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Sample records for dapsone hypersensitivity syndrome

  1. Case report: dapsone hypersensitivity syndrome associated with treatment of the bite of a brown recluse spider.

    PubMed

    Wille, R C; Morrow, J D

    1988-10-01

    Dapsone (4-4-diaminodiphenyl-sulfone) is a member of the sulfone group of antibiotics used in the treatment of leprosy and various dermatitidies and more recently employed in the management of local reactions to the bite of the brown recluse spider, Loxosceles reclusa. A dapsone hypersensitivity syndrome, consisting of fever, headache, nausea, vomiting, lymphadenopathy, hepatitis, hemolysis, leukopenia, and mononucleosis, has been described in patients treated with the drug for leprosy. A case report of the hypersensitivity syndrome occurring in a patient being treated with dapsone for a brown recluse spider bite is presented.

  2. 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.

  3. Hypersensitivity reactions to dapsone: a systematic review.

    PubMed

    Lorenz, Maria; Wozel, Gottfried; Schmitt, Jochen

    2012-03-01

    Dapsone is widely used in the treatment of leprosy and several chronic inflammatory dermatological conditions. Hypersensitivity reactions to dapsone are potentially fatal adverse drug reactions with unknown prevalence and risk factors. We performed a systematic review covering all reported cases of hypersensitivity reactions, in order to systematically summarize the published evidence on prevalence, clinical course and fatality rate. Articles were identified through standardized search strategies. Included studies were reviewed for hypersensitivity characteristics and odds ratios were calculated in univariate and multivariate regression models to assess the risk factors for fatal outcome. A total of 114 articles (17 epidemiological studies, 97 case reports) totalling 336 patients with hypersensitivity reactions were included for analysis. From the epidemiological studies a total hypersensitivity reaction prevalence rate of 1.4% (95% confidence interval 1.2–1.7%) was determined. Mucosal involvement, hepatitis, higher age and disease occurrence in non-affluent countries were associated with higher risk of fatal outcome. Overall, the fatality rate was 9.9%.

  4. Drug hypersensitivity syndrome.

    PubMed

    Bonnetblanc, J M

    1993-01-01

    Some types of hypersensitivity to drugs are defined either by the generic name of the drug or descriptive terms. They are sometimes assimilated to pseudolymphoma because the causative drugs are often the same, although the eruption lacks clinical and histopathological criteria of pseudolymphoma. It is then suggested to use 'idiosyncratic drug hypersensitivity syndrome' to define this type of drug reaction. As the skin and other organs may be involved, a generic name would help to determine a better definition and a surveillance program.

  5. Multiple drug hypersensitivity syndrome.

    PubMed

    Chiriac, Anca M; Demoly, Pascal

    2013-08-01

    The multiple drug hypersensitivity syndrome (MDH) is a distinct clinical entity, different from cross-reactivity and flare-up reactions. Following its initial description in 1989 by Sullivan et al., several authors have addressed the issues surrounding this peculiar form of drug hypersensitivity. Whether this syndrome is single or can be further classified in several entities is still a matter of debate. Case reports, case series or studies involving large populations on MDH are few. The use of this term in the literature is heterogeneous, and the definitions variable. Given the major advances in the study of drug hypersensitivities in general, and ongoing research regarding severe cutaneous adverse reactions in particular, careful study of the subgroup of patients with demonstrated immunological basis of MDH has enabled the generation of possible pathogenetic hypotheses. Together with the studies (despite their limitations) to estimate the prevalence of this syndrome in adult and paediatric patients these emerging data need confirmation through larger studies with well defined populations. Bringing together the experience of groups involved in the field of drug allergy should help to move knowledge regarding this peculiar form of drug hypersensitivity forward.

  6. Ibuprofen-induced hypersensitivity syndrome.

    PubMed

    Nanau, Radu M; Neuman, Manuela G

    2010-06-01

    Ibuprofen is a widely used antipyretic and analgesic nonsteroidal antiinflammatory drug (NSAID). With the aging of the population, there will be a significant increase in the prevalence of painful degenerative and inflammatory rheumatic conditions. This increase likely will lead to a parallel increase in the use of NSAIDs, including ibuprofen. The primary effect of the NSAIDs is to inhibit cyclooxygenase (prostaglandin synthase), thereby impairing the ultimate transformation of arachidonic acid to prostaglandins, prostacyclin, and thromboxanes. Although in the majority of cases it is safe, this NSAID, ibuprofen, can produce an unpredictable, idiosyncratic, type B reaction that may pose a major concern in clinical practice. Type B reactions are known to occur in susceptible individuals. The true hypersensitivity reaction (HSR) is a systemic disease defined by the triad of fever, rash, and internal organ involvement that starts 1 day to 12 weeks after the initiation of therapy. HSR has limited the therapeutic use of many drugs, including ibuprofen. Hypersensitivity syndrome associated with ibuprofen is a host-dependent drug reaction that is idiosyncratic in nature. This reaction likely is caused by a combination of metabolic and immunologic factors. Immune mediated components, such as T-cell and their products cytokines and chemokines, can exacerbate cellular responses and create complex pathways that lead to a variety of clinical manifestations. Our review presents an ibuprofen-induced clinical manifestation of hypersensitivity syndrome and the necessity of wisely monitoring the patients clinically and by laboratory investigations when prescribing this drug.

  7. Anticonvulsant hypersensitivity syndrome treated with intravenous immunoglobulin.

    PubMed

    Dredge, David C; Parsons, Elizabeth C; Carter, Lindsay P; Staley, Kevin J

    2010-07-01

    Anticonvulsant hypersensitivity syndrome is a severe, potentially life-threatening, reaction to the aromatic anticonvulsant medications. Reported here is a case of anticonvulsant hypersensitivity syndrome secondary to phenobarbital in a 2-year-old boy; he responded to drug withdrawal, corticosteroids, and intravenous immunoglobulin. The literature regarding treatment of this syndrome is reviewed.

  8. Cytomegalovirus reactivation in drug induced hypersensitivity syndrome.

    PubMed

    Mathuram, Alice J; George, Renu E

    2014-06-01

    Drug induced hypersensitivity syndrome has been reported to a variety of drugs. Reactivation of herpes viruses is associated with relapse of symptoms even as late as five weeks after stopping the inciting drug. We report here a case of drug hypersensitivity with CMV reactivation which was treated successfully.

  9. Dapsone in rheumatoid arthritis.

    PubMed

    Chang, D J; Lamothe, M; Stevens, R M; Sigal, L H

    1996-06-01

    Dapsone, a synthetic sulfone with chemical similarities to sulfapyridine, has been used for a number of years to treat leprosy and dermatitis herpetiformis. Recently, a number of prospective, randomized, double-blind trials have shown their success in the management of rheumatoid arthritis, with dapsone being superior to placebo and comparable to chloroquine and hydroxychloroquine. Its mode of anti-inflammatory actions in rheumatoid arthritis is not clearly understood, but modulation of neutrophil activity or inhibition of neutrophil inflammatory product formation or release appear to play a role. The major limiting side effect is hemolytic anemia, which may be mitigated through careful patient selection, conservative drug dosing, close monitoring, and possibly, concurrent administration of antioxidants or cytochrome P450 inhibitors. Methemoglobinemia is another common finding among patients receiving dapsone therapy, but rarely does it result in prominent symptoms other than transient pallor. Less common adverse events to dapsone include the idiosyncratic reactions of leukopenia and agranulocytosis, cutaneous eruptions, peripheral neuropathy, psychosis, toxic hepatitis, cholestatic jaundice, nephrotic syndrome, renal papillary necrosis, severe hypoalbuminemia without proteinuria, an infectious mononucleosis-like syndrome, and minor neurological and gastrointestinal complaints. In this report, two patients with advanced rheumatoid arthritis, who were safely and effectively treated with dapsone after failure with other second-line agents, are described and the literature is reviewed. We suggest that dapsone is an effective second-line agent in the treatment of rheumatoid arthritis.

  10. Drug-Hypersensitivity Syndrome: Diagnosis and Treatment

    PubMed Central

    Hamm, Rose L.

    2012-01-01

    Drug-induced hypersensitivity syndrome is a systemic autoimmune disorder that results in mucocutaneous symptoms ranging in severity from mild pruritus to life-threatening skin and mucosal loss, with different nomenclature depending on the severity of the symptoms. The purpose of this article is to review the recent advances in understanding the pathology of drug-induced hypersensitivity syndrome, as well as current recommendations for both medical and wound management. PMID:24527369

  11. Drug-hypersensitivity syndrome: diagnosis and treatment.

    PubMed

    Hamm, Rose L

    2011-12-01

    Drug-induced hypersensitivity syndrome is a systemic autoimmune disorder that results in mucocutaneous symptoms ranging in severity from mild pruritus to life-threatening skin and mucosal loss, with different nomenclature depending on the severity of the symptoms. The purpose of this article is to review the recent advances in understanding the pathology of drug-induced hypersensitivity syndrome, as well as current recommendations for both medical and wound management.

  12. Anticonvulsant hypersensitivity syndrome secondary to carbamazepine

    PubMed Central

    Brown, Shannon C.

    2017-01-01

    Anticonvulsant hypersensitivity syndrome (AHS) is a potentially fatal multiorgan drug reaction that presents with various cutaneous eruptions. There is a genetic predisposition to such reactions. We present a young woman with AHS due to carbamazepine that presented as an atypical erythema multiforme with elevated liver enzymes. PMID:28127149

  13. Anticonvulsant hypersensitivity syndrome: incidence, prevention and management.

    PubMed

    Knowles, S R; Shapiro, L E; Shear, N H

    1999-12-01

    Although the anticonvulsant hypersensitivity syndrome was first described in 1950, confusion still abounds regarding the syndrome. The triad of fever, rash and internal organ involvement occurring 1 to 8 weeks after exposure to an anticonvulsant heralds this rare (1 in 1,000 to 10,000 exposures) but serious reaction. Aromatic anticonvulsants [phenytoin, phenobarbital (phenobarbitone) and carbamazepine] are the most frequently involved drugs; however, there have also been several cases of anticonvulsant hypersensitivity syndrome associated with lamotrigine. Fever, in conjunction with malaise and pharyngitis, is often the first sign. This is followed by a rash which can range from a simple exanthem to toxic epidermal necrolysis. Internal organ involvement usually involves the liver, although other organs such as the kidney, CNS or lungs may be involved. Hypothyroidism may be a complication in these patients approximately 2 months after occurrence of symptoms. The aromatic anticonvulsants are metabolised to hydroxylated aromatic compounds, such as arene oxides. If detoxification of this toxic metabolite is insufficient, the toxic metabolite may bind to cellular macromolecules causing cell necrosis or a secondary immunological response. Cross-reactivity among the aromatic anticonvulsants may be as high as 75%. In addition, there is a familial tendency to hypersensitivity to anticonvulsants. Discontinuation of the anticonvulsant is essential in patients who develop symptoms compatible with anticonvulsant hypersensitivity syndrome. A minimum battery of laboratory tests, such as liver transaminases, complete blood count and urinalysis and serum creatinine, should be performed. Corticosteroids are usually administered if symptoms are severe. Patients with anticonvulsant hypersensitivity syndrome should avoid all aromatic anticonvulsants; benzodiazepines, valproic acid (sodium valproate) or one of the newer anticonvulsants can be used for seizure control. However, valproic

  14. Drug hypersensitivity: pharmacogenetics and clinical syndromes.

    PubMed

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

    2011-03-01

    Severe cutaneous adverse reactions include syndromes such as drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). An important advance has been the discovery of associations between HLA alleles and many of these syndromes, including abacavir-associated hypersensitivity reaction, allopurinol-associated 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 severe cutaneous adverse reactions. The rollout 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, in which the positive predictive value of HLA-B∗1502 is low and the negative predictive value of HLA-B∗1502 for SJS/TEN might not be 100% in all ethnic groups. International collaborative consortia have been formed with the goal of developing phenotypic standardization and undertaking HLA and genome-wide analyses in diverse populations with these syndromes.

  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. 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

  17. Dapsone Topical

    MedlinePlus

    ... drugs'), or any of the ingredients in dapsone gel. Ask your pharmacist for a list of the ingredients.tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. ...

  18. Laryngeal sensory dysfunction in laryngeal hypersensitivity syndrome.

    PubMed

    Vertigan, Anne E; Bone, Sarah L; Gibson, Peter G

    2013-08-01

    Diseases associated with laryngeal dysfunction include chronic refractory cough (CRC), paradoxical vocal fold movement (PVFM), muscle tension dysphonia (MTD) and globus pharyngeus. We hypothesized the presence of a common sensory laryngeal dysfunction, the 'laryngeal hypersensitivity' syndrome, in these conditions. The aim of the study was to compare symptoms and sensory function in patients with CRC, PVFM, MTD and globus. The 103 participants included healthy controls (n = 13) and four case groups: CRC (n = 33), PVFM (n = 28), globus pharyngeus (n = 11) and MTD (n = 18). Participants completed self-report questionnaires: Symptom Frequency and Severity Scale, Voice Handicap Index and the Laryngeal Paraesthesia Questionnaire; and quantitative sensory testing: capsaicin cough reflex sensitivity, hypertonic saline challenge, the timed swallow test, acoustic voice testing, cough frequency monitor and a voice stress test. All case groups reported a high-symptom burden in comparison to controls. The case groups showed a similar pattern of symptoms, with impairment in each of the cough, respiration, vocal and upper airway symptom domains. Objective testing revealed significant sensory impairment in the case groups compared to controls and also showed an overlap in sensory dysfunction between the four case groups. Furthermore, there was cross-sensory stimulation of symptoms whereby stimulation of a particular response resulted in symptoms in another domain. These discrete clinical laryngeal syndromes display considerable overlap in their clinical features and a common sensory dysfunction, supporting the 'laryngeal hypersensitivity' hypothesis. Reconceptualizing functional laryngeal disorders as a form of laryngeal hypersensitivity syndrome provides an alternative approach to management of these perplexing conditions. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

  19. Drug hypersensitivity syndrome induced by meglumine antimoniate.

    PubMed

    Jeddi, Fakhri; Caumes, Eric; Thellier, Marc; Jauréguiberry, Stéphane; Mazier, Dominique; Buffet, Pierre A

    2009-06-01

    We report a case of drug hypersensitivity syndrome (drug reaction with eosinophilia and systemic symptoms [DRESS]) induced by parenteral meglumine antimoniate (Glucantime) in a 40-year-old man who traveled to Bolivia and was treated for mucocutaneous leishmaniasis. Two weeks after starting therapy, the patient had fever, joint pain, a cutaneous eruption, and hypereosinophilia (1,358 cells/mm(3)). These symptoms resolved after drug withdrawal but reappeared upon reintroduction of the drug. Pentavalent antimonials should be definitively withdrawn in patients with hypereosinophilia > 1,000 cells/mm(3) accompanied by systemic manifestations consistent with DRESS.

  20. Multiple organ dysfunction syndrome: infection or hypersensitivity reaction?

    PubMed

    Dreesman, Alexandra; Hoorens, Anne; Hachimi-Idrissi, Said

    2010-08-01

    Anticonvulsant hypersensitivity syndrome is a potentially life-threatening delayed hypersensitivity reaction characterized by the triad of fever, rash and multiorgan involvement, which usually occurs within the first weeks of introduction of an antiepileptic drug. It mimics several life-threatening diseases, which makes it potentially difficult to recognize. We describe the case of a 6-year-old boy admitted with anticonvulsant hypersensitivity syndrome after the association of lamotrigine treatment with sodium valproic acid for reluctant epilepsy.

  1. Drug hypersensitivity syndrome with significant gastrointestinal involvement.

    PubMed

    Chung, Wan-Ling; Teo, Lynn; Wang, Yi-Shi; Liu, Tsun-Tsien

    2012-11-01

    Drug hypersensitivity syndrome (DHS) is an idiosyncratic systemic reaction to a drug. The clinical presentation of this syndrome comprises a diverse spectrum, ranging from mild to fulminating organ failure. Nonspecific gastrointestinal symptoms are common in DHS, but severe morbidities and mortalities attributed to gut disease in DHS are rarely described. We present a case of DHS with significant gastrointestinal symptoms of prolonged profuse watery diarrhoea and persistent hypokalaemia requiring judicious intravenous water and electrolyte replacement. The symptoms resolved only after the introduction of intravenous hydrocortisone. It is important to consider intravenous corticosteroids if the gastrointestinal system is involved, as accelerated gut motility and mucosal damage would affect absorption of oral medications. Supportive treatment with the monitoring of fluid and electrolytes status and judicious replacement remains fundamental in the management of DHS patients with gut involvement.

  2. [Anticonvulsant hypersensitivity syndrome: an entity to be remembered].

    PubMed

    Crespo Pérez, Laura; Moreira Vicente, Víctor; Cano Ruiz, Ana; Gobernado Serrano, José María; Cobo Ibañez, Natalia; Milicua Salamero, José María

    2009-12-01

    Anticonvulsant hypersensitivity syndrome is an unpredictable, potentially fatal drug reaction to aromatic anticonvulsants such as carbamazepine, phenytoin and phenobarbital. The hallmark features include fever, eosinophilia, rash and involvement of one or more internal organs. Clearly established diagnostic criteria and treatment guidelines are lacking. A high index of suspicion is required to identify this syndrome, allowing early withdrawal of the drug and avoiding re-exposure. We report an illustrative case of anticonvulsant hypersensitivity syndrome and review the published literature.

  3. The cough hypersensitivity syndrome: a novel paradigm for understanding cough.

    PubMed

    Morice, Alyn H

    2010-01-01

    For many years patients with chronic cough have been investigated in an attempt to diagnose the cause of the cough. Here I suggest that the overwhelming majority of patients with chronic cough have a single diagnosis: cough hypersensitivity syndrome. This is demonstrated by the homogeneous nature of the clinical history and investigational results of patients attending cough clinics. The hypersensitivity facet of the syndrome is demonstrated by objective testing with capsaicin and other protussive agents. Within the cough hypersensitivity syndrome there are different phenotypes. Those patients with a predominantly Th2-type immune response will develop eosinophilic inflammation and either cough-variant asthma or eosinophilic bronchitis. Those with predominantly heartburn symptoms will have a phenotype that reflects GERD and cough. However, the similarities between the different phenotypes far outweigh differences in a unifying diagnosis of the cough hypersensitivity syndrome, providing a more rational understanding of chronic cough.

  4. Neonatal isolated rectal bleeding and the risk of hypersensitivity syndromes.

    PubMed

    Reiter, O; Morag, I; Mazkereth, R; Strauss, T; Maayan-Metzger, A

    2014-01-01

    When rectal bleeding occurs in an otherwise asymptomatic child, it can be classified as isolated rectal bleeding (IRB). Among the different etiologies suggested for IRB, one of the most common is a hypersensitivity reaction of the bowel mucosa to digested antigens. The objective of this study was to assess the long-term outcomes and the risk of developing hypersensitivity syndromes among infants following an IRB event. A historical prospective comparative study was carried out. The study compared 77 infants who were born at the Sheba Medical Center in Israel during the period 2002 to 2009 and who experienced a neonatal IRB event to 77 infants with the same gestational age, but without IRB. Data were obtained from hospital records and from phone interviews with the parents regarding hypersensitivity syndrome between the ages of 3 and 10 years. The IRB group was not at an increased risk of developing a hypersensitivity syndrome or gastrointestinal symptoms compared to the control group. Longer duration of breast-feeding was found to be related to a lower incidence of hypersensitivity symptoms. An IRB event in the neonatal period does not increase the risk of developing hypersensitivity syndromes or food allergies during childhood.

  5. Hypersensitivity to proton pump inhibitors: lansoprazole-induced Kounis syndrome.

    PubMed

    Vlahos, Nicholas P; Vavilis, George K; Giannelou, Ageliki G; Georgopoulou, Christina N; Kommata, Varvara J; Kougias, Constantinos T; Tsartsalis, Dimitrios N; Kounis, George N; Mazarakis, Andreas; Batsolaki, Maria; Gouvelou-Deligianni, Geogia V; Hahalis, George; Kounis, Nicholas G

    2009-05-29

    Proton pump inhibitors are commonly used in clinical practice for the treatment of peptic ulcer and gastroesophageal reflux and are well tolerated by the patients. Their use is rarely associated with hypersensitivity and anaphylactic reactions. According to the reports in the Uppsala Monitoring Center database the frequency of hypersensitivity reactions out of all reported adverse reactions for proton pump inhibitors and H2-histamine receptor antagonists was between 0.2% and 0.7%. A few cases of hypersensitivity to lansoprazole have been reported. We report a patient who developed Kounis syndrome after taking 30 mg of lansoprazole. This is the first report of Kounis syndrome associated with lansoprazole administration in the world literature.

  6. Trichloroethylene hypersensitivity syndrome: a disease of fatal outcome.

    PubMed

    Jung, Hyun Gul; Kim, Hyung Hun; Song, Bong Gun; Kim, Eun Jin

    2012-01-01

    Trichloroethylene is commonly used as an industrial solvent and degreasing agent. The clinical features of acute and chronic intoxication with trichloroethylene are well-known and have been described in many reports, but hypersensitivity syndrome caused by trichloroethylene is rarely encountered. For managing patients with trichloroethylene hypersensitivity syndrome, avoiding trichloroethylene and initiating glucocorticoid have been generally accepted. Generally, glucocorticoid had been tapered as trichloroethylene hypersensitivity syndrome had ameliorated. However, we encountered a typical case of trichloroethylene hypersensitivity syndrome refractory to high dose glucocorticoid treatment. A 54-year-old Korean man developed jaundice, fever, red sore eyes, and generalized erythematous maculopapular rashes. A detailed history revealed occupational exposure to trichloroethylene. After starting intravenous methylprednisolone, his clinical condition improved remarkably, but we could not reduce prednisolone because his liver enzyme and total bilirubin began to rise within 2 days after reducing prednisolone under 60 mg/day. We recommended an extended admission for complete recovery, but the patient decided to leave the hospital against medical advice. The patient visited the emergency department due to pneumonia and developed asystole, which did not respond to resuscitation.

  7. [Allopurinol hypersensitivity syndrome. A report of two cases].

    PubMed

    Rodríguez-Arámbula, Adriana; Arenas-Velázquez, Elsa; Castanedo-Cázares, Juan Pablo; Hernández-Blanco, Diana; Oros-Ovalle, Cuauhtémoc; Torres-Álvarez, Bertha

    2016-01-01

    Patients in treatment with allopurinol are in risk of having life threatening adverse reactions particularly at the beginning of the treatment. Two percent of the patients prescribed with this drug have associated severe cutaneous adverse reactions. We present two cases of allopurinol hypersensitivity syndrome in mexican patients in which asymptomatic hyperuricemia was the indication to its use. The general physician and the specialist must be alert of this syndrome that causes elevate morbidity and mortality.

  8. Acute kidney injury caused by zonisamide-induced hypersensitivity syndrome.

    PubMed

    Fujita, Yoshiro; Hasegawa, Midori; Nabeshima, Kuihiro; Tomita, Makoto; Murakami, Kazutaka; Nakai, Shigeru; Yamakita, Takashi; Matsunaga, Kayoko

    2010-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a severe adverse drug reaction affecting multiple organs caused by drug treatment. The current report describes a man who was prescribed zonisamide for epilepsy and subsequently developed widespread skin rash, acute kidney injury, high-grade fever, eosinophilia, liver dysfunction, lymphadenopathy and an increase in antihuman herpesvirus-6 immunoglobulin G titer. Hypersensitivity to zonisamide was confirmed by the skin patch test. Based on these findings, the patient was diagnosed with DRESS/DIHS caused by zonisamide. This is the first report of acute kidney injury due to zonisamide-induced DRESS/DIHS.

  9. Cellular hypersensitivity in Guillain-Barré syndrome

    PubMed Central

    Sheremata, William A.; Rocklin, Ross E.; David, John

    1974-01-01

    The Guillain-Barré syndrome is hypothesized to be secondary to cellular hypersensitivity to peripheral nerve antigens. To test this theory lymphocytes from 100 subjects were studied using the macrophage-migration-inhibition factor (MIF) assay. Thirty-four normal controls gave a mean migration of 100.4 ± 9%. Of 34 patients with peripheral nervous system disease, only those with the Guillain-Barré syndrome showed hypersensitivity with a mean migration of 72 ± 11%. Of 34 patients with central nervous system disease only three with multiple sclerosis and two with stroke gave similar results. Positive results in the Guillain-Barré syndrome were found only in patients presenting with classical disease and who were ill at the time of study. PMID:4366128

  10. Drug Hypersensitivity Syndrome with Prolonged Course Complicated by Parvovirus Infection.

    PubMed

    Coughlin, Carrie C; Jen, Melinda V; Boos, Markus D

    2016-11-01

    Drug hypersensitivity syndrome (DHS) is a severe medication reaction involving multiple organ systems that is characterized by rash, lymphadenopathy, and laboratory aberrations, including hepatic enzyme changes. Viral reactivation in the setting of DHS can significantly affect the course of disease. We report two children in whom parvovirus infection prolonged and complicated their course of DHS. Most other DHS-complicating viruses are herpesviruses; this report broadens the scope of DHS-modifying infections to include activation of Parvoviridae. © 2016 Wiley Periodicals, Inc.

  11. [Anticonvulsant Hypersensitivity Syndrome: A Case Report].

    PubMed

    Valderrama Escudero, Felipe; Montoya González, Laura Elisa

    2014-01-01

    DRESS syndrome (skin reaction with eosinophilia and systemic symptoms) is an idiosyncratic drug reaction characterized by rash, fever, lymphadenopathy, and internal organ dysfunction. This case report is on a patient with bipolar affective disorder who presented with a systemic inflammatory response associated with the use of valproic acid, and an important activation of symptoms when used with other drugs with a different pharmacological action mechanism. The diagnosis of DRESS syndrome is primarily by exclusion, and its detection may be difficult, which could potentially become fatal for the patient.

  12. [Hypocomplementemic vasculitis treated with dapsone].

    PubMed

    Hérault, M; Mazet, J; Beurey, P; Cuny, J-F; Barbaud, A; Schmutz, J-L; Bursztejn, A-C

    2010-01-01

    Hypocomplementemic urticarial vasculitis, described by MacDuffie in 1973, is rare. Some doubt surrounds its classification. We report a case of hypocomplementemic urticarial vasculitis (MacDuffie syndrome) treated with dapsone with a favorable outcome. Over a number of years, a 43-year-old man presented urticarial vasculitis attacks with palpebral oedema and systemic symptoms such as fever and arthralgia. In 2006, MacDuffie syndrome was diagnosed on the grounds of positive anti-C1q antibodies. Treatment with dapsone was started and resulted in considerable improvement. Hypocomplementemic urticarial vasculitis is characterized by urticarial vasculitis lesions, leucocytoclastic vasculitis and systemic symptoms. The latter symptoms are similar to those of systemic lupus erythematosus (SLE), and some authors have suggested that MacDuffie syndrome may in fact belong to SLE. Diagnosis is based on clinical appearance, histology and the presence of anti-C1q antibodies. There is no specific treatment for hypocomplementemic urticarial vasculitis. Immunosuppressant therapy can be used for lesions refractory to systemic corticosteroids. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  13. Irritable bowel syndrome in childhood: visceral hypersensitivity and psychosocial aspects.

    PubMed

    Iovino, P; Tremolaterra, F; Boccia, G; Miele, E; Ruju, F M; Staiano, A

    2009-09-01

    Visceral hypersensitivity is often considered to play a major etiologic role in the pathophysiology of irritable bowel syndrome in adults, and some authors argue that this increased sensitivity is mainly due to psychological factors. In contrast, there are no data in children with irritable bowel syndrome which confirm this relationship. The aim of the study was to evaluate the relationship between psychosocial aspects and sensorymotor function in children affected by irritable bowel syndrome. Ten children fulfilling the Rome II criteria for irritable bowel syndrome and seven healthy controls were enrolled. We studied the thresholds and the perception of visceral stimuli in the rectum by means of an electronic barostat (isobaric phasic distentions, 3 mmHg/1 min, interval 1 min) and a validated questionnaire. Personality features were evaluated by means of the Big Five Questionnaire for Children. Sleep, mood disturbance, anxiety and individual performance (missed school days, school results and social activities) were also evaluated. Children with irritable bowel syndrome showed significantly lower thresholds for discomfort (14.8 +/- 3.5 vs 22.3 +/- 6.9 mmHg, P = 0.010) and a higher cumulative perception score (28.2 +/- 11.1 vs 12.3 +/- 8.0, P = 0.005) compared with healthy controls. A higher emotional instability (57.8 +/- 7.0 vs 48.7 +/- 10.1, P = 0.047), sleep disturbance (7.2 +/- 1.0 vs 9.3 +/- 0.5, P = 0.004) and anxiety (6.3 +/- 2.0 vs 2.3 +/- 1.7, P = 0.009) were observed in irritable bowel syndrome patients. Moreover, in a multivariate analysis, the cumulative perception score was significantly related to emotional instability (P = 0.042). In conclusion children with irritable bowel syndrome exhibit visceral hypersensitivity and psychosocial impairment. Emotional instability, as a personality feature in these children, seems to modulate the perception response to visceral stimulations.

  14. [Drug-induced hypersensitivity syndrome and HHV-6 reactivation].

    PubMed

    Tohyama, Mikiko; Hashimoto, Koji

    2009-06-01

    Drug-induced hypersensitivity syndrome (DIHS) is an adverse reaction with clinical signs of fever, rash, and internal organ involvement. The culprit drugs of DIHS are limited to several drugs such as carbamazepine, phenytoin, phenobarbital, zonisamide, allopurinol, salazosulfapyridine, diaphenylsulphone, and mexiletine. The association of HHV-6 reactivation with DIHS has been known. Flaring of symptoms such as fever and hepatitis is closely related to HHV-6 reactivation. A combination of immunologic reaction to a drug and HHV-6 reactivation results in the severe course of DIHS.

  15. Intestinal Membrane Permeability and Hypersensitivity In the Irritable Bowel Syndrome

    PubMed Central

    Zhou, QiQi; Zhang, Buyi; Verne, G. Nicholas

    2009-01-01

    Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the underlying pathophysiology is poorly understood; however, increased intestinal permeability in diarrhea-predominant IBS patients has been reported. Here we demonstrate diarrhea-predominant IBS patients (D-IBS) that display increased intestinal permeability. We have also found that increased intestinal membrane permeability is associated with visceral and thermal hypersensitivity in this subset of D-IBS patients. We evaluated 54 D-IBS patients and 22 controls for intestinal membrane permeability using the lactulose / mannitol method. All subjects ingested 5 g laclulose and 2 g mannitol in 100 ml of water after which their urine was collected. We also evaluated the mean mechanical visual analogue (MVAS) pain rating to nociceptive thermal and visceral stimulation in all subjects. All study participants also completed the FBDSI scale. Approximately 39% of diarrhea-predominant IBS patients have increased intestinal membrane permeability as measured by the lactulose / mannitol ratio. These IBS patients also demonstrated higher M-VAS pain intensity reading scale. Interestingly, the IBS patients with hypersensitivity and increased intestinal permeability had a higher FBDSI score (100.8±5.4) compared to IBS patients with normal membrane permeability and sensitivity (51.6±12.7) and controls (6.1 ± 5.6) (p<0.001). A subset of D-IBS patients have increased intestinal membrane permeability that is associated with an increased FBDSI score and increased hypersensitivity to visceral and thermal nociceptive pain stimuli. Thus, increased intestinal membrane permeability in D-IBS patients may lead to more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli. PMID:19595511

  16. Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome.

    PubMed

    Zhou, QiQi; Zhang, Buyi; Verne, G Nicholas

    2009-11-01

    Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the underlying pathophysiology is poorly understood; however, increased intestinal permeability in diarrhea-predominant IBS patients has been reported. Here we demonstrate that diarrhea-predominant IBS (D-IBS) patients display increased intestinal permeability. We have also found that increased intestinal membrane permeability is associated with visceral and thermal hypersensitivity in this subset of D-IBS patients. We evaluated 54 D-IBS patients and 22 controls for intestinal membrane permeability using the lactulose/mannitol method. All subjects ingested 5g of lactulose and 2g of mannitol in 100ml of water after which their urine was collected. We also evaluated the mean mechanical visual analogue scale (M-VAS) pain rating to nociceptive thermal and visceral stimulation in all subjects. All study participants also completed the FBDSI scale. Approximately 39% of diarrhea-predominant IBS patients had increased intestinal membrane permeability as measured by the lactulose/mannitol ratio. These IBS patients also demonstrated higher M-VAS pain intensity reading scale. Interestingly, the IBS patients with hypersensitivity and increased intestinal permeability had a higher FBDSI score (100.8 + or - 5.4) than IBS patients with normal membrane permeability and sensitivity (51.6 + or - 12.7) and controls (6.1 + or - 5.6) (p<0.001). A subset of D-IBS patients had increased intestinal membrane permeability that was associated with an increased FBDSI score and increased hypersensitivity to visceral and thermal nociceptive pain stimuli. Thus, increased intestinal membrane permeability in D-IBS patients may lead to more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli.

  17. Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation.

    PubMed

    Riyaz, Najeeba; Sarita, S; Arunkumar, G; Sabeena, S; Manikoth, Neeraj; Sivakumar, C P

    2012-01-01

    A 45-year-old man, on carbamazepine for the past 3 months, was referred as a case of atypical measles. On examination, he had high-grade fever, generalized itchy rash, cough, vomiting and jaundice. A provisional diagnosis of drug hypersensitivity syndrome to carbamazepine was made with a differential diagnosis of viral exanthema with systemic complications. Laboratory investigations revealed leukocytosis with eosnophilia and elevated liver enzymes. Real-time multiplex polymerase chain reaction (PCR) on throat swab and blood was suggestive of human herpesvirus-6 (HHV-6). Measles was ruled out by PCR and serology. The diagnosis of drug-induced hypersensitivity syndrome (DIHS) was confirmed, which could explain all the features manifested by the patient. HHV-6 infects almost all humans by age 2 years. It infects and replicates in CD4 T lymphocytes and establishes latency in human peripheral blood monocytes or macrophages and early bone marrow progenitors. In DIHS, allergic reaction to the causative drug stimulates T cells, which leads to reactivation of the herpesvirus genome. DIHS is treated by withdrawal of the culprit drug and administration of systemic steroids. Our patient responded well to steroids and HHV-6 was negative on repeat real-time multiplex PCR at the end of treatment.

  18. Antiepileptic hypersensitivity syndrome: clinicians beware and be aware.

    PubMed

    Bessmertny, Olga; Pham, Trinh

    2002-01-01

    Antiepileptic hypersensitivity syndrome is a serious idiosyncratic, non-dose-related adverse reaction reported to occur with phenytoin, phenobarbital, carbamazepine, primidone, and lamotrigine. The reaction usually develops 1 to 12 weeks after initiation of therapy with one of the above agents and is recognized by the classic triad of fever, rash, and internal organ involvement. Immediate discontinuation of the suspected anticonvulsant is essential for good outcome. Patients usually are managed supportively with hydration, antihistamines, H(2)-receptor blockers, and topical corticosteroids. In severe cases, the use of systemic corticosteroids may be necessary. The use of intravenous immune globulin should be limited to severe cases where Kawasaki disease or idiopathic thrombocytopenic purpura cannot be ruled out. Education of health care professionals and patients is imperative to improving outcomes and prevention of this reaction in the future.

  19. Drug-induced hypersensitivity syndrome due to carbapenem antibiotics.

    PubMed

    Goto, Mizuki; Shimizu, Fumiaki; Takeo, Naoko; Okamoto, Osamu; Katagiri, Kazumoto; Ikewaki, Junji; Ogata, Masao; Kadota, Jun-ichi; Fujiwara, Sakuhei

    2010-04-01

    Drug-induced hypersensitivity syndrome (DIHS) is characterized by a serious adverse systemic reaction that usually appears after a 3-6-week exposure to certain drugs, for example, anticonvulsants. Many different precipitating factors have been reported, but the pathophysiology of DIHS remains unknown. However, reactivation of members of the human herpesvirus (HHV) family, and of HHV-6 in particular, has been reported in patients with DIHS. We report the case of a 64-year-old man who developed a generalized erythematous rash, fever, hepatic failure, lymphadenopathy and an increased number of atypical lymphocytes. In addition, reactivation of HHV-6 and cytomegalovirus (CMV) was demonstrated by real-time quantitative amplification by polymerase chain reaction. The patient was given a diagnosis of DIHS due to carbapenem antibiotics based on his clinical course, laboratory data, and results of lymphocyte-stimulation tests with various drugs. This is the first report, to our knowledge, of DIHS induced by carbapenem antibiotics.

  20. Dapsone in dermatology and beyond.

    PubMed

    Wozel, Gottfried; Blasum, Christian

    2014-03-01

    Dapsone (4,4'-diaminodiphenylsulfone) is an aniline derivative belonging to the group of synthetic sulfones. In 1937 against the background of sulfonamide era the microbial activity of dapsone has been discovered. Shortly thereafter, the use of dapsone to treat non-pathogen-caused diseases revealed alternate antiinflammatory mechanisms that initially were elucidated by inflammatory animal models. Thus, dapsone clearly has dual functions of both: antimicrobial/antiprotozoal effects and anti-inflammatory features similarly to non-steroidal anti-inflammatory drugs. The latter capabilities primarily were used in treating chronic inflammatory disorders. Dapsone has been investigated predominantly by in vitro methods aiming to get more insights into the effect of dapsone to inflammatory effector cells, cytokines, and/or mediators, such as cellular toxic oxygen metabolism, myoloperoxidase-/halogenid system, adhesion molecules, chemotaxis, membrane-associated phospholipids, prostaglandins, leukotrienes, interleukin-8, tumor necrosis factor α, lymphocyte functions, and tumor growth. Moreover, attention has been paid to mechanisms by which dapsone mediates effects in more complex settings like impact of lifespan, stroke, glioblastoma, or as anticonvulsive agent. Additionally, there are some dermatological investigations in human being using dapsone and its metabolites (e.g., leukotriene B4-induced chemotaxis, ultraviolet-induced erythema). It could be established that dapsone metabolites by their own have anti-inflammatory properties. Pharmacology and mechanisms of action are determining factors for clinical use of dapsone chiefly in neutrophilic and/or eosinophilic dermatoses and in chronic disorders outside the field of dermatology. The steroid-sparing effect of dapsone is useful for numerous clinical entities. Future avenues of investigations will provide more information on this fascinating and essential agent.

  1. Diagnosing the tight building syndrome or diagnosing chemical hypersensitivity

    SciTech Connect

    Rogers, S.A. )

    1989-01-01

    The abrupt exposure to urea foam formaldehyde insulation served as an alert to its spectrum of symptoms, including attacks of headache, flushing, laryngitis, dizziness, nausea, extreme weakness or exhaustion, arthralgia, an inability to concentrate, unwarranted depression, arrhythmia, or muscle spasms, and baffled physicians from many specialties. Later it was learned that toluene, xylene, benzene, natural gas, trichloroethylene, and many other chemicals were also capable of triggering chemical hypersensitivity. Other names for this condition include Environmentally Induced Illness (EI), the Tight Building Syndrome (TBS), the Sick Building Syndrome, and Building-Related Illness. The very symptoms patients complain of can be provoked within minutes and then subsequently alleviated with an intradermal injection of the appropriate strength of the triggering chemical. This technique aids in convincing the patient of the EI or TBS triggers so that the patient can begin to relate symptoms to environmental exposures and initiate measure to bring the disease under control. The key to safer buildings is increased ventilation, increased filtration of air, and decreased use of off-gassing synthetic materials.

  2. Successful treatment of eosinophilic cellulitis with dapsone.

    PubMed

    Coelho de Sousa, Virgínia; Laureano Oliveira, André; Cardoso, Jorge

    2016-07-15

    A 55-year-old woman presented with a 3-year history of recurrent episodes of pruritic cellulitis-like erythematous plaques, mostly located on the limbs. Simultaneously, fever, malaise and peripheral eosinophilia were noted. The clinical diagnosis of eosinophilic cellulitis (also known as Well's syndrome) was supported by the histopathological finding of typical "flame figures". Treatment with dapsone was initiated at a dose of 50 mg per day. After one year of follow-up the patient was relapse-free. Eosinophilic cellulitis is an uncommon, recurrent inflammatory skin disease. The management is often a challenge, due to the frequent need for long-term therapy. Dapsone is an effective and safe treatment option.

  3. The microwave syndrome or electro-hypersensitivity: historical background.

    PubMed

    Carpenter, David O

    2015-01-01

    Microwave generating equipment first became common during World War 2 with the development of radar. Soviet bloc countries reported that individuals exposed to microwaves frequently developed headaches, fatigue, loss of appetite, sleepiness, difficulty in concentration, poor memory, emotional instability, and labile cardiovascular function, and established stringent exposure standards. For a variety of reasons these reports were discounted in Western countries, where the prevailing belief was that there could be no adverse health effects of electromagnetic fields (EMFs) that were not mediated by tissue heating. The reported Soviet effects were at lower intensities than those that cause heating. However, there were several accidental exposures of radar operators in Western countries that resulted in persistent symptoms similar to those described above. The Soviets irradiated the US Embassy in Moscow with microwaves during the period 1953-1975, and while no convincing evidence of elevated cancer rates was reported, there were reports of "microwave illness". Officials passed these complaints off as being due to anxiety, not effects of the microwave exposure. There is increasing evidence that the "microwave syndrome" or "electro-hypersensitivity" (EHS) is a real disease that is caused by exposure to EMFs, especially those in the microwave range. The reported incidence of the syndrome is increasing along with increasing exposure to EMFs from electricity, WiFi, mobile phones and towers, smart meters and many other wireless devices. Why some individuals are more sensitive is unclear. While most individuals who report having EHS do not have a specific history of an acute exposure, excessive exposure to EMFs, even for a brief period of time, can induce the syndrome.

  4. [Clinical characteristics of drug hypersensitivity syndrome in 10 patients].

    PubMed

    Shu, Chang; Qu, Tao; Jia, Li; Shu, Dan; Chen, Dian; Yan, Cuiyan; Zhao, Wenling; Ren, Rongxin; Sun, Qiuning

    2014-08-13

    To characterize the clinical characteristics of drug hypersensitivity syndrome (DHS). The clinical characteristics of 10 DHS patients admitted into our hospital were analyzed retrospectively. And the occurrence patterns of DHS were summarized. There were 4 males and 6 females with an age range of 17 to 66 years. Suspected drugs were anticonvulsants (n = 5), allopurinol (n = 2), antibiotics (n = 1), acetaminophen (n = 1) and unknown (n = 1). All cases developed skin rashes with fever within 14 to 60 days (n = 10). Lymphadenopathy was observed (n = 6). Morbilliform eruption was most common skin rash (n = 6); facial swelling was also appeared (n = 7). Eosinophilia was observed in all cases (n = 10). Liver involvement was common (n = 9). Autoimmune antibodies abnormality was uncommon; viral infection was complication in several cases. Glucocorticoids were applied in all cases (n = 10), 3 severe cases were administrated with intravenous immunoglobulin (IVIg). The clinical outcomes included discharging with recovery (n = 7), later diagnosed of non-Hodgkin lymphoma (n = 2) and in-hospital death (n = 1). The clinical manifestations of DHS are complicated. And the common reactive drugs include anticonvulsants, allopurinol, antiinflammatory drugs and antibiotics. Some cases may be misdiagnosed and long-term follow-ups are required.

  5. Necrotizing lymphadenitis associated with the phenytoin-induced hypersensitivity syndrome.

    PubMed

    Subbannan, Karthi; Gujral, Jaspal S

    2005-09-01

    A 32-year-old black female was started on phenytoin for seizure prophylaxis following the clipping of an aneurysm. This was stopped after 3 weeks when she developed a generalized skin rash. Over the next week she developed fever, sore throat, dysphagia, and headache. She had an erythematous throat with white exudates on the right tonsil and 1 to 3 cm firm, tender lymphadenopathy in multiple regions. Blood, throat swab and cerebrospinal fluid studies were negative for bacterial or viral infections, except for elevated liver enzymes. CT scan of chest, abdomen, and pelvis showed no lymphadenopathy. Lymph node biopsy suggested necrosis but no evidence of infection, granuloma, or lymphoma. Her lymphadenopathy resolved spontaneously and liver enzymes normalized in 3 weeks. Hypersensitivity syndrome due to antiepileptics manifests as fever, rash, generalized lymphadenopathy, and probably represents a T-cell mediated drug reaction. This reaction may persist despite cessation of the drug, and it may engender expensive evaluation. Careful observation up to 3 weeks after drug cessation may be the best management.

  6. Human herpesvirus 6 involvement in paediatric drug hypersensitivity syndrome.

    PubMed

    Ahluwalia, J; Abuabara, K; Perman, M J; Yan, A C

    2015-04-01

    Human herpesvirus (HHV)6 positivity in the context of drug hypersensitivity syndrome (DHS) may influence disease severity. Systemic corticosteroid treatment of those with DHS testing positive for HHV6 has been speculated to prolong the duration of disease. To evaluate whether paediatric HHV6-positive patients with DHS develop a more severe illness than those without presumed reactivation, and to evaluate the response to systemic corticosteroid treatment. A retrospective case series of 29 paediatric inpatients treated for DHS and tested for HHV6 was undertaken. HHV6-positive and -negative patients were identified and stratified into groups treated or not treated with systemic corticosteroids to examine their disease severity on the basis of hospital length of stay (LOS), total number of febrile days (Tfeb) and days until cessation of progression (CTP). Human herpesvirus6-positive patients had similar demographic characteristics to those of HHV6-negative patients, but had significantly longer hospital LOS (11·5 days vs. 5 days, P = 0·039), Tfeb (12·5 days vs. 3 days, P = 0·032) and CTP (4 days vs. 2 days, P = 0·014). All HHV6-positive patients and most (80%) of the HHV6-negative patients received systemic corticosteroids. Among the HHV6-negative patients, those who received corticosteroids showed significantly shorter CTP than those who did not (3 days vs. 2 days, P = 0·043). Additionally, there was a trend towards shorter hospital LOS and Tfeb among HHV6-negative patients who received corticosteroids vs. those who did not, although these differences were not statistically significant. The most common inciting drugs included trimethoprim-sulfamethoxazole (34%), phenytoin (10%) and amoxicillin (10%). Human herpesvirus6 positivity with DHS is associated with a more severe disease course. Treatment with systemic corticosteroids was associated with a trend towards reduced hospital LOS and Tfeb, and a significantly reduced number of days until cessation of

  7. Intestinal Fungal Dysbiosis Is Associated With Visceral Hypersensitivity in Patients With Irritable Bowel Syndrome and Rats.

    PubMed

    Botschuijver, Sara; Roeselers, Guus; Levin, Evgeni; Jonkers, Daisy M; Welting, Olaf; Heinsbroek, Sigrid E M; de Weerd, Heleen H; Boekhout, Teun; Fornai, Matteo; Masclee, Ad A; Schuren, Frank H J; de Jonge, Wouter J; Seppen, Jurgen; van den Wijngaard, René M

    2017-10-01

    Visceral hypersensitivity is one feature of irritable bowel syndrome (IBS). Bacterial dysbiosis might be involved in the activation of nociceptive sensory pathways, but there have been few studies of the role of the mycobiome (the fungal microbiome) in the development of IBS. We analyzed intestinal mycobiomes of patients with IBS and a rat model of visceral hypersensitivity. We used internal transcribed spacer 1-based metabarcoding to compare fecal mycobiomes of 18 healthy volunteers with those of 39 patients with IBS (with visceral hypersensitivity or normal levels of sensitivity). We also compared the mycobiomes of Long-Evans rats separated from their mothers (hypersensitive) with non-handled (normally sensitive) rats. We investigated whether fungi can cause visceral hypersensitivity using rats exposed to fungicide (fluconazole and nystatin). The functional relevance of the gut mycobiome was confirmed in fecal transplantation experiments: adult maternally separated rats were subjected to water avoidance stress (to induce visceral hypersensitivity), then given fungicide and donor cecum content via oral gavage. Other rats subjected to water avoidance stress were given soluble β-glucans, which antagonize C-type lectin domain family 7 member A (CLEC7A or DECTIN1) signaling via spleen-associated tyrosine kinase (SYK), a SYK inhibitor to reduce visceral hypersensitivity, or vehicle (control). The sensitivity of mast cells to fungi was tested with mesenteric windows (ex vivo) and the human mast cell line HMC-1. α diversity (Shannon index) and mycobiome signature (stability selection) of both groups of IBS patients differed from healthy volunteers, and the mycobiome signature of hypersensitive patients differed from that of normally sensitive patients. We observed mycobiome dysbiosis in rats that had been separated from their mothers compared with non-handled rats. Administration of fungicide to hypersensitive rats reduced their visceral hypersensitivity to normal

  8. Central and peripheral hypersensitivity in the irritable bowel syndrome

    PubMed Central

    Zhou, QiQi; Fillingim, Roger B.; Riley, Joseph L.; Malarkey, William B.; Verne, G. Nicholas

    2010-01-01

    Previous investigations of somatic hypersensitivity in IBS patients have typically involved only a single stimulus modality, and little information exists regarding whether patterns of somatic pain perception vary across stimulus modalities within a group of patients with IBS. Therefore, the current study was designed to characterize differences in perceptual responses to a battery of noxious somatic stimuli in IBS patients compared to controls. A total of 78 diarrhea-predominant and 57 controls participated in the study. We evaluated pain threshold and tolerance and sensory and affective ratings of contact thermal, mechanical pressure, ischemic stimuli, and cold pressor stimuli. In addition to assessing perceptual responses, we also evaluated differences in neuroendocrine and cardiovascular responses to these experimental somatic pain stimuli. A subset of IBS patients demonstrated the presence of somatic hypersensitivity to thermal, ischemic, and cold pressor nociceptive stimuli. The somatic hypersensitivity in IBS patients was somatotopically organized in that the lower extremities that share viscerosomatic convergence with the colon demonstrate the greatest hypersensitivity. There were also changes in ACTH, cortisol, and systolic blood pressure in response to the ischemic pain testing in IBS patients when compared to controls. The results of this study suggest that a more widespread alteration in central pain processing in a subset of IBS patients may be present as they display hypersensitivity to heat, ischemic, and cold pressor stimuli. PMID:20074857

  9. Central and peripheral hypersensitivity in the irritable bowel syndrome.

    PubMed

    Zhou, QiQi; Fillingim, Roger B; Riley, Joseph L; Malarkey, William B; Verne, G Nicholas

    2010-03-01

    Previous investigations of somatic hypersensitivity in IBS patients have typically involved only a single stimulus modality, and little information exists regarding whether patterns of somatic pain perception vary across stimulus modalities within a group of patients with IBS. Therefore, the current study was designed to characterize differences in perceptual responses to a battery of noxious somatic stimuli in IBS patients compared to controls. A total of 78 diarrhea-predominant and 57 controls participated in the study. We evaluated pain threshold and tolerance and sensory and affective ratings of contact thermal, mechanical pressure, ischemic stimuli, and cold pressor stimuli. In addition to assessing perceptual responses, we also evaluated differences in neuroendocrine and cardiovascular responses to these experimental somatic pain stimuli. A subset of IBS patients demonstrated the presence of somatic hypersensitivity to thermal, ischemic, and cold pressor nociceptive stimuli. The somatic hypersensitivity in IBS patients was somatotopically organized in that the lower extremities that share viscerosomatic convergence with the colon demonstrate the greatest hypersensitivity. There were also changes in ACTH, cortisol, and systolic blood pressure in response to the ischemic pain testing in IBS patients when compared to controls. The results of this study suggest that a more widespread alteration in central pain processing in a subset of IBS patients may be present as they display hypersensitivity to heat, ischemic, and cold pressor stimuli.

  10. 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.

  11. Evidence for reactivation of human herpesvirus 6 in generalized lymphadenopathy in a patient with drug-induced hypersensitivity syndrome.

    PubMed

    Saraya, Takeshi; Mikoshiba, Michiaki; Kamiyama, Harumi; Yoshizumi, Masakazu; Tsuchida, Shigeru; Tsukagoshi, Hiroyuki; Ishioka, Taisei; Terada, Miho; Tanabe, Eiichi; Tomioka, Chizuko; Ishii, Haruyuki; Kimura, Hirokazu; Kozawa, Kunihisa; Shiohara, Tetsuo; Takizawa, Hajime; Goto, Hajime

    2013-06-01

    The present case provides direct evidence of human herpesvirus 6 reactivation in resected lymph node tissue in a patient with drug-induced hypersensitivity syndrome. This case clearly demonstrates that appropriate pathological evaluation of lymphadenopathy for drug-induced hypersensitivity syndrome, which mimics malignant lymphoma in clinical, radiological, and pathological findings, is required.

  12. Carbamazepine-induced anticonvulsant hypersensitivity syndrome--pathogenic and diagnostic considerations.

    PubMed

    Scerri, L; Shall, L; Zaki, I

    1993-11-01

    Two epileptic patients developed an infectious mononucleosis-like illness which subsequently proved to be a carbamazepine-induced anticonvulsant hypersensitivity syndrome. Patch testing to carbamazepine 3 years later was positive in the one patient tested and negative in normal controls. The second patient died a few weeks after the illness, secondary to long-standing cardiac disease without having undergone patch testing. A skin biopsy was, however, consistent with an immune complex mediated drug reaction. Patch testing for systemically administered drugs is generally believed to be of little value in diagnosing drug allergies. However, we reinforce a previous suggestion that this investigation may be helpful in some cases of anticonvulsant hypersensitivity syndrome caused by carbamazepine. The pathogenic role of type 3 and 4 hypersensitivity is also discussed.

  13. Accidental dapsone poisoning in children.

    PubMed

    Nair, P M; Philip, E

    1984-12-01

    Accidental poisoning in children shows a trend towards poisoning with various newer drugs and chemicals used in the household. Sixty-one cases of accidental poisoning in children were seen in Sree Avittam Thirunal Hospital, (S.A.T.H.), Trivandrum, South India during the year 1982, constituting 0.61% of the total pediatric admissions. Dapsone poisoning constituted 9.8% of the total accidental poisonings, emphasising the need for safe storage of drugs out of the reach of young children. Dapsone poisoning with resultant methaemoglobinaemia responded well to intravenous ascorbic acid and other supportive measures.

  14. Permanent demand pacing for hypersensitive carotid sinus syndrome

    PubMed Central

    Peretz, Dwight I.; Gerein, Alfred N.; Miyagishima, Robert T.

    1973-01-01

    Ten patients with proved hypersensitivity of one or both carotid sinuses and with symptoms of recurrent lightheaded spells and syncope had implanted a permanent transvenous demand pacemaker. In a follow-up course ranging from 6 to 55 months there has been no recurrence of lightheadedness or syncope in any of the patients. Six of the ten have had their battery packs replaced owing to routine battery exhaustion. PMID:4704892

  15. Drug-eluting stent thrombosis: the Kounis hypersensitivity-associated acute coronary syndrome revisited.

    PubMed

    Chen, Jack P; Hou, Dongming; Pendyala, Lakshmana; Goudevenos, John A; Kounis, Nicholas G

    2009-07-01

    The advent of drug-eluting stents (DES) has revolutionized the field of interventional cardiology. Their dramatic and persistent restenotic and target lesion revascularization advantages are unquestioned. However, concerns over the rare but potentially catastrophic risk of stent thrombosis (ST) have tempered universal acceptance of these devices. Although the precise mechanism of DES ST is undoubtedly multifactorial and as yet not fully elucidated, delayed or incomplete endothelial healing clearly plays a pivotal role. Detailed histopathological data have implicated a contributory allergic or hypersensitivity component, as verified by the Food and Drug Administration's Manufacturer and User Device Experience Center and the Research on Adverse Drug/device events And Reports (RADAR) project. These findings thus suggest a potential connection with the Kounis syndrome, the concurrence of acute coronary events with allergic, hypersensitivity, anaphylactic, or anaphylactoid reactions. Potential culprits responsible for this phenomenon include: arachidonic acid metabolites such as leukotrienes and thromboxane, proteolytic enzymes such as chymase and tryptase, histamine, cytokines, and chemokines. Additionally, inflammatory cells such as macrophages, T-lymphocytes, and mast cells are probably also contributory. Autopsy-confirmed infiltrates of various inflammatory cells including lymphocytes, plasma cells, macrophages, and eosinophils have been reported in all 3 vascular wall layers and are reminiscent of those associated with the Kounis syndrome. Although the concurrence of acute coronary syndromes with hypersensitivity reactions has been long established, the specific association with DES ST remains unproven. Potential incorporation of hypersensitivity suppressive agents might represent a promising paradigm shift from efficacy to safety in future DES designs.

  16. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Methods to assess visceral hypersensitivity in irritable bowel syndrome.

    PubMed

    Keszthelyi, D; Troost, F J; Masclee, A A

    2012-07-15

    Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, characterized by recurrent abdominal pain or discomfort in combination with disturbed bowel habits in the absence of identifiable organic cause. Visceral hypersensitivity has emerged as a key hypothesis in explaining the painful symptoms in IBS and has been proposed as a "biological hallmark" for the condition. Current techniques of assessing visceral perception include the computerized barostat using rectal distensions, registering responses induced by sensory stimuli including the flexor reflex and cerebral evoked potentials, as well as brain imaging modalities such as functional magnetic resonance imaging and positron emission tomography. These methods have provided further insight into alterations in pain processing in IBS, although the most optimal method and condition remain to be established. In an attempt to give an overview of these methods, a literature search in the electronic databases PubMed and MEDLINE was executed using the search terms "assessment of visceral pain/visceral nociception/visceral hypersensitivity" and "irritable bowel syndrome." Both original articles and review articles were considered for data extraction. This review aims to discuss currently used modalities in assessing visceral perception, along with advantages and limitations, and aims also to define future directions for methodological aspects in visceral pain research. Although novel paradigms such as brain imaging and neurophysiological recordings have been introduced in the study of visceral pain, confirmative studies are warranted to establish their robustness and clinical relevance. Therefore, subjective verbal reporting following rectal distension currently remains the best-validated technique in assessing visceral perception in IBS.

  17. A C. elegans homolog for the UV-hypersensitivity syndrome disease gene UVSSA

    PubMed Central

    Babu, Vipin; Schumacher, Björn

    2016-01-01

    The transcription-coupled repair pathway (TC-NER) plays a vital role in removing transcription-blocking DNA lesions, particularly UV-induced damage. Clinical symptoms of the two TC-NER-deficiency syndromes, Cockayne syndrome (CS) and UV-hypersensitivity syndrome (UVSS) are dissimilar and the underlying molecular mechanism causing this difference in disease pathology is not yet clearly understood. UV-stimulated scaffold protein A (UVSSA) has been identified recently as a new causal gene for UVSS. Here we describe a functional homolog of the human UVSSA gene in the nematode Caenorhabditis elegans, uvs-1 (UVSSA-like-1). Mutations in uvs-1 render the animals hypersensitive to UV-B irradiation and transcription-blocking lesion-inducing illudin-M, similar to mutations in TC-NER deficient mutants. Moreover, we demonstrate that TC-NER factors including UVS-1 are required for the survival of the adult animals after UV-treatment. PMID:27043179

  18. Aminophylline suppresses stress-induced visceral hypersensitivity and defecation in irritable bowel syndrome

    PubMed Central

    Asano, Teita; Tanaka, Ken-ichiro; Tada, Arisa; Shimamura, Hikaru; Tanaka, Rikako; Maruoka, Hiroki; Takenaga, Mitsuko; Mizushima, Tohru

    2017-01-01

    Pharmacological therapy for irritable bowel syndrome (IBS) has not been established. In order to find candidate drugs for IBS with diarrhea (IBS-D), we screened a compound library of drugs clinically used for their ability to prevent stress-induced defecation and visceral hypersensitivity in rats. We selected the bronchodilator aminophylline from this library. Using a specific inhibitor for each subtype of adenosine receptors (ARs) and phosphodiesterases (PDEs), we found that both A2BARs and PDE4 are probably mediated the inhibitory effect of aminophylline on wrap restraint stress (WRS)-induced defecation. Aminophylline suppressed maternal separation- and acetic acid administration-induced visceral hypersensitivity to colorectal distension (CRD), which was mediated by both A2AARs and A2BARs. We propose that aminophylline is a candidate drug for IBS-D because of its efficacy in both of stress-induced defecation and visceral hypersensitivity, as we observed here, and because it is clinically safe. PMID:28054654

  19. [Impairment of social interaction, coordination disorder, and hypersensitivity in Asperger's syndrome].

    PubMed

    Asai, Tomoko; Sugiyam, Toshiro

    2007-03-01

    Asperger's syndrome is not accompanied with intellectual disability, however it has social impairments as well as autism and demonstrates failure to develop peer relationships according to each life stage. Social reciprocal behavior deficits are revealed typically during childhood. On the other hand, after school age these deficits are modified by environmental factors that may induce secondary disorders consequently. Hypersensitivity and coordination disorder, which are not included in diagnostic criteria for Asperger's syndrome, are often in presence. These symptoms are diminished and rarely interfere daily living as growth. However they may keep Asperger's syndrome individuals from adapting to others, so we need to take it into consideration.

  20. Occupational trichloroethylene hypersensitivity syndrome: human herpesvirus 6 reactivation and rash phenotypes.

    PubMed

    Kamijima, Michihiro; Wang, Hailan; Yamanoshita, Osamu; Ito, Yuki; Xia, Lihua; Yanagiba, Yukie; Chen, Cishan; Okamura, Ai; Huang, Zhenlie; Qiu, Xinxiang; Song, Xiangrong; Cai, Tingfeng; Liu, Lili; Ge, Yichen; Deng, Yingyu; Naito, Hisao; Yoshikawa, Tetsushi; Tohyama, Mikiko; Li, Laiyu; Huang, Hanlin; Nakajima, Tamie

    2013-12-01

    Trichloroethylene (TCE) is an industrial solvent which can cause severe generalized dermatitis, i.e., occupational TCE hypersensitivity syndrome. Reactivation of latent human herpesvirus 6 (HHV6) can occur in such patients, which has made TCE known as a causative chemical of drug-induced hypersensitivity syndrome (DIHS). This study aimed to clarify HHV6 status, cytokine profiles and their association with rash phenotypes in patients with TCE hypersensitivity syndrome. HHV6 DNA copy numbers, anti-HHV6 antibody titers, and cytokines were measured in blood prospectively sampled 5-7 times from 28 hospitalized patients with the disease. The patients (19 had exfoliative dermatitis (ED) and 9 had non-ED type rash) generally met the diagnostic criteria for DIHS. Viral reactivation defined as increases in either HHV6 DNA (≥100 genomic copies/10(6) peripheral blood mononuclear cells) or antibody titers was identified in 24 (89%) patients. HHV6 DNA, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-5, IL-6 and IL-10 concentrations were remarkably higher in the patients than in the healthy workers (p<0.01). Positive correlations between HHV6 DNA, TNF-α, IFN-γ, IL-6 and IL-10 were significant (p<0.05) except for that between HHV6 DNA and IFN-γ. An increase in HHV6 DNA was positively associated with an increase in TNF-α on admission (p<0.01). HHV6 DNA, the antibody titers, TNF-α and IL-10 concentrations were significantly higher in ED than in the non-ED type (p<0.05). Reactivated HHV6 and the increased cytokines could be biomarkers of TCE hypersensitivity syndrome. The higher-level reactivation and stronger humoral responses were associated with ED-type rash. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  1. Visceral hypersensitivity in irritable bowel syndrome: evidence for involvement of serotonin metabolism--a preliminary study.

    PubMed

    Keszthelyi, D; Troost, F J; Jonkers, D M; van Eijk, H M; Dekker, J; Buurman, W A; Masclee, A A M

    2015-08-01

    Altered serotonergic (5-HT) metabolism and visceral perception have been associated with the pathogenesis of irritable bowel syndrome (IBS). Aim of this preliminary study was to assess the effect of the direct precursor of 5-HT, 5-hydroxytryptophan (5-HTP), on systemic 5-HT metabolites and visceral perception and to assess potential differential responses between IBS and controls. 15 IBS patients and 15 healthy volunteers participated in this randomized double-blind placebo controlled study. Visceroperception was measured by rectal barostat. The 100 mg 5-HTP or placebo was ingested orally. Serotonergic metabolites were assessed in platelet poor plasma. 5-HTP induces rectal allodynia in a significant number of healthy controls; IBS patients exhibit lowered pain thresholds in both placebo and 5-HTP conditions. 5-HTP induces rectal hyperalgesia in hypersensitive but not in non-hypersensitive IBS patients. Administration of 5-HTP significantly increased plasma 5-HTP levels (p < 0.001), did not affect 5-HT levels (p > 0.05), while levels of the main metabolite of 5-HT, 5-hydroxyindoleacetic acid, increased significantly (p < 0.05) in both groups. The magnitude of these changes observed in 5-HT metabolites was significantly greater in IBS patients. Oral administration of 5-HTP induced significant alterations in systemic 5-HT metabolites that were accompanied by increased visceroperception of pain in controls and hypersensitive IBS patients. Changes in 5-HT metabolism appear to be important factors involved in visceral hypersensitivity as the 5-HTP-induced pro-nociceptive response was observed in all hypersensitive IBS patients and to a lesser magnitude in a significant number of healthy controls but in none of the non-hypersensitive IBS patients. © 2015 John Wiley & Sons Ltd.

  2. Burning mouth syndrome: the role of contact hypersensitivity.

    PubMed

    Virgili, A; Corazza, M; Trombelli, L; Arcidiacono, A

    1996-11-01

    The burning mouth syndrome is characterized by an unpleasant sensation of burning in the oral cavity, without clinical signs. Causal factors may be psychogenic, systemic or local. The aim of the study was to determine the significance of contact allergy in the pathogenesis of burning mouth syndrome. Fifteen patients with burning mouth syndrome were studied through anamnesis and laboratory analysis. Epicutaneous patch tests were performed with the Italian standard series (GIRDCA - Gruppo Italiano di Ricerca Dermatiti da Contatto ed Ambientali), preservative and dental series. The same tests were carried out in 12 healthy age- and sex-matched subjects. The number of patients affected by burning mouth syndrome with a positive reaction to patchtesting was 6 out of 15, while the number of allergic patients in the control group was 3 out of 12. No association could be found between positive reaction at patchtesting and exposure to allergens. Contact allergy in burning mouth syndrome seems not to play a primary role; nevertheless, it is advisable to perform patch tests in selected patients to identify a possible aetiological agent.

  3. Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS).

    PubMed

    Santiago, Felicidade; Gonçalo, Margarida; Vieira, Ricardo; Coelho, Sónia; Figueiredo, Américo

    2010-01-01

    In some patterns of cutaneous adverse drug reactions, and depending on the culprit drug, patch testing has been helpful in confirming its cause. Its value in Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) has not been established in a large cohort of patients. The aim of the present study is to evaluate the safety and usefulness of patch testing in DRESS. Between January 1998 and December 2008, we studied 56 patients with DRESS induced by antiepileptic agents in 33 patients (59%), allopurinol in 19 (34%) and sulfasalazine, cotrimoxazole, tenoxicam, and amoxicillin in 1 patient each (7%). A positive patch test reaction was observed in 18 patients (32.1%), of which 17 were with antiepileptics and 1 with tenoxicam. In the antiepileptic group, carbamazepine alone was responsible for 13 of 17 positive reactions (76.5%). Patch tests with allopurinol and its metabolite were negative in all cases attributed to this drug. In this study, patch testing was a safe and useful method in confirming the culprit drug in DRESS induced by antiepileptic drugs, whereas it had no value in DRESS induced by allopurinol. The pathogenesis of DRESS is not yet entirely clarified, but positive patch tests suggest a drug-dependent delayed hypersensitivity mechanism.

  4. A Case of Mexiletine-induced Hypersensitivity Syndrome Presenting as Eosinophilic Pneumonia

    PubMed Central

    Lee, Sang-Pyo; Kim, Sang-Heon; Kim, Tae Hyung; Sohn, Jang Won; Shin, Dong Ho; Park, Sung Soo

    2010-01-01

    An 82-yr-old man was presented with fever and cough accompanied by generalized erythematous rash. He had taken mexiletine for 5 months, as he had been diagnosed with dilated cardiomyopathy and ventricular arrhythmia. Laboratory studies showed peripheral blood eosinophilia and elevated liver transaminase levels. Chest radiographs showed multiple nodular consolidations in both lungs. Biopsies of the lung and skin lesions revealed eosinophilic infiltration. After a thorough review of his medication history, mexiletine was suspected as the etiologic agent. After discontinuing the mexiletine and starting oral prednisolone, the patient improved, and the skin and lung lesions disappeared. Subsequently, mexiletine was confirmed as the causative agent based on a positive patch test. Drug-induced hypersensitivity syndrome is a severe adverse reaction to drugs and results from treatment with anticonvulsants, allopurinol, sulfonamides, and many other drugs. Several cases of mexiletine-induced hypersensitivity syndrome have been reported in older Japanese males with manifestation of fever, rash, peripheral blood eosinophilia, liver dysfunction without other organ involvement. Here, we report a case of mexiletine-induced hypersensitivity syndrome which presented as eosinophilic pneumonia in a Korean male. PMID:20052362

  5. Chronic 'cough hypersensitivity syndrome': a more precise label for chronic cough.

    PubMed

    Chung, K F

    2011-06-01

    Chronic cough remains a challenge to many clinicians because there is often no diagnostic link to causation, and because indirect antitussives are largely ineffective. Chronic cough can also be a predominant symptom associated with many chronic respiratory diseases such as COPD, asthma and pulmonary fibrosis. Chronic cough itself does impair the quality of life and is associated with psychological impairment. The symptoms associated with chronic cough include persistent tickling or irritating sensation in the chest or throat, hoarse voice, dysphonia or vocal cord dysfunction. Currently, the clinical diagnosis of cough is associated with chronic cough caused by airway eosinophilic conditions such as asthma, gastrooesophageal reflux disease or post-nasal drip (or upper airway syndrome), which implies cause and effect, or with chronic cough associated with other diseases such as COPD, cancer or heart failure, that does not necessarily imply cause and effect. A recently-recognised category is idiopathic cough, with no associated or causative diagnosis. We suggest that there is a better label needed for chronic cough, that includes the common association with a hypersensitive cough response to tussive stimuli such as capsaicin or citric acid. This would invoke a hypersensitive syndrome, and there are good reasons to use a new label that would encompass the problem of chronic cough: the chronic 'cough hypersensitivity syndrome'. This would focus the problem on the cough symptomatology and lead to greater focus on understanding the mechanisms of cough sensitisation, with the ultimate aim of obtaining more effective antitussives.

  6. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Neural and neuro-immune mechanisms of visceral hypersensitivity in irritable bowel syndrome.

