[Hemolysis, serositis and exanthema induced by Mycoplasma pneumoniae infection. Report of one case].

PubMed

Mondaca P, Roberto; Pizarro C, Victoria; Cares, Víctor; Eymin, Gonzalo

2014-10-01

Mycoplasma infections have extrapulmonary manifestations that may be associated with respiratory symptoms and may have skin, heart, gastrointestinal, rheumatologic, neurologic, hematologic involvement. Cold agglutinin mediated autoimmune hemolytic anemia is the most common hematological manifestation. We report a 27-year-old woman infected with Mycoplasma pneumoniae, who presented respiratory involvement with pneumonia, exanthema, serositis and acute hemolytic anemia that required transfusion. The key for the diagnosis were the extrapulmonary manifestations associated with respiratory involvement after five days of hospitalization.

Macular exanthema in a child with rotavirus gastroenteritis: a case report.

PubMed

Zulfikar Akelma, Ahmet; Nevzat Cizmeci, Mehmet; Mete, Emin; Dilara Malli, Dilsad; Erpolat, Seval; Mujgan Sonmez, Fatma

2014-04-01

Apart from gastroenteritis, rotavirus has been rarely implicated with some cutaneous disorders such as generalized maculo-papular exanthema, infantile acute hemorrhagic edema and Gianotti-Crosti syndrome. We report a 30-month old toddler boy who developed erythematous macular skin eruptions during the course of rotavirus gastroenteritis. To our knowledge, this is the first case in the literature reporting rotavirus-related macular erythematous lesions in a pediatric patient. We therefore would like to share our experience, to keep ro-tavirus infection in the differential diagnosis of children with gastroenteritis and erythematous eruption.

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

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced by oral metronidazole.

PubMed

Şikar Aktürk, Aysun; Bayramgürler, Dilek; Salman, Selma; Yıldız, Kürşat Demir; Odyakmaz Demirsoy, Evren

2014-12-01

Baboon syndrome is a special form of systemic contact dermatitis to systemic or local administration of contact allergens. Baboon syndrome without known previous cutaneous sensitisation was also described as drug-related baboon syndrome or symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). The major drugs causing SDRIFE was beta-lactam antibiotic such as amoxicillin and ampicillin. We report a case of 16-year-old woman who developed pruritic eruptions after oral metronidazole treatment for diarrhea. She was diagnosed SDRIFE according to her clinical and histopathological findings. To our knowledge, our patient is the first case who developed SDRIFE due to metronidazole in the literature.

Aminopenicillin-induced exanthema allows treatment with certain cephalosporins or phenoxymethyl penicillin.

PubMed

Trcka, Jiri; Seitz, Cornelia S; Bröcker, Eva-B; Gross, Gerd E; Trautmann, Axel

2007-07-01

Aminopenicillin-induced exanthema poses a problem in the management of infectious diseases. Due to theoretically possible immunological cross-reactivity, all beta-lactam drugs, i.e. penicillins, penicillin derivatives and cephalosporins, are usually avoided. The available alternative antibiotics (macrolides, quinolones and glycopeptides) may be less effective, have more side effects, and their use increases medical costs. Moreover, their use contributes to the increasing bacterial resistance to antibiotics. The aim of the study is to demonstrate that patients with aminopenicillin-induced exanthema may receive specific beta-lactams for future antibiotic therapy. Skin testing followed by oral challenges to identify beta-lactams that are tolerated by patients despite confirmed delayed-type non-immunoglobulin E (IgE)-mediated allergic hypersensitivity to aminopenicillins. Sixty-nine out of 71 patients (97.2%) with non-IgE-mediated allergic hypersensitivity to aminopenicillins tolerate cephalosporins without an aminobenzyl side chain such as cefpodoxime or cefixime and 51 patients (71.8%) also tolerate phenoxymethyl penicillin. The majority of patients with non-IgE-mediated allergic hypersensitivity to aminopenicillins do not cross-react to certain cephalosporins or phenoxymethyl penicillin. Skin and drug challenge tests can be helpful to determine individual cross-reactivity.

Immediate and delayed reactions to radiocontrast media: is there an allergic mechanism?

PubMed

Brockow, Knut

2009-08-01

Radiocontrast media can cause immediate (1 hour) and nonimmediate (>1 hour) hypersensitivity reactions that remain unpredictable and a cause of concern for radiologists and cardiologists. Immediate hypersensitivity reactions resemble anaphylaxis, whereas nonimmediate ones clinically are predominated by exanthemas. Increasing evidence indicates that immediate reactions and nonimmediate skin exanthemas may be allergic reactions involving either contrast media-reactive IgE or T cells, respectively. Skin testing is a useful tool for the diagnosis of contrast media allergy. It may have an important role in the selection of a safe product in previous reactors, although validation data are still lacking. In vitro tests to search for contrast media-specific cell activation are currently under investigation.

Human herpesvirus-6 infection-associated acute encephalopathy without skin rash.

PubMed

Yamamoto, Shiho; Takahashi, Satoru; Tanaka, Ryosuke; Okayama, Akie; Araki, Akiko; Katano, Harutaka; Tanaka-Taya, Keiko; Azuma, Hiroshi

2015-09-01

Human herpesvirus-6 (HHV-6) is the etiological agent of exanthema subitum-associated encephalopathy, which usually occurs in children younger than 3 years. Brain imaging shows various abnormalities. A previously healthy 4-year-old girl developed acute encephalopathy with clinical features consisting of fever, repetitive seizures, and a disturbance of consciousness. The patient did not show skin rash suggestive of exanthema subitum during the course of her illness. The primary HHV-6 infection was diagnosed based on the absence of IgG against HHV-6 and identification of the virus DNA in the acute phase serum and a significant increase of the anti-HHV-6 IgG titers in the convalescent phase sera. Diffusion-weighted images showed transient high signal intensity in the bilateral periventricular white matter and splenium of the corpus callosum and in the gray matter structures such as the bilateral basal ganglia and thalami. Upon therapy with steroid and γ-globulin, the patient recovered without any neurological deficits. Primary HHV-6 infection can cause acute encephalopathy without exanthema subitum. The etiological diagnosis is possible only by examining the blood and cerebrospinal fluid, when the patient shows no skin rash. This condition should be included in the differential diagnosis of acute encephalopathy even in patients older than 3 years. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Occurrence of equine coital exanthema (ECE) in stallions in Japan and effectiveness of treatment with valacyclovir for ECE

PubMed Central

TOISHI, Yuko; TSUNODA, Nobuo; KIRISAWA, Rikio

2017-01-01

Equine coital exanthema (ECE) has been reported in many countries, but equine herpesvirus 3 (EHV-3) has been isolated only once in Japan. In 2015, symptoms of ECE were found, and EHV-3 was isolated in two stallions. Valacyclovir, an anti-herpesvirus agent, was administered orally. The stallions rested from mating for more than two weeks, causing enormous financial losses because of their high fees. This is the first study in which valacyclovir was administered for ECE. Though valacyclovir treatment did not shorten the duration of healing, the affected area did not expand after administration of valacyclovir. Valacyclovir therefore seems to be effective for suppression of EHV-3 infection. Further investigation about the administration protocol might be required. PMID:28123140

7 CFR 51.1015 - Serious damage.

Code of Federal Regulations, 2013 CFR

2013-01-01

... diameter; (c) Exanthema (ammoniation) which occurs as small spots over more than 25 percent of the fruit... circle one-half inch in diameter; (g) Sunburn which causes decided flattening of the fruit, marked drying...

7 CFR 51.1015 - Serious damage.

Code of Federal Regulations, 2014 CFR

2014-01-01

... diameter; (c) Exanthema (ammoniation) which occurs as small spots over more than 25 percent of the fruit... circle one-half inch in diameter; (g) Sunburn which causes decided flattening of the fruit, marked drying...

Hypersensitivity reactions to etoposide.

PubMed

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

1996-04-01

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

Systemic drug-related intertriginous and flexural exanthema (SDRIFE).

PubMed

Elmariah, Sarina B; Cheung, Wang; Wang, Nadia; Kamino, Hideko; Pomeranz, Miriam K

2009-08-15

A 72-year-old man with a history of metastatic melanoma presented with a two-day history of erythematous and edematous plaques, with scattered bullae on the neck, chest, axillae, and inguinal and gluteal folds, which began five days after infusion of an experimental drug. The clinical and histopathologic findings were consistent with systemic drug-related intertriginous and flexural exanthema (SDRIFE), which is an uncommon drug reaction that results in symmetric erythema that affects the buttocks, groin, and/or thighs as well other flexural folds. The clinical manifestations of SDRIFE are highly characteristic and include distinctive primary cutaneous lesions with a specific distribution and course; however, heterogeneity exists with respect to histopathologic features, skin test results, and in vitro investigations. The exact mechanism of SDRIFE remains unknown but is thought to result from a type IV delayed hypersensitivity immune response. Treatment is symptomatic and includes topical or oral glucocorticoids.

Diffuse exanthema in a patient receiving varenicline.

