pichler, W; Torres, M J; Terreehorst, I; Arnoux, B; Atanaskovic-Markovic, M; Barbaud, A; Bijl, A; Bonadonna, P; Burney, P G; Caimmi, S; Canonica, G W; Cernadas, J; Dahlen, B; Daures, J-P; Fernandez, J; Gomes, E; Gueant, J-L; Kowalski, M L; Kvedariene, V; Mertes, P-M; Martins, P; Nizankowska-Mogilnicka, E; Papadopoulos, N; Ponvert, C; Pirmohamed, M; Ring, J; Salapatas, M; Sanz, M L; Szczeklik, A; Van Ganse, E; De Weck, A L; Zuberbier, T; Merk, H F; Sachs, B; Sidoroff, A

    2009-02-01

    Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA(2)LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has been established under FileMaker((R)) Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA(2)LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA(2)LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments.

  9. Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum tryptase-a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity.

    PubMed

    Ruëff, Franziska; Przybilla, Bernhard; Biló, Maria Beatrice; Müller, Ulrich; Scheipl, Fabian; Aberer, Werner; Birnbaum, Joëlle; Bodzenta-Lukaszyk, Anna; Bonifazi, Floriano; Bucher, Christoph; Campi, Paolo; Darsow, Ulf; Egger, Cornelia; Haeberli, Gabrielle; Hawranek, Thomas; Körner, Michael; Kucharewicz, Iwona; Küchenhoff, Helmut; Lang, Roland; Quercia, Oliviero; Reider, Norbert; Severino, Maurizio; Sticherling, Michael; Sturm, Gunter Johannes; Wüthrich, Brunello

    2009-11-01

    Severe anaphylaxis to honeybee or vespid stings is associated with a variety of risk factors, which are poorly defined. Our aim was to evaluate the association of baseline serum tryptase concentrations and other variables routinely recorded during patient evaluation with the frequency of past severe anaphylaxis after a field sting. In this observational multicenter study, we enrolled 962 patients with established bee or vespid venom allergy who had a systemic reaction after a field sting. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, and the number of preceding minor systemic reactions before the index field sting. A severe reaction was defined as anaphylactic shock, loss of consciousness, or cardiopulmonary arrest. The index sting was defined as the hitherto first, most severe systemic field-sting reaction. Relative rates were calculated with generalized additive models. Two hundred six (21.4%) patients had a severe anaphylactic reaction after a field sting. The frequency of this event increased significantly with higher tryptase concentrations (nonlinear association). Other factors significantly associated with severe reactions after a field sting were vespid venom allergy, older age, male sex, angiotensin-converting enzyme inhibitor medication, and 1 or more preceding field stings with a less severe systemic reaction. In patients with honeybee or vespid venom allergy, baseline serum tryptase concentrations are associated with the risk for severe anaphylactic reactions. Preventive measures should include substitution of angiotensin-converting enzyme inhibitors.

  10. High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen.

    PubMed

    Steegen, Kim; Levin, Leon; Ketseoglou, Irene; Bronze, Michelle; Papathanasopoulos, Maria A; Carmona, Sergio; Stevens, Wendy

    2014-01-01

    The knowledge-base of emerging drug resistance profiles in children exposed to abacavir-based antiretroviral regimens in South Africa is very limited. This study investigated the suitability of didanosine-based 2nd-line regimens for children in the context of antiretroviral drug resistance patterns emerging after 1st-line virologic failure. A retrospective dataset of 354 antiretroviral drug resistant genotypes from children failing either abacavir (n = 81) or stavudine (n = 273) based 1st-line regimens, was analysed. Samples were sent to the HIV genotyping laboratory at Charlotte Maxeke Johannesburg Academic Hospital, for routine testing. Pol sequences were submitted to the Stanford HIV drug resistance database for genotypic predictions. Children were exposed to abacavir or stavudine-based 1st-line regimens for an average of 21 and 36 months, respectively. The frequency of reduced susceptibility to didanosine was substantial in the abacavir-exposed group (69.1%).This reduced susceptibility was commonly attributed to L74V/I (n = 44) and to a lesser extent K65R (n = 10) mutations. Didanosine resistance was observed in 43.2% of patients exposed to stavudine-based regimens. In contrast, most children remained susceptible to stavudine regardless of exposure to abacavir (77.8%) or stavudine (74.7%). At least 80% of children remained susceptible to zidovudine irrespective of stavudine or abacavir-exposure. The presence of the K65R mutation was more common after abacavir pressure (12.3% vs 1.8%). Analysis revealed that didanosine-based 2nd-line regimens have limitations for South African children, given the high frequency of mutations that confer cross-resistance to didanosine; especially after abacavir-exposure. This data has influenced South African paediatric treatment guidelines, which now recommend zidovudine-based 2nd-line regimens.

  11. Drug hypersensitivity in human immunodeficiency virus-infected patient: challenging diagnosis and management

    PubMed Central

    Widhani, Alvina; Karjadi, Teguh Harjono

    2014-01-01

    Human immunodeficiency virus (HIV)-infected patients present complex immunological alterations. Multiple drugs that usually prescribed for prevention or treatment of opportunistic infections and antiretroviral pose these patients a higher risk of developing drug hypersensitivity. All antiretroviral agents and drugs to treat opportunistic infections have been reported to cause drug hypersensitivity reactions. Allergic reactions with antiretroviral are not restricted to older agents, although newer drugs usually more tolerated. Cutaneous adverse drug reactions are the most common manifestation of drug hypersensitivity in HIV, typically manifesting as maculopapular rash with or without systemic symptoms in the presence or absence of internal organ involvement. The onset of an allergic reaction is usually delayed. Severe drug hypersensitity reactions as erythema multiforme, Stevens Johnson syndrome and toxic epidermal necrolysis develop more often in HIV-infected patients compared to other populations. Mild to moderate rash without systemic symptom or organ involvement usually do not need drug discontinuation. Appropriate diagnosis and management of drug hypersensitivity reactions are essential, especially in patients with very low CD4+ T-cell count and multiple opportunistic infections. Clinicians should aware of different half-life of each drug when decided to stop the drug. Knowledge of the metabolism, recognition of the risk factors, and the ability to suggest the probability of particular drug as causative are also important points. A step wise rechallenge test or desensitization with the offending drug might be a preferable action and more commonly used in managing drug hypersensitivity in HIV-infected patients. Desensitization protocols have been successfully done for several antiretroviral and opportunistic infection drugs. PMID:24527412

  12. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection.

    PubMed

    Walmsley, Sharon L; Antela, Antonio; Clumeck, Nathan; Duiculescu, Dan; Eberhard, Andrea; Gutiérrez, Felix; Hocqueloux, Laurent; Maggiolo, Franco; Sandkovsky, Uriel; Granier, Catherine; Pappa, Keith; Wynne, Brian; Min, Sherene; Nichols, Garrett

    2013-11-07

    Dolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. Dolutegravir, in combination with abacavir-lamivudine, may provide a simplified regimen. We conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily (DTG-ABC-3TC group) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily (EFV-TDF-FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance. A total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (88% vs. 81%, P=0.003), thus meeting the criterion for superiority. The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group (28 vs. 84 days, P<0.001), as well as greater increases in CD4+ T-cell count (267 vs. 208 per cubic millimeter, P<0.001). The proportion of participants who discontinued therapy owing to adverse events was lower in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (2% vs. 10%); rash and neuropsychiatric events (including abnormal dreams, anxiety, dizziness, and somnolence) were significantly more common in the EFV-TDF-FTC group, whereas insomnia was reported more frequently in the DTG-ABC-3TC group. No

  13. Pre-clinical methods for detecting the hypersensitivity potential of pharmaceuticals: regulatory considerations.

    PubMed

    Hastings, K L

    2001-02-02

    Immune-based systemic hypersensitivities account for a significant number of adverse drug reactions. There appear to be no adequate nonclinical models to predict systemic hypersensitivity to small molecular weight drugs. Although there are very good methods for detecting drugs that can induce contact sensitization, these have not been successfully adapted for prediction of systemic hypersensitivity. Several factors have made the development of adequate models difficult. The term systemic hypersensitivity encompases many discrete immunopathologies. Each type of immunopathology presumably is the result of a specific cluster of immunologic and biochemical phenomena. Certainly other factors, such as genetic predisposition, metabolic idiosyncrasies, and concomitant diseases, further complicate the problem. Therefore, it may be difficult to find common mechanisms upon which to construct adequate models to predict specific types of systemic hypersensitivity reactions. There is some reason to hope, however, that adequate methods could be developed for at least identifying drugs that have the potential to produce signs indicative of a general hazard for immune-based reactions.

  14. Leukocyte Agglomeration Reaction in Diagnosis of Allergy Reactions from Antibiotics,

    DTIC Science & Technology

    tested in a clinic on 80 patients with serious allergic anamnesis . The results of the studies indicate that the leukocyte agglomeration reaction is a highly sensitive immunological indicator of hypersensitivity to antibiotics.

  15. Hypersensitivity pneumonitis: an immunopathology review.

    PubMed

    Woda, Bruce A

    2008-02-01

    Hypersensitivity pneumonitis (HSP) is an immunologically mediated alveolar and interstitial lung disease caused by repeated inhalation of organic dusts and some occupational agents. The pathogenesis of HSP is uncertain. A number of unexplained features of HSP remain, namely (1) why do so few exposed individuals develop clinical HSP, (2) what triggers an acute episode after prolonged periods of previous sensitization, and (3) what leads to disease progression. This article considers these issues and aims to discuss and clarify current concepts in pathogenesis. Pertinent literature review in conjunction with the author's personal interpretive opinion. Current data suggest that individuals with a T(H)1 dominant response are likely to develop clinical disease. There is also some evidence that genetic factors such as polymorphisms in the major histocompatibility complex, tumor necrosis factor alpha, and tissue inhibitor of metalloproteinase 3 are associated with the development of or resistance to the disease.

  16. Genome-wide analysis links NFATC2 with asparaginase hypersensitivity

    PubMed Central

    Fernandez, Christian A.; Smith, Colton; Yang, Wenjian; Mullighan, Charles G.; Qu, Chunxu; Larsen, Eric; Bowman, W. Paul; Liu, Chengcheng; Ramsey, Laura B.; Chang, Tamara; Karol, Seth E.; Loh, Mignon L.; Raetz, Elizabeth A.; Winick, Naomi J.; Hunger, Stephen P.; Carroll, William L.; Jeha, Sima; Pui, Ching-Hon; Evans, William E.; Devidas, Meenakshi

    2015-01-01

    Asparaginase is used to treat acute lymphoblastic leukemia (ALL); however, hypersensitivity reactions can lead to suboptimal asparaginase exposure. Our objective was to use a genome-wide approach to identify loci associated with asparaginase hypersensitivity in children with ALL enrolled on St. Jude Children’s Research Hospital (SJCRH) protocols Total XIIIA (n = 154), Total XV (n = 498), and Total XVI (n = 271), or Children’s Oncology Group protocols POG 9906 (n = 222) and AALL0232 (n = 2163). Germline DNA was genotyped using the Affymetrix 500K, Affymetrix 6.0, or the Illumina Exome BeadChip array. In multivariate logistic regression, the intronic rs6021191 variant in nuclear factor of activated T cells 2 (NFATC2) had the strongest association with hypersensitivity (P = 4.1 × 10−8; odds ratio [OR] = 3.11). RNA-seq data available from 65 SJCRH ALL tumor samples and 52 Yoruba HapMap samples showed that samples carrying the rs6021191 variant had higher NFATC2 expression compared with noncarriers (P = 1.1 × 10−3 and 0.03, respectively). The top ranked nonsynonymous polymorphism was rs17885382 in HLA-DRB1 (P = 3.2 × 10−6; OR = 1.63), which is in near complete linkage disequilibrium with the HLA-DRB1*07:01 allele we previously observed in a candidate gene study. The strongest risk factors for asparaginase allergy are variants within genes regulating the immune response. PMID:25987655

  17. Plasma and intracellular ribavirin concentrations are not significantly altered by abacavir in hepatitis C virus-infected patients.

    PubMed

    Fuchs, Edward J; Kiser, Jennifer J; Hendrix, Craig W; Sulkowski, Mark; Radebaugh, Christine; Bushman, Lane; Ray, Michelle L; Andrade, Adriana

    2016-06-01

    The objective of this study was to evaluate the effects of abacavir on intracellular ribavirin triphosphate and plasma ribavirin trough concentrations. Hepatitis C virus-infected subjects who had been cured or failed prior treatment were randomized to 8 weeks of ribavirin alone (N = 14; weight-based dosing) or weight-based ribavirin + abacavir (N = 14; 300 mg orally every 12 h). Ribavirin trough concentrations were measured on days 14, 28, 42 and 56; PBMCs for ribavirin triphosphate determination were sampled on days 28 and 56, pre-dose and at 6 and 12 h post-dose. ClinicalTrials.gov: NCT01052701. Twenty-six subjects completed the study (24 males, 17 Caucasians, median age 52 years); 2 were excluded for missed pharmacokinetic visits. Fourteen subjects received ribavirin + abacavir and 12 received ribavirin alone. Mean ± SD plasma ribavirin trough concentrations (μg/mL) on days 14, 28, 42 and 56, respectively, were not significantly different with coadministration of abacavir (1.54 ± 0.60, 1.93 ± 0.54, 2.14 ± 0.73 and 2.54 ± 1.05) compared with ribavirin alone (1.48 ± 0.32, 2.08 ± 0.41, 2.32 ± 0.47 and 2.60 ± 0.62) (P > 0.40). Mean ribavirin triphosphate intracellular concentrations (pmol/10(6) cells) on days 28 and 56, respectively, did not differ statistically between abacavir users (11.98 ± 9.86 and 15.87 ± 12.52) and non-users (15.91 ± 15.58 and 15.93 ± 12.69) (P > 0.4). Adverse events were mild or moderate, except for three grade 3 occurrences of transaminitis, cholecystitis and low absolute neutrophil count that resolved and were judged not attributable to study medications. Abacavir did not significantly alter ribavirin or ribavirin triphosphate concentrations. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Plasma and intracellular ribavirin concentrations are not significantly altered by abacavir in hepatitis C virus-infected patients

    PubMed Central

    Fuchs, Edward J.; Kiser, Jennifer J.; Hendrix, Craig W.; Sulkowski, Mark; Radebaugh, Christine; Bushman, Lane; Ray, Michelle L.; Andrade, Adriana

    2016-01-01

    Objectives The objective of this study was to evaluate the effects of abacavir on intracellular ribavirin triphosphate and plasma ribavirin trough concentrations. Methods Hepatitis C virus-infected subjects who had been cured or failed prior treatment were randomized to 8 weeks of ribavirin alone (N = 14; weight-based dosing) or weight-based ribavirin + abacavir (N = 14; 300 mg orally every 12 h). Ribavirin trough concentrations were measured on days 14, 28, 42 and 56; PBMCs for ribavirin triphosphate determination were sampled on days 28 and 56, pre-dose and at 6 and 12 h post-dose. ClinicalTrials.gov: NCT01052701. Results Twenty-six subjects completed the study (24 males, 17 Caucasians, median age 52 years); 2 were excluded for missed pharmacokinetic visits. Fourteen subjects received ribavirin + abacavir and 12 received ribavirin alone. Mean ± SD plasma ribavirin trough concentrations (μg/mL) on days 14, 28, 42 and 56, respectively, were not significantly different with coadministration of abacavir (1.54 ± 0.60, 1.93 ± 0.54, 2.14 ± 0.73 and 2.54 ± 1.05) compared with ribavirin alone (1.48 ± 0.32, 2.08 ± 0.41, 2.32 ± 0.47 and 2.60 ± 0.62) (P > 0.40). Mean ribavirin triphosphate intracellular concentrations (pmol/106 cells) on days 28 and 56, respectively, did not differ statistically between abacavir users (11.98 ± 9.86 and 15.87 ± 12.52) and non-users (15.91 ± 15.58 and 15.93 ± 12.69) (P > 0.4). Adverse events were mild or moderate, except for three grade 3 occurrences of transaminitis, cholecystitis and low absolute neutrophil count that resolved and were judged not attributable to study medications. Conclusions Abacavir did not significantly alter ribavirin or ribavirin triphosphate concentrations. PMID:26869690

  19. Development and characterization of a long-acting nanoformulated abacavir prodrug

    PubMed Central

    Singh, Dhirender; McMillan, JoEllyn; Hilaire, James; Gautam, Nagsen; Palandri, Diana; Alnouti, Yazen; Gendelman, Howard E; Edagwa, Benson

    2016-01-01

    Aim: A myristoylated abacavir (ABC) prodrug was synthesized to extend drug half-life and bioavailability. Methods: Myristoylated ABC (MABC) was made by esterifying myristic acid to the drug's 5-hydroxy-cyclopentene group. Chemical composition, antiretroviral activity, cell uptake and retention and cellular trafficking of free MABC and poloxamer nanoformulations of MABC were assessed by proton nuclear magnetic resonance and tested in human monocyte-derived macrophages. Pharmacokinetics of ABC and nanoformulated MABC were evaluated after intramuscular injection into mice. Results: MABC antiretroviral activity in monocyte-derived macrophages was comparable to native drug. Encasement of MABC into poloxamer nanoparticles extended drug bioavailability for 2 weeks. Conclusion: MABC synthesis and encasement in polymeric nanoformulations improved intracellular drug accumulation and demonstrate translational potential as part of a long-acting antiretroviral regimen. PMID:27456759

  20. Development and characterization of a long-acting nanoformulated abacavir prodrug.

    PubMed

    Singh, Dhirender; McMillan, JoEllyn; Hilaire, James; Gautam, Nagsen; Palandri, Diana; Alnouti, Yazen; Gendelman, Howard E; Edagwa, Benson

    2016-08-01

    A myristoylated abacavir (ABC) prodrug was synthesized to extend drug half-life and bioavailability. Myristoylated ABC (MABC) was made by esterifying myristic acid to the drug's 5-hydroxy-cyclopentene group. Chemical composition, antiretroviral activity, cell uptake and retention and cellular trafficking of free MABC and poloxamer nanoformulations of MABC were assessed by proton nuclear magnetic resonance and tested in human monocyte-derived macrophages. Pharmacokinetics of ABC and nanoformulated MABC were evaluated after intramuscular injection into mice. MABC antiretroviral activity in monocyte-derived macrophages was comparable to native drug. Encasement of MABC into poloxamer nanoparticles extended drug bioavailability for 2 weeks. MABC synthesis and encasement in polymeric nanoformulations improved intracellular drug accumulation and demonstrate translational potential as part of a long-acting antiretroviral regimen.