    PubMed

    Feng, Bin; La, Jun Ho; Schwartz, Erica S; Gebhart, G F

    2012-05-15

    Irritable bowel syndrome (IBS) is characterized as functional because a pathobiological cause is not readily apparent. Considerable evidence, however, documents that sensitizing proinflammatory and lipotoxic lipids, mast cells and their products, tryptases, enteroendocrine cells, and mononuclear phagocytes and their receptors are increased in tissues of IBS patients with colorectal hypersensitivity. It is also clear from recordings in animals of the colorectal afferent innervation that afferents exhibit long-term changes in models of persistent colorectal hypersensitivity. Such changes in afferent excitability and responses to mechanical stimuli are consistent with relief of discomfort and pain in IBS patients, including relief of referred abdominal hypersensitivity, upon intra-rectal instillation of local anesthetic. In the aggregate, these experimental outcomes establish the importance of afferent drive in IBS, consistent with a larger literature with respect to other chronic conditions in which pain is a principal complaint (e.g., neuropathic pain, painful bladder syndrome, fibromyalgia). Accordingly, colorectal afferents and the environment in which these receptive endings reside constitute the focus of this review. That environment includes understudied and incompletely understood contributions from immune-competent cells resident in and recruited into the colorectum. We close this review by highlighting deficiencies in existing knowledge and identifying several areas for further investigation, resolution of which we anticipate would significantly advance our understanding of neural and neuro-immune contributions to IBS pain and hypersensitivity.

  7. Visceral hypersensitive rats share common dysbiosis features with irritable bowel syndrome patients.

    PubMed

    Zhou, Xiao-Yan; Li, Ming; Li, Xia; Long, Xin; Zuo, Xiu-Li; Hou, Xiao-Hua; Cong, Ying-Zi; Li, Yan-Qing

    2016-06-14

    To evaluate gut microbial dysbiosis in two visceral hypersensitive models in comparison with irritable bowel syndrome (IBS) patients and to explore the extent to which these models capture the dysbiosis of IBS patients. Visceral hypersensitivity was developed using the maternal separation (MS) rat model and post-inflammatory rat model. The visceral sensitivity of the model groups and control group was evaluated using the abdominal withdraw reflex score and electromyography in response to graded colorectal distention. The 16S ribosomal RNA gene from fecal samples was pyrosequenced and analyzed. The correlation between dysbiosis in the microbiota and visceral hypersensitivity was calculated. Positive findings were compared to sequencing data from a published human IBS cohort. Dysbiosis triggered by neonatal maternal separation was lasting but not static. Both MS and post-inflammatory rat fecal microbiota deviated from that of the control rats to an extent that was larger than the co-housing effect. Two short chain fatty acid producing genera, Fusobacterium and Clostridium XI, were shared by the human IBS cohort and by the maternal separation rats and post-inflammatory rats, respectively, to different extents. Fusobacterium was significantly increased in the MS group, and its abundance positively correlated with the degree of visceral hypersensitivity. Porphyromonadaceae was a protective biomarker for both the rat control group and healthy human controls. The dysbiosis MS rat model and the post-inflammatory rat model captured some of the dysbiosis features of IBS patients. Fusobacterium, Clostridium XI and Porphyromonadaceae were identified as targets for future mechanistic research.

  8. Main ion channels and receptors associated with visceral hypersensitivity in irritable bowel syndrome

    PubMed Central

    de Carvalho Rocha, Heraldo Arcela; Dantas, Bruna Priscilla Vasconcelos; Rolim, Thaísa Leite; Costa, Bagnólia Araújo; de Medeiros, Arnaldo Correia

    2014-01-01

    Irritable bowel syndrome (IBS) is a very frequent functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort and alteration of bowel habits. The IBS physiopathology is extremely complex. Visceral hypersensitivity plays an important role in the pathogenesis of abdominal pain in both in vitro and in vivo models of this functional disorder. In order to obtain a general view of the participation of the main ion channels and receptors regarding the visceral hypersensitivity in the IBS and to describe their chemical structure, a literature review was carried out. A bibliographical research in the following electronic databases: Pubmed and Virtual Library in Health (BVS) was fulfilled by using the search terms “ion channels” “or” “receptors” “and” “visceral hypersensitivity” “or” “visceral nociception” “and” “irritable bowel syndrome”. Original and review articles were considered for data acquisition. The activation of the ATP ion-gated channels, voltage-gated sodium (Nav) and calcium (Cav) channels, as well as the activation of protease-activated receptors (PAR2), transient receptor potential vanilloide-1, serotonin, cannabinoids and cholecystokinin are involved in the genesis of visceral hypersensitivity in IBS. The involvement of ion channels and receptors concerning visceral hypersensitivity is noteworthy in IBS models. PMID:24976114

  9. Carbamazepine hypersensitivity syndrome triggered by a human herpes virus reactivation in a genetically predisposed patient.

    PubMed

    Calligaris, Lorenzo; Stocco, Gabriele; De Iudicibus, Sara; Marino, Sara; Decorti, Giuliana; Barbi, Egidio; Carrozzi, Marco; Marchetti, Federico; Bartoli, Fiora; Ventura, Alessandro

    2009-01-01

    A case of severe hypersensitivity syndrome, triggered by carbamazepine in the presence of a concomitant active human herpes virus (HHV) 6 and 7 infection is described. To further understand the molecular mechanism of this adverse reaction, analyses of the genetic variants of human leukocyte antigen (HLA) and of the epoxide hydrolase gene (EPHX1), previously associated with carbamazepine hypersensitivity, were performed. A lymphocyte transformation test (LTT) was conducted in order to detect drug-specific lymphocytes. In the hypersensitive patient, 2 genetic factors previously associated with intolerance to carbamazepine were detected: the allele HLA-A*3101 and homozygosity for the variant allele of SNP rs1051740 in EPHX1. Drug-specific lymphocytes could be detected by LTT when the HHV was active (positive PCR for viral DNA and increased anti-HHV 6 IgG titer), but not when it was no longer active. In conclusion, we document a case of severe carbamazepine hypersensitivity triggered by viral reactivation in a patient presenting the interaction of 2 unfavorable genetic factors.

  10. Febuxostat hypersensitivity: another cause of DRESS syndrome in chronic kidney disease?

    PubMed

    Paschou, E; Gavriilaki, E; Papaioannou, G; Tsompanakou, A; Kalaitzoglou, A; Sabanis, N

    2016-11-01

    Febuxostat is a xanthine oxidase inhibitor that during the last years has successfully replaced allopurinol treatment in patients with chronic kidney disease (CKD) and hyperuricemia. Several adverse events have been observed during therapy with febuxostat. DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome induced by febuxostat has been poorly described, mainly in patient with CKD who previously developed allopurinol hypersensitivity syndrome. DRESS syndrome is characterized by manifold cutaneous reactions and systemic disorders with potential devastating consequences. The underlying pathogenetic mechanisms remain unidentified, though immune responses are often complicated. P-i concept can partially explain the phenomenon. The role of renal insufficiency appears to be crucial and further investigation is required. The present article describes the case of a CKD patient that developed febuxostat-related DRESS syndrome.

  11. Widespread hypersensitivity is related to altered pain inhibition processes in irritable bowel syndrome.

    PubMed

    Piché, Mathieu; Arsenault, Marianne; Poitras, Pierre; Rainville, Pierre; Bouin, Mickael

    2010-01-01

    The mechanisms of chronic pain in irritable bowel syndrome (IBS) have been widely investigated but remain unclear. The present study investigated the relation between visceral hypersensitivity, cutaneous thermal sensitivity, and central pain mechanisms. Rectal sensitivity was assessed with a barostat, and forearm and calf sensitivity with a contact thermode. Central mechanisms were assessed by counterirritation using sustained cold-pain to the hand and painful electric shocks to the ankle. Psychological symptoms were also assessed, using questionnaires. Female volunteers with diarrhea-predominant IBS (n=27) and healthy controls (n=25) participated in the study. IBS patients had lower rectal and calf pain thresholds compared to controls (p's<0.05). IBS patients also reported more pain than controls for rectal distensions, and heat pain on the calf and forearm (all p's<0.001). Cold-pain inhibited shock-pain in controls but not IBS patients (controls: -13.5+/-5.3 vs IBS: +1.9+/-10.5; p<0.01). In addition, visceral hypersensitivity was significantly correlated to cutaneous thermal hypersensitivity and pain inhibition deficits, although effects were only weak and moderate, respectively. Furthermore, covariance analyses indicated that psychological factors accounted for group differences in visceral hypersensitivity and pain inhibition deficits. In conclusion, this study confirms the relation between altered pain inhibition processes and widespread hypersensitivity in IBS. The present results also suggests that psychological symptoms and altered pain processing in IBS patients may reflect at least in part, common underlying mechanisms. Copyright 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  12. [Characteristics of hypersensitivity syndrome to lamotrigine: review of one case reported in the Regional Center of Pharmacovigilance of Nantes].

    PubMed

    Veyrac, G; Marcade, G; Chiffoleau, A; Bourin, M; Jolliet, P

    2002-01-01

    Drug-induced hypersensitivity syndrome is an uncommon but potentially life-threatening idiosyncratic drug reaction. In the literature, about five cases have been reported concerning hypersensitivity syndrome with lamotrigine. Most cases concern aromatic anticonvulsants but we report a case induced by lamotrigine which is a non aromatic anticonvulsant. A 73-year-old man was treated with lamotrigine for epilepsy due to a cerebrovascular stroke for 5 weeks. After 2 weeks with a single oral dose of 50 mg lamotrigine, the patient received 100 mg. Quickly thereafter fever, erythema and edema involving the periorbital area appeared. He was then admitted to hospital and lamotrigine was immediately discontinued. He developed acute hepatic and renal failure. During his hospital stay, he was treated with systemic and topical corticosteroids. After slow improvement, he was discharged 4 weeks later. Concerning this typical case, we review the characteristics of hypersensitivity syndrome and the different etiopathogenesis. The hypersensitivity syndrome typically develops two to six weeks after a drug is first administered, later than most other serious skin reactions. This syndrome manifests as rash, fever, tender lymphadenopathy, hepatitis and eosinophilia. The mechanism of hypersensitivity syndrome is unknown. Several theories have been proposed. The reaction is secondary to circulating antibodies or concerns toxic metabolities. On the other hand, association of human herpes virus 6 infection may play a role in the development of hypersensitivity syndrome. Hypersensitivity reactions to the aromatic antiepileptic drugs appear to have an immune etiology much like lamotrigine: bioactivation, detoxification, covalent adduct formation, processing and presentation of antigen to the immune system, and consequent formation of antibody and T-cell immune effectors. Another theory involves toxic metabolites; the aromatic antiepileptic agents are metabolised by cytochrome P-450 to an

  13. Eight International London Cough Symposium 2014: Cough hypersensitivity syndrome as the basis for chronic cough.

    PubMed

    Chung, Kian Fan; Canning, Brendan; McGarvey, Lorcan

    2015-12-01

    At the Eighth International London Cough Conference held in London in July 2014, the focus was on the relatively novel concept of cough hypersensitivity syndrome (CHS) as forming the basis of chronic cough. This concept has been formulated following understanding of the neuronal pathways for cough and a realisation that not all chronic cough is usually associated with a cause. The CHS is defined by troublesome coughing triggered by low level of thermal, mechanical or chemical exposure. It also encompasses other symptoms or sensations such as laryngeal hypersensitivity, nasal hypersensitivity and possibly also symptoms related to gastrooesopahgeal reflux. The pathophysiologic basis of the CHS is now being increasingly linked to an enhancement of the afferent pathways of the cough reflex both at the peripheral and central levels. Mechanisms involved include the interactions of inflammatory mechanisms with cough sensors in the upper airways and with neuronal pathways of cough, associated with a central component. Tools for assessing CHS in the clinic need to be developed. New drugs may be developed to control CHS. A roadmap is suggested from the inception of the CHS concept towards the development of newer antitussives at the Symposium.

  14. Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases.

    PubMed

    Ceuleers, Hannah; Van Spaendonk, Hanne; Hanning, Nikita; Heirbaut, Jelena; Lambeir, Anne-Marie; Joossens, Jurgen; Augustyns, Koen; De Man, Joris G; De Meester, Ingrid; De Winter, Benedicte Y

    2016-12-21

    Proteases, enzymes catalyzing the hydrolysis of peptide bonds, are present at high concentrations in the gastrointestinal tract. Besides their well-known role in the digestive process, they also function as signaling molecules through the activation of protease-activated receptors (PARs). Based on their chemical mechanism for catalysis, proteases can be classified into several classes: serine, cysteine, aspartic, metallo- and threonine proteases represent the mammalian protease families. In particular, the class of serine proteases will play a significant role in this review. In the last decades, proteases have been suggested to play a key role in the pathogenesis of visceral hypersensitivity, which is a major factor contributing to abdominal pain in patients with inflammatory bowel diseases and/or irritable bowel syndrome. So far, only a few preclinical animal studies have investigated the effect of protease inhibitors specifically on visceral sensitivity while their effect on inflammation is described in more detail. In our accompanying review we describe their effect on gastrointestinal permeability. On account of their promising results in the field of visceral hypersensitivity, further research is warranted. The aim of this review is to give an overview on the concept of visceral hypersensitivity as well as on the physiological and pathophysiological functions of proteases herein.

  15. Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases

    PubMed Central

    Ceuleers, Hannah; Van Spaendonk, Hanne; Hanning, Nikita; Heirbaut, Jelena; Lambeir, Anne-Marie; Joossens, Jurgen; Augustyns, Koen; De Man, Joris G; De Meester, Ingrid; De Winter, Benedicte Y

    2016-01-01

    Proteases, enzymes catalyzing the hydrolysis of peptide bonds, are present at high concentrations in the gastrointestinal tract. Besides their well-known role in the digestive process, they also function as signaling molecules through the activation of protease-activated receptors (PARs). Based on their chemical mechanism for catalysis, proteases can be classified into several classes: serine, cysteine, aspartic, metallo- and threonine proteases represent the mammalian protease families. In particular, the class of serine proteases will play a significant role in this review. In the last decades, proteases have been suggested to play a key role in the pathogenesis of visceral hypersensitivity, which is a major factor contributing to abdominal pain in patients with inflammatory bowel diseases and/or irritable bowel syndrome. So far, only a few preclinical animal studies have investigated the effect of protease inhibitors specifically on visceral sensitivity while their effect on inflammation is described in more detail. In our accompanying review we describe their effect on gastrointestinal permeability. On account of their promising results in the field of visceral hypersensitivity, further research is warranted. The aim of this review is to give an overview on the concept of visceral hypersensitivity as well as on the physiological and pathophysiological functions of proteases herein. PMID:28058009

  16. Bronchoscopic Investigation of Atypical Drug-induced Hypersensitivity Syndrome Showing Viral Lung Involvement.

    PubMed

    Hase, Isano; Arakawa, Hiroaki; Sakuma, Hideo; Kaneko, Fumio; Watanabe, Yuzuru; Fujiu, Koichi; Miyamoto, Hideaki; Ishii, Yoshiki

    We herein report a case of atypical drug-induced hypersensitivity syndrome (DIHS) involving serological reactivation of cytomegalovirus induced by carbamazepine with pulmonary and skin manifestations. These lesions were not present on admission, but developed on virus reactivation as indicated by the presence of inclusion bodies and multinucleated giant cells in alveolar cells with CD8(+) T lymphocyte infiltration on a transbronchial lung biopsy. Although the precise mechanism of DIHS remains unknown, this case suggests the crucial role of viral reactivation in pulmonary lesions in DIHS.

  17. Visceral hypersensitive rats share common dysbiosis features with irritable bowel syndrome patients

    PubMed Central

    Zhou, Xiao-Yan; Li, Ming; Li, Xia; Long, Xin; Zuo, Xiu-Li; Hou, Xiao-Hua; Cong, Ying-Zi; Li, Yan-Qing

    2016-01-01

    AIM: To evaluate gut microbial dysbiosis in two visceral hypersensitive models in comparison with irritable bowel syndrome (IBS) patients and to explore the extent to which these models capture the dysbiosis of IBS patients. METHODS: Visceral hypersensitivity was developed using the maternal separation (MS) rat model and post-inflammatory rat model. The visceral sensitivity of the model groups and control group was evaluated using the abdominal withdraw reflex score and electromyography in response to graded colorectal distention. The 16S ribosomal RNA gene from fecal samples was pyrosequenced and analyzed. The correlation between dysbiosis in the microbiota and visceral hypersensitivity was calculated. Positive findings were compared to sequencing data from a published human IBS cohort. RESULTS: Dysbiosis triggered by neonatal maternal separation was lasting but not static. Both MS and post-inflammatory rat fecal microbiota deviated from that of the control rats to an extent that was larger than the co-housing effect. Two short chain fatty acid producing genera, Fusobacterium and Clostridium XI, were shared by the human IBS cohort and by the maternal separation rats and post-inflammatory rats, respectively, to different extents. Fusobacterium was significantly increased in the MS group, and its abundance positively correlated with the degree of visceral hypersensitivity. Porphyromonadaceae was a protective biomarker for both the rat control group and healthy human controls. CONCLUSION: The dysbiosis MS rat model and the post-inflammatory rat model captured some of the dysbiosis features of IBS patients. Fusobacterium, Clostridium XI and Porphyromonadaceae were identified as targets for future mechanistic research. PMID:27298564

  18. Follow-up assessment of two cases of trichloroethylene hypersensitivity syndrome: A case report.

    PubMed

    Huang, Yong-Shun; Huang, Han-Lin; Wu, Qi-Feng; Xia, Li-Hua; Huang, Ming; Qiu, Xin-Xiang; Zhou, Shan-Yu

    2016-08-01

    The present study aimed to explore the stability, curability and sequelae of cases of Trichloroethylene (TCE) Hypersensitivity Syndrome (THS), and to investigate the causal allergens of THS. Two cases of THS were followed-up in the current study; both cases were healing following glucocorticoid therapy and were discharged >10 weeks prior to follow-up. A questionnaire investigation, health examination and patch test were performed. Allergens of TCE and its metabolites, including chloral hydrate, trichloroethanol (TCOH) and trichloroacetic acid, were applied in the patch test; 4 controls were included. The two subjects were experiencing itching, pigmentation and xerosis of the skin, and had abnormal results in the ophthalmology Schirmer I test and tear break-up time. The body temperature, liver function, superficial lymph nodes, blood, urine routine and autoimmune antibodies of two subjects were shown to be normal, and no new rashes had appeared. All mass concentration of chloral hydrate and TCOH were positive; 5.0% trichloroacetic acid was weakly positive, 0.5% trichloroacetic acid and all mass concentration of TCE were negative. All patch tests were negative in the 4 control subjects. The results suggest that THS was stable following treatment with glucocorticoid therapy. Dry eye syndrome may continue as a sequelae of THS. The patch test demonstrated that the mechanism underlying THS is delayed-type hypersensitivity induced by TCE. In addition, as the hypersensitivity state in a THS rehabilitee could be sustained over a long period of time, it suggests that the metabolites of TCE, not TCE itself, are responsible for THS. Therefore, patients with THS should avoid contact with TCE and its metabolites, and avoid using hypnotic and anticonvulsive drugs containing chloral hydra as the primary ingredient.

  19. Follow-up assessment of two cases of trichloroethylene hypersensitivity syndrome: A case report

    PubMed Central

    Huang, Yong-Shun; Huang, Han-Lin; Wu, Qi-Feng; Xia, Li-Hua; Huang, Ming; Qiu, Xin-Xiang; Zhou, Shan-Yu

    2016-01-01

    The present study aimed to explore the stability, curability and sequelae of cases of Trichloroethylene (TCE) Hypersensitivity Syndrome (THS), and to investigate the causal allergens of THS. Two cases of THS were followed-up in the current study; both cases were healing following glucocorticoid therapy and were discharged >10 weeks prior to follow-up. A questionnaire investigation, health examination and patch test were performed. Allergens of TCE and its metabolites, including chloral hydrate, trichloroethanol (TCOH) and trichloroacetic acid, were applied in the patch test; 4 controls were included. The two subjects were experiencing itching, pigmentation and xerosis of the skin, and had abnormal results in the ophthalmology Schirmer I test and tear break-up time. The body temperature, liver function, superficial lymph nodes, blood, urine routine and autoimmune antibodies of two subjects were shown to be normal, and no new rashes had appeared. All mass concentration of chloral hydrate and TCOH were positive; 5.0% trichloroacetic acid was weakly positive, 0.5% trichloroacetic acid and all mass concentration of TCE were negative. All patch tests were negative in the 4 control subjects. The results suggest that THS was stable following treatment with glucocorticoid therapy. Dry eye syndrome may continue as a sequelae of THS. The patch test demonstrated that the mechanism underlying THS is delayed-type hypersensitivity induced by TCE. In addition, as the hypersensitivity state in a THS rehabilitee could be sustained over a long period of time, it suggests that the metabolites of TCE, not TCE itself, are responsible for THS. Therefore, patients with THS should avoid contact with TCE and its metabolites, and avoid using hypnotic and anticonvulsive drugs containing chloral hydra as the primary ingredient. PMID:27446293

  20. Occupational trichloroethylene hypersensitivity syndrome with human herpesvirus-6 and cytomegalovirus reactivation.

    PubMed

    Watanabe, Hideaki; Tohyama, Mikiko; Kamijima, Michihiro; Nakajima, Tamie; Yoshida, Takemi; Hashimoto, Koji; Iijima, Masafumi

    2010-08-01

    Patients having a generalised rash with severe liver dysfunction associated with exposure to trichloroethylene (TCE) have been reported mainly in Asian countries. However, no case has been reported in Japan since the 1990s. Here, we describe a case of hypersensitivity syndrome (HS) caused by TCE in a 30-year-old Japanese man. The patient developed a rash, fever and liver dysfunction 21 days after he had been exposed to TCE at his workplace. Serum human herpesvirus (HHV)-6 and cytomegalovirus (CMV) DNA were detected 4 and 7 weeks, respectively, after the onset; the IgG antibody titres to HHV-6 and CMV were significantly elevated 6 and 9 weeks, respectively, after the onset. Patch testing was positive for the metabolites of TCE (i.e. trichloroethanol, trichloroacetic acid and chloral hydrate) but not for TCE itself; these results suggest that the TCE metabolites induced this disease. Human leucocyte antigen-B*1301, which has been reported to be strongly associated with TCE-induced HS, was identified in this patient. In addition, the clinical findings, laboratory data and period of virus reactivation after onset were quite similar to those of drug-induced hypersensitivity syndrome (DIHS). We also review TCE-induced HS from the viewpoint of the similarity to DIHS in this article. Copyright 2010 S. Karger AG, Basel.

  1. Minocycline-Induced Drug Hypersensitivity Syndrome Followed by Multiple Autoimmune Sequelae

    PubMed Central

    Brown, Rebecca J.; Rother, Kristina I.; Artman, Henry; Mercurio, Mary Gail; Wang, Roger; Looney, R. John; Cowen, Edward W.

    2010-01-01

    Background Drug hypersensitivity syndrome (DHS) is a severe, multisystem adverse drug reaction that may occur following the use of numerous medications, including anticonvulsants, sulfonamides, and minocycline hydrochloride. Long-term autoimmune sequelae of DHS have been reported, including hypothyroidism. Observations A 15-year-old female adolescent developed DHS 4 weeks after starting minocycline therapy for acne vulgaris. Seven weeks later she developed autoimmune hyperthyroidism (Graves disease), and 7 months after discontinuing minocycline therapy she developed autoimmune type 1 diabetes mellitus. In addition, she developed elevated titers of several markers of systemic autoimmune disease, including antinuclear, anti-Sjögren syndrome A, and anti-Smith antibodies. Conclusions Minocycline-associated DHS may be associated with multiple autoimmune sequelae, including thyroid disease, type 1 diabetes mellitus, and elevated markers of systemic autoimmunity. Long-term follow-up is needed in patients with DHS to determine the natural history of DHS-associated sequelae. PMID:19153345

  2. Dapsone-associated fixed drug eruption.

    PubMed

    Garcia, Daniel; Cohen, Philip R

    2017-07-01

    Dapsone is a sulfone drug used to treat infectious conditions and also numerous dermatologic diseases. Fixed drug eruption is a distinctive adverse cutaneous reaction associated with the initial administration and subsequent delivery of a specific agent. Areas covered: The authors preformed a literature search using the following keywords: dapsone, fixed drug eruption, and adverse cutaneous drug reaction. Bibliographies were also reviewed for pertinent articles. The results were combed for relevant papers and reviewed. Articles pertaining to dapsone-associated fixed drug eruption were included. Expert commentary: The majority of cases of dapsone-associated fixed drug eruption in the literature come from Africa or India where there is a high prevalence of patients treated for leprosy. Characteristics of these cases are similar to fixed drug eruption described in the western literature, with differences in frequency of multiple versus solitary lesions. Dapsone-associated fixed drug eruption should be considered when reviewing the drug history of a patient with fixed drug eruption. In the case of darker pigmented individuals, multiple fixed drug eruption lesions may be more common. Multiple lesions may mimic Kaposi's sarcoma in human immunodeficiency virus positive patients. Dapsone-associated fixed drug eruption should be considered in the differential diagnosis of multiple hyperpigmented lesions.

  3. Patch testing for the diagnosis of anticonvulsant hypersensitivity syndrome: a systematic review.

    PubMed

    Elzagallaai, Abdelbaset A; Knowles, Sandra R; Rieder, Michael J; Bend, John R; Shear, Neil H; Koren, Gideon

    2009-01-01

    Anticonvulsant hypersensitivity syndrome (AHS), also known by the other names drug rash (reaction) with eosinophilia and systemic symptoms (DRESS) and drug-induced hypersensitivity syndrome (DIHS), is a rare and potentially fatal reaction that occurs in susceptible patients after exposure to certain drugs, including aromatic anticonvulsants. Because of its ill-defined clinical picture and resemblance to other diseases, the diagnosis of AHS is often difficult and requires a safe and reliable diagnostic test. The skin patch test has been proven to be very useful for prediction and diagnosis of some types of hypersensitivity reactions such as delayed drug eruptions to beta-lactam antibacterials. However, the diagnostic value of patch testing for AHS is yet to be determined and its negative predictive values (NPVs) and positive predictive values (PPVs) are still unknown. This systematic review attempts to evaluate the usefulness of patch tests in the diagnosis of AHS and to examine different technical aspects of patch testing that may contribute to its performance. We included studies in which aromatic anticonvulsant drugs are the likely causes of the hypersensitivity reaction. Analysis of original publications from 1950 to August 2008 and cited in PubMed, MEDLINE and EMBASE has revealed contradictory findings, possibly due mainly to the use of unstandardized methods. Numerous factors have been suggested to affect the final result of the test, including the following: type of drug tested; concentration of drug and vehicle used; timing of the test after exposure; and the clinical picture of the reaction. The PPV of the test in optimal conditions was as high as 80-90% depending on the drug tested. On the other hand, this value is around 10-20% in many other published studies. Although patch testing may be a useful diagnostic test for AHS, accurate determination of its sensitivity and specificity is yet to be achievable due to the lack of a gold standard test against

  4. Azathioprine Hypersensitivity Syndrome: Two Cases of Febrile Neutrophilic Dermatosis Induced by Azathioprine

    PubMed Central

    Aleissa, Majed; Nicol, Perrine; Godeau, Marion; Tournier, Emilie; de Bellissen, Frederic; Robic, Marie-Angèle; Livideanu, Cristina Bulai; Mazereeuw-Hautier, Juliette; Paul, Carle

    2017-01-01

    Background Azathioprine is an immunosuppressive agent used in the treatment of immune-mediated diseases. Azathioprine hypersensitivity syndrome is a rare adverse reaction occurring a few days to weeks after the administration of azathioprine. Case 1 A 36-year-old male with ulcerative colitis presented with erythematous plaques, pustules and erosions on the lower back, buttocks and thighs associated with high fever (39°C) 2 weeks after the initiation of azathioprine 100 mg/day. Additional findings included leukocytosis (18.6 g/L) with neutrophilia (11.1 g/L) and elevated C-reactive protein (128 mg/L). Histopathology showed a dense infiltrate of neutrophils in the hair follicles. We increased the dose of prednisone to 1 mg/kg/day (60 mg/day) and azathioprine was discontinued. He had marked improvement within 3 weeks and did not have any relapse with a 1-year follow-up. Case 2 A 57-year-old male with ulcerative colitis presented with erythematous plaques and pustules on the lower limbs associated with high fever (40°C) 1 week after the initiation of azathioprine 75 mg/day. Leukocytosis with neutrophilia (13.6 g/L) and elevated C-reactive protein (344 mg/L) were among the laboratory findings. Histopathology showed a dense infiltrate of neutrophils in the hair follicles. The dose of prednisone was increased to 20 mg/day and azathioprine was discontinued, which led to complete remission within 7 days. He did not have any relapse with a 6-month follow-up. Conclusion The development of acute neutrophilic dermatitis 2 weeks after the initiation of azathioprine and the complete resolution after its withdrawal were in favor of azathioprine hypersensitivity syndrome. It should not be confused with Sweet syndrome associated with inflammatory bowel disease, as maintenance of azathioprine treatment may lead to life-threatening reactions. PMID:28203157

  5. A cytologic assay for diagnosis of food hypersensitivity in patients with irritable bowel syndrome.

    PubMed

    Carroccio, Antonio; Brusca, Ignazio; Mansueto, Pasquale; Pirrone, Giuseppe; Barrale, Maria; Di Prima, Lidia; Ambrosiano, Giuseppe; Iacono, Giuseppe; Lospalluti, Maria Letizia; La Chiusa, Stella M; Di Fede, Gaetana

    2010-03-01

    A percentage of patients with symptoms of irritable bowel syndrome (IBS) suffer from food hypersensitivity (FH) and improve on a food-elimination diet. No assays have satisfactory levels of sensitivity for identifying patients with FH. We evaluated the efficacy of an in vitro basophil activation assay in the diagnosis of FH in IBS-like patients. Blood samples were collected from 120 consecutive patients diagnosed with IBS according to Rome II criteria. We analyzed in vitro activation of basophils by food allergens (based on levels of CD63 expression), as well as total and food-specific immunoglobulin (Ig)E levels in serum. Effects of elimination diets and double-blind food challenges were used as standards for FH diagnosis. Twenty-four of the patients (20%) had FH (cow's milk and/or wheat hypersensitivity); their symptom scores improved significantly when they were placed on an elimination diet. Patients with FH differed from other IBS patients in that they had a longer duration of clinical history, a history of FH as children, and an increased frequency of self-reported FH; they also had hypersensitivities to other antigens (eg, egg or soy). The basophil activation assay diagnosed FH with 86% sensitivity, 88% specificity, and 87% accuracy; this level of sensitivity was significantly higher than that of serum total IgE or food-specific IgE assays. A cytometric assay that quantifies basophils after stimulation with food antigens based on cell-surface expression of CD63 had high levels of sensitivity, specificity, and accuracy in diagnosing FH. This assay might be used to diagnose FH in patients with IBS-like symptoms. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  6. Colonic N-methyl-d-aspartate receptor contributes to visceral hypersensitivity in irritable bowel syndrome.

    PubMed

    Qi, Qingqing; Chen, Feixue; Zhang, Wenxue; Wang, Peng; Li, Yanqing; Zuo, Xiuli

    2017-04-01

    N-methyl-d-aspartate receptor (NMDAR) in brain, spinal cord, and enteric nervous system is involved in visceral hypersensitivity. This study aimed to reveal the functional expression of NMDAR on mucosal cells in colon and to investigate the downstream signal pathway from colonic NMDAR activation to visceral hypersensitivity in irritable bowel syndrome (IBS). The expression of mucosal NMDAR in IBS patients and healthy controls was assessed by immunohistochemistry and Western blot and correlated with abdominal pain/discomfort scores quantified by a validated questionnaire. Electromyography recording in response to colorectal distension was recorded to measure the colonic sensitivity of mice receiving NMDA administration intracolonically. Brain-derived neurotrophic factor (BDNF) expression and extracellular signal-regulated kinase (ERK) pathway activation were examined in human colonic epithelial HT29 cells after NMDA stimulation, with or without MK801 or U0126 pretreatment. A significant upregulation of mucosal NMDAR was observed in IBS patients compared with controls, which was significantly correlated with abdominal pain/discomfort scores. Intracolonic administration of NMDA in normal mice produced increased colonic sensitivity to colorectal distension and elevated expression of BDNF and activation of ERK. Activation of NMDAR in colonic epithelial HT29 cells in vitro induced increased BDNF secretion in cell supernatants and higher BDNF expression in cells, as well as elevated phosphorylated ERK. This study demonstrated that the activation of mucosal NMDAR in colon may contribute to the visceral hypersensitivity in IBS, by increasing production of BDNF in an ERK-dependent pathway. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  7. Use of lymphoblastoid cell lines to evaluate the hypersensitivity to ultraviolet radiation in Cockayne syndrome

    SciTech Connect

    Otsuka, F.; Tarone, R.E.; Cayeux, S.; Robbins, J.H.

    1984-05-01

    Cockayne syndrome (CS) is a rare autosomal recessive disease characterized by acute sun sensitivity, cachectic dwarfism, and neurologic and skeletal abnormalities. Cultured skin fibroblasts from patients with this disease are known to be hypersensitive to the lethal effects of 254-nm UV radiation. The authors have studied the sensitivity of 254-nm UV radiation of lymphoblastoid lines derived from 3 typical CS patients, 1 atypical CS patient who had a very late age of onset of clinical manifestations, 2 patients who had both xeroderma pigmentosum (XP) and typical CS, and 3 heterozygous parents of these patients. Post-UV survival was determined by the trypan-blue dye-exclusion method. The lymphoblastoid lines from the 3 typical CS patients, the atypical CS patient, and the 2 patients with both CS and XP had decreased post-UV viability in comparison with lines from normal donors. Lines from the heterozygous parents had normal post-UV viability. The post-UV viability of the typical CS lines was similar to that of a XP complementation group C line. The relative post-UV viability of lymphoblastoid lines from the typical CS patients was similar to the relative post-UV survival of their fibroblast lines. The lymphoblastoid line from the atypical CS patient had a post-UV viability similar to that of the typical CS patients. Thus, the relative hypersensitivity of CS patients cells in vitro does not reflect the severity or age of onset of the patients clinical manifestations. The lymphoblastoid lines from the 2 patients who had both CS and XP were significantly more sensitive to the UV radiation than those from patients with only CS. Our studies demonstrate that lymphoblastoid lines from patients with CS are appropriate and useful cell lines for the study of the inherited hypersensitivity to UV radiation.

  8. Drug-reaction eosinophilia and systemic symptoms and drug-induced hypersensitivity syndrome.

    PubMed

    Fernando, Suran L

    2014-02-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a rare, severe cutaneous adverse reaction characterised by fever, rash, lymphadenopathy, eosinophilia and/or other leukocyte abnormalities, and internal organ involvement and often has a relapsing-remitting course despite withdrawal of the drug. The drugs that are most implicated include aromatic anticonvulsants, allopurinol, sulphonamides, antiretrovirals (abacavir and nevirapine), and minocycline. The pathogenesis of DRESS/DIHS is far from clear but probably involves a combination of impaired pharmacokinetics and the accumulation of drug metabolites, the sequential reactivation of the herpesvirus family and genetic susceptibility conferred by the association with certain human leukocyte antigen (HLA) class I alleles. The strong association between abacavir and HLA-B*5701 has enabled pharmacogenetics screening to be employed successfully to minimise the occurrence of hypersensitivity. A prolonged course of oral corticosteroids is required to treat DRESS/DIHS, given the relapsing-remitting nature of the condition with i.v. immunoglobulin and valgangciclovir reserved for refractory or life-threatening cases. © 2013 The Australasian College of Dermatologists.

  9. Amitriptyline modifies the visceral hypersensitivity response to acute stress in the irritable bowel syndrome.

    PubMed

    Thoua, N M; Murray, C D R; Winchester, W J; Roy, A J; Pitcher, M C L; Kamm, M A; Emmanuel, A V

    2009-03-01

    Acute physical stress causes alteration in gut autonomic function and visceral hypersensitivity in patients with irritable bowel syndrome (IBS). We have developed a model to measure this stress response. To assess whether treatment with a drug effective in treating IBS (amitriptyline) alters the response to acute stress in IBS patients. Nineteen patients with IBS were given amitriptyline 25-50 mg. Patients underwent physical stress (cold pressor) test at baseline and after 3 months of treatment. Physiological parameters measured were: stress perception; systemic autonomic tone [heart rate (HR) and blood pressure (BP)]; gut specific autonomic innervation [rectal mucosal blood flow (RMBF)] and visceral sensitivity (rectal electrosensitivity). Fourteen of 19 (74%) patients improved symptomatically after 3 months of amitriptyline. Acute stress induced increased perception of stress and systemic autonomic tone and reduced RMBF in symptomatic responders and nonresponders (P > 0.05 for all). All nonresponders but only 3 of 14 responders continued to exhibit stress-induced reduced pain threshold at 3 months (change from baseline -31% vs. +2%, P < 0.03 respectively). In this open study, amitriptyline appears to decrease stress-induced electrical hypersensitivity; this effect is independent of autonomic tone. The gut response to acute stress deserves further study as a model to study drug efficacy in IBS.

  10. Pathogenesis and clinical approaches to anticonvulsant hypersensitivity syndrome: current state of knowledge.

    PubMed

    Scaparrotta, A; Verrotti, A; Consilvio, N P; Cingolani, A; Di Pillo, S; Di Gioacchino, M; Verini, M; Chiarelli, F

    2011-01-01

    Anticonvulsant hypersensitivity syndrome (AHS) is a rare, but severe and potentially fatal, adverse reaction that occurs in patients who are treated with commonly used older anticonvulsant drugs (phenytoin, carbamazepine and phenobarbital) and/or with some newer agents (lamotrigine). Paediatric patients are at an increased risk for the development of AHS for the higher incidence of seizure disorder in the first decade of life. Hypersensitivity reactions range from simple maculopapular skin eruptions to a severe life-threatening disorder. AHS is typically associated with the development of skin rash, fever and internal organ dysfunctions. Recent evidence suggests that AHS is the result of a chemotoxic and immunologically-mediated injury, characterized by skin and mucosal bioactivation of antiepileptic drugs and by major histocompatibility complex-dependent clonal expansion of T cells. Early recognition of AHS and withdrawal of anticonvulsant therapy are essential for a successful outcome. In vivo and vitro tests can be helpful for the diagnosis that actually depends essentially on clinical recognition.

  11. Piezo2: A Candidate Biomarker for Visceral Hypersensitivity in Irritable Bowel Syndrome?

    PubMed

    Bai, Tao; Li, Ying; Xia, Jing; Jiang, Yudong; Zhang, Lei; Wang, Huan; Qian, Wei; Song, Jun; Hou, Xiaohua

    2017-07-30

    Currently, there exists no biomarker for visceral hypersensitivity in irritable bowel syndrome (IBS). Piezo proteins have been proven to play an important role in the mechanical stimulation to induce visceral pain in other tissues and may also be a biomarker candidate. The aim of this study was to test the expressions of Piezo1 and Piezo2 proteins in the intestinal epithelial cells from different intestinal segments and to explore the correlation between Piezo proteins expression and visceral pain threshold. Post-infectious IBS was induced in mice via a Trichinella spiralis infection. Visceral sensitivity was measured with abdominal withdrawal reflex to colorectal distention. Inflammation in the small intestine and colon was scored with H&E staining. Expression location of Piezo proteins was confirmed by immunohistochemistry. Abundance of Piezo proteins were measured with real-time reverse transcriptase polymerase chain reaction. Piezo1 and Piezo2 proteins were expressed in the intestinal epithelial cells. The expression levels of Piezo1 and Piezo2 were abundant in the colon than the small intestine (P < 0.001 for Piezo1, P = 0.003 for Piezo2). Expression of Piezo2 in the colon significantly correlated to the visceral sensitivity (r = -0.718, P = 0.001) rather than the mucosal inflammation. Piezo2 is a candidate biomarker for visceral hypersensitivity in IBS.

  12. Piezo2: A Candidate Biomarker for Visceral Hypersensitivity in Irritable Bowel Syndrome?

    PubMed Central

    Bai, Tao; Li, Ying; Xia, Jing; Jiang, Yudong; Zhang, Lei; Wang, Huan; Qian, Wei; Song, Jun; Hou, Xiaohua

    2017-01-01

    Background/Aims Currently, there exists no biomarker for visceral hypersensitivity in irritable bowel syndrome (IBS). Piezo proteins have been proven to play an important role in the mechanical stimulation to induce visceral pain in other tissues and may also be a biomarker candidate. The aim of this study was to test the expressions of Piezo1 and Piezo2 proteins in the intestinal epithelial cells from different intestinal segments and to explore the correlation between Piezo proteins expression and visceral pain threshold. Methods Post-infectious IBS was induced in mice via a Trichinella spiralis infection. Visceral sensitivity was measured with abdominal withdrawal reflex to colorectal distention. Inflammation in the small intestine and colon was scored with H&E staining. Expression location of Piezo proteins was confirmed by immunohistochemistry. Abundance of Piezo proteins were measured with real-time reverse transcriptase polymerase chain reaction. Results Piezo1 and Piezo2 proteins were expressed in the intestinal epithelial cells. The expression levels of Piezo1 and Piezo2 were abundant in the colon than the small intestine (P < 0.001 for Piezo1, P = 0.003 for Piezo2). Expression of Piezo2 in the colon significantly correlated to the visceral sensitivity (r = −0.718, P = 0.001) rather than the mucosal inflammation. Conclusion Piezo2 is a candidate biomarker for visceral hypersensitivity in IBS. PMID:28044050

  13. Drug-Induced Hypersensitivity Syndrome Caused by Carbamazepine Used for the Treatment of Trigeminal Neuralgia

    PubMed Central

    Ono, Yuko; Shirafuji, Yoshinori; Hamada, Toshihisa; Masui, Masanori; Obata, Kyoichi; Yao, Mayumi; Kishimoto, Koji; Sasaki, Akira

    2016-01-01

    An 88-year-old man was diagnosed with trigeminal neuralgia, and treatment of carbamazepine 200 mg/day was initiated. About 6 weeks later, the patient developed a skin rash accompanied by fever. He was admitted to hospital and diagnosed with drug-induced hypersensitivity syndrome (DIHS) caused by carbamazepine. Oral carbamazepine treatment was stopped, but blood tests showed acute liver and acute renal failure. Drug-induced lymphocyte stimulation test (DLST) for carbamazepine, human herpes virus-6 (HHV-6) IgG, and CMV-HRP were negative. Oral prednisolone therapy was begun 18 days later. The titer of HHV-6 IgG antibodies was then detected (640 times). Following treatment, liver and renal function improved and the erythema disappeared. PMID:27885344

  14. Bronchiolitis obliterans organising pneumonia associated with anticonvulsant hypersensitivity syndrome induced by lamotrigine.

    PubMed

    Ghandourah, Hasan; Bhandal, Samarjeet; Brundler, Marie-Anne; Noseworthy, Mary

    2016-01-29

    A 14-year-old girl who was known to have a seizure disorder and on lamotrigine treatment was admitted to the hospital, with a history of rash, fever and cough. Her condition deteriorated with clinical features suggestive of anticonvulsant hypersensitivity syndrome (ACHS) complicated with bronchiolitis obliterans organising pneumonia (BOOP). Her chest CT showed multifocal parenchymal opacities and lung biopsy was typical for BOOP. Initially, the lamotrigine was discontinued since the onset of the rash, then she was treated for pneumonia with antibiotics, which may have delayed the diagnosis. Eventually, BOOP was considered and she was treated with a high dose of corticosteroid. She improved clinically and her repeated chest CT showed a marked resolution of the lesions. This case illustrates the possible occurrence of BOOP as a complication of ACHS secondary to lamotrigine treatment. 2016 BMJ Publishing Group Ltd.

  15. Drug-induced hypersensitivity syndrome: recent advances in the diagnosis, pathogenesis and management.

    PubMed

    Shiohara, Tetsuo; Kano, Yoko; Takahashi, Ryo; Ishida, Tadashi; Mizukawa, Yoshiko

    2012-01-01

    Drug-induced hypersensitivity syndrome (DIHS), also referred to as drug reaction with eosinophilia with systemic symptoms, is a life-threatening multiorgan system reaction caused by a limited number of drugs such as anticonvulsants. This syndrome is characterized by fever, rash, lymphadenopathy, hepatitis, and leukocytosis with eosinophilia. DIHS has several unique features that include the delayed onset, paradoxical deterioration of clinical symptoms after withdrawal of the causative drug and unexplained cross-reactivity to multiple drugs with different structures. Because of these features and a lack of awareness of this syndrome, DIHS is undoubtedly underdiagnosed in many countries despite its worldwide distribution. The clinical variability in the presentation and course of clinical symptoms of DIHS could now be interpreted as an indication that several herpesviruses reactivate in a sequential manner independently in the different organs. Dramatic expansions of functional regulatory T (Treg) cells observed in the acute stage would serve to induce such sequential reactivations of herpesviruses while a gradual loss of Treg function occurring after resolution of DIHS could increase the risk of subsequently developing autoimmune disease. Although systemic corticosteroids are the mainstay of treatment, it remains to be determined whether this treatment is beneficial from a viewpoint of disease outcome and sequelae.

  16. [The treatment of cutaneous loxoscelism with dapsone].

    PubMed

    Benavides, M I; Moncada, X

    1990-11-01

    Previous treatment of dermic lesions caused by brown recluse spider bite has given disappointing results. Cold, steroids and surgical measures are usually ineffective. Following encouraging results reported with the use of dapsone (4-4 diamine diphenyl sulphone) we treated 2 patients with severe dermic lesions. Both recovered satisfactorily. Thus, dapsone is an effective therapy for dermic lesions caused by brown recluse spider bite. The potential toxic effects of this sulphone derivative suggest that it should be used only in severe cases of the disease.

  17. Anaphylactic Shock: Kounis Hypersensitivity-Associated Syndrome Seems to be the Primary Cause

    PubMed Central

    Kounis, Nicholas G; Soufras, George D; Hahalis, George

    2013-01-01

    Experiments have shown that anaphylaxis decreases cardiac output; increases left ventricular end diastolic pressure; induces severe early acute increase in respiratory resistance with pulmonary interstitial edema; and decreases splanchnic, cerebral, and myocardial blood flow more than what would be expected from severe arterial dilation and hypotension. This is attributed to the constrictive action of inflammatory mediators released during anaphylactic shock. Inflammatory mediators such as histamine, neutral proteases, arachidonic acid products, platelet-activating factor (PAF), and a variety of cytokines and chemokines constitute the pathophysiologic basis of Kounis hypersensitivity-associated acute coronary syndrome. Although the mechanisms of anaphylactic shock still remain to be elucidated, myocardial involvement due to vasospasm-induced coronary blood flow reduction manifesting as Kounis syndrome should be always considered. Searching current experimental and clinical literature on anaphylactic shock pathophysiology, causality, clinical appearance, and treatment via PubMed showed that differentiating global hypoperfusion from primary tissue suppression due to mast cell mediator constrictive action on systemic arterial vasculature is a challenging procedure. Combined tissue suppression from arterial involvement and peripheral vasodilatation, perhaps, occur simultaneously. In cases of anaphylactic shock treatment targeting the primary cause of anaphylaxis together with protection of coronary vasculature and subsequently the cardiac tissue seems to be of paramount importance. PMID:24404540

  18. Anaphylactic Shock: Kounis Hypersensitivity-Associated Syndrome Seems to be the Primary Cause.

    PubMed

    Kounis, Nicholas G; Soufras, George D; Hahalis, George

    2013-11-01

    Experiments have shown that anaphylaxis decreases cardiac output; increases left ventricular end diastolic pressure; induces severe early acute increase in respiratory resistance with pulmonary interstitial edema; and decreases splanchnic, cerebral, and myocardial blood flow more than what would be expected from severe arterial dilation and hypotension. This is attributed to the constrictive action of inflammatory mediators released during anaphylactic shock. Inflammatory mediators such as histamine, neutral proteases, arachidonic acid products, platelet-activating factor (PAF), and a variety of cytokines and chemokines constitute the pathophysiologic basis of Kounis hypersensitivity-associated acute coronary syndrome. Although the mechanisms of anaphylactic shock still remain to be elucidated, myocardial involvement due to vasospasm-induced coronary blood flow reduction manifesting as Kounis syndrome should be always considered. Searching current experimental and clinical literature on anaphylactic shock pathophysiology, causality, clinical appearance, and treatment via PubMed showed that differentiating global hypoperfusion from primary tissue suppression due to mast cell mediator constrictive action on systemic arterial vasculature is a challenging procedure. Combined tissue suppression from arterial involvement and peripheral vasodilatation, perhaps, occur simultaneously. In cases of anaphylactic shock treatment targeting the primary cause of anaphylaxis together with protection of coronary vasculature and subsequently the cardiac tissue seems to be of paramount importance.

  19. Anticonvulsant hypersensitivity syndrome mimicking a viral illness with skin rash: a case report.

    PubMed

    Gérard, V; Delgrange, E; de Halleux, C; Vanpee, D

    2013-01-01

    Anticonvulsant hypersensitivity syndrome (ACHSS) is rare and defined by a group of systemic symptoms: a typical clinical triad with skin rash, high fever and lymphadenopathy, with or without multiple organ dysfunctions. Its variable presentation renders diagnosis particularly difficult yet important, as delayed diagnosis can lead to serious complications. We describe a 31-year-old woman sent to the emergency department with symptoms of high fever, peripheral lymphadenopathy, arthralgia, nausea, vomiting and a vesiculobullous eruption resembling measles. First diagnostic hypothesis was that of a viral illness. However, thorough second anamnesis pointed towards a possible drug aetiology, as the patient had been prescribed lamotrigine 8 days prior to admission. Blood analysis showed an inflammatory syndrome, thrombocytopenia and moderate lymphopenia. A few days later, results indicated old immunisation for measles. Skin biopsy revealed dermal inflammation with presence of hypereosinophilia, thereby confirming ACHSS. It is important to recognise and treat this rare reaction to anticonvulsants as early as possible in order to prevent its potentially life-threatening complications.

  20. [Case of drug-induced hypersensitivity syndrome due to lamotrigine: demonstration of sequential reactivation of herpesviruses].

    PubMed

    Sato, Tatsuharu; Kuniba, Hideo; Matsuo, Mitsuhiro; Matsuzaka, Tetsuo; Moriuchi, Hiroyuki

    2012-01-01

    Drug-induced hypersensitivity syndrome (DIHS) is a rare but severe multiorgan disorder. The reactivation of human herpesvirus-6 (HHV-6) and other human herpesviruses has been reported to be associated with its pathogenesis. We herein report a case of 14-year-old female who developed DIHS during the treatment with lamotrigine, a novel antiepileptic drug. She initially presented with fever, skin rash, cervical lymphadenopathy, leukocytosis with eosinophilia and atypical lymphocytosis, liver dysfunction and hypogammaglobulinemia. Discontinuation of the drug and administration of prednisolone led to improvement;however, tapering of prednisolone and administration of midazolam and ketamine thereafter triggered clinical deterioration. She subsequently developed hyperthyroidism followed by hypothyroidism. Herpesviral loads were determined in her peripheral blood by real-time PCR during the course of the treatment, and sequential reactivation of Epstein-Barr virus (EBV), HHV-6 and cytomegalovirus was demonstrated. EBV viremia was detected throughout the course, except for a short period when HHV-6 viremia was at the peak. HHV-6 viremia developed after the secondary deterioration. Cytomegalovirus viremia appeared transiently before the hyperthyroidic state reversed and became hypothyroidic. Although this syndrome should be regarded as a systemic reaction induced by a complex interplay among herpesviruses and the immune responses against viral infections and drugs, it remains unknown how such a sequential reactivation is related to the pathogenesis of the condition.

  1. Delayed hypersensitivity reaction to acellular dermal matrix in breast reconstruction: the red breast syndrome?

    PubMed

    Ganske, Ingrid; Hoyler, Marguerite; Fox, Sharon E; Morris, Donald J; Lin, Samuel J; Slavin, Sumner A

    2014-12-01

    Acellular dermal matrix (ADM) has become a valuable tool in reconstructive breast surgery, in part because it has been considered to be a non-reactive and non-immunogenic entity. However, some patients who undergo breast reconstruction with ADMs develop postoperative erythema overlying their ADM grafts. The etiology of this phenomenon is poorly understood. In this article, we summarize clinical cases in which patients developed localized breast erythema following reconstruction with ADMs. We review what is known about postoperative breast erythema after ADM-based breast reconstructions and the possible antigenicity of biologic mesh implants. We report 4 implant-based breast reconstruction patients who developed erythematous reactions overlying the region where ADM was placed: one demonstrated a delayed-type hypersensitivity reaction on punch biopsy of the affected skin, leading to removal of the biologic product; 2 others had a similar clinical presentation that responded to corticosteroids without removal of the biologic material, with 1 patient experiencing recrudescence of erythema that responded fully to a second course of corticosteroids; and a fourth showed erythema that was only moderately responsive to antibiotic therapy but which improved consistently after the patient initiated chemotherapy. We propose that the etiology of erythema overlying ADM grafts, and the so-called red breast syndrome, may in some patients be a delayed-type hypersensitivity reaction to the ADM product. Affected patients may benefit from treatment with corticosteroids or similar medications, and that such treatment may, in some cases, enable patients to retain the ADM grafts and enable salvage of the reconstructed breast.

  2. DRESS syndrome: Addressing the drug hypersensitivity syndrome on combination of Sodium Valproate and Olanzapine.

    PubMed

    Penchilaiya, Venkatalakshmi; Kuppili, Pooja Patnaik; Preeti, K; Bharadwaj, Balaji

    2017-08-01

    A case of an adolescent with symptoms of Mania, who developed Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) syndrome on exposure to combination of oral Olanzapine and Sodium Valproate is presented. We have attempted to highlight the atypical presentation of DRESS syndrome in this patient as well as management difficulties in patient who develops DRESS syndrome with the conventional psychotropic medication. Hence, it is necessary for mental health professionals to be vigilant about this life threatening drug reaction associated with high morbidity and mortality, thus ensuring prompt diagnosis and management. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Hypersensitivity to DNA-damaging agents in cultured cells from patients with Usher's syndrome and Duchenne muscular dystrophy.

    PubMed Central

    Robbins, J H; Scudiero, D A; Otsuka, F; Tarone, R E; Brumback, R A; Wirtschafter, J D; Polinsky, R J; Barrett, S F; Moshell, A N; Scarpinato, R G

    1984-01-01

    Lymphoblastoid lines from nine Usher's syndrome (recessively inherited retinitis pigmentosa and congenital sensorineural deafness) patients (representing eight kindreds) and from ten Duchenne muscular dystrophy patients (representing seven kindreds) showed a small but statistically significant hypersensitivity to the lethal effects of X-rays, as measured by the cellular ability to exclude the vital dye trypan blue, when compared with lines from 26 normal control subjects. Fibroblast lines from the Usher's syndrome patients, treated with X-rays or the radiomimetic, DNA-damaging chemical N-methyl-N'-nitro-N-nitrosoguanidine, also showed a statistically significant hypersensitivity when compared to normal fibroblast lines. These findings are consistent with the possibility that defective DNA repair mechanisms may be involved in the pathogenesis of these degenerative diseases. PMID:6726265

  4. Allergy/hypersensitivity reactions as a predisposing factor to complex regional pain syndrome I in orthopedic patients.

    PubMed

    Li, Xinning; Kenter, Keith; Newman, Ashley; O'Brien, Stephen

    2014-03-01

    Several predisposing conditions have been associated with complex regional pain syndrome I (CRPS I). The purpose of this study was to determine the relationship between a history of allergy/hypersensitivity reactions and CRPS I in orthopedic patients. Orthopedic patients with CRPS I (n=115) who experienced pain relief after a successful sympathetic nerve blockade were identified for study inclusion; a control group (n=115) matched to the CRPS I group by age, sex, and location of injury was also included. All patients in the study had an average age of 42 years. In the CRPS I group, all participants were Caucasian and the majority (80.8%) were women. The skin of patients with CRPS I was described as fair (57.7%), mottled (57.7%), or sensitive (80.8%). Of the patients with CRPS I, 78 (67.8%) reported a statistically significant history of allergies compared with the 39 (33.9%) patients in the control group (P<.0001). Patients with CRPS I who experienced complete pain relief for at least 1 month following a single sympathetic nerve block were asked to answer a questionnaire (n=35), and some then underwent immediate hypersensitivity testing using a skin puncture technique (n=26). Skin hypersensitivity testing yielded an 83.3% positive predictive value with an accuracy of 76.9%. Based on these results, a positive history for allergy/hypersensitivity reactions is a predisposing condition for CRPS I in this subset of orthopedic patients. These hypersensitivity reactions may prove important in gaining a better understanding in the pathophysiology of CRPS I as a regional pain syndrome. Copyright 2014, SLACK Incorporated.

  5. Performance of genetic risk factors in prediction of trichloroethylene induced hypersensitivity syndrome

    PubMed Central

    Dai, Yufei; Chen, Ying; Huang, Hanlin; Zhou, Wei; Niu, Yong; Zhang, Mingrong; Bin, Ping; Dong, Haiyan; Jia, Qiang; Huang, Jianxun; Yi, Juan; Liao, Qijun; Li, Haishan; Teng, Yanxia; Zang, Dan; Zhai, Qingfeng; Duan, Huawei; Shen, Juan; He, Jiaxi; Meng, Tao; Sha, Yan; Shen, Meili; Ye, Meng; Jia, Xiaowei; Xiang, Yingping; Huang, Huiping; Wu, Qifeng; Shi, Mingming; Huang, Xianqing; Yang, Huanming; Luo, Longhai; Li, Sai; Li, Lin; Zhao, Jinyang; Li, Laiyu; Wang, Jun; Zheng, Yuxin

    2015-01-01

    Trichloroethylene induced hypersensitivity syndrome is dose-independent and potentially life threatening disease, which has become one of the serious occupational health issues and requires intensive treatment. To discover the genetic risk factors and evaluate the performance of risk prediction model for the disease, we conducted genomewide association study and replication study with total of 174 cases and 1761 trichloroethylene-tolerant controls. Fifty seven SNPs that exceeded the threshold for genome-wide significance (P < 5 × 10−8) were screened to relate with the disease, among which two independent SNPs were identified, that is rs2857281 at MICA (odds ratio, 11.92; Pmeta = 1.33 × 10−37) and rs2523557 between HLA-B and MICA (odds ratio, 7.33; Pmeta = 8.79 × 10−35). The genetic risk score with these two SNPs explains at least 20.9% of the disease variance and up to 32.5-fold variation in inter-individual risk. Combining of two SNPs as predictors for the disease would have accuracy of 80.73%, the area under receiver operator characteristic curves (AUC) scores was 0.82 with sensitivity of 74% and specificity of 85%, which was considered to have excellent discrimination for the disease, and could be considered for translational application for screening employees before exposure. PMID:26190474

  6. Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia.

    PubMed

    Miyazaki, Masayuki; Tanaka, Masatake; Ueda, Akihiro; Yoshimoto, Tsuyoshi; Kato, Masaki; Nakamuta, Makoto; Kotoh, Kazuhiro; Takayanagi, Ryoichi

    2011-11-28

    Drug-induced hypersensitivity syndrome (DIHS) is a severe reaction usually characterized by fever, rash, and multiorgan failure, occurring 2-6 wk after drug introduction. It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release. A 54-year-old woman was diagnosed with rheumatic arthritis and initiated salazosulfapyridine by mouth. About 10 d later, she had a high fever, skin rash and liver dysfunction. She was admitted to hospital and diagnosed with a drug eruption. She was treated with oral prednisolone 30 mg/d; however, she developed high fever again and her blood tests showed acute liver failure and cytopenia associated with hyperferritinemia. She was diagnosed with acute liver failure and hemophagocytosis caused by DIHS. She was transferred to the Department of Medicine and Bioregulatory Science, Kyushu University, where she was treated with arterial steroid injection therapy. Following this treatment, her liver function improved and serum ferritin immediately decreased. We hypothesized that an immune-mediated reaction in DIHS may have generated over-activation of macrophages and T-lymphocytes, followed by a cytokine storm that affected various organs. The measurement of serum ferritin might be a useful marker of the severity of DIHS.

  7. Performance of genetic risk factors in prediction of trichloroethylene induced hypersensitivity syndrome.

    PubMed

    Dai, Yufei; Chen, Ying; Huang, Hanlin; Zhou, Wei; Niu, Yong; Zhang, Mingrong; Bin, Ping; Dong, Haiyan; Jia, Qiang; Huang, Jianxun; Yi, Juan; Liao, Qijun; Li, Haishan; Teng, Yanxia; Zang, Dan; Zhai, Qingfeng; Duan, Huawei; Shen, Juan; He, Jiaxi; Meng, Tao; Sha, Yan; Shen, Meili; Ye, Meng; Jia, Xiaowei; Xiang, Yingping; Huang, Huiping; Wu, Qifeng; Shi, Mingming; Huang, Xianqing; Yang, Huanming; Luo, Longhai; Li, Sai; Li, Lin; Zhao, Jinyang; Li, Laiyu; Wang, Jun; Zheng, Yuxin

    2015-07-20

    Trichloroethylene induced hypersensitivity syndrome is dose-independent and potentially life threatening disease, which has become one of the serious occupational health issues and requires intensive treatment. To discover the genetic risk factors and evaluate the performance of risk prediction model for the disease, we conducted genomewide association study and replication study with total of 174 cases and 1761 trichloroethylene-tolerant controls. Fifty seven SNPs that exceeded the threshold for genome-wide significance (P < 5 × 10(-8)) were screened to relate with the disease, among which two independent SNPs were identified, that is rs2857281 at MICA (odds ratio, 11.92; P meta = 1.33 × 10(-37)) and rs2523557 between HLA-B and MICA (odds ratio, 7.33; P meta = 8.79 × 10(-35)). The genetic risk score with these two SNPs explains at least 20.9% of the disease variance and up to 32.5-fold variation in inter-individual risk. Combining of two SNPs as predictors for the disease would have accuracy of 80.73%, the area under receiver operator characteristic curves (AUC) scores was 0.82 with sensitivity of 74% and specificity of 85%, which was considered to have excellent discrimination for the disease, and could be considered for translational application for screening employees before exposure.

  8. In vitro testing for the diagnosis of anticonvulsant hypersensitivity syndrome: a systematic review.

    PubMed

    Elzagallaai, Abdelbaset A; Knowles, Sandra R; Rieder, Michael J; Bend, John R; Shear, Neil H; Koren, Gideon

    2009-01-01

    Anticonvulsant hypersensitivity syndrome (AHS) is a rare and potentially fatal reaction that develops in susceptible patients following exposure to certain drugs, including aromatic anticonvulsants. Because of its ill-defined clinical picture and resemblance to other diseases, the diagnosis of AHS is often difficult and requires a safe and reliable diagnostic test. Other than systemic rechallenge, which is not always ethically permissible and has its own limitations, no reliable diagnostic test is available for this type of disorder. This systematic review attempts to evaluate the usefulness of the available in vitro tests in the diagnosis of AHS - namely, the lymphocyte transformation test (LTT) and the lymphocyte toxicity assay (LTA) - and to examine the different technical aspects of these tests that may contribute to their performance. We included studies in which aromatic anticonvulsant drugs were the likely causes of the hypersensitivity reaction and either the LTT or the LTA was used to aid the diagnosis of AHS. Analysis of original publications from 1950 to the last week of March 2009 and cited in PubMed, MEDLINE and EMBASE has revealed that there are numerous factors affecting the final result of the test, including the following: the timing of the test after exposure; the clinical manifestation of the reactions; the specific drug; and the test procedure and read-out system. In vitro diagnostic tests have the advantage over in vivo tests of being safe to use; however, in vitro tests for the diagnosis of AHS are not well standardized and their sensitivity and specificity are not yet determined. From the reviewed literature, the sensitivity of the LTT and the LTA seem to be around 70% and 90%, respectively, and the positive and negative predictive values of the tests in highly imputable cases are quite high. However, the lack of a gold-standard diagnostic test to prove drug culpability, along with the paucity of large-scale studies, precludes accurate

  9. Colonic mucosal N-methyl-D-aspartate receptor mediated visceral hypersensitivity in a mouse model of irritable bowel syndrome.

    PubMed

    Qi, Qing Qing; Chen, Fei Xue; Zhao, Dong Yan; Li, Li Xiang; Wang, Peng; Li, Yan Qing; Zuo, Xiu Li

    2016-07-01

    The aim of this study was to investigate whether colonic mucosal N-methyl-D-aspartate receptor (NMDAR) participates in visceral hypersensitivity in irritable bowel syndrome (IBS). C57BL/6 mice were administered intrarectally with trinitrobenzenesulfonic acid (TNBS) for the establishment of an IBS-like visceral hypersensitivity model. Those received an equivalent volume of 50% ethanol were regarded as the controls. Abdominal withdrawal reflex (AWR) scores in response to colorectal distention (CRD) were used to assess visceral sensitivity. NMDAR levels in the colonic mucosa were detected by both immunohistochemistry and Western blot. The concentrations of glutamate and ammonia in the feces of the mice were measured. Changes in visceral sensitivity after the intracolonic administration of ammonia or NMDAR antagonist were recorded. The established IBS-like mouse model of visceral hypersensitivity showed no evident inflammation in the colon. NMDAR levels in the colonic mucosa of the IBS-like mice were significantly higher compared with the controls, and were positively associated with AWR scores. The glutamate level in the feces of the TNBS-treated mice was similar to that of the controls, although the ammonia level was significantly higher. Intracolonic administration of ammonia induced visceral hypersensitivity in mice, which was repressed by pretreatment with NMDAR antagonist MK801. Overexpressed NMDAR in the colonic mucosa may participate in the pathogenesis of visceral hypersensitivity in IBS. Our study identifies the effect of ammonia in the colonic lumen on NMDAR in the colonic mucosa as a potential novel targeted mechanism for IBS treatment. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  10. Dapsone-induced photosensitivity: a rare clinical presentation.

    PubMed

    Kar, Bikash Ranjan

    2008-10-01

    Dapsone is an efficient anti-inflammatory and antimycobacterial agent. It is one of the main constituents of multidrug therapy (MDT). It acts by interference with folate metabolism. Dapsone-induced photosensitivity is a rare, non-dose-related adverse effect of the sulfone and can occur in patients with inflammatory skin disorders treated with dapsone. So far, only 12 cases seem to have been reported in the literature. We report a case of dapsone-induced photosensitivity in an Indian patient with leprosy.

  11. Fecal assays detect hypersensitivity to cow's milk protein and gluten in adults with irritable bowel syndrome.

    PubMed

    Carroccio, Antonio; Brusca, Ignazio; Mansueto, Pasquale; Soresi, Maurizio; D'Alcamo, Alberto; Ambrosiano, Giuseppe; Pepe, Ilenia; Iacono, Giuseppe; Lospalluti, Maria Letizia; La Chiusa, Stella M; Di Fede, Gaetana

    2011-11-01

    Some patients with irritable bowel syndrome (IBS)-like symptoms suffer from food hypersensitivity (FH); their symptoms improve when they are placed on elimination diets. No assays identify patients with FH with satisfactory levels of sensitivity. We determined the frequency of FH among patients with symptoms of IBS and the ability of fecal assays for tryptase, eosinophil cationic protein (ECP), or calprotectin to diagnose FH. The study included 160 patients with IBS, 40 patients with other gastrointestinal diseases, and 50 healthy individuals (controls). At the start of the study, patients completed a symptom severity questionnaire, fecal samples were assayed, and levels of specific immunoglobulin E were measured. Patients were observed for 4 weeks, placed on an elimination diet (without cow's milk and derivatives, wheat, egg, tomato, and chocolate) for 4 weeks, and kept a diet diary. Those who reported improvements after the elimination diet period were then diagnosed with FH, based on the results of a double-blind, placebo-controlled, oral food challenge (with cow's milk proteins and then with wheat proteins). Forty of the patients with IBS (25%) were found to have FH. Levels of fecal ECP and tryptase were significantly higher among patients with IBS and FH than those without FH. The ECP assay was the most accurate assay for diagnosis of FH, showing 65% sensitivity and 91% specificity. Twenty-five percent of patients with IBS have FH. These patients had increased levels of fecal ECP and tryptase, indicating that they might cause inflammation in patients with IBS. Fecal assays for ECP could be used to identify FH in patients with IBS. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  12. The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

    PubMed Central

    Farzaei, Mohammad H; Bahramsoltani, Roodabeh; Abdollahi, Mohammad; Rahimi, Roja

    2016-01-01

    Irritable bowel syndrome (IBS) is the most common disorder referred to gastroenterologists and is characterized by altered bowel habits, abdominal pain, and bloating. Visceral hypersensitivity (VH) is a multifactorial process that may occur within the peripheral or central nervous systems and plays a principal role in the etiology of IBS symptoms. The pharmacological studies on selective drugs based on targeting specific ligands can provide novel therapies for modulation of persistent visceral hyperalgesia. The current paper reviews the cellular and molecular mechanisms underlying therapeutic targeting for providing future drugs to protect or treat visceroperception and pain sensitization in IBS patients. There are a wide range of mediators and receptors participating in visceral pain perception amongst which substances targeting afferent receptors are attractive sources of novel drugs. Novel therapeutic targets for the management of VH include compounds which alter gut-brain pathways and local neuroimmune pathways. Molecular mediators and receptors participating in pain perception and visceroperception include histamine-1 receptors, serotonin (5-hydrodytryptamine) receptors, transient receptor potential vanilloid type I, tachykinins ligands, opioid receptors, voltage-gated channels, tyrosine receptor kinase receptors, protease-activated receptors, adrenergic system ligands, cannabinoid receptors, sex hormones, and glutamate receptors which are discussed in the current review. Moreover, several plant-derived natural compounds with potential to alleviate VH in IBS have been highlighted. VH has an important role in the pathology and severity of complications in IBS. Therefore, managing VH can remarkably modulate the symptoms of IBS. More preclinical and clinical investigations are needed to provide efficacious and targeted medicines for the management of VH. PMID:27431236

  13. [Feeding disorders, ALTE syndrome, Sandifer syndrome and gastroesophageal reflux disease in the course of food hypersensitivity in 8-month old infant].

    PubMed

    Iwańczak, Barbara; Mowszet, Krystyna; Iwańczak, Franciszek

    2010-07-01

    This paper describes the occurrence of feeding disorders, atopic dermatitis, life-threatening symptoms, Sandifer syndrome, and gastroesophageal reflux disease in 8-month old infant in the course of food hypersensitivity. Used in the treatment of cow's milk protein hydrolysates with a considerable degree of hydrolysis, omeprazole, Cisapride. It was not until the introduction of elemental diet based on free amino acids resulted in the withdrawal of life-threatening child's symptoms.

  14. Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients.