PubMed

Song, Wei; Miller, William A

2008-07-01

A diffuse exanthema in a patient receiving varenicline is reported. A 71-year-old white woman, who was initially admitted to the hospital for elective vascular bypass surgery, had a three-day history of a diffuse rash, severe itching, and moderate headache. Her symptoms started two days before her admission. She denied having a fever, chills, nausea, vomiting, diarrhea, and flulike symptoms. She also denied having had contact with anyone who was ill, tick or insect bites, exposure to cats, or any changes in her diet, habits, or personal hygiene. Her medical problems included peripheral vascular disease, chronic obstructive pulmonary disease (COPD), dyslipidemia, hypertension, and hypothyroidism. In addition to several medications she had been taking for over 2 years, she had been taking varenicline as an aid for smoking cessation for eight days. The patient had been smoking for 40 years. The bright-red rash covered 70% of her torso and four extremities. She had mild swelling in her cheeks, but not on the eyelids or lips. Both of her lungs were clear on auscultation, with distant breath sounds caused by her COPD. Varenicline was discontinued, and her symptoms had completely resolved by the eighth day following discontinuation of the medication. While it is possible that other medications caused her symptoms, she had been taking most of them for over 2 years and all of them for over 1 year. Also, continuation of these drugs did not prevent her symptoms from resolving, nor did it cause a recurrence of the skin reaction. A patient developed diffuse exanthema after being treated with varenicline.

[Observations on human parvovirus B19 infection diagnosed in 2011].

PubMed

Mihály, Ilona; Trethon, András; Arányi, Zsuzsanna; Lukács, Adrienne; Kolozsi, Tímea; Prinz, Gyula; Marosi, Anikó; Lovas, Nóra; Dobner, Ilona Sarolta; Prinz, Géza; Szalai, Zsuzsanna; Pék, Tamás

2012-12-09

The incidence of human parvovirus B19 infection is unknown. A retrospective analysis of clinical and laboratory findings was carried out in patients diagnosed with human parvovirus B19 infection in 2011 in a virologic laboratory of a single centre in Hungary. Clinical and laboratory data of patients with proven human parvovirus B19 infection were analysed using in- and out-patient files. In 2011, 72 patients proved to have human parvovirus B19 infection with the use of enzyme immunoassay. The clinical diagnoses of these patients were as follows: human parvovirus B19 infection (30.6%), transient aplastic crisis (16.7%), arthritis (8.3%) and acute hepatitis (4.1%). Symptoms of each of the four phases of the infection occurred in various combinations with the exception of the monophase of cheek exanthema. This occurred without the presence of other symptoms in some cases. Leading symptoms and signs were exanthema (in 74.6% of cases), haematological disorders (in 69% of cases), fever (in 54.9% of cases) and arthritis (in 33.8% of cases). Several atypical dermatological symptoms were also observed. Acute arthritis without exanthema was noted in 8 patients. Of the 72 patients with proven human parvovirus B19 infection there were 7 pregnant women, and one of them had hydrops foetalis resulting spontaneous abortion. In 16 patients (22.5%) human parvovirus B19 IgG was undetectable despite an optimal time for testing. The observations of this study may contribute to a better recognition of clinical symptoms of human parvovirus B19 infection.

Zoledronic acid-associated symmetrical drug-related intertriginous and flexural exanthema (SDRIFE): report of baboon syndrome in a woman with recurrent metastatic breast cancer after receiving zoledronic acid.

PubMed

Cohen, Philip R

2015-08-15

Baboon syndrome is a distinctive skin reaction in which the patient typically develops erythematous buttocks that appear similar to those of a baboon. The non-contact allergenic variant of baboon syndrome is also referred to as symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). Zoledronic acid is a bisphosphonate that is used in patients with metastatic cancer to prevent bone complications. Zoledronic acid-associated baboon syndrome is described in a woman with recurrent metastatic breast cancer. PubMed was used to search the following terms, separately and in combination: baboon syndrome, breast cancer, symmetrical drug-related intertriginous and flexural exanthema, and zoledronic acid. All papers were reviewed and relevant manuscripts, along with their reference citations, were evaluated. Zoledronic acid has infrequently been associated with mucocutaneous adverse reactions. However, baboon syndrome has not previously been observed in patients receiving zoledronic acid. The reported woman developed baboon syndrome after her initial exposure to zoledronic acid. Non-contact allergenic drug-induced baboon syndrome has most commonly been associated with antibiotics such as beta-lactams and penicillins. Zoledronic acid-associated baboon syndrome has not previously been observed in cancer patients. Baboon syndrome (SDRIFE variant) was observed in a woman with recurrent metastatic breast cancer after her first exposure to zoledronic acid. In summary, SDRIFE can occur in oncology patients receiving zoledronic acid and zoledronic acid should be added to the list of medications associated with the potential to cause non-contact allergenic drug-induced baboon syndrome.

9 CFR 309.2 - Livestock suspected of being diseased or affected with certain conditions; identifying suspects...

Code of Federal Regulations, 2011 CFR

2011-01-01

... appropriate. (j) Any livestock which is affected with vesicular exanthema or vesicular stomatitis, but which... normal range, and the livestock shows a return to normal appetite and activity, shall be identified as U...

9 CFR 309.2 - Livestock suspected of being diseased or affected with certain conditions; identifying suspects...

Code of Federal Regulations, 2010 CFR

2010-01-01

... appropriate. (j) Any livestock which is affected with vesicular exanthema or vesicular stomatitis, but which... normal range, and the livestock shows a return to normal appetite and activity, shall be identified as U...

7 CFR 51.1002 - U.S. No. 2.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., broken skins which are not healed, bruises (except those incident to proper handling and packing), and hard or dry skins, and free from serious damage caused by freezing, dryness or mushy condition, sprayburn, exanthema (ammoniation), scars, thorn scratches, scale, sunburn, scab, blanching, yellow color...

7 CFR 51.1002 - U.S. No. 2.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., broken skins which are not healed, bruises (except those incident to proper handling and packing), and hard or dry skins, and free from serious damage caused by freezing, dryness or mushy condition, sprayburn, exanthema (ammoniation), scars, thorn scratches, scale, sunburn, scab, blanching, yellow color...

From past sailors’ eras to the present day: scurvy as a surprising manifestation of an uncommon gastrointestinal disease

PubMed Central

Branquinho, Diogo Ferreira; Pinto-Gouveia, Miguel; Mendes, Sofia; Sofia, Carlos

2015-01-01

A 45-year-old man presented with follicular exanthema in his lower limbs, alternating bowel habits and significant weight loss. His medical history included seronegative arthritis, bipolar disease and an inconclusive diagnostic laparoscopy. Diagnostic work up revealed microcytic anaemia and multivitamin deficiency. Skin biopsy of the exanthema suggested scurvy. Owing to these signs of malabsorption, upper endoscopy with duodenal biopsies was performed, exhibiting villous atrophy and extensive periodic acid-Schiff-positive material in the lamina propria, therefore diagnosing Whipple's disease (WD). After starting treatment with ceftriaxone and co-trimoxazole, an impressive recovery was noted, as the wide spectrum of malabsorption signs quickly disappeared. After a year of antibiotics, articular and cutaneous manifestations improved, allowing the patient to stop taking corticosteroids and antidepressants. This truly unusual presentation reflects the multisystemic nature of WD, often leading to misdiagnosis of other entities. Scurvy is a rare finding in developed countries, but its presence should raise suspicion for small bowel disease. PMID:26376699

Reemerging threat of epidemic typhus in Algeria.

PubMed

Mokrani, K; Fournier, P E; Dalichaouche, M; Tebbal, S; Aouati, A; Raoult, D

2004-08-01

We report a case of epidemic typhus in a patient from the Batna region of Algeria, who presented with generalized febrile exanthema. The clinical diagnosis was confirmed by serological cross-adsorption followed by Western blotting. Our report emphasizes the threat of epidemic typhus in the highlands of Algeria.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced by telmisartan-hydrochlorothiazide.

PubMed

Ferreira, Olga; Mota, Alberto; Morais, Paulo; Cunha, Ana Paula; Azevedo, Filomena

2010-12-01

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a drug-related eruption that characteristically involves the intertriginous or flexural folds and gluteal areas. We report the case of a 48-year-old woman with the presence of a sharply demarcated erythema of the inferior cervical folds, axillae, and gluteal area that started 4 days after the introduction of telmisartan-hydrochlorothiazide administration to treat hypertension. Skin biopsy revealed a dense perivascular and periadnexal lymphohistiocytic infiltrate in the superficial dermis, with some eosinophils and mast cells. A cutaneous drug adverse reaction was suspected, administration of telmisartan-hydrochlorothiazide was suspended, and medium-potency topical corticosteroids were prescribed, with subsequent significant improvement of the lesions. Eight months later, epicutaneous patch tests were performed in previously lesional and nonlesional skin. To the best of our knowledge, this is the first case of SDRIFE related to telmisartan-hydrochlorothiazide and illustrates an uncommon presentation of a skin-related drug reaction to an antihypertensive medication and the role of the dermatologist in diagnosis and management, in particular in follow-up of the patient.

Symmetrical drug-related intertriginous and flexural exanthema.