  1. Hypothesis on how to measure electromagnetic hypersensitivity.

    PubMed

    Tuengler, Andreas; von Klitzing, Lebrecht

    2013-09-01

    Electromagnetic hypersensitivity (EHS) is an ill-defined term to describe the fact that people who experience health symptoms in the vicinity of electromagnetic fields (EMFs) regard them as causal for their complaints. Up to now most scientists assume a psychological cause for the suffering of electromagnetic hypersensitive individuals. This paper addresses reasons why most provocation studies could not find any association between EMF exposure and EHS and presents a hypothesis on diagnosis and differentiation of this condition. Simultaneous recordings of heart rate variability, microcirculation and electric skin potentials are used for classification of EHS. Thus, it could be possible to distinguish "genuine" electromagnetic hypersensitive individuals from those who suffer from other conditions.

  2. Should patients with risk factors be tested for hypersensitivity to contrast media: a prospective study.

    PubMed

    Tepetam, Fatma Merve; Çiftaslan, Nezihe; Oruç, Özlem; Duman, Dildar; Ağca, Meltem; Bulut, İsmet; Çolakoğlu, Bahattin

    2016-08-01

    Previous hypersensitivity reactions to contrast media (CM), atopy, atopic disease, drug allergy, and age (20-29 or >55) are risk factors for CM hypersensitivity reactions. Our aim was to evaluate whether these risk factors should prompt skin testing for diagnosing CM allergy. The study was conducted among patients referred for allergy testing with CM. Skin tests were performed with non ionic or gadolinium CM, recommended by a radiologist. After completion of tests patients were telephonically queried on their symptoms of reactions. 151 risk patients (53 men, 98 women; mean age 55.2) were included in the study. Only 13 (9 %) had a history of hypersensitivity reaction to CM. Compared with the other patients, atopy was significantly more common in patients with a history of CM hypersensitivity reactions. Female gender and mean age were also higher, but not significant. All of the tests with CMs were negative. Only one patient reported urticaria within 1-2 min after administration of CM (telephonically). Atopy can increase the risk of CM allergy. However, skin tests with CMs may be inefficient, unnecessary, and time-consuming, except in cases with a history of CM allergy. Premedication protocols appear to be beneficial in patients with a history of CM allergy and cannot be recommended for patients with well-controlled asthma, rhinitis, atopic dermatitis or history of drug allergy.

  3. Hypersensitivity pneumonitis: a complex lung disease.

    PubMed

    Riario Sforza, Gian Galeazzo; Marinou, Androula

    2017-01-01

    Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is a respiratory syndrome involving the lung parenchyma and specifically the alveoli, terminal bronchioli, and alveolar interstitium, due to a delayed allergic reaction. Such reaction is secondary to a repeated and prolonged inhalation of different types of organic dusts or other substances to which the patient is sensitized and hyper responsive, primarily consisting of organic dusts of animal or vegetable origin, more rarely from chemicals. The prevalence of HP is difficult to evaluate because of uncertainties in detection and misdiagnosis and lacking of widely accepted diagnostic criteria, and varies considerably depending on disease definition, diagnostic methods, exposure modalities, geographical conditions, agricultural and industrial practices, and host risk factors. HP can be caused by multiple agents that are present in work places and in the home, such as microbes, animal and plant proteins, organic and inorganic chemicals. The number of environment, settings and causative agents is increasing over time. From the clinical point of view HP can be divided in acute/subacute and chronic, depending on the intensity and frequency of exposure to causative antigens. The mainstay in managing HP is the avoidance of the causative antigen, though the complete removal is not always possible due to the difficulties to identify the agent or because its avoidance may lead to major changes in life style or occupational settings. HP is a complex syndrome that needs urgently for more stringent and selective diagnostic criteria and validation, including wider panels of IgG, and a closer collaboration with occupational physicians, as part of a multidisciplinary expertise.

  4. Burning mouth syndrome: the role of contact hypersensitivity.

    PubMed

    Marino, R; Capaccio, P; Pignataro, L; Spadari, F

    2009-05-01

    Burning mouth syndrome is a burning sensation or stinging disorder affecting the oral mucosa in the absence of any clinical signs or mucosal lesions. Some studies have suggested that burning mouth syndrome could be caused by the metals used in dental prostheses, as well as by acrylate monomers, additives and flavouring agents, although others have not found any aetiologic role for hypersensitivity to dental materials. To evaluate the extent and severity of adverse reactions to dental materials in a group of patients with burning mouth syndrome, and investigate the possible role of contact allergy in its pathogenesis. We prospectively studied 124 consecutive patients with burning mouth syndrome (108 males; mean age 57 years, range 41-83), all of whom underwent allergen patch testing between 2004 and 2007. Sixteen patients (13%) showed positive patch test reactions and were classified as having burning mouth syndrome type 3 or secondary burning mouth syndrome (Lamey's and Scala's classifications). Although we did not find any significant association between the patients and positive patch test reactions, it would be advisable to include hypersensitivity to dental components when evaluating patients experiencing intermittent oral burning without any clinical signs.

  5. Drug Hypersensitivity and Desensitizations: Mechanisms and New Approaches

    PubMed Central

    de las Vecillas Sánchez, Leticia; Alenazy, Leila A.; Garcia-Neuer, Marlene; Castells, Mariana C.

    2017-01-01

    Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS). DS induces a temporary hyporesponsive state by incremental escalation of sub-optimal doses of the offending drug. In vitro models have shown evidence that IgE desensitization is an antigen-specific process which blocks calcium flux, impacts antigen/IgE/FcεRI complex internalization and prevents the acute and late phase reactions as well as mast cell mediator release. Through a “bench to bedside” approach, in vitro desensitization models help elucidate the molecular pathways involved in DS, providing new insights to improved desensitization protocols for all patients. The aim of this review is to summarize up to date information on the drug HSRs, the IgE mediated mechanisms of desensitization, and their clinical applications. PMID:28632196

  6. Sympathoinhibition and hypotension in carotid sinus hypersensitivity

    NASA Technical Reports Server (NTRS)

    Smith, M. L.; Ellenbogen, K. A.; Eckberg, D. L.

    1992-01-01

    Carotid sinus reflex hypersensitivity is a known cause of syncope in humans. The condition is characterized by cardioinhibition and vasodepression, each to varying degrees. The extent and importance of sympathoinhibition has not been determined in patients with carotid sinus hypersensitivity. This study reports on the extent of sympathoinhibition measured directly directly during carotid massage with and without atrioventricular sequential pacing, in a patient with symptomatic carotid sinus reflex hypersensitivity. Carotid massage elicited asystole, hypotension and complete inhibition of muscle sympathetic nerve activity. Carotid massage during atrioventricular pacing produced similar sympathoinhibition, but with minimal hypotension. Therefore, sympathoinhibition did not contribute importantly to the hypotension during carotid massage in the supine position in this patient. Further investigations are required to elucidate the relation of sympathoinhibition to hypotension in patients with carotid sinus hypersensitivity in the upright position.

  7. Effect of Cumulating Exposure to Abacavir on the Risk of Cardiovascular Disease Events in Patients From the Swiss HIV Cohort Study.

    PubMed

    Young, Jim; Xiao, Yongling; Moodie, Erica E M; Abrahamowicz, Michal; Klein, Marina B; Bernasconi, Enos; Schmid, Patrick; Calmy, Alexandra; Cavassini, Matthias; Cusini, Alexia; Weber, Rainer; Bucher, Heiner C

    2015-08-01

    Patients with HIV exposed to the antiretroviral drug abacavir may have an increased risk of cardiovascular disease (CVD). There is concern that this association arises because of a channeling bias. Even if exposure is a risk, it is not clear how that risk changes as exposure cumulates. We assess the effect of exposure to abacavir on the risk of CVD events in the Swiss HIV Cohort Study. We use a new marginal structural Cox model to estimate the effect of abacavir as a flexible function of past exposures while accounting for risk factors that potentially lie on a causal pathway between exposure to abacavir and CVD. A total of 11,856 patients were followed for a median of 6.6 years; 365 patients had a CVD event (4.6 events per 1000 patient-years). In a conventional Cox model, recent--but not cumulative--exposure to abacavir increased the risk of a CVD event. In the new marginal structural Cox model, continued exposure to abacavir during the past 4 years increased the risk of a CVD event (hazard ratio = 2.06; 95% confidence interval: 1.43 to 2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6-36 months caused the greatest increase in risk. Abacavir increases the risk of a CVD event: the effect of exposure is not immediate, rather the risk increases as exposure cumulates over the past few years. This gradual increase in risk is not consistent with a rapidly acting mechanism, such as acute inflammation.

  8. No Risk of Myocardial Infarction Associated With Initial Antiretroviral Treatment Containing Abacavir: Short and Long-Term Results from ACTG A5001/ALLRT

    PubMed Central

    Benson, Constance A.; Zheng, Yu; Koletar, Susan L.; Collier, Ann C.; Lok, Judith J.; Smurzynski, Marlene; Bosch, Ronald J.; Bastow, Barbara; Schouten, Jeffrey T.

    2011-01-01

    Background. Observational and retrospective clinical trial cohorts have reported conflicting results for the association of abacavir use with risk of myocardial infarction (MI), possibly related to issues that may bias estimation of treatment effects, such as time-varying confounders, informative dropout, and cohort loss due to competing events. Methods. We analyzed data from 5056 individuals initiating randomized antiretroviral treatment (ART) in AIDS Clinical Trials Group studies; 1704 started abacavir therapy. An intent-to-treat analysis adjusted for pretreatment covariates and weighting for informative censoring was used to estimate the hazard ratio (HR) of MIs after initiation of a regimen with or without abacavir. Results. Through 6 years after ART initiation, 36 MI events were observed in 17,404 person-years of follow-up. No evidence of an increased hazard of MI in subjects using abacavir versus no abacavir was seen (over a 1-year period: P = .50; HR, 0.7 [95% confidence interval {CI}, 0.2-2.4]); over a 6-year period: P = .24; HR, 0.6 [95% CI, 0.3-1.4]); these results were robust over as-treated and sensitivity analyses. Although the risk of MI decreased over time, there was no evidence to suggest a time-dependent abacavir effect. Classic cardiovascular disease (CVD) risk factors were the strongest predictors of MI. Conclusion. We find no evidence to suggest that initial ART containing abacavir increases MI risk over short-term and long-term periods in this population with relatively low MI risk. Traditional CVD risk factors should be the main focus in assessing CVD risk in individuals with human immunodeficiency virus infection. PMID:21427402

  9. No risk of myocardial infarction associated with initial antiretroviral treatment containing abacavir: short and long-term results from ACTG A5001/ALLRT.

    PubMed

    Ribaudo, Heather J; Benson, Constance A; Zheng, Yu; Koletar, Susan L; Collier, Ann C; Lok, Judith J; Smurzynski, Marlene; Bosch, Ronald J; Bastow, Barbara; Schouten, Jeffrey T

    2011-04-01

    Observational and retrospective clinical trial cohorts have reported conflicting results for the association of abacavir use with risk of myocardial infarction (MI), possibly related to issues that may bias estimation of treatment effects, such as time-varying confounders, informative dropout, and cohort loss due to competing events. We analyzed data from 5056 individuals initiating randomized antiretroviral treatment (ART) in AIDS Clinical Trials Group studies; 1704 started abacavir therapy. An intent-to-treat analysis adjusted for pretreatment covariates and weighting for informative censoring was used to estimate the hazard ratio (HR) of MIs after initiation of a regimen with or without abacavir. Through 6 years after ART initiation, 36 MI events were observed in 17,404 person-years of follow-up. No evidence of an increased hazard of MI in subjects using abacavir versus no abacavir was seen (over a 1-year period: P=.50; HR, 0.7 [95% confidence interval {CI}, 0.2-2.4]); over a 6-year period: P=.24; HR, 0.6 [95% CI, 0.3-1.4]); these results were robust over as-treated and sensitivity analyses. Although the risk of MI decreased over time, there was no evidence to suggest a time-dependent abacavir effect. Classic cardiovascular disease (CVD) risk factors were the strongest predictors of MI. We find no evidence to suggest that initial ART containing abacavir increases MI risk over short-term and long-term periods in this population with relatively low MI risk. Traditional CVD risk factors should be the main focus in assessing CVD risk in individuals with human immunodeficiency virus infection. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

  10. Cockatiel-induced hypersensitivity pneumonitis.

    PubMed

    McCluskey, James D; Haight, Robert R; Brooks, Stuart M

    2002-07-01

    Diagnosing an environmental or occupationally related pulmonary disorder often involves a process of elimination. Unlike commonly diagnosed conditions in other specialties, a cause-and-effect relationship may be implied, yet other factors such as temporality and biologic plausibility are lacking. Our patient was referred with a suspected work-related pulmonary disorder. For several years, she had suffered with dyspnea on exertion and repeated flulike illnesses. She worked at an automobile repair garage that performed a large number of emission tests, and there was concern that her workplace exposures were the cause of her symptoms. After a careful review of her history, physical examination, and laboratory testing, we came to the conclusion that she had hypersensitivity pneumonitis related to pet cockatiels in her home. Clinical points of emphasis include the importance of a complete environmental history and careful auscultation of the chest when performing the physical examination. In addition, we encountered an interesting physical diagnostic clue, a respiratory sound that assisted with the eventual diagnosis.

  11. Cockatiel-induced hypersensitivity pneumonitis.

    PubMed Central

    McCluskey, James D; Haight, Robert R; Brooks, Stuart M

    2002-01-01

    Diagnosing an environmental or occupationally related pulmonary disorder often involves a process of elimination. Unlike commonly diagnosed conditions in other specialties, a cause-and-effect relationship may be implied, yet other factors such as temporality and biologic plausibility are lacking. Our patient was referred with a suspected work-related pulmonary disorder. For several years, she had suffered with dyspnea on exertion and repeated flulike illnesses. She worked at an automobile repair garage that performed a large number of emission tests, and there was concern that her workplace exposures were the cause of her symptoms. After a careful review of her history, physical examination, and laboratory testing, we came to the conclusion that she had hypersensitivity pneumonitis related to pet cockatiels in her home. Clinical points of emphasis include the importance of a complete environmental history and careful auscultation of the chest when performing the physical examination. In addition, we encountered an interesting physical diagnostic clue, a respiratory sound that assisted with the eventual diagnosis. PMID:12117652

  12. Ablation of type I hypersensitivity in experimental allergic conjunctivitis by eotaxin-1/CCR3 blockade

    PubMed Central

    Nakamura, Takao; Ohbayashi, Masaharu; Kuo, Chuan Hui; Komatsu, Naoki; Yakura, Keiko; Tominaga, Takeshi; Inoue, Yoshitsugu; Higashi, Hidemitsu; Murata, Meguru; Takeda, Shuzo; Fukushima, Atsuki; Liu, Fu-Tong; Rothenberg, Marc E.; Ono, Santa Jeremy

    2009-01-01

    The immune response is regulated, in part, by effector cells whose activation requires multiple signals. For example, T cells require signals emanating from the T cell antigen receptor and co-stimulatory molecules for full activation. Here, we present evidence indicating that IgE-mediated hypersensitivity reactions in vivo also require cognate signals to activate mast cells. Immediate hypersensitivity reactions in the conjunctiva are ablated in mice deficient in eotaxin-1, despite normal numbers of tissue mast cells and levels of IgE. To further define the co-stimulatory signals mediated by chemokine receptor 3 (CCR3), an eotaxin-1 receptor, effects of CCR3 blockade were tested with an allergic conjunctivitis model and in ex vivo isolated connective tissue-type mast cells. Our results show that CCR3 blockade significantly suppresses allergen-mediated hypersensitivity reactions as well as IgE-mediated mast cell degranulation. We propose that a co-stimulatory axis by CCR3, mainly stimulated by eotaxin-1, is pivotal in mast cell-mediated hypersensitivity reactions. PMID:19147836

  13. The potential utility of iodinated contrast media (ICM) skin testing in patients with ICM hypersensitivity.

    PubMed

    Ahn, Young-Hwan; Koh, Young-Il; Kim, Joo-Hee; Ban, Ga-Young; Lee, Yeon-Kyung; Hong, Ga-Na; Jin, U-Ram; Choi, Byung-Joo; Shin, Yoo-Seob; Park, Hae-Sim; Ye, Young-Min

    2015-03-01

    Both immediate and delayed hypersensitivity reactions to iodinated contrast media (ICM) are relatively common. However, there are few data to determine the clinical utility of immunologic evaluation of ICM. To evaluate the utility of ICM skin testing in patients with ICM hypersensitivity, 23 patients (17 immediate and 6 delayed reactions) were enrolled from 3 university hospitals in Korea. With 6 commonly used ICM including iopromide, iohexol, ioversol, iomeprol, iopamidol and iodixanol, skin prick (SPT), intradermal (IDT) and patch tests were performed. Of 10 patients with anaphylaxis, 3 (30.0%) and 6 (60.0%) were positive respectively on SPTs and IDTs with the culprit ICM. Three of 6 patients with urticaria showed positive IDTs. In total, 11 (64.7%) had positive on either SPT or IDT. Three of 6 patients with delayed rashes had positive response to patch test and/or delayed IDT. Among 5 patients (3 anaphylaxis, 1 urticaria and 1 delayed rash) taken subsequent radiological examinations, 3 patients administered safe alternatives according to the results of skin testing had no adverse reaction. However, anaphylaxis developed in the other 2 patients administered the culprit ICM again. With 64.7% (11/17) and 50% (3/6) of the sensitivities of corresponding allergic skin tests with culprit ICM for immediate and delayed hypersensitivity reactions, the present study suggests that skin tests is useful for the diagnosis of ICM hypersensitivity and for selecting safe ICM and preventing a recurrence of anaphylaxis caused by the same ICM.

  14. Plasma pharmacokinetics of once-daily abacavir- and lamivudine-containing regimens and week 96 efficacy in HIV-infected Thai children.