    PubMed

    Ben m'rad, Mona; Leclerc-Mercier, Stéphanie; Blanche, Philippe; Franck, Nathalie; Rozenberg, Flore; Fulla, Yvonne; Guesmi, Myriam; Rollot, Florence; Dehoux, Monique; Guillevin, Loïc; Moachon, Laurence

    2009-05-01

    Drug-induced hypersensitivity syndrome (DIHS), also called drug rash with eosinophilia and systemic symptoms (DRESS), is a severe reaction usually characterized by fever, rash, and multiorgan failure, occurring 1-8 weeks after drug introduction. It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release, although no consensus has been reached as to its etiology. The skin, hematopoietic system, and liver are frequently involved. DIHS can mimic severe sepsis, viral infection, adult-onset Still disease (AOSD), or lymphoproliferation.We describe 24 consecutive patients with DIHS who were hospitalized between September 2004 and March 2008. Criteria for inclusion in this observational study were suspected drug reaction, eosinophilia >or=500/microL and/or atypical lymphocytes, involvement of at least 2 organs (skin being 1 of them), with suggestive chronology and exclusion of other diagnoses. Our cohort of 12 women and 12 men had a median age of 49 years (range, 22-82 yr), and 11 had skin phototype V or VI. Patients with mild or no rash were immunocompromised (7/24)- defined as treatment with prednisone (>or=10 mg/d) and another immunosuppressant drug, or human immunodeficiency virus infection. All patients were febrile (>38 degrees C), 14 had localized or generalized edema, 7 had pharyngitis, 8 had lymphadenopathy, 22 had hepatitis, 4 had nephritis, 2 had noninfectious and nonlithiasic angiocholitis or cholecystitis. Ten patients were hypotensive, 5 of whom had associated laboratory signs and/or imaging findings suggestive of acute myocardial dysfunction. Half of the patients had hemogram abnormalities, including eosinophilia. Nine DIHS patients fulfilled the Fautrel criteria for AOSD diagnosis, including glycosylated ferritin <20% in 4/11, with or without laboratory characteristics of hemophagocytosis. Twenty DIHS episodes occurred during the less sunny months of October to March.We determined 25-hydroxyvitamin D3 (25[OH]D3

  15. Delayed-Type Hypersensitivity to Metals of Environmental Burden in Patients with Takotsubo Syndrome – Is There a Clinical Relevance?

    PubMed Central

    Manousek, Jan; Stejskal, Vera; Kubena, Petr; Jarkovsky, Jiri; Nemec, Petr; Lokaj, Petr; Dostalova, Ludmila; Zadakova, Andrea; Pavlusova, Marie; Benesova, Klara; Kala, Petr; Miklik, Roman; Spinar, Jindrich; Parenica, Jiri

    2016-01-01

    Objective Takotsubo syndrome (TS) is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA®. Methodology, Results A total of 24 patients (23 women, 1 man) with a history of TS attack and 27 healthy controls were evaluated. Hypersensitivity was evaluated by a lymphocyte transformation test (LTT-MELISA®); a questionnaire of environmental burden was used to select evaluated metals. A total of 19 patients (79%) had at least one condition that might potentially be associated with pathological immune reactivity (autoimmune thyroid disease, drug allergy, bronchial asthma, cancer, contact dermatitis, rheumatoid arthritis). Hypersensitivity to metals was identified significantly more frequently in TS patients than in healthy controls (positive reaction to at least one metal was identified in 95.8% of TS patients and in 59.3% of controls; p = 0.003); the difference was statistically significant for mercury (45.8% and 14.8%, respectively; p = 0.029). Conclusion Our work shows that conditions with pathological immune reactivity occur frequently in TS patients, and our data suggest a possible association between TS and hypersensitivity to metals (mercury in particular) evaluated by LTT-MELISA®. We also suggest that apart from the triggering stress factor, potential existence of other serious conditions should be considered when taking medical history of TS patients. PMID:27824862

  16. Folliculitis spinulosa decalvans: successful therapy with dapsone.

    PubMed

    Kunte, C; Loeser, C; Wolff, H

    1998-11-01

    A 27-year-old male patient presented with scaly erythema and crusts on the scalp. Since birth, he suffered from dry skin and inflammation of the eyelids. Scarring alopecia was noticed in some regions of his scalp. Folliculitis spinulosa decalvans was diagnosed. Therapy with isotretinoin and topical corticosteroids was without effect. In contrast, 100 mg of Dapsone per day led to resolution of the inflammatory signs. This enabled him to cover the disfiguring scarring alopecia with a permanent hairpiece. His condition has been stable after 18 months without the enlargement of the scarred alopecic areas.

  17. Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) / Drug-induced Hypersensitivity Syndrome (DIHS): a review of current concepts.

    PubMed

    Criado, Paulo Ricardo; Criado, Roberta Fachini Jardim; Avancini, João de Magalhães; Santi, Claudia Giuli

    2012-01-01

    The Drug Reaction with Eosinophilia and Systemic Symptoms syndrome, also known as Drug Induced Hypersensitivity Syndrome presents clinically as an extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, causing damage to several systems, especially to the kidneys, heart, lungs, and pancreas. Recognition of this syndrome is of paramount importance, since the mortality rate is about 10% to 20%, and a specific therapy may be necessary. The pathogenesis is related to specific drugs, especially the aromatic anticonvulsants, altered immune response, sequential reactivation of herpes virus and association with HLA alleles. Early recognition of the syndrome and withdrawal of the offending drug are the most important and essential steps in the treatment of affected patients. Corticosteroids are the basis of the treatment of the syndrome, which may be associated with intravenous immunoglobulin and, in selected cases, Ganciclovir. The article reviews the current concepts involving this important manifestation of adverse drug reaction.

  18. Comparison of Electroacupuncture and Moxibustion for Relieving Visceral Hypersensitivity in Rats with Constipation-Predominant Irritable Bowel Syndrome

    PubMed Central

    Dou, Chuan-Zi

    2016-01-01

    Aim. To compare whether there is different effect between electroacupuncture (EA) and moxibustion (Mox) on visceral hypersensitivity (their analgesic effects) in constipation-predominant irritable bowel syndrome (C-IBS). Methods. EA at 1 mA and 3 mA and Mox at 43°C and 46°C were applied to the Shangjuxu (ST37, bilateral) acupoint in rats with C-IBS and normal rats. An abdominal withdrawal reflex (AWR) score was used to assess visceral hypersensitivity. Toluidine blue staining was used to assess mast cell (MC) activity in colon of rats. Immunochemistry was used to measure 5-HT and 5-HT4 receptor expression in the colon. Results. AWR scores in all EA (1 mA and 3 mA) and Mox (43°C and 46°C) treatment groups after colorectal distention (CRD) stimulation pressure of 20, 40, 60, and 80 mmHg were significantly lower than those of the model (MC) group (P all < 0.01). The MC counts and degranulation rates in the colon of all EA and Mox treatment groups and the MC group were significantly higher than those of the NC group (P all < 0.01). MC degranulation rates in the colon of all EA and Mox treatment groups were lower than those of the MC group (P all < 0.05). 5-HT expression in colon of all EA and Mox treatment groups was significantly lower than that of the MC group (P all < 0.01), and 5-HT4R expression in colon of both EA groups was significantly higher than that of the MC group (P both < 0.01). Conclusion. EA and Mox treatments may both ameliorate visceral hypersensitivity at different degree in rats with C-IBS, and EA treatment was better than Mox. PMID:27738447

  19. Comparison of Electroacupuncture and Moxibustion for Relieving Visceral Hypersensitivity in Rats with Constipation-Predominant Irritable Bowel Syndrome.

    PubMed

    Zhao, Ji-Meng; Chen, Liu; Zhou, Ci-Li; Shi, Yin; Li, Yu-Wei; Shang, Hai-Xia; Wu, Lu-Yi; Bao, Chun-Hui; Dou, Chuan-Zi; Wu, Huan-Gan

    2016-01-01

    Aim. To compare whether there is different effect between electroacupuncture (EA) and moxibustion (Mox) on visceral hypersensitivity (their analgesic effects) in constipation-predominant irritable bowel syndrome (C-IBS). Methods. EA at 1 mA and 3 mA and Mox at 43°C and 46°C were applied to the Shangjuxu (ST37, bilateral) acupoint in rats with C-IBS and normal rats. An abdominal withdrawal reflex (AWR) score was used to assess visceral hypersensitivity. Toluidine blue staining was used to assess mast cell (MC) activity in colon of rats. Immunochemistry was used to measure 5-HT and 5-HT4 receptor expression in the colon. Results. AWR scores in all EA (1 mA and 3 mA) and Mox (43°C and 46°C) treatment groups after colorectal distention (CRD) stimulation pressure of 20, 40, 60, and 80 mmHg were significantly lower than those of the model (MC) group (P all < 0.01). The MC counts and degranulation rates in the colon of all EA and Mox treatment groups and the MC group were significantly higher than those of the NC group (P all < 0.01). MC degranulation rates in the colon of all EA and Mox treatment groups were lower than those of the MC group (P all < 0.05). 5-HT expression in colon of all EA and Mox treatment groups was significantly lower than that of the MC group (P all < 0.01), and 5-HT4R expression in colon of both EA groups was significantly higher than that of the MC group (P both < 0.01). Conclusion. EA and Mox treatments may both ameliorate visceral hypersensitivity at different degree in rats with C-IBS, and EA treatment was better than Mox.

  20. P2X7 receptor-dependent intestinal afferent hypersensitivity in a mouse model of postinfectious irritable bowel syndrome.

    PubMed

    Keating, Christopher; Pelegrin, Pablo; Martínez, Carlos M; Grundy, David

    2011-08-01

    The ATP-gated P2X(7) receptor (P2X(7)R) was shown to be an important mediator of inflammation and inflammatory pain through its regulation of IL-1β processing and release. Trichinella spiralis-infected mice develop a postinflammatory visceral hypersensitivity that is reminiscent of the clinical features associated with postinfectious irritable bowel syndrome. In this study, we used P2X(7)R knockout mice (P2X(7)R(-/-)) to investigate the role of P2X(7)R activation in the in vivo production of IL-1β and the development of postinflammatory visceral hypersensitivity in the T. spiralis-infected mouse. During acute nematode infection, IL-1β-containing cells and P2X(7)R expression were increased in the jejunum of wild-type (WT) mice. Peritoneal and serum IL-1β levels were also increased, which was indicative of elevated IL-1β release. However, in the P2X(7)R(-/-) animals, we found that infection had no effect upon intracellular, plasma, or peritoneal IL-1β levels. Conversely, infection augmented peritoneal TNF-α levels in both WT and P2X(7)R(-/-) animals. Infection was also associated with a P2X(7)R-dependent increase in extracellular peritoneal lactate dehydrogenase, and it triggered immunological changes in both strains. Jejunal afferent fiber mechanosensitivity was assessed in uninfected and postinfected WT and P2X(7)R(-/-) animals. Postinfected WT animals developed an augmented afferent fiber response to mechanical stimuli; however, this did not develop in postinfected P2X(7)R(-/-) animals. Therefore, our results demonstrated that P2X(7)Rs play a pivotal role in intestinal inflammation and are a trigger for the development of visceral hypersensitivity.

  1. A Case of Sublingual Ranula That Responded Successfully to Localized Injection Treatment with OK-432 after Healing from Drug Induced Hypersensitivity Syndrome

    PubMed Central

    Yoshizawa, Kunio; Moroi, Akinori; Kawashiri, Shuichi; Ueki, Koichiro

    2016-01-01

    A ranula is a mucus retention cyst or pseudocyst caused by leakage of mucus from the sublingual gland and generally occurs in the oral floor. In addition, drug induced hypersensitivity syndrome (DIHS) is a rare but well-recognized serious adverse effect characterized by fever, skin rashes, generalized lymphadenopathy, hepatitis, and hepatosplenomegaly and oral stomatitis. This paper presents the first case of successfully treated sublingual ranula with localized injection of OK-432 after healing from drug induced hypersensitivity syndrome, which has previously been unreported in the literature. We present the case of a 38-year-old Japanese woman with sublingual ranula that responded successfully to localized injection treatment with OK-432 after healing from drug induced hypersensitivity syndrome. She was affected with cutaneous myositis and interstitial lung disease when she was 26 years old. At the age 34 years, she received additional oral treatment of diaminodiphenyl-sulfone due to deterioration of the cutaneous myositis, which resulted in drug induced hypersensitivity syndrome (DIHS) with severe oral stomatitis. Local injection of OK-432 to the ranula may be a very safe and useful treatment method even if the patient has a history of drug allergy and has connective tissue disease such as cutaneous myositis. PMID:27144039

  2. A Case of Sublingual Ranula That Responded Successfully to Localized Injection Treatment with OK-432 after Healing from Drug Induced Hypersensitivity Syndrome.

    PubMed

    Yoshizawa, Kunio; Moroi, Akinori; Kawashiri, Shuichi; Ueki, Koichiro

    2016-01-01

    A ranula is a mucus retention cyst or pseudocyst caused by leakage of mucus from the sublingual gland and generally occurs in the oral floor. In addition, drug induced hypersensitivity syndrome (DIHS) is a rare but well-recognized serious adverse effect characterized by fever, skin rashes, generalized lymphadenopathy, hepatitis, and hepatosplenomegaly and oral stomatitis. This paper presents the first case of successfully treated sublingual ranula with localized injection of OK-432 after healing from drug induced hypersensitivity syndrome, which has previously been unreported in the literature. We present the case of a 38-year-old Japanese woman with sublingual ranula that responded successfully to localized injection treatment with OK-432 after healing from drug induced hypersensitivity syndrome. She was affected with cutaneous myositis and interstitial lung disease when she was 26 years old. At the age 34 years, she received additional oral treatment of diaminodiphenyl-sulfone due to deterioration of the cutaneous myositis, which resulted in drug induced hypersensitivity syndrome (DIHS) with severe oral stomatitis. Local injection of OK-432 to the ranula may be a very safe and useful treatment method even if the patient has a history of drug allergy and has connective tissue disease such as cutaneous myositis.

  3. Review article: visceral hypersensitivity in irritable bowel syndrome: molecular mechanisms and therapeutic agents.

    PubMed

    Akbar, A; Walters, J R F; Ghosh, S

    2009-09-01

    Although development of visceral pain is an important defensive mechanism, hypersensitivity results in a significant clinical problem and is likely to be one of the major factors involved in the pathogenesis of abdominal and chest pain in functional bowel disorders (FBDs). Understanding of the molecular mechanisms involved in peripheral sensitization of visceral nociceptors has advanced as a result of the experimental studies, especially in animal models, which have led to knowledge and identification of key mediators and receptors. To provide a comprehensive review focused on the peripheral mechanisms believed to be responsible for sensitization and potential molecular targets for a disorder which is common, distressing and has sub-optimal treatment options. Literature review using Ovid and Pubmed from 1966. There is substantial interest in the development of new drugs for treatment of FBDs in the background of advances in understanding the molecular and physiological mechanisms of visceral hypersensitivity. The potential drug targets include TPRV1, ASICs, voltage-gated sodium channels, ATP, PAR-2, cannabinoid, prostaglandin, tachykinin and 5HT(3) receptors. It is anticipated that with advancing molecular understanding of the basis of visceral hypersensitivity, the next decade will see accelerated development of new molecules for treatment of functional bowel diseases.

  4. Hypersensitivity Pneumonitis

    MedlinePlus

    ... Hypersensitivity Pneumonitis Also known as extrinsic allergic alveolitis, bird fancier’s lung, farmer’s lung, hot tub lung, and humidifier lung. Hypersensitivity pneumonitis is a rare immune system disorder that affects the lungs. It occurs in ...

  5. A case of drug-induced hypersensitivity syndrome showing transient immunosuppression before viral reactivation during treatment for pemphigus foliaceus.

    PubMed

    Takahashi, H; Tanaka, M; Tanikawa, A; Toyohara, A; Ogo, Y; Morimoto, A; Harato, R; Kobayashi, M; Amagai, M

    2006-01-01

    Drug-induced hypersensitivity syndrome (DIHS) is one of the most severe drug adverse reactions, with characteristic biphasic symptoms. Reactivation of human herpesvirus-6 (HHV-6) is frequently observed, although the cause of DIHS is still unknown. A patient developed DIHS during treatment with diaminodiphenylsulphone for pemphigus foliaceus. The number of lymphocytes in his peripheral blood, and titres of serum total IgG and IgM and anti-desmoglein1 antibody transiently decreased just before reactivation of HHV-6, cytomegalovirus and Epstein-Barr virus. This observation suggests that transient suppression of both cellular and humoral immunity may trigger viral reactivation, which leads to the development of the second phase of DIHS.

  6. Activation of 5-HT and NR2B contributes to visceral hypersensitivity in irritable bowel syndrome in rats.

    PubMed

    Chen, Ming-Xian; Chen, Yu; Fu, Rui; Liu, Sai-Yue; Yang, Qin-Qin; Shen, Tang-Biao

    2016-01-01

    The roles of 5-hydroxytryptamine (5-HT) and spinal N-methyl-D-aspartic acid receptor 2B (NR2B) in visceral hypersensitivity were investigated. A rat model with irritable bowel syndrome (IBS) was established by intracolonic injections of acetic acid onpost-natal days 8-21. Rats were randomly divided into five groups: normal intact (control) group, IBS model group, Ro25-6981-treated IBS rats (Ro25-6981, a NR2B antagonist) group, amitriptyline-treated IBS rats (amitriptyline, a 5-HT antagonist) and Ro25-6981 plus amitriptyline-treated IBS rats (Ro25-6981+amitriptyline) group. The expressions of 5-HT, NR2B, 5-HT2AR, 5-HT7R, SERT, TNF-α and IL-1β in colon, dorsal root ganglion (DRG) and hypothalamus, respectively, were measured by Immunohistochemical staining, Real-Time Reverse Transcription-PCR and Western blotting. Our results showed increased DRG and hypothalamus expression of 5-HT, NR2B, 5-HT2AR, 5-HT7R in IBS model group and decreased expression of those in Ro25-6981 and amitriptyline alone or both treatment groups. Moreover, SERT expression was decreased in colorectal, DRG and hypothalamus of ISB model rats, but increased by Ro25-6981 and amitriptyline alone or both treatments. Ro25-6981 and amitriptyline treatment also decreased colorectal expression of TNF-α and IL-1β induced by IBS model. In conclusion, activation of 5-HT and NR2B may play a crucial role in visceral hypersensitivity in irritable bowel syndrome in rats.

  7. Activation of 5-HT and NR2B contributes to visceral hypersensitivity in irritable bowel syndrome in rats

    PubMed Central

    Chen, Ming-Xian; Chen, Yu; Fu, Rui; Liu, Sai-Yue; Yang, Qin-Qin; Shen, Tang-Biao

    2016-01-01

    The roles of 5-hydroxytryptamine (5-HT) and spinal N-methyl-D-aspartic acid receptor 2B (NR2B) in visceral hypersensitivity were investigated. A rat model with irritable bowel syndrome (IBS) was established by intracolonic injections of acetic acid onpost-natal days 8-21. Rats were randomly divided into five groups: normal intact (control) group, IBS model group, Ro25-6981-treated IBS rats (Ro25-6981, a NR2B antagonist) group, amitriptyline-treated IBS rats (amitriptyline, a 5-HT antagonist) and Ro25-6981 plus amitriptyline-treated IBS rats (Ro25-6981+amitriptyline) group. The expressions of 5-HT, NR2B, 5-HT2AR, 5-HT7R, SERT, TNF-α and IL-1β in colon, dorsal root ganglion (DRG) and hypothalamus, respectively, were measured by Immunohistochemical staining, Real-Time Reverse Transcription-PCR and Western blotting. Our results showed increased DRG and hypothalamus expression of 5-HT, NR2B, 5-HT2AR, 5-HT7R in IBS model group and decreased expression of those in Ro25-6981 and amitriptyline alone or both treatment groups. Moreover, SERT expression was decreased in colorectal, DRG and hypothalamus of ISB model rats, but increased by Ro25-6981 and amitriptyline alone or both treatments. Ro25-6981 and amitriptyline treatment also decreased colorectal expression of TNF-α and IL-1β induced by IBS model. In conclusion, activation of 5-HT and NR2B may play a crucial role in visceral hypersensitivity in irritable bowel syndrome in rats. PMID:28078028

  8. Piperacillin/Tazobactam-Associated Hypersensitivity Syndrome with Overlapping Features of Acute Generalized Exanthematous Pustulosis and Drug-Related Rash with Eosinophilia and Systemic Symptoms Syndrome

    PubMed Central

    Kim, Tae In; Jeong, Ki Heon; Kim, Nack In

    2016-01-01

    Acute generalized exanthematous pustulosis (AGEP) is a rare disorder characterized by acute onset of erythematous and edematous eruptions with sterile pustules, accompanied by fever, and a self-limiting condition thought to be caused by drugs, in particular, antibiotics. Drug-related rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe adverse drug-induced reaction, characterized by a generalized skin rash associated with hypereosinophilia, lymphocytosis, and internal organ involvement. These reactions differ in causative agents, as well as clinical presentation, prognosis, and treatment. Therefore, appropriate diagnostic measures should be rapidly undertaken. Herein, we described a patient who developed overlapping features of hypersensitivity syndromes, AGEP and DRESS, with the use of piperacillin and the beta-lactamase inhibitor sodium tazobactam. Coexistence of AGEP and DRESS in the same patient is quite rare. To the best of our knowledge, there have been no previous reports on the coexistence of AGEP and DRESS associated with piperacillin/tazobactam. PMID:26848226

  9. Epidermal growth factor upregulates serotonin transporter and its association with visceral hypersensitivity in irritable bowel syndrome.

    PubMed

    Cui, Xiu-Fang; Zhou, Wei-Mei; Yang, Yan; Zhou, Jun; Li, Xue-Liang; Lin, Lin; Zhang, Hong-Jie

    2014-10-07

    To investigate the role of epidermal growth factor (EGF) in visceral hypersensitivity and its effect on the serotonin transporter (SERT). A rat model for visceral hypersensitivity was established by intra-colonic infusion of 0.5% acetic acid in 10-d-old Sprague-Dawley rats. The visceral sensitivity was assessed by observing the abdominal withdrawal reflex and recording electromyographic activity of the external oblique muscle in response to colorectal distension. An enzyme-linked immunosorbent assay was used to measure the EGF levels in plasma and colonic tissues. SERT mRNA expression was detected by real-time PCR while protein level was determined by Western blot. The correlation between EGF and SERT levels in colon tissues was analyzed by Pearson's correlation analysis. SERT function was examined by tritiated serotonin (5-HT) uptake experiments. Rat intestinal epithelial cells (IEC-6) were used to examine the EGF regulatory effect on SERT expression and function via the EGF receptor (EGFR). EGF levels were significantly lower in the rats with visceral hypersensitivity as measured in plasma (2.639 ± 0.107 ng/mL vs 4.066 ± 0.573 ng/mL, P < 0.01) and in colonic tissue (3.244 ± 0.135 ng/100 mg vs 3.582 ± 0.197 ng/100 mg colon tissue, P < 0.01) compared with controls. Moreover, the EGF levels were positively correlated with SERT levels (r = 0.820, P < 0.01). EGF displayed dose- and time-dependent increased SERT gene expressions in IEC-6 cells. An EGFR kinase inhibitor inhibited the effect of EGF on SERT gene upregulation. SERT activity was enhanced following treatment with EGF (592.908 ± 31.515 fmol/min per milligram vs 316.789 ± 85.652 fmol/min per milligram protein, P < 0.05) and blocked by the EGFR kinase inhibitor in IEC-6 cells (590.274 ± 25.954 fmol/min per milligram vs 367.834 ± 120.307 fmol/min per milligram protein, P < 0.05). A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT

  10. Dapsone 7.5% Gel: A Review in Acne Vulgaris.

    PubMed

    Al-Salama, Zaina T; Deeks, Emma D

    2017-02-01

    Dapsone 7.5% gel (Aczone(®)) is indicated for the once-daily topical treatment of acne vulgaris in patients aged ≥12 years. Dapsone is a sulfone antibacterial with anti-inflammatory actions, which are thought to be largely responsible for its efficacy in treating acne vulgaris. In two phase III trials of 12 weeks' duration in patients aged ≥12 years with moderate acne vulgaris, once-daily dapsone 7.5% gel reduced acne severity (as per the Global Acne Assessment Score) and lesion counts versus vehicle. The benefits of dapsone 7.5% gel over vehicle were seen as early as week 2 for inflammatory lesion counts, and from week 4 or 8 for other outcomes. Dapsone 7.5% gel was well tolerated, with a low incidence of treatment-related adverse events, with the majority of adverse events being administration-site related and mild or moderate in severity. Thus, dapsone 7.5% gel is an effective and well tolerated option for the topical treatment of acne vulgaris in patients aged ≥12 years, with the convenience of once-daily application.

  11. Designing dapsone polymer conjugates for controlled drug delivery.

    PubMed

    Rojo, Luis; Fernandez-Gutierrez, Mar; Deb, Sanjukta; Stevens, Molly M; San Roman, Julio

    2015-11-01

    Polymer-drug conjugates have significantly influenced polymer therapeutics over the last decade via controlled pharmacokinetics. Dapsone (4,4'-diamino diphenylsulphone) is not only widely used in the treatment of leprosy but forms an essential component in the treatment of autoimmune inflammatory diseases and malaria. However, its low bioavailability and non-specific distribution in the body leads to absorption throughout organs including skin, liver, and kidneys that can cause serious side effects. Thus, in this study we report the synthesis of polymer-drug conjugates of dapsone covalently bonded to macromolecular chains towards the development of new bioactive polymeric formulations with anti-inflammatory properties. Dapsone was functionalised with an acrylic moiety in which the acrylamide residue was directly bonded to one of the aromatic rings of dapsone. This functionalisation yielded an unsymmetrical dapsone methacrylamide (DapMA) structure, which on free radical polymerisation and co-polymerisation with HEMA yielded polymers of hydrocarbon macromolecules with pendant dapsone units. Thermal and size-exclusion chromatographic analysis revealed an increase in thermal stabilisation of the homopolymer (p(DapMA)) in comparison to the copolymer (p(Dap-co-HEMA)) with relatively high average molecular weight. The polymer conjugates exhibited high stability with low dapsone release from the polymeric backbone due to hydrolysis. However, a significant anti-inflammatory activity in a nitric oxide inhibition assay confirmed that this property was the consequence of only the macromolecular composition and not related to the release of low molecular weight compounds. Thus, the conjugation of dapsone to macromolecular systems provides a synthetic route to incorporate this drug into polymeric systems, facilitating their development into new anti-inflammatory therapies. The dapsone-conjugated methacrylic monomer and polymer derivatives with anti-inflammatory properties

  12. Clinical Diagnosis of the Dampness and Mold Hypersensitivity Syndrome: Review of the Literature and Suggested Diagnostic Criteria

    PubMed Central

    Valtonen, Ville

    2017-01-01

    A great variety of non-specific symptoms may occur in patients living or working in moisture-damaged buildings. In the beginning, these symptoms are usually reversible, mild, and present irritation of mucosa and increased morbidity due to respiratory tract infections and asthma-like symptoms. Later, the disease may become chronic and a patient is referred to a doctor where the assessment of dampness and mold hypersensitivity syndrome (DMHS) often presents diagnostic challenges. Currently, unanimously accepted laboratory tests are not yet available. Therefore, the diagnosis of DMHS is clinical and is based on the patient’s history and careful examination. In this publication, I reviewed contemporary knowledge on clinical presentations, laboratory methods, and clinical assessment of DMHS. From the literature, I have not found any proposed diagnostic clinical criteria. Therefore, I propose five clinical criteria to diagnose DMHS: (1) the history of mold exposure in water-damaged buildings, (2) increased morbidity to due infections, (3) sick building syndrome, (4) multiple chemical sensitivity, and (5) enhanced scent sensitivity. If all the five criteria are met, the patient has a very probable DMHS. To resolve the current problems in assigning correct DMHS diagnosis, we also need novel assays to estimate potential risks of developing DMHS. PMID:28848553

  13. Histamine Receptor H1-Mediated Sensitization of TRPV1 Mediates Visceral Hypersensitivity and Symptoms in Patients With Irritable Bowel Syndrome.

    PubMed

    Wouters, Mira M; Balemans, Dafne; Van Wanrooy, Sander; Dooley, James; Cibert-Goton, Vincent; Alpizar, Yeranddy A; Valdez-Morales, Eduardo E; Nasser, Yasmin; Van Veldhoven, Paul P; Vanbrabant, Winde; Van der Merwe, Schalk; Mols, Raf; Ghesquière, Bart; Cirillo, Carla; Kortekaas, Inge; Carmeliet, Peter; Peetermans, Willy E; Vermeire, Séverine; Rutgeerts, Paul; Augustijns, Patrick; Hellings, Peter W; Belmans, Ann; Vanner, Stephen; Bulmer, David C; Talavera, Karel; Vanden Berghe, Pieter; Liston, Adrian; Boeckxstaens, Guy E

    2016-04-01

    Histamine sensitizes the nociceptor transient reporter potential channel V1 (TRPV1) and has been shown to contribute to visceral hypersensitivity in animals. We investigated the role of TRPV1 in irritable bowel syndrome (IBS) and evaluated if an antagonist of histamine receptor H1 (HRH1) could reduce symptoms of patients in a randomized placebo-controlled trial. By using live calcium imaging, we compared activation of submucosal neurons by the TRPV1 agonist capsaicin in rectal biopsy specimens collected from 9 patients with IBS (ROME 3 criteria) and 15 healthy subjects. The sensitization of TRPV1 by histamine, its metabolite imidazole acetaldehyde, and supernatants from biopsy specimens was assessed by calcium imaging of mouse dorsal root ganglion neurons. We then performed a double-blind trial of patients with IBS (mean age, 31 y; range, 18-65 y; 34 female). After a 2-week run-in period, subjects were assigned randomly to groups given either the HRH1 antagonist ebastine (20 mg/day; n = 28) or placebo (n = 27) for 12 weeks. Rectal biopsy specimens were collected, barostat studies were performed, and symptoms were assessed (using the validated gastrointestinal symptom rating scale) before and after the 12-week period. Patients were followed up for an additional 2 weeks. Abdominal pain, symptom relief, and health-related quality of life were assessed on a weekly basis. The primary end point of the study was the effect of ebastine on the symptom score evoked by rectal distension. TRPV1 responses of submucosal neurons from patients with IBS were potentiated compared with those of healthy volunteers. Moreover, TRPV1 responses of submucosal neurons from healthy volunteers could be potentiated by their pre-incubation with histamine; this effect was blocked by the HRH1 antagonist pyrilamine. Supernatants from rectal biopsy specimens from patients with IBS, but not from the healthy volunteers, sensitized TRPV1 in mouse nociceptive dorsal root ganglion neurons via HRH1

  14. Ice water testing reveals hypersensitivity in adult rats that experienced neonatal bladder inflammation: implications for painful bladder syndrome/interstitial cystitis.

    PubMed

    Randich, Alan; Mebane, Hannah; Ness, Timothy J

    2009-07-01

    We determined whether clinical observations of hypersensitivity to ice water testing, that is infusion of ice-cold saline into the bladder, in patients with painful bladder syndrome/interstitial cystitis have a parallel in a rat model of bladder hypersensitivity produced by neonatal inflammation. Rat pups were anesthetized as neonates (postnatal days 14 to 16). In some pups the bladder was inflamed by intravesical zymosan treatment. As adults, the rats were re-anesthetized and tested for abdominal muscle contractions to ice water testing, measured on electromyogram. Various neonatally treated groups of rats underwent bladder re-inflammation/no re-inflammation and/or bladder distention before ice water testing. Other control rats were treated only in adulthood. Rats that underwent bladder inflammation as neonates manifested bladder hypersensitivity in adulthood, as indexed by significantly greater mean electromyogram responses during ice water testing. This bladder hypersensitivity did not require adult re-inflammation to manifest. Hypersensitivity was also observed with or without prior bladder distention, although the magnitude of electromyogram responses during ice water testing significantly correlated with the magnitude of electromyogram responses to bladder distention. Neonatally induced effects were not significantly related to estrous cycle phase. Exposure to menthol did not significantly enhance the overall magnitude of the electromyogram response to ice water testing in neonatally treated rats. Current results parallel those in a recent study showing that most patients with painful bladder syndrome/interstitial cystitis experience pain when undergoing ice water testing after previous urodynamic testing. These findings suggest that this animal model may be useful for understanding the etiology of and treatment for painful bladder syndrome/interstitial cystitis.

  15. Laryngeal hypersensitivity in chronic cough.

    PubMed

    Hull, J H; Menon, A

    2015-12-01

    Patients with chronic cough often report symptoms arising in the throat, in response to non-specific stimuli. Accordingly, the concept of a 'hypersensitivity' of the larynx in chronic cough has evolved over the past ten years. Patients with cough and laryngeal hypersensitivity frequently report features that overlap other laryngeal dysfunction syndromes, including a tendency for the vocal cords to inappropriately adduct. The mechanisms underlying laryngeal hypersensitivity in chronic cough are currently unclear, however recent studies provide new clinical and physiological techniques to aid detection and monitoring of laryngeal hypersensitivity. This review provides an overview of the current state of knowledge in this field. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Drug hypersensitivity.

    PubMed

    Yawalkar, N

    2009-01-01

    Drug hypersensitivity represents an immune-mediated reaction to a drug. Although several drug hypersensitivity reactions are confined to the skin and rather mild, some may be life threatening and also involve further organs such as liver, kidney and bone marrow. The exact pathogenesis of many drug hypersensitivity reactions is still obscure. In this review the concepts on how small molecular drugs can activate the immune system are discussed and the hapten, prohapten and p-i concept are explained. Furthermore, the classification of drug hypersensitivity reactions and some common and severe clinical manifestations of drug-induced T cell mediated reactions are presented.

  17. Unilateral rhinorrhea after translabyrinthine surgery due to parasympathetic hypersensitive syndrome: differentiation from cerebrospinal fluid leakage.

    PubMed

    Huy, Patrice Tran Ba; Sauvaget, Elisabeth

    2010-09-01

    Unilateral rhinorrhea after translabyrinthine surgery for vestibular or facial schwannoma usually suggests cerebrospinal fluid (CSF) leakage and requires specific measures, including revision surgery. To draw attention to the possibility of postoperative unilateral rhinorrhea with concomitant hyperlacrimation and hypersialorrhea without a CSF origin and reflecting more a neuroplastic phenomenon. Retrospective study in a tertiary care center university clinic. For 1 case of intratemporal facial schwannoma and 2 cases of vestibular schwannoma, surgery was by a translabyrinthine approach with sacrifice of the facial nerve and hypoglossofacial anastomosis in the first case. Postoperative unilateral hydrorhinorrhea associated with various degrees of lacrimation and/or salivary hypersecretion occurred mainly during exercise or under stressful situations. With unilateral rhinorrhea after translabyrinthine surgery for vestibular or facial schwannoma, concomitant symptoms such as lacrimation or hypersialorrhea may not be explained by CSF leakage through the eustachian tube. Misinterpretation may lead to detrimental revision surgery. The pathophysiogenetic mechanism suggests a neuroplastic phenomenon involving a denervation hypersensitivity reaction of the autonomous system. A simple diagnostic test with a nasal anticholinergic agent may be beneficial.

  18. Linear IgA/IgG bullous dermatosis: successful treatment with dapsone and mycophenolate mofetil.

    PubMed

    Passos, Leny; Rabelo, Renata Fernandes; Matsuo, Christiane; Santos, Mônica; Talhari, Sinesio; Talhari, Carolina

    2011-01-01

    A 21-year-old female presenting linear IgA and IgG disease initially responded well to dapsone therapy. However, the treatment with dapsone was withdrawn due to severe anemia induced by malaria, which led to worsening of the clinical picture. Although prednisone and methylprednisolone were tried, the patient responded only to the association of dapsone and mycophenolate mofetil.

  19. Drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome: clinical features of 27 patients.

    PubMed

    Avancini, J; Maragno, L; Santi, C G; Criado, P R

    2015-12-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) [also called drug-induced hypersensitivity syndrome (DIHS)] includes severe reactions to drugs that need to be promptly recognized by physicians. To explore heterogeneity in the clinical presentation of DRESS/DIHS at a large academic hospital in Latin America, using the criteria defined by the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system. A retrospective medical record review of 60 patients with diagnostic suspicion of DRESS/DIHS admitted to our hospital between July 2008 and April 2012 was performed, including demographic data, clinical features, laboratory findings and treatment. Of the 60 patients, 27 fulfilled the criteria for DRESS/DIHS. Maculopapular exanthema (85.1%), fever (96.2%) and hepatic involvement (85.1%) were the most common features. Anticonvulsants were the most common causal drugs (77.7%); Phenytoin was the most common individual drug (44.4%), followed by carbamazepine (29.6%). All patients were treated initially with prednisone 1 mg/kg/day. Mortality rate was 4%. The major findings of this study (to our knowledge the largest collection of data on DRESS/DIHS in Latin America) include a positive statistical association between presence of atypical lymphocytes and higher levels of alanine aminotransferase (P < 0.001) and reinforce the importance of anticonvulsants in the pathogenesis of this severe reaction. © 2015 British Association of Dermatologists.

  20. Management of Periocular Granuloma Annulare Using Topical Dapsone

    PubMed Central

    Patel, Mayha; Shitabata, Paul; Horowitz, David

    2015-01-01

    Granuloma annulare is a disease characterized by granulomatous inflammation of the dermis. Localized granuloma annulare may resolve spontaneously, while generalized granuloma annulare may persist for decades. The authors present the case of a 41-year-old Hispanic man with a two-week history of periocular granuloma annulare. Due to previously reported success in the use of systemic dapsone for the treatment of granuloma annulare, and the periocular proximity of the patient’s lesion, topical dapsone was used for treatment. Various additional therapies for the management of granuloma annulare have been reported, such as topical and systemic steroids, isotretinoin, pentoxifylline, cyclosporine, Interferon gamma, potassium iodide, nicotinamide, niacinamide, salicylic acid, fumaric acid ester, etanercept, infliximab, and hydroxychloroquine. Additional clinical trials are necessary to further evaluate the effectiveness of topical dapsone in the management of granuloma annulare. PMID:26203321

  1. Repeated electro-acupuncture attenuates chronic visceral hypersensitivity and spinal cord NMDA receptor phosphorylation in a rat irritable bowel syndrome model.

    PubMed

    Tian, Shun-Lian; Wang, Xiao-Yan; Ding, Guang-Hong

    2008-08-29

    Acupuncture has been used in clinical trials for the treatment of abdominal pain in patients with irritable bowel syndrome (IBS). However, scientific evidence is still lacking and the underlying mechanism remains largely unexplored. The aim of this study was to examine the effects of repeated administration of electro-acupuncture (EA) on chronic visceral hypersensitivity and on the phosphorylation of spinal cord N-methyl-D-aspartic acid (NMDA) receptors in a rat model of IBS. The results showed that repeated administration of EA at bilateral points of Zu-san-li (ST-36) and Shang-ju-xu (ST-37) significantly attenuated chronic visceral hypersensitivity induced in young adult rats by neonatal colon irritation. Such an effect was not seen in either of the two controls: sham-EA at ST-36 and ST-37 without electrical stimulation and EA at control points (BL-62 and tail). Furthermore, rats with chronic visceral hypersensitivity exhibited high-level expression of phosphorylated NMDA receptor subunit 1 (pNR1) in the spinal cord (L4-L5 segments), which was markedly attenuated by EA treatment. In addition, EA at ST-36 and ST-37 neither altered the pain threshold of normal rats nor affected the expression of pNR1 in the lumbosacral spinal cord. Altogether, these data indicate that the EA-mediated attenuation of chronic visceral hypersensitivity is correlated with the down-regulation of NMDA receptors phosphorylation at the spinal level.

  2. 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

  3. 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 . ...

  4. PDIA3 gene induces visceral hypersensitivity in rats with irritable bowel syndrome through the dendritic cell-mediated activation of T cells

    PubMed Central

    Zhuang, Zhaomeng; Zhang, Lu; Wang, Xiaoteng; Tao, Liyuan

    2016-01-01

    This study investigated the mechanism of protein disulfide-isomerase A3 (PDIA3)-induced visceral hypersensitivity in irritable bowel syndrome (IBS). Rats were treated with saline (control), acetic acid and restraint stress (IBS model), empty vector (RNAi control) and PDIA3-RNAi vector (PDIA3-RNAi). Mesenteric lymph node DCs (MLNDCs) and splenic CD4+/CD8+ T cells were isolated for co-cultivation. Compared with control, MLNDCs co-cultured with CD4+ or CD8+ T cells showed an increased ability to promote T cell proliferation and produced more IL-4 or IL-9 secretion. Compared with the RNAi control, MLNDCs from the PDIA3 knockdown models were less effective in promoting the proliferation of CD4+/CD8+ T cells. It is concluded that PDIA3 plays an important role in the development of IBS through the DC-mediated activation of T cells, resulting in degranulation of MCs and visceral hypersensitivity. PMID:27896022

  5. Ofuji's disease in an immunocompetent patient successfully treated with dapsone

    PubMed Central

    Anjaneyan, Gopikrishnan; Manne, Sindhura; Panicker, Vinitha Varghese; Eapen, Malini

    2016-01-01

    Eosinophilic pustular folliculitis or Ofuji's disease is a non-infectious eosinophilic infiltration of hair follicles, which usually presents with itchy papules and pustules in a circinate configuration. We report this case of an immunocompetent patient with erythematous papules and plaques without macropustules diagnosed as eosinophilic pustular folliculitis—a rarely reported entity outside Japan. He was successfully treated with oral dapsone. PMID:27730038

  6. Stevens-Johnson syndrome and toxic epidermal necrolysis due to anticonvulsants share certain clinical and laboratory features with drug-induced hypersensitivity syndrome, despite differences in cutaneous presentations.

    PubMed

    Teraki, Y; Shibuya, M; Izaki, S

    2010-10-01

    Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is characterized by late disease onset, fever, rash, hepatic dysfunction, haematological abnormalities, lymphadenopathy and often, human herpesvirus (HHV) reactivation. The diagnosis of DIHS is based on the combined presence of these findings. Anticonvulsants are a major cause of DIHS and may also cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We examined whether SJS/TEN due to anticonvulsants display similar clinical and laboratory features seen in DIHS. Patients diagnosed with SJS or TEN due to anticonvulsants (n = 8) were examined and their clinical features and laboratory findings were compared with patients with anticonvulsant-related DIHS (n = 6). Seven of the eight patients with SJS/TEN developed symptoms > 3 weeks after starting anticonvulsants. Hepatic dysfunction was present in six patients with SJS/TEN and five patients with DIHS. Leucocytosis and/or eosinophilia was noted in seven patients with SJS/TEN and four patients with DIHS. Only one patient in the SJS/TEN group had atypical lymphocytosis; this was present in four patients with DIHS. Reactivation of HHV-6 was detected in one of the four patients tested in the SJS/TEN group, although it was seen in five of the six patients with DIHS. TSJS/TEN due to anticonvulsants may exhibit some clinical and laboratory features of DIHS. The nature of the cutaneous involvement should be emphasized in the diagnosis of DIHS. © 2009 The Author(s). Journal compilation © 2009 British Association of Dermatologists.

  7. Pharmacokinetic difference of berberine between normal and chronic visceral hypersensitivity irritable bowel syndrome rats and its mechanism.

    PubMed

    Gong, Zipeng; Chen, Ying; Zhang, Ruijie; Yang, Qing; Wang, Yajie; Guo, Yan; Zhou, Bingbing; Weng, Xiaogang; Liu, Xuchen; Li, Yujie; Zhu, Xiaoxin; Dong, Yu

    2015-10-01

    Berberine is one of active alkaloids from Rhizoma coptidis in traditional Chinese medicine. The pharmacokinetics of berberine in rat plasma were compared between normal and chronic visceral hypersensitivity irritable bowel syndrome rats (CVH-IBS) established by mechanical colon irritation using angioplasty balloons for 2 weeks after oral administration of berberine hydrochloride (25 mg/kg) with the equivalent dose of 22 mg/kg for berberine according to body weight. Immunohistochemical analysis of c-fos and myosin light chain kinase (MLCK) and immunofluorescence analysis of MLCK in rat colon were conducted. Quantification of berberine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. The great different pharmacokinetic behavior of berberine was observed between normal and CVH-IBS model rats. Compared with normal group, T1/2 and AUC(0-t) of berberine in the model group were significantly increased, respectively (573.21 ± 127.53 vs 948.22 ± 388.57 min; 8,657.19 ± 1,562.54 vs 11,415.12 ± 1,670.72 min.ng/ml). Cl/F of berberine in the model group significantly decreased, respectively (13.89 ± 1.69 vs 9.19 ± 2.91 L/h/kg). Additionally, the expressions of c-fos and MLCK in model group were higher than those in normal group. The pharmacokinetic behavior of berberine was significantly altered in CVH-IBS pathological conditions, which indicated the dosage modification of berberine hydrochloride in CVH-IBS were necessary. Especially, improved exposure to berberine in rat plasma in CVH-IBS model rats was attributed to increased the expression of MLCK.

  8. Minocycline-induced hypersensitivity syndrome presenting with meningitis and brain edema: a case report

    PubMed Central

    Lefebvre, Nicolas; Forestier, Emmanuel; Farhi, David; Mahsa, Mohseni Zadeh; Remy, Véronique; Lesens, Olivier; Christmann, Daniel; Hansmann, Yves

    2007-01-01

    Background Hypersentivity Syndrome (HS) may be a life-threatening condition. It frequently presents with fever, rash, eosinophilia and systemic manifestations. Mortality can be as high as 10% and is primarily due to hepatic failure. We describe what we believe to be the first case of minocycline-induced HS with accompanying lymphocytic meningitis and cerebral edema reported in the literature. Case presentation A 31-year-old HIV-positive female of African origin presented with acute fever, lymphocytic meningitis, brain edema, rash, eosinophilia, and cytolytic hepatitis. She had been started on minocycline for inflammatory acne 21 days prior to the onset of symptoms. HS was diagnosed clinically and after exclusion of infectious causes. Minocycline was withdrawn and steroids were administered from the second day after presentation because of the severity of the symptoms. All signs resolved by the seventh day and steroids were tailed off over a period of 8 months. Conclusion Clinicians should maintain a high index of suspicion for serious adverse reactions to minocycline including lymphocytic meningitis and cerebral edema among HIV-positive patients, especially if they are of African origin. Safer alternatives should be considered for treatment of acne vulgaris. Early recognition of the symptoms and prompt withdrawal of the drug are important to improve the outcome. PMID:17511865

  9. Cicatrizing Conjunctivitis in a Patient Diagnosed With Drug Reaction With Eosinophilia and Systemic Symptoms/Drug-Induced Hypersensitivity Syndrome but With Features of Stevens-Johnson Syndrome.

    PubMed

    Bohm, Kelley J; Ciralsky, Jessica B; Harp, Joanna L; Bajaj, Shirin; Sippel, Kimberly C

    2016-06-01

    Severe cutaneous adverse reactions to drugs (SCARs) such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS) serve as one of the main reasons for inpatient ophthalmic consultation. Although it is well-recognized that SJS/TEN is associated with severe ocular mucosal inflammation and cicatrizing, potentially blinding, sequelae, this association has not been described in relation to other SCARs. We present a patient fulfilling the diagnostic criteria for probable DRESS/DIHS but not for SJS/TEN, yet exhibiting the severe ocular surface involvement characteristic of SJS/TEN. Case report. A 64-year-old man presented with bilateral pseudomembranous conjunctivitis and conjunctival denudation (sloughing) in the setting of a maculopapular rash, fever, liver dysfunction, and hematologic abnormalities 1 month after initiating several medications. A skin biopsy was not consistent with SJS/TEN. The patient was diagnosed with probable DRESS/DIHS and treated with high-dose systemic corticosteroids. The ocular surface inflammation was addressed with intensive topical corticosteroid ointment. The pseudomembranes resolved over a 6-week period, but the patient exhibited residual conjunctival scarring of all palpebral surfaces. The development of severe ocular surface mucosal inflammation and denudation with cicatrizing sequelae in a patient carrying a diagnosis of DRESS/DIHS has diagnostic and therapeutic implications for the ophthalmologist. Careful ophthalmic assessment is indicated in any SCAR patient with ophthalmic symptoms, regardless of formal diagnosis. Furthermore, the early therapeutic interventions recently recommended in SJS/TEN to limit the ophthalmic cicatricial sequelae, such as systemic or topical corticosteroids, may be indicated.

  10. Role of T Cells and Gamma Interferon during Induction of Hypersensitivity to Lipopolysaccharide by Toxic Shock Syndrome Toxin 1 in Mice

    PubMed Central

    Dinges, Martin M.; Schlievert, Patrick M.

    2001-01-01

    The superantigenic function of toxic shock syndrome toxin 1 (TSST-1) is generally regarded as an important determinant of its lethal effects in humans or experimental animals. This study examined the role of superantigenicity in a BALB/c mouse model of lethal TSST-1-induced hypersensitivity to lipopolysaccharide (LPS). In this model, TSST-1 greatly potentiated both LPS-induced lethality, as well as LPS-induced serum tumor necrosis factor alpha (TNF-α) activity. Although BALB/c-SCID mice were resistant to these LPS enhancement effects of TSST-1, BALB/c-SCID mice reconstituted with T cells were completely susceptible to the enhancement effect of TSST-1 on LPS-induced serum TNF-α. Mice pretreated with cyclosporine (Cs) or neutralizing antibodies against gamma interferon (IFN-γ) did not develop lethal LPS hypersensitivity when injected with TSST-1, and these agents reduced the enhancement effect of TSST-1 on LPS-induced serum TNF-α by 99 and 85%, respectively. Cs pretreatment also completely inhibited the known capacity of TSST-1 to amplify LPS-induced levels of IFN-γ in serum. In contrast, mice given Cs after a priming injection of TSST-1, but before LPS, still exhibited lethal hypersensitivity to LPS. Cs given after TSST-1 also did not inhibit enhancement of LPS-induced serum TNF-α by TSST-1 but inhibited the enhancement effect of TSST-1 on LPS-induced serum IFN-γ by 50%. These experiments support the theory that TSST-1-induced hypersensitivity to LPS is mediated primarily by IFN-γ derived from superantigen-activated T cells. PMID:11179286

  11. Hypersensitivity Pneumonitis.

    PubMed

    Wysong, Kristi; Phillips, Jennan A; Hammond, Stephanie

    2016-06-01

    Chronic exposure to a broad array of antigens after workers inhale aerosolized organic dust particles from mold, animal dander, bird droppings, and chemicals, especially pesticides or herbicides, increases risk for hypersensitivity pneumonitis. Several demographic characteristics of immigrant workers in farming, poultry processing, construction, and landscaping increase this worker population's risk. © 2016 The Author(s).

  12. Colon Hypersensitivity to Distension, Rather Than Excessive Gas Production, Produces Carbohydrate-Related Symptoms in Individuals With Irritable Bowel Syndrome.

    PubMed

    Major, Giles; Pritchard, Sue; Murray, Kathryn; Alappadan, Jan Paul; Hoad, Caroline L; Marciani, Luca; Gowland, Penny; Spiller, Robin

    2017-01-01

    Poorly digested, fermentable carbohydrates may induce symptoms of irritable bowel syndrome (IBS) via unclear mechanisms. We performed a randomized trial with magnetic resonance imaging (MRI) analysis to investigate correlations between symptoms and changes in small- and large-bowel contents after oral challenge. We performed a 3-period, cross-over study of 29 adult patients with IBS (based on Rome III criteria, with symptoms of abdominal pain or discomfort for at least 2 days/wk) and reported bloating. In parallel, we performed the same study of 29 healthy individuals (controls). Studies were performed in the United Kingdom from January 2013 through February 2015. On 3 separate occasions (at least 7 days apart), subjects were given a 500-mL drink containing 40 g of carbohydrate (glucose in the first period, fructose in the second, and inulin in the third, in a random order). Levels of breath hydrogen were measured and intestinal content was assessed by MRI before and at various time points after consumption of each drink. Symptoms were determined based on subjects' responses to the Hospital Anxiety and Depression Scale questionnaire and the Patient Health Questionnaire-15. The primary end point was whether participants had a clinically important symptom response during the 300 minutes after consumption of the drink. More patients with IBS reached the predefined symptom threshold after intake of inulin (13 of 29) or fructose (11 of 29) than glucose (6 of 29). Symptoms peaked sooner after intake of fructose than inulin. Fructose increased small-bowel water content in both patients and controls whereas inulin increased colonic volume and gas in both. Fructose and inulin increased breath hydrogen levels in both groups, compared with glucose; fructose produced an earlier increase than inulin. Controls had lower symptom scores during the period after drink consumption than patients with IBS, despite similar MRI parameters and breath hydrogen responses. In patients who

  13. Adverse reactions associated with dapsone therapy in HIV-positive patients: a case presentation and review.

    PubMed

    Stroup, Jeffrey S; Stephens, Johnny R; Reust, Randall; Miller, J Angela

    2006-01-01

    Dapsone is commonly used for the prophylaxis of Pneumocystis jiroveci pneumonia in patients with a diagnosis of HIV infection who have allergies to sulfa-based drugs. Dapsone has several adverse effects in its profile that make it a potentially dangerous second-line agent. We report an adverse effect encountered in an HIV-positive patient receiving dapsone and review the common adverse effects encountered with this alternative treatment option.

  14. Raman and i.r. studies of the antileprotic drug Dapsone

    NASA Astrophysics Data System (ADS)

    D'Cunha, Romola; Kartha, V. B.; Gurnani, S.

    No information is available on the mode of action of Dapsone in leprosy treatment, the phenomena of drug resistance and toxicity. Information on the interaction of Dapsone with serum proteins can be obtained at the molecular level by spectroscopic investigations on structural changes of the system. As a first step in these investigations, the i.r. and laser Raman spectra of Dapsone and N-deutero Dapsone have been obtained. The characteristic vibrational frequencies of the NH 2 group, the SO 2 group and the aromatic ring have been identified and assigned from isotope shifts and studies in various solvents.

  15. [Dapsone efficacy in lupus miliaris disseminatus faciei: two cases].

    PubMed

    El Benaye, J; Oumakhir, S; Ghfir, M; Sedrati, O

    2011-01-01

    Lupus miliaris disseminatum faciei (LMDF) is a rare, chronic and benign facial dermatosis that is regarded as an enigmatic diagnostic and therapeutic entity with spontaneous regression in 2 to 4 years leaving pock-like scars. We present two cases of LMDF: the first concerns a 46-year-old woman who 6 months earlier presented a papular and pustular eruption on her face leaving small pitted scars. The inefficacy of treatment with cyclines, metronidazole and crotamiton as well as the clinical and histological examination results allowed a diagnosis of lupus miliaris disseminatus faciei to be made. The patient was placed on dapsone 100mg per day, which led to a remarkable improvement in the second week, but with depressed scars. The second case concerned an 18-year-old man who for 3 months had been presenting red-brown papules of the face that were resistant to cyclines and to topical retinoids and caused scarring. This clinical aspect, consolidated by the histological result, allowed the diagnosis of LMDF to be made. Administration of dapsone 100mg per day resulted in improvement from the first month, although there were residual cupuliform scars. Dapsone appears to be effective in the management of this disease, as illustrated in our two case reports. However, further studies are needed to confirm these results. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  16. Copper hypersensitivity.

    PubMed

    Fage, Simon W; Faurschou, Annesofie; Thyssen, Jacob P

    2014-10-01

    The world production of copper is steadily increasing. Although humans are widely exposed to copper-containing items on the skin and mucosa, allergic reactions to copper are only infrequently reported. To review the chemistry, biology and accessible data to clarify the implications of copper hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common. As a metal, it possesses many of the same qualities as nickel, which is a known strong sensitizer. Cumulative data on subjects with presumed related symptoms and/or suspected exposure showed that a weighted average of 3.8% had a positive patch test reaction to copper. We conclude that copper is a very weak sensitizer as compared with other metal compounds. However, in a few and selected cases, copper can result in clinically relevant allergic reactions.

  17. Drug hypersensitivity.

    PubMed

    Bircher, Andreas J

    2014-01-01

    Before the arrival of modern pharmacotherapy, drug hypersensitivity reactions were virtually unknown. Toxicity from the many plant-, animal- and inorganic material-derived remedies must have been much more common. One famous example is the intoxications from mercury, which has been used in many ailments, but particularly for the treatment of syphilis. It was only in the 19th century when more and more active principles from e.g. plants were identified, and when the observations of skin reactions became more prevalent. In 1877, Heinrich Köbner used for the first time the term 'drug exanthema' (Arznei-Exanthem). Since then, many different types of exanthemas from the mild macular-papular forms to the severe life-threatening bullous exanthemas such as toxic epidermal necrolysis have been observed from numerous drugs. The systematic investigation of severe drug reactions has only started in the second half of the 20th century, parallel to the increasing knowledge in immunology. Drug hypersensitivity reactions still remain one of the most challenging problems in allergology due to their manifold clinical manifestations and their very diverse pathophysiology. The introduction of new drugs and in turn the emergence of new hypersensitivity reactions will remain a challenge in the future. © 2014 S. Karger AG, Basel.

  18. Computational Modelling of Dapsone Interaction With Dihydropteroate Synthase in Mycobacterium leprae; Insights Into Molecular Basis of Dapsone Resistance in Leprosy.

    PubMed

    Chaitanya V, Sundeep; Das, Madhusmita; Bhat, Pritesh; Ebenezer, Mannam

    2015-10-01

    The molecular basis for determination of resistance to anti-leprosy drugs is the presence of point mutations within the genes of Mycobacterium leprae (M. leprae) that encode active drug targets. The downstream structural and functional implications of these point mutations on drug targets were scarcely studied. In this study, we utilized computational tools to develop native and mutant protein models for 5 point mutations at codon positions 53 and 55 in 6-hydroxymethyl-7, 8-dihydropteroate synthase (DHPS) of M. leprae, an active target for dapsone encoded by folp1 gene, that confer resistance to dapsone. Molecular docking was performed to identify variations in dapsone interaction with mutant DHPS in terms of hydrogen bonding, hydrophobic interactions, and energy changes. Schrodinger Suite 2014-3 was used to build homology models and in performing molecular docking. An increase in volume of the binding cavities of mutant structures was noted when compared to native form indicating a weakening in interaction (60.7 Å(3) in native vs. 233.6 Å(3) in Thr53Ala, 659.9 Å(3) in Thr53Ile, 400 Å(3) for Thr53Val, 385 Å(3) for Pro55Arg, and 210 Å(3) for Pro55Leu). This was also reflected by changes in hydrogen bonds and decrease in hydrophobic interactions in the mutant models. The total binding energy (ΔG) decreased significantly in mutant forms when compared to the native form (-51.92 Kcal/mol for native vs. -35.64, -35.24, -46.47, -47.69, and -41.36 Kcal/mol for mutations Thr53Ala, Thr53Ile, Thr53Val, Pro55Arg, and Pro55Leu, respectively. In brief, this analysis provided structural and mechanistic insights to the degree of dapsone resistance contributed by each of these DHPS mutants in leprosy.

  19. Is the drug-induced hypersensitivity syndrome (DIHS) due to human herpesvirus 6 infection or to allergy-mediated viral reactivation? Report of a case and literature review

    PubMed Central

    2010-01-01

    Background Drug-Induced Hypersensitivity Syndrome (DIHS) is a severe and rare systemic reaction triggered by a drug (usually an antiepileptic drug). We present a case of DISH and we review studies on the clinical features and treatment of DIHS, and on its pathogenesis in which two elements (Herpesvirus infection and the drug) interact with the immune system to trigger such a syndrome that can lead to death in about 20% of cases. Case presentation We report the case of a 26-year old woman with fever, systemic maculopapular rash, lymphadenopathy, hepatitis and eosinophilic leukocytosis. She had been treated with antibiotics that gave no benefit. She was taking escitalopram and lamotrigine for a bipolar disease 30 days before fever onset. Because the patient's general condition deteriorated, betamethasone and acyclovir were started. This treatment resulted in a mild improvement of symptoms. Steroids were rapidly tapered and this was followed with a relapse of fever and a worsening of laboratory parameters. Human herpesvirus 6 (HHV-6) DNA was positive as shown by PCR. Drug-Induced Hypersensitivity Syndrome (DIHS) was diagnosed. Symptoms regressed on prednisone (at a dose of 50 mg/die) that was tapered very slowly. The patient recovered completely. Conclusions The search for rare causes of fever led to complete resolution of a very difficult case. As DIHS is a rare disease the most relevant issue is to suspect and include it in differential diagnosis of fevers of unknown origin. Once diagnosed, the therapy is easy (steroidal administration) and often successful. However our case strongly confirms that attention should be paid on the steroidal tapering that should be very slow to avoid a relapse. PMID:20205923

  20. Is the drug-induced hypersensitivity syndrome (DIHS) due to human herpesvirus 6 infection or to allergy-mediated viral reactivation? Report of a case and literature review.

    PubMed

    Gentile, Ivan; Talamo, Maria; Borgia, Guglielmo

    2010-03-06

    Drug-Induced Hypersensitivity Syndrome (DIHS) is a severe and rare systemic reaction triggered by a drug (usually an antiepileptic drug). We present a case of DISH and we review studies on the clinical features and treatment of DIHS, and on its pathogenesis in which two elements (Herpesvirus infection and the drug) interact with the immune system to trigger such a syndrome that can lead to death in about 20% of cases. We report the case of a 26-year old woman with fever, systemic maculopapular rash, lymphadenopathy, hepatitis and eosinophilic leukocytosis. She had been treated with antibiotics that gave no benefit. She was taking escitalopram and lamotrigine for a bipolar disease 30 days before fever onset. Because the patient's general condition deteriorated, betamethasone and acyclovir were started. This treatment resulted in a mild improvement of symptoms. Steroids were rapidly tapered and this was followed with a relapse of fever and a worsening of laboratory parameters. Human herpesvirus 6 (HHV-6) DNA was positive as shown by PCR. Drug-Induced Hypersensitivity Syndrome (DIHS) was diagnosed. Symptoms regressed on prednisone (at a dose of 50 mg/die) that was tapered very slowly. The patient recovered completely. The search for rare causes of fever led to complete resolution of a very difficult case. As DIHS is a rare disease the most relevant issue is to suspect and include it in differential diagnosis of fevers of unknown origin. Once diagnosed, the therapy is easy (steroidal administration) and often successful. However our case strongly confirms that attention should be paid on the steroidal tapering that should be very slow to avoid a relapse.

  1. Multiple Drug Hypersensitivity

    PubMed Central

    Pichler, Werner J.; Srinoulprasert, Yuttana; Yun, James; Hausmann, Oliver

    2017-01-01

    Multiple drug hypersensitivity (MDH) is a syndrome that develops as a consequence of massive T-cell stimulations and is characterized by long-lasting drug hypersensitivity reactions (DHR) to different drugs. The initial symptoms are mostly severe exanthems or drug rash with eosinophilia and systemic symptoms (DRESS). Subsequent symptoms due to another drug often appear in the following weeks, overlapping with the first DHR, or months to years later after resolution of the initial presentation. The second DHR includes exanthema, erythroderma, DRESS, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hepatitis, and agranulocytosis. The eliciting drugs can be identified by positive skin or in vitro tests. The drugs involved in starting the MDH are the same as for DRESS, and they are usually given in rather high doses. Fixed drug combination therapies like sulfamethoxazole/trimethoprim or piperacillin/tazobactam are frequently involved in MDH, and 30–40% of patients with severe DHR to combination therapy show T-cell reactions to both components. The drug-induced T-cell stimulation appears to be due to the p-i mechanism. Importantly, a permanent T-cell activation characterized by PD-1+/CD38+ expression on CD4+/CD25low T cells can be found in the circulation of patients with MDH for many years. In conclusion, MDH is a drug-elicited syndrome characterized by a long-lasting hyperresponsiveness to multiple, structurally unrelated drugs with clinically diverse symptoms. PMID:28315874

  2. Hypersensitivity of skin fibroblasts from basal cell nevus syndrome patients to killing by ultraviolet B but not by ultraviolet C radiation

    SciTech Connect

    Applegate, L.A.; Goldberg, L.H.; Ley, R.D.; Ananthaswamy, H.N. )

    1990-02-01

    Basal cell nevus syndrome (BCNS) is an autosomal dominant genetic disorder in which the afflicted individuals are extremely susceptible to sunlight-induced skin cancers, particularly basal cell carcinomas. However, the cellular and molecular basis for BCNS is unknown. To ascertain whether there is any relationship between genetic predisposition to skin cancer and increased sensitivity of somatic cells from BCNS patients to killing by UV radiation, we exposed skin fibroblasts established from unexposed skin biopsies of several BCNS and age- and sex-matched normal individuals to either UV-B (280-320 nm) or UV-C (254 nm) radiation and determined their survival. The results indicated that skin fibroblasts from BCNS patients were hypersensitive to killing by UV-B but not UV-C radiation as compared to skin fibroblasts from normal individuals. DNA repair studies indicated that the increased sensitivity of BCNS skin fibroblasts to killing by UV-B radiation was not due to a defect in the excision repair of pyrimidine dimers. These results indicate that there is an association between hypersensitivity of somatic cells to killing by UV-B radiation and the genetic predisposition to skin cancer in BCNS patients. In addition, these results suggest that DNA lesions (and repair processes) other than the pyrimidine dimer are also involved in the pathogenesis of sunlight-induced skin cancers in BCNS patients. More important, the UV-B sensitivity assay described here may be used as a diagnostic tool to identify presymptomatic individuals with BCNS.

  3. Pharmacogenetics of hypersensitivity drug reactions.

    PubMed

    Negrini, Simone; Becquemont, Laurent

    2017-04-01

    Adverse drug reactions are a significant cause of morbidity and mortality and represent a major burden on the healthcare system. Some of those reactions are immunologically mediated (hypersensitivity reactions) and can be clinically subdivided into two categories: immediate reactions (IgE-related) and delayed reactions (T-cell-mediated). Delayed hypersensitivity reactions include both systemic syndromes and organ-specific toxicities and can be triggered by a wide range of chemically diverse drugs. Recent studies have demonstrated a strong genetic association between human leukocyte antigen alleles and susceptibility to delayed drug hypersensitivity. Most notable examples include human leukocyte antigen (HLA)-B*57:01 allele and abacavir hypersensitivity syndrome or HLA-B*15:02 and HLA-B*58:01 alleles related to severe cutaneous reactions induced by carbamazepine and allopurinol, respectively. This review aims to explore our current understanding in the field of pharmacogenomics of HLA-associated drug hypersensitivities and its translation into clinical practice for predicting adverse drug reactions. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  4. Drug hypersensitivity in Phramongkutklao Hospital.

    PubMed

    Sangasapasviliya, Atik; Prakongwong, Tharatip; Ayuthaya, Pinyapat Kanechorn Na; Ayuthaya, Rajyani Kanechaun Na

    2010-11-01

    To evaluate the prevalence of drug hypersensitivity, clinical manifestations, type of drugs involved, severity, and patients demographic data. A cross-sectional descriptive study. The study was performed from January 1st, 2008 to December 31th, 2008 at Phramongkutklao Hospital. Data were collected from Pharmaceutical Department, Dermatology Unit, Department of Medicine including adverse events reported by pharmacists. All records of in-patients and out-patients including gender, age, causative drugs, type of drug hypersensitivity and severity of hypersensitivity were collected. A total of 140 patients who had drug hypersensitivity were recorded. The most common drug hypersensitivity was due to antimicrobial agents which penicillin group was the most frequently involved. Of 61 patients (43.57%), 27 (19.28%) received anti-inflammatory and muscle relaxant drugs and 18 (12.85%) had drugs acting on the central nervous system. The most common manifestration of drug allergy was maculopapular rash (34.99%), followed by nonspecific erythrematous rash (16.42%), fixed drug eruption (9.28%) and Stevens-Johnson syndrome (8.57%), respectively. Majority (80.71%) of drug hypersensitivity was mild in severity. Moderate, severe and lethal hypersensitivity accounted for 8.51%, 10.0%, 0.71% respectively. Female were 51.77% while 48.22% were male. The mean age was 47.0 years (ranged from 8-100 years). There were 57 (40.71%) patients over 50 years of age and 103 (73.57%) patients had taken more than one medication. Antimicrobial agents were the common cause while maculopapular rash was the most frequent clinical manifestation of drug hypersensitivity.

  5. Pustular-type drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to carbamazepine with systemic muscle involvement.

    PubMed

    Matsuda, Haruna; Saito, Kanami; Takayanagi, Yoshikazu; Okazaki, Toshio; Kashima, Kenji; Ishikawa, Kazushi; Kai, Yoshitaka; Takeo, Naoko; Hatano, Yutaka; Okamoto, Osamu; Fujiwara, Sakuhei

    2013-02-01

    Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe reaction usually associated with maculopapular eruptions and systemic involvement. Here we report the first case, to our knowledge, of DIHS/DRESS due to carbamazepine with acute generalized pustular bacterid-like (AGPB-like) eruptions and skeletal muscle involvement. Reviewing our case and the published work, we discuss pustular-type DIHS/DRESS which, in most cases, involves acute generalized exanthematous pustulosis (AGEP)-like skin eruptions in response to carbamazepine. Pustular eruptions may appear in relatively few cases of DIHS/DRESS, in particular, when the causative drug is carbamazepine and, even in cases of intractable pustular bacterid-like eruptions, a reaction to a drug should be suspected. Skeletal muscle involvement may be associated with DIHS/DRESS as one of its systemic manifestations. © 2012 Japanese Dermatological Association.

  6. Drug induced hypersensitivity syndrome by triple therapy of peginterferon alpha2b, ribavirin and telaprevir in patient with double positive for HBV and HCV.

    PubMed

    Takagi, Hitoshi; Hoshino, Takashi; Naganuma, Atsushi; Koitabashi, Eri; Uehara, Sanae; Sakamoto, Naomi; Kudo, Tomohiro; Ryusaki, Keiichirou; Kakizaki, Satoru; Okamoto, Hiroaki

    2013-10-01

    Sixty year-old male positive for both HCV-RNA and HBsAg was treated by triple therapy of peginterferon alpha2b, ribavirin and telaprevir. Eight weeks after the beginning of the therapy, the patient developed drug induced hypersensitivity syndrome (DIHS) with general erythema multiforme and 64 times anti-HHV6 antibody elevation. Sixty milligram of prednisolone was administered with gradual dose reduction and the skin lesion was improved. HBV-DNA and transaminase elevated one week after the steroid induction and entecavir improved them. DIHS itself and the aggravation of hepatitis B by corticosteroid should be kept in mind in cases with dual infection of HBV and HCV treated by antivirals including telaprevir.

  7. Inhibition of dapsone-induced methaemoglobinaemia by cimetidine in the presence of trimethoprim in the rat.

    PubMed

    Coleman, M D; Russell, R M; Tingle, M D; Park, B K

    1992-02-01

    Administration of dapsone in combination with trimethoprim and cimetidine to male rats resulted in a marked decrease (P less than 0.05) in measured methaemoglobin levels (46.2 +/- 24% Met Hb h) compared with administration of dapsone alone (124.5 +/- 24.4% Met Hb h). The elimination half-life of dapsone (814 +/- 351 min) was more than doubled in the presence of trimethoprim and cimetidine compared with control (355 +/- 160 min, P less than 0.05). However, there were no significant differences in AUC and clearance when dapsone was administered in combination with trimethoprim and cimetidine compared with dapsone alone. Co-administration of trimethoprim with dapsone in the absence of cimetidine did not affect either methaemoglobin formation, AUCs, half-lives, or clearance values of dapsone compared with control. There was a threefold increase in the AUC of trimethoprim (6296 +/- 2249 micrograms min mL-1) in the presence of dapsone compared with trimethoprim alone (2122 +/- 552 micrograms min mL-1). There was also a corresponding decrease in the clearance of trimethoprim in the presence of dapsone compared with control (19.1 +/- 6.9 vs 60.8 +/- 21.0 mL min-1). However, there was no change in the elimination half-life of trimethoprim between the two experimental groups (273 +/- 120 vs 292 +/- 54 min). The AUC of trimethoprim increased more than threefold in the presence of cimetidine (7100 +/- 1501 micrograms min mL-1) compared with trimethoprim alone (2122 +/- 552 micrograms min mL-1).(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Use of Dapsone 5% Gel as Maintenance Treatment of Acne Vulgaris Following Completion of Oral Doxycycline and Dapsone 5% Gel Combination Treatment.