PubMed

Tan, Sze-Chin; Tan, Justina W-L

2011-08-01

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), previously termed drug-related baboon syndrome, is a benign and self-limiting type IV hypersensitivity reaction characterized by symmetrical erythema involving the gluteal and intertriginous areas in the absence of systemic involvement. It may also occur in the absence of previous drug exposure. Antibiotics, in particular beta-lactams, comprise the majority of causes of SDRIFE. Other drugs which have been implicated include antihypertensives, radiocontrast media, chemotherapeutic agents, and biologics. Histology of lesional skin is variable with predominance of superficial perivascular inflammatory cell infiltrates. Outcomes of allergy tests are variable with positive delayed intradermal tests reported for penicillin V, allopurinol; positive patch tests for erythromycin, mitomycin, nystatin, pseudoephdrine; positive lymphocyte transformation tests for erythromycin; and positive drug provocation tests for clindamycin, cimetidine, corticosteroids, terbinafine, and valacyclovir. Diagnosis of SDRIFE is dependent upon recognition of the clinical morphology and distribution of the rash, and its temporal relationship to the use of the suspected drug. Outcomes of in-vivo and in-vitro tests have been inconsistent, and thus may not be useful in the identification of the putative drug.

Vesicular exanthema of swine.

PubMed

Smith, A W; Akers, T G

1976-10-01

Vesicular exanthema of swine (VES) was first recognized in 1932. At the time, eradication measures and, later, quarantine procedures were instituted and extension of the disease to surrounding farms appeared to have been prevented. Between 1932 and 1936, however, seemingly unrelated epizootics continued among swine herds being fed raw garbage. In 1936, VES disappeared only to reappear in 1939. The disease was contained within California until 1952, at which time it spread to all the major swine producing areas of the United States. The disease was eradicated in 1959, through the enforcement of laws prohibiting the feeding of raw garbage to swine. Other than the association with raw garbage, a reservoir for VES virus (VESV) was never found. In 1972, a virus isolated from California sea lions--and thus named the San Miguel sea lion virus (SMSV)--proved to be distinguishable from VESV. When SMSV was injected into swine, clinical signs of vesicular exanthema developed, leading to the conclusion that, for all practical purposes, SMSV and VESV were the same. To date, 5 species of marine mammals and 2 species of terrestrial mammals, including feral swine, have been shown to possess antibodies to 1 or more of the 4 distinct SMSV serotypes. Current evidence suggests that SMSV infections occur among both terrestrial and marine mammals inhabiting the California coastal zones. This and the practice of shipping frozen meats known to contain SMSV to mink ranches in Utah point to the possibility that domestic swine in the United States are occasionally being exposed to SMSV. Although marine mammals are a source of SMSV, the primary virus reservoir is thought to be 1 or more submammalian marine species common to the southern California coastline. Such a primary reservoir presumably is the source of a new SMSV serotypes infecting marine mammals and may have been the original source of the VESV serotypes that infected swine through the intermediary of raw garbage.

Impact of the HLA-B(*)58:01 Allele and Renal Impairment on Allopurinol-Induced Cutaneous Adverse Reactions.

PubMed

Ng, Chau Yee; Yeh, Yu-Ting; Wang, Chuang-Wei; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Ya-Ching; Chang, Wan-Chun; Lin, Yu-Jr; Chang, Chee-Jen; Su, Shih-Chi; Fan, Wen-Lang; Chen, Der-Yuan; Wu, Yeong-Jian Jan; Tian, Ya-Chung; Hui, Rosaline Chung-Yee; Chung, Wen-Hung

2016-07-01

Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 × 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate < 30ml/minute/1.73 m(2)) should be cautious and avoid using allopurinol. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Predicting the characteristics of the aetiological agent for Kawasaki disease from other paediatric infectious diseases in Japan.

PubMed

Nagao, Y; Urabe, C; Nakamura, H; Hatano, N

2016-02-01

Although Kawasaki disease (KD), which was first reported in the 1960s, is assumed to be infectious, its aetiological agent(s) remains unknown. We compared the geographical distribution of the force of infection and the super-annual periodicity of KD and seven other paediatric infectious diseases in Japan. The geographical distribution of the force of infection, which was estimated as the inverse of the mean patient age, was similar in KD and other paediatric viral infections. This similarity was due to the fact that the force of infection was determined largely by the total fertility rate. This finding suggests that KD shares a transmission route, i.e. sibling-to-sibling infection, with other paediatric infections. The super-annual periodicity, which is positively associated with the sum of an infectious disease's incubation period and infectious period, was much longer for KD and exanthema subitum than other paediatric infectious diseases. The virus for exanthema subitum is known to persist across the host's lifespan, which suggests that the aetiological agent for KD may also be capable of persistent infection. Taken together, these findings suggest that the aetiological agent for KD is transmitted through close contact and persists asymptomatically in most hosts.

First case of symmetric drug-related intertriginous and flexural exanthema (sdrife) due to rivastigmine?

PubMed

Allain-Veyrac, Gwenaëlle; Lebreton, Anne; Collonnier, Catherine; Jolliet, Pascale

2011-06-01

The term 'baboon syndrome' was introduced in 1984 to describe a special form of systemic, contact-type dermatitis that occurs after ingestion or systemic absorption of a contact allergen in individuals previously sensitized by topical exposure to the same allergen in the same areas. Its clinical picture presents as an erythema of the buttocks and upper inner thighs resembling the red bottom of baboons. This reaction was originally observed with mercury, nickel, and ampicillin. In 2004, some authors proposed the acronym SDRIFE standing for 'symmetric drug-related intertriginous and flexural exanthema' specifically for cases elicited by systemically administered drugs. Since 1984, about 100 cases have been reported in the literature; for most of the concerned drugs, previous skin sensitization or possible cross-sensitization has not been shown. We report the first case of SDRIFE due to rivastigmine, with the exception of an erythematous maculopapular eruption due to rivastigmine that was previously reported. Rivastigmine is a reversible and noncompetitive acetylcholinesterase inhibitor used for the treatment of Alzheimer disease. SDRIFE is an important condition to keep in mind in order to avoid a misdiagnosis when dealing with other exanthematous disorders and to prevent re-exposure to the responsible allergen in the future.

Symmetrical Drug-related Intertriginous and Flexural Exanthema Induced by Doxycycline

PubMed Central

Thomas, Cristina; Weintraub, Gil S; Mostaghimi, Arash

2017-01-01

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug reaction characterized by erythema over the buttocks, thighs, groin, and flexural regions most commonly associated with the use of beta-lactam antibiotics. Although the exact pathophysiology of this disease remains unknown, it is theorized to be the result of a delayed hypersensitivity response presenting as a cutaneous eruption days to weeks after exposure to the drug. The treatment involves discontinuation of the suspected medication, symptomatic control of pruritus, and topical steroid therapy. A 51-year-old woman with homocystinuria and fibromyalgia was admitted with fevers, pancytopenia (later diagnosed to be acute myelogenous leukemia), and a targetoid cutaneous eruption in the setting of a recent tick bite. She was subsequently noted to have symmetric, pruritic, erythematous papules over the lateral neck, retroauricular regions, lateral aspects of the inframammary regions, medial upper arms, axillae, and the lower abdomen two weeks after starting doxycycline. Considering the morphology, distribution, and intense pruritis associated with the eruption, a diagnosis of SDRIFE was made. Doxycycline discontinuation along with topical steroid therapy resulted in the resolution of the eruption and pruritus. Given the widespread use of doxycycline, clinicians should be aware of this possible side effect. PMID:29340257

Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients

PubMed Central

McCormack, Mark; Gui, Hongsheng; Ingason, Andrés; Speed, Doug; Wright, Galen E.B.; Zhang, Eunice J.; Secolin, Rodrigo; Yasuda, Clarissa; Kwok, Maxwell; Wolking, Stefan; Becker, Felicitas; Rau, Sarah; Avbersek, Andreja; Heggeli, Kristin; Leu, Costin; Depondt, Chantal; Sills, Graeme J.; Marson, Anthony G.; Auce, Pauls; Brodie, Martin J.; Francis, Ben; Johnson, Michael R.; Koeleman, Bobby P.C.; Striano, Pasquale; Coppola, Antonietta; Zara, Federico; Kunz, Wolfram S.; Sander, Josemir W.; Lerche, Holger; Klein, Karl Martin; Weckhuysen, Sarah; Krenn, Martin; Gudmundsson, Lárus J.; Stefánsson, Kári; Krause, Roland; Shear, Neil; Ross, Colin J.D.; Delanty, Norman; Pirmohamed, Munir; Carleton, Bruce C.; Cendes, Fernando; Lopes-Cendes, Iscia; Liao, Wei-ping; O'Brien, Terence J.; Sisodiya, Sanjay M.; Cherny, Stacey; Kwan, Patrick; Baum, Larry

2018-01-01

Objective To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. Methods We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed. Results We report an association between a rare variant in the complement factor H–related 4 (CFHR4) gene and phenytoin-induced MPE in Europeans (p = 4.5 × 10–11; odds ratio [95% confidence interval] 7 [3.2–16]). This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, our results reinforce the association between HLA-A*31:01 and carbamazepine hypersensitivity. We did not identify significant genetic associations with MPE among Han Chinese patients. Conclusions The identification of genetic predictors of MPE in CFHR4 and CFH, members of the complement factor H–related protein family, suggest a new link between regulation of the complement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients. PMID:29288229

Human Herpesvirus 6 Infection Presenting as an Acute Febrile Illness Associated with Thrombocytopenia and Leukopenia

PubMed Central

Avšič-Županc, Tatjana; Uršič, Tina; Petrovec, Miroslav

2016-01-01

We present an infant with acute fever, thrombocytopenia, and leukopenia, coming from an endemic region for tick-borne encephalitis, human granulocytic anaplasmosis, and hantavirus infection. The primary human herpesvirus 6 infection was diagnosed by seroconversion of specific IgM and IgG and by identification of viral DNA in the acute patient's serum. The patient did not show skin rash suggestive of exanthema subitum during the course of illness. PMID:27980872

Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients.