    PubMed

    Bunupuradah, Torsak; Punyahotra, Passorn; Cressey, Tim R; Srimuan, Amornrat; Thammajaruk, Narukjaporn; Sophonphan, Jiratchaya; Sriheara, Chulalak; Burger, David M; Puthanakit, Thanyawee; Ananworanich, Jintanat

    2015-07-01

    Abacavir and lamivudine are approved for once-daily use in HIV-infected adults. Limited pharmacokinetic (PK) data for abacavir and lamivudine in children are available. A crossover study to compare PK of once- versus twice-daily abacavir and lamivudine was conducted in virologically suppressed HIV-infected Thai children aged <18years, with bodyweight of at least 14 kg, HIV RNA <50 copies/mL and HLA-B*5701 negative. Abacavir and lamivudine daily doses by bodyweight were 300 and 150 mg for 14-<20 kg, 450 and 300 mg for 20-<25 kg, and 600 and 300 mg for ≥25 kg, respectively. Originator abacavir and lamivudine scored tablets were administered. Intensive PK sampling was performed after 14 days of each dose. PK parameters were determined using non-compartmental analysis. Thirty children (57% male) were enrolled, 10 per weight band. Median (IQR) age was 8.8 (6.6-11.3) years and bodyweight was 21.9 (19.2-30.6) kg. The geometric means (GM) AUC0-24 of once- and twice-daily abacavir were 14.43 and 10.65 mg.h/L, respectively. The geometric mean ratio (GMR) of AUC0-24 for once- versus twice-daily abacavir dosing was 1.36 [90% confidence interval (CI) 1.11-1.66]. The GM AUC0-24 of once- and twice-daily lamivudine were 17.70 and 18.11 mg.h/L, respectively. The GMR of AUC0-24 for once- versus twice-daily lamivudine dosing was 0.98 (90% CI 0.84-1.14). At 96 weeks, 90% had HIV RNA <50 copies/mL and there were no serious adverse events. Abacavir exposure was greater with once-daily dosing, while lamivudine once- and twice-daily exposures were bioequivalent. Once-daily abacavir and lamivudine using weight-band dosing is a treatment option for children.

  15. Investigation of the Role of Breast Cancer Resistance Protein (Bcrp/Abcg2) on Pharmacokinetics and Central Nervous System Penetration of Abacavir and Zidovudine in the Mouse

    PubMed Central

    Giri, Nagdeep; Shaik, Naveed; Pan, Guoyu; Terasaki, Tetsuya; Mukai, Chisato; Kitagaki, Shinji; Miyakoshi, Naoki; Elmquist, William F.

    2016-01-01

    Many anti-human immunodeficiency virus 1 nucleoside reverse-transcriptase inhibitors have low central nervous system (CNS) distribution due in part to active efflux transport at the blood-brain barrier. We have previously shown that zidovudine (AZT) and abacavir (ABC) are in vitro substrates for the efflux transport protein breast cancer resistance protein (Bcrp) 1. We evaluated the influence of Bcrp1 on plasma pharmacokinetics and brain penetration of zidovudine and abacavir in wild-type and Bcrp1-deficient (Bcrp1−/−) FVB mice. There was no difference in either area under the concentration-time profiles for plasma (AUCplasma) or brain (AUCbrain) for zidovudine between the wild-type and Bcrp1−/− mice. The AUCplasma of abacavir was 20% lower in the Bcrp1−/− mice, whereas the AUCbrain was 20% greater. This difference resulted in a 1.5-fold increase in abacavir brain exposure in the Bcrp1−/− mice. The effect of selective and nonselective transport inhibitors on the ABC brain/plasma ratio at a single time point was evaluated. 3-(6-Isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indol-3-yl)-propionicacid tert-butyl ester (Ko143), N[4[2-(6, 7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]phenyl]-5-methoxy-9-oxo-10H-acridine-4-carboxamide (GF120918), probenecid, and Pluronic P85 increased abacavir plasma concentrations in the wild-type mice. Abacavir plasma concentrations in Bcrp1−/− mice were increased by (R)-4-((1aR,6R,10bS)-1,2-difluoro-1,1a,6,10b-tetrahydrodibenzo(a,e)cyclopropa(c)cycloheptan-6-yl)-α-((5-quinoloyloxy)methyl)-1-piperazineethanol trihydrochloride (LY335979), GF120918, and probenecid, but not by Ko143. Brain/plasma concentration ratios in both the wild-type and Bcrp1−/− mice were increased by the P-glycoprotein inhibitors LY335979 and GF120918, but not by BCRP-selective inhibitors. These data indicate that deletion of Bcrp1 has little influence on the pharmacokinetics or brain

  16. Pharmacokinetic study of once–daily versus twice-daily abacavir and lamivudine in HIV type-1-infected children aged 3–<36 months

    PubMed Central

    2013-01-01

    Background Once-daily dosing of abacavir and lamivudine has been approved for adults, but paediatric data are insufficient. We conducted a pharmacokinetic study of once-daily and twice-daily abacavir and lamivudine in children aged 3–<36 months. Methods Children with stable HIV type-1 (HIV-1) RNA levels after 12 weeks treatment with twice-daily abacavir (8 mg/kg) with or without lamivudine (4 mg/kg) underwent plasma pharmacokinetic sampling. Children then switched to once-daily abacavir (16 mg/kg) with or without lamivudine (8 mg/kg), and sampling was repeated 4 weeks later. The area under the plasma concentration–time curve over 24 h (AUC0–24) and the maximum concentration (Cmax) were compared using geometric mean ratios (GMRs); 90% confidence intervals (CIs) within the range of 0.80–1.25 were considered bioequivalent. Results A total of 18 children (4, 6 and 8 in the 3–<12, 12–<24 and 24–<36 month age ranges, respectively) provided pharmacokinetic data for abacavir (17 for lamivudine). The GMR of AUC0–24, once-daily versus twice-daily, was 1.07 (90% CI 0.92–1.23) for abacavir and 0.91 (90% CI 0.79–1.06) for lamivudine. Cmax almost doubled on once-daily versus twice-daily dosing: abacavir and lamivudine GMRs were 2.04 (90% CI 1.73–2.42) and 1.78 (90% CI 1.52–2.09), respectively. At baseline, 12, 24 and 48 weeks, 89%, 94%, 100% and 89% of children had HIV-1 RNA<400 copies/ml, respectively. Conclusions Bioequivalence was demonstrated on AUC0–24 between twice-daily and once-daily abacavir; very similar AUC0–24 values were seen for twice-daily and once-daily lamivudine. Given that viral load suppression rates were maintained, these data suggest that once-daily abacavir and lamivudine might be an option for children aged 3–<36 months. PMID:20516550

  17. Seven Steps to the Diagnosis of NSAIDs Hypersensitivity: How to Apply a New Classification in Real Practice?

    PubMed Central

    Makowska, Joanna S.

    2015-01-01

    Frequent use of non-steroidal anti-inflammatory drugs (NSAIDs) has been paralleled by increasing occurrence of adverse reactions, which vary from mild local skin rashes or gastric irritation to severe, generalized symptoms and even life-threatening anaphylaxis. NSAID-induced hypersensitivity reactions may involve both immunological and non-immunological mechanisms and should be differentiated from type A adverse reactions. Clinical diagnosis and effective management of a hypersensitive patient cannot be achieved without identifying the underlying mechanism. In this review, we discuss the current classification of NSAID-induced adverse reactions and propose a practical diagnostic algorithm that involves 7 steps leading to the determination of the type of NSAID-induced hypersensitivity and allows for proper patient management. PMID:25749768

  18. Practical Management of Patients with a History of Immediate Hypersensitivity to Common non-Beta-Lactam Drugs.

    PubMed

    Macy, Eric

    2016-01-01

    Immediate hypersensitivity reactions to medications are among the most feared adverse drug reactions, because of their close association with anaphylaxis. This review discusses a practical management approach for patients with a history of an immediate hypersensitivity to a non-beta-lactam medication, where reexposure to the implicated, or similar, medication is clinically necessary. Mechanisms associated with severe immediate hypersensitivity reactions include IgE-mediated mast cell activation, complement-mediated mast cell activation, and direct mast cell activation. Immediate hypersensitivity reactions may also be mediated by vasodilators, other pharmacologic mechanisms, or be secondary to underlying patient-specific biochemical abnormalities such as endocrine tumors or chronic spontaneous urticaria. The key features in the reaction history and the biochemistry of the implicated medication are discussed. Most individuals with a history of immediate hypersensitivity to a medication, who require reuse of that drug, can be safely retreated with a therapeutic course of the implicated drug after a full-dose challenge, graded challenge, or desensitization, with or without premedication and/or any preliminary diagnostic testing, depending on the specific situation.

  19. Brief Report: Dolutegravir Plus Abacavir/Lamivudine for the Treatment of HIV-1 Infection in Antiretroviral Therapy-Naive Patients: Week 96 and Week 144 Results From the SINGLE Randomized Clinical Trial.

    PubMed

    Walmsley, Sharon; Baumgarten, Axel; Berenguer, Juan; Felizarta, Franco; Florence, Eric; Khuong-Josses, Marie-Aude; Kilby, J Michael; Lutz, Thomas; Podzamczer, Daniel; Portilla, Joaquin; Roth, Norman; Wong, Deborah; Granier, Catherine; Wynne, Brian; Pappa, Keith

    2015-12-15

    The SINGLE study was a randomized, double-blind, noninferiority study that evaluated the safety and efficacy of 50 mg dolutegravir + abacavir/lamivudine versus efavirenz/tenofovir/emtricitabine in 833 ART-naive HIV-1 + participants. Of 833 randomized participants, 71% in the dolutegravir + abacavir/lamivudine arm and 63% in the efavirenz/tenofovir/emtricitabine arm maintained viral loads of <50 copies per milliliter through W144 (P = 0.01). Superior efficacy was primarily driven by fewer discontinuations due to adverse events in the dolutegravir + abacavir/lamivudine arm [dolutegravir + abacavir/lamivudine arm, 16 (4%); efavirenz/tenofovir/emtricitabine arm, 58 (14%)] through W144 [corrected]. No treatment-emergent integrase or nucleoside resistance was observed in dolutegravir + abacavir/lamivudine recipients through W144.

  20. Lung Transplantation for Hypersensitivity Pneumonitis

    PubMed Central

    Singer, Jonathan P.; Koth, Laura; Mooney, Joshua; Golden, Jeff; Hays, Steven; Greenland, John; Wolters, Paul; Ghio, Emily; Jones, Kirk D.; Leard, Lorriana; Kukreja, Jasleen; Blanc, Paul D.

    2015-01-01

    BACKGROUND: Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF). METHODS: To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling. RESULTS: We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts. CONCLUSIONS: Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft. PMID:25412059

  1. Hypersensitive prostaglandin and thromboxane response to hormones in rabbit colitis

    SciTech Connect

    Zipser, R.D.; Patterson, J.B.; Kao, H.W.

    1985-10-01

    Inflammation of the colon is associated with increased production of prostaglandins (PG) and thromboxanes (Tx), and these eicosanoids may contribute to the inflammatory, secretory, and motility dysfunctions in colitis. To evaluate the potential role of peptide hormones in the enhanced eicosanoid release, colitis was established in rabbits by a delayed-type hypersensitivity reaction to dinitrochlorobenzene and by an immune-complex-mediated reaction. PG and Tx were identified in the venous effluent of isolated perfused colons by radiochromatography after ( UC)arachidonic acid prelabeling, as well as by bioassay, and then quantitated by immunoassay. The two colitis models were morphologically similar. Basal release of PGE2,more » PGI2, and TxA2 was two- to threefold greater from colitis tissue than from control tissue. Bradykinin (BK) and angiotensin II (ANG II) increased release of UC-labeled eicosanoids, whereas several gastrointestinal hormones had no effect. In control colons, BK and ANG II increased PGE2 and PGI2 release (by about 2-fold) but did not alter TxA2. In contrast, BK and ANG II markedly exaggerated the release of eicosanoids in colitis. Since BK and possibly ANG II are increased at sites of inflammation, the hypersensitive eicosanoid response to these peptides may augment the eicosanoid-mediated manifestations of colitis.« less

  2. Immediate Type Hypersensitivity to Heparins: Two Case Reports and a Review of the Literature.

    PubMed

    Cesana, Philipp; Scherer, Kathrin; Bircher, Andreas J

    2016-01-01

    Immediate type hypersensitivity reactions due to heparins are rare, and the exact immunologic pathomechanism has not been identified so far. In our 2 case reports, we describe first a 50-year-old female who received dalteparin (Fragmin®) and developed signs of an immediate type hypersensitivity reaction. The personal history revealed a previous application of dalteparin (Fragmin®). Evaluation with a skin prick test showed positive results for dalteparin. The second case deals with a 73-year-old female with a suspected immediate type reaction after the administration of dalteparin (Fragmin®). A skin prick test was negative but intracutaneous tests showed a positive reaction to the causative agent. Both cases indicated cross-reactivity reactions for low-molecular-weight heparin (LMWH) but not for unfractioned heparin (UFH) or fondaparinux. In conclusion, our case reports including a review of published cases of immediate type hypersensitivity reactions after the application of heparins illustrate this rare complication. Mostly, the causative agent can be identified with a skin test, which is highly suggestive of an IgE-mediated reaction. Therapeutic alternatives for patients with sensitization to an LMWH are UFH and fondaparinux. Both agents have a small risk of cross-reactivity compared to heparins of the same substance class. © 2017 S. Karger AG, Basel.

  3. [Preventive dentistry 3. Prevalence, aetiology and diagnosis of dentine (hyper)sensitivity].

    PubMed

    van der Weijden, F N; van Loveren, C; Slot, D E; van der Weijden, G A

    2017-02-01

    Many people sometimes experience pain when they inhale breath across the cingula, or sensitivity and/or pain when they eat ice cream, for example. In some cases, however, this can become seriously unpleasant. In those cases, one can speak of dentine hypersensitivity. In Europe, an average of 27% of the population suffers from this. Dentine hypersensitivity is characterised by a short, sharp pain reaction after a warm or cold sensation. The external sensation causes an accelerated or converse flow of fluid in the dentinal tubules that excites the extremities of the nerve cells, which results in the sensation pain. For the external sensation, it is necessary that the cingula are exposed and the dentinal tubules are open. Dentine hypersensitivity is diagnosed after other possibilities have been eliminated.

  4. Reflux Hypersensitivity: A New Functional Esophageal Disorder

    PubMed Central

    Yamasaki, Takahisa; Fass, Ronnie

    2017-01-01

    Reflux hypersensitivity, recently introduced by Rome IV as a new functional esophageal disorder, is currently considered as the presence of typical heartburn symptoms in patients with normal upper endoscopy and esophageal biopsies, normal esophageal pH test and with evidence of a close correlation between patients’ heartburn and reflux events. Reflux hypersensitivity is very common and together with functional heartburn accounts for more than 90% of the heartburn patients who failed treatment with proton pump inhibitor twice daily. In addition, reflux hypersensitivity affects primarily young to middle aged women, commonly overlaps with another functional gastrointestinal disorders, and is often associated with some type of psychological comorbidity. Diagnosis is made by using endoscopy with esophageal biopsies, pH-impedance, and high-resolution esophageal manometry. Reflux hypersensitivity is primarily treated with esophageal neuromodulators, such as tricyclic anti-depressants and selective serotonin reuptake inhibitors among others. Surgical anti-reflux management may also play an important role in the treatment of reflux hypersensitivity. PMID:28992673

  5. A diagnostic model for chronic hypersensitivity pneumonitis.

    PubMed

    Johannson, Kerri A; Elicker, Brett M; Vittinghoff, Eric; Assayag, Deborah; de Boer, Kaïssa; Golden, Jeffrey A; Jones, Kirk D; King, Talmadge E; Koth, Laura L; Lee, Joyce S; Ley, Brett; Wolters, Paul J; Collard, Harold R

    2016-10-01

    The objective of this study was to develop a diagnostic model that allows for a highly specific diagnosis of chronic hypersensitivity pneumonitis using clinical and radiological variables alone. Chronic hypersensitivity pneumonitis and other interstitial lung disease cases were retrospectively identified from a longitudinal database. High-resolution CT scans were blindly scored for radiographic features (eg, ground-glass opacity, mosaic perfusion) as well as the radiologist's diagnostic impression. Candidate models were developed then evaluated using clinical and radiographic variables and assessed by the cross-validated C-statistic. Forty-four chronic hypersensitivity pneumonitis and eighty other interstitial lung disease cases were identified. Two models were selected based on their statistical performance, clinical applicability and face validity. Key model variables included age, down feather and/or bird exposure, radiographic presence of ground-glass opacity and mosaic perfusion and moderate or high confidence in the radiographic impression of chronic hypersensitivity pneumonitis. Models were internally validated with good performance, and cut-off values were established that resulted in high specificity for a diagnosis of chronic hypersensitivity pneumonitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. A diagnostic model for chronic hypersensitivity pneumonitis

    PubMed Central

    Johannson, Kerri A; Elicker, Brett M; Vittinghoff, Eric; Assayag, Deborah; de Boer, Kaïssa; Golden, Jeffrey A; Jones, Kirk D; King, Talmadge E; Koth, Laura L; Lee, Joyce S; Ley, Brett; Wolters, Paul J; Collard, Harold R

    2017-01-01

    The objective of this study was to develop a diagnostic model that allows for a highly specific diagnosis of chronic hypersensitivity pneumonitis using clinical and radiological variables alone. Chronic hypersensitivity pneumonitis and other interstitial lung disease cases were retrospectively identified from a longitudinal database. High-resolution CT scans were blindly scored for radiographic features (eg, ground-glass opacity, mosaic perfusion) as well as the radiologist’s diagnostic impression. Candidate models were developed then evaluated using clinical and radiographic variables and assessed by the cross-validated C-statistic. Forty-four chronic hypersensitivity pneumonitis and eighty other interstitial lung disease cases were identified. Two models were selected based on their statistical performance, clinical applicability and face validity. Key model variables included age, down feather and/or bird exposure, radiographic presence of ground-glass opacity and mosaic perfusion and moderate or high confidence in the radiographic impression of chronic hypersensitivity pneumonitis. Models were internally validated with good performance, and cut-off values were established that resulted in high specificity for a diagnosis of chronic hypersensitivity pneumonitis. PMID:27245779

  7. Reflux Hypersensitivity: A New Functional Esophageal Disorder.

    PubMed

    Yamasaki, Takahisa; Fass, Ronnie

    2017-10-30

    Reflux hypersensitivity, recently introduced by Rome IV as a new functional esophageal disorder, is currently considered as the presence of typical heartburn symptoms in patients with normal upper endoscopy and esophageal biopsies, normal esophageal pH test and with evidence of a close correlation between patients' heartburn and reflux events. Reflux hypersensitivity is very common and together with functional heartburn accounts for more than 90% of the heartburn patients who failed treatment with proton pump inhibitor twice daily. In addition, reflux hypersensitivity affects primarily young to middle aged women, commonly overlaps with another functional gastrointestinal disorders, and is often associated with some type of psychological comorbidity. Diagnosis is made by using endoscopy with esophageal biopsies, pH-impedance, and high-resolution esophageal manometry. Reflux hypersensitivity is primarily treated with esophageal neuromodulators, such as tricyclic anti-depressants and selective serotonin reuptake inhibitors among others. Surgical anti-reflux management may also play an important role in the treatment of reflux hypersensitivity.