    PubMed

    Kircik, Leon H

    2016-02-01

    Acne vulgaris is a common, chronic skin disease that requires long-term therapy. Oral antibiotics are a mainstay of treatment, but extended use is associated with the development of bacterial resistance. Topical therapies are often combined with oral antibiotics to achieve an initial improvement, after which the oral agents may be discontinued and the topical therapy used as maintenance. To assess the safety and efficacy of combination therapy with dapsone 5% gel with oral doxycycline hyclate 100mg, followed by monotherapy with dapsone 5% gel in improving and maintaining response in patients with moderate to severe acne. In this open-label study, all patients applied dapsone 5% gel twice daily along with doxycycline hyclate 100mg once daily for 12 weeks. Subjects who achieved a qualifying improvement at week 12 continued to the second phase of the study in which they applied only dapsone 5% gel twice daily for maintenance therapy of 12 more weeks. Subjects were evaluated for safety and efficacy at weeks 4, 8, 12, 16, 20, and 24. All subjects (n=30) in the initial phase qualified to enter the maintenance phase. 82% of participants maintained their treatment response (Investigator's Global Assessment score) at week 24. The regimen was safe and well tolerated. The combination oral doxycycline hyclate 100 mg with topical dapsone 5% gel twice daily is an effective and well-tolerated regimen to treat moderate to severe acne vulgaris. After discontinuation of doxycycline, topical dapsone 5% gel is effective at maintaining a therapeutic response. These data suggest that topical dapsone 5% gel can be used effectively for long-term acne maintenance treatment without the risk of developing antibiotic resistance.

  9. Elevated expression of c-fos in central nervous system correlates with visceral hypersensitivity in irritable bowel syndrome (IBS): a new target for IBS treatment.

    PubMed

    Zhang, Ru; Zou, Ning; Li, Ji; Lv, Hong; Wei, Jing; Fang, Xiu-Cai; Qian, Jia-Ming

    2011-08-01

    Although visceral hypersensitivity is a major pathophysiological feature of irritable bowel syndrome (IBS), its molecular mechanisms are still poorly understood. c-fos is a well-established marker of cell activation. Accumulating evidence demonstrates that norepinephrine (NE) system is dysregulated in IBS; however, very little is known on its mechanism. It is our hypothesis that elevated expression of c-fos in central nervous system (CNS) correlates with visceral hypersensitivity in rat model of IBS. Furthermore, we explored the changes of NE system in IBS patients. The rat model of IBS was induced by heterotypic chronic and acute stress. Tissues obtained from rat model were analyzed for c-fos levels in CNS (frontal lobe, hippocampus, cornu dorsale) and colon by immunohistochemistry. Real-time reverse transcription polymerase chain reaction was used to detect tyrosine hydroxylase (TH) in the colonic tissues obtained from IBS patients. The rat model of IBS was associated with increased expression of c-fos in different parts of CNS (P = 0.001, P = 0.002, and P = 0.002, respectively), but normal in colon (P = 0.207). The clinical parameters (colonic motility and sensation) of rat model were significantly correlated with elevated c-fos in CNS (P < 0.05). Enterochromaffin cells and serotonin in colon were related to the elevated c-fos in CNS (P < 0.05). The TH messenger ribonucleic acid (mRNA level of IBS-D patients was almost four times as much as that of controls. Elevated expression of c-fos in CNS might be one of key mechanisms in etiology of IBS. Therefore, regulation of CNS activation could be a major targeting effect when treating IBS patients.

  10. Transmission of Dapsone-Resistant Leprosy Detected by Molecular Epidemiological Approaches▿

    PubMed Central

    Li, Wei; Sakamuri, Rama M.; Lyons, Danielle E.; Orcullo, Florenda M.; Shinde, Vidyagouri; Pena, Edred Lao Dela; Maghanoy, Armi A.; Mallari, Irene B.; Tan, Esterlina V.; Nath, Indira; Brennan, Patrick J.; Balagon, Marivic; Vissa, Varalakshmi

    2011-01-01

    Drug resistance surveillance identified six untreated leprosy patients in the Philippines with Mycobacterium leprae folP1 mutations which confer dapsone resistance. Five patients share a village of residence; four who carried the mutation, Thr53Val, were also linked by M. leprae variable-number tandem repeat (VNTR) strain types. In India, folP1 mutations were detected in two relapse patients with a history of dapsone treatment. Mutations were not found in the rifampin target gene rpoB. These findings indicate that dapsone resistance is being transmitted. PMID:21859943

  11. Safety and Pharmacokinetics of Once-Daily Dapsone Gel, 7.5% in Patients With Moderate Acne Vulgaris.

    PubMed

    Jarratt, Michael T; Jones, Terry M; Chang-Lin, Joan-En; Tong, Warren; Berk, David R; Lin, Vince; Kaoukhov, Alexandre

    2016-10-01

    Reducing the dosing frequency of topical acne treatments to once daily may improve adherence. Evaluate pharmacokinetics (PK), safety, and tolerability of 3 formulations of once-daily dapsone gel, 7.5% and of twice-daily dapsone gel, 5% over 28 days in patients with moderate acne vulgaris. This phase 1, multicenter, parallel-group study randomized males and females aged 16 to 35 years to 1 of 3 dapsone gel, 7.5% formulations (DAP-11078, DAP-11079, or DAP-11080 double-blind; applied once daily) or to dapsone gel, 5% (investigator-blinded only, applied twice-daily). Blood samples were collected for PK assessments of dapsone and its metabolites, N-acetyl dapsone (NAD) and dapsone hydroxylamine (DHA), before the morning dose on days 1, 7, 14, 18, 21, 26, 27, and 28, and at several follow-up time points (days 29-32). Safety profile assessments included adverse events (AEs), physical examinations, laboratory tests, and local tolerability assessments. Steady-state dapsone, NAD, and DHA concentrations were reached within 7 days of the first dose in all treatment groups. Daily systemic exposures of the 3 dapsone gel, 7.5% formulations were approximately 25% to 40% lower than that for dapsone gel, 5%, and these differences were statistically significant. Among the 3 dapsone gel, 7.5% formulations, the highest daily exposure of dapsone (per the AUC) was observed with DAP-11080, with respective Cmax and AUC0-24 being approximately 28.6% and 28.7% lower relative to dapsone gel, 5%. Most AEs were mild to moderate in intensity. The safety profiles for all 3 formulations of once-daily dapsone, 7.5% gel and twice-daily dapsone gel, 5% were similar following 28 days of topical administration. All 4 dapsone formulations were well tolerated. This study demonstrated lower systemic exposure with all 3 once-daily dapsone gel, 7.5% formulations than with twice-daily dapsone gel, 5%. All 4 formulations were well tolerated and demonstrated similar safety profiles.

    J Drugs

  12. Transient generalized glucocorticoid hypersensitivity.

    PubMed

    Nicolaides, Nicolas C; Lamprokostopoulou, Agaristi; Polyzos, Alexandros; Kino, Tomoshige; Katsantoni, Eleni; Triantafyllou, Panagiota; Christophoridis, Athanasios; Katzos, George; Dracopoulou, Maria; Sertedaki, Amalia; Chrousos, George P; Charmandari, Evangelia

    2015-12-01

    Transient generalized glucocorticoid hypersensitivity is a rare disorder characterized by increased tissue sensitivity to glucocorticoids and compensatory hypo-activation of the hypothalamic-pituitary-adrenal axis. The condition itself and the underlying molecular mechanisms have not been elucidated. To present the clinical manifestations, endocrinologic evaluation and transcriptomic profile in a patient with transient generalized glucocorticoid hypersensitivity. A 9-year-old girl presented with an 8-month history of clinical manifestations suggestive of Cushing syndrome. Endocrinologic evaluation revealed undetectable 08:00 h ACTH (<1 pg/mL) and cortisol (0·025 μg/dL) concentrations, which remained decreased throughout the 24-h period and did not respond to stimulation with ovine CRH. The disease gradually resolved spontaneously over the ensuing 3 months. Sequencing of the human glucocorticoid receptor gene revealed no mutations or polymorphisms. Western blot analysis in peripheral blood mononuclear cells revealed equal protein expression of hGRα of the patient in the disease and postresolution phases compared with a control subject. Transcriptomic analysis in peripheral blood mononuclear cells in the disease and postresolution phases identified 903 differentially expressed genes. Of these, 106 genes were up-regulated and 797 were down-regulated in the disease compared with the resolution phase. Bioinformatics analysis on the differentially expressed gene networks revealed Nuclear Factor-κB as the predominant transcription factor influencing the expression of the majority of differentially expressed genes. Our findings indicate that a transient postreceptor defect, or a virus- or bacterium-encoded molecule, may have enhanced glucocorticoid signal transduction, leading to transient generalized glucocorticoid hypersensitivity and hypo-activation of the HPA axis. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

  13. Brown recluse spider bites. A comparison of early surgical excision versus dapsone and delayed surgical excision.

    PubMed Central

    Rees, R S; Altenbern, D P; Lynch, J B; King, L E

    1985-01-01

    In a prospective study, 31 patients with brown recluse spider bites were treated by either immediate surgical excision or with the leukocyte inhibitor, dapsone, followed by delayed surgical excision. Patients were matched for age, gender, and lesion size and were excluded if the typical history and physical findings were not present. In patients treated with immediate surgical excision (N = 14), delayed wound healing (N = 5) and objectional scarring (N = 7) were common complications. However, pretreatment treatment with dapsone reduced the incidence of wound complications (N = 1) and objectional scarring (N = 1) (p less than 0.05), while reducing the need for surgical excision (N = 1). There were no severe drug reactions due to dapsone, although one patient had persistent G.I. upset. Pretreatment with dapsone not only reduced surgical complications but also improved the outcome of patients bitten by the brown recluse spider. PMID:4051613

  14. Sulphadimidine, pyrimethamine and dapsone in the treatment of toxoplasmosis in mice

    PubMed Central

    Beverley, J. K. A.; Fry, B. A.

    1957-01-01

    Sulphadimidine, dapsone, and pyrimethamine have been tested alone and in various combinations for their therapeutic effect against toxoplasma infection in mice. In the treatment of active infection, sulphadimidine by itself was effective, but relapses were common. Pyrimethamine gave complete cures and prevented the carrier state when used in doses near to the toxic level. Dapsone alone was not as good as either of the other two drugs tested. The best combination was found to be sulphadimidine and pyrimethamine, which were synergic. In doses well below the toxic level, this combination not only controlled the acute infection but also prevented relapses and the development of the carrier state. Dapsone and pyrimethamine were also synergic, but were not as effective as the previous combination. No synergy was found between dapsone and sulphadimidine. The mechanism of relapse and the development of the carrier state and the modes of action of the drugs alone and in combination are discussed. PMID:13446372

  15. Conformational analysis and vibrational spectroscopic studies on dapsone

    NASA Astrophysics Data System (ADS)

    Ildiz, Gulce Ogruc; Akyuz, Sevim

    2012-11-01

    In this study, the theoretical conformation analysis of free dapsone has been performed by single point energy calculations at both semi-empirical PM3 and DFT/B3LYP-3-21G theory levels and three stable conformers were determined. Both the IR and Raman spectra of the molecule in solid phase have been recorded. The IR intensities and harmonic vibrational wavenumbers of each conformer were calculated by DFT method at B3LYP/6-31++G(d,p) theory level. For the fundamental characterization, the total energy distribution (TED) calculations of the vibrational modes were done using parallel quantum mechanic solution program (SQM) and the fundamental modes were assigned. The theoretical results are in agreement with the experimental ones.

  16. Penetration of dapsone into pulmonary lining fluid of human immunodeficiency virus type 1-infected patients.

    PubMed Central

    Cruciani, M; Gatti, G; Mengoli, C; Cazzadori, A; Lazzarini, L; Miletich, F; Graziani, M S; Malena, M; Bassetti, D

    1997-01-01

    We studied the penetration of dapsone into the epithelial lining fluid (ELF) of sixteen human immunodeficiency virus type 1-infected patients who had received the drug at a dose of 100 mg twice weekly as primary prophylaxis for Pneumocystis carinii pneumonia. Bronchoscopy, bronchoalveolar lavage (BAL), and venipuncture were performed for each patient at a specific time after administration of the last dose of dapsone. Dapsone concentrations in plasma and BAL were determined by high-performance liquid chromatography. The apparent volume of ELF recovered by BAL was determined by using urea as an endogenous marker. The mean concentrations of dapsone in ELF at 2 h (five patients), 4 h (three patients), 12 h (two patients), 24 h (three patients), and 48 h (three patients) were 0.95, 0.70, 1.55, 0.23, and 0.45 mg/liter, respectively, while concentrations in plasma were 1.23, 0.79, 1.31, 0.83, and 0.18 mg/liter, respectively. Dapsone concentrations in ELF were 76, 79, 115, 65, and 291% of those observed in plasma at the same times, respectively. These data show that dapsone is well distributed into ELF and that a twice-weekly 100-mg prophylactic regimen results in sustained concentrations in this compartment. PMID:9145873

  17. Formulation development and stabililty testing of extemporaneous suspension prepared from dapsone tablets.

    PubMed

    Kaila, Nitin; El-Ries, Mohamed; Riga, A; Alexander, Kenneth; Dollimore Posthumously, D

    2003-01-01

    The qualification and quantification of dapsone in suspension were developed and shown to be stability indicating by means of a reverse-phase high-performance liquid chromatographic method. The real solubility of dapsone in water was calculated to be 0.208mg/mL at 25 deg C. The enthalpy of solution and the entropy of solution were calculated to be -175.6 J/g and -43605.7 J/K/M, respectively. An extemporaneous suspension was formulated from commercially available dapsone rablets, and the chemical stability of dapsone in the suspension was determined by means of accelerated stability testing. The 91-day analytical stabilty testing study was conducted at 4, 30, 50, 60, and 70 deg C. The energy of activation for the suspension was determined to be -23288.35 J/K/M. The zero-order rate of degradation for dapsone (k0,25) in suspension at 25 deg C was found to be 0.040845 day -1. The first-order rate of degradation for dapsone in solution was found to be 0.196370 (mg/mL)(day-1). The shelf life for the suspension was calulated to be 31.67 days at 25 deg C and 230.76 days under refrigeration at 4 deg C.

  18. The use of cimetidine as a selective inhibitor of dapsone N-hydroxylation in man.

    PubMed Central

    Coleman, M D; Scott, A K; Breckenridge, A M; Park, B K

    1990-01-01

    1. The N-hydroxylation of dapsone is thought to be responsible for the methaemoglobinaemia and haemolysis associated with this drug. We wished to investigate the effect of concurrent administration of cimetidine (400 mg three times per day) on the disposition of a single dose (100 mg) of dapsone in seven healthy volunteers in order to inhibit selectively N-hydroxylation. 2. The AUC of dapsone (31.0 +/- 7.2 micrograms ml-1 h) was significantly increased (P less than 0.001) in the presence of cimetidine (43.3 +/- 8.8 micrograms ml-1 h). 3. Peak methaemoglobin levels observed after dapsone administration (2.5 +/- 0.6%) were significantly (P less than 0.05) reduced in the presence of cimetidine (0.98 +/- 0.35%). 4. The percentage of the dose excreted in urine as the glucuronide of dapsone hydroxylamine was significantly (P less than 0.05) reduced in the presence of cimetidine (34.2 +/- 9.3 vs 23.1 +/- 4.2%). 5. Concurrent cimetidine therapy might reduce some of the haematological side-effects of dapsone. PMID:2271376

  19. The endogenous hydrogen sulfide producing enzyme cystathionine-beta synthase contributes to visceral hypersensitivity in a rat model of irritable bowel syndrome.

    PubMed

    Xu, Guang-Yin; Winston, John H; Shenoy, Mohan; Zhou, Shufang; Chen, Jiande D Z; Pasricha, Pankaj J

    2009-08-06

    The pathogenesis of visceral hypersensitivity, a characteristic pathophysiological feature of irritable bowel syndrome (IBS), remains elusive. Recent studies suggest a role for hydrogen sulfide (H2S) in pain signaling but this has not been well studied in visceral models of hyperalgesia. We therefore determined the role for the endogenous H2S producing enzyme cystathionine-beta-synthetase (CBS) in a validated rat model of IBS-like chronic visceral hyperalgesia (CVH). CVH was induced by colonic injection of 0.5% acetic acid (AA) in 10-day-old rats and experiments were performed at 8-10 weeks of age. Dorsal root ganglion (DRG) neurons innervating the colon were labeled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate) into the colon wall. In rat DRG, CBS-immunoreactivity was observed in approximately 85% of predominantly small- and medium-sized neurons. Colon specific DRG neurons revealed by retrograde labeling DiI were all CBS-positive. CBS-positive colon neurons co-expressed TRPV1 or P2X3 receptors. Western blotting analysis showed that CBS expression was significantly increased in colon DRGs 8 weeks after neonatal AA-treatment. Furthermore, the CBS inhibitor hydroxylamine markedly attenuated the abdominal withdrawal reflex scores in response to colorectal distention in rats with CVH. By contrast, the H2S donor NaHS significantly enhanced the frequency of action potentials of colon specific DRG neurons evoked by 2 times rheobase electrical stimulation. Our results suggest that upregulation of CBS expression in colonic DRG neurons and H2S signaling may play an important role in developing CVH, thus identifying a specific neurobiological target for the treatment of CVH in functional bowel syndromes.

  20. TLR4 upregulates CBS expression through NF-κB activation in a rat model of irritable bowel syndrome with chronic visceral hypersensitivity.

    PubMed

    Yuan, Bo; Tang, Wei-Hong; Lu, Li-Juan; Zhou, Yuan; Zhu, Hong-Yan; Zhou, You-Lang; Zhang, Hong-Hong; Hu, Chuang-Ying; Xu, Guang-Yin

    2015-07-28

    To investigate the roles of toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB on cystathionine β synthetase (CBS) expression and visceral hypersensitivity in rats. This study used 1-7-wk-old male Sprague-Dawley rats. Western blot analysis was employed to measure the expression of TLR4, NF-κB and the endogenous hydrogen sulfide-producing enzyme CBS in colon dorsal root ganglia (DRG) from control and "irritable bowel syndrome" rats induced by neonatal colonic inflammation (NCI). Colon-specific DRG neurons were labeled with Dil and acutely dissociated to measure excitability with patch-clamp techniques. Immunofluorescence was employed to determine the co-expression of TLR4, NF-κB and CBS in DiI-labeled DRG neurons. NCI significantly upregulated the expression of TLR4 in colon-related DRGs (0.34 ± 0.12 vs 0.72 ± 0.02 for the control and NCI groups, respectively, P < 0.05). Intrathecal administration of the TLR4-selective inhibitor CLI-095 significantly enhanced the colorectal distention threshold of NCI rats. CLI-095 treatment also markedly reversed the hyperexcitability of colon-specific DRG neurons and reduced the expression of CBS (1.7 ± 0.1 vs 1.1 ± 0.04, P < 0.05) and of the NF-κB subunit p65 (0.8 ± 0.1 vs 0.5 ± 0.1, P < 0.05). Furthermore, the NF-κB-selective inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced the upregulation of CBS (1.0 ± 0.1 vs 0.6 ± 0.1, P < 0.05) and attenuated visceral hypersensitivity in the NCI rats. In vitro, incubation of cultured DRG neurons with the TLR4 agonist lipopolysaccharide significantly enhanced the expression of p65 (control vs 8 h: 0.9 ± 0.1 vs 1.3 ± 0.1; control vs 12 h: 0.9 ± 0.1 vs 1.3 ± 0.1, P < 0.05; control vs 24 h: 0.9 ± 0.1 vs 1.6 ± 0.1, P < 0.01) and CBS (control vs 12 h: 1.0 ± 0.1 vs 2.2 ± 0.4; control vs 24 h: 1.0 ± 0.1 vs 2.6 ± 0.1, P < 0.05), whereas the inhibition of p65 via pre-incubation with PDTC significantly reversed the upregulation of CBS expression (1.2 ± 0

  1. Zidovudine, trimethoprim, and dapsone pharmacokinetic interactions in patients with human immunodeficiency virus infection.

    PubMed Central

    Lee, B L; Safrin, S; Makrides, V; Gambertoglio, J G

    1996-01-01

    Zidovudine is widely prescribed for the treatment of human immunodeficiency virus (HIV) infection. Trimethoprim and dapsone are commonly used in the management of Pneumocystis carinii pneumonia in HIV-infected patients. To examine the pharmacokinetic interactions among these drugs, eight HIV-infected patients (26 to 43 years old) with a mean CD4 count of 524.4 +/- 405.7 cells per mm3 received zidovudine (200 mg), trimethoprim (200 mg), and dapsone (100 mg) as single agents and in two- and three-drug combinations. Blood and urine samples were collected at a specified time and analyzed for zidovudine, zidovudine-glucuronide, trimethoprim, dapsone, and monoacetyl-dapsone concentrations under single-dose and steady-state conditions. Zidovudine did not influence the pharmacokinetic disposition of dapsone or trimethoprim. Dapsone had no effect on the pharmacokinetic disposition of zidovudine. Trimethoprim significantly decreased the renal clearance of zidovudine by 58% (5.0 +/- 1.8 versus 2.1 +/- 0.5 ml/min/kg of body weight [P < 0.05]). There was a concurrent 54% decrease in the mean urinary recovery of zidovudine (11.7 +/- 3.5 versus 5.4 +/- 3.0 [P < 0.05]), and the metabolic ratio was decreased by 78% (0.32 +/- 0.4 versus 0.07 +/- 0.05 [P < 0.05]). The mean area under the concentration-time curve from 0 to 6 h of the zidovudine-glucuronide/ zidovudine ratio was unchanged. We conclude that zidovudine, trimethoprim, and dapsone can be coadministered to patients with AIDS without significant pharmacokinetic interaction. However, in AIDS patients with liver impairment and impaired glucuronidation, doses of zidovudine may need to be decreased. PMID:8723472

  2. 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

  3. Effects of β-(1,3-1,6)-D-glucan on irritable bowel syndrome-related colonic hypersensitivity.

    PubMed

    Asano, Teita; Tanaka, Ken-ichiro; Suemasu, Shintaro; Ishihara, Tomoaki; Tahara, Kayoko; Suzuki, Toshio; Suzuki, Hidekazu; Fukudo, Shin; Mizushima, Tohru

    2012-04-06

    Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain associated with altered bowel habits. Since the prevalence of IBS is very high and thus, involves elevated health-care costs, treatment of this condition by methods other than prescribed medicines could be beneficial. β-(1,3)-D-glucan with β-(1,6) branches (β-glucan) has been used as a nutritional supplement for many years. In this study, we examined the effect of β-glucan on fecal pellet output and visceral pain response in animal models of IBS. Oral administration of β-glucan suppressed the restraint stress- or drug-induced fecal pellet output. β-Glucan also suppressed the visceral pain response to colorectal distension. These results suggest that β-glucan could be beneficial for the treatment and prevention of IBS.

  4. Pharmacokinetics and protein binding interactions of dapsone and pyrimethamine.

    PubMed

    Ahmad, R A; Rogers, H J

    1980-11-01

    1 Seven normal volunteers received oral doses of 100 mg dapsone (DDS), 25 mg pyrimethamine (PYR) singly or in combination in random order. 2 Plasma and salivary DDS and plasma monoacetyldapone (MADDS) and PYR were estimated simultaneously by a hitherto unpublished quantitative absorption thin layer chromatographic method. This assay was shown to be satisfactory for pharmacokinetic studies. 3 The half-life of DDS was unaltered by PYR but the apparent volume of distribution was significantly increased from a mean of 1.53 1 kg-1 to 1.93 1 kg-1 and the peak DDS plasma levels measured fell by 17%. 4 The pharmacokinetic parameters of PYR were unchanged by DDS. 5 The half-life of MADDS was unchanged by PYR and was not affected by the acetylator status of the subject. 6 Salivary DDS excretion reflects the free plasma DDS concentration. Administration of PYR with DDS significantly alters the mean saliva/plasma DDS ratio from 0.265 to 0.358 suggesting an increase in free DDS with PYR therapy. 7 In vitro studies of plasma protein DDS binding indicate that DDS binds to a single class of binding sites on human plasma protein and PYR competitively displaces DDS from these sites. 8 The usefulness of salivary drug measurements in detecting increases of free drug in plasma in man is demonstrated.

  5. Effects of chili on postprandial gastrointestinal symptoms in diarrhoea predominant irritable bowel syndrome: evidence for capsaicin-sensitive visceral nociception hypersensitivity.

    PubMed

    Gonlachanvit, S; Mahayosnond, A; Kullavanijaya, P

    2009-01-01

    Irritable bowel syndrome (IBS) patients often complain of gastrointestinal symptoms after eating chili. However, the effect of chili ingestion on gastrointestinal symptoms in IBS patients has not been characterized. To study the effect of chili-containing foods on postprandial gastrointestinal symptoms in diarrhoea-predominant IBS (IBS-D), 20 IBS-D patients underwent gastrointestinal symptoms and postprandial colonic transit evaluations after ingesting three different meals: (i) a standard meal, (ii) a spicy meal (a standard meal mixed with 2 g chili), and (iii) a standard meal with 2 g chili in capsules, in a randomized crossover fashion. Postprandial gastrointestinal symptoms were scored every 15 min for 2 h using visual analogue scales. Thirty-eight healthy volunteers were used as controls. In healthy volunteers, the spicy meals and meals with chili capsules induced only mild abdominal burning relative to the standard meals (P < 0.05), whereas it induced significant levels of abdominal pain and burning in IBS-D patients (P < 0.05). Other gastrointestinal symptoms and postprandial colonic transit after spicy meals and meals with chili capsules did not differ from standard meals in IBS-D and controls (P > 0.05). Diarrhoea-predominant IBS patients and controls reported similar oral burning symptoms when eating spicy meals (P > 0.05). Both the spicy meal and the standard meal with chili capsules led to similar severity of gastrointestinal symptoms (P > 0.05). Diarrhoea-predominant IBS patients exhibit gut hypersensitivity to chili. Chili ingestion produced more abdominal pain and burning in IBS-D patients than in healthy volunteers, but was associated with similar oral burning symptoms.

  6. In vitro susceptibilities of oxacillin-resistant Staphylococcus aureus to dapsone and sulfamethoxazole alone and in combination with trimethoprim.

    PubMed Central

    Lambertus, M W; Kwok, R Y; Mulligan, M E

    1990-01-01

    The in vitro activity of trimethoprim plus dapsone against oxacillin-resistant Staphylococcus aureus was comparable to that of trimethoprim plus sulfamethoxazole. Because of its different pharmacologic properties, dapsone may be a useful agent in combination with trimethoprim for the treatment of patients colonized with oxacillin-resistant S. aureus. PMID:2117420

  7. A short history of dapsone, or an alternative model of drug development.

    PubMed

    Barr, Justin

    2011-10-01

    From 1936 until 1996, the drug dapsone treated a diverse array of diseases, including tuberculosis, leprosy, malaria, and AIDS-related pneumonia. This article explores how dapsone transformed from a cure for one disease into a treatment for a totally different malady. This process of reinvention in the clinic represents an alternative model of drug development that the historical literature, focused on success in the laboratory, has largely ignored. The core of the paper discusses the reinvention of dapsone as an antimalarial in the Vietnam War through trials led by Robert J. T. Joy, a physician and military officer. As a case study, it offers a fresh perspective on the clinic-as-laboratory approach that other scholars have addressed in a civilian context. Viewing the randomized clinical trial (RCT) through a military prism will demonstrate how a combat environment combined with the regimentation of the armed forces affected the standard methodology of the RCT.

  8. ELISA tests for dapsone and pyrimethamine and their application in a malaria chemoprophylaxis programme

    PubMed Central

    Greenwood, B. M.; Greenwood, A. M.; Bradley, A. K.; Shenton, F. C.; Smith, A. W.; Snow, R. W.; Williams, K.; Eggelte, T. A.; Huikeshoven, H.; de Wit, M.

    1986-01-01

    Enzyme-linked immunosorbent asays (ELISAs) are described for determining levels of dapsone and pyrimethamine in urine. Both assays have a sensitivity of about 20 μg/l and are reproducible, but each produces some false positives. The problem of false positive reactions was partially obviated by requiring positive results in both assays. In a pilot study involving 50 children aged 3 months to 4 years who were given a single dose of Maloprim (pyrimethamine + dapsone), 75% were positive for dapsone 7 days after administration of the drug, while 25% were still positive 15 days after its administration. The corresponding proportions for pyrimethamine were 73% and 30%, respectively. Comparison of the results obtained in a larger chemoprophylaxis trial with those from the pilot study indicated that the assays described could be used to investigate whether antimalarials had been taken. PMID:3493860

  9. Reactivation of Human Herpes Virus-6 in the Renal Tissue of a Patient with Drug-induced Hypersensitivity Syndrome/Drug Rash with Eosinophilia and Systemic Symptoms (DIHS/DRESS).

    PubMed

    Hagiya, Hideharu; Iwamuro, Masaya; Tanaka, Takehiro; Hasegawa, Kou; Hanayama, Yoshihisa; Kimura, Maya; Otsuka, Fumio

    2016-01-01

    A 74-year-old man who had been administered trimethoprim-sulfamethoxazole for three weeks suffered from drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/DRESS). In the early stage of the clinical course, he developed renal dysfunction. A renal biopsy showed granulomatous tubulointerstitial nephritis accompanying the proliferation of human herpes virus (HHV)-6 in tubular epithelial cells. With corticosteroid therapy, the systemic rash and renal function gradually improved. The present patient is the second case of DIHS/DRESS demonstrating a possible reactivation of HHV-6 in the renal tissue. The clinical role of viral reactivation in DIHS/DRESS must be further elucidated.

  10. [Hypersensitivity reactions to insulin].

    PubMed

    Becerril-Ángeles, Martín; Moctezuma-Trejo, Cristina; Espinosa-Larrañaga, Francisco

    2012-01-01

    Hypersensitivity reactions to insulin are infrequent, yet of clinical importance. The mechanisms of hypersensitivity involved can be of three types: I, III and IV. To describe the pathophysiology of hypersensitivity to insulin, its clinical features and diagnostic and therapeutic approach, that help identify the cases of allergy to insulin and begin a treatment, or if necessary, to refer patients to a specialists or appropriate medical attention. An electronic search of papers related to insulin hypersensitivity was performed in PubMed and the articles selected were those considered the most relevant for this review. Thirty eight papers about pathophysiology, mechanisms of injury and the different types of insulin involved in hypersensitivity reactions were included. Likewise, information for the diagnosis of insulin hypersensitivity and some options of treatment for first contact physicians or the referral of patients to specialists in endocrinology and allergy were included. Insulin hypersensitivity has a low prevalence and diverse clinical manifestations. The different types of insulin suitable allow the majority of cases of hypersensitivity to continue the treatment in a efficient and flexible manner.

  11. Treating dentin hypersensitivity

    PubMed Central

    Cunha-Cruz, Joana; Wataha, John C.; Zhou, Lingmei; Manning, Walter; Trantow, Michael; Bettendorf, Meishan M.; Heaton, Lisa J.; Berg, Joel

    2011-01-01

    Background Methods used by dental practitioners to diagnose and treat dentin hypersensitivity are not well documented. The authors conducted a survey of dentists in the Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry (PRECEDENT) to ascertain the treatment methods they used. Methods Via an Internet survey, the authors collected data regarding methods used for diagnosis and treatment of dentin hypersensitivity from 209 Northwest PRECEDENT dentists. Results The PRECEDENT dentists indicated that they most often used fluoride varnishes and gels, advice regarding toothbrushing and diet, bonding agents, restorative materials and glutaraldehyde/2-hydroxyethyl methacrylate (HEMA) to treat dentin hypersensitivity. They reported that the most successful treatments were fluorides, glutaraldehyde/HEMA, bonding agents, potassium nitrates and restorative treatments; they considered observation, advice regarding toothbrushing and diet and laser therapy to be the least successful. Dentists listed fluorides, calcium phosphates, glutaraldehyde/HEMA and bonding agents as the treatments most desirable for inclusion in a future randomized clinical trial of dental hypersensitivity treatments. Conclusions Dentists rely on patients to assess the severity of dentin hypersensitivity. Modalities for the diagnosis and treatment of hypersensitivity are diverse. Methods used to diagnose and treat dentin hypersensitivity in practice are challenging to justify. Clinical Implications Practitioners should be aware of the diversity of methods available for diagnosing and treating dentin hypersensitivity as they manage the care of their patients with this condition. PMID:20807910

  12. Delayed cutaneous manifestations of drug hypersensitivity.

    PubMed

    Bircher, Andreas J; Scherer, Kathrin

    2010-07-01

    Drugs may elicit a considerable variety of clinical signs, often affecting the skin and the mucous membranes. The most common are maculopapular exanthemas and urticaria, more rarely pustules, bullae vasculitic lesions, and lichenoid lesions may also be observed. Apart from the morphology, the chronology of the occurrence and the evolution of single skin lesions and exanthema are also paramount in the clinical diagnosis of cutaneous drug hypersensitivity. Often, the skin represents the only organ manifestation; however, it may be the herald for a systemic involvement of internal organs, such as in severe drug-induced hypersensitivity syndromes or anaphylaxis.

  13. Topical Tacrolimus and Oral Dapsone Combination Regimen in Lichen Planus Pigmentosus.

    PubMed

    Verma, Prashant; Pandhi, Deepika

    2015-01-01

    Lichen planus pigmentosus is a well-recognized variant of lichen planus; however, its etiopathogenesis is still unclear. An effective and safe treatment for lichen planus pigmentosus is needed; therefore, the authors examined a series of five patients with lichen planus pigmentosus with successful response to a combination of topical tacrolimus and oral dapsone.

  14. Dapsone-induced pure red cell aplasia and cholestatic jaundice: A new experience for diagnosis and management

    PubMed Central

    Sawlani, Kamal Kumar; Chaudhary, Shyam Chand; Singh, Jitendra; Raja, Deep Chandh; Mishra, Sanjay; Goel, Madhu Mati

    2016-01-01

    Dapsone (4,4’- diaminodiphenylsulfone) is the parent compound of the sulfones, and it has potent antiparasitic, anti-inflammatory, and immunomodulatory effects. It is used in the treatment of leprosy, dermatitis herpetiformis, and prophylactically to prevent Pneumocystis pneumonia and toxoplasmosis in patients unable to tolerate trimethoprim with sulfamethoxazole. We hereby report a case of dapsone toxicity who developed pure red cell aplasia and cholestatic jaundice in a suspected case of dermatitis herpetiformis. Patient had an excellent response to corticosteroids after withdrawal of dapsone. PMID:27512715

  15. Population pharmacokinetics of dapsone administered biweekly to human immunodeficiency virus-infected patients.

    PubMed Central

    Gatti, G; Merighi, M; Hossein, J; Travaini, S; Casazza, R; Karlsson, M; Cruciani, M; Bassetti, D

    1996-01-01

    The population pharmacokinetics of dapsone were examined in human immunodeficiency virus-infected patients receiving dapsone at a dosage of 100 mg twice weekly for the prevention of Pneumocystis carinii pneumonia. Nonlinear mixed-effect modeling was used to determine the best pharmacostatistical model for the data. A one-compartment open model with first-order absorption and elimination was used as the structural pharmacokinetic model. Several covariates were tested for their influence on pharmacokinetic parameters. Rifampin was found to increase the values of clearance/bioavailability (CL/F) and volume of distribution/ bioavailability (V/F) by approximately 70%. CL/F and V/F were 1.83 liters/h and 69.6 liters, respectively, for patients not taking rifampin. The effect of rifampin on the pharmacokinetic parameters of dapsone was appreciably less than expected on the basis of studies with healthy volunteers. Increased bilirubin levels were associated with a significant decrease in the absorption rate constant (Ka). However, this finding may be considered clinically irrelevant because the post hoc Bayesian estimates of Ka for patients with high bilirubin levels ( > 1.2 mg/dl) were at the lower bound of the values for patients with normal bilirubin levels. The value of Ka was 0.957 h-1 for a patient with a bilirubin level of 0.7 mg/dl. After inclusion of covariates in the model, the interpatient variability was 35% for CL/F, not significant for V/F, and 85% for Ka. Simulation of plasma concentration-versus-time curves indicated that the administration of 100 mg of dapsone biweekly is associated with sustained dapsone levels in the plasma of the majority of the patients. Dosage adjustments for patients concomitantly treated with rifampin may be necessary. PMID:9124833

  16. Hypersensitivity reaction to azathioprine.

    PubMed

    Fields, C L; Robinson, J W; Roy, T M; Ossorio, M A; Byrd, R P

    1998-05-01

    Adverse drug reactions can vary from a simple rash to anaphylactic shock. While certain medications including the penicillins are well known to cause such reactions, other drugs are not as commonly recognized. Azathioprine hypersensitivity reactions tend to be benign and self-limiting with cessation of drug ingestion. We report a patient who had a hypersensitivity reaction to azathioprine, which manifested as distributive shock that mimicked sepsis. We also reviewed the English language literature for risk factors for a hypersensitivity reaction to azathioprine and its possible mechanism.

  17. Hypersensitivity to antineoplastic agents.

    PubMed

    Castells, M C

    2008-01-01

    The need to offer first line therapy for primary and recurrent cancers has spurred the clinical development of rapid desensitizations for chemotherapy and monoclonal antibodies. Rapid desensitizations allow patients to be treated with medications to which they have presented with hypersensitivity reactions (HSRs), including anaphylaxis. Rapid desensitization achieves temporary tolerization to full therapeutic doses by slow administration of incremental doses of the drug inducing the HSR. Protocols are available for most chemotherapy agents, including taxanes, platins, doxorubicin, monoclonal antibodies, and others. Candidate patients include those who present with type I HSRs, mast cell/IgE dependent, including anaphylaxis, and non-IgE mediated HSRs, during the chemotherapy infusion or shortly after. Idiosyncratic reactions, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis are not amenable to rapid desensitization. The recommendation for rapid desensitization can only be made by allergy and immunology specialists and can only be performed in settings with one-to-one nurse-patient care and where resuscitation personnel and resources are readily available. Repeated desensitizations can be safely performed in outpatient settings with similar conditions, which allow cancer patients to remain in clinical studies. We have generated a universal 12-step protocol that was applied to 413 cases of intravenous and intraperitoneal rapid desensitizations using taxanes, platins, liposomal doxorubicin, doxorubicin, rituximab, and other chemotherapy drugs. Under this protocol all patients were able to complete their target dose, and 94% of the patients had limited or no reactions. No deaths or codes were reported, indicating that the procedure was safe and effective in delivering first line chemotherapy drugs.

  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. Platinum hypersensitivity and desensitization.

    PubMed

    Miyamoto, Shingo; Okada, Rika; Ando, Kazumichi

    2015-09-01

    Platinum agents are drugs used for various types of cancer. With increased frequency of administration of platinum agents, hypersensitivity reactions appear more frequently, occurring in over 25% of cases from the seventh cycle or second line onward. It then becomes difficult to conduct treatment using these agents. Various approaches have been investigated to address hypersensitivity reactions to platinum agents. Desensitization, which gradually increases the concentration of the anticancer drug considered to be the antigen until the target dosage, has been reported as being particularly effective, with a success rate of 80-100%. The aims of this paper are to present the current findings regarding hypersensitivity reactions to platinum agents and to discuss attempts of using desensitization against hypersensitivity reactions worldwide. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Exercise-induced hypersensitivity syndromes in recreational and competitive athletes: a PRACTALL consensus report (what the general practitioner should know about sports and allergy).

    PubMed

    Schwartz, L B; Delgado, L; Craig, T; Bonini, S; Carlsen, K H; Casale, T B; Del Giacco, S; Drobnic, F; van Wijk, R G; Ferrer, M; Haahtela, T; Henderson, W R; Israel, E; Lötvall, J; Moreira, A; Papadopoulos, N G; Randolph, C C; Romano, A; Weiler, J M

    2008-08-01

    Exercise-induced (EI) hypersensitivity disorders are significant problems for both recreational and competitive athletes. These include EI-asthma, EI-bronchoconstriction, EI-rhinitis, EI-anaphylaxis and EI-urticaria. A group of experts from the European Academy of Allergology and Clinical Immunology and the American Academy of Allergy Asthma and Immunology met to discuss the pathogenesis of these disorders and how to diagnose and treat them, and then to develop a consensus report. Key words (exercise with asthma, bronchoconstriction, rhinitis, urticaria or anaphylaxis) were used to search Medline, the Cochrane database and related websites through February 2008 to obtain pertinent information which, along with personal reference databases and institutional experience with these disorders, were used to develop this report. The goal is to provide physicians with guidance in the diagnosis, understanding and management of EI-hypersensitivity disorders to enable their patients to safely return to exercise-related activities.

  1. Cardiac Iodine-123-Meta-Iodo-Benzylguanidine Uptake in Carotid Sinus Hypersensitivity.

    PubMed

    Tan, Maw Pin; Murray, Alan; Hawkins, Terry; Chadwick, Thomas J; Kerr, Simon R J; Parry, Steve W

    2015-01-01

    Carotid sinus syndrome is the association of carotid sinus hypersensitivity with syncope, unexplained falls and drop attacks in generally older people. We evaluated cardiac sympathetic innervation in this disorder in individuals with carotid sinus syndrome, asymptomatic carotid sinus hypersensitivity and controls without carotid sinus hypersensitivity. Consecutive patients diagnosed with carotid sinus syndrome at a specialist falls and syncope unit were recruited. Asymptomatic carotid sinus hypersensitivity and non-carotid sinus hypersensitivity control participants recruited from a community-dwelling cohort. Cardiac sympathetic innervation was determined using Iodine-123-metaiodobenzylguanidine (123-I-MIBG) scanning. Heart to mediastinal uptake ratio (H:M) were determined for early and late uptake on planar scintigraphy at 20 minutes and 3 hours following intravenous injection of 123-I-MIBG. Forty-two subjects: carotid sinus syndrome (n = 21), asymptomatic carotid sinus hypersensitivity (n = 12) and no carotid sinus hypersensitivity (n = 9) were included. Compared to the non- carotid sinus hypersensitivity control group, the carotid sinus syndrome group had significantly higher early H:M (estimated mean difference, B = 0.40; 95% confidence interval, CI = 0.13 to 0.67, p = 0.005) and late H:M (B = 0.32; 95%CI = 0.03 to 0.62, p = 0.032). There was, however, no significant difference in early H:M (p = 0.326) or late H:M (p = 0.351) between the asymptomatic carotid sinus hypersensitivity group and non- carotid sinus hypersensitivity controls. Cardiac sympathetic neuronal activity is increased relative to age-matched controls in individuals with carotid sinus syndrome but not those with asymptomatic carotid sinus hypersensitivity. Blood pressure and heart rate measurements alone may therefore represent an over simplification in the assessment for carotid sinus syndrome and the relative increase in cardiac sympathetic innervation provides additional clues to

  2. Spectrophotometric determination of dapsone in pharmaceutical products using sodium 1,2-naphthoquinone-4-sulfonic as the chromogenic reagent

    NASA Astrophysics Data System (ADS)

    Wang, Huai You; Xu, Li Xiao; Xiao, Yan; Han, Juan

    2004-10-01

    Spectrophotometric determination of dapsone is described. The dapsone reacts with sodium 1,2-naphthoquinone-4-sulfonic in pH 6.98 buffer solution to form a salmon pink compound, and its maximum absorption wavelength is at 525 nm, ɛ525=3.68×10 4 l mol -1 cm -1. The absorbance of dapsone from 0.40 to 10 μg ml -1 obeys Beer's law. The linear regression equation of the calibration graph is C=0.2334 A+0.01288, with a linear regression correlation coefficient of 0.9998, the detection limit is 0.24 μg ml -1, and recovery is from 99.2 to 102.4%. Effects of pH, surfactant, organic solvents, foreign ions, and standing time on the determination of dapsone have been examined. This method is simple and can be used for the determination of dapsone in injection solution of dapsone. The results obtained by this method agreed with those by the official method (dead-stop titration method [The Chinese Pharmacopoeia, Pharmacopoeia Commission, Ministry of Health, vol. 2, fifth ed., PRC Chemical Industry Press, Beijing, 2000, p.720]).

  3. Surgical stress induced depressive and anxiety like behavior are improved by dapsone via modulating NADPH oxidase level.

    PubMed

    Zhang, Tao; Tian, Xiaosheng; Wang, Qiudian; Tong, Yawei; Wang, Hecheng; Li, Zhengqian; Li, Lunxu; Zhou, Ting; Zhan, Rui; Zhao, Lei; Sun, Yang; Fan, Dongsheng; Lu, Lin; Zhang, Jing; Jin, Yinglan; Xiao, Weizhong; Guo, Xiangyang; Chui, Dehua

    2015-01-12

    Surgical stress induced depression and anxiety like behavior are common complications among aged individuals suffering from surgery. Recent studies proposed that accumulation of oxidative stress is involved in the etiology of stress induced depression and anxiety. Dapsone possesses antioxidant properties, however, whether dapsone is effective in modulating surgical stress induced brain oxidative damage remains uncertain. The present study aimed to investigate the effect of dapsone on surgical stress induced depressive and anxiety like behavior, and brain oxidative stress in a well-established surgical stress model. Depressive and anxiety like behavior accompanied by elevated brain oxidative stress were observed in aged mice underwent abdominal surgery. Pretreatment with 5 mg/kg dapsone significantly improved the behavioral disorder and ameliorated brain oxidative stress in this model. Further investigation, revealed that surgical stress increased brain NADPH oxidase level, while pretreatment with dapsone abrogated the elevation of NADPH oxidase triggered by surgical stress. These findings suggest that dapsone is effective in improving surgical stress induced brain oxidative damage via down-regulating NADPH oxidase level in aged mice. Copyright © 2014. Published by Elsevier Ireland Ltd.

  4. Spectrophotometric determination of dapsone in pharmaceutical products using sodium 1,2-naphthoquinone-4-sulfonic as the chromogenic reagent.

    PubMed

    Wang, Huai You; Xu, Li Xiao; Xiao, Yan; Han, Juan

    2004-10-01

    Spectrophotometric determination of dapsone is described. The dapsone reacts with sodium 1,2-naphthoquinone-4-sulfonic in pH 6.98 buffer solution to form a salmon pink compound, and its maximum absorption wavelength is at 525 nm, epsilon525=3.68 x 10(4) l mol(-1) cm(-1). The absorbance of dapsone from 0.40 to 10 microg ml(-1) obeys Beer's law. The linear regression equation of the calibration graph is C=0.2334 A + 0.01288, with a linear regression correlation coefficient of 0.9998, the detection limit is 0.24 microg ml(-1), and recovery is from 99.2 to 102.4%. Effects of pH, surfactant, organic solvents, foreign ions, and standing time on the determination of dapsone have been examined. This method is simple and can be used for the determination of dapsone in injection solution of dapsone. The results obtained by this method agreed with those by the official method (dead-stop titration method [The Chinese Pharmacopoeia, Pharmacopoeia Commission, Ministry of Health, vol. 2, fifth ed., PRC Chemical Industry Press, Beijing, 2000, p.720]).

  5. The prevalence of widespread central hypersensitivity in chronic pain patients.

    PubMed

    Schliessbach, J; Siegenthaler, A; Streitberger, K; Eichenberger, U; Nüesch, E; Jüni, P; Arendt-Nielsen, L; Curatolo, M

    2013-11-01

    Chronic pain is associated with generalized hypersensitivity and impaired endogenous pain modulation (conditioned pain modulation; CPM). Despite extensive research, their prevalence in chronic pain patients is unknown. This study investigated the prevalence and potential determinants of widespread central hypersensitivity and described the distribution of CPM in chronic pain patients. We examined 464 consecutive chronic pain patients for generalized hypersensitivity and CPM using pressure algometry at the second toe and cold pressor test. Potential determinants of generalized central hypersensitivity were studied using uni- and multivariate regression analyses. Prevalence of generalized central hypersensitivity was calculated for the 5th, 10th and 25th percentile of normative values for pressure algometry obtained by a previous large study on healthy volunteers. CPM was addressed on a descriptive basis, since normative values are not available. Depending on the percentile of normative values considered, generalized central hypersensitivity affected 17.5-35.3% of patients. 23.7% of patients showed no increase in pressure pain threshold after cold pressor test. Generalized central hypersensitivity was more frequent and CPM less effective in women than in men. Unclearly classifiable pain syndromes showed higher frequencies of generalized central hypersensitivity than other pain syndromes. Although prevalent in chronic pain, generalized central hypersensitivity is not present in every patient. An individual assessment is therefore required in order to detect altered pain processing. The broad basic knowledge about central hypersensitivity now needs to be translated into concrete clinical consequences, so that patients can be offered an individually tailored mechanism-based treatment. © 2013 European Federation of International Association for the Study of Pain Chapters.

  6. Reaginic hypersensitivity in ulcerative colitis

    PubMed Central

    Jewell, D. P.; Truelove, S. C.

    1972-01-01

    Reaginic hypersensitivity in ulcerative colitis has been investigated in respect of a hypersensitivity to the cow's milk proteins and the frequency of atopic asthma, hay fever, and eczema. Intradermal tests were frequently positive, especially to casein, but the results did not differ from those found in healthy individuals and in groups of patients with Crohn's disease, hypolactasia, and the irritable colon syndrome. No circulating IgE-specific antibodies to the milk proteins were found. An increased frequency of atopic diseases was found in patients suffering from ulcerative colitis (15·7%) and Crohn's disease (13·3%) compared with the findings in a control group (1·2%). It is concluded that, if an allergy to milk proteins is a factor in the pathogenesis of ulcerative colitis, it is not mediated by reaginic antibodies. It is possible, however, that the frequent occurrence of atopy indicates a susceptibility to develop reaginic responses even though this mechanism does not apply to the milk proteins. PMID:4646293

  7. Pharmacogenetics of antiepileptic drug-induced hypersensitivity.

    PubMed

    Bloch, Katarzyna M; Sills, Graeme J; Pirmohamed, Munir; Alfirevic, Ana

    2014-04-01

    Antiepileptic drugs can induce potentially life-threatening hypersensitivity reactions such as Stevens-Johnson syndrome at a frequency of one in 10,000 to one in 1000 treated patients. There is a considerable cross-reactivity among different antiepileptic drugs but the mechanisms are not known. In this review we have summarized current evidence on antiepileptic drug-induced hypersensitivity reactions and performed meta-analyses of published case-control studies that investigated associations between HLA alleles and several antiepileptic drugs in diverse populations. As the heterogeneity between studies was high, we conducted subsequent subgroup analyses and showed that HLA-B*15:02 was associated with carbamazepine, lamotrigine and phenytoin-induced Stevens-Johnson syndrome in Asian populations indicating that pretreatment testing may prevent cross-reactivity. Additionally, we explored the potential of new, high-throughput technologies that may help to understand the mechanisms and predict the risk of adverse drug reactions in the future.

  8. Determination of dapsone in meat and milk by liquid chromatography tandem mass spectrometry.

    PubMed

    Hadjigeorgiou, M; Papachrysostomou, Ch; Theodorou, Z; Kanari, P; Constantinou, S

    2009-04-01

    Within the EU the use of dapsone (4,4-diaminodiphenylsulfone) is prohibited in food-producing animals and consequently it's included in the Annex IV of the Directive 90/2377/EC. A quantitative confirmatory method has been developed and validated according to the criteria defined in the Commission Decision 2002/657/EC, for the determination of dapsone in meat and milk. Samples, after homogenization in alkaline conditions and organic solvent extraction, were purified on silica gel solid phase extraction cartridges. The eluate was evaporated and redissolved in mobile phase and was analysed by liquid chromatography tandem mass spectrometry (LC-MS/MS) in positive electrospray ionisation (ESI) using deuterium labelled Sulphadimidine-d7 as internal standard. The calculated value for, decision limit, CCalpha is 0.12 microgkg(-1), and the detection capability; CCbeta value is 0.16 microgkg(-1).

  9. Type I immediate hypersensitivity reaction to cyanocobalamin but not hydroxycobalamin.

    PubMed

    Moloney, F J; Hughes, R; O'Shea, D; Kirby, B

    2008-07-01

    We report a case of a 42-year-old woman with a background of autoimmune polyglandular syndrome, who developed a type I immediate hypersensitivity reaction to intramuscular cyanocobalamin. Intradermal testing showed a positive reaction to cyanocobalamin. The patient was subsequently treated with intramuscular hydroxycobalamin after negative intradermal testing to this alternative B(12) compound. A review of previously described cases of hypersensitivity to either compound provides a rationale for the management of this rare but serious side-effect.

  10. The effect of clarithromycin, fluconazole, and rifabutin on dapsone hydroxylamine formation in individuals with human immunodeficiency virus infection (AACTG 283).

    PubMed

    Winter, Helen R; Trapnell, Carol B; Slattery, John T; Jacobson, Mark; Greenspan, Debra L; Hooton, Thomas M; Unadkat, Jashvant D

    2004-12-01

    Dapsone hydroxylamine formation is thought to be the cause of the high rates of adverse reactions to dapsone in human immunodeficiency virus (HIV)-infected individuals. Therefore we studied the effect of the commonly coadministered drugs fluconazole, clarithromycin, and rifabutin on hydroxylamine formation in individuals with HIV infection. HIV-infected subjects (CD4 + > or =200 cells/mm 3 ) were enrolled in a 2-part (A or B) open-label drug interaction study. In part A, subjects (n = 12) received dapsone (100-mg tablet once daily) alone for 2 weeks and then, in a randomly assigned order, received dapsone and either fluconazole (200 mg daily), rifabutin (300 mg daily), or fluconazole plus rifabutin, each for a 2-week period. Part B (n = 11) was identical to part A except that clarithromycin (500 mg twice daily) was substituted for rifabutin. On the last study day of each 2-week period, plasma and urine were collected over ascorbic acid for 24 hours. In part A, fluconazole decreased the area under the plasma concentration-time curve, percent of dose excreted in 24-hour urine, and formation clearance of the hydroxylamine by 49%, 53%, and 55% (n = 12, P < .05), respectively. This inhibition of in vivo hydroxylamine formation was quantitatively consistent with that predicted from human liver microsomal experiments. Rifabutin had no effect on hydroxylamine area under the plasma concentration-time curve or percent excreted in 24-hour urine but increased formation clearance of the hydroxylamine by 92% (n = 12, P < .05). Dapsone clearance was increased by rifabutin or rifabutin plus fluconazole (67% and 38%, respectively) (n = 12, P < .05) but was unaffected by fluconazole or clarithromycin. In part B, hydroxylamine production was unaffected by clarithromycin but was affected by fluconazole in a manner identical to that in part A. On the basis of these data and with the assumption that the exposure to the hydroxylamine is a determinant of dapsone toxicity, we predict that

  11. HLA Associations and Clinical Implications in T-Cell Mediated Drug Hypersensitivity Reactions: An Updated Review

    PubMed Central

    Cheng, Chi-Yuan; Chen, Chi-Hua; Chen, Wei-Li; Deng, Shin-Tarng; Chung, Wen-Hung

    2014-01-01

    T-cell mediated drug hypersensitivity reactions may range from mild rash to severe fatal reactions. Among them, drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS), Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN), are some of the most life-threatening severe cutaneous adverse reactions (SCARs). Recent advances in pharmacogenetic studies show strong genetic associations between human leukocyte antigen (HLA) alleles and susceptibility to drug hypersensitivity. This review summarizes the literature on recent progresses in pharmacogenetic studies and clinical application of pharmacogenetic screening based on associations between SCARs and specific HLA alleles to avoid serious conditions associated with drug hypersensitivity. PMID:24901010

  12. Clinical heterogeneity of drug hypersensitivity.

    PubMed

    Roujeau, Jean-Claude

    2005-04-15

    Skin is the most frequent target of drug reactions that are reported, may be because they are easily detected. Most (probably more than 90%) are related to drug hypersensitivity, i.e. an individually tailored, unexpected effect mediated by a drug specific activation of the immune response. The clinical presentation of "drug eruptions" is highly variable, from the most common transient and benign erythema that occurs 6-9 days after the introduction of a new drug in 1 to 3 % of users to the most severe forms, that fortunately affect less than 1/10,000 users. Even though there are some overlapping or unclassifiable cases, it is important for clinicians to recognize and categorize severe cutaneous adverse reactions/SCAR (bullous fixed drug eruptions/bFDE, acute generalized exanthematous pustulosis/AGEP, drug reaction with eosinophilia and systemic symptoms/DRESS, Stevens-Johnson syndrome/SJS, toxic epidermal necrolysis/TEN). First they must suspect rapidly that an unusual eruption with high fever and severe constitutional symptoms is caused by a medication and not by an infection. Second they have to look for involvement of organs that differ according to the type of reaction. Third they can determine a prognosis, the mortality rate being virtually 0 for bFDE, 5% for AGEP, 10% for "hypersensitivity syndrome"/DRESS and 25% for SJS or TEN. In addition if some medications are "usual suspects" for all types (e.g. anticonvulsants), some other are more specific of a given pattern (pristinamycine, hydroxychloroquine, diltiazem for AGEP, minocycline for DRESS, anti-infectious sulfonamides, allopurinol for epidermal necrolysis). The "phenotypic" diversity of the final expression drug reactions can be explained by the engagement of a variety of cytokines and inflammatory cells and by regulatory mechanisms. For example, memory cytotoxic T-Cells are key effectors in both localized blisters of bFDE and in extensive blisters of epidermal necrolysis.

  13. The Efficacy of Colchicine and Dapsone Combination Therapy in Relapsed Immune Thrombocytopenia

    PubMed Central

    Rattanathammethee, Thanawat; Theerajangkhaphichai, Wasan; Rattarittamrong, Ekarat; Hantrakool, Sasinee; Chai-Adisaksopha, Chatree; Norasetthada, Lalita; Tantiworawit, Adisak

    2017-01-01

    The aim of the present paper is to evaluate the efficacy and safety of colchicine and dapsone combination therapy in cases of steroid-dependent, relapsed and refractory immune thrombocytopenia (ITP). This is a retrospective study of ITP patients who attended the Hematology Clinic at Chiang Mai University Hospital (Thailand) from 1 January 2008 to 30 September 2014. Medical records and clinical data were reviewed for efficacy and adverse effects. Sixty-four ITP patients received the combination therapy. The median age was 46 years and 70.3% were female. The majority (65.6%) were relapsed ITP patients. Median platelet count before starting treatment was 22.6×109/L. The response rate was 82.8%, with 75.0% of patients having a complete response. Median time to response was 8 weeks. The response rate was higher in relapsed patients (90.4%) compared to refractory (61.5%) and steroid-dependent patients (77.8%). Steroid treatment was discontinued in 30 patients (50%) following combination therapy. The most common side effect was hemolysis due to dapsone which was found in eight patients (12.5%). We can therefore conclude that combination therapy with colchicine and dapsone is an alternative second-line therapy option in relapsed ITP cases with acceptable side effects. PMID:28286634

  14. Chlorproguanil-dapsone-artesunate versus chlorproguanil-dapsone: a randomized, double-blind, phase III trial in African children, adolescents, and adults with uncomplicated Plasmodium falciparum malaria.

    PubMed

    Tiono, Alfred B; Dicko, Alassane; Ndububa, Dennis A; Agbenyega, Tsiri; Pitmang, Simon; Awobusuyi, Jacob; Pamba, Allan; Duparc, Stephan; Goh, Li-Ean; Harrell, Emma; Carter, Nick; Ward, Stephen A; Greenwood, Brian; Winstanley, Peter A

    2009-12-01

    This multi-center, randomized, parallel-group, double-blind, double-dummy study compared the efficacy and safety of chlorproguanil-dapsone-artesunate (CDA) and chlorproguanil-dapsone (CPG-DDS) in the treatment of falciparum malaria in Africa (Burkina Faso, Ghana, Mali, Nigeria). Six hundred patients (>or= 1 year of age) received CDA 2.0/2.5/4.0 mg/kg, and 292 CPG-DDS 2.0/2.5 mg/kg, once daily for 3 days. Day 28 parasitologic cure rate (polymerase chain reaction [PCR]-corrected, per-protocol population) was 89.1% (416/467) for CDA, non-inferior but also superior to CPG-DDS, 83.0% (176/212) (treatment difference 6.1%; 95% confidence interval [CI] 0.3, 11.9). Glucose-6-phosphate dehydrogenase (G6PD) genotype was available for 844/892 (95%) patients. Occurrences of a composite hemoglobin safety endpoint (hemoglobin drop >or= 40 g/L or >or= 40% versus baseline, hemoglobin < 50 g/L, or blood transfusion) were CDA 13/44 (30%), CPG-DDS 7/24 (29%) in G6PD-deficient patients versus CDA 4/448 (< 1%), CPG-DDS 6/221 (3%) in G6PD-normal patients. No deaths occurred. CDA was more efficacious than CPG-DDS. However, the hemolytic potential in G6PD-deficient patients does not support further development of CDA.

  15. Discovery of a potential lead compound for treating leprosy with dapsone resistance mutation in M. leprae folP1.

    PubMed

    Nisha, J; Ramanathan, K; Nawaz Khan, F; Dhanasekaran, D; Shanthi, V

    2016-06-21

    Dapsone resistance is a serious impediment to the implementation of the present leprosy control strategies. In the recent past, many studies have been undertaken to address the antibiotic activity and binding pattern of dapsone against both native and mutant (Pro55Leu) folP1. Yet, there is no well-developed structural basis for understanding drug action and there is dire need for new antibacterial therapies. In the present study, molecular simulation techniques were employed alongside experimental strategies to address and overcome the mechanism of dapsone resistance. In essence, we report the identification of small molecule compounds to effectively and specifically inhibit the growth of M. leprae through targeting dihydropteroate synthase, encoded by folP1 which is involved in folic acid synthesis. Initially, ADME and toxicity studies were employed to screen the lead compounds, using dapsone as standard drug. Subsequently, molecular docking was employed to understand the binding efficiency of dapsone and its lead compounds against folP1. Further, the activity of the screened lead molecule was studied by means of molecular dynamics simulation techniques. Furthermore, we synthesized 4-(2-fluorophenylsulfonyl)benzenamine, using (2-fluorophenyl)boronic acid and 4-aminobenzenesulfonyl chloride, and the compound structure was confirmed by (1)H NMR and (13)C NMR spectroscopic techniques. Most importantly, the antibacterial activity of the compound was also examined and compared against dapsone. Overall, the result from our analysis suggested that CID21480113 (4-(2-fluorophenylsulfonyl)benzenamine) could be developed into a promising lead compound and could be effective in treating dapsone resistant leprosy cases.

  16. Metal Hypersensitivity and Total Knee Arthroplasty.

    PubMed

    Lachiewicz, Paul F; Watters, Tyler Steven; Jacobs, Joshua J

    2016-02-01

    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. Some 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.

  17. 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

  18. Hypersensitivity to ticagrelor and low response to clopidogrel: a case report

    PubMed Central

    Dai, Jing; Ge, Changjiang

    2017-01-01

    Ticagrelor is widely used to treat acute coronary syndrome. Hypersensitivity reaction of ticagrelor is rarely recognized. A low response to clopidogrel, which occurs in up to 23% of patients, is an independent risk factor for stent thrombosis. Management of patients with a low response to clopidogrel and ticagrelor hypersensitivity who are undergoing antithrombotic therapy remains to be a challenge. Herein, we report a patient with low response to clopidogrel and ticagrelor hypersensitivity, who was successfully managed using aspirin and warfarin. PMID:28154807

  19. [Electromagnetic fields hypersensitivity].

    PubMed

    Sobiczewska, Elzbieta; Szmigielski, Stanisław

    2009-01-01

    The development of industry, particularly of new technologies in communication systems, gives rise to the number and diversty of electromagnetic field (EMF) sources in the environment. These sources, including power-frequent, radiofrequent and microwaves, make human life richer, safer and easier. But at the same time, there is growing concern about possible health risks connected with EMF exposure. An increasing number of persons have recently reported on a variety of health problems induced, in their opinion, by exposure to EMF. It is important to note that EMF levels to which these individuals are exposed are generally well below the recommended exposure limits and are certainly far below those known to produce any adverse effects. These persons call themselves "electromagnetic hypersensitivity individuals" And complain about experiencing various types of non-specific symptoms, including dermatological, neurological and vegetative. In the present paper, the problem of electromagnetic hypersensitivity phenomenon is discussed based on the recently published literature.

  20. [Food hypersensitivity in children].

    PubMed

    Kolacek, Sanja

    2011-01-01

    Food hypersensitivity affects children and adults with an increasing prevalence, and is therefore an important public health problem in the majority of developed countries. Moreover, self-reported reactions to food are of several times higher prevalence, compared to hypersensitivity diagnosed following well established evidence-based diagnostic guidelines. In children, allergic food reactions are more common compared to non-allergic food hypersensitivity reactions, and 90% of them are caused with only 8 food allergens: cow's milk, soya, egg, fish, shellfish, peanut, tree-nuts and gluten. Diagnosis should be based on challenge tests with the potentially offending food allergens. Concerning other, more conservative diagnostic procedures, negative serology and negative skin-prick tests can exclude IgE-mediated food allergy, but positive tests, due to high rate of false positive reactions are not sufficient for diagnosis. Strict dietary avoidance of incriminated allergens is the only well established management strategy. However, this should be applied only if food allergy is well documented - following the exposition tests. Introducing elimination diet in a paediatric population, particularly with the elimination of multiple foods, could cause inappropriate growth and disturb organ maturation. Concerning allergy prevention, avoidance of allergens is not efficacious either during pregnancy and lactation or weaning period, and is therefore, not recommended neither as a population preventive measure, nor in children at risk.

  1. The IL-8 release from cultured human keratinocytes, mediated by antibodies to bullous pemphigoid autoantigen 180, is inhibited by dapsone

    PubMed Central

    Schmidt, E; Reimer, S; Kruse, N; Bröcker, E-B; Zillikens, D

    2001-01-01

    Bullous pemphigoid (BP) is a subepidermal blistering disease associated with autoantibodies to the hemidesmosomal 180 kD BP autoantigen (BP180). However, the binding of autoantibodies to BP180 alone is not sufficient for blister formation in this disease and the infiltration of neutrophils into the skin is required. Dapsone and nicotinamide inhibit neutrophil chemotaxis and are used effectively in treating BP. IL-8 is a known chemoattractant for neutrophils and has been implicated in the inflammatory process of both human and experimental murine BP. We have recently shown that antibodies to BP180 mediate a dose and time-dependent release of IL-6 and IL-8 from cultured normal human epidermal keratinocytes (NHEK). In the present study, we addressed the question whether dapsone or nicotinamide influence this cytokine release. We demonstrate that dapsone, but not nicotinamide, in its pharmacological range, inhibits the IL-8, but not the IL-6 release from NHEK, induced by anti-BP180 IgG, in a dose-dependent fashion as detected by ELISA. IL-8 mRNA levels, as determined by RT-PCR, were the same in cells treated with BP IgG alone compared to cells treated with BP IgG plus dapsone. This observation suggests that dapsone inhibits the BP IgG-induced IL-8 release from cultured NHEK by mechanisms at the post-transcriptional level. Our findings contribute to the understanding how dapsone leads to a reduced influx of neutrophils into BP lesions and, finally, to the cessation of blister formation in this disease. PMID:11359455

  2. Acute dapsone poisoning in a 3-year-old child: Case report with review of literature

    PubMed Central

    Sunilkumar, Menon Narayanankutty; Ajith, Thekkuttuparambil Ananthanarayanan; Parvathy, Vadakut Krishnan

    2015-01-01

    Dapsone (DDS-diamino diphenyl sulphone) is a sulfone antibiotic being used for a variety of clinical conditions. Poisoning in children by DDS is rarely reported. Poisoning in acute cases will be frequently unrecognized due to relative lack of severe signs and symptoms. Methemoglobinemia is the major life-threatening situation associated with poisoning of DDS. Hence, any delay for medical attention can lead to increased rate of mortality. In this case, we describe acute DDS poisoning in a 3-year-old child and the successful management using intravenous methylene blue. PMID:26488029

  3. Dapsone in the treatment of pemphigus vulgaris: adverse effects and its importance as a corticosteroid sparing agent*

    PubMed Central

    Quaresma, Maria Victória; Bernardes Filho, Fred; Hezel, Janaína; Peretti, Murilo Calvo; Kac, Bernard Kawa; Azulay-Abulafia, Luna

    2015-01-01

    Pemphigus vulgaris is an autoimmune disease characterized by suprabasal blisters with acantholysis, which has a fatal course in a large number of untreated patients. Systemic corticosteroid therapy is considered first-line therapy. Adjuvant treatment with the goal of sparing corticosteroids include, among others, dapsone. This drug is not without side effects and its use requires clinical and laboratory control. We present a patient with PV initially managed with suboptimal dose of prednisone, evolving into drug-induced hepatitis after introduction of dapsone. PMID:26312673

  4. Management Strategies for Clopidogrel Hypersensitivity.

    PubMed

    Beavers, Craig J; Carris, Nicolas W; Ruf, Kathryn M

    2015-06-01

    Clopidogrel is a cornerstone of dual antiplatelet therapy. Hypersensitivity reactions potentially limit the use of this treatment and present a significant clinical challenge. The authors have developed recommendations for the management of clopidogrel hypersensitivity with consideration for the etiology, pathophysiology, and critical evaluation of potential management strategies. The clopidogrel hypersensitivity reaction is complex in mechanism and presents generally around day 5 of treatment. Generalized reactions are most common, but the reaction may also be localized or systemic. Screening patients for hypersensitivity is not always possible because the type IV delayed reaction is not detected reliably by conventional skin prick, intradermal challenge, or patch testing. Proposed strategies for management of clopidogrel hypersensitivity include treatment of the reaction with corticosteroids, clopidogrel desensitization, substituting an alternative P2Y12 inhibitor, or clopidogrel avoidance. The safety, efficacy, and cost of each potential strategy must be considered when managing a patient with clopidogrel hypersensitivity.

  5. [Nonallergic hypersensitivity to environmental factors].

    PubMed

    Rakhmanin, Iu A; Fedoseeva, V N; Makovetskaia, A K; Fedoskova, T G

    2013-01-01

    The prevalence and severity of manifestations of non-allergic hypersensitivity to chemical environmental factors pose the question about the need to study the mechanisms of its formation in population. It should be borne in mind that, in the absence of immunological mechanisms of formation of the mentioned state, the term "chemical sensitization" must be replaced by the term "non-allergic hypersensitivity." The investigation of this problem should permit to reduce the risk of formation of different types of hypersensitivity in population.