PubMed

McCormack, Mark; Gui, Hongsheng; Ingason, Andrés; Speed, Doug; Wright, Galen E B; Zhang, Eunice J; Secolin, Rodrigo; Yasuda, Clarissa; Kwok, Maxwell; Wolking, Stefan; Becker, Felicitas; Rau, Sarah; Avbersek, Andreja; Heggeli, Kristin; Leu, Costin; Depondt, Chantal; Sills, Graeme J; Marson, Anthony G; Auce, Pauls; Brodie, Martin J; Francis, Ben; Johnson, Michael R; Koeleman, Bobby P C; Striano, Pasquale; Coppola, Antonietta; Zara, Federico; Kunz, Wolfram S; Sander, Josemir W; Lerche, Holger; Klein, Karl Martin; Weckhuysen, Sarah; Krenn, Martin; Gudmundsson, Lárus J; Stefánsson, Kári; Krause, Roland; Shear, Neil; Ross, Colin J D; Delanty, Norman; Pirmohamed, Munir; Carleton, Bruce C; Cendes, Fernando; Lopes-Cendes, Iscia; Liao, Wei-Ping; O'Brien, Terence J; Sisodiya, Sanjay M; Cherny, Stacey; Kwan, Patrick; Baum, Larry; Cavalleri, Gianpiero L

2018-01-23

To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed. We report an association between a rare variant in the complement factor H-related 4 ( CFHR4 ) gene and phenytoin-induced MPE in Europeans ( p = 4.5 × 10 -11 ; odds ratio [95% confidence interval] 7 [3.2-16]). This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H ( CFH ) gene. In addition, our results reinforce the association between HLA-A*31:01 and carbamazepine hypersensitivity. We did not identify significant genetic associations with MPE among Han Chinese patients. The identification of genetic predictors of MPE in CFHR4 and CFH, members of the complement factor H-related protein family, suggest a new link between regulation of the complement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Histopathology of the Exanthema in DRESS Is Not Specific but May Indicate Severity of Systemic Involvement.

PubMed

Gonçalo, Margarida M; Cardoso, José C; Gouveia, Miguel P; Coutinho, Inês; Gameiro, Ana R; Brites, Maria M; Tellechea, Óscar E

2016-06-01

Exanthema in drug reaction with eosinophilia and systemic symptoms (DRESS) has no specific clinical diagnostic hallmark and there are few histopathologic studies. The aim of this study was to describe dermal-epidermal histopathologic features in DRESS and correlate them with the culprit drug, viral reactivation, or systemic organ involvement. Skin biopsies were independently evaluated by 2 dermatopathologists who characterized the main histological patterns and scored dermal and epidermal changes, which were further correlated with clinical and laboratorial data. In 15 DRESS patients (9 male/6 female patients, mean age 53.3 years), the main observation was lymphocyte exocytosis (1.87 ± 1.25), spongiosis (0.93 ± 0.94), scattered keratinocyte necrosis (1.70 ± 1.44), basal cell vacuolization (2.13 ± 1.42), lymphocyte infiltration around dermal vessels (2.93 ± 0.92) or at the dermal-epidermal junction (2.07 ± 1.12), often with eosinophils and extravasated erythrocytes, swollen endothelial cells, and intravascular neutrophils but no vasculitis. Histopathologic patterns were classified mainly as spongiotic (5), erythema multiforme-like (3), or lichenoid (2). There was a significant positive correlation between the intensity of lymphocyte infiltration and the severity of hepatic cytolysis (r = 0.51; P < 0.05) and eosinophilia (r = 0.51; P < 0.05). No correlation was observed between the intensity and type of dermal inflammation and the degree of epidermal damage or the culprit drug. Human herpes virus type 6-positive patients had a pseudolymphomatous reaction or a perifollicular localization of the infiltrate. Histopathology in DRESS is variable with no specific diagnostic aspect, but there is a possible correlation between the intensity of the lymphocyte infiltrate and DRESS severity, namely, liver cytolysis.

Acute Zika Virus Infection in an Endemic Area Shows Modest Proinflammatory Systemic Immunoactivation and Cytokine-Symptom Associations.

PubMed

Barros, Jéssica Barletto de Sousa; da Silva, Paulo Alex Neves; Koga, Rosemary de Carvalho Rocha; Gonzalez-Dias, Patrícia; Carmo Filho, José Rodrigues; Nagib, Patrícia Resende Alo; Coelho, Verônica; Nakaya, Helder I; Fonseca, Simone Gonçalves; Pfrimer, Irmtraut Araci Hoffmann

2018-01-01

An early immune response to Zika virus (ZIKV) infection may determine its clinical manifestation and outcome, including neurological effects. However, low-grade and transient viremia limits the prompt diagnosis of acute ZIKV infection. We have investigated the plasma cytokine, chemokine, and growth factor profiles of 36 individuals from an endemic area displaying different symptoms such as exanthema, headache, myalgia, arthralgia, fever, hyperemia, swelling, itching, and nausea during early-phase infection. These profiles were then associated with symptoms, revealing important aspects of the immunopathophysiology of ZIKV infection. The levels of some cytokines/chemokines were significantly higher in acute ZIKV-infected individuals compared to healthy donors, including interferon (IFN) gamma-induced protein 10 (IP-10), regulated on activation, normal T cell expressed and secreted (RANTES), IFN-γ, interleukin (IL)-9, IL-7, IL-5, and IL-1ra, including some with predominantly immunoregulatory activity. Of note, we found that higher levels of IP-10 and IL-5 in ZIKV-infected individuals were strongly associated with exanthema and headache, respectively. Also, higher levels of IL-1ra were associated with subjects with arthralgia, whereas those with fever showed lower levels of granulocyte-colony stimulating factor (G-CSF). No correlation was observed between the number of symptoms and ZIKV viral load. Interestingly, only IP-10 showed significantly decreased levels in the recovery phase. In conclusion, our results indicate that acute ZIKV infection in a larger cohort resident to an endemic area displays a modest systemic immune activation profile, involving both proinflammatory and immunoregulatory cytokines and chemokines that could participate of virus control. In addition, we showed that differential cytokine/chemokine levels are related to specific clinical symptoms, suggesting their participation in underlying mechanisms.

Cytokine and chemokine expression in the skin from patients with maculopapular exanthema to drugs.

PubMed

Fernandez, T D; Mayorga, C; Torres, M J; Cornejo-Garcia, J A; López, S; Chaves, P; Rondon, C; Blanca, M

2008-06-01

Maculopapular exanthema (MPE) is the most frequent clinical manifestation of nonimmediate allergic reactions to drugs and T helper 1 (Th1) cytokines and CD4(+) T cells have been shown to play an important role in its pathogenesis. We assessed the role of cytokines and chemokines and their receptors in the pathogenesis of MPE. We evaluated skin biopsies and peripheral CD4(+) and CD8(+) T cells from 27 patients during the acute phase of the reaction and 26 exposed controls. Semiquantitative real-time PCR was performed to determine the expression of cytokines and chemokines and their receptors and immunohistochemistry was used to determine the same chemokines and their receptor proteins in skin. There was a high expression of the Th1 cytokines interferon-gamma (P = 0.006) and tumor necrosis factor-alpha (P = 0.022) in skin and CD4(+) T cells (P = 0.007 and P = 0.005, respectively); and of the Th1 chemokines CXCL9 (P = 0.005) and CXCL10 (P = 0.028) in the skin, while their receptor CXCR3 was increased in skin (P = 0.006) and CD4(+) T cells (P = 0.03). Homing chemokine receptors were also increased: CCR6 in skin (P = 0.026) and CD4(+) T cells (P = 0.016), and CCR10 only in CD4(+) T cells (P = 0.016), as well as their ligands, CCL20 and CCL27, in skin alone. Immunohistochemistry confirmed these results. These data show significant differences in the expression of chemokines and chemokine receptors, related with a Th1 profile, in both skin biopsies and peripheral CD4(+) T cells in patients with drug-induced MPE.

Role of effector cells (CCR7(-)CD27(-)) and effector-memory cells (CCR7(-)CD27(+)) in drug-induced maculopapular exanthema.