  8. 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV. San Diego, California, USA 22-25 September 2002.

    PubMed

    Nolan, David; Christiansen, Frank

    2003-01-01

    Highlights are presented from this annual workshop, which was devoted to the investigation of adverse effects associated with antiretroviral therapy for HIV infection. Topics covered included the lipodystrophy syndrome, which encompasses body composition changes (subcutaneous fat wasting, visceral fat accumulation) and metabolic abnormalities (insulin resistance and dyslipidaemia). The relevance of HIV protease inhibitor-induced metabolic abnormalities to cardiovascular disease is discussed. Research in the areas of hyperlactataemia, abacavir hypersensitivity, and bone mineral density in the context of HIV infection is also briefly reviewed.

  9. TRPA1 Contributes to Cold Hypersensitivity

    PubMed Central

    Camino, Donato del; Murphy, Sarah; Heiry, Melissa; Barrett, Lee B.; Earley, Taryn J.; Cook, Colby A.; Petrus, Matt J.; Zhao, Michael; D'Amours, Marc; Deering, Nate; Brenner, Gary J.; Costigan, Michael; Hayward, Neil J.; Chong, Jayhong A.; Fanger, Christopher M.; Woolf, Clifford J.; Patapoutian, Ardem; Moran, Magdalene M.

    2010-01-01

    TRPA1 is a non-selective cation channel expressed by nociceptors. While it is widely accepted that TRPA1 serves as a broad irritancy receptor for a variety of reactive chemicals, its role in cold sensation remains controversial. Here, we demonstrate that mild cooling markedly increases agonist-evoked rat TRPA1 currents. In the absence of an agonist, even noxious cold only increases current amplitude slightly. These results suggest that TRPA1 is a key mediator of cold hypersensitivity in pathological conditions where reactive oxygen species and pro-inflammatory activators of the channel are present, but likely plays a comparatively minor role in acute cold sensation. Supporting this, cold hypersensitivity can be induced in wild-type but not Trpa1-/- mice by subcutaneous administration of a TRPA1 agonist. Furthermore, the selective TRPA1 antagonist HC-030031 reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain. PMID:21068322

  10. Entomologic evaluation of insect hypersensitivity in horses.

    PubMed

    Greiner, E C

    1995-04-01

    Potential methods of incriminating insects as the cause of insect hypersensitivity are presented. A listing of the biting midges known to attack horses in North America is presented also. An example of how species may be determined to be the cause of the hypersensitivity is given using data from a recent study in Florida. Light trap collections indicated the temporal and geographic distribution of potential contributing species and collections made by vacuuming horses further delineated species by proving they feed on horses and the correct locations on the horses to match lesion distribution. Culicoides hypersensitivity in horses in Florida seems to be caused by a series of species active and feeding on the horses at different times of the year.

  11. Evaluation of basophil activation test in suspected food hypersensitivity.

    PubMed

    Pignatti, Patrizia; Yacoub, Mona-Rita; Testoni, Claudia; Pala, Gianni; Corsetti, Maura; Colombo, Giselda; Meriggi, Antonio; Moscato, Gianna

    2017-07-01

    Food hypersensitivity is characterized by a wide range of symptoms. The relationship between symptoms and food is more frequently suspected than objectively proven. Basophil activation test (BAT) is based on the evaluation of activation markers on blood basophils in vitro stimulated with drugs or allergens. The aim of the study was to evaluate the usefulness of BAT when introduced in the routine work-up of suspected food hypersensitivity. BAT was requested in subjects with food adverse reactions when a discrepancy existed among history and skin prick test (SPT) and/or specific IgE. Data from 150 subjects were analysed using CD63 as basophil activation marker. Thirty controls were evaluated for cut-offs. Immunoblots was performed with the sera of representative subjects positive for BAT and negative for SPT and sIgE. 1,024 BAT were carried out, the agreement (positive/positive and negative/negative) was 78.5% for BAT vs. SPT and 78.3% for BAT vs. IgE. Atopic patients, but not atopic controls, more frequently had a positive BAT than non-atopic patients (P < 0.0001). Among subjects with positive BAT, those with negative sIgE had lower total IgE, P = 0.001. Nearly 23.3% of all subjects had positive BAT (for at least one tested food) and both negative sIgE and SPT. Immunoblots revealed the presence of sIgE for the tested foods in representative patients with positive BAT, negative SPT and sIgE. Introduction of BAT in routine of food hypersensitivity, limited to subjects with a discrepancy between history and traditional tests, might be useful particularly when total IgE are low. © 2015 International Clinical Cytometry Society. © 2015 International Clinical Cytometry Society.

  12. Population Pharmacokinetics and Pharmacodynamic Modeling of Abacavir (1592U89) from a Dose-Ranging, Double-Blind, Randomized Monotherapy Trial with Human Immunodeficiency Virus-Infected Subjects

    PubMed Central

    Weller, Stephen; Radomski, Kristine M.; Lou, Yu; Stein, Daniel S.

    2000-01-01

    Abacavir (formerly 1592U89) is a carbocyclic nucleoside analog with potent anti-human immunodeficiency virus (anti-HIV) activity when administered alone or in combination with other antiretroviral agents. The population pharmacokinetics and pharmacodynamics of abacavir were investigated in 41 HIV type 1 (HIV-1)-infected, antiretroviral naive adults with baseline CD4+ cell counts of ≥100/mm3 and plasma HIV-1 RNA levels of >30,000 copies/ml. Data for analysis were obtained from patients who received randomized, blinded monotherapy with abacavir at 100, 300, or 600 mg twice-daily (BID) for up to 12 weeks. Plasma abacavir concentrations from sparse sampling were analyzed by standard population pharmacokinetic methods, and the effects of dose, combination therapy, gender, weight, and age on parameter estimates were investigated. Bayesian pharmacokinetic parameter estimates were calculated to determine the peak concentration of abacavir in plasma (Cmax) and the area under the concentration-time curve from time zero to infinity (AUC0–∞) for individual subjects. The pharmacokinetics of abacavir were dose proportional over the 100- to 600-mg dose range and were unaffected by any covariates. No significant correlations were observed between the incidence of the five most common adverse events (headache, nausea, diarrhea, vomiting, and malaise or fatigue) and AUC0–∞. A significant correlation was observed between Cmax and nausea by categorical analysis (P = 0.019), but this was of borderline significance by logistic regression (odds ratio, 1.45; 95% confidence interval, 0.95 to 2.32). The log10 time-averaged AUC0–∞ minus baseline (AAUCMB) values for HIV-1 RNA and CD4+ cell count correlated significantly with Cmax and AUC0–∞, but with better model fits for AUC0–∞. The increase in AAUCMB values for CD4+ cell count plateaued early for drug exposures that were associated with little change in AAUCMB values for plasma HIV-1 RNA. There was less than a 0.4 log

  13. Hypersensitivity to aspirin and urgent percutaneous coronary intervention: A therapeutic challenge.

    PubMed

    Duarte, Tatiana; Gonçalves, Sara; Sá, Catarina; Marinheiro, Rita; Rodrigues, Rita; Seixo, Filipe; Tomas, Elza; Caria, Rui

    2016-11-01

    Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs are common and five types of reactions have been defined. The prevalence of such reactions in patients with myocardial infarction is unclear, and so antiplatelet therapy in this population is a challenge. Various desensitization protocols have been developed but there are no specific guidelines for their use. The authors present the case of a patient with acute coronary syndrome and aspirin hypersensitivity referred for urgent coronary angiography. Aspirin desensitization therapy is safe and successful in many patients, but more randomized trials are needed to confirm its benefits in coronary artery disease patients. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Management of stinging insect hypersensitivity: a 5-year retrospective medical record review.

    PubMed

    Johnson, Thomas; Dietrich, Jeffrey; Hagan, Larry

    2006-08-01

    The Joint Task Force on Practice Parameters for Allergy and Immunology recommends that patients with a history of a systemic reaction to an insect sting be educated on ways to avoid insect stings, carry injectable epinephrine for emergency self-treatment, undergo specific IgE testing for stinging insect sensitivity, and be considered for immunotherapy. To review frontline providers' documented care and recommendations for imported fire ant and flying insect hypersensitivity reactions. A retrospective medical record review was performed of emergency department and primary care clinic visits between November 1, 1999, and November 30, 2004. Using International Classification of Diseases, Ninth Revision, codes, medical records were selected for review to identify patients with potential insect hypersensitivity. A total of 769 medical records from patients who experienced an insect sting were reviewed. Of 120 patients with a systemic reaction, 66 (55.0%) received a prescription for injectable epinephrine, and 14 (11.7%) were given information regarding avoidance of the offending insect. Forty-seven patients with systemic reactions (39.2%) were referred to an allergist. Of 28 patients who kept their appointments and underwent skin testing, 3 had negative results and 25 (89%) had positive results and were advised to start immunotherapy. Adherence to the stinging insect hypersensitivity practice parameter recommendations is poor. Many patients who have experienced a systemic reaction after an insect sting and have sought medical care are not afforded an opportunity for potentially lifesaving therapy.

  15. Single-Dose Pharmacokinetics and Safety of Abacavir (1592U89), Zidovudine, and Lamivudine Administered Alone and in Combination in Adults with Human Immunodeficiency Virus Infection

    PubMed Central

    Wang, Laurene H.; Chittick, Gregory E.; McDowell, James A.

    1999-01-01

    Abacavir (1592U89), a nucleoside reverse transcriptase inhibitor with in vitro activity against human immunodeficiency virus type-1 (HIV-1), has been evaluated for efficacy and safety in combination regimens with other nucleoside analogs, including zidovudine (ZDV) and lamivudine (3TC). To evaluate the potential pharmacokinetic interactions between these agents, 15 HIV-1-infected adults with a median CD4+ cell count of 347 cells/mm3 (range, 238 to 570 cells/mm3) were enrolled in a randomized, seven-period crossover study. The pharmacokinetics and safety of single doses of abacavir (600 mg), ZDV (300 mg), and 3TC (150 mg) were evaluated when each drug was given alone or when any two or three drugs were given concurrently. The concentrations of all drugs in plasma and the concentrations of ZDV and its 5′-glucuronide metabolite, GZDV, in urine were measured for up to 24 h postdosing, and pharmacokinetic parameter values were calculated by noncompartmental methods. The maximum drug concentration (Cmax), the area under the concentration-time curve from time zero to infinity (AUC0–∞), time to Cmax (Tmax), and apparent elimination half-life (t1/2) of abacavir in plasma were unaffected by coadministration with ZDV and/or 3TC. Coadministration of abacavir with ZDV (with or without 3TC) decreased the mean Cmax of ZDV by approximately 20% (from 1.5 to 1.2 μg/ml), delayed the median Tmax for ZDV by 0.5 h, increased the mean AUC0–∞ for GZDV by up to 40% (from 11.8 to 16.5 μg · h/ml), and delayed the median Tmax for GZDV by approximately 0.5 h. Coadministration of abacavir with 3TC (with or without ZDV) decreased the mean AUC0–∞ for 3TC by approximately 15% (from 5.1 to 4.3 μg · h/ml), decreased the mean Cmax by approximately 35% (from 1.4 to 0.9 μg/ml), and delayed the median Tmax by approximately 1 h. While these changes were statistically significant, they are similar to the effect of food intake (for ZDV) or affect an inactive metabolite (for GZDV) or are

  16. Maraviroc Intensification Improves Endothelial Function in Abacavir-Treated Patients, an Open-Label Randomized Cross-Over Pilot Study.

    PubMed

    Krikke, Maaike; Tesselaar, Kiki; Arends, Joop E; Drylewicz, Julia; Otto, Sigrid A; van Lelyveld, Steven F L; Visseren, Frank J L; Hoepelman, Andy I M

    2016-09-01

    The increased risk of abacavir in cardiovascular disease (CVD) in HIV-infected patients is still being debated. Maraviroc, a CCR5 blocker, has been shown to decrease immune activation and monocyte infiltration in atherosclerotic plaques in murine experiments. Therefore, we examined the effect of maraviroc intensification on flow-mediated dilatation (FMD) in abacavir-treated HIV-infected patients and its effect on immunological and inflammatory parameters. A open-label prospective crossover study with a duration of 16 weeks: 8 weeks of intervention (maraviroc intensification) and 8 weeks of control (unchanged cART regimen). FMD, HIV-specific variables, expression of HIV co-receptors, markers of inflammation and coagulation and cellular markers of immune activation were measured at weeks 0, 8 and 16. The changes (Δ) in these variables were compared between intervention and control periods using non-parametric tests. To evaluate the relation with the change in FMD, linear regression modeling was used. Twenty-one male patients with suppressed plasma HIV-RNA, on cART, had a known HIV infection for 9.2 years (IQR 6.9-13.5) with abacavir use for 6.5 years (2.8-9.3). A significantly increased FMD of 0.73% (IQR -0.25 to 1.70) was seen after maraviroc intensification compared to a decrease of -0.42% (IQR -1.89 to 0.25; p = 0.049) in the control period. There was a negative relation between ΔFMD with ΔD-dimer (β -22.70, 95% CI -39.27; -6.13, p = 0.011) and ΔCD95+ CD4+ T cells (β -0.16, 95% CI -0.28; -0.04, p = 0.013), adjusted for age and duration of HIV. Maraviroc intensification modestly improves endothelial function in HIV-infected patients on an abacavir-containing regimen. NCT01389063.

  17. Occupational hypersensitivity pneumonitis in a koji brewer.

    PubMed

    Ishiguro, Takashi; Kawai, Shoko; Kojima, Ayako; Shimizu, Yoshihiko; Kamei, Katsuhiko; Takayanagi, Noboru

    2018-03-01

    Koji is a fermenting agent used in many traditional Japanese foods , and Aspergillus oryzae is the most frequently used microorganism in koji production. Few cases of hypersensitivity pneumonitis due to A. oryzae have been reported. However, physicians should recognize the disease because of the increasing globalization of food production.

  18. Metal Hypersensitivity and Total Knee Arthroplasty

    PubMed Central

    Lachiewicz, Paul F.; Watters, Tyler Steven; Jacobs, Joshua J.

    2015-01-01

    Metal hypersensitivity in patients with a total knee arthroplasty (TKA) is a controversial topic. The diagnosis is difficult, given the lack of robust clinical validation of the utility of cutaneous and in vitro testing. Metal hypersensitivity after TKA is quite rare and should be considered after eliminating other causes of pain and swelling, such as low-grade infection, instability, component loosening or malrotation, referred pain, and chronic regional pain syndrome. Anecdotal observations suggest that two clinical presentations of metal hypersensitivity may occur after TKA: dermatitis or a persistent painful synovitis of the knee. Patients may or may not have a history of intolerance to metal jewelry. Laboratory studies, including erythrocyte sedimentation rate, C-reactive protein level, and knee joint aspiration, are usually negative. Cutaneous and in vitro testing have been reported to be positive, but the sensitivity and specificity of such testing has not been defined. Anecdotal reports suggest that, if metal hypersensitivity is suspected and nonsurgical measures have failed, then revision to components fabricated of titanium alloy or zirconium coating can be successful in relieving symptoms. Revision should be considered as a last resort, however, and patients should be informed that no evidence-based medicine is available to guide the management of these conditions, particularly for decisions regarding revision. Given the limitations of current testing methods, the widespread screening of patients for metal allergies before TKA is not warranted. PMID:26752739

  19. The canine model of dietary hypersensitivity.

    PubMed

    Day, Michael J

    2005-11-01

    IgE-mediated dietary hypersensitivity affects approximately 1% of the canine population. There are no breed associations and < or =50% of the patients are aged <1 year at presentation. The most common causative allergens are beef, chicken, milk, eggs, maize, wheat and soyabean. Affected dogs generally display cutaneous disease and 10-15% of the patients may have concurrent alimentary involvement. Diagnosis is currently based on dietary restriction followed by provocation. Procedures for the detection of serum allergen-specific IgE and IgG antibodies are widely available, but these tests correlate poorly with clinical presentation and dietary testing. Recent studies have demonstrated the allergen specificity of IgE antibodies by immunoblotting and have described blood lymphocyte proliferative responses to food allergens. In addition to investigations of spontaneously-arising dietary hypersensitivity, it has also proved possible to study this disorder experimentally. Small colonies of dogs sensitive to particular dietary proteins have been used to study clinical and serological responses to allergen challenge. Hypersensitivity has been experimentally induced in dogs of an atopic phenotype by repeated subcutaneous injection of alum-adjuvanted dietary allergen during neonatal life. These models have been used to trial a range of modified protein or hydrolysate diets. The dog provides a unique large-animal model for investigation of the immunopathogenesis of human dietary hypersensitivity. The dog is closely related genetically to man and shares environmental disease triggers with man. Spontaneously arising canine dietary hypersensitivity is a good clinical mimic of the human disease, and ability to therapeutically manipulate this adverse response in the dog might lead to benefits for human patients.