  6. A case of methemoglobinemia after ingestion of an aphrodisiac, later proven as dapsone.

    PubMed

    Lee, S W; Lee, J Y; Lee, K J; Kim, M; Kim, M J

    1999-08-01

    Methemoglobin (MetHb) is an oxidation product of hemoglobin in which the sixth coordination position of ferric iron is bound to a water molecule or to a hydroxyl group. The most common cause of acquired MetHb-emia is accidental poisoning which usually is the result of ingestion of water containing nitrates or food containing nitrite, and sometimes the inhalation or ingestion of butyl or amyl nitrite used as an aphrodisiac. We herein report a case of MetHb-emia after ingestion of an aphrodisiac, later identified as dapsone by gas chromatograph/mass selective detector (GC/MSD). A 24-year old male was admitted due to cyanosis after ingestion of a drug purchased as an aphrodisiac. On arterial blood gas analysis, pH was 7.32, PaCO2 26.8 mmHg, PaO2 75.6 mmHg, and bicarbonate 13.9 mmol/L. Initial pulse oxymetry was 89%. With 3 liter of nasal oxygen supplement, oxygen saturation was increased to 90-92%, but cyanosis did not disappear. Despite continuous supplement of oxygen, cyanosis was not improved. On the fifth hospital day, MetHb was 24.9%. Methylene blue was administered (2 mg/kg intravenously) and the patient rapidly improved. We proved the composition of aphrodisiac as dapsone by the method of GC/MSD.

  7. Systemic Lupus Erythematosus and Bullous Pemphigoid with Dramatic Response to Dapsone

    PubMed Central

    Maggio, Maria Cristina; Corsello, Giovanni; Prinzi, Eugenia; Cimaz, Rolando

    2017-01-01

    Patient: Female, 11 Final Diagnosis: Bullous pemphigoid in systemic lupus erythematosus Symptoms: Bullous lupus • photosensitive rash • synovitis Medication:— Clinical Procedure: Pharmacological treatment Specialty: Rheumatology Objective: Unusual clinical course Background: Bullous pemphigoid is an autoimmune blistering disease, with relapses, isolated or associated with other autoimmune diseases such as systemic lupus erythematosus (SLE). Joint manifestations rapidly respond to small or moderate doses of corticosteroids, whereas skin manifestations usually respond to antimalarial drugs. Case Report: We describe the clinical case of an 11-year-old girl with SLE. She showed bullous skin lesions with arthralgia, mild proteinuria, resolved after steroid treatment. At the tapering of her prednisone dose, the patient had new skin lesions requiring an increased dose of prednisone. She started dapsone at the dosage of 1 mg/kg/day, maintaining low dose prednisone; this treatment was successfully followed by the dramatic disappearance of skin lesions and limb pain. Conclusions: Bullous skin lesions can represent the first clinical presentation of pediatric SLE and could influence the treatment and the outcome of these patients. This case showed an atypical course as both skin manifestations and arthritis promptly and persistently resolved with dapsone without the use of high-dose glucocorticoids. Only a few cases of patients with SLE associated with bullous pemphigoid have been reported in the literature, and very few in the pediatric population. PMID:28352068

  8. Detection of haptenated proteins in organotypic human skin explant cultures exposed to dapsone.

    PubMed

    Roychowdhury, Sanjoy; Cram, Albert E; Aly, Al; Svensson, Craig K

    2007-09-01

    Bioactivation of parent drug to reactive metabolite(s) followed by protein haptenation has been suggested to be a critical step in the elicitation of cutaneous drug reactions. Although liver is believed to be the primary organ of drug bioactivation quantitatively, other organs including skin may also metabolize drugs. Cultured human epidermal keratinocytes and dermal fibroblasts have been shown to be capable of bioactivating sulfonamides and sulfones, giving rise to haptenated proteins. It is, however, unclear whether metabolic events in these isolated cells reflect bioactivation in vivo. Hence, split-thickness human skin explants were exposed to dapsone (DDS) or its arylhydroxylamine metabolite (dapsone hydroxylamine, D-NOH) and probed for protein haptenation. DDS and D-NOH were applied either epicutaneously or mixed in the medium (to mimic its entry into skin from the systemic circulation). DDS-protein adducts were readily detected in skin explants exposed to either DDS or D-NOH. Adducts were detected mainly in the upper epidermal region in response to epicutaneous application, whereas adducts were formed all over the explants when DDS/D-NOH were mixed in the culture medium. In addition, adducts were visible in HLA-DR+ cells, indicating their presence in the dendritic cell population in the skin. Our results demonstrate the ability of intact human skin to bioactivate DDS leading to protein haptenation.

  9. [Study of rifampin and dapsone resistance in three patients with recurring leprosy].

    PubMed

    Hernández, Elkin; Cardona-Castro, Nora; Rodríguez, Gerzaín; Villegas, Sonia; Beltrán, Camilo; Kimura, Miyako; Vissa, Varalakshmi D; Gómez, Yenny

    2008-02-01

    To detect the presence of rifampin- and dapsone-resistant strains of Mycobacterium leprae in three patients with recurring leprosy and clinically-suspected antimicrobial resistance through molecular techniques. A retrospective, descriptive study was conducted of three multibacillary patients at the "Agua de Dios" Sanitarium in Cundinamarca, Colombia, that presented leprosy relapses that were documented by medical history, bacilloscopy, and biopsy. Biopsies were taken of the skin lesions and the bacteria were subject to DNA extraction and purification. Regions of the rpoB and folP1 genes associated with antimicrobial resistance were amplified and subjected to touch-down polymerase chain reaction and the amplified products were sequenced using the Sanger method. A punctual mutation was identified in nucleotide 1367 of the rpoB gene in two of the samples studied. This mutation was not found in the folP1 gene of any of the three patients. The mutation identified showed strains of rifampin-resistant M. leprae in two of the three patients with recurring leprosy. Mutations that indicate dapsone-resistance were not detected in any of the three patients.

  10. Use of dapsone in the treatment of Pneumocystis carinii pneumonia in a foal.

    PubMed

    Clark-Price, Stuart C; Cox, Judy H; Bartoe, Joshua T; Davis, Elizabeth G

    2004-02-01

    A 6-month-old male Quarter Horse was evaluated for chronic respiratory tract disease. Diagnostic investigations revealed pulmonary inflammation; Pneumocystis carinii was detected within macrophages. Lymphocyte subpopulation phenotyping and immunoglobulin concentration analysis were performed and results suggested immune suppression. Trimethoprim-sulfamethoxazole administration was initiated; the colt was discharged but was reexamined 8 days later because of profuse diarrhea and endotoxemia. Bacterial culture of feces recovered Salmonella spp resistant to trimethoprim-sulfamethoxazole, and a diagnosis of antimicrobial-associated colitis was made. Bilateral fibrinous hypopyon developed and was treated with topical medication and intracameral injections of human recombinant tissue plasminogen activator. Dapsone (3 mg/kg [1.4 mg/lb], PO, q 24 h; dose extrapolated from human data) was administered for treatment of P carinii pneumonia (56-day treatment period). The colt recovered from the pneumonia and diarrhea. Dapsone may be a useful adjunct to traditional treatment for P carinii pneumonia in horses or as a sole medication for horses that cannot tolerate other treatments.

  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. Longitudinal analysis of antibody profiles against plakins in severe drug eruptions: emphasis on correlation with tissue damage in drug-induced hypersensitivity syndrome and drug reaction with eosinophilia and systemic symptoms.

    PubMed

    Takehara, A; Aoyama, Y; Kurosawa, M; Shirafuji, Y; Umemura, H; Kamiya, K; Ushigome, Y; Kano, Y; Shiohara, T; Iwatsuki, K

    2016-11-01

    The evidence for severe drug eruption as a trigger for autoimmune disease has recently increased. No information is available on how tissue damage in severe drug eruptions can induce autoimmune responses. To investigate whether the generation of autoantibodies (autoAbs) against plakin family proteins could be the cause or result of tissue damage in patients with severe drug eruptions and whether the generation of autoAbs could be prevented by systemic corticosteroids during the acute stage. We retrospectively analysed alterations of serum levels of autoAbs against plakin family proteins in patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) during the acute stage and long after resolution over a period of more than 10 years. AutoAbs against plakin family proteins were detected in patients with either SJS/TEN or DiHS/DRESS regardless of the epidermal damage in the acute stage, and were sustained even long after resolution in DiHS/DRESS, indicating that those autoAbs are neither the cause nor the consequence of epidermal damage, at least in DiHS/DRESS. Severe liver damage and noncorticosteroid therapy during the early and acute stages of DiHS/DRESS were associated with the subsequent generation of these autoAbs. These autoAbs are neither necessarily the cause nor the result of epidermal damage in DiHS/DRESS, because the presence of these autoAbs was not restricted to patients with SJS/TEN but was also observed in those with DiHS/DRESS, which is characterized by lack of epidermal damage. Severe liver damage and/or immune responses that could be prevented by corticosteroids in the acute stage of DiHS/DRESS are among the causal factors contributing to the generation of autoimmune responses. © 2016 British Association of Dermatologists.

  13. Chapter 28: Classification of hypersensitivity reactions.

    PubMed

    Uzzaman, Ashraf; Cho, Seong H

    2012-01-01

    The original Gell and Coomb's classification categorizes hypersensitivity reactions into four subtypes according to the type of immune response and the effector mechanism responsible for cell and tissue injury: type I, immediate or IgE mediated; type II, cytotoxic or IgG/IgM mediated; type III, IgG/IgM immune complex mediated; and type IV, delayed-type hypersensitivity or T-cell mediated. The classification has been improved so that type IIa is the former type II and type IIb is antibody-mediated cell stimulating (Graves Disease and the "autoimmune" type of chronic idiopathic urticaria). Type IV has four major categories: type IVa is CD4(+)Th1 lymphocyte mediated with activation of macrophages (granuloma formation and type I diabetes mellitus); type IVb is CD4(+)Th2 lymphocyte mediated with eosinophilic involvement (persistent asthma and allergic rhinitis); type IVc is cytotoxic CD8(+) T lymphocyte with involvement of perforin-granzme B in apoptosis (Stevens-Johnson syndrome and toxic epidermal necrolysis); type IVd is T-lymphocyte-driven neutrophilic inflammation (pustular psoriasis and acute generalized exanthematous pustulosis). Some diseases have multiple types of immunologic hypersensitivity.

  14. Aczone, a topical gel formulation of the antibacterial, anti-inflammatory dapsone for the treatment of acne.

    PubMed

    Scheinfeld, Noah

    2009-05-01

    Allergen Inc has launched Aczone, a topical gel formulation of the antibacterial, anti-inflammatory agent dapsone, for the potential treatment of acne vulgaris. Oral dapsone has demonstrated efficacy in acne, but was associated with severe side effects such as anemia, which was particularly serious in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Aczone was developed to overcome this limitation, and is formulated using solvent-microparticle technology for improved absorption and action and for fewer side effects. In a phase I clinical trial, systemic exposure to dapsone was 126-fold lower following treatment with Aczone compared with oral dapsone. Aczone significantly reduced lesion counts in patients with acne in phase III trials, and was particularly effective in reducing inflammatory lesions. In a phase IV trial, Aczone was safely applied to patients with G6PD deficiency without inducing anemia. Phase IV trials in patients with acne were ongoing at the time of publication to assess safety and to compare Aczone monotherapy with combinations of Aczone and other anti-acne therapeutics. At the time of publication, Allergen was also developing Aczone for the treatment of rosacea; the drug was undergoing phase II trials for this indication. Aczone appears to be a novel promising anti-acne therapeutic option, particularly for patients with inflammatory acne.

  15. Functional dyspepsia: The role of visceral hypersensitivity in its pathogenesis

    PubMed Central

    Keohane, John; Quigley, Eamonn M M

    2006-01-01

    Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD. PMID:16718751

  16. Functional dyspepsia: the role of visceral hypersensitivity in its pathogenesis.

    PubMed

    Keohane, John; Quigley, Eamonn M M

    2006-05-07

    Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.

  17. Gut pain & visceral hypersensitivity

    PubMed Central

    Aziz, Qasim

    2013-01-01

    Visceral pain is a highly complex entity whose experience is variable in health and disease. It can occur in patients with organic disease and also in those without any readily identifiable structural or biochemical abnormality such as in the functional gastrointestinal disorders (FGID). Despite considerable progress in our understanding of the culpable underlying mechanisms significant knowledge gaps remain, representing a significant unmet need in gastroenterology. A key, but not universal, pathological feature is that patients with FGID often display heightened sensitivity to experimental gut stimulation, termed visceral hypersensitivity. A plethora of factors have been proposed to account for this epiphenomenon including peripheral sensitization, central sensitization, aberrant central processing, genetic, psychological and abnormalities within the stress responsive systems. Further research is needed, bringing together complementary research themes from a diverse array of academic disciplines ranging from gastroenterology to nociceptive physiology to functional neuro-imaging, to address this unmet need. PMID:26516496

  18. Hypersensitivity reactions to fluoroquinolones.

    PubMed

    Scherer, Kathrin; Bircher, Andreas J

    2005-01-01

    Fluoroquinolone antibiotics cause immediate and delayed hypersensitivity reactions, and may also affect internal organs and circulating blood cells. The underlying pathomechanisms are only partly understood. The extent of cross-reactivity among different quinolones depends on the type of clinical manifestation and its underlying mechanism. Despite recent advances, reliable diagnostic tests are still lacking. Recent studies have shown quinolone-specific IgE in vitro in more than 50% of patients with immediate-type reactions and a considerable cross-reactivity with related compounds. In maculopapular drug exanthems from ciprofloxacin, specific T-cell clones were identified, and cross-reactivity to related compounds was detected in approximately 50% of the clones. From re-exposure studies in patients with exanthems, cross-reactivity appears to be lower. Cellular tests such as lymphocyte transformation tests are currently not very useful. For prick and intradermal skin tests, widely divergent nonirritant test concentrations have been recommended. Desensitization may be possible in selected patients.

  19. Insect and arachnid hypersensitivity.

    PubMed

    Bevier, D E

    1999-11-01

    Insect hypersensitivity reactions can have a large number of clinical presentations. The majority of reactions are pruritic and involve the short- or sparsely haired areas of the body. Most are associated with eosinophilic infiltration into the skin, often in a perivascular pattern. The diagnosis may be based on compatible clinical signs and improvement with aggressive insect control and, in some cases, confirmation via provocative exposure. Intradermal, prick, or serum testing for allergen-specific IgE can be used to document the presence of reaginic antibodies against insect allergens. Treatments include avoidance, aggressive insect control, and symptomatic support; in some cases, immunotherapy may be useful in decreasing the severity of clinical reactions to insects.

  20. Food hypersensitivity by inhalation

    PubMed Central

    Ramirez, Daniel A; Bahna, Sami L

    2009-01-01

    Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization. PMID:19232116

  1. Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR).

    PubMed

    Kano, Yoko; Tohyama, Mikiko; Aihara, Michiko; Matsukura, Setsuko; Watanabe, Hideaki; Sueki, Hirohiko; Iijima, Masafumi; Morita, Eishin; Niihara, Hiroyuki; Asada, Hideo; Kabashima, Kenji; Azukizawa, Hiroaki; Hashizume, Hideo; Nagao, Keisuke; Takahashi, Hayato; Abe, Riichiro; Sotozono, Chie; Kurosawa, Michiko; Aoyama, Yumi; Chu, Chia-Yu; Chung, Wen-Hung; Shiohara, Tetsuo

    2015-03-01

    Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse drug reaction caused by specific drug. It is characterized by visceral organ involvement and reactivation of various human herpesviruses. Although sporadic reports have documented certain conditions that appear after the resolution of DIHS/DRESS, little information is available on sequelae after resolution of DIHS/DRESS in a large patient population. The Asian Research Committee on Severe Cutaneous Adverse Reactions, comprised of doctors from Japan and Taiwan, conducted a survey on sequelae and deterioration of the underlying disease in patients with DIHS/DRESS. This was achieved by directly interviewing patients who had been followed-up by experts or through a questionnaire mailed to patients. Questions were asked about new onset cardiovascular disease, collagen disease or autoimmune disease, gastrointestinal disease, renal disease, respiratory disease, neoplasms, and other diseases such as herpes zoster and diabetes mellitus, as well as deterioration of the underlying disease. A total of 145 patients were analyzed in this study. The following newly developed diseases after recovery from DIHS/DRESS were observed: Graves' disease (n = 2), Hashimoto's disease (n = 3), painless thyroiditis (n = 2), fulminant type 1 diabetes mellitus (n = 5), and infectious diseases (n = 7). Several DIHS/DRESS patients with pre-existing renal dysfunction required lifelong hemodialysis. DIHS/DRESS is a condition that increases the risk of new onset of disease. Long-term observation of DIHS/DRESS can provide an opportunity to investigate substantial diseases from onset to the full-blown stage. Patients with DIHS/DRESS require careful long-term follow-up. © 2015 Japanese Dermatological Association.

  2. Early behavioural changes in scrapie-affected mice and the influence of dapsone.

    PubMed

    Guenther, K; Deacon, R M; Perry, V H; Rawlins, J N

    2001-07-01

    Behavioural testing can reveal effects in scrapie-infected mice long before overt clinical signs appear (Betmouni et al., 1999, Psychobiology, 27, 63-71). These effects may be partly attributable to an early, atypical inflammatory response in the brain (Betmouni et al., 1996, Neuroscience, 74, 1-5). The present study replicated and extended these findings, and examined the effect of chronic treatment with dapsone. This anti-inflammatory compound has been reported to delay disease onset in a rat model of Creutzfeldt-Jakob disease (Manuelidis et al., 1998, Lancet, 352, 456). Although the doses used in the present study were higher than those of Manuelidis et al. (1998), no attenuation of the disease was seen in either behavioural or subsequent histological tests. Burrowing, i.e. displacing food pellets from a tube in the home cage, decreased from around week 12 in scrapie-infected mice, as did consumption of palatable glucose solution. Concurrently, ambulation in an open field increased, as did rearing at around week 17. Spontaneous alternation was impaired around this time. Around 18 weeks, motor performance on an inverted screen, horizontal bar, rotating rod and static rods decreased. Nest construction was impaired at 20 weeks. Overt clinical signs (reduction in mobility, hunched posture, poor coat condition, bladder enlargement) only occurred after week 20, when the mice were prepared for histology. The ME7 scrapie-infected mice thus showed a characteristic complex of neurological and behavioural changes during the course of the disease that were not ameliorated by dapsone. These changes appeared well before clinical signs were prominent.

  3. Clinical Oxidative Stress during Leprosy Multidrug Therapy: Impact of Dapsone Oxidation

    PubMed Central

    Schalcher, Taysa Ribeiro; Borges, Rosivaldo S.; Coleman, Michael D.; Batista Júnior, João; Salgado, Claudio G.; Vieira, Jose Luiz F.; Romão, Pedro R. T.; Oliveira, Fabio R.; Monteiro, Marta Chagas

    2014-01-01

    This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 µg/mL) and paucibacillary (0.662±0.123 µg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDT-supervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software. PMID:24465659

  4. Efficacy, Safety, and Dermal Tolerability of Dapsone Gel, 7.5% in Patients with Moderate Acne Vulgaris: A Pooled Analysis of Two Phase 3 Trials

    PubMed Central

    Kircik, Leon; McMichael, Amy; Cook-Bolden, Fran E.; Tyring, Stephen K.; Berk, David R.; Chang-Lin, Joan-En; Lin, Vince; Kaoukhov, Alexandre

    2016-01-01

    Objective: Assess efficacy and safety of once-daily topical dapsone gel, 7.5% compared with vehicle for treating acne vulgaris (acne). Design: A pooled analysis of data from two identically designed, randomized, double-blind, vehicle-controlled, multicenter, 12-week clinical trials. Setting: Study sites in the United States and Canada. Participants: overall, 4,340 patients were randomized 1:1 to dapsone and vehicle. Criteria included age 12 years or older with acne diagnosis, 20 to 50 facial inflammatory lesions (papules and pustules), 30 to 100 facial noninflammatory lesions (open and closed comedones), and acne grade of 3 (moderate) on the Global Acne Assessment Score scale. Measurements: Efficacy assessments included the Global Acne Assessment Score success rate (proportion of patients with Global Acne Assessment Score of 0 [none] or 1 [minimal]) and percentage change from baseline in inflammatory and noninflammatory lesions at Week 12. Results: Global Acne Assessment Score success rates were 29.8 percent and 21.1 percent for patients who received dapsone gel, 7.5% and vehicle, respectively (p<0.001). Patients receiving dapsone gel, 7.5% had greater percentage change in lesion counts than patients receiving vehicle (inflammatory lesions: -54.6% vs. -48.1%; p<0.001; -45.1 %; noninflammatory lesions: -39.4%; p<0.001). Most adverse events were mild to moderate in severity. Mean dermal tolerability scores for stinging/burning, dryness, scaling, and erythema were similarly low with dapsone gel, 7.5% and vehicle. Conclusion: Dapsone gel, 7.5%, with a 50-percent greater dapsone concentration than twice-daily dapsone gel, 5% formulation, is applied topically once daily for acne, is effective, safe, and well-tolerated over 12 weeks, and has local tolerability similar to that of vehicle. www.clinicaltrials.gov identifiers: NCT01974141 and NCT01974323 PMID:27847545

  5. Genetic and ethnic risk factors associated with drug hypersensitivity.

    PubMed

    Kim, Seung-Hyun; Ye, Young-Min; Palikhe, Nami Shrestha; Kim, Jeong-Eun; Park, Hae-Sim

    2010-08-01

    The purpose of this article is to review the recent findings of studies reporting on the genetic and ethnic factors associated with hypersensitivity reactions to common drugs such as acetyl salicylic acid/NSAIDs, antibiotics, antituberculus medications, and other drugs including carbamazepine (CBZ), abacarvir, and allopurinol that can cause severe hypersensitivity reactions. Aspirin hypersensitivity has recently been associated with a variety of genetic polymorphisms associated with leukotriene overproduction, eosinophil infiltration, and histamine-related genes. Recently, beta-lactam antibiotic hypersensitivity has been reported to be associated with interleukin (IL)-4 and IL-13 receptors in Italian, Chinese, and French populations. Moreover, a significant association of CYP2E1 in the Chinese, NAT2 in Koreans and glutathione S-transferase genotypes in Caucasians has been reported with antituberculus drug-induced hepatitis. The association of the HLA-B*1502 allele with CBZ-induced Stevens-Johnson syndrome in Asian population has also recently been observed. Aspirin hypersensitivity has been associated with various genetic polymorphisms. Human leukocyte antigen (HLA)-related markers and a variety of genetic polymorphisms of leukotriene-related genes, eosinophil-related genes, and genes associated with immune function have been described according to ethnicity. The genetic mechanisms of antibiotic hypersensitivity have been reported in Italian, French, and Chinese populations in addition to antibiotics-induced cutaneous reactions in the Korean population. Most prior genetic studies on antituberculus drug-induced hepatitis have focused on a few drug-metabolizing enzymes such as cytochrome P450 and N-acetyltransferase 2. HLA-related markers associated with CBZ, lamotrigine, and abacavir-induced severe hypersensitivity reactions have been described.

  6. Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.

    PubMed

    Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H

    2015-12-01

    Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity.

  7. RECQL4-deficient cells are hypersensitive to oxidative stress/damage: Insights for osteosarcoma prevalence and heterogeneity in Rothmund-Thomson syndrome

    SciTech Connect

    Werner, Sean R.; Prahalad, Agasanur K. . E-mail: aprahala@iupui.edu; Yang Jieping; Hock, Janet M.

    2006-06-23

    Rothmund-Thomson syndrome (RTS) is a heterogeneous disease, associated with increased prevalence of osteosarcoma in very young patients with a mutated RECQL4 gene. In this study, we tested the ability of RECQL4 deficient fibroblasts, derived from a RTS patient to recover from hydrogen peroxide (H{sub 2}O{sub 2})-induced oxidative stress/damage. Immunoperoxidase staining for 8-oxo-deoxyguanosine (8-oxo-dG) formation in RTS and normal human fibroblasts were compared to assess DNA damage. We determined DNA synthesis, cell growth, cell cycle distribution, and viability in RTS and normal human fibroblasts before and after H{sub 2}O{sub 2} treatment. H{sub 2}O{sub 2} induces 8-oxo-dG formation in both RTS and normal fibroblasts. In normal human fibroblasts, RECQL4 was predominantly localized to cytoplasm; nuclear translocation and foci formation occurred in response to oxidant stimulation. After recovery from oxidant exposure, viable RTS fibroblasts showed irreversible growth arrest compared to normal fibroblasts. DNA synthesis decreased significantly in treated RTS cells, with concomitant reduction of cells in the S-phase. These results suggest that enhanced oxidant sensitivity in RECQL4 deficient fibroblasts derived from RTS patients could be attributed to abnormal DNA metabolism and proliferation failure. The ramifications of these findings on osteosarcoma prevalence and heterogeneity in RTS are discussed.

  8. Sulfite hypersensitivity. A critical review

    SciTech Connect

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

    1987-01-01

    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 review 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.

  9. Modulation of enteric neurons by interleukin-6 and corticotropin-releasing factor contributes to visceral hypersensitivity and altered colonic motility in a rat model of irritable bowel syndrome

    PubMed Central

    Buckley, Maria M; O'Halloran, Ken D; Rae, Mark G; Dinan, Timothy G; O'Malley, Dervla

    2014-01-01

    Abstract The search for effective therapeutic strategies for irritable bowel syndrome (IBS) is hampered by an incomplete understanding of its underlying pathophysiology. Stress and altered plasma cytokine profiles indicative of immune activation are characteristic of the disorder. The neuromodulatory effects of interleukin-6 (IL-6) and corticotropin-releasing factor receptor (CRFR) 1 in visceral pain and stress-induced defecation in the Wistar Kyoto (WKY) rat model of IBS were investigated. Sprague Dawley and WKY rats were administered anti-IL-6 receptor antibodies (xIL-6R, 0.5 mg kg−1 i.p) with or without the CRFR1 antagonist antalarmin (10 mg kg−1 i.p). Post-intervention, the pain threshold to colorectal distension and stress-induced faecal output were compared and changes in colonic mucosal protein expression were investigated. The neuro-stimulatory effects of IBS plasma on the myenteric plexus is mediated by IL-6, IL-8 and CRF. The stimulatory effects of these soluble factors on myenteric neuron excitability and colonic contractility were additive. Moreover, inhibition of IL-6 and CRF1 receptors in vivo in the WKY IBS rat model normalized stress-induced defecation (P < 0.01) and visceral pain sensitivity (P < 0.001) with associated changes in protein expression of the tight junction proteins occludin and claudin 2, the visceral pain-associated T-type calcium channel CaV3.2 and intracellular signalling molecules STAT3, SOCS3 and ERK1/2. These studies demonstrate the additive effects of immune and stress factors on myenteric neuronal excitability. Moreover, combined targeting of peripheral IL-6 and CRF1 receptors is effective in alleviating IBS-like symptoms in the WKY rat. Thus, crosstalk between stress and immune factors during IBS flares may underlie symptom exacerbation. PMID:25260633

  10. Jaundice induced by stanozolol hypersensitivity

    PubMed Central

    Slater, S. D.; Davidson, J. F.; Patrick, R. S.

    1976-01-01

    A 66-year-old male patient developed jaundice after 7 months of treatment with the anabolic steroid, stanozolol. When the drug was withdrawn he made a full and uneventful recovery. A liver biopsy showed the histology of a hypersensitivity reaction. This is believed to be the first time jaundice has been recorded with stanozolol therapy and the first time a hypersensitivity-type jaundice has been recorded with any anabolic steroid. ImagesFig. 2Fig. 3 PMID:1273017

  11. Lymphocyte transformation studies in drug hypersensitivity

    PubMed Central

    Warrington, R.J.; Tse, K.S.

    1979-01-01

    In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents. Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects. For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test. It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs. PMID:445303

  12. Lymphocyte transformation studies in drug hypersensitivity.

    PubMed

    Warrington, R J; Tse, K S

    1979-05-05

    In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents.Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects.For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test.It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs.

  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. Hypersensitivity to fluoroquinolones

    PubMed Central

    Fernández, Tahia D.; Ariza, Adriana; Palomares, Francisca; Montañez, María I.; Salas, María; Martín-Serrano, Angela; Fernández, Rubén; Ruiz, Arturo; Blanca, Miguel; Mayorga, Cristobalina; Torres, María J.

    2016-01-01

    Abstract Although fluoroquinolones (FQs) are generally well-tolerated antibiotics, increasing numbers of hypersensitivity reactions have been reported. These can be evaluated in vitro by basophil activation tests (BATs); however, sensitivity is not optimal. Many factors could influence sensitivity such as basophil activation markers. The objective of this study was to evaluate the influence of 2 different activations markers, CD63 and CD203c, on the sensitivity of BAT to FQ. We studied 17 patients with immediate allergic reactions to FQ. BAT was performed with moxifloxacin and ciprofloxacin using CD193 (CCR3) for basophil selection and CD203c or CD63 as activation markers. Stimulation with ciprofloxacin induced a significantly higher expression of CD63 in ciprofloxacin-allergic patients compared to moxifloxacin-allergic patients (P = 0.002). In patients allergic to moxifloxacin with anaphylactic shock, we have observed an increase in the percentage of cells that upregulate CD203c, whereas patients with anaphylaxis preferentially upregulate CD63. The best sensitivity–specificity was obtained using a cutoff of 3 and the culprit FQ, using CD203c for moxifloxacin-allergic patients (sensitivity = 36.4%; specificity = 94.4%), and CD63 for ciprofloxacin-allergic patients (sensitivity = 83.3%; specificity = 88.9%). A negative correlation was found between the upregulation of CD63 and CD203c and the time interval between the reaction occurrence and the performance of the test (Spearman r = −0.446; P < 0.001 for CD63 and Spearman r = −0.386; P < 0.001 for CD203c). The performance of BAT for FQ allergy must be optimized for each drug, taking into account possible differences in the stimulation mechanism that leads to the upregulation of different activation markers. PMID:27281069

  15. Allopurinol hypersensitivity reactions: desensitization strategies and new therapeutic alternative molecules.

    PubMed

    Calogiuri, Gianfranco; Nettis, Eustachio; Di Leo, Elisabetta; Foti, Caterina; Ferrannini, Antonio; Butani, Lavjay

    2013-02-01

    Allopurinol, an analog of hypoxanthine has been worldwide used for the treatment of hyperuricemia and gout for over 40 years. Unfortunately some patients assuming this medication have developed hypersensitivity reactions ranging from mild cutaneous eruption to more severe clinical manifestations such as allopurinol hypersensitivity syndrome or Steven-Johnson syndrome and lethal toxic epidermal necrolysis. Various strategies of slow desensitization have been elaborated to reintroduce allopurinol in a part of these patients, mainly patients affected by mild skin reactions as fixed drug eruption or exanthema. However, several new uricosuric therapies have been recently introduced. Actually drugs as recombinant urate oxidase and febuxostat are under post-marketing surveillance to control potential adverse effects related to their immunogenicity even.

  16. Successful treatment of Miescher's cheilitis in Melkersson-Rosenthal syndrome with betamethasone injections and doxycycline

    PubMed Central

    Oudrhiri, Lamia; Chiheb, Soumiya; Marnissi, Farida; Zamiati, Soumaya; Benchikhi, Hakima

    2012-01-01

    We report a case of a 19-year-old girl who presented with 5-year history of swelling of upper lip and fissured tongue treated with dapsone then oral steroids without any improvement. Clinical examination found peripheral facial nerve paralysis and Labial mucosa biopsy showed non-necrotizing giganto-epithelioid granuloma. Diagnosis of Melkersson-Rosenthal syndrome was retaind because of association of cheilitis, lingua plicata and facial paralysis. Given the failure of dapsone and oral steroid we suggested an association of betamethasone injection and doxycycline. Gradual and permanent reduction of the upper lip volume was observed. One year follow up objectified no reactivation of cheilitis. PMID:23397029

  17. Antibiotic hypersensitivity reactions and approaches to desensitization.

    PubMed

    Legendre, Davey P; Muzny, Christina A; Marshall, Gailen D; Swiatlo, Edwin

    2014-04-01

    Before initiating antibiotic therapy, drug hypersensitivity is an important consideration, and a common strategy is to avoid giving patients medications when a high likelihood of severe reactions exists. With an increase in antibiotic resistance and a decrease in novel antibiotics, there is greater pressure to consider antibiotics in patients with a history of adverse reactions. The major concerns include IgE-mediated, or type I, reactions, anaphylaxis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Some antibiotics with similar characteristics, such as cephalosporins and penicillins, may be given safely to patients with a certain allergy profile. There is still greater concern when considering antibiotics for patients with reported allergy. Desensitization is a strategy to safely induce drug tolerance to a specific drug to limit the possibility of a type I reaction.

  18. Immunological Mechanisms of Drug Hypersensitivity.

    PubMed

    Meng, Xiaoli; Ariza, Adriana; Waddington, James; Park, Kevin; Naisbitt, Dean

    2016-01-01

    Drug hypersensitivity reactions (DHRs) are adverse drug reactions that may be divided into several categories; namely pharmacologic intolerance, idiosyncratic reactions, pseudo-allergic reactions and allergic reactions. Drug allergic reactions are those DHRs that are mediated by either antibodies or drug-specific T cells. They vary in terms of severity, time-to-onset of clinical manifestations and target organ. Skin is most commonly implicated in drug hypersensitivity reactions; however, it is now apparent that reactions targeting internal organs fall under the definition of drug hypersensitivity. Multiple hypotheses have been proposed to explain the diverse immune mechanisms involved and the heterogeneous clinical presentation. The discovery of human leukocyte antigen (HLA) risk alleles for some DHRs has provided insights in the pathogenesis of these reactions. In this review we summarize immune cells involved in DHRs, discuss the possible immunological mechanisms of DHRs, with an emphasis on the IgE-mediated immediate reactions and T cell-dependent delayed type reactions.

  19. Cockroach hypersensitivity in asthmatic patients.

    PubMed

    Pola, J; Valdivieso, R; Zapata, C; Moneo, I; Duce, F; Larrad, L; Losada, E

    1988-01-01

    Hypersensitivity to cockroach antigen has been recognized as an important cause of perennial allergic rhinitis and asthma. To assess the frequency of cockroach hypersensitivity in our country, 150 asthmatic atopic subjects were studied using skin testing and in vitro assays for cockroach-specific IgE antibodies (Oriental and German cockroaches). Twenty-two of 61 patients who had a positive history of cockroach exposure had positive skin tests, and only 3 of 89 patients who had no history of exposure had positive skin reactions. Of 25 patients with positive skin tests, 23 showed specific IgE antibodies against oriental and German cockroaches using RAST and EIA techniques. In summary, approximately 15% of asthmatic atopics in Madrid area are sensitive to cockroaches (positive skin test + specific IgE antibodies). These results indicate that cockroach hypersensitivity should be considered in every patient with perennial asthma.

  20. Maternal Separation Induced Visceral Hypersensitivity from Childhood to Adulthood.

    PubMed

    Yi, Lisha; Zhang, Haiqin; Sun, Huihui; Zhou, Lu; Chen, Ying; Xuan, Liqian; Jiang, Yuanxi; Xu, Shuchang

    2017-04-30

    Early adverse life events (EALs) are relevant to irritable bowel syndrome in adulthood. Maternal separation (MS), as one of the EALs, has proved to induce visceral hypersensitivity in adult rats. However, the effect of MS on visceral hypersensitvity from the post-weaning period to adulthood remains unknown. One hundred and ten neonatal Sprague-Dawley rats were randomly divided into 2 groups: rats in the MS group were exposed to 3 hours daily MS on postnatal day (PND) 2-14; the normal control (NC) group remained undisturbed. Visceral sensitivity was determined by measuring the visceromotor response to colorectal distention on PND21, 35, and 56. Anxiety-like behaviors were measured by the open field test. Compared with NC rats, MS rats showed significant visceral hypersensitivity from the post-weaning period to adult. The proportion of visceral hypersensitive rats decreased with age from 87.5% to 70.0% in the female MS group and from 90.0% to 66.7% in the male MS group. The relative VMR ratio of MS and NC on PND21 was higher than PND35 and PND56. MS rats showed decreased ability of movement and exploration to the novel environment in the post-weaning period, obesity in the prepubertal period, and more anxiety-like behaviors in adulthood. MS can significantly affect visceral sensitivity and behaviors of rats in different age stages, especially in the post-weaning period. Visceral hypersensitivity of MS rats is more pronounced in the post-weaning period and slightly restored in adults. Thus, visceral hypersensitivity in the post-weaning period might play a more meaningful pathophysiologic role in the formation of adult irritable bowel syndrome.

  1. Maternal Separation Induced Visceral Hypersensitivity from Childhood to Adulthood

    PubMed Central

    Yi, Lisha; Zhang, Haiqin; Sun, Huihui; Zhou, Lu; Chen, Ying; Xuan, Liqian; Jiang, Yuanxi; Xu, Shuchang

    2017-01-01

    Background/Aims Early adverse life events (EALs) are relevant to irritable bowel syndrome in adulthood. Maternal separation (MS), as one of the EALs, has proved to induce visceral hypersensitivity in adult rats. However, the effect of MS on visceral hypersensitvity from the post-weaning period to adulthood remains unknown. Methods One hundred and ten neonatal Sprague-Dawley rats were randomly divided into 2 groups: rats in the MS group were exposed to 3 hours daily MS on postnatal day (PND) 2–14; the normal control (NC) group remained undisturbed. Visceral sensitivity was determined by measuring the visceromotor response to colorectal distention on PND21, 35, and 56. Anxiety-like behaviors were measured by the open field test. Results Compared with NC rats, MS rats showed significant visceral hypersensitivity from the post-weaning period to adult. The proportion of visceral hypersensitive rats decreased with age from 87.5% to 70.0% in the female MS group and from 90.0% to 66.7% in the male MS group. The relative VMR ratio of MS and NC on PND21 was higher than PND35 and PND56. MS rats showed decreased ability of movement and exploration to the novel environment in the post-weaning period, obesity in the prepubertal period, and more anxiety-like behaviors in adulthood. Conclusions MS can significantly affect visceral sensitivity and behaviors of rats in different age stages, especially in the post-weaning period. Visceral hypersensitivity of MS rats is more pronounced in the post-weaning period and slightly restored in adults. Thus, visceral hypersensitivity in the post-weaning period might play a more meaningful pathophysiologic role in the formation of adult irritable bowel syndrome. PMID:28238254

  2. Rituximab-Induced Hypersensitivity Pneumonitis

    PubMed Central

    Tonelli, Adriano R.; Lottenberg, Richard; Allan, Robert W.; Sriram, P.S.

    2009-01-01

    Rituximab is a chimeric anti-CD20 monoclonal antibody used to treat CD20+ non-Hodgkin's lymphoma. Although pulmonary adverse reactions such as cough, rhinitis, bronchospasm, dyspnea and sinusitis are relatively common, other respiratory conditions like cryptogenic organizing pneumonia, interstitial pneumonitis and diffuse alveolar hemorrhage have rarely been reported. Only 2 possible cases of rituximab-associated hypersensitivity pneumonitis have been described to date. We present a case of hypersensitivity pneumonitis with classic radiographic and histopathologic findings in a patient treated with rituximab who responded to prednisone. PMID:18843175

  3. Role of human cyclooxygenase-2 in the bioactivation of dapsone and sulfamethoxazole.

    PubMed

    Vyas, Piyush M; Roychowdhury, Sanjoy; Svensson, Craig K

    2006-01-01

    Sulfamethoxazole (SMX) and dapsone (4,4'-diaminodiphenylsulfone, DDS) are believed to mediate their adverse effects subsequent to bioactivation to their respective arylhydroxylamine and arylnitroso metabolites, resulting in covalent adduct formation with intracellular proteins. Various bioactivating enzymes, such as cytochromes P450 and myeloperoxidase, have been shown to be capable of catalyzing the N-oxidation of these compounds. We assessed the role of human cyclooxygenase-2 (COX-2) in the metabolism and subsequent adduct formation of DDS and SMX using recombinant human COX-2. Using an adduct-specific enzyme-linked immunosorbent assay, we found that the complete enzyme system gave rise to covalent adducts. However, the nonspecific COX inhibitor indomethacin did not reduce the amount of covalent adduct formed. Formation of the arylhydroxylamine metabolites was demonstrated via high performance liquid chromatography coupled with UV absorption. Metabolite formation was found to be secondary to the H2O2 in the incubation mixture and was not enzyme-mediated. Hence, COX-2 does not play a direct role in the bioactivation of these parent drugs to their arylhydroxylamine metabolites.

  4. Bioactivation, protein haptenation, and toxicity of sulfamethoxazole and dapsone in normal human dermal fibroblasts

    SciTech Connect

    Bhaiya, Payal; Roychowdhury, Sanjoy; Vyas, Piyush M.; Doll, Mark A.; Hein, David W.; Svensson, Craig K. . E-mail: craig-svensson@uiowa.edu

    2006-09-01

    Cutaneous drug reactions (CDRs) associated with sulfonamides are believed to be mediated through the formation of reactive metabolites that result in cellular toxicity and protein haptenation. We evaluated the bioactivation and toxicity of sulfamethoxazole (SMX) and dapsone (DDS) in normal human dermal fibroblasts (NHDF). Incubation of cells with DDS or its metabolite (D-NOH) resulted in protein haptenation readily detected by confocal microscopy and ELISA. While the metabolite of SMX (S-NOH) haptenated intracellular proteins, adducts were not evident in incubations with SMX. Cells expressed abundant N-acetyltransferase-1 (NAT1) mRNA and activity, but little NAT2 mRNA or activity. Neither NAT1 nor NAT2 protein was detected. Incubation of NHDF with S-NOH or D-NOH increased reactive oxygen species formation and reduced glutathione content. NHDF were less susceptible to the cytotoxic effect of S-NOH and D-NOH than are keratinocytes. Our studies provide the novel observation that NHDF are able to acetylate both arylamine compounds and bioactivate the sulfone DDS, giving rise to haptenated proteins. The reactive metabolites of SMX and DDS also provoke oxidative stress in these cells in a time- and concentration-dependent fashion. Further work is needed to determine the role of the observed toxicity in mediating CDRs observed with these agents.

  5. In Vitro Protective Effect and Antioxidant Mechanism of Resveratrol Induced by Dapsone Hydroxylamine in Human Cells

    PubMed Central

    Albuquerque, Rosyana V.; Malcher, Nívea S.; Amado, Lílian L.; Coleman, Michael D.; dos Santos, Danielle C.; Borges, Rosivaldo Sa.; Valente, Sebastião Aldo S.; Valente, Vera C.; Monteiro, Marta Chagas

    2015-01-01

    Dapsone (DDS) hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV) on DDS hydroxylamine (DDS-NHOH) mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mechanism was also studied using in-silico methods. In addition, RSV provided intracellular protection by inhibiting DNA damage in human lymphocytes induced by DDS-NHOH. However, whilst pretreatment with RSV (10–1000 μM significantly attenuated DDS-NHOH-induced methemoglobinemia, but it was not only significantly less effective than methylene blue (MET), but also post-treatment with RSV did not reverse methemoglobin formation, contrarily to that observed with MET. DDS-NHOH inhibited catalase (CAT) activity and reactive oxygen species (ROS) generation, but did not alter superoxide dismutase (SOD) activity in erythrocytes. Pretreatment with RSV did not alter these antioxidant enzymes activities in erythrocytes treated with DDS-NHOH. Theoretical calculations using density functional theory methods showed that DDS-NHOH has a pro-oxidant effect, whereas RSV and MET have antioxidant effect on ROS. The effect on methemoglobinemia reversion for MET was significantly higher than that of RSV. These data suggest that the pretreatment with resveratrol may decrease heme-iron oxidation and DNA damage through reduction of ROS generated in cells during DDS therapy. PMID:26284371

  6. Tetanus immunisation in hypersensitive individuals.

    PubMed

    Williams, A N; Kabuubi, J B L; Owen, J P; Wells, J

    2002-06-01

    We report on a case of an officer cadet who was inadvertently allowed to commence training with a history suggestive of hypersensitivity to tetanus immunisation and who, eventually, successfully underwent a graduated immunisation regimen. This case combines a search for good evidence with the extraordinary complexities of military medical management and the law. It is a lesson in all three.

  7. Drug hypersensitivity reactions involving skin.

    PubMed

    Hausmann, Oliver; Schnyder, Benno; Pichler, Werner J

    2010-01-01

    Immune reactions to drugs can cause a variety of diseases involving the skin, liver, kidney, lungs, and other organs. Beside immediate, IgE-mediated reactions of varying degrees (urticaria to anaphylactic shock), many drug hypersensitivity reactions appear delayed, namely hours to days after starting drug treatment, showing a variety of clinical manifestations from solely skin involvement to fulminant systemic diseases which may be fatal. Immunohistochemical and functional studies of drug-specific T cells in patients with delayed reactions confirmed a predominant role for T cells in the onset and maintenance of immune-mediated delayed drug hypersensitivity reactions (type IV reactions). In these reactions, drug-specific CD4+ and CD8+ T cells are stimulated by drugs through their T cell receptors (TCR). Drugs can stimulate T cells in two ways: they can act as haptens and bind covalently to larger protein structures (hapten-carrier model), inducing a specific immune response. In addition, they may accidentally bind in a labile, noncovalent way to a particular TCR of the whole TCR repertoire and possibly also major histocompatibility complex (MHC)-molecules - similar to their pharmacologic action. This seems to be sufficient to reactivate certain, probably in vivo preactivated T cells, if an additional interaction of the drug-stimulated TCR with MHC molecules occurs. The mechanism was named pharmacological interaction of a drug with (immune) receptor and thus termed the p-i concept. This new concept may explain the frequent skin symptoms in drug hypersensitivity to oral or parenteral drugs. Furthermore, the various clinical manifestations of T cell-mediated drug hypersensitivity may be explained by distinct T cell functions leading to different clinical phenotypes. These data allowed a subclassification of the delayed hypersensitivity reactions (type IV) into T cell reactions which, by releasing certain cytokines and chemokines, preferentially activate and recruit

  8. Plasmodium falciparum: in vitro activity of sulfadoxine and dapsone in field isolates from Kenya: point mutations in dihydropteroate synthase may not be the only determinants in sulfa resistance.

    PubMed

    Mberu, Edward K; Nzila, Alexis M; Nduati, Eunice; Ross, Amanda; Monks, Stephanie M; Kokwaro, Gilbert O; Watkins, William M; Hopkins Sibley, Carol

    2002-01-01

    We have determined the relationship between point mutations in the gene that encodes the sulfa target, dihydropteroate synthase (DHPS) and the chemosensitivity profile to sulfadoxine and dapsone in 67 isolates from Kilifi, Kenya. We assessed the presence of mutations at codons 436, 437, 540, 581, and 613 of dhps. The results showed that the dhps genotype had a strong influence on the sensitivity to sulfadoxine and dapsone, but that the correlation was far from perfect. Eleven isolates carried a wild-type dhps allele, but were resistant to sulfadoxine (IC(50) values >10 microg/ml), and 4/28 isolates were classed as sensitive to sulfadoxine (IC(50) values <10 microg/ml), but carried a triple mutant (436/437/613) allele of dhps. These data show that in low folate medium in vitro, the dhps genotype alone did not account completely for sulfadoxine or dapsone resistance; other factors such as the utilisation of exogenous folate must also be considered.

  9. Central hypersensitivity in chronic musculoskeletal pain.

    PubMed

    Curatolo, Michele; Arendt-Nielsen, Lars

    2015-05-01

    Clinical research has consistently detected alteration in central pain processing leading to hypersensitivity. Most methods used in humans are reliable and have face validity to detect widespread central hypersensitivity. However, construct validity is difficult to investigate due to lack of gold standards. Reference values in the pain-free population have been generated, but need replication. Research on pain biomarkers that reflect specific central hypersensitivity processes is warranted. Few studies have analyzed the prognostic value of central hypersensitivity. Most medications acting at central level and some non-pharmacological approaches, including psychological interventions, are likely to attenuate central hypersensitivity.

  10. The efficacy of 5% dapsone gel plus oral isotretinoin versus oral isotretinoin alone in acne vulgaris: A randomized double-blind study

    PubMed Central

    Faghihi, Gita; Rakhshanpour, Mehrdad; Abtahi-Naeini, Bahareh; Nilforoushzadeh, Mohammad Ali

    2014-01-01

    Background: Acne vulgaris, a common human skin condition, is an inflammatory disease characterized by comedones, papules, nodules and possibly scarring. This study aimed to evaluate the efficacy of a combination of 5% dapsone gel plus oral isotretinoin in the treatment of acne vulgaris. Materials and Methods: A randomized, placebo-controlled, study was carried out on patients with moderate to severe acne. The patients were randomly divided in two groups: (dapsone gel and vehicle gel). All Patients were administered oral isotretinoin 20 mg daily and topical gel twice a day for 8 weeks. The Global Acne Assessment Score (GAAS), the number lesions and side-effects were documented at base line and weeks 4, 8 and 12. Results: A total of 58 patients (age range: 18-25 years) were included in our study. The number of lesions was significantly lower in the dapsone-treated group at all follow-up visits (P < 0.001). The mean GAAS score in the dapsone-treated group and in the Placebo-treated group decreased, but there was no statistical difference in two groups (P < 0.001). The side-effects on the dapsone-treated group were a mild burning sensation in 7 patients (24.13%), mild erythema of the skin and mild dryness in 4 (13.79%) and 3 (10.34%) cases respectively (P < 0.001). In our study, adverse effects were common but they were minor and tolerable. No clinically significant changes in laboratory parameters were observed (P < 0.001). Conclusions: Dapsone gel was an effective medication for patients who received isotretinoin for acne vulgaris treatment resulting in a significant reduction of the number of lesions. PMID:25250291

  11. The Efficacy and Safety of Topical Dapsone Gel, 5% for the Treatment of Acne Vulgaris in Adult Females With Skin of Color.

    PubMed

    Alexis, Andrew F; Burgess, Cheryl; Callender, Valerie D; Herzog, Jo L; Roberts, Wendy E; Schweiger, Eric S; Stockton, Toni C; Gallagher, Conor J

    2016-02-01

    Topical dapsone gel, 5% is approved for treatment of acne vulgaris but has not been studied specifically in women with skin of color (SOC; Fitzpatrick skin types IV, V, or VI). Evaluate safety and efficacy of dapsone gel, 5% applied topically twice daily for 12 weeks in women with SOC. Females with SOC aged 18 years and older with facial acne participated in a multicenter, open-label, single-group, 12-week pilot study of twice-daily monotherapy with dapsone gel, 5%. The investigator-rated 5-point Global Acne Assessment Score (GAAS) was used to assess efficacy. The impact of acne on subjects was assessed using the validated Acne Symptom and Impact Scale (ASIS). The study enrolled and treated 68 women with SOC and facial acne. GAAS decreased significantly from baseline to week 12 (mean, -1.2 [95% CI, -1.4, -1.0]; P<.001), a 39.0% improvement. Overall, 42.9% of subjects were responders based on a GAAS of 0 or 1 at week 12. Subjects also experienced significant reductions in mean total lesions (52% decrease), inflammatory lesions (65%), and comedo counts (41%; all P<.001). Dapsone gel, 5% monotherapy was associated with significant improvement in subject-assessed acne signs (P<.001) and impact on quality of life (QOL; P<.001), based on ASIS. Dapsone gel, 5% used twice daily was well tolerated, with no treatment-related adverse events. The local dermal tolerability scores tended to remain stable or decrease from baseline to week 12. Monotherapy with dapsone gel, 5% administered twice daily was safe and effective for treatment of facial acne in women with SOC. Significant improvement in overall acne severity and both inflammatory lesions and comedones was observed. Further, study subjects reported considerable improvement in both acne signs and impact on QOL.

  12. [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.

  13. Longitudinal study on relapses of leprosy in Polynesian multibacillary patients on dapsone monotherapy between 1946 and 1970.

    PubMed

    Cartel, J L; Boutin, J P; Spiegel, A; Plichart, R; Roux, J F

    1991-06-01

    Between 1946 and 1970, 295 new leprosy patients were detected in French Polynesia, of whom 145 were multibacillary. Of these 145, put on dapsone monotherapy, 131 reached bacteriological negativity in a period of time ranging from 2 to 12 years (average 4.72 years) and were followed-up for a period of time ranging from 19 to 43 years (median follow-up period after bacteriological negativity; 18 years). Among the 131 patients, 36 relapses were detected, the first one 4 years after bacteriological negativity and the last one 26 years after. The crude relapse rate was 27.5%, the risk of relapse was 1.39 per 100 patient years and the cumulative relapse probability, calculated using the lifetable method, reached 0.38 +/- 11 by year 31 of the study. From these findings one may assume that, at least in French Polynesia, one-third to one-half of multibacillary patients put on dapsone monotherapy would relapse if still present 36 years after bacteriological negativity. Such results re-emphasize the need for leprosy patients to be treated with multidrug therapy as recommended by WHO.

  14. Dapsone gel 5% in combination with adapalene gel 0.1%, benzoyl peroxide gel 4% or moisturizer for the treatment of acne vulgaris: a 12-week, randomized, double-blind study.

    PubMed

    Fleischer, Alan B; Shalita, Alan; Eichenfield, Lawrence F; Abramovits, William; Lucky, Anne; Garrett, Steven

    2010-01-01

    To evaluate the safety and efficacy of dapsone gel 5% in the treatment of acne when used in combination with adapalene gel 0.1%, benzoyl peroxide gel 4% or moisturizer. This was a twelve-week, randomized, double-blind study. Patients aged 12 years and older (n=301) applied dapsone gel twice daily and were randomly assigned (1:1:1) to one of three additional treatments, applied once daily. By week 12, dapsone gel combined with any of the three additional treatments reduced the mean number of inflammatory lesions. However, the authors did not detect a significant difference in the reduction of inflammatory lesions when dapsone was used in combination with adapalene gel or with benzoyl peroxide gel compared to the dapsone plus moisturizer combination group (P=0.052 for both versus moisturizer combination). Patients treated with dapsone gel combined with adapalene showed a significantly better response in reduction in non-inflammatory and total acne lesion count than those who received the moisturizer combination. Local adverse reactions in all three treatment groups were minimal and generally mild in severity. Dapsone gel in combination with adapalene gel or benzoyl peroxide gel is safe and well tolerated for the treatment of acne vulgaris.

  15. Rare association of hyper IgE syndrome with cervical rib and natal teeth.

    PubMed

    Roshan, Anupama S; Janaki, C; Parveen, B; Gomathy, N

    2009-01-01

    Hyper IgE syndrome (HIES) is a rare immunodeficiency syndrome characterized by a triad of cutaneous abscesses, mostly caused by Staphylococus aureus; pneumonia; and raised IgE levels. Nonimmunological associations include course facial features, multiple bone fractures, joint hyperextensibility, and retained primary dentition. Patients require long-term antibiotic therapy. We report here a classical case of HIES with rare associations of natal teeth, bilateral cervical ribs, and conductive deafness. The patient was being treated with monteleukast and dapsone.

  16. Steroid-sparing effect and toxicity of dapsone treatment in giant cell arteritis

    PubMed Central

    Ly, Kim Heang; Dalmay, François; Gondran, Guillaume; Palat, Sylvain; Bezanahary, Holy; Cypierre, Anne; Fauchais, Anne-Laure; Liozon, Eric

    2016-01-01

    Abstract Although a glucocorticoid (GC)-sparing strategy is needed for patients with giant cell arteritis (GCA) suffering from refractory disease or serious treatment-related complications, evidence of efficacy in this setting of immunosuppressive drugs and biotherapies is lacking. Herein, we evaluated the GC-sparing effects and tolerability of addition of dapsone (DDS) to prednisone therapy in patients with GCA. We retrospectively assessed data on 18 GCA patients who received DDS as a first-line treatment (DDS-1 group) and 52 patients who received it as a second- or third-line treatment for refractory GCA, with or without excessive GC-related toxicity (DDS-2 group). Of these 70 patients, 63 belonged to an inception cohort of 478 patients, whereas the remaining 7 were referred to our department for resistant GCA. In all, 52 patients were assessable for DDS efficacy. The baseline characteristics of the DDS-1 patients were similar to those of 395 GCA patients (control group) who received prednisone alone. DDS-1 patients had a more sustained decrease in GC dose with a lower mean prednisone dose at 12 months, and they comprised higher proportions who achieved GC withdrawal within the first year, who stopped prednisone treatment, and who recovered from GCA (P < 0.001 for each variable). Patients in the DDS-2 group achieved a mean rate of prednisone reduction of 65% and a prednisone dose reduction of 16.9 ± 13.3 mg/d. The monthly decreases in the prednisone dose were 2.4 and 1.25 mg in DDS-1 and DDS-2 patients, respectively. DDS-induced side effects were recorded in 44 (64%) assessable patients. These side effects led to lowering of the DDS dose by 25 mg/d in 11 (16%) patients and permanent cessation of DDS in 14 patients (20%), due to allergic skin rash in 7, agranulocytosis in 2, icteric hepatitis in 2, and excessive hemolysis in 2 patients. DDS is a potent GC-sparing agent in GCA that should be evaluated in prospective studies. However, DDS use should

  17. Chlorproguanil-dapsone versus sulfadoxine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi: a randomised clinical trial.

    PubMed

    Sulo, J; Chimpeni, P; Hatcher, J; Kublin, J G; Plowe, C V; Molyneux, M E; Marsh, K; Taylor, T E; Watkins, W M; Winstanley, P A

    2002-10-12

    Chlorproguanil-dapsone exerts lower resistance pressure on Plasmodium falciparum than does sulfadoxine-pyrimethamine, but is rapidly eliminated. We aimed to find out whether chlorproguanil-dapsone results in a higher retreatment rate for malaria than sulfadoxine-pyrimethamine. In a randomised trial of paediatric outpatients with uncomplicated falciparum malaria, patients received either chlorproguanil-dapsone or sulfadoxine-pyrimethamine and were followed up for up to 1 year. Sites were in Kenya (n=410) and Malawi (n=500). We used per-protocol analysis to assess the primary outcome of annual malaria incidence. Drop-outs were 117 of 410 (28.5%) in Kenya, and 342 of 500 (68.4%) in Malawi. Follow-up was for a median of 338 days (IQR 128-360) and 342 days (152-359) in Kilifi (chlorproguanil-dapsone and sulfadoxine-pyrimethamine, respectively), and for 120 days (33-281) and 84 days (26-224) in Blantyre. Mean annual malaria incidence was 2.5 versus 2.1 in Kenya (relative risk 1.16, 95% CI 0.98-1.37), and 2.2 versus 2.8 in Malawi (0.77, 0.63-0.94). 4.3% versus 12.8%, and 5.4% versus 20.1%, of patients were withdrawn for treatment failure in Kenya and Malawi, respectively. In Kenya haemoglobin concentration of 50 g/L or less caused exit in 6.9% of chlorproguanil-dapsone patients and 1.5% of sulfadoxine-pyrimethamine patients, but most anaemia occurred before re-treatment. In Malawi only one patient exited because of anaemia. Despite the rapid elimination of chlorproguanil-dapsone, children treated with this drug did not have a higher incidence of malaria episodes than those treated with sulfadoxine-pyrimethamine. Treatment failure was more common with sulfadoxine-pyrimethamine. Cause of anaemia in Kenya was probably not adverse reaction to chlorproguanil-dapsone, but this observation requires further study.

  18. 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.

  19. 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

  20. Histone hyperacetylation modulates spinal type II metabotropic glutamate receptor alleviating stress-induced visceral hypersensitivity in female rats

    PubMed Central

    Cao, Dong-Yuan; Bai, Guang; Ji, Yaping; Karpowicz, Jane

    2016-01-01

    Stress is often a trigger to exacerbate chronic pain including visceral hypersensitivity associated with irritable bowel syndrome, a female predominant functional bowel disorder. Epigenetic mechanisms that mediate stress responses are a potential target to interfere with visceral pain. The purpose of this study was to examine the effect of a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, on visceral hypersensitivity induced by a subchronic stressor in female rats and to investigate the involvement of spinal glutamate receptors. Three daily sessions of forced swim induced visceral hypersensitivity. Intrathecal suberoylanilide hydroxamic acid prevented or reversed the stress-induced visceral hypersensitivity, increased spinal histone 3 acetylation and increased mGluR2 and mGluR3 expression. Chromatin immunoprecipitation (ChIP) analysis revealed enrichment of H3K9Ac and H3K18Ac at several promoter Grm2 and Grm3 regions. The mGluR2/3 antagonist LY341495 reversed the inhibitory effect of suberoylanilide hydroxamic acid on the stress-induced visceral hypersensitivity. In surprising contrast, stress and/or suberoylanilide hydroxamic acid had no effect on spinal NMDA receptor expression or function. These data reveal histone modification modulates mGluR2/3 expression in the spinal cord to attenuate stress-induced visceral hypersensitivity. HDAC inhibitors may provide a potential approach to relieve visceral hypersensitivity associated with irritable bowel syndrome. PMID:27385724

  1. Dapsone improves functional deficit and diminishes brain damage evaluated by 3-Tesla magnetic resonance image after transient cerebral ischemia and reperfusion in rats.

    PubMed

    Diaz-Ruiz, Araceli; Roldan-Valadez, Ernesto; Ortiz-Plata, Alma; Mondragón-Lozano, Rodrigo; Heras-Romero, Yessica; Mendez-Armenta, Marisela; Osorio-Rico, Laura; Nava-Ruiz, Concepción; Ríos, Camilo

    2016-09-01

    Stroke is a frequent cause of death and the first of disability in the world population. We have shown that dapsone acts as an antioxidant, antiinflammatory and antiapoptotic agent after brain Ischemia reperfusion (I/R) in rats; however, its therapeutic efficacy, measured by imaging has not been characterized. In this context, the aim of this study was to evaluate the neuroprotective effect of dapsone by magnetic resonance imaging (MRI) and to correlate imaging markers with motor function and oxidative stress after transient cerebral ischemia and reperfusion (I/R). We used male rats throughout the experiment. Functional deficit after I/R was assessed by using Longa scale. The area of brain tissue damage was measured by histology. The nuclear factor erythroid 2-related factor 2 (Nrf-2) and the amount of reactive oxygen species (ROS) were measured as biomarkers of oxidative stress. Finally, difussion tensor MRI was employed to measure the fractional anisotropy (FA), as a MRI marker of the pathophysiologic brain status. Results showed a better functional recovery and less damaged tissue in animals treated with dapsone vs control group. The values of FA were higher in animals receiving treatment, indicating a better preservation of brain structure. At early stages of the damage, dapsone was able to reduce both oxidative markers (Nrf-2 and ROS). Our findings provide new evidence for the efficacy of dapsone when administered during the acute phase after I/R and that quantitative sequences of MRI are useful for characterizing its potential therapeutic benefits after stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Food hypersensitivity among adult patients: epidemiological and clinical aspects.

    PubMed

    Castillo, R; Delgado, J; Quiralte, J; Blanco, C; Carrillo, T

    1996-01-01

    Food hypersensitivity (FH) is lesser frequent among adult patients than in childhood. Foods implicated in hypersensitivity reactions vary with sociocultural and diet habits from a geographic place to other. We studied 142 adult patients sensitized to foods, among 7698 patients visited at our Outpatient Clinic. Hundred and twenty patients referred clinical symptoms after consumption of one or more foods consistently. From the latest, 107 patients (89.2%) were atopics (92 of them sensitizes to dust mites) and 54 (45%) referred atopic familiar background. Most frequent recorded symptoms were: urticaria/angioedema 84 cases (70%), oral syndrome 65 (54%), asthma 48 (37%) and anaphylaxis 33 patients (27.5%). Shellfish sensitization occurred in 50 patients, fresh fruits in 33 and nuts in 29 cases. Shrimp (48 patients), squid (33), kiwi (14), papaya (14), avocado (13) and banana (12 cases) were the most frequent causes of FH. Significant statistical association between foods and inhalants was observed for fresh fruits and latex (p < 0.001), fresh fruits and pollens (p < 0.01), and shellfish and Blatta germanica (p < 0.001). Prevalence of FH among patients at our Area is around 1.6%. Tropical fruits, as other kind of fruits, seem to share common IgE-epitopes to pollens. High prevalence of shellfish and cockroach hypersensitivity could be more easily developed by previous domestic mites sensitization.

  3. Unusual formaldehyde-induced hypersensitivity in two schoolgirls

    SciTech Connect

    Gammage, R.B. ); Hanna, W.T.; Painter, P.B. )

    1990-01-01

    Two schoolgirls developed a syndrome resembling Henoch-Schonlein purpura while attending a recently opened school insulated with urea-formaldehyde foam (UFFI). Skin rashes and swellings were accompanied by bizarre, blue-green discoloration of the skin. Subsequent investigations by county, state and federal authorities, and low measured concentrations of formaldehyde, prompted initial conclusions that in-school formaldehyde exposures were not responsible for the girls' problems. Subsequent controlled exposures to UFFI and formaldehyde while in hospital elicited the whole cascade of symptoms. The chronology of the onset and amplification of systems make it probable that the formaldehyde exposures precipitating the girls' hypersensitivity, occurred in the school. 3 refs.

  4. IgE-mediated food hypersensitivity disorders.

    PubMed

    Gotua, M; Lomidze, N; Dolidze, N; Gotua, T

    2008-04-01

    Food allergy has become a serious health concern especially in developed countries in the past two decades. In general population approximately 4-6% of children and 1-3% of adults experience food allergy. The article reviews IgE-mediated food hypersensitivity disorders. Epidemiology, Mechanism, Clinical manifestations, Genetically modified crops (GMOs), Diagnosis, Prevention and Treatment of IgE-mediated food allergies are discussed. The investigations show that over 90% of IgE-mediated food allergies in childhood are caused by: cow's milk, hen's egg, soy, peanuts, tree nuts, wheat, fish and shellfish. Also the causes of food allergy are food additives, genetically modified crops. Risk factors for food-dependent exercise-induced anaphylaxis include asthma and previous allergic reactions to the causative food. Food allergy is one of the most common causes of systematic anaphylaxis and anaphylactoid reactions, with an annual incidence of four cases per million populations and estimated 500 deaths annually. In addition to gastrointestinal symptoms, individuals may experience urticaria, angioedema, atopic dermatitis, oral syndrome, asthma, rhinitis, conjunctivitis, hypotension, shock and cardiac arrhythmias, caused by the massive release of mediators from mast cells and basophiles. Diagnosis of food allergy is based on history, detailed dietary analysis, skin testing, measuring specific IgE in blood serum and challenge tests. Treatment and prevention includes: avoidance diet, application of auto-injectable epinephrine, H1 and H2 antihistamines, corticosteroids, antileukotrienes, prostaglandin synthetase inhibitors, cromolyn sodium, etc.

  5. A patient with severe black fly (Simuliidae) hypersensitivity referred for evaluation of suspected immunodeficiency.

    PubMed

    Orange, Jordan S; Song, Leslie A; Twarog, Frank J; Schneider, Lynda C

    2004-02-01

    Biting flies of the Diptera order and specifically the black fly (Simuliidae family) can be rare causes of severe hypersensitivity reactions. To describe a patient referred for evaluation of immunodeficiency whose clinical course is explained by severe Simuliidae hypersensitivity. The patient's immune system was investigated using standard laboratory evaluations. Hypersensitivity to Simuliidae was pursued because of historical features of her presentation and was specifically examined by skin prick and intradermal testing with whole body extract. The patient's history was notable for recurrent and severe seasonal episodes of presumed cellulitis after black fly bites that responded poorly to intravenous antibiotics. One episode was followed by acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome) and another by minimal change nephrotic syndrome. The results of immunologic investigations were unremarkable, but cutaneous hypersensitivity to Simuliidae was demonstrated with a 6.5-mm wheel and 35-mm flare reaction to intradermal injection of only 0.0005 microg of whole body extract. Similar to Hymenoptera, Simuliidae can rarely result in extreme hypersensitivity and should be considered in appropriate cases. This patient illustrates how severe reactions toinsect bites can be misdiagnosed.

  6. Methemoglobinemia in Young Patients With Hematologic Cancer or Aplastic Anemia Treated With Dapsone

    ClinicalTrials.gov

    2010-11-04

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Methemoglobinemia; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Nonmalignant Neoplasm

  7. Hypersensitivity reactions to titanium: diagnosis and management.

    PubMed

    Wood, Megan M; Warshaw, Erin M

    2015-01-01

    Titanium is notable for its biocompatibility and is used as biologic implant material across surgical specialties, especially in metal-sensitive individuals. However, rare cases of titanium hypersensitivity reactions are reported in the literature. This article discusses the properties and biological behavior of titanium and provides a thorough review of the literature on reported cases, diagnostic techniques, and approach to management of titanium hypersensitivity.

  8. Metal hypersensitivity: can it mimic infection?

    PubMed

    Anand, Ashish; McGlynn, Fred; Jiranek, William

    2009-08-01

    Metal hypersensitivity leading onto hardware rejection is reported as a rare phenomenon. If not suspected, it can be a harrowing experience for the patient because it can lead to a seemingly never-ending cycle of tests and procedures. This case highlights the fact that although metal hypersensitivity is rare, it should be included in the differential once infection has been excluded.

  9. Hypersensitivity reactions to synthetic haemodialysis membranes.

    PubMed

    Sánchez-Villanueva, Rafael J; González, Elena; Quirce, Santiago; Díaz, Raquel; Alvarez, Laura; Menéndez, David; Rodríguez-Gayo, Lucía; Bajo, M Auxiliadora; Selgas, Rafael

    2014-01-01

    Undergoing a haemodialysis (HD) session poses a certain risk of hypersensitivity adverse reactions as large quantities of blood are in contact with various synthetic materials. Hypersensitivity reactions to ethylene oxide and non-biocompatible membranes, such as cuprophane, have been described in HD. Cases of hypersensitivity with biocompatible membranes, such as polysulfone, and even polysulfone-polyvinylpyrrolidone, have also been reported. In this article we describe six cases of mostly early-stage hypersensitivity reactions to HD occurring in our department, characterised by malaise, desaturation, bronchospasm and arterial hypotension, with good response to the session’s temporary suspension and with reappearance in subsequent sessions that used a synthetic dialyser. No hypersensitivity reactions reappeared in successive observations when the sessions were carried out using a cellulose membrane.

  10. Allergic or Hypersensitivity Reactions to Orthopaedic Implants.

    PubMed

    Roberts, Timothy T; Haines, Colin M; Uhl, Richard L

    2017-10-01

    Allergic or hypersensitivity reactions to orthopaedic implants can pose diagnostic and therapeutic challenges. Although 10% to 15% of the population exhibits cutaneous sensitivity to metals, deep-tissue reactions to metal implants are comparatively rare. Nevertheless, the link between cutaneous sensitivity and clinically relevant deep-tissue reactions is unclear. Most reactions to orthopaedic devices are type IV, or delayed-type hypersensitivity reactions. The most commonly implicated allergens are nickel, cobalt, and chromium; however, reactions to nonmetal compounds, such as polymethyl methacrylate, antibiotic spacers, and suture materials, have also been reported. Symptoms of hypersensitivity to implants are nonspecific and include pain, swelling, stiffness, and localized skin reactions. Following arthroplasty, internal fixation, or implantation of similarly allergenic devices, the persistence or early reappearance of inflammatory symptoms should raise suspicions for hypersensitivity. However, hypersensitivity is a diagnosis of exclusion. Infection, as well as aseptic loosening, particulate synovitis, instability, and other causes of failure must first be eliminated.