PubMed

Fernandez, T D; Torres, M J; Lopez, S; Antunez, C; Gomez, E; Del Prado, M F; Canto, G; Blanca, M; Mayorga, C

2010-01-01

Maculopapular exanthema (MPE) induced by drugs is a T-cell mediated reaction and effector cells may play an important role in its development. We assessed the effector and cutaneous homing phenotype in peripheral blood cells from allergic patients after drug stimulation. This study included 10 patients and 10 controls. The effector phenotype (CCR7(-)CD27(+/-)), chemokine receptors (CCR4 and CCR10), and activation (CD25(low)) and regulatory markers (CD25(high)) were measured by flow cytometry in both peripheral blood mononuclear cells (PBMCs) and CD4-T-lymphocytes. Proliferation was determined by 5-(-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) assay and the migratory capacity by a chemotaxis assay using CCL17 and CCL27. Compared to controls, CCR7(-)CD27(-) cells were increased in patients without (p=0.003) and with drug stimulation (p less than 0.001) and had significantly higher proliferation (p=0.010). CCR10 expression was increased in patients after drug stimulation in total and memory CD27(+) T-cells. Lymphocyte migration with CCL27 was higher in patients with drug stimulation (p=0.048), with a decrease in CCR7(-)CD27(-) (p less than 0.0001) and an increase in CCR7(-)CD27(+) (p=0.017). In patients, CD4-T-lymphocytes were significantly activated after drug stimulation (p less than 0.001). In conclusion, we show that effector memory CD4(+) T-cells (CCR7(-)CD27(+)) respond specifically to the drug responsible for MPE and confirm previous data about the involvement of CCR10 in cell trafficking to the skin.

Isolation of equine herpesvirus 3 (EHV-3) from equine coital exanthema of two stallions and sero-epidemiology of EHV-3 infection in Japan

PubMed Central

KIRISAWA, Rikio; TOISHI, Yuko; AKAMATSU, Ai; SOEJIMA, Kosuke; MIYASHITA, Taisuke; TSUNODA, Nobuo

2017-01-01

In the spring of 2015, two stallions reared in Farms A and B in Hokkaido in Japan showed symptoms of equine coital exanthema. Equine herpesvirus 3 (EHV-3) was isolated from penis swab samples of both stallions, and the isolates from each stallion in Farms A and B were designated as SS-1 and YS-1 strains, respectively. BamHI restriction profiles of SS-1 and Japanese reference strain Iwate-1 were indistinguishable, but the BamHI-A fragment of YS-1 was larger than those of SS-1 and Iwate-1 by 1.9 kbp because of the lack of two BamHI sites. Nucleotide sequence analyses of glycoprotein G (gG), gB, gC and VP13/14 coding regions revealed that SS-1 and YS-1 had 99.77% to 100% identities to each other. These results suggested that the origins of SS-1 and YS-1 were different. For a sero-epidemiological survey, serum neutralizing tests using SS-1 against 319 sera of horses from eight farms in Hokkaido were conducted. Six of the eight farms were EHV-3 antibody-positive, and positive rates ranged from 2.6% to 17.6%. To determine the infection time of four EHV-3 antibody-positive horses, a retrospective study was conducted. Infection time of the four horses was in the breeding season, and re-infection or reactivation of latently infected EHV-3 might have occurred in one horse. However, these four horses had never shown any clinical symptoms. The results suggested that several EHV-3 strains are distributed in Japan and that infection is maintained widely in horses without clinical symptoms. PMID:28132964

Pityriasis Rosea, Gianotti-Crosti Syndrome, Asymmetric Periflexural Exanthem, Papular-Purpuric Gloves and Socks Syndrome, Eruptive Pseudoangiomatosis, and Eruptive Hypomelanosis: Do Their Epidemiological Data Substantiate Infectious Etiologies?

PubMed Central

Zawar, Vijay; Sciallis, Gabriel F.; Kempf, Werner; Lee, Albert

2016-01-01

Many clinical and laboratory-based studies have been reported for skin rashes which may be due to viral infections, namely pityriasis rosea (PR), Gianotti-Crosti syndrome (GCS), asymmetric periflexural exanthem/unilateral laterothoracic exanthem (APE/ULE), papular-purpuric gloves and socks syndrome (PPGSS), and eruptive pseudo-angiomatosis (EP). Eruptive hypomelanosis (EH) is a newly discovered paraviral rash. Novel tools are now available to investigate the epidemiology of these rashes. To retrieve epidemiological data of these exanthema and analyze whether such substantiates or refutes infectious etiologies. We searched for articles published over the last 60 years and indexed by PubMed database. We then analyzed them for universality, demography, concurrent patients, temporal and spatial-temporal clustering, mini-epidemics, epidemics, and other clinical and geographical associations. Based on our criteria, we selected 55, 60, 29, 36, 20, and 4 articles for PR, GCS, APE/ULE, PPGSS, EP, and EH respectively. Universality or multiple-continental reports are found for all exanthema except EH. The ages of patients are compatible with infectious causes for PR, GCS, APE/ULE, and EH. Concurrent patients are reported for all. Significant patient clustering is demonstrated for PR and GCS. Mini-epidemics and epidemics have been reported for GCS, EP, and EH. The current epidemiological data supports, to a moderate extent, that PR, GCS, and APE could be caused by infectious agents. Support for PPGSS is marginal. Epidemiological evidences for infectious origins for EP and EH are inadequate. There might be growing epidemiological evidence to substantiate or to refute our findings in the future. PMID:27103975

Brazilian Spotted Fever: the importance of dermatological signs for early diagnosis*

PubMed Central

Couto, Daíne Vargas; Medeiros, Marcelo Zanolli; Hans, Gunter; de Lima, Alexandre Moretti; Barbosa, Aline Blanco; Vicari, Carolina Faria Santos

2015-01-01

Brazilian spotted fever is an acute febrile infectious disease caused by Rickettsia rickettsii, transmitted by tick bite. As this disease is rare and has high mortality rates in Brazil, the clinical aspects and epidemiological data may help the diagnosis. We report a case of Brazilian spotted fever in a 19-year-old patient who presented maculopapular exanthema in the palmar region and upper limbs, lymphadenopathy, fever, chills, headache, conjunctival hyperemia, nausea, vomiting, dyspnea, myalgia, developing neurological signs and abdominal pain. He was treated with doxycycline with clinical improvement. We emphasize the importance of the recognition of this disease by dermatologists as cutaneous manifestations are the key findings to establish early diagnosis and prevent complications. PMID:25830998

[Toxic shock syndrome after open ankle fracture].

PubMed

Klüter, T; Fitschen-Oestern, S; Weuster, M; Fickenscher, H; Seekamp, A; Lippross, S

2015-07-01

The treatment of open fractures is a challenge for the attending surgeon. Depending on the severity, the risk of infection rises up to 50%. Local infection up to the point of sepsis can develop in spite of surgical and antimicrobial therapy. The present case demonstrates the case of an 18-year-old man who developed toxic shock syndrome (TSS) after an open ankle fracture. This potentially life-threating syndrome usually presents with the main symptoms of fever, hypotension and exanthema and is caused by toxins, such as toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxins A-D. In some cases it is associated with cardiopulmonary decompensation and can rapidly progress to multiorgan failure.

Clinical experience with intravenous Augmentin in the treatment of paediatric infections.

PubMed

Ploechl, E; Huber, E G

1986-01-01

The clinical efficacy of intravenous Augmentin (a formulation containing amoxycillin plus clavulanic acid) was investigated in an open study in fifty-eight children with a mean age of 6 years (range 1-15 years). The normal dosage was in the range 100-200 mg/kg/day Augmentin, administered parenterally by short i.v. infusion in 3 or 4 divided doses. Most patients were hospitalised for lower respiratory tract infections. Complete clinical cure or distinct clinical improvement was achieved in all assessable cases. Bacteriological success was obtained in 92% of the assessable cases. In two patients, mild, transient exanthema was noted after i.v. Augmentin was replaced by oral Augmentin. No additional therapeutic measures were required.

Intravenous immunoglobulin therapy leading to dramatic improvement in a patient with systemic juvenile idiopathic arthritis and severe pericarditis resistant to steroid pulse therapy.

PubMed

Aizawa-Yashiro, Tomomi; Oki, Eishin; Tsuruga, Kazushi; Nakahata, Tohru; Ito, Etsuro; Tanaka, Hiroshi

2012-05-01

A 7-year-old Japanese boy with a 4-month history of systemic juvenile idiopathic arthritis (s-JIA) experienced disease flare with spiking fever, exanthema and arthralgia. He then developed progressive dyspnea due to severe pericarditis, and proinflammatory hypercytokinemia was suspected. Methylprednisolone pulse therapy was ineffective and echocardiography showed massive pericardial effusion had persisted. Alternatively, subsequent intravenous immunoglobulin (IVIG) therapy resulted in dramatic resolution of the pericardial effusion, and his general condition significantly improved within a few days. This case report may lend further support the use of IVIG for selected patients with s-JIA and severe pericarditis.