  20. Early virologic response to abacavir/lamivudine and tenofovir/emtricitabine during ACTG A5202

    PubMed Central

    Grant, Philip M.; Tierney, Camlin; Budhathoki, Chakra; Daar, Eric S.; Sax, Paul E.; Collier, Ann C.; Fischl, Margaret A.; Zolopa, Andrew R.; Balamane, Maya; Katzenstein, David

    2014-01-01

    Background ACTG A5202 randomized treatment-naive individuals to tenofovir-emtricitabine (TDF/FTC) or abacavir-lamivudine (ABC/3TC) combined with efavirenz (EFV) or atazanavir/ritonavir (ATV/r). Individuals in the high screening viral load (VL) stratum (≥100,000 copies/mL) had increased rates of virologic failure with ABC/3TC. Objective Compare regimen-specific early virologic response. Methods Using Wilcoxon rank-sum tests, we compared regimen-specific VL changes from entry to week 4 in A5202 subjects (n=1813) and from entry to week 1, 2 and 4 in a 179-patient substudy. We evaluated associations between week 4 VL change and time to virologic failure with Cox proportional-hazards models. Results TDF/FTC- and ABC/3TC produced similar Week 4 viral load declines in the entire study population and in the high VL stratum. EFV produced greater VL declines from baseline at week 4 than ATV/r (median −2.1 vs. −1.9 log10 copies/mL; p<0.001). In the substudy of subjects with week 1, 2 and 4 VL data, there was no difference in viral load decline in those randomized to TDF/FTC versus ABC/3TC, but EFV resulted in greater VL decline from entry at each of these timepoints than ATV/r. Smaller Week 4 viral load decline was associated with increased risk of virologic failure. Conclusions Within all treatment arms, a less robust week 4 virologic response was associated with higher risk for subsequent virologic failure. However, between-regimen differences in week 4 VL declines did not parallel the previously reported differences in longer term virologic efficacy in A5202, suggesting that between-regimen differences in responses were not due to intrinsic differences in antiviral activity. PMID:24334181

  1. The Reverse Transcription Inhibitor Abacavir Shows Anticancer Activity in Prostate Cancer Cell Lines

    PubMed Central

    Molinari, Agnese; Parisi, Chiara; Bozzuto, Giuseppina; Toccacieli, Laura; Formisano, Giuseppe; De Orsi, Daniela; Paradisi, Silvia; Grober, OlÌ Maria Victoria; Ravo, Maria; Weisz, Alessandro; Arcieri, Romano; Vella, Stefano; Gaudi, Simona

    2010-01-01

    Background Transposable Elements (TEs) comprise nearly 45% of the entire genome and are part of sophisticated regulatory network systems that control developmental processes in normal and pathological conditions. The retroviral/retrotransposon gene machinery consists mainly of Long Interspersed Nuclear Elements (LINEs-1) and Human Endogenous Retroviruses (HERVs) that code for their own endogenous reverse transcriptase (RT). Interestingly, RT is typically expressed at high levels in cancer cells. Recent studies report that RT inhibition by non-nucleoside reverse transcriptase inhibitors (NNRTIs) induces growth arrest and cell differentiation in vitro and antagonizes growth of human tumors in animal model. In the present study we analyze the anticancer activity of Abacavir (ABC), a nucleoside reverse transcription inhibitor (NRTI), on PC3 and LNCaP prostate cancer cell lines. Principal Findings ABC significantly reduces cell growth, migration and invasion processes, considerably slows S phase progression, induces senescence and cell death in prostate cancer cells. Consistent with these observations, microarray analysis on PC3 cells shows that ABC induces specific and dose-dependent changes in gene expression, involving multiple cellular pathways. Notably, by quantitative Real-Time PCR we found that LINE-1 ORF1 and ORF2 mRNA levels were significantly up-regulated by ABC treatment. Conclusions Our results demonstrate the potential of ABC as anticancer agent able to induce antiproliferative activity and trigger senescence in prostate cancer cells. Noteworthy, we show that ABC elicits up-regulation of LINE-1 expression, suggesting the involvement of these elements in the observed cellular modifications. PMID:21151977

  2. Investigation of Seminal Plasma Hypersensitivity Reactions (AIBS GWI 0046)

    DTIC Science & Technology

    1999-10-01

    Kit (Cat. No. 29304). The sequences for the 20-mer PCR primers for the urease gene off/, urealyticum (termed UU1 and UU2) and PCR methods were adapted...Ureaplasma urealyticum urease primer was unsuccessful. We therefore sent DNA samples of GW and control civilian couples to an outside laboratory to

  3. [Hypersensitivity to platinum salts and taxanes: The value of skin tests and tolerance induction procedures].

    PubMed

    Brault, F; Waton, J; Poreaux, C; Schmutz, J-L; Barbaud, A

    2017-11-01

    The rate of hypersensitivity reactions to platinum salts (PS) and taxanes (TX) is on the increase. The aim of our study was to show the value of skin testing and efficacy of rapid drug desensitization. This was a retrospective study conducted between January 2007 and February 2016 in patients consulting for immediate or delayed hypersensitivity to PS and TX. Skin prick tests (pT) and intradermal reaction tests (IDR) were performed according to the ENDA/EAACI recommendations. We used a 12-step desensitization protocol for rapid drug desensitization. Among the 99 patients included (30 men, 69 women, age 60.4) PS were suspected in 86 cases and taxanes in 13 cases. Skin tests were positive in 25 patients (7 pT, 18 IDR), 23 for platinum salts and 2 for taxanes. Rapid drug desensitization was proposed in 50 patients and performed in 33 (30 PS and 3 TX), proved effective in 29 patients, with protocol adaptation being necessary in 7 cases, and was ineffective in 4 patients. The skin tests for the latter 4 patients were positive. Seventy-five percent of patients with positive skin tests to oxaliplatin presented hypersensitivity reactions during desensitization, i.e. twice as many as patients having negative skin tests. Two percent of patient for PS and 7% for TX had cross reactivity. This French study confirms the efficacy of the 12-step protocol that allows patients to receive chemotherapy after hypersensitivity reaction. Skin test permits the detection of cross-reactions but their practice must be considered based on the patient's history. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Type IV Hypersensitivity to Gold Weight Upper-Eyelid Implant: Case Report and Review of the Literature.

    PubMed

    Kilduff, Caroline L S; Casswell, Edward J; Imonikhe, Richard; Marjanovic, Branka

    2017-05-04

    Complications associated with gold-weight insertion for lagophthalmos are uncommon, recent reports have provided evidence to suggest that type IV hypersensitivity to gold can cause a persistent inflammatory reaction. We present a case of a 46-year-old man who experienced persistent post-operative inflammation, and summarize previously documented cases. This patient underwent uncomplicated insertion of an upper eyelid gold weight for right-sided facial nerve palsy. He had no allergies or implanted metalwork. Post-operatively erythema was noted at seven-weeks and did not resolve. The weight was removed after six-months. The histopathological findings were in keeping with type IV hypersensitivity and similar to previous cases. Although infrequent, this complication has poor outcomes. The definitive management is removal of the weight. Information regarding implanted gold, and previous reactions should be elicited pre-operatively. Type IV hypersensitivity should be considered in patients with persistent inflammation that do not respond to antibiotic or steroid therapy.

  5. Childhood hypersensitivity pneumonitis associated with fungal contamination of indoor hydroponics.

    PubMed

    Engelhart, Steffen; Rietschel, Ernst; Exner, Martin; Lange, Lars

    2009-01-01

    Childhood hypersensitivity pneumonitis (HP) is often associated with exposure to antigens in the home environment. We describe a case of HP associated with indoor hydroponics in a 14-year-old girl. Water samples from hydroponics revealed Aureobasidium pullulans as the dominant fungal micro-organism (10(4)CFU/ml). The diagnosis is supported by the existence of serum precipitating antibodies against A. pullulans, lymphocytic alveolitis on bronchoalveolar lavage (BAL) fluid, a corresponding reaction on a lung biopsy, and the sustained absence of clinical symptoms following the removal of hydroponics from the home. We conclude that hydroponics should be considered as potential sources of fungal contaminants when checking for indoor health complaints.

  6. Incidence and risk factors for food hypersensitivity in UK infants: results from a birth cohort study.

    PubMed

    Grimshaw, Kate E C; Bryant, Trevor; Oliver, Erin M; Martin, Jane; Maskell, Joe; Kemp, Terri; Clare Mills, E N; Foote, Keith D; Margetts, Barrie M; Beyer, Kirsten; Roberts, Graham

    2015-01-01

    The prevalence of food hypersensitivity in the UK is still largely open to debate. Additionally its pathogenesis is also unclear although it is known that there are differing phenotypes. Determining its prevalence, along with identifying those factors associated with its development will help to assess its clinical importance within the national setting and also add to the debate on appropriate prevention strategies. A population based birth cohort study conducted in Hampshire, UK as part of the EuroPrevall birth cohort study. 1140 infants were recruited with 823 being followed up until 2 years of age. Infants with suspected food reactions were assessed including specific IgE measurement and skin prick testing. Diagnosis of food hypersensitivity was by positive double-blind, placebo-controlled food challenge (DBPCFC) where symptoms up to 48 h after the end of the food challenge were considered indicative of a food hypersensitivity. Factors associated with food hypersensitivity and its two phenotypes of IgE-mediated and non-IgE-mediated disease were modelled in a multivariable logistic regression analysis. Cumulative incidence of food hypersensitivity by 2 years of age was 5.0 %. The cumulative incidence for individual food allergens were hens' egg 2.7 % (1.6-3.8); cows' milk 2.4 % (1.4-3.5); peanut 0.7 % (0.1-1.3); soy 0.4 % (0.0-0.8); wheat 0.2 % (0.0-0.5) and 0.1 % (0.0-0.32) for fish. The cumulative incidence of IgE-mediated food allergy was 2.6 % with 2.1 % reacting to hens' egg. For non-IgE-mediated food allergy the cumulative incidence was 2.4 % (cows' milk 1.7 %). Predictors for any food hypersensitivity were wheeze, maternal atopy, increasing gestational age, age at first solid food introduction and mean healthy dietary pattern score. Predictors for IgE mediated allergy were eczema, rhinitis and healthy dietary pattern score whereas for non-IgE-mediated food allergy the predictors were dog in the home, healthy dietary pattern score, maternal

  7. Population pharmacokinetics and maximum a posteriori probability Bayesian estimator of abacavir: application of individualized therapy in HIV-infected infants and toddlers.

    PubMed

    Zhao, Wei; Cella, Massimo; Della Pasqua, Oscar; Burger, David; Jacqz-Aigrain, Evelyne

    2012-04-01

    Abacavir is used to treat HIV infection in both adults and children. The recommended paediatric dose is 8 mg kg(-1) twice daily up to a maximum of 300 mg twice daily. Weight was identified as the central covariate influencing pharmacokinetics of abacavir in children. A population pharmacokinetic model was developed to describe both once and twice daily pharmacokinetic profiles of abacavir in infants and toddlers. Standard dosage regimen is associated with large interindividual variability in abacavir concentrations. A maximum a posteriori probability Bayesian estimator of AUC(0-) (t) based on three time points (0, 1 or 2, and 3 h) is proposed to support area under the concentration-time curve (AUC) targeted individualized therapy in infants and toddlers. To develop a population pharmacokinetic model for abacavir in HIV-infected infants and toddlers, which will be used to describe both once and twice daily pharmacokinetic profiles, identify covariates that explain variability and propose optimal time points to optimize the area under the concentration-time curve (AUC) targeted dosage and individualize therapy. The pharmacokinetics of abacavir was described with plasma concentrations from 23 patients using nonlinear mixed-effects modelling (NONMEM) software. A two-compartment model with first-order absorption and elimination was developed. The final model was validated using bootstrap, visual predictive check and normalized prediction distribution errors. The Bayesian estimator was validated using the cross-validation and simulation-estimation method. The typical population pharmacokinetic parameters and relative standard errors (RSE) were apparent systemic clearance (CL) 13.4 () h−1 (RSE 6.3%), apparent central volume of distribution 4.94 () (RSE 28.7%), apparent peripheral volume of distribution 8.12 () (RSE14.2%), apparent intercompartment clearance 1.25 () h−1 (RSE 16.9%) and absorption rate constant 0.758 h−1 (RSE 5.8%). The covariate analysis

  8. Signal interactions between nitric oxide and reactive oxygen intermediates in the plant hypersensitive disease resistance response.

    PubMed

    Delledonne, M; Zeier, J; Marocco, A; Lamb, C

    2001-11-06

    Nitric oxide (NO) and reactive oxygen intermediates (ROIs) play key roles in the activation of disease resistance mechanisms both in animals and plants. In animals NO cooperates with ROIs to kill tumor cells and for macrophage killing of bacteria. Such cytotoxic events occur because unregulated NO levels drive a diffusion-limited reaction with O(2)(-) to generate peroxynitrite (ONOO(-)), a mediator of cellular injury in many biological systems. Here we show that in soybean cells unregulated NO production at the onset of a pathogen-induced hypersensitive response (HR) is not sufficient to activate hypersensitive cell death. The HR is triggered only by balanced production of NO and ROIs. Moreover, hypersensitive cell death is activated after interaction of NO not with O(2)- but with H(2)O(2) generated from O(2)(-) by superoxide dismutase. Increasing the level of O(2)(-) reduces NO-mediated toxicity, and ONOO(-) is not a mediator of hypersensitive cell death. During the HR, superoxide dismutase accelerates O(2)(-) dismutation to H(2)O(2) to minimize the loss of NO by reaction with O(2)(-) and to trigger hypersensitive cell death through NO/H(2)O(2) cooperation. However, O(2)(-) rather than H(2)O(2) is the primary ROI signal for pathogen induction of glutathione S-transferase, and the rates of production and dismutation of O(2)(-) generated during the oxidative burst play a crucial role in the modulation and integration of NO/H(2)O(2) signaling in the HR. Thus although plants and animals use a similar repertoire of signals in disease resistance, ROIs and NO are deployed in strikingly different ways to trigger host cell death.

  9. Polymorphism in glutamate cysteine ligase catalytic subunit (GCLC) is associated with sulfamethoxazole-induced hypersensitivity in HIV/AIDS patients

    PubMed Central

    2012-01-01

    Background Sulfamethoxazole (SMX) is a commonly used antibiotic for prevention of infectious diseases associated with HIV/AIDS and immune-compromised states. SMX-induced hypersensitivity is an idiosyncratic cutaneous drug reaction with genetic components. Here, we tested association of candidate genes involved in SMX bioactivation and antioxidant defense with SMX-induced hypersensitivity. Results Seventy seven single nucleotide polymorphisms (SNPs) from 14 candidate genes were genotyped and assessed for association with SMX-induced hypersensitivity, in a cohort of 171 HIV/AIDS patients. SNP rs761142 T > G, in glutamate cysteine ligase catalytic subunit (GCLC), was significantly associated with SMX-induced hypersensitivity, with an adjusted p value of 0.045. This result was replicated in a second cohort of 249 patients (p = 0.025). In the combined cohort, heterozygous and homozygous carriers of the minor G allele were at increased risk of developing hypersensitivity (GT vs TT, odds ratio = 2.2, 95% CL 1.4-3.7, p = 0.0014; GG vs TT, odds ratio = 3.3, 95% CL 1.6 – 6.8, p = 0.0010). Each minor allele copy increased risk of developing hypersensitivity 1.9 fold (95% CL 1.4 – 2.6, p = 0.00012). Moreover, in 91 human livers and 84 B-lymphocytes samples, SNP rs761142 homozygous G allele carriers expressed significantly less GCLC mRNA than homozygous TT carriers (p < 0.05). Conclusions rs761142 in GCLC was found to be associated with reduced GCLC mRNA expression and with SMX-induced hypersensitivity in HIV/AIDS patients. Catalyzing a critical step in glutathione biosynthesis, GCLC may play a broad role in idiosyncratic drug reactions. PMID:22824134

  10. Cervical Lymphadenopathy Mimicking Angioimmunoblastic T-Cell Lymphoma after Dapsone-Induced Hypersensitivity Syndrome

    PubMed Central

    Rim, Min Young; Hong, Junshik; Yo, Inku; Park, Hyeonsu; Chung, Dong Hae; Ahn, Jeong Yeal; Park, Jinny; Kim, Yun Soo; Lee, Jae Hoon

    2012-01-01

    A 36-year-old woman presented with erythematous confluent macules on her whole body with fever and chills associated with jaundice after 8 months of dapsone therapy. Her symptoms had developed progressively, and a physical examination revealed bilateral cervical lymphadenopathy and splenomegaly. Excisional biopsy of a cervical lymph node showed effacement of the normal architecture with atypical lymphoid hyperplasia and proliferation of high endothelial venules compatible with angioimmunoblastic T-cell lymphoma. However, it was assumed that the cervical lymphadenopathy was a clinical manifestation of a systemic hypersensitivity reaction because her clinical course was reminiscent of dapsone-induced hypersensitivity syndrome. A liver biopsy revealed drug-induced hepatitis with no evidence of lymphomatous involvement. Intravenous glucocorticoid was immediately initiated and her symptoms and clinical disease dramatically improved. The authors present an unusual case of cervical lymphadenopathy mimicking angioimmunoblastic T-cell lymphoma as an adverse reaction to dapsone. PMID:23323115

  11. Efficacy and Safety of Available Protocols for Aspirin Hypersensitivity for Patients Undergoing Percutaneous Coronary Intervention: A Survey and Systematic Review.

    PubMed

    Bianco, Matteo; Bernardi, Alessandro; D'Ascenzo, Fabrizio; Cerrato, Enrico; Omedè, Pierluigi; Montefusco, Antonio; DiNicolantonio, James J; Zoccai, Giuseppe Biondi; Varbella, Ferdinando; Carini, Giovanni; Moretti, Claudio; Pozzi, Roberto; Gaita, Fiorenzo

    2016-01-01

    The most suitable approach for patients with aspirin hypersensitivity undergoing percutaneous coronary intervention remains to be assessed. Pubmed, Google Scholar, and Cochrane were systematically searched for papers describing protocols about aspirin hypersensitivity in the percutaneous coronary intervention setting. Discharge from hospital with aspirin was the primary end point, whereas rates of adverse reactions being a secondary outcome. An online international survey was performed to critically analyze rates of aspirin hypersensitivity and its medical and interventional management. Eleven studies with 283 patients were included. An endovenous desensitization protocol was performed on one of them, with high efficacy rate (98%) and a low adverse reaction rate when compared with oral administration. No significant differences were reported among the oral protocols in terms of efficacy (less versus more fractionated [95.8% {95.4%-96.2%} versus 95.9% {95.2-96.5%}]), whereas higher incidence of rash and angioedema were reported for protocols with <6 doses escalation (2.6% [1.1%-4.1%] versus 2.6% [1.9%-3.2%]). In the survey, we collected answer from 86 physician of the 100 interviewed. Fifty-six percent of them managed aspirin hypersensitivity changing the therapeutic regimen (eg, clopidogrel monotherapy and indobufen). Despite the previous safety data, desensitization protocols were adopted by only 42% of surveyed cardiologist. Available protocols for aspirin hypersensitivity are effective and safe, representing a feasible approach for patients needing dual antiplatelet therapy. © 2016 American Heart Association, Inc.