  11. pH-sensitive nanoparticles for improved oral delivery of dapsone: risk assessment, design, optimization and characterization.

    PubMed

    Chaves, Luíse L; Costa Lima, Sofia A; Vieira, Alexandre Cc; Barreiros, Luísa; Segundo, Marcela A; Ferreira, Domingos; Sarmento, Bruno; Reis, Salette

    2017-08-01

    To optimize the production of pH-sensitive dapsone (DAP) nanoparticles based on Eugradit L100 (NPs-EL100-DAP) for oral delivery. NPs-EL100-DAP were optimized using a Plackett-Burman design and a Box-Behnken design. The physicochemical properties of the obtained nanoparticles were monitored by microscopy, dynamic light scattering, Fourier transform infrared spectroscopy, differential scanning calorimetry, in vitro release assays, and examined for cytotoxicity and permeation across intestinal barrier. The in vitro release assay of NPs-EL100-DAP confirmed the nanoparticles' pH sensitivity and the ability to deliver DAP at intestinal environment. NPs-EL100-DAP demonstrated enhanced intestinal interactions in comparison to free DAP, across Caco-2 monolayers. These studies demonstrate the potential of NPs-EL100-DAP as a therapeutic platform for oral treatment of leprosy.

  12. Pain hypersensitivity and spinal nociceptive hypersensitivity in chronic pain: prevalence and associated factors.

    PubMed

    Curatolo, Michele; Müller, Monika; Ashraf, Aroosiah; Neziri, Alban Y; Streitberger, Konrad; Andersen, Ole K; Arendt-Nielsen, Lars

    2015-11-01

    Hypersensitivity of pain pathways is considered a relevant determinant of symptoms in chronic pain patients, but data on its prevalence are very limited. To our knowledge, no data on the prevalence of spinal nociceptive hypersensitivity are available. We studied the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity in 961 consecutive patients with various chronic pain conditions. Pain threshold and nociceptive withdrawal reflex threshold to electrical stimulation were used to assess pain hypersensitivity and spinal nociceptive hypersensitivity, respectively. Using 10th percentile cutoff of previously determined reference values, the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity (95% confidence interval) was 71.2 (68.3-74.0) and 80.0 (77.0-82.6), respectively. As a secondary aim, we analyzed demographic, psychosocial, and clinical characteristics as factors potentially associated with pain hypersensitivity and spinal nociceptive hypersensitivity using logistic regression models. Both hypersensitivity parameters were unaffected by most factors analyzed. Depression, catastrophizing, pain-related sleep interference, and average pain intensity were significantly associated with hypersensitivity. However, none of them was significant for both unadjusted and adjusted analyses. Furthermore, the odds ratios were very low, indicating modest quantitative impact. To our knowledge, this is the largest prevalence study on central hypersensitivity and the first one on the prevalence of spinal nociceptive hypersensitivity in chronic pain patients. The results revealed an impressively high prevalence, supporting a high clinical relevance of this phenomenon. Electrical pain thresholds and nociceptive withdrawal reflex explore aspects of pain processing that are mostly independent of sociodemographic, psychological, and clinical pain-related characteristics.

  13. Visceral hypersensitivity and electromechanical dysfunction as therapeutic targets in pediatric functional dyspepsia

    PubMed Central

    Rosen, John M; Cocjin, Jose T; Schurman, Jennifer V; Colombo, Jennifer M; Friesen, Craig A

    2014-01-01

    Functional gastrointestinal disorders (FGID) are common clinical syndromes diagnosed in the absence of biochemical, structural, or metabolic abnormalities. They account for significant morbidity and health care expenditures and are identifiable across variable age, geography, and culture. Etiology of abdominal pain associated FGIDs, including functional dyspepsia (FD), remains incompletely understood, but growing evidence implicates the importance of visceral hypersensitivity and electromechanical dysfunction. This manuscript explores data supporting the role of visceral hypersensitivity and electromechanical dysfunction in FD, with focus on pediatric data when available, and provides a summary of potential therapeutic targets. PMID:25133041

  14. [Hypersensitivity Pneumonitis (extrinsic allergic alveolitis)].

    PubMed

    Cebollero, P; Echechipía, S; Echegoyen, A; Lorente, M P; Fanlo, P

    2005-01-01

    Farmer's lung was first described in 1932. We can define hypersensitivity pneumonitis as a pulmonary and systemic disease that is accompanied by dyspnoea and coughing; it is caused by an immunological type of inflammation of the alveolar walls and the terminal airways and it is secondary to the repeated inhalation of a variety of antigens by a susceptible host. It can be said that it is an underdiagnosed disease and only a high degree of clinical manifestations and a detailed history of exposure can lead to an early diagnosis and satisfactory treatment. A combination among clinical-radiological, functional, cytological or pathological findings leads in some cases to a diagnosis. Treatment is based on avoiding further exposure to the causal agent and in the more serious cases the administration of systemic corticoid treatment.

  15. 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.

  16. Metal hypersensitivity in total joint arthroplasty.

    PubMed

    Pinson, Michelle L; Coop, Christopher A; Webb, Charles N

    2014-08-01

    To review the clinical manifestations, testing methods, and treatment options for hypersensitivity reactions to total joint arthroplasty procedures. Studies were identified using MEDLINE and reference lists of key articles. Randomized controlled trials were selected when available. Systematic reviews and meta-analyses of peer-reviewed literature were included, as were case series and observational studies of clinical interest. Total joint arthroplasty procedures are increasing, as are the hypersensitivity reactions to these implants. Evidence is not conclusive as to whether metal joint implants increase metal sensitivity or whether metal sensitivity leads to prosthesis failure. Currently, patch testing is still the most widely used method for determining metal hypersensitivity; however, there are no standardized commercial panels specific for total joint replacements available currently. In vitro testing has shown comparable results in some studies, but its use in the clinical setting may be limited by the cost and need for specialized laboratories. Hypersensitivity testing is generally recommended before surgery for patients with a reported history of metal sensitivity. In cases of metal hypersensitivity-related joint failure, surgical revision ultimately may be required. Knowledge about joint replacement hypersensitivity reactions becomes vital because the approach to the evaluation depends on appropriate testing to guide recommendations for future arthroplasty procedures. Evaluation of hypersensitivity reactions after total joint arthroplasty requires a systematic approach, including a careful history, targeted evaluation with skin testing, and in vitro studies. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. The prognosis of wheat hypersensitivity in children.

    PubMed

    Kotaniemi-Syrjänen, Anne; Palosuo, Kati; Jartti, Tuomas; Kuitunen, Mikael; Pelkonen, Anna S; Mäkelä, Mika J

    2010-03-01

    The study was aimed to determine the natural history of wheat hypersensitivity, to define risk factors for persistent wheat hypersensitivity, and to evaluate the development of respiratory allergy in children with wheat hypersensitivity. The development and subsequent disappearance of wheat hypersensitivity, clinical findings, skin prick test (SPT) reactivity, and the development of allergic rhinoconjunctivitis and asthma were charted retrospectively in 28 children with wheat hypersensitivity proven by the open oral challenge at the median age of 21 months (range 6 to 75 months). Appearance of skin symptoms during the diagnostic wheat challenge was related to SPT-positive wheat hypersensitivity, while the appearance of gastrointestinal symptoms alone was associated with SPT-negative wheat hypersensitivity (p=0.002). Wheat was tolerated by 59%, 69%, 84%, and 96%, by age 4, 6, 10, and 16, respectively. Sensitization to gliadin with a SPT wheal of >or=5 mm at the time of the diagnostic challenge was associated with a slower course of recovery from wheat hypersensitivity (p=0.019), and a SPT wheal of >or=3 mm to gliadin at any time was associated with the development of asthma (p=0.022). SPT reactivity to wheat was associated with later SPT reactivity to birch pollen (p=0.001), and the development of allergic rhinoconjunctivitis (p=0.001). In conclusion, almost all children with wheat hypersensitivity can tolerate wheat by adolescence. Sensitization to gliadin is associated with a slower achievement of tolerance and an increased risk of asthma. Copyright (c) 2009 John Wiley & Sons A/S

  18. 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.

  19. 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.

  20. Involvement of protein kinase ζ in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity.

    PubMed

    Chen, Aiqin; Bao, Chengjia; Tang, Ying; Luo, Xiaoqing; Guo, Lixia; Liu, Bin; Lin, Chun

    2015-05-01

    The hippocampal long-term potentiation (LTP) was implicated in the formation of visceral hypersensitivity in rats with irritable bowel syndrome in our previous study. Recent studies have shown that protein kinase M ζ (PKMζ) may be responsible for the maintenance of LTP in memory formation. However, it remains unclear whether PKMζ is involved in the visceral hypersensitivity. In this study, a rat model of visceral hypersensitivity was generated by neonatal maternal separation (NMS). The visceral hypersensitivity was assessed by recording responses of the external oblique abdominal muscle to colorectal distension. Our results demonstrated that hippocampal LTP and visceral hypersensitivity were enhanced significantly in rats of NMS. ζ-Pseudosubstrate inhibitory peptide (ZIP) could dose dependently inhibit the maintenance of Cornu Ammonis area 1 LTP in rats of NMS. Furthermore, Western blot data showed that the expression of hippocampal phosphorylated PKMζ (p-PKMζ) significantly increased in rats of NMS. In addition, bilateral intrahippocampal injections of ZIP attenuated the visceral hypersensitivity dose dependently in rats of NMS. The maximal inhibition was observed at 30 min, and significant inhibition lasted for 1.5-2 h after ZIP application. Besides, data from the open-field test and Morris water maze showed that ZIP did not influence the movement and spatial procedural memory in rats of NMS. In conclusion, p-PKMζ might be a critical protein in the maintenance of hippocampal LTP, which could result in visceral hypersensitivity.

  1. Involvement of protein kinase ζ in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity

    PubMed Central

    Chen, Aiqin; Bao, Chengjia; Tang, Ying; Luo, Xiaoqing; Guo, Lixia; Liu, Bin

    2015-01-01

    The hippocampal long-term potentiation (LTP) was implicated in the formation of visceral hypersensitivity in rats with irritable bowel syndrome in our previous study. Recent studies have shown that protein kinase M ζ (PKMζ) may be responsible for the maintenance of LTP in memory formation. However, it remains unclear whether PKMζ is involved in the visceral hypersensitivity. In this study, a rat model of visceral hypersensitivity was generated by neonatal maternal separation (NMS). The visceral hypersensitivity was assessed by recording responses of the external oblique abdominal muscle to colorectal distension. Our results demonstrated that hippocampal LTP and visceral hypersensitivity were enhanced significantly in rats of NMS. ζ-Pseudosubstrate inhibitory peptide (ZIP) could dose dependently inhibit the maintenance of Cornu Ammonis area 1 LTP in rats of NMS. Furthermore, Western blot data showed that the expression of hippocampal phosphorylated PKMζ (p-PKMζ) significantly increased in rats of NMS. In addition, bilateral intrahippocampal injections of ZIP attenuated the visceral hypersensitivity dose dependently in rats of NMS. The maximal inhibition was observed at 30 min, and significant inhibition lasted for 1.5–2 h after ZIP application. Besides, data from the open-field test and Morris water maze showed that ZIP did not influence the movement and spatial procedural memory in rats of NMS. In conclusion, p-PKMζ might be a critical protein in the maintenance of hippocampal LTP, which could result in visceral hypersensitivity. PMID:25761958

  2. Hypersensitivity myocarditis confirmed by cardiac magnetic resonance imaging and endomyocardial biopsy.

    PubMed

    Park, Yumi; Ahn, Sung Gyun; Ko, Anna; Ra, Sang Ho; Cha, Jaehwang; Jee, Yong Gwan; Lee, Ji Hyun

    2014-03-01

    Myocarditis often occurs due to viral infections and postviral immune-mediated responses. Hypersensitivity myocarditis is a rare form of myocarditis. Numerous drugs can induce myocarditis, which is typically reversible after withdrawal of the causative agent. Here, we report a case of hypersensitivity myocarditis that was probably triggered by amoxicillin and that resolved completely with heart failure management as well as discontinuation of the drug. A 68-year-old woman presented with acute chest pain mimicking acute coronary syndromes, but the coronary angiography was normal. A recent history of taking medications, skin rash, and peripheral eosinophilia suggested a diagnosis of hypersensitivity myocarditis, which was confirmed by cardiac magnetic resonance imaging and endomyocardial biopsy.

  3. Efficacy and Safety of Once-Daily Dapsone Gel, 7.5% for Treatment of Adolescents and Adults With Acne Vulgaris: First of Two Identically Designed, Large, Multicenter, Randomized, Vehicle-controlled Trials.

    PubMed

    Stein Gold, Linda F; Jarratt, Michael T; Bucko, Alicia D; Grekin, Steven K; Berlin, Joshua M; Bukhalo, Michael; Weiss, Jonathan S; Berk, David R; Chang-Lin, Joan-En; Lin, Vince; Kaoukhov, Alexandre

    2016-05-01

    Treatment of acne vulgaris (acne) with dapsone gel, 5% requires twice-daily dosing, and some patients may not adhere to this regimen.
    The objective of this study was to assess the efficacy and safety of a new, once-daily formulation of dapsone gel, 7.5%, with a 50% higher dapsone concentration, versus vehicle over 12 weeks in patients with acne.
    This 12-week, randomized, double-blind, vehicle-controlled, multicenter clinical trial enrolled patients with moderate acne aged 12 years and older with 20 to 50 inflammatory lesions and 30 to 100 noninflammatory lesions on the face, and an acne grade of 3 (moderate) on the Global Acne Assessment Score (GAAS). Patients were randomized to receive topical dapsone gel, 7.5% or vehicle once daily for 12 weeks. Investigators assessed GAAS success rate (proportion of patients with GAAS of 0 or 1) and percent change from baseline in inflammatory, noninflammatory, and total lesions.
    The intent-to-treat population comprised 2102 patients, 1044 in the dapsone gel, 7.5% group and 1058 in the vehicle group. At week 12, 29.9% of patients in the dapsone gel, 7.5% group and 21.2% in the vehicle group (P<.001) had GAAS success. Mean inflammatory lesions decreased by 55.5% and 49.0%, noninflammatory lesions decreased by 44.4% and 38.4%, and total lesions decreased by 48.7% and 42.4% in the dapsone gel, 7.5% and vehicle groups (all P<.001), respectively, at week 12. The incidence of adverse events was similar in the dapsone gel, 7.5% (19.1%) and vehicle (20.6%) groups. Most events in both groups were mild or moderate in severity. Most patients receiving dapsone gel, 7.5% and vehicle had a severity rating of "none" for stinging/burning, dryness, scaling, and erythema scales at all time points.
    Dapsone gel, 7.5% applied topically once daily is an effective, safe, and well-tolerated treatment for acne.

    J Drugs Dermatol. 2016;15(5):553-561.

  4. 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.

  5. 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.

  6. Adduct Formation and Context Factors in Drug Hypersensitivity: Insight from Proteomic Studies.

    PubMed

    Gonzalez-Morena, Juan M; Montanez, Maria I; Aldini, Giancarlo; Sanchez-Gomez, Francisco J; Perez-Sala, Dolores

    2016-01-01

    Drug hypersensitivity reactions result from the activation of the immune system by drugs or their metabolites. The clinical presentations of drug hypersensitivity can range from relatively mild local manifestations to severe systemic syndromes that can be lifethreatening. As in other allergic reactions, the causes are multifactorial as genetic, metabolic and concomitant factors may influence the occurrence of drug hypersensitivity. Formation of drug protein adducts is considered a key step in drug adverse reactions, and in particular in the immunological recognition in drug hypersensitivity reactions. Nevertheless, noncovalent interactions of drugs with receptors in immune cells or with MHC clefts and/or exposed peptides can also play an important role. In recent years, development of proteomic approaches has allowed the identification and characterization of the protein targets for modification by drugs in vivo and in vitro, the nature of peptides exposed on MHC molecules, the changes in protein levels induced by drug treatment, and the concomitant modifications induced by danger signals, thus providing insight into context factors. Nevertheless, given the complexity and multifactorial nature of drug hypersensitivity reactions, understanding the underlying mechanisms also requires the integration of knowledge from genomic, metabolomic and clinical studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit

    PubMed Central

    Wang, Peng; Du, Chao; Chen, Fei-Xue; Li, Chang-Qing; Yu, Yan-Bo; Han, Ting; Akhtar, Suhail; Zuo, Xiu-Li; Tan, Xiao-Di; Li, Yan-Qing

    2016-01-01

    The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF+/− mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cγ1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently, and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS-like visceral hypersensitivity, and this process is likely initiated by BDNF-TrkB pathway activation. PMID:26837784

  8. BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit.

    PubMed

    Wang, Peng; Du, Chao; Chen, Fei-Xue; Li, Chang-Qing; Yu, Yan-Bo; Han, Ting; Akhtar, Suhail; Zuo, Xiu-Li; Tan, Xiao-Di; Li, Yan-Qing

    2016-02-03

    The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF(+/-) mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cγ1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently, and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS-like visceral hypersensitivity, and this process is likely initiated by BDNF-TrkB pathway activation.

  9. Colonic mast cell infiltration in rats with TNBS-induced visceral hypersensitivity.

    PubMed

    Ohashi, Katsuyo; Sato, Yasushi; Iwata, Hiroshi; Kawai, Mitsuhisa; Kurebayashi, Yoichi

    2007-12-01

    Colonic mucosal mast cells are implicated in the pathogenesis of visceral hypersensitivity associated with irritable bowel syndromes. This study was designed to investigate the roles of mucosal mast cells in development of an experimental visceral hypersensitivity induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rats. TNBS, when injected into the proximal colon through laparotomy, produced a significant decrease in pain threshold of the distal colon to mechanical distention, indicating a visceral hypersensitivity. In the proximal colon that was directly insulted by TNBS, mucosal necrosis and extensive inflammatory cell infiltration were observed with concomitant increase in tissue myeloperoxide (MPO) activity. In the distal colon where distention stimuli were applied, the number of mucosal mast cells significantly increased following TNBS treatment, although neither mucosal injury nor increase in tissue MPO activity was observed. In an organ culture, spontaneous release of a mucosal mast cell-specific protease (RMCP-2) from the distal colon tissue of TNBS-treated rats was significantly larger than that of sham animals. Furthermore, TNBS-induced visceral hypersensitivity was significantly suppressed by subcutaneous pretreatment with a mast cell stabilizer doxantrazole in a dose-dependent manner. These findings suggest that prominent colonic mast cell infiltration associated with an enhanced spontaneous mediator release is responsible, at least partly, for development of visceral hypersensitivity induced by TNBS in rats.

  10. Rate of relapse in multibacillary patients after cessation of long-course dapsone monotherapy supplemented by a final supervised single dose of 1500 mg of rifampin.

    PubMed

    Cartel, J L; Naudin, J C

    1994-06-01

    When multidrug therapy was implemented in Senegal, 406 multibacillary (MB) patients who had been treated for more than 10 years by dapsone alone, and who had become clinically inactive and skin-smear negative, were released from treatment. Of these 406 patients, 298 were given a supervised single dose of 1500 mg of rifampin. Subsequently, 302 of them (229 who had been given rifampin and 73 who had not) were followed up by means of annual clinical and bacteriological examinations. Of the former 229 followed up for a mean period of 4.9 years, 34 patients relapsed (22 males and 12 females), giving a crude relapse rate of 15% and an overall risk of relapse of 3.1 per 100 patient-years. Of the latter 73 followed up for a mean period of 2.4 years, 5 relapsed (4 males and 1 female), giving a crude relapse rate of 6.8% and an overall risk of relapse of 2.9 per 100 patient-years. Such results, which are in agreement with those of a similar study conducted recently in Mali, indicate that the intake of a single dose of 1500 mg of rifampin by MB patients when they are released from long-course dapsone monotherapy does not result in a decrease of the relapse rate. Therefore, MB patients who have been treated with dapsone alone, even for long periods, should be put under multidrug therapy prior to their release from control.

  11. Hypersensitivity reactions associated with endovascular devices.

    PubMed

    Honari, Golara; Ellis, Stephen G; Wilkoff, Bruce L; Aronica, Mark A; Svensson, Lars G; Taylor, James S

    2008-07-01

    Allergic reactions to endoprostheses are uncommon and reported in association with orthopaedic, dental, endovascular and other implanted devices. Hypersensitivity reactions to the biomaterials used in endovascular prostheses are among the infrequent reactions that may lead to local or systemic complications following cardiovascular therapeutic interventions. This article reviews potential immunotoxic effects of commonly used biomaterials. Reports of putative hypersensitivity reactions to endovascular devices, including coronary stents, perforated foramen occluders, pacemakers and implantable cardioverter defibrillators are also reviewed.

  12. Chemotherapy and biotherapy-induced hypersensitivity reactions.

    PubMed

    Van Gerpen, Ruth

    2009-01-01

    Nearly all chemotherapy and biotherapy drugs used in cancer treatment today can cause hypersensitivity reactions. Certain groups of drugs frequently associated with these reactions include the asparaginases, taxanes, platinum compounds, epipodophyllotoxins, and the monoclonal antibodies. Recognizing and managing hypersensitivity reactions are critical when caring for patients receiving these drugs because the reactions are potentially life-threatening. A thorough understanding of the drugs is necessary to assist the nurse in prevention, early recognition, and timely management.

  13. Drug Induced Hypersensitivity and the HLA Complex

    PubMed Central

    Alfirevic, Ana; Pirmohamed, Munir

    2011-01-01

    Drug-induced hypersensitivity reactions are of major concern and present a burden for national healthcare systems due to their often severe nature, high rate of hospital admissions and high mortality. They manifest with a wide range of symptoms and signs, and can be initiated by a wide range of structurally diverse chemical compounds. The pathophysiological mechanisms underlying hypersensitivity reactions are not well understood, but it is thought that they are immune mediated. MHC region on Chromosome 6 contains many genes with immune function. Classical MHC molecules are highly polymorphic cell surface glycoproteins whose function is to present peptide antigens to T cells. In addition to conferring protection from some diseases, HLA alleles are also associated with an increased risk of other diseases, including drug-induced hypersensitivity. Pharmacogenetic approach to predict the risk of drug-induced hypersensitivity has been established for several drugs. We will discuss the progress of hypersensitivity pharmacogenetics over the last few years and focus on current efforts of the international community to develop consortia which aim to standardize disease phenotypes and to identify affected individuals through international collaborations. In addition, we will discuss the clinical utility of HLA typing as predictive or diagnostic testing for drug-induced hypersensitivity.

  14. 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.

  15. Hypersensitivity to biomedical implants: Prevention and diagnosis.

    PubMed

    Rosner, Gregory A; Fonacier, Luz S

    2017-05-01

    There has been growing interest in the potential for adverse immunologic reactions to metals in biomedical devices and increasing referrals for the evaluation and management of metal hypersensitivity reactions reported in orthopedic, cardiac, gynecologic, and dental implant devices. However, there are few studies that give evidence-based recommendations on how to evaluate this issue in our practices. We reviewed reasonable evidence and expert opinion on biomedical device hypersensitivity and published guidelines on pre- and postimplantation evaluation of delayed hypersensitivity reactions in patients suspected of possible metal hypersensitivity to biomedical devices. There is consensus that routine preimplantation evaluation in individuals with no history of adverse cutaneous reactions to metals or a history of implant-related adverse events is not necessary. However, patients with a history of metal hypersensitivity of a magnitude sufficient to cause concern for the patient or health care provider may benefit from evaluation by patch testing (PT) before device implantation. Patients after implantation and with chronic unexplained implant failure or with dermatitis may benefit from patch test evaluation after other causes, such as infection and biomechanical issues, are ruled out. However, a positive metal patch test result does not prove symptom causality, and the decision regarding implant revision can only be made after a thorough discussion among the patient, the allergist or dermatologist, and the orthopedic surgeon. Consensus guidelines for the evaluation of hypersensitivity to biomedical devices can be used by the practicing physician while awaiting for the results of further investigations.

  16. Esophageal hypersensitivity in noncardiac chest pain.

    PubMed

    Min, Yang Won; Rhee, Poong-Lyul

    2016-09-01

    Noncardiac chest pain (NCCP) is an often-encountered clinical problem. Although many patients suffer from persistent or recurrent chest pain, treatment remains a challenge owing to its various possible etiologies. Gastroesophageal reflux disease (GERD) is the most common cause of NCCP. In GERD-related NCCP, proton pump inhibitor treatment appears to be effective. However, the pathophysiology remains to be fully elucidated in NCCP patients without GERD. Treatment for non-GERD-related NCCP has been aimed at esophageal motility disorders and visceral hypersensitivity. As there is growing evidence that esophageal visceral hypersensitivity plays a role in NCCP, pain modulators have become the mainstay of therapy in patients with non-GERD-related NCCP. However, there is an unmet need for the treatment of esophageal hypersensitivity in NCCP due to modest evidence for the benefit of pain modulators, including antidepressants, in non-GERD-related NCCP. Recent studies have demonstrated that esophageal mast cell infiltration and impaired mucosal integrity are related to visceral hypersensitivity in patients with NCCP. Thus, esophageal mast cell stabilization and restoration of esophageal mucosal integrity could be considered potential therapeutic targets in selected NCCP patients with hypersensitivity. However, further observations are necessary to shed light on esophageal hypersensitivity in NCCP.

  17. [DRESS syndrome induced by ciprofloxacine].

    PubMed

    Sahnoun, Rym; El Aïdli, Sihem; Zaïem, Ahmed; Lakhoua, Ghozlane; Kastalli, Sarrah; Daghfous, Riadh

    2015-04-01

    The Drug rash with hypereosinophilia and systemic symptoms (DRESS) syndrome, or hypersensitivity syndrome, is a severe drug-induced hypersensitivity syndrome. It has been exceptionally described with ciprofloxacin. We report a 47-year-old-woman who developed DRESS syndrome, 2 days after taking ciprofloxacin for a urinary infection. She had a generalized maculopapular rash, severe rhabdomyolysis, liver involvement, renal failure and hypereosinophilia. Clinical symptoms had completely resolved after ciprofloxacin withdrawal. Renal failure has decrease after short corticosteroid treatment. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  18. Allergic acute coronary syndrome (Kounis syndrome)

    PubMed Central

    Chhabra, Lovely; Masrur, Shihab; Parker, Matthew W.

    2015-01-01

    Anaphylaxis rarely manifests as a vasospastic acute coronary syndrome with or without the presence of underlying coronary artery disease. The variability in the underlying pathogenesis produces a wide clinical spectrum of this syndrome. We present three cases of anaphylactic acute coronary syndrome that display different clinical variants of this phenomenon. The main pathophysiological mechanism of the allergic anginal syndromes is the inflammatory mediators released during a hypersensitivity reaction triggered by food, insect bites, or drugs. It is important to appropriately recognize and treat Kounis syndrome in patients with exposure to a documented allergen. PMID:26130889

  19. 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

  20. Association between pollen hypersensitivity and edible vegetable allergy: a review.

    PubMed

    Caballero, T; Martín-Esteban, M

    1998-01-01

    Over the last three decades several authors have described the existence of an association between sensitivity to different pollens and sensitivity to diverse edible vegetables. An association between ragweed pollinosis and hypersensitivity to Cucurbitaceae vegetables (e.g., watermelon, melon, cucumber) and banana has been reported. Other authors have found a relationship between birch pollinosis and sensitization to hazelnut, apple, carrot, potato, kiwi and other vegetables. Additionally, several papers have shown the association between mugwort pollinosis and sensitization to celery, carrot, spices, nuts, mustard and Leguminoseae vegetables. Later, some studies showed association between grass pollinosis and sensitization to tomato, potato, green- pea, peanut, watermelon, melon, apple, orange and kiwi. Finally, an association between sensitization to plantain pollen and melon hypersensitivity was also described. The association between pollinosis and edible vegetable sensitization has been explained by the combination of different hypotheses, such as the following: 1) presence of lectins in edible vegetables; 2) existence of IgE to carbohydrates of the glycoproteins (cross-reactive carbohydrate determinants); and, 3) existence of common allergens between pollens and edible vegetables. Up to now three allergens have been identified as responsible for cross-reactivity in these associations: profilin, a 14 kd protein that regulates actin; Bet v 1, the 18 kd birch pollen allergen; and a 60-69 kd allergen. It is important to study in depth these associated sensitizations and the common allergens responsible for them in order to improve diagnostic methods and treatment of these syndromes.

  1. A Case of Occupational Hypersensitivity Pneumonitis Associated with Trichloroethylene

    PubMed Central

    Kim, Young Jae; Hwang, Eu Dong; Leem, Ah Young; Kang, Beo Deul; Chang, Soo Yun; Kim, Ho Keun; Park, In Kyu; Kim, Song Yee; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Park, Moo Suk; Kim, Young Sam; Kim, Se Kyu; Chang, Joon

    2014-01-01

    Trichloroethylene (TCE) is a toxic chemical commonly used as a degreasing agent, and it is usually found in a colorless or blue liquid form. TCE has a sweet, chloroform-like odor, and this volatile chlorinated organic chemical can cause toxic hepatitis, neurophysiological disorders, skin disorders, and hypersensitivity syndromes. However, the hypersensitivity pneumonitis (HP) attributed to TCE has rarely been reported. We hereby describe a case of HP associated with TCE in a 29-year-old man who was employed as a lead welder at a computer repair center. He was installing the capacitors on computer chip boards and had been wiped down with TCE. He was admitted to our hospital with complaints of dry coughs, night sweats, and weight losses for the past two months. HP due to TCE exposure was being suspected due to his occupational history, and the results of a video-associated thoracoscopic biopsy confirmed the suspicions. Symptoms have resolved after the steroid pulse therapy and his occupational change. TCE should be taken into consideration as a potential trigger of HP. Early recognition and avoidance of the TCE exposure in the future is important for the treatment of TCE induced HP. PMID:24624216

  2. Efficacy and Safety of Once-Daily Dapsone Gel, 7.5% for Treatment of Adolescents and Adults With Acne Vulgaris: Second of Two Identically Designed, Large, Multicenter, Randomized, Vehicle-Controlled Trials.

    PubMed

    Eichenfield, Lawrence F; Lain, Ted; Frankel, Ellen H; Jones, Terry M; Chang-Lin, Joan-En; Berk, David R; Ruan, Shiling; Kaoukhov, Alexandre

    2016-08-01

    Dapsone gel, 5% is administered twice daily for the treatment of acne vulgaris, and some patients may find adherence challenging.
    The study objective was to assess the efficacy and safety, compared with vehicle, of acne treatment with a recently FDA-approved, once-daily formulation of dapsone gel, 7.5%, with a 50% greater concentration of dapsone.
    This 12-week, randomized, double-blind, vehicle-controlled, multicenter clinical trial enrolled patients aged 12 years and older with 20-50 facial inflammatory lesions, 30-100 facial noninflammatory lesions, and an acne grade of 3 (moderate) on the Global Acne Assessment Score (GAAS). Patients were randomized (1:1 ratio) to topical dapsone gel, 7.5% or vehicle once daily for 12 weeks. Investigators assessed GAAS success rate (proportion of patients with a GAAS of 0 or 1) and percent change from baseline in inflammatory, noninflammatory, and total lesions.
    The intent-to-treat population comprised 2238 patients (1118 in the dapsone gel, 7.5% group and 1120 in the vehicle group). The GAAS success rates were 29.8% for the dapsone gel, 7.5% group and 20.9% for the vehicle group (P<0.001) at week 12. At week 12, mean inflammatory lesions decreased from baseline by 53.8% and 47.3%, noninflammatory lesions decreased by 45.9% and 40.4%, and total lesions decreased by 48.9% and 43.2% for the dapsone gel, 7.5% group and the vehicle group, respectively (all, P<0.001). The incidence of treatment-emergent adverse events was similar for dapsone gel, 7.5% (17.6%) and vehicle (17.1%). Most adverse events were mild to moderate in severity. The most frequently reported increase in severity for all of the dermal tolerability scales was from "none" to "mild."
    Dapsone gel, 7.5% applied topically once daily is an effective, safe, and well-tolerated treatment for acne vulgaris. Improvements in acne severity and lesions were observed over the 12-week course of treatment.

    J Drugs

  3. Micronucleus assay in human fibroblasts: a measure of spontaneous chromosomal instability and mutagen hypersensitivity

    SciTech Connect

    Rudd, N.L.; Hoar, D.I.; Greentree, C.L.; Dimnik, L.S.; Hennig, U.S.S.

    1988-01-01

    By comparing fibroblast strains derived from individuals exhibiting chromosome instability and/or mutagen hypersensitivity (Cockayne syndrome, ataxia telangiectasia, and Fanconi anemia) with strains derived from health donors, the fibroblast micronucleus assay has been established as a reproducible measure of the genotypic variation in spontaneous or mitomycin C (MMC)-induced chromosomal instability. The patient strains that were moderately or exquisitely sensitive to MMC could be distinguished readily from the control strains, both in levels of spontaneous micronuclei and in sensitivity to MMC, whereas the mildly sensitive strain (Cockayne syndrome) overlapped with the control range. The reproducibility of the assay was evaluated within and between experiments. In addition to its value as a test system for genotoxins, the fibroblast micronucleus assay may be useful for investigating genetically determined hypersensitivity to mutagens, elevated spontaneous chromosomal breakage, and chromosome segregation errors.

  4. Hypersensitivity to hypercapnia: definition/(s).

    PubMed

    Vickers, Kristin

    2012-05-15

    Empirical evidence indicates that panic disorder (PD) patients experience hypersensitivity to hypercapnia, a condition in which the blood level of carbon dioxide exceeds the normal value. The importance of this research line is substantial and indeed, hypercapnic hypersensitivity has been advanced as a possible endophenotype of panic. Definitions of "hypersensitivity," however, have varied. The purpose of this brief review is to delineate and critique different definitions of hypercapnic hypersensitivity. Several definitions - panic attack rate, panic symptoms including dyspnea, subjective anxiety, and respiratory disturbance - are explored. The review concludes that although no ideal definition has emerged, marked anxiety post-hypercapnia has substantial support as a putative trait marker of PD. The term "subjective hypersensitivity" (Coryell et al., 2001) is re-introduced to denote pronounced anxiety post-hypercapnia and recommended for use along with its previous definition: increased self-reported anxiety measured on a continuous visual analog scale, already widely in use. Due to the well-established link between panic and respiration, definitional candidates focusing on aberrant respiratory response - less investigated as trait markers of PD in high risk studies - warrant scrutiny as well. Several reasons why definitional clarity might be beneficial are presented, along with ideas for future research.

  5. [Hypersensitivity of estrogen receptors as a cause of gigantomasty in two girls].

    PubMed

    Noczyńska, A; Wasikowa, R; Myczkowski, T

    2001-12-01

    The authors present two girls with gigantomastia, 14 and 15 years of age. Laboratory examinations demonstrate an increase of estrogen receptors in the glandular tissue. In the immunohistochemical investigations ascertained was a receptor hypersensitivity of estrogen and progesterone receptors. In one of the girls shown was hyperprolactinemia in the metoclopramide test (patient J.K.) In the physical examination hyperlordosis, kyphosis, gigantomastia was observed. Additional in patient K.S.--anorexia and patient J.K.--Sjögren's syndrome.

  6. Defective DNA cross-link removal in Chinese hamster cell mutants hypersensitive to bifunctional alkylating agents

    SciTech Connect

    Hoy, C.A.; Thompson, L.H.; Mooney, C.L.; Salazar, E.P.

    1985-04-01

    DNA repair-deficient mutants from five genetic complementation groups isolated previously from Chinese hamster cells were assayed for survival after exposure to the bifunctional alkylating agents mitomycin C or diepoxybutane. Groups 1, 3, and 5 exhibited 1.6- to 3-fold hypersensitivity compared to the wild-type cells, whereas Groups 2 and 4 exhibited extraordinary hypersensitivity. Mutants from Groups 1 and 2 were exposed to 22 other bifunctional alkylating agents in a rapid assay that compared cytotoxicity of the mutants to the wild-type parental strain, AA8. With all but two of the compounds, the Group 2 mutant (UV4) was 15- to 60-fold more sensitive than AA8 or the Group 1 mutant (UV5). UV4 showed only 6-fold hypersensitivity to quinacrine mustard. Alkaline elution measurements showed that this compound produced few DNA interstrand cross-links but numerous strand breaks. Therefore, the extreme hypersensitivity of mutants from Groups 2 and 4 appeared specific for compounds the main cytotoxic lesions of which were DNA cross-links. Mutant UV5 was only 1- to 4-fold hypersensitive to all the compounds. Although the initial number of cross-links was similar for the three cell lines, the efficiency of removal of cross-links was lowest in UV4 and intermediate in UV5. These results suggest that the different levels of sensitivity are specifically related to different efficiencies of DNA cross-link removal. The phenotype of hypersensitivity to both UV radiation and cross-link damage exhibited by the mutants in Groups 2 and 4 appears to differ from those of the known human DNA repair syndromes.

  7. Adrenergic β2-receptors mediates visceral hypersensitivity induced by heterotypic intermittent stress in rats.

    PubMed

    Zhang, Chunhua; Rui, Yun-Yun; Zhou, Yuan-Yuan; Ju, Zhong; Zhang, Hong-Hong; Hu, Chuang-Ying; Xiao, Ying; Xu, Guang-Yin

    2014-01-01

    Chronic visceral pain in patients with irritable bowel syndrome (IBS) has been difficult to treat effectively partially because its pathophysiology is not fully understood. Recent studies show that norepinephrine (NE) plays an important role in the development of visceral hypersensitivity. In this study, we designed to investigate the role of adrenergic signaling in visceral hypersensitivity induced by heterotypical intermittent stress (HIS). Abdominal withdrawal reflex scores (AWRs) used as visceral sensitivity were determined by measuring the visceromoter responses to colorectal distension. Colon-specific dorsal root ganglia neurons (DRGs) were labeled by injection of DiI into the colon wall and were acutely dissociated for whole-cell patch-clamp recordings. Blood plasma level of NE was measured using radioimmunoassay kits. The expression of β2-adrenoceptors was measured by western blotting. We showed that HIS-induced visceral hypersensitivity was attenuated by systemic administration of a β-adrenoceptor antagonist propranolol, in a dose-dependent manner, but not by a α-adrenoceptor antagonist phentolamine. Using specific β-adrenoceptor antagonists, HIS-induced visceral hypersensitivity was alleviated by β2 adrenoceptor antagonist but not by β1- or β3-adrenoceptor antagonist. Administration of a selective β2-adrenoceptor antagonist also normalized hyperexcitability of colon-innervating DRG neurons of HIS rats. Furthermore, administration of β-adrenoceptor antagonist suppressed sustained potassium current density (IK) without any alteration of fast-inactivating potassium current density (IA). Conversely, administration of NE enhanced the neuronal excitability and produced visceral hypersensitivity in healthy control rats, and blocked by β2-adrenoceptor antagonists. In addition, HIS significantly enhanced the NE concentration in the blood plasma but did not change the expression of β2-adrenoceptor in DRGs and the muscularis externa of the colon. The

  8. 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

  9. Abolishment of TNBS-induced visceral hypersensitivity in mast cell deficient rats.

    PubMed

    Ohashi, Katsuyo; Sato, Yasushi; Kawai, Mitsuhisa; Kurebayashi, Yoichi

    2008-02-13

    Mucosal mast cells are implicated in visceral hypersensitivity associated with irritable bowel syndrome (IBS). In this study, we investigated the role of mast cells in the development of visceral hypersensitivity by using mast cell deficient (Ws/Ws) rats and their control (W+/W+). In W+/W+ rats, an injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the proximal colon produced a significant decrease in pain threshold of the distal colon. Severe mucosal necrosis and inflammatory cell infiltration with concomitant increase in tissue myeloperoxidase activity were observed in the proximal colon that was directly insulted by TNBS, whereas neither necrosis nor increased myeloperoxidase activity occurred in the distal colon, indicating that TNBS-induced hypersensitivity is not caused by the local tissue damage or inflammation in the region of the gut where distention stimuli were applied. On the other hand, TNBS failed to elicit visceral hypersensitivity in Ws/Ws rats. This finding indicates that mast cells are essential for development of TNBS-induced visceral hypersensitivity in rats. Since the severity of TNBS-induced proximal colon injury and MPO activity was not affected by mast cell deficiency, it is unlikely that abolishment of visceral hypersensitivity in mast cell deficient rats was a result of altered development of the primary injury in the proximal colon. There was no difference between sham-operated Ws/Ws and W+/W+ rats in colonic pain threshold to distention stimuli, indicating that mast cells play no modulatory roles in normal colonic nociception. The present results support the view that mucosal mast cells play key roles in the pathogenesis of IBS.

  10. 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

  11. [The reactions of hypersensitivity: the mechanisms of development, clinical manifestations, principles of diagnostic (a lecture)].

    PubMed

    Tukavkina, S Yu; Kharseyeva, G G

    2014-05-01

    The article considers the principles of modern classification of hypersensitivity, pathogenic mechanisms of formation of its various types resulting in development of typical clinical symptoms and syndromes. The knowledge and comprehension of these issues is important for physicians of different specializations since it permits to properly make out and formulate diagnosis and timely send patient for examination and treatment to such specialist as allergist-immunologist. The particular attention was paid to description of pathogenesis of diseases and syndromes underlaid by IgE-mediated type of hypersensitivity since their share is highest and clinical manifestations frequently require emergency medical care. The diagnostic of allergic diseases is to be implemented sequentially (step-by-step) and include common clinical and special (specific) methods. In case of choosing of extent of specialized allergological examination the diagnostic significance of techniques and their safety is to be taken into account concerning condition of patient. The diagnosis is objectively formulated only by complex of examination results. It is worth to remember about possibility of development of syndromes similar to IgE-mediated allergy by their clinical manifestations but belonging to non-allergic type of hypersensitivity. It is important to know main causes, mechanisms and ways of formation of such reactions previously named as anaphylactoid ones.

  12. Assessing the potential to induce respiratory hypersensitivity.

    PubMed

    Holsapple, Michael P; Jones, David; Kawabata, Thomas T; Kimber, Ian; Sarlo, Kathy; Selgrade, MaryJane K; Shah, Jui; Woolhiser, Michael R

    2006-05-01

    Acute and repeat dose inhalation studies have been an important part of the safety assessment of drugs, chemicals, and other products throughout the world for many years. It is known that damage to the respiratory tract can be triggered either by nonspecific irritation or by specific immune-mediated pathogenesis, and it is acknowledged that traditional inhalation studies are not designed to address fully the impact of the latter. It is also recognized that different types of immune-mediated responses can be triggered by different classes of compounds and that some immune reactions in the lung are life threatening. As such, it is important to understand as fully as possible the basis for the immune-mediated damage to the lung in order to characterize adequately the risks of individual chemicals or proteins. It is against this background that a review of the methods used to assess the potential for immune-mediated respiratory hypersensitivity was conducted. The primary objectives of this review are to discuss appropriate methods for identifying and characterizing respiratory hypersensitivity hazards and risks; and to identify key data gaps and related research needs with respect to respiratory hypersensitivity testing. The following working definition of respiratory hypersensitivity was formulated: a hypersensitivity response in the respiratory tract precipitated by a specific immune response, mediated by multiple mechanisms, including IgE antibody. Because of the importance played by various classes of compounds, the subsequent sections of this review will consider protein-specific, chemical-specific, and drug-specific aspects of respiratory hypersensitivity.

  13. Reversal of visceral and somatic hypersensitivity in a subset of hypersensitive rats by intracolonic lidocaine

    PubMed Central

    Zhou, QiQi; Price, Donald D.; Verne, G. Nicholas

    2010-01-01

    Chronic abdominal pain is a common gastrointestinal symptom experienced by patients. We have previously shown that IBS patients with visceral hypersensitivity also have evidence of thermal hypersensitivity of the hand and foot that is reversed by rectal lidocaine jelly. We have also recently developed an animal model of chronic visceral and somatic hypersensitivity in rats treated with intracolonic trinitrobenzene sulfonic acid (TNBS). The objective of the current study was to determine the effects of intracolonic lidocaine on visceral/somatic hypersensitivity in TNBS-treated rats. A total of 20 hypersensitive rats received either 20 mg intracolonic lidocaine (n = 10) or saline jelly (n = 10). In comparison to saline jelly, intracolonic lidocaine jelly reduced responses to nociceptive visceral/somatic stimuli in hypersensitive rats. The effects were present within 5–30 min after administration of lidocaine and lasted for 6 h. Lidocaine had no effects on recovered rats or control rats that had originally been treated with intracolonic saline instead of TNBS. Local anesthetic blockade of peripheral impulse input from the colon reduces both visceral and somatic hypersensitivity in TNBS-treated rats, similar to results in IBS patients. The results provide further evidence that visceral and secondary somatic hypersensitivity in a subset of TNBS-treated rats reflect central sensitization mechanisms maintained by tonic impulse input from the colon. This study evaluates the reversal of visceral/somatic hypersensitivity in a subset of TNBS-treated rats with intracolonic lidocaine. This animal model may be used in the future to study the mechanisms of local anesthetic agents applied to the gut to reduce visceral pain. PMID:18486344

  14. Non-celiac gluten hypersensitivity.

    PubMed

    Ashat, Munish; Kochhar, Rakesh

    2014-01-01

    There has been an increasing interest in non-celiac gluten sensitivity (NCGS) in recent years. The condition is characterized by both gastrointestinal and extra-intestinal symptoms that respond to gluten withdrawal. Most of the symptoms are subjective and for many years such patients remain in a diagnostic dilemma. Although symptomalogy is similar to irritable bowel syndrome (IBS), NCGS is now regarded as a distinct clinical entity. However, the disease pathology is not well elucidated and our knowledge of NCGS is still very rudimentary. This review highlights the importance of this new clinical entity, outlines its pathological mechanisms and suggests a diagnostic algorithm for its management.

  15. How to manage asparaginase hypersensitivity in acute lymphoblastic leukemia.

    PubMed

    Burke, Michael J

    2014-12-01

    Outcomes for children with acute lymphoblastic leukemia (ALL) have improved significantly in recent decades, primarily due to dose-intensified, multi-agent chemotherapy regimens, of which asparaginase has played a prominent role. Despite this success, hypersensitivity remains a significant problem, often requiring the termination of asparaginase. Failure to complete the entire asparaginase therapy course due to clinical hypersensitivity, subclinical hypersensitivity (i.e., silent inactivation), or other treatment-related toxicity is associated with poor ALL outcomes. Thus, it is critical to rapidly identify patients who develop clinical/subclinical hypersensitivity and switch these patients to an alternate asparaginase formulation. This article provides an overview of asparaginase hypersensitivity, identification and management of hypersensitivity and subclinical hypersensitivity, and issues related to switching patients to asparaginase Erwinia chrysanthemi following hypersensitivity reaction.

  16. Comparison of chloroquine, pyrimethamine and sulfadoxine, and chlorproguanil and dapsone as treatment for falciparum malaria in pregnant and non-pregnant women, Kakamega District, Kenya.

    PubMed

    Keuter, M; van Eijk, A; Hoogstrate, M; Raasveld, M; van de Ree, M; Ngwawe, W A; Watkins, W M; Were, J B; Brandling-Bennett, A D

    1990-09-08

    To compare treatment and protection against falciparum malaria in pregnant and non-pregnant women with three drug regimens. Prospective intervention study with six weeks' follow up. Patients received one of three drug regimens in order of entry. Primary care hospital and secondary girls' school in rural western Kenya. 158 of 988 pregnant women (89 primigravid and 69 multigravid) in the third trimester and 105 of 1488 non-pregnant schoolgirls of reproductive age were parasitaemic (more than 500 asexual forms/microliter. These women were divided into three treatment groups by gravid state. Women were treated with chloroquine base 25 mg/kg over three days or pyrimethamine 75 mg and sulfadoxine 1500 mg as a single dose or chlorproguanil 1.2 mg/kg and dapsone 2.4 mg/kg as a single dose. Parasitaemia and haemoglobin concentrations measured at seven day intervals for six weeks. Primigravid women were more likely to be parasitaemic on follow up than multigravidas or nulligravidas, whose response was about the same. Parasites did not clear by day 7 in primigravidas in six (20%) of 30 who received chloroquine, three (8%) of 35 treated with pyrimethamine and sulfadoxine, and none of 23 treated with chlorproguanil and dapsone. At day 28, 83%, 19%, and 67% of primigravidas in these treatment groups were parasitaemic. Haemoglobin concentrations rose in all women, but improvement was sustained only in women who remained free of parasites. Clearance of parasites was better with either pyrimethamine and sulfadoxine or chlorproguanil and dapsone than with chloroquine. Longest protection was obtained with pyrimethamine and sulfadoxine.

  17. Comparison of chloroquine, pyrimethamine and sulfadoxine, and chlorproguanil and dapsone as treatment for falciparum malaria in pregnant and non-pregnant women, Kakamega District, Kenya.

    PubMed Central

    Keuter, M; van Eijk, A; Hoogstrate, M; Raasveld, M; van de Ree, M; Ngwawe, W A; Watkins, W M; Were, J B; Brandling-Bennett, A D

    1990-01-01

    OBJECTIVE--To compare treatment and protection against falciparum malaria in pregnant and non-pregnant women with three drug regimens. DESIGN--Prospective intervention study with six weeks' follow up. Patients received one of three drug regimens in order of entry. SETTING--Primary care hospital and secondary girls' school in rural western Kenya. PATIENTS--158 of 988 pregnant women (89 primigravid and 69 multigravid) in the third trimester and 105 of 1488 non-pregnant schoolgirls of reproductive age were parasitaemic (more than 500 asexual forms/microliter. These women were divided into three treatment groups by gravid state. INTERVENTIONS--Women were treated with chloroquine base 25 mg/kg over three days or pyrimethamine 75 mg and sulfadoxine 1500 mg as a single dose or chlorproguanil 1.2 mg/kg and dapsone 2.4 mg/kg as a single dose. MAIN OUTCOME MEASURES--Parasitaemia and haemoglobin concentrations measured at seven day intervals for six weeks. RESULTS--Primigravid women were more likely to be parasitaemic on follow up than multigravidas or nulligravidas, whose response was about the same. Parasites did not clear by day 7 in primigravidas in six (20%) of 30 who received chloroquine, three (8%) of 35 treated with pyrimethamine and sulfadoxine, and none of 23 treated with chlorproguanil and dapsone. At day 28, 83%, 19%, and 67% of primigravidas in these treatment groups were parasitaemic. Haemoglobin concentrations rose in all women, but improvement was sustained only in women who remained free of parasites. CONCLUSIONS--Clearance of parasites was better with either pyrimethamine and sulfadoxine or chlorproguanil and dapsone than with chloroquine. Longest protection was obtained with pyrimethamine and sulfadoxine. PMID:2207399

  18. Tactile Sensitivity in Asperger Syndrome

    ERIC Educational Resources Information Center

    Blakemore, Sarah-Jayne; Tavassoli, Teresa; Calo, Susana; Thomas, Richard M.; Catmur, Caroline; Frith, Uta; Haggard, Patrick

    2006-01-01

    People with autism and Asperger syndrome are anecdotally said to be hypersensitive to touch. In two experiments, we measured tactile thresholds and suprathreshold tactile sensitivity in a group of adults with Asperger syndrome. In the first experiment, tactile perceptual thresholds were measured. Two frequencies of vibrotactile stimulation were…

  19. Tactile Sensitivity in Asperger Syndrome

    ERIC Educational Resources Information Center

    Blakemore, Sarah-Jayne; Tavassoli, Teresa; Calo, Susana; Thomas, Richard M.; Catmur, Caroline; Frith, Uta; Haggard, Patrick

    2006-01-01

    People with autism and Asperger syndrome are anecdotally said to be hypersensitive to touch. In two experiments, we measured tactile thresholds and suprathreshold tactile sensitivity in a group of adults with Asperger syndrome. In the first experiment, tactile perceptual thresholds were measured. Two frequencies of vibrotactile stimulation were…

  20. Loss of Central Inhibition: Implications for Behavioral Hypersensitivity after Contusive Spinal Cord Injury in Rats

    PubMed Central

    Berrocal, Yerko A.; Almeida, Vania W.; Puentes, Rocio; Knott, Eric P.; Hechtman, Jaclyn F.; Pearse, Damien D.

    2014-01-01

    Behavioral hypersensitivity is common following spinal cord injury (SCI), producing significant discomfort and often developing into chronic pain syndromes. While the mechanisms underlying the development of behavioral hypersensitivity after SCI are poorly understood, previous studies of SCI contusion have shown an increase in amino acids, namely, aspartate and glutamate, along with a decrease in GABA and glycine, particularly below the injury. The current study sought to identify alterations in key enzymes and receptors involved in mediating central inhibition via GABA and glycine after a clinically-relevant contusion SCI model. Following thoracic (T8) 25.0 mm NYU contusion SCI in rodents, significant and persistent behavioral hypersensitivity developed as evidenced by cutaneous allodynia and thermal hyperalgesia. Biochemical analyses confirmed upregulation of glutamate receptor GluR3 with downregulation of the GABA synthesizing enzyme (GAD65/67) and the glycine receptor α3 (GLRA3), notably below the injury. Combined, these changes result in the disinhibition of excitatory impulses and contribute to behavioral hyperexcitability. This study demonstrates a loss of central inhibition and the development of behavioral hypersensitivity in a contusive SCI paradigm. Future use of this model will permit the evaluation of different antinociceptive strategies and help in the elucidation of new targets for the treatment of neuropathic pain. PMID:25180088

  1. Transient Receptor Potential Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades Underlying Visceral Hypersensitivity.

    PubMed

    Balemans, Dafne; Boeckxstaens, Guy E; Talavera, Karel; Wouters, Mira M

    2017-04-06

    Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders (FGID) including functional dyspepsia, irritable bowel syndrome (IBS) and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family. A variety of TRP channels are present in the gastrointestinal tract (TRPV1, TRPV3, TRPV4, TRPA1, TRPM2, TRPM5 and TRPM8) and modulation of their function by increased activation or sensitization (decreased activation threshold) or altered expression in visceral afferents, have been reported in visceral hypersensitivity. TRP channels directly detect or transduce osmotic, mechanical, thermal and chemosensory stimuli. In addition, pro-inflammatory mediators released in tissue damage or inflammation can activate receptors of the G-protein coupled receptor (GPCR) superfamily leading to TRP channel sensitization and activation, which amplify pain and neurogenic inflammation. In this review, we highlight the current knowledge on the functional roles of neuronal TRP channels in visceral hypersensitivity and discuss the signaling pathways that underlie TRP channel modulation. We propose that a better understanding of TRP channels and their modulators may facilitate the development of more selective and effective therapies to treat visceral hypersensitivity.

  2. Sulfadoxine-pyrimethamine, chlorproguanil-dapsone, or chloroquine for the treatment of Plasmodium vivax malaria in Afghanistan and Pakistan: a randomized controlled trial.

    PubMed

    Leslie, Toby; Mayan, M Ismail; Hasan, M Anwar; Safi, M Hanif; Klinkenberg, Eveline; Whitty, Christopher J M; Rowland, Mark

    2007-05-23

    In areas where Plasmodium falciparum and Plasmodium vivax coexist and treatments for the 2 species differ, misdiagnosis can lead to poor outcomes in either disease. A unified therapy effective against both species would reduce reliance on species-specific diagnosis, which in many areas is difficult to maintain. The antifolates are an important and affordable antimalarial class to which it is often assumed P vivax malaria is intrinsically resistant. To test the relative efficacy and safety of 2 antifolate drugs against P vivax malaria and compare each with chloroquine. An open-label randomized controlled trial comparing chloroquine, sulfadoxine-pyrimethamine, and chlorproguanil-dapsone for the treatment of P vivax malaria was conducted in eastern Afghanistan and northwestern Pakistan, areas in which P vivax malaria predominates. A total of 20,410 patients older than 3 years were screened; 767 patients (315 in Pakistan and 452 in Afghanistan) with confirmed P vivax malaria were enrolled and followed up daily for 4 days, then weekly for 28 days, between March 2004 and June 2006. Complete clearance of parasites with no recrudescence by day 14. Secondary outcomes included being parasite-free by day 28, clinical failure, and anemia. By day 14, only 1 patient in the sulfadoxine-pyrimethamine group had parasites. By day 28, failure rates were found in 2 of 153 patients (1.3%) in the chloroquine group, 5 of 290 patients (1.7%) in the sulfadoxine-pyrimethamine group, and 27 of 272 patients (9.9%) in the chlorproguanil-dapsone group. Chlorproguanil-dapsone was less effective than sulfadoxine-pyrimethamine (adjusted odds ratio [OR], 6.4; 95% confidence interval [CI], 2.4-17.0; P<.001) and chloroquine (adjusted OR, 8.4; 95% CI, 2.0-36.5; P = .004). Chloroquine and sulfadoxine-pyrimethamine were equivalent in efficacy at day 28 (adjusted OR, 1.3; 95% CI, 0.3-7.0; P = .73). Chloroquine cleared gametocytes and asexual parasites more rapidly than sulfadoxine-pyrimethamine or

  3. Flow injection chemiluminescence sensor using core-shell molecularly imprinted polymers as recognition element for determination of dapsone.

    PubMed

    Lu, Fuguang; Yang, Jinlong; Sun, Min; Fan, Lulu; Qiu, Huamin; Li, Xiangjun; Luo, Chuannan

    2012-07-01

    This paper reports the preparation of dapsone (DDS) imprinted polymer layer-coated silica submicron particles (SiO(2)) combined with chemiluminescence (CL) toward analysis of tracing DDS in practical samples. To induce the selective occurrence of surface polymerization, the amino groups were first grafted at the surface of SiO(2) by the (3-aminopropyl)triethoxysilane (APTES). The molecularly imprinted polymers (MIP) were coated at the surface of modified SiO(2) by the graft copolymerization. After the removal of templates, recognition sites of DDS were exposed in the polymer layers. The DDS-imprinted products were characterized by FT-IR, SEM, TEM, dynamic adsorption, and static adsorption tests. The proximity between the thickness of MIP layer and the spatial size of DDS indicated that the imprinted sites almost situated at the surface of MIP, leading to rapid adsorption saturation within 90 min. The apparent maximum binding amount of MIP toward DDS was evaluated as 14.98 mg·g(-1), which was much higher than that of non-molecularly imprinted polymers. The CL sensor provided a wide linear range for DDS within 1.0 × 10(-6) to 1.0 × 10(-4) mol·L(-1) with a detection limit of 5.27 × 10(-7) mol·L(-1) and the relative standard deviation of 1.8 % (n = 11) by determinations of 5.0 × 10(-6) mol·L(-1) DDS. This method was applied to determine DDS in urine samples and satisfactory results were obtained.

  4. Severe Hyperacusis, Photophobia, and Skin Hypersensitivity

    PubMed Central

    Fioretti, Alessandra Barbara; Varakliotis, Theodoros; Poli, Otello; Cantagallo, Manuela; Eibenstein, Alberto

    2016-01-01

    We report a case of a patient with severe hyperacusis, photophobia, and skin hypersensitivity. The patient was initially treated with sound therapy and medical therapy for 4 months and successfully with a selective serotonin reuptake inhibitor (SSRI) and cognitive behavioral therapy which improved her mood and the tolerance for sounds and light. PMID:26981300

  5. 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

  6. Hydrocodone snorting leading to hypersensitivity pneumonitis

    PubMed Central

    Vijayaraghavan, Vimala

    2016-01-01

    We present a case of hypersensitivity pneumonitis caused by intranasal abuse of the prescription narcotic hydrocodone. The patient's clinical course was complicated by acute respiratory failure. A chest radiograph showed diffuse bilateral opacities. The patient was treated with noninvasive ventilation, a high dose of intravenous steroids, and bronchodilators, resulting in improvement of symptoms and radiographic appearance. PMID:27365873

  7. Benign hypersensitivity reactions to smallpox vaccine.

    PubMed

    Bessinger, G Todd; Smith, Sidney B; Olivere, Joseph W; James, Bruce L

    2007-05-01

    With the reinstitution of smallpox vaccinations, physicians are seeing significant numbers of adverse events for the first time since the 1980s. The most common adverse events seen in our large military population are benign. We observed a clinically and histopathologically distinct reaction pattern that has not been fully characterized previously. All smallpox-vaccinated patients at Fort Hood, Texas with adverse cutaneous reactions were referred to the dermatology clinic at Darnall Army Community Hospital. Patients were evaluated by a staff dermatologist who performed a skin biopsy and took clinical photographs. If the patients had intact vesicles or pustules, direct fluorescent antibody testing, viral and bacterial cultures, and polymerase chain reaction (PCR) assays were also performed. Three hypersensitivity reaction patterns were seen: exanthematous, erythema multiforme-like (EM-like), and urticarial. The patterns had distinct clinical and histopathologic findings. Of the 11,058 vaccinees, six had the exanthematous reaction pattern, two had the urticarial reaction pattern, and one had the EM-like pattern. We describe a new exanthematous type of hypersensitivity reaction to the smallpox vaccine. Hypersensitivity reactions occur at a rate higher than previously reported. In a carefully screened military population, these three hypersensitivity reactions are much more common than life-threatening or serious reactions. Although the reactions have distinct clinical and pathologic features, they are all characterized by mild or absent systemic symptoms and a benign outcome.

  8. Hypersensitivity of human subjects to environmental electric and magnetic field exposure: a review of the literature.

    PubMed Central

    Levallois, Patrick

    2002-01-01

    Hypersensitivity to exposure to electric and magnetic fields (EMFs) has been reported for nearly 20 years; however, the literature on the subject is still very limited. Nearly all the literature published concerns a dermatological syndrome that consists of mainly subjective symptoms (itching, burning, dryness) and a few objective symptoms (redness, dryness) appearing after individuals begin working with video display units and decreasing during absence from work. Case-control studies as well as some good but limited double-blind trials have not found any clear relationship between this syndrome and exposure to EMFs. A "general syndrome" with more general symptoms has been rarely described but seems to have a worse prognosis. The symptoms often associated with skin disorders are mainly of neurasthenic type and can cover a lot of nonspecific symptoms present in other atypical syndromes such as multiple chemical sensitivity or chronic fatigue. Most of these symptoms are allegedly triggered by exposure to different sources of EMFs, but there have been no valid etiological studies published on this more general syndrome. It appears that the so-called hypersensitivity to environmental electric and magnetic fields is an unclear health problem whose nature has yet to be determined. PMID:12194895

  9. Treatments for hypersensitive noncarious cervical lesions

    PubMed Central

    Veitz-Keenan, Analia; Barna, Julie Ann; Strober, Brad; Matthews, Abigail G.; Collie, Damon; Vena, Donald; Curro, Frederick A.; Thompson, Van P.

    2014-01-01

    Background The Practitioners Engaged in Applied Research and Learning (PEARL) Network conducted a three-armed randomized clinical study to determine the comparative effectiveness of three treatments for hypersensitive noncarious cervical lesions (NCCLs): use of a potassium nitrate dentifrice for treatment of hypersensitivity, placement of a resin-based composite restoration and placement of a sealant. Methods Seventeen trained practitioner-investigators (P-Is) in the PEARL Network enrolled participants (N = 304) with hypersensitive posterior NCCLs who met enrollment criteria. Participants were assigned to treatments randomly. Evaluations were conducted at baseline and at one, three and six months thereafter. Primary outcomes were the reduction or elimination of hypersensitivity as measured clinically and by means of patient-reported outcomes. Results Lesion depth and pretreatment sensitivity (mean, 5.3 on a 0- to 10-point scale) were balanced across treatments, as was sleep bruxism (present in 42.2 percent of participants). The six-month participant recall rate was 99 percent. Treatments significantly reduced mean sensitivity (P < .01), with the sealant and restoration groups displaying a significantly higher reduction (P < .01) than did the dentifrice group. The dentifrice group’s mean (standard deviation) sensitivity at six months was 2.1 (2.1); those of the sealant and restoration groups were 1.0 (1.6) and 0.8 (1.4), respectively. Patient-reported sensitivity (to cold being most pronounced) paralleled clinical measurements at each evaluation. Conclusions Sealing and restoration treatments were effective overall in reducing NCCL hypersensitivity. The potassium nitrate dentifrice reduced sensitivity with increasing effectiveness through six months but not to the degree offered by the other treatments. Practical Implications Sealant or restoration placement is an effective method of immediately reducing NCCL sensitivity. Although a potassium nitrate dentifrice

  10. Is Tadpole Pupil in an Adolescent Girl Caused by Denervation Hypersensitivity?

    PubMed

    Hansen, Jonas Kjeldbjerg; Møller, Hans Ulrik

    2017-01-04

    Tadpole pupil is a rarely encountered phenomenon caused by episodic, segmental iris dilator muscle spasm of short duration (2-15 minutes), occurring in clusters without a known precipitating factor. It has most commonly been described in women aged 28 to 48 years. A few hypotheses on pathogenesis have been discussed but none has been proved. Here, we present an adolescent girl with bilateral tadpole pupil that appeared during physical exercise. This is the first pediatric case of tadpole pupil, not caused by preceding surgery, to be published. Based on (1) this case in which tadpole pupil developed when the norepinephrine level rose during exercise, (2) the high ratio of patients with tadpole pupil who concurrently have or later develop Horner syndrome, in which denervation hypersensitivity is well described, (3) a previous report of a patient with both tadpole pupil and Horner syndrome who had denervation hypersensitivity on pharmacological testing, (4) a 29-year-old man with unilateral tadpole pupil induced by exercise, and (5) a 19-year-old man with bilateral tadpole pupil and possible autonomic neuropathy, we suggest denervation hypersensitivity as a probable pathogenic mechanism causing tadpole pupil. In addition, a suggestion for investigations to be performed in future pediatric cases is provided.

  11. Electroacupuncture at ST-36 relieves visceral hypersensitivity and decreases 5-HT(3) receptor level in the colon in chronic visceral hypersensitivity rats.

    PubMed

    Chu, Dan; Cheng, Pengfei; Xiong, Huiling; Zhang, Junjun; Liu, Shi; Hou, Xiaohua

    2011-05-01

    Visceral hypersensitivity is an important pathological mechanism of irritable bowel syndrome. Electroacupuncture (EA) could relieve chronic visceral hypersensitivity (CVH) in rats. However, little information is available about the mechanism. The aim of this study was to confirm the effects of EA at acupoint ST-36 (Zusanli) on CVH induced by the chemical colorectal irritation during postnatal development of rats, and to explore the possible 5-HT(3) receptor mechanism. Rats were randomized into four groups, including the normal control group, CVH group, CVH with EA group, and CVH with sham EA group. The abdominal electromyogram (EMG) in response to colorectal distension was selected as the index for measurement of visceral hypersensitivity. 5-HT(3) receptors were analyzed through reverse transcription-polymerase chain reaction and western blot. EA at ST-36 significantly decreased evoked EMG. The expression of 5-HT(3) receptor in the colon was increased in rats with CVH, and decreased after EA treatment. EA at acupoint ST-36 attenuates CVH in rats and decreases 5-HT(3) receptor level in the colon. Decreased 5-HT(3) receptor level in the colon may mediate the beneficial effect of EA in rats with CVH.

  12. Drug hypersensitivity reactions during hematopoietic stem cell transplantation.

    PubMed

    Bircher, Andreas J; Scherer Hofmeier, Kathrin

    2012-01-01

    Drugs may elicit a considerable variety of clinical signs, often affecting the skin and the mucous membranes. The most common are maculopapular exanthema, urticaria and angioedema. More rarely pustular, vesiculobullous, vasculitic and lichenoid lesions may be observed. Apart from the morphology, also the chronology of the occurrence and the evolution of the single skin lesions and the exanthema are paramount in the clinical diagnosis. Often, the skin is the only affected organ; however, it may herald a systemic involvement of internal organs, such as in severe drug-induced hypersensitivity syndromes or anaphylaxis. Cutaneous manifestations, particularly maculopapular exanthemas have a high incidence among patients treated with hematopoietic stem cell transplantation. In many cases, a virus- or drug-induced origin or a combination of both is responsible. However, the transplantation itself may also induce similar skin changes. These exanthemas include most often graft-versus-host disease, and rarely engraftment syndrome or eruption of lymphocyte recovery. The elucidation of the underlying cause of the exanthemas occurring in immune compromised patients and the determination of the correct diagnosis remain challenging. An extensive differential diagnosis has to be put forward. This includes several groups of disorders with sometimes very similar cutaneous manifestations. Manifestations form the underlying disease, complications from therapy, infections and drug reactions are the most common differential diagnoses.

  13. 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.

  14. The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota.

    PubMed

    Crouzet, L; Gaultier, E; Del'Homme, C; Cartier, C; Delmas, E; Dapoigny, M; Fioramonti, J; Bernalier-Donadille, A

    2013-04-01

    Alterations of intestinal microbiota and hypersensitivity to colonic distension are two features of the irritable bowel syndrome (IBS). However, the role of intestinal microbiota in visceral hypersensitivity of IBS patients is far to be established. The aim of our study was to determine whether the intestinal microbiota is involved in the visceral hypersensitivity in IBS. The painful response to colorectal distension and colonic mucosal parameters were assessed in gnotobiotic rats. Germfree (GF) rats were inoculated with the fecal microbiota from IBS patients characterized by hypersensitivity to colorectal distension (IBS HMA rats) or from non-hypersensitive healthy volunteers (Healthy HMA rats). Conventional rats were studied as normosensitivity control. Fecal microbial analyses were carried out in human and HMA rats fecal samples using cultural and molecular approaches. The microbial dysbiosis of the IBS gut microbiota (more sulfate-reducing bacteria and Enterobacteriaceae and less bifidobacteria) could be maintained in gnotobiotic rats. The number of abdominal contractions in response to colorectal distensions was significantly higher in IBS HMA rats than in healthy HMA rats. No difference was observed between healthy HMA and conventional rats. Colorectal compliance, epithelial paracellular permeability, and density of colonic mucosal mast cells were similar in the three groups of rats. We herein showed that sensitivity to colonic distension of IBS patients can be transferred to rats by the fecal microbiota. Mucosal alterations associated with microbiota transfer are not involved in this hypersensitivity. The altered IBS microbiota may have important role in the hypersensitivity characterizing IBS patients through specific bacterial metabolites. © 2013 Blackwell Publishing Ltd.

  15. Hypersensitivity to mosquito bites as the primary clinical manifestation of a juvenile type of Epstein-Barr virus-associated natural killer cell leukemia/lymphoma.