Association between HLA-B Alleles and Carbamazepine-Induced Maculopapular Exanthema and Severe Cutaneous Reactions in Thai Patients

PubMed Central

Chaichan, Chonlawat; Nakkrut, Thapanat; Satapornpong, Patompong; Jaruthamsophon, Kanoot; Jantararoungtong, Thawinee; Koomdee, Napatrupron; Sririttha, Suthida; Medhasi, Sadeep; Oo-Puthinan, Sarawut; Rerkpattanapipat, Ticha; Klaewsongkram, Jettanong; Rerknimitr, Pawinee; Tuchinda, Papapit; Chularojanamontri, Leena; Tovanabutra, Napatra; Puangpetch, Apichaya

2018-01-01

The HLA-B∗15:02 allele has been reported to have a strong association with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Thai patients. The HLA-B alleles associated with carbamazepine-induced maculopapular exanthema (MPE) and the drug reaction with eosinophilia and systemic symptoms (DRESS) among the Thai population have never been reported. The aim of the present study was to carry out an analysis of the involvement of HLA-B alleles in carbamazepine-induced cutaneous adverse drug reactions (cADRs) in the Thai population. A case-control study was performed by genotyping the HLA-B alleles of Thai carbamazepine-induced hypersensitivity reaction patients (17 MPE, 16 SJS/TEN, and 5 DRESS) and 271 carbamazepine-tolerant controls. We also recruited 470 healthy Thai candidate subjects who had not taken carbamazepine. HLA-B∗15:02 showed a significant association with carbamazepine-induced MPE (P = 0.0022, odds ratio (OR) (95% confidence interval [CI]) = 7.27 (2.04–25.97)) and carbamazepine-induced SJS/TEN (P = 4.46 × 10−13; OR (95% CI) = 70.91(19.67–255.65)) when compared with carbamazepine-tolerant controls. Carbamazepine-induced SJS/TEN also showed an association with HLA-B∗15:21 allele (P = 0.013; OR (95% CI) = 9.54 (1.61–56.57)) when compared with carbamazepine-tolerant controls. HLA-B∗58:01 allele was significantly related to carbamazepine-induced MPE (P = 0.007; OR (95% CI) = 4.73 (1.53–14.66)) and DRESS (P = 0.0315; OR (95% CI) = 7.55 (1.20–47.58)) when compared with carbamazepine-tolerant controls. These alleles may serve as markers to predict carbamazepine-induced cADRs in the Thai population. PMID:29546073

Slow desensitization of imatinib-induced nonimmediate reactions and dynamic changes of drug-specific CD4+CD25+CD134+ lymphocytes.

PubMed

Klaewsongkram, Jettanong; Thantiworasit, Pattarawat; Sodsai, Pimpayao; Buranapraditkun, Supranee; Mongkolpathumrat, Pungjai

2016-11-01

Imatinib is a tyrosine kinase inhibitor indicated for the treatment of gastrointestinal stromal tumors (GISTs) and certain neoplastic diseases; however, nonimmediate adverse reactions are common. To describe the process of imatinib slow desensitization in patients who experienced nonimmediate reactions to imatinib and the dynamic change in drug-specific CD4 + CD25 + CD134 + T-lymphocyte percentages. Five patients diagnosed as having GISTs and with a recent history of imatinib-induced nonimmediate reactions (maculopapular exanthema with eosinophilia, exfoliative dermatitis, palmar-plantar erythrodysesthesia, and drug rash with eosinophilia and systemic symptoms) were desensitized using a slow desensitization protocol. The reintroduced imatinib dosage was stepped up every week starting from 10 mg/d and increasing to 25, 50, 75, 100, 150, 200, and 300 mg/d until the target dose of 400 mg/d was achieved. Prednisolone of up to 30 mg/d was allowed if allergic reactions recurred. The percentages of CD4 + CD25 + CD134 + T cells present after incubating peripheral blood mononuclear cells with imatinib, at baseline and after successful desensitization, were analyzed using flow cytometric analysis. By using a slow desensitization technique, all patients were able to receive 400 mg/d of imatinib, and prednisolone was gradually tapered off. The percentages of imatinib-induced CD4 + CD25 + CD134 + T cells decreased from a mean (SD) of 11.3% (6.5%) and 13.4% (7.3%) at baseline to 3.2% (0.7%) and 3.0% (1.1%) after successful desensitization, when stimulating peripheral blood mononuclear cells with 1 and 2 μM of imatinib, respectively. Slow desensitization is a helpful procedure in treating patients with imatinib-induced nonimmediate reactions other than simple maculopapular exanthema. The reduced percentages of imatinib-induced CD4 + CD25 + CD134 + T cells in these patients may be associated with immune tolerance. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A systematic approach to systemic contact dermatitis and symmetric drug-related intertriginous and flexural exanthema (SDRIFE): a closer look at these conditions and an approach to intertriginous eruptions.

PubMed

Winnicki, Monika; Shear, Neil H

2011-06-01

Systemic contact dermatitis is a condition that occurs when an individual sensitized to a contact allergen is exposed to that same allergen or a cross-reacting molecule through a systemic route. Systemic exposure to allergens can include transcutaneous, transmucosal, oral, intravenous, intramuscular, and inhalational routes. Baboon syndrome is perhaps the most recognizable form of systemic contact dermatitis, presenting with diffuse, well demarcated erythema of the buttocks, upper inner thighs, and axillae. Other forms of systemic contact dermatitis include dermatitis at sites of previous exposure to the allergen such as at a previous site of dermatitis or at sites of previous positive patch tests, dyshidrotic hand eczema, flexural dermatitis, exanthematous rash, erythroderma, and vasculitis-like lesions. The most common causes of systemic contact dermatitis consist of three groups of allergens: (i) metals including mercury, nickel, and gold; (ii) medications including aminoglycoside antibacterials, corticosteroids, and aminophylline; and (iii) plants and herbal products including the Compositae and Anacardiaceae plant families and Balsam of Peru. Baboon syndrome caused by systemic medications without a known history of previous cutaneous sensitization in the patient has been termed drug-related baboon syndrome (DRBS) or symmetric drug-related intertriginous and flexural exanthema (SDRIFE). Criteria for SDRIFE include exposure to systemic drug at first or repeated dose, erythema of the gluteal/perianal area and/or V-shaped erythema of the inguinal area, involvement of at least one other intertriginous localization, symmetry of affected areas, and absence of systemic toxicity. The most common causes are aminopenicillins, β-lactam antibacterials, and certain chemotherapeutic agents, though the list of etiologic agents continues to grow. Baboon syndrome and SDRIFE should be strongly considered in a patient presenting with a symmetric intertriginous eruption involving multiple body folds. With the knowledge of the most frequent causes of these conditions, a detailed history and review of exposures will guide the clinician in the search for the most likely etiologic agent.

[Fever and petechial exanthema in children].

PubMed

Soult Rubio, J A; Navarro González, J; Olano Claret, P

1992-11-01

In an attempt to determine clinical and analytical predictive parameters of a possible grave disease, we have carried out a retrospective study of 172 children admitted to our hospital with fever and petechiae as initial symptoms. The ages ranged between 1 month and 10 years. Even though we have not found a clinical symptom or analysis sufficiently sensitive as to predict all grave diseases, the general clinical state of the child associated with either a high or low white cell count and an abnormal coagulation study should be alert signals for a serious infectious disease. On the contrary, if the clinical and analytical parameters are within normal limits the risk of a grave disease is low. We emphasize the high incidence of meningococcal disease (26%).

Unilateral laterothoracic exanthema with coincident evidence of Epstein Barr virus reactivation: exploration of a possible link.

PubMed

Scheinfeld, Noah

2007-07-13

Unilateral laterothoracic exanthem (ULE) was first described in 1962 in the United States and comprehensively elaborated in 1992. Although ULE most commonly occurs in children, ULE can occur in adults. ULE may or may not be preceded by a viral prodrome and is marked by coalescing erythematous papules predominately on one side of the body. ULE usually lasts 4-6 weeks but can last as little as 2 weeks. It has inconsistently been linked to viral infection, in particular parvovirus B-19. I note ULE in an adult with concurrent reactivation of Epstein Barr virus (EBV) that lasted 4 weeks. The role of the reactivation of EBV in human disease and ULE is explored.

Immunological aspects of nonimmediate reactions to beta-lactam antibiotics.

PubMed

Rodilla, Esther Morena; González, Ignacio Dávila; Yges, Elena Laffond; Bellido, Francisco Javier Múñoz; Bara, María Teresa Gracia; Toledano, Félix Lorente

2010-09-01

beta-lactam antibiotics are the agents most frequently implied in immune drug adverse reactions. These can be classified as immediate or nonimmediate according to the time interval between the last drug administration and their onset. Mechanisms of immediate IgE-mediated reactions are widely studied and are therefore better understood. Nonimmediate reactions include a broad number of clinical entities like mild maculopapular exanthemas, the most common, and other less frequent but more severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, acute exanthematic pustulosis or cytopenias. These nonimmediate reactions are mainly mediated by T cells but the precise underlying mechanisms are not well elucidated. This fact complicates the allergological evaluation of patients with this type of reaction and available tests have demonstrated poor sensitivity and specificity.

Detection of human herpes virus 6 (HHV 6) in the skin of a patient with primary HHV 6 infection and erythroderma.

PubMed Central

Sumiyoshi, Y; Akashi, K; Kikuchi, M

1994-01-01

Human herpes virus 6 (HHV 6) has been implicated as the causative agent of exanthema subitum in young children. Recently, we reported two cases of a severe, infectious, mononucleosis-like syndrome resulting from a primary HHV 6 infection in immunocompetent adults. Both of these patients had the skin condition generally referred to as "erythroderma". A skin-biopsy specimen from one of them, a 43 year old man, was examined. Using immunohistochemical staining and in situ hybridisation, lymphocytes infected with HHV 6 were found in the skin. It is proposed that the erythroderma in immunocompetent adults infected with primary HHV 6 is provoked by infiltration of infected inflammatory cells or infected neoplastic lymphocytes into the dermis. Images PMID:7962635

[Imported dengue: an emerging arbovirosis in Spain].