  12. Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection.

    PubMed

    Descamps, V; Mahe, E; Houhou, N; Abramowitz, L; Rozenberg, F; Ranger-Rogez, S; Crickx, B

    2003-05-01

    Association of drug-induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant-induced hypersensitivity syndrome. We report a case of severe allopurinol-induced hypersensitivity syndrome with pancreatitis associated with Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6 was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug-induced hypersensitivity syndrome.

  13. Making Sense of Metal Allergy and Hypersensitivity to Metallic Implants in Relation to Hand Surgery.

    PubMed

    Christensen, Thomas J; Samant, Shefali A; Shin, Alexander Y

    2017-09-01

    All metals implanted into a biological system undergo some degree of corrosion depending upon its composition. The electrochemical process of corrosion produces free metal ions, which may activate the host's immune system through a variety of mechanisms. Whereas dermal metal hypersensitivity is common, affecting 10% to 15% of the population, the immune reaction from implanted metals is much less common (< 0.1%), but has been associated with metal allergy and hypersensitivity producing a multitude of patient symptoms. Superficial symptoms may be mild to severe forms of dermatitis, urticaria, pruritus, and vasculitis, whereas deep sequelae include metallosis-related pseudotumor, implant loosening, and joint stiffness. Currently, there are clinical tests to evaluate patients for metal hypersensitivity, but there is little agreement regarding the ideal timing and clinical situation prompting the work-up of a patient for a metal allergy or hypersensitivity. An understanding of the epidemiology, etiology, basic science, diagnostic testing, and treatment of patients with suspected metal allergy, as it pertains to the current literature, will aid orthopedic and plastic surgeons of all subspecialties in the management of patients requiring metallic implants. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  14. Idiosyncratic Adverse Drug Reactions: Current Concepts

    PubMed Central

    Naisbitt, Dean J.

    2013-01-01

    Idiosyncratic drug reactions are a significant cause of morbidity and mortality for patients; they also markedly increase the uncertainty of drug development. The major targets are skin, liver, and bone marrow. Clinical characteristics suggest that IDRs are immune mediated, and there is substantive evidence that most, but not all, IDRs are caused by chemically reactive species. However, rigorous mechanistic studies are very difficult to perform, especially in the absence of valid animal models. Models to explain how drugs or reactive metabolites interact with the MHC/T-cell receptor complex include the hapten and P-I models, and most recently it was found that abacavir can interact reversibly with MHC to alter the endogenous peptides that are presented to T cells. The discovery of HLA molecules as important risk factors for some IDRs has also significantly contributed to our understanding of these adverse reactions, but it is not yet clear what fraction of IDRs have a strong HLA dependence. In addition, with the exception of abacavir, most patients who have the HLA that confers a higher IDR risk with a specific drug will not have an IDR when treated with that drug. Interindividual differences in T-cell receptors and other factors also presumably play a role in determining which patients will have an IDR. The immune response represents a delicate balance, and immune tolerance may be the dominant response to a drug that can cause IDRs. PMID:23476052

  15. A Systematic Desensitization Paradigm to Treat Hypersensitivity to Auditory Stimuli in Children with Autism in Family Contexts

    ERIC Educational Resources Information Center

    Koegel, Robert L.; Openden, Daniel; Koegel, Lynn Kern

    2004-01-01

    Many children with autism display reactions to auditory stimuli that seem as if the stimuli were painful or otherwise extremely aversive. This article describes, within the contexts of three experimental designs, how procedures of systematic desensitization can be used to treat hypersensitivity to auditory stimuli in three young children with…

  16. Once vs twice-daily abacavir and lamivudine in African children.

    PubMed

    Musiime, Victor; Kasirye, Philip; Naidoo-James, Bethany; Nahirya-Ntege, Patricia; Mhute, Tawanda; Cook, Adrian; Mugarura, Lincoln; Munjoma, Marshall; Thoofer, Navdeep K; Ndashimye, Emmanuel; Nankya, Immaculate; Spyer, Moira J; Thomason, Margaret J; Snowden, Wendy; Gibb, Diana M; Walker, Ann Sarah

    2016-07-17

    Antiretroviral therapy (ART) adherence is critical for successful HIV treatment outcomes. Once-daily dosing could improve adherence. Plasma concentrations of once-daily vs twice-daily abacavir + lamivudine are bioequivalent in children, but no randomized trial has compared virological outcomes. Children taking abacavir + lamivudine-containing first-line regimens twice daily for more than 36 weeks in the ARROW trial (NCT02028676, ISRCTN24791884) were randomized to continue twice-daily vs move to once-daily abacavir + lamivudine (open-label). Co-primary outcomes were viral load suppression at week 48 (12% noninferiority margin, measured retrospectively) and lamivudine or abacavir-related grade 3/4 adverse events. Six hundred and sixty-nine children (median 5 years, range 1-16) were randomized to twice daily (n = 333) vs once daily (n = 336) after median 1.8 years on twice-daily abacavir + lamivudine-containing first-line ART. Children were followed for median 114 weeks. At week 48, 242/331 (73%) twice daily vs 236/330 (72%) once daily had viral load less than 80 copies/ml [difference -1.6% (95% confidence interval -8.4,+5.2%) P = 0.65]; 79% twice daily vs 78% once daily had viral load less than 400 copies/ml (P = 0.76) (week 96 results similar). One grade 3/4 adverse event was judged uncertainly related to abacavir + lamivudine (hepatitis; once daily). At week 48, 9% twice daily vs 10% once daily reported missing one or more ART pills in the last 4 weeks (P = 0.74) and 8 vs 8% at week 96 (P = 0.90). Carers strongly preferred once-daily dosing. There was no difference between randomized groups in postbaseline drug-resistance mutations or drug-susceptibility; WHO 3/4 events; ART-modifying, grade 3/4 or serious adverse events; CD4% or weight-for-age/height-for-age (all P > 0.15). Once-daily abacavir + lamivudine was noninferior to twice daily in viral load suppression, with similar resistance, adherence, clinical

  17. Hipersensitivity Reactions to Corticosteroids.

    PubMed

    Berbegal, L; DeLeon, F J; Silvestre, J F

    2016-03-01

    Corticosteroids are widely used drugs in the clinical practice, especially by topic application in dermatology. These substances may act as allergens and produce immediate and delayed hypersensitivity reactions. Allergic contact dermatitis is the most frequent presentation of corticosteroid allergy and it should be studied by patch testing in specific units. The corticosteroids included in the Spanish standard battery are good markers but not ideal. Therefore, if those makers are positive, it is useful to apply a specific battery of corticosteroids and the drugs provided by patients. Immediate reactions are relatively rare but potentially severe, and it is important to confirm the sensitization profile and to guide the use of alternative corticosteroids, because they are often necessary in several diseases. In this article we review the main concepts regarding these two types of hypersensitivity reactions in corticosteroid allergy, as well as their approach in the clinical practice. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  18. Contact reactions to fragrances.

    PubMed

    Katsarou, A; Armenaka, M; Kalogeromitros, D; Koufou, V; Georgala, S

    1999-05-01

    The most common reaction to fragrances is contact dermatitis, a delayed hypersensitivity reaction; however, other reactions include immediate contact reactions (contact urticaria) and photo-allergic reactions. Fragrance mix (FM) and balsam of Peru (BP) are used to screen for fragrance allergy. To study the different types of allergic skin reactions to fragrance compounds. Delayed hypersensitivity reactions to FM and BP were studied in 4,975 patients with suspected contact dermatitis by routine patch testing interpreted at 48 and 96 hours. In 664 of the patients, patch tests were read at 30 minutes to evaluate for immediate (wheal-and-flare) contact reactions and again at 48 and 96 hours. Photopatch tests to FM were performed in 111 patients with suspected photo-allergic dermatitis. Delayed contact reactions to FM occurred in 6.6% of females and 5.4% of males and to BP in 3.9% of females and 4.1% of males. Analysis of data over time (12 study years) showed an increased trend for reactions to fragrances, particularly in males. Sensitivity to other contact allergens (polysensitivity) was found in 62% of patients and polysensitivity presented more often with generalized contact dermatitis. The most sensitizing components of the fragrance mix that were tested in 38 patients were cinnamic alcohol, oak moss, and cinnamic aldehyde. There were 112 immediate patch test reactions to FM and 113 to BP in 664 patients. Immediate contact reactions were followed by delayed contact reactions in 13.4% of patients for FM and 8.8% for BP, representing a significant increase in the frequency of delayed contact reactions. Patients with immediate contact reactions to fragrances did not have a higher incidence of atopy (25.9%). No cases of positive photopatch test reactions to FM were seen. Fragrances commonly cause both delayed and immediate patch test reactions and patients with immediate contact reactions have an increase in delayed contact reactions to the same allergen.

  19. Antigen-specific histamine release in dogs with food hypersensitivity.

    PubMed

    Ishida, Rinei; Masuda, Kenichi; Sakaguchi, Masahiro; Kurata, Keigo; Ohno, Koichi; Tsujimoto, Hajime

    2003-03-01

    An in vitro evidence of IgE-mediated hypersensitivity to food allergens was detected by positive results of antigen-specific histamine release in dogs with food hypersensitivity. Eight dogs were diagnosed to have food hypersensitivity based on identification of offending food allergens with food elimination followed by oral food provocation. The percentages of histamine release against the stimulation of offending food allergens in the cases ranged from 2.1% to 70.9%. Six of the 8 cases showed histamine release higher than those of healthy control dogs. Four dogs showed relatively high histamine release at the percentage beyond 10% that was compatible with a positive value of histamine release in humans with food hypersensitivity. These findings would suggest that IgE-mediated hypersensitivity against food allergens could be involved in canine food hypersensitivity.

  20. Outcome of pediatric patients with acute lymphoblastic leukemia/lymphoblastic lymphoma with hypersensitivity to pegaspargase treated with PEGylated Erwinia asparaginase, pegcrisantaspase: A report from the Children's Oncology Group

    PubMed Central

    Rau, Rachel E.; Dreyer, ZoAnn; Choi, Mi Rim; Liang, Wei; Skowronski, Roman; Allamneni, Krishna P.; Devidas, Meenakshi; Raetz, Elizabeth A.; Adamson, Peter C.; Blaney, Susan M.; Loh, Mignon L; Hunger, Stephen P.

    2018-01-01

    Background Erwinia asparaginase is a Food and Drug Administration approved agent for the treatment of acute lymphoblastic leukemia (ALL) for patients who develop hypersensitivity to Escherichia coli derived asparaginases. Erwinia asparaginase is efficacious, but has a short half-life, requiring six doses to replace one dose of the most commonly used first-line asparaginase, pegaspargase, a polyethylene glycol (PEG) conjugated E. coli asparaginase. Pegcristantaspase, a recombinant PEGylated Erwinia asparaginase with improved pharmacokinetics, was developed for patients with hypersensitivity to pegaspargase. Here, we report a series of patients treated on a pediatric phase 2 trial of pegcrisantaspase. Procedure Pediatric patients with ALL or lymphoblastic lymphoma and hypersensitivity to pegaspargase enrolled on Children's Oncology Group trial AALL1421 (Jazz 13-011) and received intravenous pegcrisantaspase. Serum asparaginase activity (SAA) was monitored before and after dosing; immunogenicity assays were performed for antiasparaginase and anti-PEG antibodies and complement activation was evaluated. Results Three of the four treated patients experienced hypersensitivity to pegcrisantaspase manifested as clinical hypersensitivity reactions or rapid clearance of SAA. Immunogenicity assays demonstrated the presence of anti-PEG immunoglobulin G antibodies in all three hypersensitive patients, indicating a PEG-mediated immune response. Conclusions This small series of patients, nonetheless, provides data, suggesting preexisting immunogenicity against the PEG moiety of pegaspargase and poses the question as to whether PEGylation may be an effective strategy to optimize Erwinia asparaginase administration. Further study of larger cohorts is needed to determine the incidence of preexisting antibodies against PEG-mediated hypersensitivity to pegaspargase. PMID:29090524

  1. [Allergic and non-allergic hypersensitivity to non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs in children: epidemiology, clinical aspects, pathophysiology, diagnosis and prevention].

    PubMed

    Ponvert, C

    2012-05-01

    Non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs are widely used, but suspected allergic reactions to these drugs are rare, especially in children. Most frequent reactions are cutaneous (urticaria, angioedema) and respiratory (rhinitis, asthma). Other reactions (anaphylaxis, potentially harmful toxidermias) are rare. In a few patients, reactions may result from a specific (allergic) hypersensitivity, with positive responses in prick and intradermal tests (anaphylaxis, immediate urticaria and/or angioedema) and in intradermal and patch tests (non-immediate reactions). However, most reactions result from a non-specific (non-allergic) hypersensitivity (intolerance), with a frequent cross-reactivity between the various families of analgesics, antipyretics and nonsteroidal anti-inflammatory drugs, including paracetamol. Based on a convincing clinical history and/or positive responses in challenge tests, intolerance to non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs has been diagnosed in 13 to 50% of the patients with allergic-like reactions to these drugs. Risk factors are a personal atopy and age. Prevention is based on administration of other (families of) analgesics, antipyretics and nonsteroidal anti-inflammatory drugs in patients with allergic hypersensitivity to these drugs. In patients with non-allergic hypersensitivity, prevention is based on administration of drugs with a low cyclo-oxygenase-1 inhibitory activity (if tolerated). Desensitization is efficient in patients with respiratory reactions, but does not work in patients with mucocutaneous reactions and anaphylaxis. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  2. Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to Asparaginase Hypersensitivity

    PubMed Central

    Kutszegi, Nóra; Semsei, Ágnes F.; Gézsi, András; Sági, Judit C.; Nagy, Viktória; Csordás, Katalin; Jakab, Zsuzsanna; Lautner-Csorba, Orsolya; Gábor, Krisztina Míta; Kovács, Gábor T.; Erdélyi, Dániel J.; Szalai, Csaba

    2015-01-01

    L-asparaginase (ASP) is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL). However, hypersensitivity reactions (HSRs) to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin—Frankfurt—Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs) in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01–0.26); p = 4.70E-04), while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176) were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09–0.53); p = 8.48E-04 and OR = 3.02 (1.36–6.73); p = 6.76E-03, respectively). Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect. PMID:26457809

  3. Glycerol Hypersensitivity in a Drosophila Model for Glycerol Kinase Deficiency Is Affected by Mutations in Eye Pigmentation Genes

    PubMed Central

    Wightman, Patrick J.; Jackson, George R.; Dipple, Katrina M.

    2012-01-01

    Glycerol kinase plays a critical role in metabolism by converting glycerol to glycerol 3-phosphate in an ATP dependent reaction. In humans, glycerol kinase deficiency results in a wide range of phenotypic variability; patients can have severe metabolic and CNS abnormalities, while others possess hyperglycerolemia and glyceroluria with no other apparent phenotype. In an effort to help understand the pathogenic mechanisms underlying the phenotypic variation, we have created a Drosophila model for glycerol kinase deficiency by RNAi targeting of dGyk (CG18374) and dGK (CG7995). As expected, RNAi flies have reduced glycerol kinase RNA expression, reduced phosphorylation activity and elevated glycerol levels. Further investigation revealed these flies to be hypersensitive to fly food supplemented with glycerol. Due to the hygroscopic nature of glycerol, we predict glycerol hypersensitivity is a result of greater susceptibility to desiccation, suggesting glycerol kinase to play an important role in desiccation resistance in insects. To evaluate a role for genetic modifier loci in determining severity of the glycerol hypersensitivity observed in knockdown flies, we performed a preliminary screen of lethal transposon insertion mutant flies using a glycerol hypersensitive survivorship assay. We demonstrate that this type of screen can identify both enhancer and suppressor genetic loci of glycerol hypersensitivity. Furthermore, we found that the glycerol hypersensitivity phenotype can be enhanced or suppressed by null mutations in eye pigmentation genes. Taken together, our data suggest proteins encoded by eye pigmentation genes play an important role in desiccation resistance and that eye pigmentation genes are strong modifiers of the glycerol hypersensitive phenotype identified in our Drosophila model for glycerol kinase deficiency. PMID:22427807

  4. Opioid Hypersensitivity: Predictors of Allergy and Role of Drug Provocation Testing.

    PubMed

    Li, Philip H; Ue, Kok Loong; Wagner, Annette; Rutkowski, Ryszard; Rutkowski, Krzysztof

    True IgE-mediated hypersensitivity to opioids is rare and many reactions are due to direct mast cell degranulation. Opioid drug provocation testing (DPT) is the gold standard for diagnosis but is underutilized. The objective of this study was to evaluate the clinical characteristics and predictors of opioid hypersensitivity, as well as outcomes of opioid DPT. Patients referred for opioid DPT over the past 9 years were studied. Patient characteristics, indications for opioid use, symptoms of index reaction, and outcomes of DPT were analyzed. Association analysis was performed to study variables associated with a diagnosis of opioid hypersensitivity. Of the total of 98 patients referred with suspected opioid hypersensitivity, 15 (15%) were diagnosed with opioid allergy. Angioedema (odds ratio [OR]: 5.66; 95% confidence interval [CI]: 1.49-21.47; P = .011) and hypotension (OR: 5.00; 95% CI: 1.15-21.70; P = .032) were significantly more frequent in opioid allergic patients than those with a negative DPT. Patients who received opioids during anesthesia were significantly more likely to be opioid allergic (OR: 6.74; 95% CI: 2.05-22.13; P = .001). In contrast, a negative association was identified with patients who received opioids for analgesia (OR: 0.27; 95% CI: 0.08-0.86; P = .008). Only 15% of our cohort were diagnosed with opioid allergy, emphasizing the importance of DPT in preventing erroneous overdiagnosis. Patients with a history of angioedema or hypotension as their index reaction were significantly more likely to be opioid allergic. DPT are safe when performed by experienced clinicians after risk stratification and using individualized protocols. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Hypersensitivities to sesame and other common edible seeds.