    PubMed

    Tokura, Y; Ishihara, S; Tagawa, S; Seo, N; Ohshima, K; Takigawa, M

    2001-10-01

    Hypersensitivity to mosquito bites or mosquito allergy is a mysterious disorder that has been reported mainly in Japanese patients (at least 58 patients) in the first two decades of life. The skin lesion at bite sites is typically a bulla that develops into necrosis. Patients simultaneously exhibit a high temperature and general malaise and subsequently may experience lymphadenopathy and hepatosplenomegaly. Recent studies have revealed that this mosquito hypersensitivity is associated with chronic Epstein-Barr virus infection and natural killer cell leukemia/lymphoma. The natural killer cell, infected with monoclonal (or oligoclonal) Epstein-Barr virus, seems to be involved in the pathogenesis of the hypersensitivity. Half of the patients reported died of hemophagocytic syndrome (or malignant histiocytosis), granular lymphocyte proliferative disorder, or lymphomas. We propose that this disease, defined as the triad of hypersensitivity to mosquito bites, chronic Epstein-Barr virus infection, and natural killer cell leukemia/lymphoma, is a clinical entity mostly seen in Asians.

  16. Allotype specific interactions of drugs and HLA molecules in hypersensitivity reactions.

    PubMed

    Illing, Patricia T; Mifsud, Nicole A; Purcell, Anthony W

    2016-10-01

    It is hypothesised that associations between adverse drug reactions and specific alleles of the human leukocyte antigens arise due to specific interactions between the human leukocyte antigen molecules and the causative drug that stimulate immune responses targeting drug exposed tissues. To date this has only been definitively demonstrated for abacavir, an antiretroviral that causes a systemic adverse drug reaction, abacavir hypersensitivity syndrome, solely in HLA-B*57:01(+) individuals. Whilst this has informed the modification of abacavir to remove immunogenicity, there remains an imperative to define other interactions between drugs and specific HLA in order to understand the scope of interactions that can drive T cell mediated drug hypersensitivity. Here we review the current state of understanding of these interactions.

  17. 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.

  18. [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.

  19. Modulation of visceral hypersensitivity by glial cell line-derived neurotrophic factor family receptor α-3 in colorectal afferents

    PubMed Central

    Shinoda, M.; Feng, B.; Albers, K. M.; Gebhart, G. F.

    2011-01-01

    Irritable bowel syndrome is characterized by colorectal hypersensitivity and contributed to by sensitized mechanosensitive primary afferents and recruitment of mechanoinsensitive (silent) afferents. Neurotrophic factors are well known to orchestrate dynamic changes in the properties of sensory neurons. Although pain modulation by proteins in the glial cell line-derived neurotrophic factor (GDNF) family has been documented in various pathophysiological states, their role in colorectal hypersensitivity remains unexplored. Therefore, we investigated the involvement of the GDNF family receptor α-3 (GFRα3) signaling in visceral hypersensitivity by quantifying visceromotor responses (VMR) to colorectal distension before and after intracolonic treatment with 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baseline responses to colorectal distension did not differ between C57BL/6 and GFRα3 knockout (KO) mice. Relative to intracolonic saline treatment, TNBS significantly enhanced the VMR to colorectal distension in C57BL/6 mice 2, 7, 10, and 14 days posttreatment, whereas TNBS-induced visceral hypersensitivity was significantly suppressed in GFRα3 KO mice. The proportion of GFRα3 immunopositive thoracolumbar and lumbosacral colorectal dorsal root ganglion neurons was significantly elevated 2 days after TNBS treatment. In single fiber recordings, responses to circumferential stretch of colorectal afferent endings in C57BL/6 mice were significantly increased (sensitized) after exposure to an inflammatory soup, whereas responses to stretch did not sensitize in GFRα3 KO mice. These findings suggest that enhanced GFRα3 signaling in visceral afferents may contribute to development of colorectal hypersensitivity. PMID:21193524

  20. Hippocampal microglial activation and glucocorticoid receptor down-regulation precipitate visceral hypersensitivity induced by colorectal distension in rats.

    PubMed

    Zhang, Gongliang; Zhao, Bing-Xue; Hua, Rong; Kang, Jie; Shao, Bo-Ming; Carbonaro, Theresa M; Zhang, Yong-Mei

    2016-03-01

    Visceral hypersensitivity is a common characteristic in patients suffering from irritable bowel syndrome (IBS) and other disorders with visceral pain. Although the pathogenesis of visceral hypersensitivity remains speculative due to the absence of pathological changes, the long-lasting sensitization in neuronal circuitry induced by early life stress may play a critical role beyond the digestive system even after complete resolution of the initiating event. The hippocampus integrates multiple sources of afferent inputs and sculpts integrated autonomic outputs for pain and analgesia regulation. Here, we examined the hippocampal mechanism in the pathogenesis of visceral hypersensitivity with a rat model induced by neonatal and adult colorectal distensions (CRDs). Neither neonatal nor adult CRD evoked behavioral abnormalities in adulthood; however, adult re-exposure to CRD induced persistent visceral hypersensitivity, depression-like behaviors, and spatial learning impairment in rats that experienced neonatal CRD. Rats that experienced neonatal and adult CRDs presented a decrease in hippocampal glucocorticoid receptor (GR) immunofluorescence staining and protein expression, and increases in hippocampal microglial activation and cytokine (IL-1β and TNF-α) accumulation. The decrease in hippocampal GR expression and increase in hippocampal IL-1β and TNF-α accumulation could be prevented by hippocampal local infusion of minocycline, a microglial inhibitor. These results suggest that neonatal CRD can increase the vulnerability of hippocampal microglia, and adult CRD challenge facilitates the hippocampal cytokine release from the sensitized microglia, which down-regulates hippocampal GR protein expression and, subsequently, precipitates visceral hypersensitivity.

  1. Hypersensitivity pneumonitis due to an ultrasonic humidifier.

    PubMed

    Alvarez-Fernández, J A; Quirce, S; Calleja, J L; Cuevas, M; Losada, E

    1998-02-01

    We describe a woman with hypersensitivity pneumonitis that was related to using a home ultrasonic humidifier. A micronodular infiltrate was seen in her chest radiograph. The inhalation challenge test was performed with the humidifier, and she exhibited a positive response. The cultures of the humidifier water grew Candida albicans, Rhodotorula spp., and Aspergillus spp. The test for precipitating antibodies against the humidifier water gave a positive response, and specific IgG, IgM, and IgA antibodies against extracts of A. fumigatus, C. albicans, and Rhodotorula spp. were demonstrated in the patient's serum by ELISA. A strong, dose-dependent inhibition of Rhodotorula IgG-ELISA by humidifier water was observed, suggesting that Rhodotorula might be the cause of hypersensitivity pneumonitis in this patient.

  2. Hypersensitivity pneumonitis associated with environmental mycobacteria.

    PubMed

    Beckett, William; Kallay, Michael; Sood, Akshay; Zuo, Zhengfa; Milton, Donald

    2005-06-01

    A previously healthy man working as a machine operator in an automotive factory developed respiratory symptoms. Medical evaluation showed abnormal pulmonary function tests, a lung biopsy showed hypersensitivity pneumonitis, and his illness was traced to his work environment. His physician asked the employer to remove him from exposure to metalworking fluids. Symptoms reoccurred when he was later reexposed to metalworking fluids, and further permanent decrement in his lung function occurred. Investigation of his workplace showed that five of six large reservoirs of metalworking fluids (cutting oils) grew Mycobacterium chelonae (or Mycobacterium immunogenum), an organism previously associated with outbreaks of hypersensitivity pneumonitis in automaking factories. His lung function remained stable after complete removal from exposure. The employer, metalworking fluid supplier, union, and the National Institute for Occupational Safety and Health were notified of this sentinel health event. No further cases have been documented in this workplace.

  3. Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria

    PubMed Central

    Beckett, William; Kallay, Michael; Sood, Akshay; Zuo, Zhengfa; Milton, Donald

    2005-01-01

    A previously healthy man working as a machine operator in an automotive factory developed respiratory symptoms. Medical evaluation showed abnormal pulmonary function tests, a lung biopsy showed hypersensitivity pneumonitis, and his illness was traced to his work environment. His physician asked the employer to remove him from exposure to metalworking fluids. Symptoms reoccurred when he was later reexposed to metalworking fluids, and further permanent decrement in his lung function occurred. Investigation of his workplace showed that five of six large reservoirs of metalworking fluids (cutting oils) grew Mycobacterium chelonae (or Mycobacterium immunogenum), an organism previously associated with outbreaks of hypersensitivity pneumonitis in automaking factories. His lung function remained stable after complete removal from exposure. The employer, metalworking fluid supplier, union, and the National Institute for Occupational Safety and Health were notified of this sentinel health event. No further cases have been documented in this workplace. PMID:15929902

  4. 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.

  5. [Prevalence of latex hypersensitivity among medical personnel].

    PubMed

    Camacho Ibarra, V C; López García, A I; Galindo García, J A; Paz Martínez, D; Papaqui Tapia, J S

    1997-01-01

    In order to determine the latex hypersensitivity prevalence in medical residents from Hospital Universitario de Puebla, it was carried out a transversal, observational and descriptive study including the medical staff of all specialties. The epicutancous test was effectuated with 1:20 latex antigen dilution. It was studied a total of 90 medical residents, 68.9% were males and 31.1% females. The mean age was 30.6 years (SD 3.8). The 50% were from clinical specialties and 50% else were from surgical. The global latex hypersensitivity prevalence was 8%. It will be convenient to carry out a follow up of studied cohort to establish if continual exposition, years later, will determine skin reactivity to latex in professional practice.

  6. An unexpected positive hypersensitive reaction to eugenol.

    PubMed

    Tammannavar, Praveen; Pushpalatha, C; Jain, Shrenik; Sowmya, S V

    2013-09-18

    Eugenol is an active, principal aromatic liquid responsible for several pharmacological activities. It is widely used in dental practice to relieve pain arising from various sources, such as pulpitis and dentinal hypersensitivity. As a primary irritant and sensitiser, it is known to cause contact urticaria as well as chronic urticaria. However, eugenol causes allergic contact dermatitis, possibly because it can react directly with proteins to form conjugate and reactive haptens. It is found that eugenol in various dental preparations-especially in the case of some zinc oxide-contains preparations such as periodontal dressings and root canal cements. This can cause hypersensitivity when it comes in contact with gingiva or teeth. This article presents a case of immediate allergic contact urticaria to eugenol during dental treatment.

  7. Phenytoin-induced acute hypersensitivity pneumonitis.

    PubMed

    Periwal, Pallavi; Joshi, Sharad; Gothi, Rajesh; Talwar, Deepak

    2015-01-01

    Lungs are target organs for toxic effects of various drugs due to many reasons. Diphenylhydantoin (DPH) is reported to have many extrapulmonary side effects. We are presenting a case of acute hypersensitivity pneumonitis (HP) secondary to DPH, presenting with respiratory failure. Acute HP with respiratory failure is an uncommon drug side effect of the DPH therapy and is a diagnosis of exclusion. It requires detailed workup and exclusion of other causes along with evidence of improvement in the patient's condition after withholding DPH.

  8. [Rare, severe hypersensitivity reaction to potassium iodide].

    PubMed

    Korsholm, Anne Sofie; Ebbehøj, Eva; Richelsen, Bjørn

    2014-07-07

    The literature reports a large variety of adverse reactions to potassium iodide. A severe hypersensitivity reaction to potassium iodide in a 51-year-old woman with Graves' thyrotoxicosis is described. Following administration the patient developed sialadenitis, conjunctivitis, stomatitis and acneiform iododerma that responded dramatically to withdrawal of the potassium iodide and administration with corticosteroids. Awareness of these adverse reactions may prevent prolonged hospitalization and unnecessary tests and treatments.

  9. Zeta Inhibitory Peptide as a Novel Therapy to Control Chronic Visceral Hypersensitivity in a Rat Model

    PubMed Central

    Chen, Yu; Guo, Lixia; Dai, Hengfen; Huang, Yang; Chen, Qianqian; Lin, Chun

    2016-01-01

    Background The pathogenesis of multiple chronic visceral pain syndromes, such as irritable bowel syndrome (IBS), is not well known, and as a result current therapies are ineffective. The objective of this study was to investigate the effect of spinal protein kinase M zeta (PKMζ) on visceral pain sensitivity in rats with IBS to better understand the pathogenesis and investigate the effect of zeta inhibitory peptide (ZIP) as a therapy for chronic visceral pain. Methods Visceral hypersensitivity rats were produced by neonatal maternal separation (NMS). Visceral pain sensitivity was assessed by electromyographic (EMG) responses of abdominal muscles to colorectal distention (CRD). Spinal PKMζ and phosphorylated PKMζ (p-PKMζ) were detected by western blot. Varying doses of ZIP were intrathecally administered to investigate the role of spinal PKMζ in chronic visceral hypersensitivity. The open field test was used to determine if ZIP therapy causes spontaneous motor activity side effects. Results Graded CRD pressure significantly increased EMG responses in NMS rats compared to control rats (p < 0.05). p-PKMζ expression increased in the thoracolumbar and lumbosacral spinal cord in the IBS-like rats with notable concomitant chronic visceral pain compared to control rats (p < 0.05). EMG data revealed that intrathecal ZIP injection (1, 5, and 10 μg) dose-dependently attenuated visceral pain hypersensitivity in IBS-like rats. Conclusions Phosphorylated PKMζ may be involved in the spinal central sensitization of chronic visceral hypersensitivity in IBS, and administration of ZIP could effectively treat chronic visceral pain with good outcomes in rat models. PMID:27776136

  10. Stent hypersensitivity and infection in sinus cavities

    PubMed Central

    Soufras, George D.; Hahalis, George

    2013-01-01

    Persistent mucosal inflammation, granulation tissue formation, hypersensitivity, and multifactorial infection are newly described complications of retained drug-eluting stents from endoscopic sinus surgery for refractory rhinosinusitis. In an important report published in Allergy and Rhinology, a 45-year-old male patient suffering from recalcitrant chronic rhinosinusitis underwent functional endoscopic sinus surgery and was found, for the first time, to have steroid-eluting catheters that were inadvertently left in the ethmoid and frontal sinuses. The retained catheters had caused persistent mucosal inflammation and formation of granulation tissue denoting hypersensitivity reaction. These consequences had induced perpetuation of symptoms of chronic rhinosinusitis. Meticulous removal of the retained stents with the nitinol wings from inflamed tissues of the frontal, ethmoidal, and sphenoethmoidal recesses in which they were completely imbedded was successfully performed without polypoid regrowth. Cultures of specimens taken from both left and right stents showed heavy growth of Stenotrophomonas maltophilia and moderate growth of Klebsiella oxytoca, coagulase negative Staphylococcus, and beta-hemolytic Streptococcus anginosus. Fungal infection was not detected. The current knowledge and experience regarding stent hypersensitivity and infection in relation with the use of stents in sinus cavities is reviewed. PMID:24498522

  11. TRPA1 contributes to cold hypersensitivity.

    PubMed

    del Camino, Donato; 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

    2010-11-10

    TRPA1 is a nonselective cation channel expressed by nociceptors. Although 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 in which reactive oxygen species and proinflammatory 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 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide] reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain.

  12. Hypersensitivity reactions to fluoroquinolones: analysis of the factors involved.

    PubMed

    Blanca-López, N; Ariza, A; Doña, I; Mayorga, C; Montañez, M I; Garcia-Campos, J; Gomez, F; Rondón, C; Blanca, M; Torres, M J

    2013-05-01

    Hypersensitivity reactions to fluoroquinolones seem to be on the increase, especially immediate type reactions. The aim of this study was to determine whether several conditions, including gender, age, type of reaction, time interval between the reaction and the study, type of symptoms, the specific fluoroquinolone involved in the reaction and previous confirmed hypersensitivity to betalactams or to other drugs were factors contributing to the development of hypersensitivity to fluoroquinolones. We analysed retrospectively all patients attending our allergy department between January 2005 and December 2010 because of a reaction associated with fluoroquinolone administration. The diagnosis was confirmed by basophil activation test or drug provocation tests. In accordance with the results, patients were then classified as having hypersensitivity or non-hypersensitivity to fluoroquinolones. A group of 218 patients was evaluated; 69 were confirmed as having hypersensitivity, 146 as non-hypersensitivity and 3 were excluded. Comparisons between groups showed that the allergic patients more often had a previous confirmed hypersensitivity to betalactams (P = 0.029), immediate reactions (P = 0.001) and anaphylaxis (P = 0.000), and moxifloxacin was the fluoroquinolone most frequently involved (P = 0.027). The logistic regression analysis showed three factors associated with the diagnosis of hypersensitivity reactions to fluoroquinolones: previous hypersensitivity to betalactams (OR: 4.571; 95% CI: 0.987-21.171; adjusted OR: 23.654; 95% CI: 1.529-365.853), immediate reactions (OR: 17.333; 95% CI: 4.374-68.691; adjusted OR: 52.493; 95% CI: 6.621-416.200) and reactions induced by moxifloxacin (OR: 3.091; 95% CI: 1.160-8.239; adjusted OR: 13.610; 95% CI: 2.419-76.565). In patients who develop reactions to fluoroquinolones, hypersensitivity is more often confirmed in those with immediate reactions and when moxifloxacin is involved. Moreover, patients with hypersensitivity to

  13. Development of the Sensory Hypersensitivity Scale (SHS): a self-report tool for assessing sensitivity to sensory stimuli.

    PubMed

    Dixon, Eric A; Benham, Grant; Sturgeon, John A; Mackey, Sean; Johnson, Kevin A; Younger, Jarred

    2016-06-01

    Sensory hypersensitivity is one manifestation of the central sensitization that may underlie conditions such as fibromyalgia and chronic fatigue syndrome. We conducted five studies designed to develop and validate the Sensory Hypersensitive Scale (SHS); a 25-item self-report measure of sensory hypersensitivity. The SHS assesses both general sensitivity and modality-specific sensitivity (e.g. touch, taste, and hearing). 1202 participants (157 individuals with chronic pain) completed the SHS, which demonstrated an adequate overall internal reliability (Cronbach's alpha) of 0.81, suggesting the tool can be used as a cross-modality assessment of sensitivity. SHS scores demonstrated only modest correlations (Pearson's r) with depressive symptoms (0.19) and anxiety (0.28), suggesting a low level of overlap with psychiatric complaints. Overall SHS scores showed significant but relatively modest correlations (Pearson's r) with three measures of sensory testing: cold pain tolerance (-0.34); heat pain tolerance (-0.285); heat pain threshold (-0.271). Women reported significantly higher scores on the SHS than did men, although gender-based differences were small. In a chronic pain sample, individuals with fibromyalgia syndrome demonstrated significantly higher SHS scores than did individuals with osteoarthritis or back pain. The SHS appears suitable as a screening measure for sensory hypersensitivity, though additional research is warranted to determine its suitability as a proxy for central sensitization.

  14. Delayed drug hypersensitivity reactions - new concepts.

    PubMed

    Posadas, S J; Pichler, W J

    2007-07-01

    Immune reactions to small molecular compounds such as drugs can cause a variety of diseases mainly involving skin, but also liver, kidney, lungs and other organs. In addition to the well-known immediate, IgE-mediated reactions to drugs, many drug-induced hypersensitivity reactions appear delayed. Recent data have shown that in these delayed reactions drug-specific CD4(+) and CD8(+) T cells recognize drugs through their T cell receptors (TCR) in an MHC-dependent way. Immunohistochemical and functional studies of drug-reactive T cells in patients with distinct forms of exanthems revealed that distinct T cell functions lead to different clinical phenotypes. Taken together, these data allow delayed hypersensitivity reactions (type IV) to be further subclassified into T cell reactions, which by releasing certain cytokines and chemokines preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd). Moreover, cytotoxic functions by either CD4(+) or CD8(+) T cells (type IVc) seem to participate in all type IV reactions. Drugs are not only immunogenic because of their chemical reactivity, but also because they may bind in a labile way to available TCRs and possibly MHC-molecules. This seems to be sufficient to stimulate certain, probably preactivated T cells. The drug seems to bind first to the fitting TCR, which already exerts some activation. For full activation, an additional interaction of the TCR with the MHC molecules is needed. The drug binding to the receptor structures is reminiscent of a pharmacological interaction between a drug and its (immune) receptor and was thus termed the p-i concept. In some patients with drug hypersensitivity, such a response occurs within hours even upon the first exposure to the drug. The T cell reaction to the drug might thus not be due to a classical, primary response, but is due to peptide-specific T cells which happen to be stimulated by a drug. This new concept has major implications

  15. Symptom hypersensitivity to acid infusion is associated with hypersensitivity of esophageal contractility.

    PubMed

    Bhalla, Vikas; Liu, Jianmin; Puckett, James L; Mittal, Ravinder K

    2004-07-01

    Several investigators have observed that repeated acid infusions induce stronger symptoms (symptom hypersensitivity). The goal of our study was to determine whether symptom hypersensitivity is associated with esophageal contractile hypersensitivity. Subjects with chronic heartburn symptoms underwent simultaneous pressure and ultrasound imaging of esophagus. Normal saline and 0.1 N HCl were sequentially infused into the esophagus, and subjects scored heartburn symptoms on a 1-10 scale. Saline and HCl infusions were repeated in 10 subjects with a positive Bernstein test. Esophageal contraction amplitude and duration and muscularis propria thickness were measured using a computerized method during recording. Acid infusion induced heartburn. Esophageal contractions had higher amplitudes (pressure 114.2 +/- 7.0%) and longer duration (116.8 +/- 4.4%) during acid infusion compared with saline infusion. Average muscle thickness was greater during acid infusion than saline infusion (107.0 +/- 2.0%). Sustained esophageal contractions (SECs) were identified during acid infusion. A second acid infusion (acid-2) induced heartburn with shorter latency (93.0 +/- 15.0 vs. 317.0 +/- 43.0 s) and stronger severity (8.5 +/- 0.5 vs. 5.3 +/- 0.8) than the first acid infusion (acid-1). Contraction amplitudes (140.2 +/- 13.0%), average muscle thickness (118.0 +/- 3.3%), and contraction duration (148.5 +/- 5.6 vs. 116.8 +/- 4.4%) were higher during acid-2 than acid-1. Also, numbers of SECs were greater during acid-2 than acid-1 (31 in 8 subjects vs. 11 in 6 subjects). Our data show that acid infusion into esophagus induces esophageal hypersensitivity and that a close temporal correlation exists between symptom hypersensitivity and contractility hypersensitivity.

  16. A physiologic differentiation between delayed and immediate hypersensitivity

    PubMed Central

    Apicella, Michael A.; Allen, James C.

    1969-01-01

    Studies have been made of movement of various macromolecules into and out of the pleural space of guinea pigs during the course of a delayed hypersensitivity reaction to purified protein derivative (PPD), and a passively transferred immediate hypersensitivity reaction to ovalbumin. While the immediate hypersensitivity reaction transiently alters vascular permeability as shown by increased movement of macromolecules into the chest, the delayed hypersensitivity reaction is marked by a decreased capacity to resorb macromolecules from the pleural space. The data suggest that the two hypersensitivity reactions may be distinguished by these physiologic differences. Additional data from studies of a chemically induced pleural effusion in these animals suggest that some type of outflow obstruction is necessary for the development of effusion, but that the outflow defect caused by the irritating chemical is based on a different mechanism than that seen during the delayed hypersensitivity reaction. PMID:4179171

  17. Immediate and Delayed Hypersensitivity Reactions to Corticosteroids: Evaluation and Management.

    PubMed

    Otani, Iris M; Banerji, Aleena

    2016-03-01

    Corticosteroids are anti-inflammatory medications used widely to treat allergic inflammation. Although the endocrine and gastrointestinal side effects of corticosteroids have been described, the occurrence of immediate hypersensitivity reactions and delayed contact dermatitis due to corticosteroids remains under-recognized. Hypersensitivity reactions can occur to a corticosteroid itself, or to the additives and vehicles in corticosteroid preparations. Skin testing and oral graded challenge can help confirm the suspected culprit agent in immediate hypersensitivity reactions and help identify an alternative tolerated corticosteroid. Patch testing can help identify the culprit agents in delayed hypersensitivity contact dermatitis. Cross-reactivity patterns have not been observed for immediate hypersensitivity reactions as they have been for delayed contact dermatitis. Sensitization in contact dermatitis exhibits cross-reactivity patterns based on corticosteroid structure. We review the current understanding regarding the clinical presentation, evaluation, and management of immediate and delayed hypersensitivity reactions to corticosteroids.

  18. Evaluation of Lymphocyte Transformation Test Results in Patients with Delayed Hypersensitivity Reactions following the Use of Anticonvulsant Drugs.

    PubMed

    Karami, Zahra; Mesdaghi, Mehrnaz; Karimzadeh, Parvaneh; Mansouri, Mahboubeh; Taghdiri, Mohammad Mehdi; Kayhanidoost, Zarrintaj; Jebelli, Bita; Shekarriz Foumani, Reza; Babaie, Delara; Chavoshzadeh, Zahra

    2016-01-01

    Administration of the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and lamotrigine can be associated with severe hypersensitivity reactions. The lymphocyte transformation test (LTT) is a method to determine which drug has caused the hypersensitivity reaction. This study was done to evaluate the results of LTT in patients with delayed hypersensitivity reactions following the administration of anticonvulsants. Twenty-four patients with hypersensitivity reactions, e.g. drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), following the administration of anticonvulsant drugs, and 24 patients who had used anticonvulsant drugs but did not have hypersensitivity reactions (the control group) were included in this study. Peripheral blood mononuclear cells were isolated. The cells were stimulated with the drugs, phytohemagglutinin as a mitogen and Candida as an antigen (positive controls). Lymphocyte proliferation was measured using the BrdU proliferation assay kit (Roche, Germany). The stimulation index was calculated as the mean ratio of the OD of stimulated cells divided by the OD of unstimulated cells. The results in the case and control groups were compared. Of 24 patients in the test group, 14 (58.3%) had positive LTT results and 10 (41.7%) had negative results. Among patients in the control group, 1 (4.2%) had a positive LTT result and 23 (95.8%) had negative results. Among the patients who had received carbamazepine and phenytoin, there was a significant difference between the results of LTT in the case and control groups (p = 0.002 and p = 0.028, respectively). Although patients receiving lamotrigine and phenobarbital had more positive LTT results in the case group than in the control group, these differences were not statistically significant. The sensitivity, specificity, positive predictive value and negative predictive value of LTT

  19. Tourette Syndrome

    PubMed Central

    Murray, T. J.

    1982-01-01

    Tourette syndrome (Gilles de la Tourette disease) is a disorder of involuntary muscular tics, vocalizations and compulsive behavior. The tics and muscle movements vary in form and course; the complex repetitive patterns are eventually replaced by other patterns. The vocalization may be in the form of sounds, words or profanities and sometimes echolalia, echopraxia and palilalia. The onset may be from age two to 15 but is usually between ages eight and 12. Recent studies suggest that there is a hypersensitivity of dopamine receptors. Most patients respond well to haloperidol, but other drugs that may be of value include clonidine, pimozide, fluphenazine and trifluoroperazine. PMID:21286050

  20. Horner's syndrome following cervical spinal surgery in the dog.

    PubMed

    Boydell, P

    1995-11-01

    Two dobermanns exhibited Horner's syndrome following the surgical treatment of cervical spondylopathy. Denervation hypersensitivity testing demonstrated a 2nd order lesion in both. Spontaneous resolution occurred within one month.

  1. Two factors responsible for the development of denervation hypersensitivity

    PubMed Central

    Jones, Rosemary; Vrbová, Gerta

    1974-01-01

    1. Innervated adult skeletal muscle is sensitive to acetylcholine at the end-plate region only. After denervation the entire muscle membrane becomes chemosensitive. The period of greatest increase in sensitivity in rat soleus muscles following section of the sciatic nerve in the thigh is between 48 and 72 hr post-operatively. 2. Direct electrical stimulation was found to prevent the onset of the development of denervation hypersensitivity during the first 2-3 days after nerve section. Thereafter, electrical stimulation only reduced the sensitivity of denervated muscles to acetylcholine (ACh). 3. The period of greatest increase in sensitivity follows loss of transmission and degeneration of the nerve terminals. Once this degeneration is under way, electrical stimulation is no longer as effective in preventing the development of denervation hypersensitivity. 4. Hypersensitivity is also seen in muscles on which a small piece of thread or degenerating nerve has been placed. Hypersensitivity following these procedures declines within a few days, unlike denervation hypersensitivity which persists until innervation is restored. 5. The present results suggest that activity alone cannot prevent the development of hypersensitivity in the presence of degenerating nerve fibres, or muscle damage. Activity does however counteract increased sensitivity. It is suggested that two factors interact to produce denervation hypersensitivity; the presence of degenerating nerve tissue and concomitant cellular changes bring about changes in the muscle fibre membrane causing it to become hypersensitive; and the loss of muscle activity, resulting in the persistence of hypersensitivity until innervation is restored. ImagesPlate 1 PMID:4822574

  2. New insights into visceral hypersensitivity--clinical implications in IBS.

    PubMed

    Zhou, QiQi; Verne, G Nicholas

    2011-06-01

    A subset of patients with IBS have visceral hypersensitivity and/or somatic hypersensitivity. Visceral hypersensitivity might have use as a clinical marker of IBS and could account for symptoms of urgency for bowel movements, bloating and abdominal pain. The mechanisms that lead to chronic visceral hypersensitivity in patients who have IBS are unclear. However, several working models may be considered, including: nociceptive input from the colon that leads to hypersensitivity; increased intestinal permeability that induces a visceral nociceptive drive; and alterations in the expression of microRNAs in gastrointestinal tissue that might be delivered via blood microvesicles to other target organs, such as the peripheral and/or central nervous system. As such, the chronic visceral hypersensitivity that is present in a subset of patients with IBS might be maintained by both peripheral and central phenomena. The theories underlying the development of chronic visceral hypersensitivity in patients with IBS are supported by findings from new animal models in which hypersensitivity follows transient inflammation of the colon. The presence of somatic hypersensitivity and an alteration in the neuroendocrine system in some patients who have IBS suggests that multisystemic factors are involved in the overall disorder. Thus, IBS is similar to other chronic pain disorders, such as fibromyalgia, chronic regional pain disorder and temporomandibular joint disorder, as chronic nociceptive mechanisms are activated in all of these disorders.

  3. X-ray induction of persistent hypersensitivity to mutation

    SciTech Connect

    Frank, J.P.; Williams, J.R.

    1982-04-16

    The progeny of x-irradiated V79 cells are hypersensitive to PUVA-(8-methoxypsoralen plus longwave ultraviolet light) induced mutation at the locus for hypoxanthine-guanine phosphoribosyl transferase. This hypersensitivity is most evident at low doses of pUVA that do not induce mutation in non-x-irradiated cells. The hypersensitivity is evoked by x-irradiation delivered as a single dose or as multiple fractions over a long period and persists for at least 108 days of exponential growth. This radiation-induced hypersensitivity to subsequent mutation is a new phenomenon that may be relevant to multistage carcinogenesis.

  4. Titanium hypersensitivity. A hidden threat for dental implant patients?

    PubMed

    Bilhan, Hakan; Bural, Canan; Geckili, Onur

    2013-01-01

    Titanium and its alloys have been widely used for dental prosthetic devices because of their superior mechanical properties and biocompatibility. However, the incidence of titanium hypersensitivity or allergy is still unknown and the discussion about its existence is ongoing. Unexplained implant failures have also forced dental clinicians to investigate the possibility of titanium hypersensitivity or allergy. This review focuses on the potential of dental implant-related titanium hypersensitivity or allergic reactions. It includes an examination of the existing scientific literature and current knowledge. Evidence-based data and studies related to titanium hypersensitivity in dental implant patients are also discussed.

  5. [HLA-B*5701 and abacavir hypersensitivity reaction].

    PubMed

    Servonnet, A; Leclercq, E; Delacour, H; Ceppa, F

    2010-12-01

    A potentially life-threatening hypersensitive reaction occurs in association with initiation of HIV nucleoside analogue abacavir therapy in 4 to 8% of patients. Preliminary studies appear to confirm the role of the immune system in abacavir hypersensitivity. The reaction is possibly the result of presentation of drug peptides onto HLA, that may induce a pathogenic T-cell response. Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele and prospective HLA-B*5701 genetic screening has now been instituted in clinical practice to reduce the risk of hypersensitivity reaction. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  6. Use of contact hypersensitivity in immunotoxicity testing.

    PubMed

    Descotes, Jacques

    2010-01-01

    The histopathological examination of lymphoid organs together with a T-dependent antibody (TDAR) assay are the primary components of preclinical immunotoxicity assessment. Additional testing including measurement of cellular immunity may be considered. Besides ex vivo lymphocyte proliferation assays, either delayed or contact hypersensitivity models can be used. Contact hypersensitivity testing is typically performed either in mice or in guinea pigs and is directly derived from classical models used for the detection of contact sensitizing chemicals. Whatever the selected model, it is comprised of a sensitizing phase where the animals are applied a strong contact sensitizer topically, then a rest phase, and finally an eliciting phase where sensitized animals are challenged topically with the same contact sensitizer.In mice, the ear-swelling test is the reference procedure in which mice are sensitized to the ear or shaved abdominal skin and then challenged on the ear. Ear swelling usually measured from ear thickness reflects a cell-mediated immune response. In guinea pigs, a strong sensitizer is applied on the shaved skin of the abdomen or the interscapular area. The sensitized animals are challenged on another area of the shaved abdomen, and the cell-mediated response is assessed semiquantitatively from the magnitude of induced erythema inconsistently associated with edema. Treatment or exposure with immunosuppressive chemicals can result in a significantly decreased ear swelling or skin reaction. Contact hypersensitivity models are seldom used nowadays in preclinical immunotoxicity testing, most likely because of the lack of standardization and extensive validation as well as their use being restricted to mice or guinea pigs.

  7. Hypersensitivity pneumonitis induced by Shiitake mushroom spores.

    PubMed

    Ampere, Alexandre; Delhaes, Laurence; Soots, Jacques; Bart, Frederic; Wallaert, Benoit

    2012-08-01

    Hypersensitivity pneumonitis (HP) is a pulmonary granulomatosis involving an immunoallergic mechanism caused by chronic inhalation of antigens, most frequently organic substances, as well as chemicals. We report the first European case of hypersensitivity pneumonitis due to the inhalation of Shiitake mushroom spores. A 37-year-old French Caucasian man with a one-month history of persistent dry cough, shortness of breath and loss of weight was admitted to our hospital on December 2010. Anamnesis showed he was involved in mushroom production beginning in the summer of 2010. His temperature on admission was 36.6°C and he had a normal blood pressure (135/90 mmHg). Bilateral fine crackles were audible in the base of both lungs. Pulmonary function tests showed a mild restrictive pattern with decreased DLco and a PaO(2) of 65 mmHg, Chest CT scan revealed reticulo-nodular shadows, slight ground glass opacities, liner atelectasis, and subpleural opacities in both lung fields. Bronchoscopy was normal but cytological examination of BAL revealed a predominant lymphocytosis (55%). Serum precipitins to the Shiitake mushroom spores were positive (3 precipitins arcs with high intensity) and as a result we advised the patient to cease his mushroom production activities. The diagnosis of hypersensitivity pneumonitis due to inhalation of Shiitake mushroom spores was established as a result of the improvement of all of his clinical symptoms, i.e., cough, weight loss, bilateral fine crackles, mild restrictive pattern of pulmonary function, and reticulo-nodular shadows on chest CT, once exposure was eliminated. Recent interest in exotic mushrooms varieties, e.g., Shiitake, in developed countries because of their possible medicinal properties might increase the potential risk of HP among mushrooms workers. Therefore, healthcare professionals have to take this new potential respiratory disease into account.

  8. LLLT in treating dentinary hypersensitivity: new concepts

    NASA Astrophysics Data System (ADS)

    Brugnera, Aldo, Jr.; Zanin, Fatima; Ladalardo, Thereza C.; Pinheiro, Antonio; Pecora, Jesus D.

    2006-02-01

    Dental hypersensitivity has been studied for several years and it is reported as a strikingly painful condition originating from the exposition of dentinal tubuli . The exposed area is subjected to several kinds of stimuli, resulting in a rapid sharp acute pain. LLLT has been shown to have antiinflammatory, analgesic and cellular effects in both hyperemia and inflammation of the dental pulp. Our previous histological study showed that irradiated animals presented an increased production of dentine and shutting of dentinal tubuli. On the other hand, non-irradiated subjects still showed signals of intense inflammatory reaction and even necrosis at the same experimental times. Irradiated teeth did not show cell degeneration. The LLLT was shown to be efficient in the stimulation of odontoblast cells, producing reparative dentin and closing dentin tubuli. Our clinical studies with 660nm, 790nm and 830nm diode laser, and the total dose per tooth of 4J/cm was shown effective in treating dentinal hypersensitivity as it quickly reduces pain and maintains a prolonged painless status in 91.27 % to 97% of the cases. In a recent study our team observed that significant levels of dentinal desensitization were only found in patients belonging to the 25-35 age group. In conclusion, the results demonstrated indeed that LLLT, when based on the use of correct irradiations parameters is effective in treating hypersensitivity, but the age of patients is one of the factors that may alter the success of treatment due to dentinal sclerosis, which makes the penetration of light more difficult.

  9. Hypersensitivity to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs).

    PubMed

    de Weck, A L; Gamboa, P M; Esparza, R; Sanz, M L

    2006-01-01

    Hypersensitivity to aspirin and other non steroidal anti-inflammatory drugs (NSAIDs) manifesting in the airways (rhinosinusitis, polyps, asthma) or in the skin (urticaria, angioedema) is the second most frequent untoward allergic reaction to drugs. Various aspects of this syndrome, such as its clinical features, the cell types and mediators involved, the role of underlying chronic inflammatory processes, the patterns of cross-reactivity between NSAIDs, the major role of sulfidoleukotrienes (LTC4) and of some other mediators such as prostaglandin E2 (PGE2) and C5a are briefly reviewed. It has been assumed for a long time that there were no reliable in vitro tests for that condition and that diagnostic confirmation can only be ascertained by provocation challenge. This appears no longer to be true, since several recent studies using a leukotriene release test (CAST) or a basophil activation test (BAT) on blood basophils, or a combination of both tests, yields positive results (70-75%) in a sizeable number of clinically validated cases, with a high specificity (above 85%). The finding in that syndrome of hyperreactive basophils suggests that the NSAID hypersensitivity syndrome is due to the associated effect of several factors: 1) Localized inflammatory processes causing a non specific cellular hyperreactivity; 2) An abnormal pharmacogenetic reaction to NSAIDs resulting in a hyperproduction of LTC4 and other mediators by activated mast cells, basophils and eosinophils.

  10. Hypersensitivity and nanoparticles: update and research trends

    PubMed Central

    MOCAN, TEODORA; MATEA, CRISTIAN T.; IANCU, CORNEL; AGOSTON-COLDEA, LUCIA; MOCAN, LUCIAN; ORASAN, REMUS

    2016-01-01

    Nanotechnology holds a great promise for a wide range of medical-intent applications (diagnostic, treatment and prophylaxis of various diseases). Their advantages are due to their size, versatility and potential for multiple simultaneous applications. However, concerns have been formulated by scientific world due to insufficient data on toxicity of nanomaterials. One area of interest is represented by the interactions between nanoparticles and the components of the immune system. We review herein reported data on hypersensitivity reactions. The role exerted by nanoparticles in both immunostimulation and immunosuppression in allergen-driven mechanisms was studied, as well as future trends in worldwide research. PMID:27152071

  11. Management of nonimmediate hypersensitivity reactions to drugs.

    PubMed

    Roujeau, Jean-Claude; Haddad, Cynthia; Paulmann, Maren; Mockenhaupt, Maja

    2014-08-01

    Nonimmediate hypersensitivity to drugs has a huge diversity of clinical presentations affecting exclusively or predominantly a single organ (most often the skin) or multiple organs. The latter is the rule with drug reaction with eosinophilia and systemic symptoms, and with drug-induced vasculitis. The management includes a dozen successive steps. Finally, the patient should be provided clear information on the suspected cause of the reaction, recommendations for follow-up after severe reactions associated with a risk of sequelae, and clear recommendations for future use of medications. Pharmacovigilance networks should be informed.

  12. Acute eosinophilic pneumonia: a hypersensitivity phenomenon?

    PubMed

    Badesch, D B; King, T E; Schwarz, M I

    1989-01-01

    A previously healthy young man presented with acute respiratory distress and diffuse bilateral infiltrates on chest radiograph. Eosinophilic pneumonia was diagnosed by bronchoalveolar lavage and confirmed by transbronchial lung biopsy. There was no evidence of an infectious etiology, and the patient rapidly improved with corticosteroid therapy. Most cases of eosinophilic pneumonia reported previously have followed a chronic course. The case presented here was acute in onset, suggesting a hypersensitivity reaction. High levels of bronchoalveolar lavage eosinophils indicate the diagnosis but not the etiology of eosinophilic pneumonia.

  13. Validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of sulfonamides, trimethoprim and dapsone in muscle, egg, milk and honey.

    PubMed

    Varenina, Ivana; Bilandžić, Nina; Kolanović, Božica Solomun; Božić, Đurđica; Sedak, Marija; Đokić, Maja; Varga, Ines

    2016-01-01

    A quantitative multi-residue method that includes 13 sulfonamides, trimethoprim and dapsone was developed and validated according to Commission Decision 2002/657/EC for muscle, milk egg and honey samples. For all matrices, the same extraction procedure was used. Samples were extracted with an acetone/dichloromethane mixture and cleaned up on aromatic sulfonic acid (SO3H) SPE cartridges. After elution and concentration steps, analytes were identified and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data were acquired according to the multiple reaction-monitoring approach (MRM) and analytes were quantified both by the isotope dilution and the matrix-matched approaches calculating the response factors for the scanned product ions. The developed method shows good linearity, specificity, precision (repeatability and within-laboratory reproducibility), and trueness. Estimated CCβ for sulfonamides ranged between 5.6 and 8.2 µg kg(-1) for eggs, between 11.1 and 69.9 µg kg(-1) for milk, between 64.7 and 87.9 µg kg(-1) for muscle, and between 2.7 and 5.3 µg kg(-1) for honey. CCβ values for dapsone were 3.1, 0.6, 0.7 and 1.5 µg kg(-1) and for trimethoprim were 3.1, 6.7, 81.7 and 3.0 µg kg(-1) calculated for eggs, milk, muscle and honey, respectively. Recovery for all matrices was in the range from 89.1% and 109.7%. In matrix effect testing, no significant deviations were found between different samples of muscle and milk; however, a matrix effect was observed when testing different types of honey. The validation results demonstrate that the method is suitable for routine veterinary drug analysis and confirmation of suspect samples.

  14. UPLC-MS-MS method for simultaneous determination of caffeine, tolbutamide, metoprolol, and dapsone in rat plasma and its application to cytochrome P450 activity study in rats.

    PubMed

    Liu, Yan; Li, Xiang; Yang, Chunjuan; Tai, Sheng; Zhang, Xiangning; Liu, Gaofeng

    2013-01-01

    A specific ultra-performance liquid chromatography tandem mass spectrometry method has been described for the simultaneous determination of caffeine, tolbutamide, metoprolol and dapsone in rat plasma, which are the four probe drugs of the four cytochrome P450 (CYP450) isoforms CYP1A2, CYP2C9, CYP2D6 and CYP3A4. The chromatographic separation was achieved using a Waters Acquity UPLC BEH HILIC C(18) column (2.1 × 50 mm, 1.7 µm). The mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) (15:85, v/v). The triple quadrupole mass spectrometric detection was operated by positive electrospray ionization. Phenacetin was chosen as internal standard. Plasma samples were extracted with dichloromethane-butanol (10:1, v/v). The recoveries ranged from 67.5% to 98.5%. The calibration curves in plasma were linear in the range of 2.5-1,000 ng/mL for caffeine and dapsone, 5-5,000 ng/mL for tolbutamide and 2.5-250 ng/mLfor metoprolol, with correlation coefficient (r(2)) of 0.9936, 0.9966, 0.9990 and 0.9998, respectively. The method was successfully applied to pharmacokinetic studies of the four probe drugs of the four CYP450 isoforms and used to evaluate the effects of breviscapine on the activities of CYP1A2, CYP2C9, CYP2D6 and CYP3A4 in rats.

  15. Susceptibility of thymectomized and irradiated mice to challenge with several organisms and the effect of dapsone on infection with Mycobacterium leprae.

    PubMed

    Levy, L; Ng, H; Evans, M J; Krahenbuhl, J L

    1975-05-01

    B6C3F1 mice that had been thymectomized at 8 to 12 weeks of age, subjected to 950 R of whole-body X irradiation, and transfused with syngeneic bone marrow were challenged in a footpad with Mycobacterium leprae or M. marinum, or intravenously or intraperitioneally with Listeria monocytogenes. Also, mice inoculated with M. leprae in a hind footpad were administered dapsone in the mouse chow. The thymectomized-irradiated (T + R) mice did not survive as well as non-thymectomized mice when housed in the vivarium with no special precautions, but survived sufficiently well to permit the completion of some long-term experiments. M. leprae multiplied to a higher "ceiling" and survived longer in the T + R mice than in the non-thymectomized controls. But a ceiling to multiplication of M. leprae was imposed, and finally the organisms were killed. The histopathological appearance of the footpad tissues, studied by electron microscopy, was consistent with the measurements of bacterial numbers and viability. Swelling of the footpad after local inoculation with M. marinum was greater in T + R mice than in non-thymectomized controls. Similarly, the number of L. monocytogenes following intravenous challenge was greater in the spleens of T + R than of non-thymectomized mice, and the survival of the T + R mice was impaired after intraperitoneal challenge with L.monocytogenes, compared to the survival of non-thymectomized mice. None of these differences was striking, suggesting that these T + R mice had retained or regained some immune competence. The effects of dapsone treatment of T + R mice inoculated with M. leprae were much the same as those of treatment of non-thymectomized mice. Because these T + R mice were not greatly immunosuppressed, they would not have provided a model of human lepromatous leprosy suitable for chemotherapeutic studies.

  16. Adrenergic Stimulation Mediates Visceral Hypersensitivity to Colorectal Distension following Heterotypic Chronic Stress

    PubMed Central

    Winston, John H.; Xu, Guang-Yin; Sarna, Sushil K.

    2009-01-01

    Background & Aims Chronic stress exacerbates or causes relapse of symptoms such as abdominal pain and cramping in patients with irritable bowel syndrome (IBS). We investigated whether chronic stress increases plasma norepinephrine and sensitizes colon-specific dorsal root ganglion (DRG) neurons by increasing the expression of nerve growth factor (NGF) in the colon wall. Methods Heterotypic chronic stress (HeCS) was induced in male Wistar rats and neurologic and molecular responses were analyzed. Tissues were analyzed for NGF expression. Results HeCS significantly increased the visceromoter response to colorectal distension; expression of NGF increased in colonic muscularis externa and mucosa/submucosa. Rheobase decreased, resting membrane potential was depolarized, and electrogenesis of action potentials increased in colon-specific thoracolumbar DRG neurons. Luminal administration of resiniferatoxin in distal colon, systemic administration of anti-NGF antibody, or inhibition of the NGF receptor TrkA by k252A or antisense oligonucleotides in thoracolumbar DRG blocked the chronic stress-induced visceral hypersensitivity to colorectal distension. Blockade of α1/α2- and β1/β2-adrenergic receptors prevented the stress-induced visceral hypersensitivity and increased expression of NGF in the colon wall. HeCS did not induce any inflammatory response in the colon wall. Conclusion The peripheral stress mediator norepinephrine induces visceral hypersensitivity to colorectal distension in response to HeCS by increasing the expression of NGF in the colon wall, which sensitizes primary afferents in the absence of an inflammatory response. PMID:19800336

  17. 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

  18. 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

  19. Duodenal administered seal oil for patients with subjective food hypersensitivity: an explorative open pilot study

    PubMed Central

    Gregersen, Kine; Lind, Ragna A; Valeur, Jørgen; Bjørkkjær, Tormod; Berstad, Arnold; Lied, Gülen Arslan

    2010-01-01

    Short-term duodenal administration of n-3 polyunsaturated fatty acid (PUFA)-rich seal oil may improve gastrointestinal complaints in patients with subjective food hypersensitivity, as well as joint pain in patients with inflammatory bowel disease (IBD). The aim of the present explorative pilot study was to investigate whether 10-day open treatment with seal oil, 10 mL self-administrated via a nasoduodenal tube 3 times daily, could also benefit nongastrointestinal complaints and quality of life (QoL) in patients with subjective food hypersensitivity. Twenty-six patients with subjective food hypersensitivity, of whom 25 had irritable bowel syndrome (IBS), were included in the present study. Before and after treatment and 1 month posttreatment, patients filled in the Ulcer Esophagitis Subjective Symptoms Scale (UESS) and the Gastrointestinal Symptom Rating Scale (GSRS) for gastrointestinal symptoms and subjective health complaints (SHC) inventory for nongastrointestinal symptoms in addition to short form of the Nepean dyspepsia index (SF-NDI) for evaluation of QoL. Compared with baseline, gastrointestinal, as well as nongastrointestinal, complaints and QoL improved significantly, both at end of treatment and 1 month posttreatment. The consistent improvements following seal oil administration warrant further placebo-controlled trials for confirmation of effect. PMID:21189836

  20. 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.

  1. Vasovagal syncope in the Canon of Avicenna: the first mention of carotid artery hypersensitivity.

    PubMed

    Shoja, Mohammadali M; Tubbs, R Shane; Loukas, Marios; Khalili, Majid; Alakbarli, Farid; Cohen-Gadol, Aaron A

    2009-05-29

    Ibn Sina, known as Avicenna in the West, was a celebrated Persian thinker, philosopher, and physician who is remembered for his masterpiece, The Canon of Medicine. The Canon that served as an essential medical encyclopedia for scholars in the Islamic territories and Europe for almost a millennium consisted of 5 books. In the third book, Avicenna described patients with symptoms of carotid hypersensitivity syndrome. These patients, who had excessive yawning, fatigue, and flushing, dropped following pressure on their carotids. Based on such history, it seems that Avicenna was the first to note the carotid sinus hypersensitivity, which presents with vasovagal syncope following compression of the carotid artery. In this paper, we presented a brief account of Avicenna's life and works and discuss his description of the so-called carotid hypersensitivity syncope. Notwithstanding his loyalty to the Greek theory of humoralism, Avicenna set forth his own version of "theory of spirits" to explain the mechanism of this disease. An account of the theory of spirits is also given.

  2. Neonatal parenteral nutrition hypersensitivity: a case report implicating bisulfite sensitivity in a newborn infant.

    PubMed

    Huston, Robert K; Baxter, Louise M; Larrabee, Paige B

    2009-01-01

    This report describes a case of parenteral nutrition hypersensitivity in a 37 weeks' gestation infant with congenital diaphragmatic hernia complicated by bowel necrosis and functional short bowel syndrome. The patient developed a rash with subsequent urticaria beginning on the 50th day of life. The reactions were confirmed with a positive rechallenge. After the amino acid solution was replaced with a non-bisulfite-containing product, the infant was able to continue to receive nutrition support through parenteral nutrition without recurrence of symptoms. It is speculated that the bisulfite additive in the amino acid solution may have interacted with the lipid emulsion to sensitize the patient.

  3. Liver dysfunction induced by systemic hypersensitivity reaction to lamotrigine: case report.

    PubMed

    Im, Sung Gyu; Yoo, Sun Hong; Park, Young Min; Lee, Sang Jin; Jang, Sun Kyung; Jeon, Dong Ok; Cho, Hyo Jin; Oh, Mi Jung

    2015-06-01

    Lamotrigine is an anticonvulsant drug used to treat partial and generalized seizure disorders. Hypersensitivity to lamotrigine usually causes mild symptoms such as fever, rash, and slight invasion of internal organs. However, a 33-year-old male patient who was admitted with Stevens-Johnson syndrome after taking lamotrigine for 15 days experienced hepatic failure and died 5 days after admission. This case demonstrates the importance of realizing that lamotrigine can lead to fatal hepatic failure, and that tests for the normal liver function should be performed when administering lamotrigine.

  4. Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats.

    PubMed

    Yan, Chi; Xin-Guang, Liu; Hua-Hong, Wang; Jun-Xia, Li; Yi-Xuan, Li

    2012-10-01

    Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT(4) receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT(4) receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT(4) receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg · kg(-1) · day(-1), days 36-42), tegaserod (1 mg · kg(-1) · day(-1), day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT(4) receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT(4) receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.

  5. Horner's syndrome associated with Neospora infection.

    PubMed

    Boydell, P; Brogan, N

    2000-12-01

    A working collie cross was presented with a three-month history of vague neurological signs and a right-sided Horner's syndrome. Denervation hypersensitivity testing suggested a first order syndrome. There was a significant positive titre to Neospora and clinical signs resolved completely following treatment.

  6. [DRESS syndrome secondary to antituberculosis drugs: about a case].

    PubMed

    Jridi, Siham; Azzeddine, Rajae; Bourkadi, Jamal Eddine

    2017-01-01

    Drug hypersensitivity syndrome or Drug Rash with Eosinophilia and Systemic Symptoms or DRESS syndrome is a severe and potentially life-threatening toxidermia. It should be suspected in patients developing cutaneous reaction following drug intake. We report the case of a 45-year old patient treated for pulmonary tuberculosis (TPM+) who developed DRESS syndrom induced by antibacillaries.

  7. HLA-A*31:01 and HLA-B*15:02 as genetic markers for carbamazepine hypersensitivity in children

    PubMed Central

    Amstutz, Ursula; Ross, Colin J.D.; Castro-Pastrana, Lucila I.; Rieder, Michael J.; Shear, Neil H.; Hayden, Michael R.; Carleton, Bruce C.

    2013-01-01

    The occurrence of hypersensitivity reactions including rare but life-threatening Stevens-Johnson syndrome (SJS) and drug-induced hypersensitivity syndrome (HSS) limits the use of the anticonvulsant carbamazepine (CBZ). HLA-B*15:02 and HLA-A*31:01 have been identified as predictive genetic markers for CBZ hypersensitivity in Asian and European patients. To replicate these genetic associations in pediatric patients from North America with a diverse ethnic background, we investigated HLA-A*31:01 and HLA-B*15:02 in 42 children with CBZ hypersensitivity, and 91 CBZ-tolerant children from across Canada. HLA-A*31:01 was significantly associated with CBZ-HSS (odds ratio (OR): 26.4, p=0.0025) and maculopapular exanthems (OR: 8.6, p=0.0037), but not with CBZ-SJS. Conversely, HLA-B*15:02 was associated with CBZ-SJS (OR: 38.6, p=0.002), but not HSS and maculopapular exanthems. This study is the first to demonstrate the association of HLA-A*31:01 with CBZ hypersensitivity in children, providing important replication of this association and highlighting the importance of HLA-A*31:01 as a predictive biomarker across various ancestries. PMID:23588310

  8. 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.

  9. 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.

  10. Specific Aspects of Drug Hypersensitivity in Children.

    PubMed

    Bergmann, Marcel; Caubet, Jean-Christoph

    2016-01-01

    Suspicion for drug hypersensitivity (DH) is a common reason for children's referral to an allergy department, with β-lactam antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) as the most frequently involved drugs. The prevalence of DH in children remains not well defined as epidemiologic studies in children are lacking, and the most of those take into account adverse drug reactions (ADR) without a systematic allergy work-up to confirm or exclude hypersensitivity. The clinical history is mandatory in order to classify the reaction as being immediate or non-immediate and then to subsequently adapt the allergy work-up. Mainly due to the lack of studies, the same guidelines used for diagnosis of drug allergy in adults are generally used in the pediatric population, and the diagnosis is based mainly on in vivo tests (i.e. skin tests and/or drug provocation test) and rarely on in vitro tests. However, specific aspects of management of DH in children have been recently highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Giardia duodenalis induces paracellular bacterial translocation and causes postinfectious visceral hypersensitivity

    PubMed Central

    Halliez, Marie C. M.; Motta, Jean-Paul; Feener, Troy D.; Guérin, Gaetan; LeGoff, Laetitia; François, Arnaud; Colasse, Elodie; Favennec, Loic; Gargala, Gilles; Lapointe, Tamia K.; Altier, Christophe

    2016-01-01

    Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder. It is characterized by abdominal hypersensitivity, leading to discomfort and pain, as well as altered bowel habits. While it is common for IBS to develop following the resolution of infectious gastroenteritis [then termed postinfectious IBS (PI-IBS)], the mechanisms remain incompletely understood. Giardia duodenalis is a cosmopolitan water-borne enteropathogen that causes intestinal malabsorption, diarrhea, and postinfectious complications. Cause-and-effect studies using a human enteropathogen to help investigate the mechanisms of PI-IBS are sorely lacking. In an attempt to establish causality between giardiasis and postinfectious visceral hypersensitivity, this study describes a new model of PI-IBS in neonatal rats infected with G. duodenalis. At 50 days postinfection with G. duodenalis (assemblage A or B), long after the parasite was cleared, rats developed visceral hypersensitivity to luminal balloon distension in the jejunum and rectum, activation of the nociceptive signaling pathway (increased c-fos expression), histological modifications (villus atrophy and crypt hyperplasia), and proliferation of mucosal intraepithelial lymphocytes and mast cells in the jejunum, but not in the rectum. G. duodenalis infection also disrupted the intestinal barrier, in vivo and in vitro, which in turn promoted the translocation of commensal bacteria. Giardia-induced bacterial paracellular translocation in vitro correlated with degradation of the tight junction proteins occludin and claudin-4. The extensive observations associated with gut hypersensitivity described here demonstrate that, indeed, in this new model of postgiardiasis IBS, alterations to the gut mucosa and c-fos are consistent with those associated with PI-IBS and, hence, offer avenues for new mechanistic research in the field. PMID:26744469

  12. Giardia duodenalis induces paracellular bacterial translocation and causes postinfectious visceral hypersensitivity.

    PubMed

    Halliez, Marie C M; Motta, Jean-Paul; Feener, Troy D; Guérin, Gaetan; LeGoff, Laetitia; François, Arnaud; Colasse, Elodie; Favennec, Loic; Gargala, Gilles; Lapointe, Tamia K; Altier, Christophe; Buret, André G

    2016-04-15

    Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder. It is characterized by abdominal hypersensitivity, leading to discomfort and pain, as well as altered bowel habits. While it is common for IBS to develop following the resolution of infectious gastroenteritis [then termed postinfectious IBS (PI-IBS)], the mechanisms remain incompletely understood. Giardia duodenalis is a cosmopolitan water-borne enteropathogen that causes intestinal malabsorption, diarrhea, and postinfectious complications. Cause-and-effect studies using a human enteropathogen to help investigate the mechanisms of PI-IBS are sorely lacking. In an attempt to establish causality between giardiasis and postinfectious visceral hypersensitivity, this study describes a new model of PI-IBS in neonatal rats infected with G. duodenalis At 50 days postinfection with G. duodenalis (assemblage A or B), long after the parasite was cleared, rats developed visceral hypersensitivity to luminal balloon distension in the jejunum and rectum, activation of the nociceptive signaling pathway (increased c-fos expression), histological modifications (villus atrophy and crypt hyperplasia), and proliferation of mucosal intraepithelial lymphocytes and mast cells in the jejunum, but not in the rectum. G. duodenalis infection also disrupted the intestinal barrier, in vivo and in vitro, which in turn promoted the translocation of commensal bacteria. Giardia-induced bacterial paracellular translocation in vitro correlated with degradation of the tight junction proteins occludin and claudin-4. The extensive observations associated with gut hypersensitivity described here demonstrate that, indeed, in this new model of postgiardiasis IBS, alterations to the gut mucosa and c-fos are consistent with those associated with PI-IBS and, hence, offer avenues for new mechanistic research in the field. Copyright © 2016 the American Physiological Society.

  13. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome: suspected association with titanium bioprosthesis.

    PubMed

    Nawaz, Fareha; Wall, Barry M

    2007-09-01

    Drug rash with eosinophilia and systemic symptoms (DRESS), also known as hypersensitivity syndrome, is an idiosyncratic drug reaction presenting with fever, diffuse lymphadenopathy, exfoliative dermatitis, and visceral involvement, which may include hepatitis, pneumonitis, pericarditis, myocarditis, nephritis, and colitis. This report describes a 19-year-old, previously healthy man with manifestations of hypersensitivity (DRESS) syndrome after acquiring a titanium bioprosthesis for a spinal fracture. To our knowledge, there have been no prior reports of DRESS syndrome in association with titanium bioprosthetic implants.

  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. Hypersensitivity to laminaria: a case report and review of literature.

    PubMed

    Sierra, Tania; Figueroa, Melissa M; Chen, Katherine T; Lunde, Britt; Jacobs, Adam

    2015-04-01

    We report a case of laminaria hypersensitivity treated with diphenhydramine and corticosteroids. A literature review identified 10 previously reported cases, with 8 recognized as anaphylaxis, and good outcomes with corticosteroids and antihistamines despite limited epinephrine utilization. Laminaria hypersensitivity is likely IgE mediated with an increased anaphylaxis risk with prior exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Teenagers' experiences of living with food hypersensitivity: a qualitative study.

    PubMed

    MacKenzie, Heather; Roberts, Graham; van Laar, Darren; Dean, Taraneh

    2010-06-01

    Teenagers are a high-risk group for food-hypersensitivity fatalities, engage in risk-taking behaviours and may experience impaired quality of life. Understanding their experience is important to inform their care. This study aimed to describe the lived experiences of teenagers with food hypersensitivity. Individual semi-structured interviews were conducted with 21 teenagers (13-18 yr) with food hypersensitivity to a variety of foods and analysed using a phenomenological approach. Teenagers described living with (or coming to know) food hypersensitivity (FHS) as a way of life but still found living with food hypersensitivity to be burdensome. A necessary part of living with food hypersensitivity was coping with associated burden; a variety of coping strategies were employed to this effect. Teenagers described ways in which the burden of living with food hypersensitivity was alleviated or exacerbated by others. Management of food hypersensitivity was based on an assessment of acceptable risk resulting in varying levels of precaution taking. Teenagers' understanding of their FHS and ability to cope with it needs to be regularly assessed. Educational support may be required to ensure they take an appropriate level of precautions to minimize the chance of future reactions while not over compromising their quality of life. Psychological support may be required to help them to utilize healthy adaptive strategies to cope with the stresses of living with FHS. This approach is also likely to facilitate the smooth handover of responsibility from parent to teenager.

  17. 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...

  18. 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...

  19. 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...

  20. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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...

  1. Virus antibody levels and delayed hypersensitivity in rheumatoid arthritis.

    PubMed Central

    Phillips, P E; Waxman, J; Hirshaut, Y; Kaplan, M H

    1976-01-01

    Epstein-Barr virus and cytomegalovirus antibody levels were not higher in patients with rheumatoid arthritis compared to matched controls. Delayed hypersensitivity, measured by skin test reactivity, was depressed in rheumatoid arthritis. There was no correlation between virus antibody titres and delayed hypersensitivity. PMID:182092

  2. Radiocontrast media hypersensitivity in the Asia Pacific region.

    PubMed

    Lee, Suh-Young; Lim, Kyoung-Whan; Chang, Yoon-Seok

    2014-04-01

    Radiocontrast media (RCM) is a major cause of drug hypersensitivity reactions as the medical application of RCM is increasing recently. RCM induced hypersensitivity reactions are considered as unpredictable type B reactions. Underlying mechanism of RCM induced hypersensitivity was previously regarded as nonimmunological mechanisms but recent studies suggest that immunological mechanisms could also be involved. As a result, the roles of skin tests and premedication are revisiting. As there has been no report that comprehensively summarized and analyzed the results of the studies on RCM hypersensitivity in the Asia Pacific region, we aimed to review the literatures on hypersensitivity reactions to RCM in terms of prevalence clinical manifestations, diagnostic approach, and preventive measures in the Asia Pacific region.

  3. Radiocontrast media hypersensitivity in the Asia Pacific region

    PubMed Central

    Lee, Suh-Young; Lim, Kyoung-Whan

    2014-01-01

    Radiocontrast media (RCM) is a major cause of drug hypersensitivity reactions as the medical application of RCM is increasing recently. RCM induced hypersensitivity reactions are considered as unpredictable type B reactions. Underlying mechanism of RCM induced hypersensitivity was previously regarded as nonimmunological mechanisms but recent studies suggest that immunological mechanisms could also be involved. As a result, the roles of skin tests and premedication are revisiting. As there has been no report that comprehensively summarized and analyzed the results of the studies on RCM hypersensitivity in the Asia Pacific region, we aimed to review the literatures on hypersensitivity reactions to RCM in terms of prevalence clinical manifestations, diagnostic approach, and preventive measures in the Asia Pacific region. PMID:24809018

  4. [Questionnaire about the intake of and hypersensitivity to fruits, vegetables and nuts including birch pollen related foods].

    PubMed

    Yamamoto, Tetsuo; Asakura, Kohji; Shirasaki, Hideaki; Himi, Tetsuo

    2013-07-01

    In Hokkaido and Scandinavia, birch pollen allergic persons are common and they often report oral and pharyngeal hypersensitivity to fruits and vegetables (oral allergy syndrome, OAS), because of immunological cross-reactivity. In Scandinavia, nuts as well as Rosaceae fruits such as apples were the foods most often reported to elicit symptoms. On the other hand, nuts are minor foods causing hypersensitivity in Japan. Even in Japan, regional differences of foods causing hypersensitivity have been reported, which may be related to the regional differences of elementary habit and pollen dispersion. In the present study, we evaluated the intake history of the foods and the frequency of food hypersensitivity in adults from the general population. Three hundreds and thirty nine subjects (20-67 years old) took part in the study. With a questionnaire survey, we asked them about their intake history and hypersensitive symptoms for 33 kinds of fruit, vegetables, and nuts. 30% of subjects had eaten Brazil nuts, 80% had eaten pomegranates, and 81% had eaten hazelnuts. And over 95% of subjects had eaten the other 30 foods. Those who had lived in Hokkaido for more than 20 years had a higher frequency of plum consumption than the others. Those who had lived in Hokkaido for more than 20 years had a lower frequency of loquat, fig and pomegranate consumption than the others. Food hypersensitivity was found in 52 subjects (15.3%). The most common symptom was OAS (46 subjects, 13.6%), and foods most frequently causing OAS were peach (21 subjects, 6.2%), cherry (19 subjects, 5.6%) and apple (17 subjects, 5.0%). 26 subjects (7.7%) reported OAS to Rosaceae fruits. The ratio of having OAS to consuming Rosaceae fruits was 11.0% in the group who had lived in Hokkaido for more than 20 years, which was higher than the group who has lived in Hokkaido for less than 20 years. The intake history of hazelnuts and Brazil nuts was very low, with a correspondingly low frequency of food

  5. Stress induces transient auditory hypersensitivity in rats.

    PubMed

    Mazurek, Birgit; Haupt, Heidemarie; Joachim, Ricarda; Klapp, Burghard F; Stöver, Timo; Szczepek, Agnieszka J

    2010-01-01

    Exposure to harsh environment induces stress reactions that increase probability of survival. Stress influences the endocrine, nervous and immune systems and affects the functioning of a variety of organs. Numerous researchers demonstrated that a 24-h exposure to an acoustic rodent repellent provokes stress reaction in exposed animals. In addition to the activated hypothalamic-pituitary-adrenal (HPA) axis, exposed animals had pathological reactions in the reproductive organs, bronchia and skin. Here, we examined the effect of above stress model on the auditory system of Wistar rats. We found that 24-h stress decreases the thresholds and increases the amplitudes of auditory brainstem responses and distortion product otoacoustic emissions. Resultant auditory hypersensitivity was transient and most pronounced between 3 and 6h post-stress, returning to control levels one week later. The concentration of corticosterone and tumor necrosis factor alpha was systemically elevated in stressed animals between 3 and 6h post-stress, confirming the activation of the HPA axis. In addition, expression of the HPA-axis-associated genes: glucocorticoid receptor (GR) and hypoxia-inducible factor 1 alpha (Hif1a) was modulated in the auditory tissues. In detail, in the inferior colliculus, we found an up-regulation of GR mRNA 3h post-stress and continuous up-regulation of Hif1a up to 24h post-stress. In the spiral ganglion, we found no differences in gene expression between stressed and control animals. In the organ of Corti, expression of GR mRNA remained stable, whereas that of Hif1a was significantly down-regulated one week after stress. In addition, the expression of an outer hair cell marker prestin was significantly up-regulated 6h post-stress. We conclude that 24-h stress induces transient hypersensitivity of the auditory system and modulates gene expression in a tissue-specific manner. Stress-induced auditory hypersensitivity could have evolutionary consequence by giving animals

  6. Selective immediate hypersensitivity reactions to NSAIDs.

    PubMed

    Canto, Maria Gabriela; Andreu, Isabel; Fernandez, Javier; Blanca, Miguel

    2009-08-01

    Selective immediate reactions to NSAIDs imply that patients develop a urticarial/anaphylactic response to a single drug with good tolerance to other compounds. No systematic review of these reactions has yet been made. With the increase in consumption of NSAIDs, these have become one of the most common drugs inducing hypersensitivity reactions. Although cross-intolerance reactions are the most common, a significant proportion is selective responses. As specific IgE antibodies are not always found, there is only indirect evidence supporting an IgE-mediated mechanism in selective NSAID reactors. Selective immediate reactions to NSAIDs must be considered when a patient develops urticaria or anaphylaxis after intake of one drug with good tolerance to drugs from other groups or even a drug from the same group with a slightly different chemical structure. Further research is required to identify the antigenic determinant structures recognized.

  7. Hypersensitivity to Ticks and Lyme Disease Risk

    PubMed Central

    Burke, Georgine; Wikel, Stephen K.; Spielman, Andrew; Telford, Sam R.; McKay, Kathleen

    2005-01-01

    Although residents of Lyme disease–endemic regions describe frequent exposure to ticks, Lyme disease develops in relatively few. To determine whether people who experience cutaneous hypersensitivity against tick bite have fewer episodes of Lyme disease than those who do not, we examined several factors that might restrict the incidence of Lyme disease among residents of Block Island, Rhode Island. Of 1,498 study participants, 27% (95% confidence interval [CI] 23%–31%) reported >1 tick bites, and 17% (95% CI 13%–21%) reported itch associated with tick bite in the previous year. Borrelia burgdorferi infected 23% (95% CI 20%–26%) of 135 nymphal Ixodes scapularis (I. dammini) ticks. The likelihood of Lyme disease infection decreased with >3 reports of tick-associated itch (odds ratio 0.14, 95% CI 0.94–0.03, p = 0.01). Prior exposure to uninfected vector ticks protects residents of disease-endemic sites from Lyme disease. PMID:15705320

  8. Non-surgical management of tooth hypersensitivity.

    PubMed

    Clark, Danielle; Levin, Liran

    2016-10-01

    Tooth sensitivity is a common complaint of patients in dental practices. Studies have demonstrated dentinal hypersensitivity to affect 10-30% of the population. There are various potential causes of tooth sensitivity and a variety of available treatment options. This narrative review will discuss the possible aetiology of this condition, as well as the treatment modalities available. A tailor-made treatment plan that starts with the most non-invasive treatment options and escalates only when those options have proven insufficient in alleviating symptoms should be provided for each patient. Only after all non- and less-invasive methods have failed to reduce the symptoms should more invasive treatment options, such as root-coverage, be considered.