PubMed

Ramos Geldres, T T; García López-Hortelano, M; Baquero-Artigao, F; Montero Vega, D; López Quintana, B; Mellado Peña, M J

2015-01-01

Dengue is caused by one of 4 serotypes of dengue virus. Only imported cases have been reported in Spain. The main clinical findings are fever and exanthema, although there may be severe forms, particularly in secondary infections. Five children with a primary, non severe dengue infection are presented. The diagnosis was based on clinical suspicion and epidemiological history, and confirmed by immunochromatography and ELISA tests. The outcome was favourable in all cases. It is important to consider this diagnosis in international travellers that present with fever within the 14 days of returning from an endemic area, in order to get an early diagnosis, adequate treatment and a good prognosis. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

[Childhood diseases with exanthema].

PubMed

Opstelten, Wim; Eekhof, Just A H; Knuistingh Neven, Arie

2011-01-01

- Due to high vaccination coverage, measles and rubella (German measles) are now rarely seen in the Netherlands, which makes recognition of these diseases difficult. - Measles can also occur in people who have been immunized, as a result of vaccination failure. - Swift recognition of measles and rubella is necessary in order to manage them adequately and to prevent spreading of the disease. - Measles, rubella, and erythema infectiosum ('fifth disease') may result in complications during pregnancy. - Measles, rubella, scarlet fever, erythema infectiosum, and roseola ('sixth disease') can be difficult to differentiate. - In the Netherlands, diagnosis of a patient with measles or rubella, or of more than 1 patient with erythema infectiosum within one institution, must be reported to the local health authority within 1 working day. - Exclusion from school or a day-care facility is not required for any if the diseases discussed.

[The Antonine plague].

PubMed

Haas, Charles

2006-01-01

During the reign of Marcus Aurelius, the Roman Empire was struck by a long and destructive epidemic. It began in Mesopotamia in late AD 165 or early AD 166 during Verus' Parthian campaign, and quickly spread to Rome. It lasted at least until the death of Marcus Aurelius in AD 180 and likely into the early part of Commodus' reign. Its victims were "innumerable". Galen had first-hand knowledge of the disease. He was in Rome when the plague reached the city in AD 166. He was also present during an outbreak among troops stationed at Aquileia during the winter of AD 168-169. His references to the plague are scattered and brief but enough information is available to firmly identify the plague as smallpox. His description of the exanthema is fairly typical of the smallpox rash, particularly in the hemorrhagic phase of the disease.

Comparison of camelpox viruses isolated in Dubai.

PubMed

Pfeffer, M; Meyer, H; Wernery, U; Kaaden, O R

1996-03-01

Between October 1993 and March 1994, outbreaks of pox-like exanthemas were observed in several camel raising farms in Dubai. Scabs from twenty camels with either local or generalized lesions were examined, seven of them had previously been vaccinated with a modified live camelpox virus vaccine. Inspection of scabs by electron microscopy confirmed an infection with orthopox viruses (OPV) in 10 animals and with parapox virus in one camel. Investigation of the scabs by polymerase chain reaction and dot blot assay revealed the presence of OPV in 15 or 13 samples, respectively. OPV could be isolated in cell culture in 14 cases. Restriction enzyme profiles characterized all isolates as camelpox virus. Their DNA patterns were virtually identical displaying only slight variations in the terminal fragments. In contrast, the vaccine strain showed a distinct restriction enzyme profile, indicating that it was not involved in the infections.

[Fatal case of rickettsiosis in a toddler from southeastern Mexico].

PubMed

Lugo-Caballero, César; Dzul-Rosado, Karla; Rodríguez-Moreno, Georgina; Tello-Martín, Raúl; López-Ávila, Karina; Zavala-Castro, Jorge

2017-02-01

Rocky Mountain spotted fever is a disease caused by Rickettsia rickettsii, a bacteria transmitted by infected ticks. It is characterized by fever, exanthema, arthralgias and myalgias; but sometimes its clinical presentation is non specific. Due to its similarities with other exanthematic diseases like dengue or chikungunya, Rocky Mountain spotted fever is not a first line diagnosis, even though countries like Mexico show the ecologic and socioeconomic characteristics that favor its transmission, with a 30% mortality rate among pediatric patients. This mortality rate has been associated to a delayed diagnosis and therapy, due to a poor knowledge among physicians regarding this disease; this favors the occurrence of atypical and fulminant cases. The objective of this work is to describe a fulminant case of Rocky Mountain spotted fever, expecting that this disease could be later considered among the differential diagnosis which could directly impact its mortality rate. Sociedad Argentina de Pediatría.

[Severe Yellow fever vaccine-associated disease: a case report and current overview].

PubMed

Slesak, Günther; Gabriel, Martin; Domingo, Cristina; Schäfer, Johannes

2017-08-01

History and physical examination  A 56-year-old man developed high fever with severe headaches, fatigue, impaired concentration skills, and an exanthema 5 days after a yellow fever (YF) vaccination. Laboratory tests  Liver enzymes and YF antibody titers were remarkably elevated. YF vaccine virus was detected in urine by PCR. Diagnosis and therapy  Initially, severe YF vaccine-associated visceral disease was suspected and treated symptomatically. Clinical Course  His fever ceased after 10 days in total, no organ failure developed. However, postencephalitic symptoms persisted with fatigue and impaired concentration, memory, and reading skills and partly incapability to work for over 3 months. A diagnosis was made of suspected YF vaccine-associated neurotropic disease. Conclusion  Severe vaccine-derived adverse effects need to be considered in the indication process for YF vaccination. © Georg Thieme Verlag KG Stuttgart · New York.

[Infections after bite wounds : For example rat bite fever due to Streptobacillus moniliformis].

PubMed

Hof, Herbert; Binder, Rudolf; Schäfer, Christian; Stuber, Madeleine; Licht, Andreas; Bozenhardt-Stavrakidis, Iris; Bode, Konrad

2018-04-11

Rat bite fever due to Streptobacillus moniliformis induces typical but not pathognomonic clinical signs, such as local purulent wound infection followed by maculopapular exanthema, myalgia as well as purulent joint infections. Severe complications, such as osteomyelitis and endocarditis are possible. it seems that this infection is rarely diagnosed but this infection could be much more common because the final diagnostic proof is difficult to achieve. Firstly, the culture of these bacteria is critical because the bacteria are fastidious and secondly the exact differentiation of the isolates is hardly possible by standard laboratory methods. Modern techniques such as mass spectroscopy (MALDI-TOF) and molecular biology allow a precise clarification. Surgical cleansing of infection sites in combination with a rational antibiotic therapy, for example with beta-lactam antibiotics, are generally able to cure the infection if treatment is started early enough. In addition, vaccinations, for example against tetanus and rabies have to be considered in this situation as for all other bite wound infections.

A new proposal for a clinical-oriented subclassification of baboon syndrome and a review of baboon syndrome.

PubMed

Miyahara, Atsushi; Kawashima, Hisashi; Okubo, Yukari; Hoshika, Akinori

2011-06-01

To review baboon syndrome (BS). Date sources were obtained from PubMed and Google Scholar: Photographs of baboon syndrome were obtained from our patient. PubMed and Google Scholar were searched up to June 30, 2010. The search terms were "baboon syndrome", "SDRIFE" and "thimerosal allergy". Reverse references from relevant articles and Google Scholar were also used. As BS is a classical disease and cases of offending agents were relatively old, some references were more than five years old. In order to gather as many cases of offending agents as possible, more than 50 references were collected. We divided BS into as 4 groups; classical baboon syndrome, topical drug-induced baboon syndrome, systemic drug-induced baboon syndrome and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). The pathomechanism of BS is still unknown. A delayed type of hypersensitivity reaction, a recall phenomenon, pharmacologic interaction with immune-receptors and anatomical factors may be involved in the causation of BS.

Genetic variants associated with phenytoin-related severe cutaneous adverse reactions.

PubMed

Chung, Wen-Hung; Chang, Wan-Chun; Lee, Yun-Shien; Wu, Ying-Ying; Yang, Chih-Hsun; Ho, Hsin-Chun; Chen, Ming-Jing; Lin, Jing-Yi; Hui, Rosaline Chung-Yee; Ho, Ji-Chen; Wu, Wei-Ming; Chen, Ting-Jui; Wu, Tony; Wu, Yih-Ru; Hsih, Mo-Song; Tu, Po-Hsun; Chang, Chen-Nen; Hsu, Chien-Ning; Wu, Tsu-Lan; Choon, Siew-Eng; Hsu, Chao-Kai; Chen, Der-Yuan; Liu, Chin-San; Lin, Ching-Yuang; Kaniwa, Nahoko; Saito, Yoshiro; Takahashi, Yukitoshi; Nakamura, Ryosuke; Azukizawa, Hiroaki; Shi, Yongyong; Wang, Tzu-Hao; Chuang, Shiow-Shuh; Tsai, Shih-Feng; Chang, Chee-Jen; Chang, Yu-Sun; Hung, Shuen-Iu

2014-08-06

The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10(-17)). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z=8.58; P < .00001) for CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease. This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.

[Rocky Mountain spotted fever in an American tourist].