    PubMed

    Patel, A; Bahna, S L

    2016-10-01

    Several seeds have been increasingly incorporated in various food items, with consequent risk of hypersensitivity reactions that are often severe. Identification of the specific seed as the culprit is often not explored or is difficult to verify. In this article, we reviewed the English literature from January 1930 to March 2016 using PubMed and Google Scholar searching for publications relevant to hypersensitivity to common edible seeds, namely sesame, sunflower seed, poppy seed, pumpkin seed, flaxseed, and mustard seed. Considering the worldwide consumption of those seeds, the number of published articles on the subject was relatively small and was mainly as case reports rather than large series. Allergy to sesame was more reported than to other seeds, with an estimated prevalence of 0.1-0.2%. In this review, we summarize the information relevant to each of the six seeds and their oils regarding the manifestations, routes of exposure, identified major allergens, and cross-reactivity with other seeds or other foods. We also addressed the important role of a thorough history taking in suspecting seed allergy, the limited reliability of routine diagnostic procedures, and the importance of verification by appropriate challenge tests. At present, management is basically dietary avoidance and the use of symptomatic medications that may include epinephrine auto-injectors. We did not encounter any well-designed studies on immunotherapy for seed allergy, but it is hoped that such a gap be filled by the development of safe effective protocols in the near future. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Drug-Drug Interaction between the Direct-Acting Antiviral Regimen of Ombitasvir-Paritaprevir-Ritonavir plus Dasabuvir and the HIV Antiretroviral Agent Dolutegravir or Abacavir plus Lamivudine.

    PubMed

    Khatri, Amit; Trinh, Roger; Zhao, Weihan; Podsadecki, Thomas; Menon, Rajeev

    2016-10-01

    The direct-acting antiviral regimen of 25 mg ombitasvir-150 mg paritaprevir-100 mg ritonavir once daily (QD) plus 250 mg dasabuvir twice daily (BID) is approved for the treatment of hepatitis C virus genotype 1 infection, including patients coinfected with human immunodeficiency virus. This study was performed to evaluate the pharmacokinetic, safety, and tolerability effects of coadministering the regimen of 3 direct-acting antivirals with two antiretroviral therapies (dolutegravir or abacavir plus lamivudine). Healthy volunteers (n = 24) enrolled in this phase I, single-center, open-label, multiple-dose study received 50 mg dolutegravir QD for 7 days or 300 mg abacavir plus 300 mg lamivudine QD for 4 days, the 3-direct-acting-antiviral regimen for 14 days, followed by the 3-direct-acting-antiviral regimen with dolutegravir or abacavir plus lamivudine for 10 days. Pharmacokinetic parameters were calculated to compare combination therapy with 3-direct-acting-antiviral or antiretroviral therapy alone, and safety/tolerability were assessed throughout the study. Coadministration of the 3-direct-acting-antiviral regimen increased the geometric mean maximum plasma concentration (Cmax) and the area under the curve (AUC) of dolutegravir by 22% (central value ratio [90% confidence intervals], 1.219 [1.153, 1.288]) and 38% (1.380 [1.295, 1.469]), respectively. Abacavir geometric mean Cmax and AUC values decreased by 13% (0.873 [0.777, 0.979]) and 6% (0.943 [0.901, 0.986]), while those for lamivudine decreased by 22% (0.778 [0.719, 0.842]) and 12% (0.876 [0.821, 0.934]). For the 3-direct-acting-antiviral regimen, geometric mean Cmax and AUC during coadministration were within 18% of measurements made during administration of the 3-direct-acting-antiviral regimen alone, although trough concentrations for paritaprevir were 34% (0.664 [0.585, 0.754]) and 27% (0.729 [0.627, 0.847]) lower with dolutegravir and abacavir-lamivudine, respectively. All study treatments were generally

  7. Patch Testing for Evaluation of Hypersensitivity to Implanted Metal Devices: A Perspective From the American Contact Dermatitis Society.

    PubMed

    Schalock, Peter C; Crawford, Glen; Nedorost, Susan; Scheinman, Pamela L; Atwater, Amber Reck; Mowad, Christen; Brod, Bruce; Ehrlich, Alison; Watsky, Kalman L; Sasseville, Denis; Silvestri, Dianne; Worobec, Sophie M; Elliott, John F; Honari, Golara; Powell, Douglas L; Taylor, James; DeKoven, Joel

    2016-01-01

    The American Contact Dermatitis Society recognizes the interest in the evaluation and management of metal hypersensitivity reactions. Given the paucity of robust evidence with which to guide our practices, we provide reasonable evidence and expert opinion-based guidelines for clinicians with regard to metal hypersensitivity reaction testing and patient management. Routine preoperative evaluation in individuals with no history of adverse cutaneous reactions to metals or history of previous implant-related adverse events is not necessary. Patients with a clear self-reported history of metal reactions should be evaluated by patch testing before device implant. Patch testing is only 1 element in the assessment of causation in those with postimplantation morbidity. Metal exposure from the implanted device can cause sensitization, but a positive metal test does not prove symptom causality. The decision to replace an implanted device must include an assessment of all clinical factors and a thorough risk-benefit analysis by the treating physician(s) and patient.

  8. T regulatory cells in contact hypersensitivity.

    PubMed

    Cavani, Andrea

    2008-08-01

    The review summarizes the recent investigations focused on T regulatory cells in hapten diseases. Multiple mechanisms ensure tolerance to small chemicals penetrating the skin. Among these, specific T regulatory cells play a major role in controlling harmful immune responses to environmental antigens. Most of the T regulatory cells involved in this process belongs to the CD4 subset and suppress hapten-specific immune response through the release of IL-10 and through direct interaction with effector T cells, blocking their function. Methods for in-vitro and in-vivo expansion of specific T regulatory cells may represent an innovative approach for the cure of contact hypersensitivity.

  9. Immediate hypersensitivity to moxifloxacin with tolerance to ciprofloxacin: report of three cases and review of the literature.

    PubMed

    Chang, Brenda; Knowles, Sandra R; Weber, Elizabeth

    2010-04-01

    To report 3 cases of immediate hypersensitivity reactions to moxifloxacin in patients who tolerated ciprofloxacin. A 71-year-old man, a 44-year-old woman, and a 70-year-old woman with a history of a moxifloxacin reaction developed an immediate hypersensitivity reaction upon oral challenge with moxifloxacin in our Drug Safety Clinic. The reaction was mainly characterized by pruritus and urticaria, although dyspnea and hypotension were noted in the first and second patient, respectively. Two of the patients had negative oral challenge tests with ciprofloxacin and all 3 patients tolerated full treatment courses of oral ciprofloxacin. In all 3 cases, use of the Naranjo probability scale indicated a highly probable adverse drug reaction. Moxifloxacin, similar to other fluoroquinolones, can cause immediate hypersensitivity reactions. Previous publications have reported both cross-reactivity and a lack of cross-reactivity among various fluoroquinolones. The 3 patients discussed demonstrated a lack of cross-reactivity between moxifloxacin and ciprofloxacin since they tolerated oral challenge tests and full treatment courses of ciprofloxacin. Moxifloxacin has unique side chains at positions 7 and 8 on its bicyclic ring structure. Antigenic specificity to particular side chains at positions 7 and 8 on the bicyclic ring structure of moxifloxacin may explain this lack of cross-reactivity. Higher reporting rates of anaphylaxis to moxifloxacin compared to other fluoroquinolones may also be related to side chain specificity, although definitive evidence for this is lacking. Based on our experience, patients who develop immediate hypersensitivity reactions to moxifloxacin may receive ciprofloxacin therapy in an appropriately monitored setting if they have previously tolerated full treatment courses of ciprofloxacin. Research into whether there is a specific side chain reaction unique to moxifloxacin is warranted.

  10. Ultraviolet radiation-induced suppression of contact hypersensitivity in relation to padimate O and oxybenzone.

    PubMed

    Fisher, M S; Menter, J M; Willis, I

    1989-03-01

    Contact hypersensitivity (CHS) in mice can be induced by cutaneous sensitization followed by elicitation via ear-painting with trinitrochlorobenzene (TNCB). This CHS reaction is systemic and can be suppressed by exposure of mice to suberythemogenic doses of 280-315 nm radiation. In this study, we investigated whether a commercially available water-resistant sunscreen, either SPF-6 or SPF-15, containing Padimate O (UVB absorber) and oxybenzone (UVA absorber), was effective in preventing systemic suppression of CHS induced by either FS36 sunlamp exposure or solar simulating radiation. We observed that these two sunscreen preparations were totally incapable of preventing the immunologic suppression of contact hypersensitivity by UV radiation. These results indicate that application of sunscreen does not retard the development of suppression of CHS following repeated UV exposure under conditions where erythema is not clinically observed. Thus, erythema may not be a good end point for assessing systemic immune suppression and its consequences.

  11. Cough reflex hypersensitivity: A role for neurotrophins.

    PubMed

    El-Hashim, Ahmed Z; Jaffal, Sahar M

    2017-03-01

    Cough is one of the most common complaints for which sufferers seek medical assistance. However, currently available drugs are not very effective in treating cough, particularly that which follows an upper respiratory tract infection. Nonetheless, there has been a significant increase in our understanding of the mechanisms and pathways of the defensive cough as well as the hypersensitive/pathophysiological cough, both at airway and central nervous system (CNS) levels. Numerous molecules and signaling pathways have been identified as potential targets for antitussive drugs, including neurotrophins (NTs). NTs belong to a family of trophic factors and are critical for the development and maintenance of neurons in the central and peripheral nervous system including sympathetic efferents, sensory neuron afferents, and immune cells. Nerve growth factor (NGF) was the first member of the NT family to be discovered, with wide ranging actions associated with synapse formation, survival, proliferation, apoptosis, axonal and dendritic outgrowth, expression and activity of functionally important proteins such as ion channels, receptors, and neurotransmitters. In addition, NGF has been implicated in several disease states particularly neuropathic pain and most recently in the sensitization of the cough reflex. This review will briefly address the peripheral and central sensitization mechanisms of airway neurons and will then focus on NGF signaling and its role in cough hypersensitivity.

  12. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hypersensitivity pneumonitis immunological test...

  13. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure by...

  14. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure by...

  15. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure by...

  16. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure by...

  17. Delayed Dermal Hypersensitivity in Mice to Spherule and Mycelial Extracts of Coccidioides immitis

    PubMed Central

    Kong, Yi-Chi M.; Savage, D. C.; Kong, Leighton N. L.

    1966-01-01

    Kong, Yi-chi M. (University of California, Berkeley), D. C. Savage, and Leighton N. L. Kong. Delayed dermal hypersensitivity in mice to spherule and mycelial extracts of Coccidioides immitis. J. Bacteriol. 91:876–883. 1966.—A delayed hypersensitivity reaction to spherule and mycelial extracts of Coccidioides immitis was elicited in the footpads of mice vaccinated with killed spherules. Emulsification of the spherules with Freund's adjuvants was unnecessary, but a high concentration of antigen was required to elicit the reaction. Injection of the extracts produced, initially, a swelling which subsided within 4 hr, and then induration, which began at 6 to 8 hr and reached a maximum at 24 hr. The time course of the reaction corresponded to that of the tuberculin reaction in BCG-vaccinated mice. The histological response to coccidioidal extracts was characterized by the early infiltration of both polymorphonuclear and mononuclear cells, and the subsequent predominance of mononuclear cells at 24 to 48 hr. By 72 hr, the mononuclear cells comprised >90% of the cellular infiltrate. Animals infected intranasally with arthrospores (1 to 5 ld50) reacted negatively before and during the crisis period; thereafter (by 28 to 31 days after infection), up to 50% of the survivors showed a delayed reaction. Images PMID:5894227

  18. [The assessment of subjective distress related to hyperacusis with a self-rating questionnaire on hypersensitivity to sound].

    PubMed

    Nelting, M; Rienhoff, N K; Hesse, G; Lamparter, U

    2002-05-01

    So far there has been no adequate measure to assess or illustrate, in terms of different levels, subjective distress related to hypersensitivity to sound. The here presented work describes and discusses the construction of a questionnaire to assess subjective distress related to hypersensitivity to sound (GUF). Between May and September 2000 226 patients that experienced suffering from hypersensitivity to sound as well as from chronic tinnitus, completed a first version of the questionnaire on admittance to the hospital. Of these patients 27.9 % were out-patients and 72.1 % were in-patients. In addition, the in-patients completed the questionnaire again during their last week of treatment. The 27 items of the GUF were interpreted by factor analysis to explore and determine the structure of the questionnaire; the number of items was reduced under the aspects of consistency and reliability. Finally, the revised version of the GUF underwent a first validation. The factor analysis shows three factors explaining 50.65 % variance (factor 1 [KRH], cognitive reactions to hyperacusis; factor 2 [ASV], actional/somatic behaviour; factor 3 [ERG], emotional reaction to external noises). First attempts to validate the questionnaire are promising; it appears that the GUF is also sensitive to therapy effects. The here presented questionnaire is suitable for identifying distinct levels of subjective distress related to hypersensitivity to sound. Thus, for the first time, there is an adequate measure for assessment available. Furthermore, results of part of the sample show that the GUF is also suitable for therapy evaluation.

  19. Skin testing for immediate hypersensitivity to corticosteroids: a case series and literature review.

    PubMed

    Baker, A; Empson, M; The, R; Fitzharris, P

    2015-03-01

    Immediate hypersensitivity to corticosteroids is reported to occur with an incidence of 0.1%. The largest previous case series reporting corticosteroid skin testing has seven patients. We identified 23 patients (mean age 50 years, 65% female) from Auckland City Hospital who underwent skin testing (ST) for suspected corticosteroid hypersensitivity between July 2005 and April 2012. We performed a retrospective clinical case note review detailing clinical history of reaction, skin test results and subsequent management. Most patients (21/23) had a standard panel of testing with prednisolone, triamcinolone, methylprednisolone, hydrocortisone and dexamethasone. Skin tests used a 10% steroid stock concentration for skin prick tests (SPT) and dilutions of 1 : 1000, 1 : 100 and 1 : 10 for subsequent intradermal testing. A weal 3 mm greater than the negative control was considered positive. A total of 23 patients were identified who had skin testing for suspected acute hypersensitivity to corticosteroids, eight of which had a history of anaphylaxis. From 28 reactions (in 23 patients), the most common route of administration was intra-articular (13), followed by oral (7), intravenous (3) and other (5). Skin tests were positive in 8/23 patients, and 7/8 of these patients had a history of corticosteroid-associated anaphylaxis. Skin tests were positive at either the skin prick test or intradermal stages. There was evidence suggesting clinical and skin test cross-reactivity between corticosteroids in one patient. One patient had a positive skin test, but negative oral challenge suggesting the skin test was false positive. Skin tests were negative in 15/23 patients. One patient had a negative prednisolone skin test and positive unblinded oral challenge, suggesting a false-negative skin test. Skin testing can provide sufficient evidence to diagnose allergy in patients with a clear history of immediate hypersensitivity to corticosteroids such as anaphylaxis. Both skin prick

  20. Immediate hypersensitivity to iodinated contrast media: diagnostic accuracy of skin tests and intravenous provocation test with low dose.

    PubMed

    Sesé, L; Gaouar, H; Autegarden, J-E; Alari, A; Amsler, E; Vial-Dupuy, A; Pecquet, C; Francès, C; Soria, A

    2016-03-01

    The diagnosis of HSR to iodinated contrast media (ICM) is challenging based on clinical history and skin tests. This study evaluates the negative predictive value (NPV) of skin tests and intravenous provocation test (IPT) with low-dose ICM in patients with suspected immediate hypersensitivity reaction (HSR) to ICM. Thirty-seven patients with suspected immediate hypersensitivity reaction to ICM were included retrospectively. Skin tests and a single-blind placebo-controlled intravenous provocation test (IPT) with low-dose iodinated contrast media (ICM) were performed. Skin tests with ICM were positive in five cases (one skin prick test and five intradermal test). Thirty-six patients were challenged successfully by IPT, and only one patient had a positive challenge result, with a grade I reaction by the Ring and Messmer classification. Ten of 23 patients followed up by telephone were re-exposed to a negative tested ICM during radiologic examination; two experienced a grade I immediate reaction. For immediate hypersensitivity reaction to ICM, the NPV for skin tests and IPT with low dose was 80% (95% CI 44-97%). © 2016 John Wiley & Sons Ltd.