  9. Squid hypersensitivity: a clinical and immunologic study.

    PubMed

    Carrillo, T; Castillo, R; Caminero, J; Cuevas, M; Rodriguez, J C; Acosta, O; Rodriguez de Castro, F

    1992-06-01

    Hypersensitivity to mollusk has rarely been described in the literature. Among the mollusks, the cephalopods are a group of great importance as a food source. We report seven patients who had had symptoms highly suggestive of IgE-mediated reactions after ingesting squid or inhaling vapors from cooking squid. All had previously suffered from persistent rhinitis or asthma for years. In addition, six of the seven patients had had symptoms after ingesting shrimp. Skin prick tests were strongly positive for boiled squid extract and for various commercial crustacean extracts. Specific IgE antibodies against boiled extract and several crustacean extracts were demonstrated in all patients by RAST and reverse enzyme immunoassay. Cross reactivity between squid and shrimp and other crustaceans was demonstrated by reverse immunoassay inhibition studies. Cross reactivity could not be demonstrated between squid and octopus, which are both cephalopods, nor between squid and other mollusks.

  10. Hypersensitivity to ticks and Lyme disease risk.

    PubMed

    Burke, Georgine; Wikel, Stephen K; Spielman, Andrew; Telford, Sam R; McKay, Kathleen; Krause, Peter J

    2005-01-01

    Although residents of Lyme disease-endemic regions describe frequent exposure to ticks, Lyme disease develops in relatively few. To determine whether people who experience cutaneous hypersensitivity against tick bite have fewer episodes of Lyme disease than those who do not, we examined several factors that might restrict the incidence of Lyme disease among residents of Block Island, Rhode Island. Of 1,498 study participants, 27% (95% confidence interval [CI] 23%-31%) reported > or = 1 tick bites, and 17% (95% CI 13%-21%) reported itch associated with tick bite in the previous year. Borrelia burgdorferi infected 23% (95% CI 20%-26%) of 135 nymphal Ixodes scapularis (I. dammini) ticks. The likelihood of Lyme disease infection decreased with >3 reports of tick-associated itch (odds ratio 0.14, 95% CI 0.94-0.03, p = 0.01). Prior exposure to uninfected vector ticks protects residents of disease-endemic sites from Lyme disease.

  11. [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.

  12. Shoulder arthroplasty in the patient with metal hypersensitivity.

    PubMed

    Morwood, Michael P; Garrigues, Grant E

    2015-07-01

    The in vivo effects of metal hypersensitivity remain a topic of much debate. At the core of this debate is the possible, although still hotly contested, link between metal hypersensitivity and poorly functioning or failing implants. There are multiple studies on this topic in the hip and knee arthroplasty literature, but the applicability of this experience to shoulder arthroplasty remains unclear. Although how often metal hypersensitivity affects shoulder arthroplasty patients remains uncertain, a multitude of case reports have implicated metallic implants as a source of local and systemic allergic reactions. We recommend a cautious approach to patients with a history of metal hypersensitivity, including a careful evaluation of suspected metal hypersensitivities in all patients undergoing shoulder arthroplasty. If available, we recommend a metallic implant with low to no nickel content in patients with metal hypersensitivity. Given the large and increasing, number of total shoulder arthroplasty procedures and the high percentage of the population having a known or suspected metal hypersensitivity, this review is intended to guide and educate the shoulder surgeon in the evaluation and treatment of this patient population and to point out the areas where evidence-based recommendations are lacking. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  13. Availability of Total Knee Arthroplasty Implants for Metal Hypersensitivity Patients

    PubMed Central

    Ajwani, Sanil Harji; Charalambous, Charalambos P.

    2016-01-01

    Purpose To provide information on the type of “hypersensitivity-friendly” components available for primary total knee arthroplasty (TKA) in the current market. Materials and Methods Implant manufactures were identified using the 2013 National Joint Registries of the United Kingdom and Sweden and contacted to obtain information about the products they offer for patients with metal hypersensitivity. Results Information on 23 TKA systems was provided by 13 implant manufacturers. Of these, 15 systems had options suitable for metal hypersensitivity patients. Two types of “hypersensitivity-friendly” components were identified: 10 implants were cobalt chrome prostheses with a “hypersensitivity-friendly” outer coating and 5 implants were made entirely from non-cobalt chrome alloys. Conclusions The results of this study suggest that several hypersensitivity TKA options exist, some of which provide the same designs and surgical techniques as the conventional implants. The information in this study can guide TKA surgeons in making informed choices about implants and identifying implants that could be examined in future controlled studies comparing outcomes between “hypersensitivity-friendly” and conventional implants. PMID:27894179

  14. Immediate hypersensitivity reaction to gadolinium-based MR contrast media.

    PubMed

    Jung, Jae-Woo; Kang, Hye-Ryun; Kim, Min-Hye; Lee, Whal; Min, Kyung-Up; Han, Moon-Hee; Cho, Sang-Heon

    2012-08-01

    To determine the incidence and risk factors of immediate hypersensitivity reactions to gadolinium-based magnetic resonance (MR) contrast agents. Institutional review board approval and a waiver of informed consent were obtained. A retrospective study of patients who had been given gadolinium-based MR contrast media between August 2004 and July 2010 was performed by reviewing their electronic medical records. In addition to data on immediate hypersensitivity reaction, the kinds of MR contrast media and demographic data including age, sex, and comorbidity were collected. To compare the groups, the χ(2) test, Fisher exact test, χ(2) test for trend, Student t test, analysis of variance test, and multiple logistic regression test were performed. A total of 112 immediate hypersensitivity reactions (0.079% of 141 623 total doses) were identified in 102 patients (0.121% of 84 367 total patients). Among the six evaluated MR contrast media, gadodiamide had the lowest rate (0.013%) of immediate hypersensitivity reactions, while gadobenate dimeglumine had the highest rate (0.22%). The rate for immediate hypersensitivity reactions was significantly higher in female patients (odds ratio = 1.687; 95% confidence interval: 1.143, 2.491) and in patients with allergies and asthma (odds ratio = 2.829; 95% confidence interval: 1.427, 5.610). Patients with a previous history of immediate hypersensitivity reactions had a higher rate of recurrence after reexposure to MR contrast media (30%) compared with the incidence rate in total patients (P < .0001). The incidence of immediate hypersensitivity reactions increased depending on the number of times patients were exposed to MR contrast media (P for trend = .036). The most common symptom was urticaria (91.1%), and anaphylaxis occurred in 11 cases (9.8%). The mortality rate was 0.0007% because of one fatality. The incidence of immediate hypersensitivity reactions to MR contrast media was 0.079%, and the recurrence rate of hypersensitivity

  15. [Causes and treatment of hypersensitivity in tooth root].

    PubMed

    Skaleric, U; Petelin, M

    1989-01-01

    The review article describes aetiology and treatment of dental root hypersensitivity. The three main theories of pain transduction from the exposed dentin surface to pain receptors in dental pulp are described. In addition, therapeutic compounds used to stimulate reparatory dentin formation and mineralization of peritubular dentin are described as well. The application of resins and adhesives on exposed dentin root surfaces is advocated in cases of chronic hypersensitivity. Finally, the authors emphasize the need for correct oral hygiene and early orthodontic treatment, if indicated, to prevent gingival recession and hypersensitivity of exposed root surfaces.

  16. 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.

  17. Role of Delayed Hypersensitivity in Blastomycosis of Mice

    PubMed Central

    Spencer, Harry D.; Cozad, George C.

    1973-01-01

    C57BL/6J mice rendered hypersensitive to Blastomyces dermatitidis were protected from the lethal effects of a blastomyces infection. This protection was observed following a lethal intraperitoneal challenge with viable cells 15 days after subcutaneous inoculation with 3.9 × 104 viable cells. Delayed hypersensitivity was induced in C57 mice by two injections of Merthiolate-killed cells in adjuvant or by a single injection of viable cells. Development of hypersensitivity was determined at appropriate intervals by footpad injection with killed yeast cells. PMID:4713689

  18. Drugs that may provoke Kounis syndrome.

    PubMed

    Rodrigues, Maria Catarina Luís; Coelho, Daniela; Granja, Cristina

    2013-01-01

    Kounis Syndrome (KS) is the contemporary occurrence of Acute Coronary Syndromes (ACS) with an allergic or hypersensitivity reaction. This syndrome has been reported in association with a variety of drugs, food, insect stings, environmental exposures and medical conditions. Cases of KS seem to be more often encountered in everyday clinical practice than anticipated. It is believed that the lack of awareness of this association may lead to underreporting. We report a case of KS secondary to diclofenac intake.

  19. Reduction of sulfamethoxazole and dapsone hydroxylamines by a microsomal enzyme system purified from pig liver and pig and human liver microsomes.

    PubMed

    Clement, Bernd; Behrens, Detlef; Amschler, Juliane; Matschke, Katrin; Wolf, Stephanie; Havemeyer, Antje

    2005-05-27

    Biotransformation involving nitrogen are of pharmacological and toxicological relevance. In principle, nitrogen containing functional groups can undergo all the known biotransformation processes such as oxidation, reduction, hydrolysis and formation of conjugates. For the N-reduction of benzamidoxime an oxygen-insensitive liver microsomal enzyme system that required cytochrome b5, NADH-cytochrome b5 reductase and a cytochrome P450 isoenzyme of the subfamily 2D has been described. In previous studies it was demonstrated that N-hydroxylated derivates of strongly basic functional groups are easily reduced by this enzyme system. The N-hydroxylation of sulfonamides such sulfamethoxazole (SMX) and dapsone (DDS) to sulfamethoxazole-hydroxylamine (SMX-HA) and dapsone-hydroxylamine (DDS-N-OH), respectively is the first step in the formation of reactive metabolites. Therefore it seemed reasonable to study the potential of cytochrome b5, NADH-cytochrome b5 reductase and CYP2D to detoxify these N-hydroxylated metabolites by N-reduction. Metabolites were analysed by HPLC analysis. SMX-HA and DDS-N-OH are reduced by cytochrome b5, NADH-cytochrome b5 reductase and CYP2D but also only by cytochrome b5 and NADH-cytochrome b5 reductase without addition of CYP2D. The reduction rate for SMX-HA by cytochrome b5, NADH-cytochrome b5 reductase and CYP2D was 0,65 +/- 0,1 nmol SMX/min/mg protein. The reduction rate by b5 and b5 reductase was 0,37 +/- 0,15 nmol SMX/min/mg protein. For DDS-N-OH the reduction rate by cytochrome b5, NADH-cytochrome b5 reductase and CYP2D was 1.79 +/- 0.85 nmol DDS/min/mg protein and by cytochrome b5 and NADH-cytochrome b5 reductase 1.25 +/- 0.15 nmol DDS/min/mg protein. Cytochrome b5, NADH-cytochrome b5 reductase are therefore involved in the detoxification of these reactive hydroxylamines and CYP2D increased the N-reduction.

  20. Vestibular hypersensitivity to sound (Tullio phenomenon): structural and functional assessment.

    PubMed

    Watson, S R; Halmagyi, G M; Colebatch, J G

    2000-02-08

    To establish the role of high-resolution CT imaging and tests of vestibulocollic reflexes in diagnosing and understanding the pathogenesis of the Tullio phenomenon. The Tullio phenomenon is a syndrome in which acoustic stimulation produces symptoms and signs of vestibular activation. It has previously been associated with an abnormally low threshold for click-evoked vestibulocollic responses and also with dehiscence of the roof of the anterior (superior) semicircular canal on high-resolution CT scans of the temporal bones. High-resolution CT scans of the temporal bones and vestibulocollic responses in sternocleidomastoid to both clicks and transmastoid galvanic stimulation (3 mA/2 msec) were studied in four patients with the Tullio phenomenon (one bilateral). Click-evoked thresholds were low for all affected ears (four at 65 dB nHL, one at 55 dB nHL) and normal (>70 dB nHL) for the three unaffected ears. In contrast, galvanic-evoked vestibulocollic responses were symmetric and of normal size in all patients. The bony roof of the anterior (superior) semicircular canal was thin, possibly absent, on CT of all affected ears and also in two out of three unaffected ears. The normal galvanic vestibulocollic responses indicate that sound sensitivity in patients with the Tullio phenomenon is likely to occur distal to the vestibular nerve, probably at the level of the receptors. Both click hypersensitivity and dehiscence of the anterior (superior) semicircular canal are associated with the Tullio phenomenon but as the CT scan abnormality can occur in clinically unaffected ears, click testing is important for specific diagnosis. Abnormal sound sensitivity, as demonstrated by click responses, confirms that the radiologic abnormality is function significant.

  1. [Hypersensitivity to metals in patients with orthopedic implants].

    PubMed

    Sánchez Olivas, Manuel Anastacio; Valencia Zavala, Martha Patricia; Sánchez Olivas, Jesús Alberto; Sepúlveda Velázquez, Guadalupe

    2010-01-01

    All metals in contact with biological systems suffer corrosion, which is an electrochemical process that causes metallic ions formation, known as haptens, which link with endogenous or exogenous proteins, therefore inducing an immune response. A hypersensitivity response to an implanted material should be suspected when cutaneous lesions or inflammatory reactions occur proximal to or surrounding the site of the metallic orthopedic implant. At present there is no a reliable diagnostic test for the determination of hypersensitivity to implanted metallic devices. It has been shown that the products of corrosive degradation are associated with dermatitis, urticaria and vasculitis. Cutaneous lesions in patients with unsuccessful metallic implants are more frequent than in non-rejected implants or the general population. Although the cellular and humoral hypersensitivity response in metallic orthopedic implants has been clearly identified, the risk is very low. Nowadays the importance of hypersensitivity to metals as a contributing factor in the failure of implants is unknown.

  2. Hypersensitivity Reactions to Implanted Metal Devices: Facts and Fictions.

    PubMed

    Teo Wendy, Z W; Schalock, P C

    The use of metals in the medical field has become increasingly prevalent over the past few decades. Patients find themselves being exposed to metals in a variety of ways, ranging from external exposure to instruments such as the stainless steel in surgical blades to internal exposure via medical devices being implanted in their bodies. There has been growing interest in the possibility of developing hypersensitivity reactions to constituent metals in medical implant devices, both in cutaneous and systemic forms. Hypersensitivity reactions to metals are uncommon, but they are reported and require appropriate evaluation and management, particularly if they are symptomatic. In view of the lack of consensus in the field on the appropriate steps to evaluate and manage patients with suspected metal hypersensitivity reactions, this review aims to analyze current evidence on hypersensitivity reactions to metallic implants in orthopedic surgery, endovascular surgery, obstetrics and gynecology, and dental surgery.

  3. Total Knee Arthroplasty Failure Induced by Metal Hypersensitivity.

    PubMed

    Gupta, Ryan; Phan, Duy; Schwarzkopf, Ran

    2015-08-17

    Metal hypersensitivity is an uncommon complication after total knee arthroplasty (TKA) that can lead to significant functional impairment and aseptic prosthesis failure. We describe a 70-year-old patient who presented with persistent pain, swelling, and instability 2 years after a primary TKA. The patient had a history of metal hypersensitivity following bilateral metal-on-metal total hip arthroplasty (THA) that was revised to ceramic-on-polyethylene implants. Knee radiographs showed severe osteolysis with implant loosening. Serum cobalt was elevated and serum chromium was significantly elevated, while joint aspiration and inflammatory marker levels ruled out a periprosthetic infection. Revision TKA was performed, with intraoperative tissue pathology and postoperative leukocyte transformation testing confirming metal hypersensitivity as the cause for aseptic implant failure. This case report demonstrates the clinical and laboratory signs that suggest metal hypersensitivity in total knee arthroplasty and the potential for joint function restoration with revision surgery.

  4. Allergic and hypersensitivity reactions in the intensive care unit.

    PubMed

    Kanji, Salmaan; Chant, Clarence

    2010-06-01

    Hypersensitivity reactions are defined as immunologically based adverse reactions to chemicals or medicinal agents. These reactions are common in the intensive care unit and can present as a simple, mildly symptomatic rash or as life-threatening anaphylactic reactions. Hypersensitivity reactions have traditionally been classified as types I to IV reactions based on the underlying immune mechanisms, although the clinical relevance of the classification is unclear, and new subtypes to this system have been recently proposed. Given the immunologic and often unpredictable nature of these reactions, avoidance or prevention is not a feasible option. Therefore, management has primarily consisted of withdrawal of potential offending agents, supportive therapy, symptomatic management, and, in some specific examples, targeted pharmacotherapy. This article outlines the background and types of hypersensitivity reactions and provides descriptions and management strategies when applicable to common types of hypersensitivity reactions encountered in the intensive care unit.

  5. Effectiveness of Lasers in the Treatment of Dentin Hypersensitivity

    PubMed Central

    Asnaashari, Mohammad; Moeini, Masoumeh

    2013-01-01

    Dentin hypersensitivity (DH) is a relatively common painful condition among dental problems. Although many studies have been performed regarding the diagnosis and treatment of DH, dental practitioners are still confused about the definite diagnosis and treatment.The use of lasers as a treatment for dentin hypersensitivity was first introduced in 1985.Laser treatment in dentin hypersensitivity is an interesting and controversial issue and many investigations have been done on its mechanism of action, advantages, and unclear points.The present literature review tries to go over the definition, diagnosis, etiology , predisposing factors, various laser types in the treatment of DH alone or in combination with topical desensitizing agents. Since a certain treatment has not yet introduced for dentin hypersensitivity, a combination of laser therapy and topical desensitizing factors ,can increase the success of the treatment compared with either treatments alone. PMID:25606300

  6. Low Ubiquinone Content in Escherichia coli Causes Thiol Hypersensitivity

    PubMed Central

    Zeng, H.; Snavely, I.; Zamorano, P.; Javor, G. T.

    1998-01-01

    Thiol hypersensitivity in a mutant of Escherichia coli (IS16) was reversed by complementation with a plasmid that carried the ubiX gene. The mutant had low ubiquinone content. Complementation elevated the ubiquinone level and eliminated thiol hypersensitivity. Analysis of chromosomal ubiX genes indicated that both parent and mutant strains were ubiX mutants. The low ubiquinone content of IS16 was possibly caused by a ubiD ubiX genotype. A ubiA mutant also exhibited thiol hypersensitivity. Neither IS16 nor the ubiA mutant strain could produce alkaline phosphatase (in contrast to their parent strains) after 2 h of induction, thus showing Dsb− phenotypes. The phenomena of thiol hypersensitivity and low ubiquinone content may be linked by their connections to the periplasmic disulfide bond redox machinery. PMID:9658014

  7. Nonsteroidal anti-inflammatory drug hypersensitivity among children.

    PubMed

    Guvenir, Hakan; Dibek Misirlioglu, Emine; Vezir, Emine; Toyran, Muge; Ginis, Tayfur; Civelek, Ersoy; Kocabas, Can N

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAID) are the second-most frequent drugs that cause hypersensitivity reactions among children. Studies related to NSAIDs hypersensitivity in children are limited. In this study, we aimed to evaluate children admitted with suspicion of NSAIDs reaction. Between January 1, 2011, and November 30, 2014, we included patients with suspicion of NSAIDs hypersensitivity in our clinic. For evaluation, skin tests and oral provocation tests with the drug (suspected or alternative) were proposed. Reactions were classified and defined according to the latest European Academy of Allergy and Clinical Immunology position paper on NSAID hypersensitivity. During the study period, 123 patients (with 136 drug reactions) were admitted to our clinic with suspected NSAID hypersensitivity. The mean (standard deviation) age of the patients, 67 female (55%), was 83.10 ± 56.05 months. Thirteen patients described reactions to more than one chemically unrelated NSAID, and 110 patients described reactions with chemically similar drugs. Eight patients were not included because they did not have provocation tests. Thus, 115 patients were evaluated. A hundred and thirty provocations were performed. Twenty patients (17.4%) were diagnosed with NSAID hypersensitivity (13 patients diagnosed by provocation tests and 7 patients diagnosed according to their history). The most frequently encountered agent was ibuprofen (50% [10/20]). Eighty percent (16 patients) of the reactions were considered "non-cross-reactive type." Fifteen patients (75%) were classified as having single-NSAID-induced urticaria and/or angioedema, three patients were classified as having NSAID-induced urticaria and/or angioedema, one patient was classified as having NSAID-exacerbated respiratory disease, and the other patients were classified as having single-NSAID-induced delayed hypersensitivity reactions. Detailed history and drug provocation tests are important to verify NSAID hypersensitivity

  8. Non-steroidal anti-inflammatory drug hypersensitivity in children.

    PubMed

    Alves, C; Romeira, A M; Abreu, C; Carreiro-Martins, P; Gomes, E; Leiria-Pinto, P

    There are rather few publications about hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAID) in the paediatric age. In this study, we aimed to assess the frequency of confirmed NSAID hypersensitivity in children with a previous reported reaction to NSAID in order to investigate the role of the drug provocation test (DPT) in the diagnostic workup and to explore the factors associated with confirmed NSAID hypersensitivity. We conducted a retrospective analysis of the clinical files from every patient under 18 years old who attended two Portuguese paediatric allergy outpatient clinics, from January 2009 to August 2014, due to a suspected NSAID hypersensitivity. We included 119 patients, with a median age of nine years (P25-P75: 5-14). Ibuprofen was the commonest implicated NSAID in the patients' reports (n=94-79%). After DPT, NSAID hypersensitivity was confirmed in nine (7.6%) patients, excluded in 93 (78.2%) and was inconclusive in 17 (14.3%). In the majority (n=95-79.8%), the reaction occurred in the first 24h after intake. Eighty-four patients (70.6%) reported only cutaneous manifestations and 18 (15.1%) had systemic symptoms. Anaphylaxis represented a relative risk to NSAID hypersensitivity confirmation. No association was found for atopy and the number of previous reactions. In our study, NSAID hypersensitivity was confirmed in a small proportion of the patients with a previous reported reaction. Ibuprofen was the most implicated drug with urticaria/angio-oedema as the commonest manifestation. Anaphylaxis was associated with confirmed drug hypersensitivity. The drug provocation test was essential to establish the diagnosis. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

  9. Hypersensitivity due to ceftriaxone mimicking measles in a child.

    PubMed

    Arulraj, Russelian; Venkatesh, Chandrasekaran; Chhavi, Nanda; Soundararajan, Palanisamy

    2013-01-01

    Ceftriaxone is a commonly used antibiotic in children for various infections like respiratory tract infection, urinary tract infection and enteric fever. Hypersensitive reactions following ceftriaxone therapy are uncommon but are potentially life-threatening. The rash can resemble viral exanthems and may lead to a delay in the recognition and prompt treatment. Here we report a 7-year-old boy who presented with fever and rash with emphasis on recognizing ceftriaxone hypersensitivity and its management.

  10. Metal Hypersensitivity and Orthopedic Implants: Survey of Orthopedic Surgeons.

    PubMed

    Hallock, Katherine; Vaughn, Natalie H; Juliano, Paul; Marks, James G

    There is no clear consensus among orthopedic surgeons concerning metal hypersensitivity screening and orthopedic implants. This study investigated practices and opinions about metal hypersensitivity and orthopedic implants via a survey administered to practicing orthopedists. A questionnaire was sent to members of the Pennsylvania Orthopaedic Society electronically. Respondents were asked about preoperative and postoperative screening habits concerning metal hypersensitivity and implants. Forty-four physicians completed the survey. Only 11% of respondents reported that they always or often screen patients for metal hypersensitivity. Fifty percent of respondents stated that they only rarely refer patients for patch testing (and the remainder never do). If, however, patients were found to have a positive patch test, most providers were very likely to use a different implant. Other respondents were skeptical of the relationship between metal hypersensitivity and implant failure. Dermatitis, pain, and loosening were common reasons for postoperative testing. Seventy percent of respondents said that patch testing rarely or never changed their decision making. This study is reflective of the lack of consensus between orthopedists regarding patch testing. It demonstrates the diversity of opinions among orthopedists, the need for additional dialogue between orthopedic and dermatology specialties, and the need for larger studies investigating outcomes and metal hypersensitivity.

  11. Visceral and Somatic Hypersensitivity in TNBS induced Colitis in Rats

    PubMed Central

    Zhou, QiQi; Price, Donald D.; Caudle, Robert M.; Verne, G. Nicholas

    2010-01-01

    Inflammation of visceral structures in rats has been shown to produce visceral/somatic hyperalgesia. Our objectives were to determine if trinitrobenzene sulfonic acid (TNBS) induced colitis in rats leads to visceral/somatic hypersensitivity. Male Sprague-Dawley rats (200g–250g) were treated with 20 mg of TNBS in 50% ethanol (n=40) or an equivalent volume of ethanol (n=40) or saline (n=25) via the colon. Colonic distension, Von-Frey, Hargreaves, and tail reflex test were used to evaluate for visceral, mechanical, and thermal sensitivity. The rats demonstrated visceral hypersensitivity at 2–28 days following TNBS (p<0.0001). The ethanol treated rats also demonstrated visceral hypersensitivity that resolved after day 14. TNBS treated rats demonstrated somatic hypersensitivity at days 14–28 (p<0.0001) in response to somatic stimuli of the hind-paw. TNBS colitis is associated with visceral and somatic hypersensitivity in areas of somatotopic overlap. This model of colitis should allow further investigation into the mechanisms of visceral and somatic hypersensitivity. PMID:17703363

  12. Short report: comparison of chlorproguanil-dapsone with a combination of sulfadoxine-pyrimethamine and chloroquine in children with malaria in northcentral Nigeria.

    PubMed

    Ogunfowokan, Oluwagbenga; Dankyau, Musa; Madaki, Aboi J K; Thacher, Tom D

    2009-02-01

    Effective and affordable treatment of malaria is critical in the face of resistance of Plasmodium falciparum to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP). We conducted a randomized controlled trial comparing the efficacy of chlorproguanil-dapsone (CD) with a combination SP plus CQ in children in Nigeria less than five years of age with malaria. Of 264 children enrolled, 122 (89.7%) and 118 (92.2%) completed the study in the SP + CQ and CD groups, respectively. By day 3, 96 (78.7%) and 94 (79.7%) had cleared their parasitemia (P = 0.79), and 107 (87.7%) and 109 (92.4%) were symptom free (P = 0.32) in the SP + CQ and CD groups, respectively. Adequate clinical and parasitologic response at day 14 occurred in 111 (94.1%; 95% confidence interval [CI] = 91.6-95.7%) in the CD group and 113 (92.6%; 95% CI = 89.9-94.3%) in the SP + CQ group (P = 0.85). SP + CQ and CD had similar antimalarial efficacy and still provide affordable treatment of uncomplicated malaria in northcentral Nigeria.

  13. Feasibility of amlodipine besylate, chloroquine phosphate, dapsone, phenytoin, pyridoxine hydrochloride, sulfadiazine, sulfasalazine, tetracycline hydrochloride, trimethoprim and zonisamide in SyrSpend(®) SF PH4 oral suspensions.

    PubMed

    Ferreira, Anderson O; Polonini, Hudson C; Silva, Sharlene L; Patrício, Fernando B; Brandão, Marcos Antônio F; Raposo, Nádia R B

    2016-01-25

    The objective of this study was to evaluate the feasibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend(®) SF PH4 liquid): (i) amlodipine, (as besylate) 1.0mg/mL; (ii) chloroquine phosphate,15.0 mg/mL; (iii) dapsone, 2.0 mg/mL; (iv) phenytoin, 15.0 mg/mL; (v) pyridoxine hydrochloride, 50.0 mg/mL; (vi) sulfadiazine, 100.0 mg/mL; (vii) sulfasalazine, 100.0 mg/mL; (viii) tetracycline hydrochloride, 25.0 mg/mL; (ix) trimethoprim, 10.0 mg/mL; and (x) zonisamide, 10.0 mg/mL. All suspensions were stored both at controlled refrigeration (2-8 °C) and controlled room temperature (20-25 °C). Feasibility was assessed by measuring the percent recovery at varying time points throughout a 90-day period. API quantification was performed by high-performance liquid chromatography (HPLC-UV), via a stability-indicating method. Given the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was at least 90 days for all suspensions with regard to both the controlled temperatures. This suggests that the vehicle is stable for compounding APIs from different pharmacological classes.

  14. Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin.

    PubMed

    Kast, Richard E; Hill, Quentin A; Wion, Didier; Mellstedt, Håkan; Focosi, Daniele; Karpel-Massler, Georg; Heiland, Tim; Halatsch, Marc-Eric

    2017-05-01

    Increased ratio of circulating neutrophils to lymphocytes is a common finding in glioblastoma and other cancers. Data reviewed establish that any damage to brain tissue tends to cause an increase in G-CSF and/or GM-CSF (G(M)-CSF) synthesized by the brain. Glioblastoma cells themselves also synthesize G(M)-CSF. G(M)-CSF synthesized by brain due to damage by a growing tumor and by the tumor itself stimulates bone marrow to shift hematopoiesis toward granulocytic lineages away from lymphocytic lineages. This shift is immunosuppressive and generates the relative lymphopenia characteristic of glioblastoma. Any trauma to brain-be it blunt, sharp, ischemic, infectious, cytotoxic, tumor encroachment, or radiation-increases brain synthesis of G(M)-CSF. G(M)-CSF are growth and motility enhancing factors for glioblastomas. High levels of G(M)-CSF contribute to the characteristic neutrophilia and lymphopenia of glioblastoma. Hematopoietic bone marrow becomes entrained with, directed by, and contributes to glioblastoma pathology. The antibiotic dapsone, the lipid-lowering agent fenofibrate, and the antiviral drug ribavirin are Food and Drug Administration- and European Medicines Agency-approved medicines that have potential to lower synthesis or effects of G(M)-CSF and thus deprive a glioblastoma of some of the growth promoting contributions of bone marrow and G(M)-CSF.

  15. Hypersensitivity pneumonitis associated with home ultrasonic humidifiers.

    PubMed

    Suda, T; Sato, A; Ida, M; Gemma, H; Hayakawa, H; Chida, K

    1995-03-01

    We describe five patients with hypersensitivity pneumonitis (HP) that was related to using home ultrasonic humidifiers. All patients had micronodular infiltrates on their chest radiograph, and their lung biopsy specimens revealed alveolitis with or without epithelioid cell granulomas. Challenge tests were performed on two patients with the humidifier water and three patients using the humidifier. All patients tested exhibited a positive response. Tests for precipitating antibodies against an extract of the humidifier water gave strongly positive reactions in all patients tested. Precipitins to Cephalosporium acremonium and Candida albicans were also present in all cases, whereas precipitins to thermophilic actinomycetes were not detected. Although cultures of the water grew a variety of fungal and bacterial organisms, thermophilic actinomycetes could not be detected. These findings suggest that thermophilic organisms may not be the causative antigens of HP associated with ultrasonic humidifiers. All five patients had an increase in the bronchoalveolar lavage (BAL) lymphocytes that were predominantly CD4+ lymphocytes. The T helper cell count (CD4) to suppressor T cell count (CD8) ratio was significantly higher than that observed in summer-type HP, and lower than that observed in bird fancier's lung, indicating that the phenotypes of the BAL lymphocytes may vary with the type of HP.

  16. Mouse Model of Halogenated Platinum Salt Hypersensitivity ...

    EPA Pesticide Factsheets

    Occupational exposure to halogenated platinum salts can trigger the development of asthma. Concern for increased asthma risk exists for the general population due to the use of platinum (Pt) in catalytic converters and its emerging use as a diesel fuel additive. To investigate airway responses to Pt, we developed a mouse model of Pt hypersensitivity. Previously, we confirmed the dermal sensitizing potency of ammonium hexachloroplatinate (AHCP) using an ex vivo [3H]methyl thymidine labeling version of the local lymph node assay in BALB/c mice. Here, we investigated the ability of AHCP to induce airway responses in mice sensitized by the dermal route. Mice were sensitized through application of 100 µL 1% AHCP in DMSO to the shaved back on days 0, 5 and 19, and 25 µl to each ear on days 10, 11 and 12. Unsensitized mice received vehicle. On day 24, mice were challenged by oropharyngeal aspiration (OPA) with 0 or 100 µg AHCP in saline. Before and immediately after challenge, airway responses were assessed using whole body plethysmography (WBP). On day 26, changes in ventilatory responses to methacholine (Mch) aerosol were assessed by WBP; dose-dependent increases in Mch responsiveness occurred in sensitized mice. Bronchoalveolar lavage fluid harvested from sensitized mice contained an average of 7.5% eosinophils compared to less than 0.5% in control mice (p < 0.05). This model will be useful for assessing both relative sensitizing potency and cross-reacti

  17. Dentin hypersensitivity: Recent trends in management

    PubMed Central

    Miglani, Sanjay; Aggarwal, Vivek; Ahuja, Bhoomika

    2010-01-01

    Dentinal hypersensitivity (DH) is a common clinical condition usually associated with exposed dentinal surfaces. It can affect patients of any age group and most commonly affects the canines and premolars of both the arches. This article concisely reviews the patho-physiology, mechanism and clinical management of the DH. Treatment of DH should start with an accurate diagnosis. Differential diagnosis should be made and all other probable causes should be excluded. An often neglected phase of clinical management of DH is the identification and treatment of the causative factors of DH. By removing the etiological factors, the condition can be even prevented from occurring or recurring. There are various treatment modalities available which can be used at home or may be professionally applied. The “at home” desensitizing agents include toothpastes, mouthwashes or chewing gums and they act by either occluding the dentinal tubules or blocking the neural transmission. This article also discusses the recent treatment options like bioglass, Portland cement, lasers and casein phosphopeptide. PMID:21217949

  18. Type III Hypersensitivity Reaction in Mushroom Growers

    PubMed Central

    Choi, Byoung-Whui; Min, Kyung-Up; Kim, You-Young; Moon, Hee-Bom; Chang, Suk-II; Kang, Seock-Young; Kim, Sang-Jae; Kim, Sin-Ok

    1991-01-01

    Some respiratory symptoms in mushroom growers such as mushroom worker’s lung develop by inhalation of certain agents arising from the environment of mushroom cultivation. Recently we observed mushroom workers who had respiratory symptoms which might be type III hypersensitivity reaction to the antigen of Pleurotus floridae. We gave questionaires to all the mushroom growers at one of the biggest cultivation areas of mushrooms, Pleurotus floridae in Pocheon, Kyunggi Province. Those with respiratory symptoms were subjects for the study. CBC, chest X-ray, pulmonary function test, skin test with Pleurotus floridae extract, and precipitin antibody test to Pleurotus floridae were performed in the study subjects. Out of a total 308 mushroom workers, 23 workers (14 males, 9 females) had respiratory symptoms. Their mean age was 45 years, and their mean duration of engagement was 3.4 years. Their main symptoms were cough (100%), sputum (82.6%), dyspnea (43.5%), and fever with chills (13.0%). Two cases showed increased interstitial lung markings on chest X-ray films. Sixteen cases (73.9%) showed precipitin antibodies against P. floridae extract by counterimmunoelectrophoresis. Antibodies against Micropolyspora faeni and Thermoactinomyces vulgaris were not detected in any subject. PMID:1742253

  19. Immediate and delayed type hypersensitivity to malathion.

    PubMed

    Schanker, H M; Rachelefsky, G; Siegel, S; Katz, R; Spector, S; Rohr, A; Rodriquiz, C; Woloshin, K; Papanek, P J

    1992-12-01

    Between December 1989 and June 1990, 1,874 reports of alleged malathion application related illness from repeated spraying of a mixture of malathion corn syrup bait to eradicate a Mediterranean fruit fly infestation in Southern California were received by the Toxics Epidemiology Program of Los Angeles County. Among these complaints were 47 reports of urticaria, 38 reports of angioedema and 213 reports of a nonspecific skin rash. In order to determine whether these alleged skin reactions were the result of an immediate or delayed type of hypersensitivity reaction to malathion or to the corn syrup bait we studied ten subjects referred for testing by the local health department. All ten subjects had no reaction on patch testing. One child exhibited a positive reaction to the bait and one child had irritant reactions to malathion and to the bait. This study documented one case of a possible immediate IgE reaction to malathion bait. Due to the low participation rates in this study, no specific conclusions concerning the rate of sensitivity in the population can be drawn, although it appears that such reactions are uncommon.

  20. Visceral pain hypersensitivity in functional gastrointestinal disorders.

    PubMed

    Farmer, A D; Aziz, Q

    2009-01-01

    Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders whose diagnostic criteria are symptom based in the absence of a demonstrable structural or biochemical abnormality. Chronic abdominal pain or discomfort is a defining characteristic of these disorders and a proportion of patients may display heightened pain sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity (VPH). We examined the most recent literature in order to concisely review the evidence for some of the most important recent advances in the putative mechanisms concerned in the pathophysiology of VPH. VPH may occur due to anomalies at any level of the visceral nociceptive neuraxis. Important peripheral and central mechanisms of sensitization that have been postulated include a wide range of ion channels, neurotransmitter receptors and trophic factors. Data from functional brain imaging studies have also provided evidence for aberrant central pain processing in cortical and subcortical regions. In addition, descending modulation of visceral nociceptive pathways by the autonomic nervous system, hypothalamo-pituitary-adrenal axis and psychological factors have all been implicated in the generation of VPH. Particular areas of controversy have included the development of efficacious treatment of VPH. Therapies have been slow to emerge, mainly due to concerns regarding safety. The burgeoning field of genome wide association studies may provide further evidence for the pleiotropic genetic basis of VPH development. Tangible progress will only be made in the treatment of VPH when we begin to individually characterize patients with FGIDs based on their clinical phenotype, genetics and visceral nociceptive physiology.

  1. Handedness as a marker for drug hypersensitivity.

    PubMed

    Coren, S

    1998-04-01

    Several causal observations and a few recent studies suggest that left-handers may have greater reactivity to various drugs. A sample of 747 adults was surveyed to determine if they had had signs of hypersensitivity to commonly prescribed pharmaceutical drugs. Left-handers were significantly more likely to experience constipation, dizziness, and skin rashes, and were nearly three times more likely to experience other, miscellaneous, negative drug reactions. In addition left-handers were nearly twice as likely to have experienced situations where their physician felt it necessary to reduce drug dosages because of unwanted side-effects of medication. A second experiment using 840 adults indicated that a potential confound that would result if left-handers simply used more medical drugs in general, which would then give them more occasions on which reactions could occur, does not explain these results. Mechanisms that might account for these differences in drug sensitivity include differences in brain morphology, birth stress related neuropathy, and differences in immune system responses, all of which have been found to differ as a function of handedness.

  2. Advances in upper airway cough syndrome.

    PubMed

    Yu, Li; Xu, Xianghuai; Lv, Hanjing; Qiu, Zhongmin

    2015-05-01

    Upper airway cough syndrome (UACS), previously referred to as postnasal drip syndrome, is one of the most common causes of chronic cough. However, the pathogenesis of UACS/postnasal drip syndrome remains unclear, and physicians in countries throughout the world have different definitions and ways of treating this disease. The various proposed pathogeneses of UACS include the early postnasal drip theory, subsequent chronic airway inflammation theory, and a recent sensory neural hypersensitivity theory. Additionally, some researchers suggest that UACS is a clinical phenotype of cough hypersensitivity syndrome. While the general principles involved in treating UACS are similar throughout the world, the specific details of treatment differ. This review summarizes the various definitions, pathogenic mechanisms, treatments, and other aspects of UACS, to aid clinicians in expanding their knowledge of how to diagnose and treat this syndrome.

  3. Increased frequency of delayed type hypersensitivity to metals in patients with connective tissue disease.

    PubMed

    Stejskal, Vera; Reynolds, Tim; Bjørklund, Geir

    2015-01-01

    Connective tissue disease (CTD) is a group of inflammatory disorders of unknown aetiology. Patients with CTD often report hypersensitivity to nickel. We examined the frequency of delayed type hypersensitivity (DTH) (Type IV allergy) to metals in patients with CTD. Thirty-eight patients; 9 with systemic lupus erythematosus (SLE), 16 with rheumatoid arthritis (RA), and 13 with Sjögren's syndrome (SS) and a control group of 43 healthy age- and sex-matched subjects were included in the study. A detailed metal exposure history was collected by questionnaire. Metal hypersensitivity was evaluated using the optimised lymphocyte transformation test LTT-MELISA(®) (Memory Lymphocyte Immuno Stimulation Assay). In all subjects, the main source of metal exposure was dental metal restorations. The majority of patients (87%) had a positive lymphocyte reaction to at least one metal and 63% reacted to two or more metals tested. Within the control group, 43% of healthy subjects reacted to one metal and only 18% reacted to two or more metals. The increased metal reactivity in the patient group compared with the control group was statistically significant (P<0.0001). The most frequent allergens were nickel, mercury, gold and palladium. Patients with SLE, RA and SS have an increased frequency of metal DTH. Metals such as nickel, mercury and gold are present in dental restorative materials, and many adults are therefore continually exposed to metal ions through corrosion of dental alloys. Metal-related DTH will cause inflammation. Since inflammation is a key process in CTDs, it is possible that metal-specific T cell reactivity is an etiological factor in their development. The role of metal-specific lymphocytes in autoimmunity remains an exciting challenge for future studies. Copyright © 2015 Elsevier GmbH. All rights reserved.

  4. Enhanced responses of the anterior cingulate cortex neurones to colonic distension in viscerally hypersensitive rats

    PubMed Central

    Gao, Jun; Wu, Xiaoyin; Owyang, Chung; Li, Ying

    2006-01-01

    The anterior cingulate cortex (ACC) is critically involved in processing the affective component of pain sensation. Visceral hypersensitivity is a characteristic of irritable bowel syndrome. Electrophysiological activity of the ACC with regard to visceral sensitization has not been characterized. Single ACC neuronal activities in response to colorectal distension (CRD) were recorded in control, sham-treated rats and viscerally hypersensitive (EA) rats (induced by chicken egg albumin injection, i.p). The ACC neurones of controls failed to respond to 10 or 30 mmHg CRD; only 22% were activated by 50 mmHg CRD. Among the latter, 16.4% exhibited an excitatory response to CRD and were labelled ‘CRD-excited’ neurones. In contrast, CRD (10, 30 and 50 mmHg) markedly increased ACC neuronal responses of EA rats (10%, 28% and 47%, respectively). CRD produced greater pressure-dependent increases in ACC spike firing rates in EA rats compared with controls. Splanchnicectomy combined with pelvic nerve section abolished ACC responses to CRD in EA rats. Spontaneous activity in CRD-excited ACC neurones was significantly higher in EA rats than in controls. CRD-excited ACC neurones in control and EA rats (7 of 16 (42%) and 8 of 20 (40%), respectively) were activated by transcutaneous electrical and thermal stimuli. However, ACC neuronal activity evoked by noxious cutaneous stimuli did not change significantly in EA rats. This study identifies CRD-responsive neurones in the ACC and establishes for the first time that persistence of a heightened visceral afferent nociceptive input to the ACC induces ACC sensitization, characterized by increased spontaneous activity of CRD-excited neurones, decreased CRD pressure threshold, and increased response magnitude. Enhanced ACC nociceptive transmission in viscerally hypersensitive rats is restricted to visceral afferent input. PMID:16239277

  5. Schisandra chinensis reverses visceral hypersensitivity in a neonatal-maternal separated rat model.

    PubMed

    Yang, Jia-Ming; Xian, Yan-Fang; Ip, Paul S P; Wu, Justin C Y; Lao, Lixing; Fong, Harry H S; Sung, Joseph J Y; Berman, Brian; Yeung, John H K; Che, Chun-Tao

    2012-03-15

    Visceral hypersensitivity is an important characteristic feature of functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). This study evaluated the effect of Schisandra chinensis on visceral hyperalgesia induced by neonatal maternal separation (NMS) in an IBS rat model. The visceromotor responses to colorectal balloon distension (CRD) were measured by abdominal withdrawal reflex (AWR) and electromyographic (EMG) activities. NMS control rats (receiving vehicle) underwent aggravated visceral pain in response to CRD as compared to normal rats, evidenced by the reduced pain threshold, enhanced AWR scores and EMG responses. Treatment with a 70% ethanol extract of S. chinensis (0.3g/kg and 1.5g/kg/day) for 7 days resulted in an increase in the pain threshold (NMS control: 19.1±1.0mmHg vs low-dose: 24.8±1.3mmHg and high-dose: 25.2±1.8mmHg, p<0.01), and abolished the elevated AWR and EMG responses to CRD in NMS rats (AUC values of EMG response curve were: 1952±202 in NMS control group vs 1074±90 in low-dose group and 1145±92 in high-dose group, p<0.001), indicating that S. chinensis could reverse the visceral hypersensitivity induced by early-life stress event. The result of ELSA measurement shows that the elevated serotonin (5-HT) level in the distal colon of NMS rats returned to normal level after treatment with S. chinensis. Moreover, the increase in pain threshold in rats treated with S. chinensis was associated with a decline of the mRNA level of 5-HT(3) receptor in the distal colon. All available results demonstrate that S. chinensis can reverse visceral hypersensitivity induced by neonatal-maternal separation, and the effect may be mediated through colonic 5-HT pathway in the rat.

  6. Schisandra chinensis reverses visceral hypersensitivity in a neonatal-maternal separated rat model

    PubMed Central

    Yang, Jia-Ming; Xian, Yan-Fang; Ip, Paul SP; Wu, Justin CY; Lao, Lixing; Fong, Harry HS; Sung, Joseph JY; Berman, Brian; Yeung, John HK; Che, Chun-Tao

    2012-01-01

    Visceral hypersensitivity is an important characteristic feature of functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). This study evaluated the effect of Schisandra chinensis on visceral hyperalgesia induced by neonatal maternal separation (NMS) in an IBS rat model. The visceromotor responses to colorectal balloon distension (CRD) were measured by abdominal withdrawal reflex (AWR) and electromyographic activities (EMG). NMS control rats (receiving vehicle) underwent aggravated visceral pain in response to CRD as compared to normal rats, evidenced by the reduced pain threshold, enhanced AWR scores and EMG responses. Treatment with a 70% ethanol extract of S. chinensis (0.3 g/kg and 1.5 g/kg per day) for seven days resulted in an increase in the pain threshold (NMS control: 19.1 ± 1.0 mmHg vs low-dose: 24.8 ± 1.3 mmHg and high-dose: 25.2 ± 1.8 mmHg, p<0.01), and abolished the elevated AWR and EMG responses to CRD in NMS rats (AUC values of EMG response curve were: 1952 ± 202 in NMS control group vs 1074 ± 90 in low-dose group and 1145 ± 92 in high-dose group, p<0.001), indicating that S. chinensis could reverse the visceral hypersensitivity induced by early-life stress event. The result of ELSA measurement shows that the elevated serotonin (5-HT) level in the distal colon of NMS rats returned to normal level after treatment with S. chinensis. Moreover, the increase in pain threshold in rats treated with S. chinensis was associated with a decline of the mRNA level of 5-HT3 receptor in the distal colon. All available results demonstrate that S. chinensis can reverse visceral hypersensitivity induced by neonatal-maternal separation, and the effect may be mediated through colonic 5-HT pathway in the rat. PMID:22230486

  7. Distractibility and hypersensitivity. Two behavior factors in elementary school children.

    PubMed

    Victor, J B; Halverson, C F

    1975-01-01

    The present paper reports on the development of a modified problem checklist for use in normal samples of elementary school children. The two factors, Hypersensitivity and Distractibility, replicated over male and female samples. Hypersensitivity showed a significant grade effect, with a decrease between the first and second grade for both boys and girls. In contrast, boys scored higher than girls on Distractibility and there were no grade differences. Convergent validitiy data from peer judgments, in-class activity level, physical fitness measures, standardized achievement scores, and a comparison with another teacher judgment are presented. In addition, three Behavioral Problem Checklist (Quay & Peterson, 1967) dimensions, Conduct Problem, Personality Problem, and Inadequacy--Immaturity, were developed and their relationships to the independent measures, as well as to the new dimensions, are presented. The pattern of correlations of Distractibility was quite similar for boys and girls, with both being rated as Mean-Noisy by their peers. The findings for Hypersensitivity were somewhat weaker. Distractibility and Conduct Problem scores reflected a similar pattern of correlations with other variables; in a like manner, Hypersensitivity and Personality Problem scores reflected a similar pattern of correlations with other variables. Distractibility was related to an increased activity level and Hypersensitivity was related to a decreased activity level in young boys. The total number of behavior problems was related to a decrease in activity level for young girls. Older Distractible and Hypersensitive girls showed different patterns of activity level. It is proposed that problem behavior is more complex for older children and that Distractibility may be less influenced by the usual socialization process of school than is Hypersensitivity and may have some congenital antecedents.

  8. Isolation and Characterization of mAMSA-hypersensitive Mutants

    PubMed Central

    Rogojina, Anna T.; Nitiss, John L.

    2008-01-01

    Topoisomerase II (Top2) is the primary target for active anti-cancer agents. We developed an efficient approach for identifying hypersensitive Top2 mutants and isolated a panel of mutants in yeast Top2 conferring hypersensitivity to the intercalator N-[4-(9-acridinylamino)-3-methoxyphenyl]methanesulphonanilide (mAMSA). Some mutants conferred hypersensitivity to etoposide as well as mAMSA, whereas other mutants exhibited hypersensitivity only to mAMSA. Two mutants in Top2, changing Pro473 to Leu and Gly737 to Val, conferred extraordinary hypersensitivity to mAMSA and were chosen for further characterization. The mutant proteins were purified, and their biochemical activities were assessed. Both mutants encode enzymes that are hypersensitive to inhibition by mAMSA and other intercalating agents and exhibited elevated levels of mAMSA-induced Top2:DNA covalent complexes. While Gly737 → Val Top2p generated elevated levels of Top2-mediated double strand breaks in vitro, the Pro473 → Leu mutant protein showed only a modest increase in Top2-mediated double strand breaks but much higher levels of Top2-mediated single strand breaks. In addition, the Pro473 → Leu mutant protein also generated high levels of mAMSA-stabilized covalent complexes in the absence of ATP. We tested the role of single strand cleavage in cell killing with alleles of Top2 that could generate single strand breaks, but not double strand breaks. Expression in yeast of a Pro473 → Leu mutant that could only generate single strand breaks conferred hypersensitivity to mAMSA. These results indicate that generation of single strand breaks by Top2-targeting agents can be an important component of cell killing by Top2-targeting drugs. PMID:18723844

  9. Acid hypersensitivity in patients with eosinophilic oesophagitis.

    PubMed

    Krarup, Anne Lund; Villadsen, Gerda Elisabeth; Mejlgaard, Else; Olesen, Søren Schou; Drewes, Asbjørn Mohr; Funch-Jensen, Peter

    2010-03-01

    Painful symptoms are prevalent in patients with eosinophilic oesophagitis but experimental data are sparse. The aim of this study was to compare the pain response to experimental oesophageal stimulation in 14 patients with eosinophilic oesophagitis and 15 healthy volunteers. A multimodal probe was placed in the oesophagus. The participants were subjected to mechanical, thermal and electrical pain stimuli followed by perfusion with 0.1 M HCl. Pain scores, referred pain areas and evoked brain potentials to electrical stimulation of the oesophagus were recorded. Patients tolerated significantly less acid perfused in the oesophagus (median 123 versus 200 ml; P = 0.02) and felt the burning sensation evoked by the acid earlier (median 2.0 versus 5.0 min; P = 0.01). Eight patients had coexisting gastro-oesophageal reflux disease. Six patients had pure eosinophilic oesophagitis, and this group felt the acid earlier than those with concomitant reflux or the healthy volunteers (median 0.8 versus 2.0 and 5.0 min; P = 0.03). There were no differences between patients and controls in the responses to mechanical or thermal stimulation (P > 0.4). Furthermore, no differences were found for the proxies of central nervous system sensitization (response to electrical stimulations, referred pain areas or evoked brain potentials; P > 0.1). Patients with eosinophilic oesophagitis are hypersensitive to acid perfused in the oesophagus, and pathophysiologic findings are likely confined to the peripheral tissue. Reflux from physiological acid may play a role in the symptoms of eosinophilic oesophagitis.

  10. Hypersensitivity myocarditis associated with ephedra use.

    PubMed

    Zaacks, S M; Klein, L; Tan, C D; Rodriguez, E R; Leikin, J B

    1999-01-01

    Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has not yet been associated with either ephedrine or its plant derivative ephedra. A 39-year-old African American male with hypertension presented to Rush Presbyterian St. Luke's Medical Center with a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. He was taking Ma Huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed a male in mild respiratory distress. The lung fields had rales at both bases without audible wheezes. Internal jugular venous pulsations were 5 cm above the sternal notch. Medical therapy with intravenous furosemide and oral enalapril was initiated upon admission. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated with azothioprine 200 mg daily and prednisone 60 mg per day with a tapering course over 6 months. Anticoagulation with warfarin and diuretics was initiated and angiotensin-converting enzyme inhibition was continued. Hydralazine was added later. One month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal (EFN 50%) and the patient asymptomatic. Ephedra (Ma Huang) is the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis.

  11. [Pathogenesis and treatment of hypersensitivity pneumonitis].

    PubMed

    Ando, M

    2000-01-01

    Hypersensitivity pneumonitis (HP) is a granulomatous interstitial lung disease resulting from an immunologic reaction to the repeated inhalation of organic dusts and active chemicals. There are 50 or more groups of HP, but the prevalence varies from country to country, and even within a country, depending on a variety of occupational or environmental inhalants. In Western coutries farmer's lung, bird fancier's disease, humidifier lung, and air-conditioner disease are common, but in Japan summer-type HP is the most prevalent group. Summer-type HP is a house-related illnes induced by Trichosporon asahii and Trichosporon mucoides which contaminate the patients' home environments in hot and humid conditions. The polysaccharide antigen contains mannan backbone attached with short side chains consi-sting of mannose, xylose, and glucuronic acid residues. Both immune complex-mediated and T cell-mediated immune responses to the yeast are involved in the induction and development of the disease. Host factors such as HLA-DQw3 and cigarette smoking also play an important role in the develop-ment or suppression of the disease. An assay for serum anti-Trichosporon antibody by a Triko Kit is very useful for the serodiagnosis, and sanitization by cleaning, disinfecting, and removing from the colonizing location of Trichosporon prevents recurrence of the disease. Summer-type HP induced by Trichosporon is a new type of HP. It can be found in other countries including most Western countries, because Trichosporon asahii and Trichosporon mucoides distribute in the temperate and subtropical areas of the world.

  12. A rare cause of acute coronary syndrome: Kounis syndrome.

    PubMed

    Almeida, João; Ferreira, Sara; Malheiro, Joana; Fonseca, Paulo; Caeiro, Daniel; Dias, Adelaide; Ribeiro, José; Gama, Vasco

    2016-12-01

    Kounis syndrome is an acute coronary syndrome in the context of a hypersensitivity reaction. The main pathophysiological mechanism appears to be coronary vasospasm. We report the case of a patient with a history of allergy to quinolones, who was given ciprofloxacin before an elective surgical procedure and during drug administration developed symptoms and electrocardiographic changes suggestive of ST-segment elevation acute coronary syndrome. The drug was suspended and coronary angiography excluded epicardial coronary disease. Two hours after withdrawal of the drug the symptoms and ST elevation had resolved completely. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Poly(ADP-Ribose) Polymerase Inhibitor Hypersensitivity in Aggressive Myeloproliferative Neoplasms

    PubMed Central

    Pratz, Keith W.; Koh, Brian; Patel, Anand G.; Flatten, Karen S.; Poh, Weijie; Herman, James G.; Dilley, Robert; Harrell, Maria I.; Smith, B. Douglas; Karp, Judith E.; Swisher, Elizabeth M.; McDevitt, Michael A.; Kaufmann, Scott H.

    2016-01-01

    Purpose DNA repair defects have been previously reported in myeloproliferative neoplasms (MPNs). Inhibitors of poly(ADP-ribose) polymerase (PARP) have shown activity in solid tumors with defects in homologous recombination (HR). The present study was performed to assess MPN sensitivity to PARP inhibitors ex vivo. Experimental Design HR pathway integrity in circulating myeloid cells was evaluated by assessing formation of RAD51 foci after treatment with ionizing radiation or PARP inhibitors. Sensitivity of MPN erythroid and myeloid progenitors to PARP inhibitors was evaluated using colony formation assays. Results Six of 14 MPN primary samples had reduced formation of RAD51 foci after exposure to ionizing radiation, suggesting impaired HR. This phenotype was not associated with a specific MPN subtype, JAK2 mutation status or karyotype. MPN samples showed increased sensitivity to the PARP inhibitors veliparib and olaparib compared to normal myeloid progenitors. This hypersensitivity, which was most pronounced in samples deficient in DNA damage-induced RAD51 foci, was observed predominantly in samples from patients with diagnoses of chronic myelogenous leukemia, chronic myelomonocytic leukemia or unspecified myelodysplastic/MPN overlap syndromes. Conclusions Like other neoplasms with HR defects, MPNs exhibit PARP inhibitor hypersensitivity compared to normal marrow. These results suggest that further preclinical and possibly clinical study of PARP inhibitors in MPNs is warranted. PMID:26979391

  14. Hypersensitivity reactions to aprotinin re-exposure in paediatric surgery.

    PubMed

    Siehr, Stephanie; Stuth, Eckehard; Tweddell, James; Hoffman, George; Troshynski, Todd; Jones, Deborah; Mitchell, Michael; Ghanayem, Nancy

    2010-02-01

    Hypersensitivity to aprotinin is low (1-3%) but more likely with re-exposure. The manufacturer issued a black box warning which lists aprotinin re-exposure within 1 year of prior exposure as a contraindication. We investigated the temporal relationship between re-exposure interval and hypersensitivity in children. With Human Research Review Board approval, charts of all patients exposed to aprotinin during cardiac surgery were reviewed. We extracted data for re-exposure interval and hypersensitivity to skin tests, intravenous test dosing or infusion of the loading dose. We defined systemic hypersensitivity as haemodynamic instability, respiratory symptoms or diffuse skin reaction temporally related to exposure. From March 1994 to June 2007, there were a total of 2333 aprotinin exposures in 1824 patients. A total of 509 re-exposures occurred in 381 patients: 280 in 244 patients with early (within 1 year) re-exposure and 229 in 222 patients with late (after 1 year) re-exposure. Thirteen systemic hypersensitivity reactions occurred in the 509 re-exposures (2.6%): two during skin testing and 11 during the loading dose. Although the incidence of local hypersensitivity was increased with early re-exposure (6/280 or 2.1% vs 0/229, p=0.019), the incidence of the systemic reaction was not different between early and late re-exposures (6/280 or 2.1% (CI 0.8-4.6%) vs 7/229 or 3.1% (CI 1.2-6.2%), p=0.6). Six patients with a previous hypersensitivity reaction had an additional re-exposure to aprotinin; one of these patients had a systemic reaction during the third exposure. The incidence and type of hypersensitivity to aprotinin re-exposure in our cohort is consistent with previous reports. Repeat exposure within 1 year did not increase the risk of systemic hypersensitivity. Copyright 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

  15. Effect of premedications in a murine model of asparaginase hypersensitivity.

    PubMed

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

    2015-03-01

    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.

  16. An animal model of hypersensitivity pneumonitis in the rabbit.

    PubMed Central

    Moore, V L; Hensley, G T; Fink, J N

    1975-01-01

    This study was devised to produce an animal model of hypersensitivity pneumonitis in order to study both the induction and the elicitation of the disease. Rabbits exposed by aerosol to large quantities of pigeon antigens developed a humoral, but not cellular, immunologic response. Moreover, their lungs were essentially normal histologically. A single i.v. injection of killed BCG in oil permitted the induction of pulmonary cell-medid hypersensitivity to the inhaled antigen, as well as the development of pulmonary lesions which were more severe than that caused by the administration of BCG alone. The humoral immunologic response to the inhaled antigen was not increased after BCG injection. Since many individuals are exposed to the etiologic agents of hypersensitivity pneumonitis for extended periods without developing the disease, these findings in animals suggest that some event may occur to induce cell mediated hypersensitivity in order to initiate the disease process. In addition, we have shown that animals with normal lung histology and circulating complement-fixing antibodies undergo serum complement (CH50) depression after an aerosol challenge with the specific antigen. Animals with circulating, complement-fixing antibodies, and inflamed lungs (BCG-induced failed to undergo a complement depression subsequent to an aerosol challenge with specific antigens. These results re consistent with those seen in symptomatic and asymptomatic pigeon breeders and suggest that antigen distribution through the lung is important in the pathogenesis of hypersensitivity pneumonitis. Images PMID:1099122

  17. Hypersensitivity to thrombin of platelets from hypercholesterolemic rats

    SciTech Connect

    Winocour, P.D.; Rand, M.L.; Kinlough-Rathbone, R.L.; Mustard, J.F.

    1986-03-01

    Hypersensitivity of platelets to thrombin has been associated with hypercholesterolemia. The authors have examined the mechanisms involved in this hypersensitivity. Rats were given diets rich in milk fat and containing added cholesterol and taurocholate to produce hypercholesterolemia (HC) (262 +/- 25 mg%) or added sitosterol as a normocholesterolemic control (NC) (89 +/- 6 mg%). Washed platelets were prelabelled with /sup 14/C-serotonin. In the presence of acetylsalicyclic acid (ASA) (to inhibit thromboxane A/sub 2/ (TXA/sub 2/) formation) and creatine phosphate/creatine phosphokinase (CP/CPK) (to remove released ADP), HC platelets aggregated more (26 +/- 1%) and released more /sup 14/C (9.1 +/- 2.0%) than NC platelets (aggregation: 0%, p < 0.001; /sup 14/C release: 1.5 +/- 0.5%, p < 0.002) in response to thrombin (0.075 U/ml). Thus, a pathway independent of released ADP or TXA/sub 2/ formation is involved in the hypersensitivity of HC platelets to thrombin. Total binding of /sup 125/I-thrombin to HC platelets was less than that to NC platelets but HC platelets were smaller and had less protein than NC platelets; the thrombin binding per mg platelet protein was the same for HC and NC platelets, indicating that hypersensitivity to thrombin of HC platelets does not result from increased thrombin binding. Thus, hypersensitivity of HC platelets to thrombin is not due to TXA/sub 2/ formation, the action of released ADP or increased thrombin binding.

  18. Angiotensin II receptor type 2 activation is required for cutaneous sensory hyperinnervation and hypersensitivity in a rat hind paw model of inflammatory pain

    PubMed Central

    Chakrabarty, Anuradha; Liao, Zhaohui; Smith, Peter G.

    2014-01-01

    Many pain syndromes are associated with abnormal proliferation of peripheral sensory fibers. We showed previously that angiotensin II, acting through its type 2 receptor (AT2), stimulates axon outgrowth by cultured dorsal root ganglion neurons. In this study, we assessed whether AT2 mediates nociceptor hyperinnervation in the rodent hind paw model of inflammatory pain. Plantar injection of complete Freund’s adjuvant (CFA), but not saline, produced marked thermal and mechanical hypersensitivity through 7 days. This was accompanied by proliferation of dermal and epidermal PGP9.5- and calcitonin gene-related peptide-immunoreactive (CGRP-ir) axons, and dermal axons immunoreactive for GFRα2 but not tyrosine hydroxylase or neurofilament H. Continuous infusion of the AT2 antagonist PD123319 beginning with CFA injection completely prevented hyperinnervation as well as hypersensitivity over a 7 day period. A single PD123319 injection 7 days after CFA also reversed thermal hypersensitivity and partially reversed mechanical hypersensitivity 3 hours later, without affecting cutaneous innervation. Angiotensin II synthesizing proteins renin and angiotensinogen were largely absent after saline but abundant in T-cells and macrophages in CFA-injected paws with or without PD123319. Thus, emigrant cells at the site of inflammation apparently establish a renin-angiotensin system, and AT2 activation elicits nociceptor sprouting and heightened thermal and mechanical sensitivity. Perspective Short-term AT2 activation is a potent contributor to thermal hypersensitivity, while long-term effects (such as hyperinnervation) also contribute to mechanical hypersensitivity. Pharmacological blockade of AT2 signaling represents a potential therapeutic strategy aimed at biological mechanisms underlying chronic inflammatory pain. PMID:23726047

  19. Hypersensitivity and reduced inhibition of DNA synthesis in ataxia telangiectasia lymphoblasts treated with low levels of neocarzinostatin.

    PubMed

    Babilon, R W; Soprano, K J; Henderson, E E

    1985-07-01

    The effects of neocarzinostatin (NCS) on lymphoblastoid cell lines (LCLs) established from ataxia telangiectasia (A-T) were determined. A-T lymphoblasts were found to be hypersensitive to low levels of NCS as measured by cell growth and cell survival. On the other hand, A-T lymphoblasts failed to postpone DNA synthesis to the same degree as normal lymphoblasts following treatment with NCS. LCLs established from Nijmegen breakage syndrome (NBS) could be distinguished from ataxia and normal cell lines by their intermediate level of survival following exposure to NCS.

  20. Chromosome instability and X-ray hypersensitivity in a microcephalic and growth-retarded child

    SciTech Connect

    Barbi, G.; Scheres, J.M.; Schindler, D.; Taalman, R.D.; Rodens, K.; Mehnert, K.; Mueller, M.S.; Seyschab, H. )

    1991-07-01

    The authors report on a microcephalic, growth-retarded newborn girl without major anomalies who has chromosome instability in lymphocytes and fibroblasts. Frequent involvement of bands 7p13, 7q34, 14q11, and 14q32 suggested the diagnosis of ataxia telangiectasia (AT) or a related disorder. Supportive evidence was radioresistant DNA synthesis in fibroblasts and radiation hypersensitivity of short-term lymphocyte cultures. Follow-up for nearly 4 years showed largely normal development, and no signs of telangiectasia, ataxia, or immunodeficiency. Serum AFP levels turned from elevated at age 5 months to normal at age 2 years. They propose that their patient belongs to the expanding category of AT-related genetic disorders, probably to the Nijmegen breakage syndrome.

  1. 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

  2. Colloidal silica-induced hypersensitivity: myth or reality.

    PubMed

    Ben Fredj, Nadia; Ben Fadhel, Najeh; Chaabane, Amel; Chadly, Zohra; Ben Romdhane, Haifa; Boughattas, Abderrazzek; Aouam, Karim

    2016-02-01

    Many excipients have been reported to induce drug hypersensitivity (e.g. colouring additives, preservatives). Colloidal silica has never been reported to induce drug hypersensitivity reactions. We report herein a 40-year-old patient who developed a skin eruption 2 days after Voltarene(®) (diclofenac) intake, confirmed by a positive patch test. Investigation of cross reactivity, assessed by patch testing to other non steroidal anti-inflammatory drugs, have showed a positive reaction only to piroxicam (Piroxen(®)), ketoprofen (Oki(®)) and indometacin (Indocid(®)). A hypersensivity to colloidal silica, a common excipient, was suspected. A patch test to this compound was performed showing a positive reaction. Colloidal silica, a compound widely used in drug manufacturing, could be another culprit excipient in inducing skin hypersensitivity reactions.

  3. Culicoides species attracted to horses with and without insect hypersensitivity.

    PubMed

    van der Rijt, Renske; van den Boom, Robin; Jongema, Yde; van Oldruitenborgh-Oosterbaan, Marianne M Sloet

    2008-10-01

    The aims of this study were to determine (1) which species of Culicoides is most commonly attracted to horses, (2) whether horses suffering insect hypersensitivity attract more Culicoides spp. than unaffected horses, and (3) the times when Culicoides spp. are most active. Horses affected by insect hypersensitivity and unaffected horses were placed inside mosquito netting tents for 30 min at different times of the day. All Culicoides spp. trapped inside the tents were collected and identified. C. obsoletus was the most common species found, followed by C. pulicaris. Healthy horses attracted slightly more midges than horses that were affected with insect hypersensitivity. All of the Culicoides species were most active at sunset, less so at sunrise and very few or no midges were trapped in the afternoon or at night.

  4. Clozapine-induced hypersensitivity myocarditis presenting as sudden cardiac death

    PubMed Central

    Balla, Sudarshan; Aggarwal, Kul

    2016-01-01

    Hypersensitivity myocarditis is a rare but serious adverse effect of clozapine, a commonly used psychiatric drug. We report the case of sudden cardiac death from clozapine-induced hypersensitivity myocarditis diagnosed at autopsy. A 54-year-old Caucasian male on clozapine therapy for bipolar disorder presented with a sudden onset of shortness of breath. Laboratory studies were significant for elevated N-terminal prohormone of brain natriuretic peptide. During his hospital stay, the patient died of sudden cardiac arrest from ventricular tachycardia. The autopsy revealed hypersensitivity myocarditis, which usually occurs in the first 4 weeks after the initiation of clozapine. A 4-week monitoring protocol, including laboratory assessment of troponin and C-reactive protein, may assist in the early diagnosis of this potentially fatal condition. PMID:28210568

  5. Type IV hypersensitivity to a textured silicone breast implant.

    PubMed

    Dargan, D; McGoldrick, C; Khan, K

    2012-07-01

    We present a case of hypersensitivity to a breast implant in a 57-year old female with breast cancer and hypersensitivity to adhesive dressings. A mastectomy, axillary node clearance, latissimus dorsi flap and silicone implant-based reconstruction were performed. The mammary wound dehisced within three weeks and the implant required removal. No pus was present, and cultures were negative. Three years later, a further silicone implant was inserted. Within three weeks from insertion, the patient required readmission with serous discharge from the wound, flu-like symptoms, low-grade pyrexia and painful swelling at the operative site. The implant was removed. Capsule biopsies demonstrated a large lymphoid cell reaction, in keeping with a delayed hypersensitivity reaction. Patch testing to samples of the implant was positive. Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  6. Dentin Hypersensitivity: Etiology, Diagnosis and Treatment; A Literature Review

    PubMed Central

    Davari, AR; Ataei, E; Assarzadeh, H

    2013-01-01

    The objective of this review is to inform practitioners about dentin hypersensitivity (DH); to provide a brief overview of the diagnosis, etiology and clinical management of dentin hypersensitivity and to discuss technical approaches to relieve sensitivity. This clinical information is described in the context of the underlying biology. The author used PUBMED to find relevant English-language literature published in the period 1999 to 2010. The author used combinations of the search terms “dentin*”, “tooth”, “teeth”, “hypersensit*”, “desensitiz*”. Abstracts and also full text articles to identify studies describing etiology, prevalence, clinical features, controlled clinical trials of treatments and relevant laboratory research on mechanisms of action were used. PMID:24724135

  7. [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.

  8. Contact hypersensitivity response to isophorone diisocyanate in mice

    SciTech Connect

    Stern, M.L.; Brown, T.A.; Brown, R.D.; Munson, A.E. )

    1989-09-01

    Isophorone diisocyanate was evaluated for its potential as a sensitizing agent for allergic contact hypersensitivity in mice. Female B6C3F1 mice were sensitized with 0.1, 0.3, and 1.0% isophorone diisocyanate and challenged with 3.0% isophorone diisocyanate. Doses of isophorone diisocyanate were selected from assays for primary irritancy. Mice received 20 microliters by direct dermal application, for 5 days, to sites prepared by shaving, dermabrading and, in some mice, with intra dermal injection of complete Freund's adjuvant. The rest period was 7 days. Measurement of the contact hypersensitivity response in mice was by radioisotopic assay two days after challenge and mouse ear swelling one and two days after challenge. Mice demonstrated statistically significant dose-dependent contact hypersensitivity responses to iso