  1. Improved reactive nanoparticles to treat dentin hypersensitivity.

    PubMed

    Toledano-Osorio, Manuel; Osorio, Estrella; Aguilera, Fátima S; Luis Medina-Castillo, Antonio; Toledano, Manuel; Osorio, Raquel

    2018-05-01

    The aim of this study was to evaluate the effectiveness of different nanoparticles-based solutions for dentin permeability reduction and to determine the viscoelastic performance of cervical dentin after their application. Four experimental nanoparticle solutions based on zinc, calcium or doxycycline-loaded polymeric nanoparticles (NPs) were applied on citric acid etched dentin, to facilitate the occlusion and the reduction of the fluid flow at the dentinal tubules. After 24 h and 7 d of storage, cervical dentin was evaluated for fluid filtration. Field emission scanning electron microscopy, energy dispersive analysis, AFM and Nano-DMA analysis were also performed. Complex, storage, loss modulus and tan delta (δ) were assessed. Doxycycline-loaded NPs impaired tubule occlusion and fluid flow reduction trough dentin. Tubules were 100% occluded in dentin treated with calcium-loaded NPs or zinc-loaded NPs, analyzed at 7 d. Dentin treated with both zinc-NPs and calcium-NPs attained the highest reduction of dentinal fluid flow. Moreover, when treating dentin with zinc-NPs, complex modulus values attained at intertubular and peritubular dentin were higher than those obtained after applying calcium-NPs. Zinc-NPs are then supposed to fasten active dentin remodeling, with increased maturity and high mechanical properties. Zinc-based nanoparticles are then proposed for effective dentin remineralization and tubular occlusion. Further research to finally prove for clinical benefits in patients with dentin hypersensitivity using Zn-doped nanoparticles is encouraged. Erosion from acids provokes dentin hypersensitivity (DH) which presents with intense pain of short duration. Open dentinal tubules and demineralization favor DH. Nanogels based on Ca-nanoparticles and Zn-nanoparticles produced an efficient reduction of fluid flow. Dentinal tubules were filled by precipitation of induced calcium-phosphate deposits. When treating dentin with Zn-nanoparticles, complex modulus

  2. Association of Human Leukocyte Antigen Alleles and Nevirapine Hypersensitivity in a Malawian HIV-Infected Population

    PubMed Central

    Carr, Daniel F.; Chaponda, Mas; Jorgensen, Andrea L.; Castro, Elena Cornejo; van Oosterhout, Joep J.; Khoo, Saye H.; Lalloo, David G.; Heyderman, Robert S.; Alfirevic, Ana; Pirmohamed, Munir

    2013-01-01

    Background. The nonnucleoside reverse transcriptase inhibitor nevirapine is the cornerstone of treatment for human immunodeficiency virus (HIV) in many sub-Saharan African countries. However, nevirapine is associated with a 6%–10% risk of developing a hypersensitivity reaction, with different phenotypes, including the blistering conditions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Our aim was to identify predictive human leukocyte antigen (HLA) markers that are associated with nevirapine hypersensitivity. Methods. We identified 117 HIV-infected Malawian adults with nevirapine hypersensitivity (15 drug-induced liver injury [DILI], 33 SJS/TEN, 20 hypersensitivity syndrome, and 46 nevirapine-induced rash plus 3 with both DILI and SJS phenotype) and 155 age-, sex- and ethnicity-matched nevirapine-exposed controls. HLA typing for 5 loci (A, B, C, DRB1, and DQB1) was undertaken using a sequence-based high-resolution protocol. Logistic regression analysis included CD4+ cell count as a covariate. Results. HLA-C*04:01 was found to markedly increase the risk for SJS (odds ratio [OR] = 17.52; 95% confidence interval, 3.31–92.80) and all hypersensitivity phenotypes (OR = 2.64; 95% CI, 1.13–6.18) when compared to the baseline rare allele group in a binary logistic regression model. The OR for absolute risk of SJS/TEN associated with carriage of HLA-C*04:01 was 5.17 (95% CI, 2.39–11.18). Positive predictive value was 2.6% and negative predictive value was 99.2%. In addition, a number of alleles within the HLA-DQB1 loci protected against nevirapine-induced hypersensitivity phenotypes. Conclusions. Our study has identified HLA-C*04:01 carriage as a risk factor for nevirapine-induced SJS/TEN in a Malawian HIV cohort. Validation of these findings in a larger cohort of patients and mechanistic investigation of the pathogenesis are required. PMID:23362284

  3. Efficacy of 6-mercaptopurine treatment after azathioprine hypersensitivity in inflammatory bowel disease

    PubMed Central

    Nagy, Ferenc; Molnár, Tamás; Szepes, Zoltán; Farkas, Klaudia; Nyári, Tibor; Lonovics, János

    2008-01-01

    AIM:To investigate the efficacy of 6-mercaptopurine (6-MP) in cases of azathioprine (AZA) hypersensitivity in patients with inflammatory bowel disease. METHODS: Twenty nine previously confirmed Crohn’s disease (CD) (n = 14) and ulcerative colitis (UC) (n = 15) patients with a known previous (AZA) hypersensitivity reaction were studied prospectively. The 6-MP doses were gradually increased from 0.5 up to 1.0-1.5 mg/kg per day. Clinical activity indices (CDAI/CAI), laboratory variables and daily doses of oral 5-ASA, corticosteroids, and 6-MP were assessed before and in the first, sixth and twelfth months of treatment. RESULTS: In 9 patients, 6-MP was withdrawn in the first 2 wk due to an early hypersensitivity reaction. Medication was ineffective within 6 mo in 6 CD patients, and myelotoxic reaction was observed in two. Data were evaluated at the end of the sixth month in 12 (8 UC, 4 CD) patients, and after the first year in 9 (6 UC, 3 CD) patients. CDAI decreased transiently at the end of the sixth month, but no significant changes were observed in the CDAI or the CAI values at the end of the year. Leukocyte counts (P = 0.01), CRP (P = 0.02), and serum iron (P = 0.05) values indicated decreased inflammatory reactions, especially in the UC patients at the end of the year, making the possibility to taper oral steroid doses. CONCLUSION: About one-third of the previously AZA-intolerant patients showed adverse effects on taking 6MP. In our series, 20 patients tolerated 6MP, but it was ineffective in 8 CD cases, and valuable mainly in ulcerative colitis patients. PMID:18666323

  4. Pharmacokinetics of [14C]Abacavir, a Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcriptase Inhibitor, Administered in a Single Oral Dose to HIV-1-Infected Adults: a Mass Balance Study

    PubMed Central

    McDowell, James A.; Chittick, Gregory E.; Ravitch, Joshua R.; Polk, Ronald E.; Kerkering, Thomas M.; Stein, Daniel S.

    1999-01-01

    Abacavir (1592U89) {(−)-(1S, 4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol} is a 2′-deoxyguanosine analogue with potent activity against human immunodeficiency virus (HIV) type 1. To determine the metabolic profile, routes of elimination, and total recovery of abacavir and metabolites in humans, we undertook a phase I mass balance study in which six HIV-infected male volunteers ingested a single 600-mg oral dose of abacavir including 100 μCi of [14C]abacavir. The metabolic disposition of the drug was determined through analyses of whole-blood, plasma, urine, and stool samples, collected for a period of up to 10 days postdosing, and of cerebrospinal fluid (CSF), collected up to 6 h postdosing. The radioactivity from abacavir and its two major metabolites, a 5′-carboxylate (2269W93) and a 5′-glucuronide (361W94), accounted for the majority (92%) of radioactivity detected in plasma. Virtually all of the administered dose of radioactivity (99%) was recovered, with 83% eliminated in urine and 16% eliminated in feces. Of the 83% radioactivity dose eliminated in the urine, 36% was identified as 361W94, 30% was identified as 2269W93, and 1.2% was identified as abacavir; the remaining 15.8% was attributed to numerous trace metabolites, of which <1% of the administered radioactivity was 1144U88, a minor metabolite. The peak concentration of abacavir in CSF ranged from 0.6 to 1.4 μg/ml, which is 8 to 20 times the mean 50% inhibitory concentration for HIV clinical isolates in vitro (0.07 μg/ml). In conclusion, the main route of elimination for oral abacavir in humans is metabolism, with <2% of a dose recovered in urine as unchanged drug. The main route of metabolite excretion is renal, with 83% of a dose recovered in urine. Two major metabolites, the 5′-carboxylate and the 5′-glucuronide, were identified in urine and, combined, accounted for 66% of the dose. Abacavir showed significant penetration into CSF. PMID:10582871

  5. Nevirapine/zidovudine/lamivudine has superior immunological and virological responses not reflected in clinical outcomes in a 48-week randomized comparison with abacavir/zidovudine/lamivudine in HIV-infected Ugandan adults with low CD4 cell counts.

    PubMed

    Munderi, P; Walker, A S; Kityo, C; Babiker, A G; Ssali, F; Reid, A; Darbyshire, J H; Grosskurth, H; Mugyenyi, P; Gibb, D M; Gilks, C F

    2010-05-01

    Triple nucleoside reverse transcriptase inhibitor regimens have advantages as first-line antiretroviral therapy (ART), avoiding hepatotoxicity and interactions with anti-tuberculosis therapy, and sparing two drug classes for second-line ART. Concerns exist about virological potency; efficacy has not been assessed in Africa. A safety trial comparing nevirapine with abacavir was conducted in two Ugandan Development of Antiretroviral Therapy in Africa (DART) centres: 600 symptomatic antiretroviral-naïve HIV-infected adults with CD4 counts <200 cells/microL were randomized to zidovudine/lamivudine plus abacavir or nevirapine (placebo-controlled to 24-week primary toxicity endpoint, and then open-label). Documented World Health Organization (WHO) stage 4 events were independently reviewed and plasma HIV-1 RNA assayed retrospectively. Exploratory efficacy analyses are intention-to-treat. The median pre-ART CD4 count was 99 cells/microL, and the median pre-ART viral load was 284 600 HIV-1 RNA copies/mL. A total of 563 participants (94%) completed 48 weeks of follow-up, 25 (4%) died and 12 (2%) were lost to follow-up. The randomized drug was substituted in 21 participants (7%) receiving abacavir vs. 34 (11%) receiving nevirapine (P=0.09). At 48 weeks, 62% of participants receiving abacavir vs. 77% of those receiving nevirapine had viral loads <50 copies/mL (P<0.001), and mean CD4 count increases from baseline were +147 vs. +173 cells/microL, respectively (P=0.006). Nine participants (3%) receiving abacavir vs. 16 (5%) receiving nevirapine died [hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.24-1.25; P=0.15]; 20 receiving abacavir vs. 32 receiving nevirapine developed new or recurrent WHO 4 events or died (HR=0.60; 95% CI 0.34-1.05; P=0.07) and 48 receiving abacavir vs. 68 receiving nevirapine developed new or recurrent WHO 3 or 4 events or died (HR=0.67; 95% CI 0.46-0.96; P=0.03). Seventy-one participants (24%) receiving abacavir experienced 91 grade 4 adverse

  6. Hypersensitivity to aeroallergens in adult patients with atopic dermatitis develops due to the different immunological mechanisms.

    PubMed

    Samochocki, Zbigniew; Owczarek, Witold; Rujna, Paweł; Raczka, Alicja

    2007-01-01

    Atopic dermatitis (AD) is a disease with a complex pathomechanism, it is very difficult to establish the exact factors which can either trigger or exacerbate the disease. Knowledge of the mechanisms involved in AD development can be increased by, among others, applying new diagnostic tests and careful assessment of the results obtained. The aim of this study was to determine the allergic mechanisms of hypersensitivity to selected aeroallergens in patients with AD. The study comprised 109 AD patients. In all the patients the total IgE level was measured and atopy patch tests and skin prick tests were performed. We also assessed the presence of specific IgE against house dust mite, birch-tree, mixed grass pollen and cat dander. The highest incidence of positive results was found for house dust mite allergens, irrespective of the test employed. Analysing hypersensitivity to all the examined allergens we revealed the presence of allergic mechanisms in 85.3% of the patients. In 30.2% of the examined individuals we proved a type I immunological response, in 45.9% -- both types I and IV in 9.2% -- only type IV in one patient. In 14.7% of the patients the results of all the tests performed were negative. Analysing hypersensitivity to particular aeroallergens, negative test results to house dust mite were observed in 25.8% of the patients. The percentage of positive results for birch pollen, grass pollen and cat dander were 45.0, 44.1 and 53.2, respectively. Analysis of the results showed that allergic reactions to the same aeroallergens may develop via different mechanisms. We also revealed that the coexistence of various mechanisms involved in the development of hypersensitivity to a particular aeroallergen may occur in individual patients.

  7. Anisakis hypersensitivity in Italy: prevalence and clinical features: a multicenter study.

    PubMed

    2011-12-01

    Anisakis simplex (As), a parasite in fish, is able to sensitize humans via the alimentary tract. The prevalence of hypersensitivity and allergy to As outside the Iberian peninsula has not been investigated so far. We investigated Anisakis hypersensitivity in different areas of Italy. Consecutive subjects seen at 34 Italian allergy centers from October to December 2010 were investigated both by specific interview and by skin prick test (SPT) with As extract. A total of 10 570 subjects were screened, of which 474 (4.5%) scored positive on Anisakis SPT and 66 of these (14% of those sensitized; 0.6% of the studied population) had a history of As allergy. Marinated anchovies were the most frequent cause of allergic reactions. Thirty-four (52%) patients were mono-sensitized to Anisakis. Sensitization rate showed marked geographic differences (range: 0.4-12.7%), being highest along the Adriatic and Tyrrhenian coasts, where homemade marinated anchovies are an age-old tradition. In inland centers in northern Italy, the prevalence was directly related to the number of inhabitants. The analysis of the impact of immigration on the prevalence of Anisakis hypersensitivity showed that about 60% of sensitized subjects in Milano and Torino came from southern Italy or from non-European countries. Anisakis hypersensitivity and allergy are mainly a matter of dietary habits. Areas where marinated anchovies are popular can be considered as 'endemic' for this type of food allergy, whereas immigration and, possibly, new or imported trendy food styles, such as eating raw fish carpaccios or sushi, are a major causative factor in big cities of inland zones. © 2011 John Wiley & Sons A/S.

  8. Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity

    PubMed Central

    Audicana, M. Teresa; Kennedy, Malcolm W.

    2008-01-01

    Summary: Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (“gastroallergic anisakiasis”), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive. PMID:18400801

  9. Egg hypersensitivity and measles-mumps-rubella vaccine administration.

    PubMed

    Beck, S A; Williams, L W; Shirrell, M A; Burks, A W

    1991-11-01

    Because reports have described egg-sensitive individuals in whom anaphylaxis developed after measles vaccination, current recommendations include delaying administration of egg-derived vaccines until skin testing can be performed. Specifically, the 1988 Red Book recommends skin testing via scratch, prick, or puncture with 1:10 dilution of the vaccine and, if the result is negative, intradermal testing is suggested. The purpose of this study was to evaluate the likelihood of reaction to measles-mumps-rubella (MMR) vaccine in patients with documented egg sensitivity and to delineate the efficacy of skin-prick testing (SPT) to MMR as a predictor of hypersensitivity to the vaccine. Egg sensitivity was documented by initial SPT to egg and then, if possible, double-blind placebo-controlled food challenge (DBPCFC). Patients with a positive DBPCFC to egg or a history of anaphylactic egg sensitivity had a SPT with the MMR vaccine and then were given the MMR vaccine. Additionally, children with atopic dermatitis who had been previously proven egg sensitive via DBPCFCs were evaluated retrospectively for sensitivity to the MMR vaccine. Sixteen children with a history of egg sensitivity underwent SPT to egg, with a positive result 3 mm greater than the negative control found in 12 patients. Eight of these children had a positive DBPCFC to egg. The SPT to MMR vaccine was negative in all 16 children; vaccine administration followed with no resultant systemic problems. Three children had a local reaction at the site of injection. Twelve additional children with atopic dermatitis and egg sensitivity were reviewed. Each child had a positive SPT and DBPCFC to egg.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Mesalamine hypersensitivity and Kounis syndrome in a pediatric ulcerative colitis patient

    PubMed Central

    Kounis, George N; Kouni, Sophia A; Hahalis, George; Kounis, Nicholas G

    2008-01-01

    5-aminosalicylic acid (mesalamine) rarely induces hypersensitivity reactions. If chest pain associated with atypical electrocardiographic changes are seen during its administration, one should always bear in mind typeIvariant of Kounis syndrome. This variant includes patients, of any age, with normal coronary arteries, without predisposing factors for coronary artery disease, in whom the acute release of inflammatory mediators from mast cells can induce either sudden coronary artery narrowing, without increase of cardiac enzymes and troponins, or coronary artery spasm that progresses to acute myocardial infarction, with elevated cardiac enzymes and troponins. PMID:19084925

  11. Investigation of a cutaneous delayed hypersensitivity response as a means of detecting Salmonella dublin infection in cattle.

    PubMed

    Aitken, M M; Hall, G A; Jones, P W

    1978-05-01

    Delayed hypersensitivity reactions developed 48 to 96 h after intradermal injection of killed Salmonella dublin in 25 of 28 cattle which had been inoculated intravenously, and in five of 10 cattle which had been inoculated orally with S dublin 24 to 493 days previously. Control animals showed no delayed hypersensitivity reactions. Persistence of infection in five of the intravenously inoculated and in four of the orally inoculated animals was confirmed by isolation of S dublin from the carcases at necropsy one week after skin testing. Failure to isolate the organism from the carcases of 21 animals which had reacted positively to the intradermal test did not eliminate the possibility of their being carriers of S dublin. Skin testing was concluded to be a reliable means of identifying animals which had been, and possibly still were, infected systemically with S dublin. However recovered animals might be falsely identified as infected. Repeated testing gave misleading results.

  12. Dynamical optical imaging monocytes/macrophages migration and activation in contact hypersensitivity (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Zhang, Zhihong

    2017-02-01

    Inflammatory monocytes/macrophages (Mon/Mφ) play an important role in cutaneous allergic inflammation. However, their migration and activation in dermatitis and how they accelerate the inflammatory reaction are largely unknown. Optical molecular imaging is the most promising tool for investigating the function and motility of immune cells in vivo. We have developed a multi-scale optical imaging approach to evaluate the spatio-temporal dynamic behavior and properties of immune cells from the whole field of organs to the cellular level at the inflammatory site in delayed type hypersensitivity reaction. Here, we developed some multi-color labeling mouse models based on the endogenous labeling with fluorescent proteins and the exogenous labeling with fluorescent dyes. We investigated the cell movement, cell interaction and function of immunocytes (e.g. Mon/Mφ, DC, T cells and neutrophils) in the skin allergy inflammation (e.g., contact hypersensitivity) by using intravital microscopy. The long-term imaging data showed that after inflammatory Mon/Mφ transendothelial migration in dermis, they migrating in interstitial space of dermis. Depletion of blood monocyte with clodronate liposome extremely reduced the inflammatory reaction. Our finding provided further insight into inflammatory Mon/Mφ mediating the inflammatory cascade through functional migration in allergic contact dermatitis.

  13. Immunological diagnosis of cutaneous-pulmonary hypersensitivity vasculitis.

    PubMed

    Skjodt, Neil M; Elliot, Tracey L; Puttagunta, Lakshmi; Yacyshyn, Elaine A; Tron, Victor A

    2007-11-01

    A 47-year-old woman had episodic dyspnoea, fatigue, chest radiograph opacifications, and palpable purpura whose biopsy showed leucocytoclastic vasculitis. Negative immunoglobulin A immunofluorescence staining and clinical exclusion of other disorders narrowed her diagnosis to cutaneous pulmonary hypersensitivity vasculitis.

  14. The radiation hypersensitivity of cells at mitosis.

    PubMed

    Stobbe, C C; Park, S J; Chapman, J D

    2002-12-01

    Mitotic cells are hypersensitive to ionizing radiation, exhibiting single-hit inactivation coefficients near to those of repair deficient cell lines and lymphocytes. To elucidate possible mechanisms for this hypersensitivity, the kinetics of oxygen radiosensitization, the proportion of indirect effect by OH radicals and the kinetics of radiation-induced DNA strand breakage in the chromatin of mitotic cells were investigated. Synchronized populations of