PubMed

de Pender, A M G; Bauer, A G C; van Genderen, P J J

2005-04-02

In a 28-year-old male American tourist who presented in the hospital with fever, cold shivers, headache, nausea, myalgia and arthralgia, Rocky Mountain spotted fever was suspected, partly because he came from an endemic region (the state of Georgia). The patient was treated with doxycycline, 100 mg b.i.d.; 9 days after the first appearance of the symptoms, the diagnosis was confirmed by the report of a positive antibody titre against Rickettsia rickettsii. The patient did not have exanthema. He was discharged in good general condition after two weeks of treatment. Rocky Mountain spotted fever, caused by the Gram-negative bacterium R. rickettsii, is a serious rickettsiosis. The disease is seen only sporadically in the Netherlands because the ticks in the Netherlands do not carry the bacterium. The travel history is still not a standard component of the anamnesis and is therefore often forgotten. This can lead to under-diagnosis and delayed treatment of diseases that were formerly limited to the continent. The early recognition and treatment of Rocky Mountain spotted fever is important since delayed treatment is associated with a clear increase in both morbidity and mortality.

Clinic–Epidemiologic Study of Human Infection by Granada Virus, a New Phlebovirus within the Sandfly Fever Naples Serocomplex

PubMed Central

Navarro-Marí, José María; Gómez-Camarasa, Cristina; Pérez-Ruiz, Mercedes; Sanbonmatsu-Gámez, Sara; Pedrosa-Corral, Irene; Jiménez-Valera, María

2013-01-01

Granada virus (GRV), a new phlebovirus within the Naples serocomplex, has been recently described in phlebotomine sandflies from Spain. The presence of anti-GRV immunoglobulin G (IgG) antibodies was investigated by indirect fluorescence assay (IFA) and neutralization test (NT) in 920 serum samples from the Granada population. By IFA, an overall GRV seroprevalence of 15.8% (N = 145) was observed, significantly increasing up to 65 years. NT was positive in 18% of anti-GRV IFA-positive samples. IgG antibodies against Toscana virus (TOSV), a hyperendemic phlebovirus within Granada province, were detected in 40% of anti-GRV–positive cases. Anti-GRV IgM antibodies were detected in 36 (6.6%) of 547 acute-phase serum samples from individuals with febrile illness, exanthema, and/or acute respiratory infection. All positives were anti-TOSV IgM-negative. GRV may infect humans, with most cases being asymptomatic. The codetection of anti-GRV and anti-TOSV IgG antibodies could be attributable to cross-reactivity or exposure to the same transmission vector. PMID:23419365

Clinic-epidemiologic study of human infection by Granada virus, a new phlebovirus within the sandfly fever Naples serocomplex.

PubMed

Navarro-Marí, José María; Gómez-Camarasa, Cristina; Pérez-Ruiz, Mercedes; Sanbonmatsu-Gámez, Sara; Pedrosa-Corral, Irene; Jiménez-Valera, María

2013-05-01

Granada virus (GRV), a new phlebovirus within the Naples serocomplex, has been recently described in phlebotomine sandflies from Spain. The presence of anti-GRV immunoglobulin G (IgG) antibodies was investigated by indirect fluorescence assay (IFA) and neutralization test (NT) in 920 serum samples from the Granada population. By IFA, an overall GRV seroprevalence of 15.8% (N = 145) was observed, significantly increasing up to 65 years. NT was positive in 18% of anti-GRV IFA-positive samples. IgG antibodies against Toscana virus (TOSV), a hyperendemic phlebovirus within Granada province, were detected in 40% of anti-GRV-positive cases. Anti-GRV IgM antibodies were detected in 36 (6.6%) of 547 acute-phase serum samples from individuals with febrile illness, exanthema, and/or acute respiratory infection. All positives were anti-TOSV IgM-negative. GRV may infect humans, with most cases being asymptomatic. The codetection of anti-GRV and anti-TOSV IgG antibodies could be attributable to cross-reactivity or exposure to the same transmission vector.

An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity

PubMed Central

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

2018-01-01

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

Linear immunoglobulin A dermatosis mimicking toxic epidermal necrolysis: a case report of etanercept treatment.

PubMed

Prieto-Barrios, M; Velasco-Tamariz, V; Tous-Romero, F; Burillo-Martinez, S; Zarco-Olivo, C; Rodriguez-Peralto, J L; Ortiz-Romero, P L

2018-03-01

A 65-year-old pluripathological woman attended our hospital with a cutaneous eruption of sudden appearance after vancomycin treatment. She presented targetoid lesions affecting approximately 25-30% of her body surface, large erosions with mucosal lesions and positive Nikolsky sign. Under the initial clinical suspicion of toxic epidermal necrolysis (TEN), and considering the recent literature of successful use of etanercept in these cases, she was treated with a single dose of this antitumour necrosis factor (anti-TNF) agent. Subsequently, the exanthema progression stopped and resolution of the lesions happened in a few days. Later on, histopathology revealed a subepidermal blister with dense neutrophilic infiltrate and linear deposits of immunoglobulin A (IgA) on the dermoepidermal junction, allowing us to establish the diagnosis of drug-induced linear IgA dermatosis mimicking TEN. Linear IgA dermatosis can have severe clinical manifestations, even mimicking TEN, and can have high mortality, especially in drug-induced cases. We have not found any other report of linear IgA dermatosis treated with etanercept in the English literature. Anti-TNF medications could represent useful therapeutic alternatives in this dermatosis. © 2017 British Association of Dermatologists.

Intensive Care in a Patient with Toxic Epidermal Necrolysis

PubMed Central

Fischer, M.

2017-01-01

Toxic epidermal necrolysis (TEN) is a serious adverse drug reaction with high lethality, which usually requires intensive-medical care. A 44-year-old man developed generalized exanthema with increasing exfoliation and mucosal involvement after taking allopurinol, ibuprofen, and etoricoxib. The clinical diagnosis of TEN was histologically confirmed. Prednisolone therapy with 3 mg/kg body weight (BW) was not able to prevent further progress to finally 80% of the body surface, and infliximab 5 mg/kg BW was given as a single dose. This prevented further progression of the TEN. Despite marked improvement in skin findings, the ICU stay was prolonged by a complex analgosedation, transient kidney failure, volume management, positioning therapy, and vegetatively impeded weaning. Moreover, there was colonization with multiresistant bacteria (MRSA and VRE). Nonetheless, the patient could be restored to health and was released after four weeks. Infliximab seems to be effective in the treatment of TEN, especially in cases of rapid progression. Moreover, patients with TEN are difficult to handle in intensive-medical care, whereby attention should especially be paid to sufficient pain therapy, and the positioning of the patient is a particular challenge. PMID:29225976

Phenotype-genotype analysis of cryopyrin-associated periodic syndromes (CAPS): description of a rare non-exon 3 and a novel CIAS1 missense mutation.

PubMed

Jesus, Adriana A; Silva, Clovis A; Segundo, Gesmar R; Aksentijevich, Ivona; Fujihira, Erika; Watanabe, Mônica; Carneiro-Sampaio, Magda; Duarte, Alberto J S; Oliveira, João B

2008-03-01

We describe in this paper the phenotype-genotype analysis of a Brazilian cohort of patients with cryopyrin-associated periodic syndromes (CAPS). Patient 1 presented with an urticarial rash and recurrent fever exacerbated by cold weather, arthritis, and anterior uveitis, thus, receiving a clinical diagnosis of familial cold autoinflammatory syndrome. CIAS1 sequencing identified the T436I mutation, previously associated to a clinical phenotype of chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease. Patient 2 developed a papular exanthema with daily fever shortly after birth, frontal bossing, patellae enlargement, and cognitive and motor impairments. Sequencing identified the exceedingly rare G755R CIAS1 mutation in exon 4. Patient 3 developed skin rash and articular symptoms 6 h after birth, followed by aseptic meningitis. He was found to have the novel C148Y missense mutation in CIAS1. This report expands the spectrum of CIAS1 mutations associated to clinical disease, suggests that the same mutation can be associated with different clinical syndromes, and supports the evidence that CAPS patients should always be screened for mutations outside exon 3.

Immunohistopathological Findings of Severe Cutaneous Adverse Drug Reactions

PubMed Central

2017-01-01

Diagnosis of severe cutaneous adverse drug reactions should involve immunohistopathological examination, which gives insight into the pathomechanisms of these disorders. The characteristic histological findings of erythema multiforme (EM), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) provide conclusive evidence demonstrating that SJS/TEN can be distinguished from EM. Established SJS/TEN shows full-thickness, extensive keratinocyte necrosis that develops into subepidermal bullae. Drug-induced hypersensitivity syndrome (DIHS) and exanthema in drug reaction with eosinophilia and systemic symptoms (DRESS) each display a variety of histopathological findings, which may partly correlate with the clinical manifestations. Although the histopathology of DRESS is nonspecific, the association of two or more of the four patterns—eczematous changes, interface dermatitis, acute generalized exanthematous pustulosis- (AGEP-) like patterns, and EM-like patterns—might appear in a single biopsy specimen, suggesting the diagnosis and severe cutaneous manifestations of DRESS. Cutaneous dendritic cells may be involved in the clinical course. AGEP typically shows spongiform superficial epidermal pustules accompanied with edema of the papillary dermis and abundant mixed perivascular infiltrates. Mutations in IL36RN may have a definite effect on pathological similarities between AGEP and generalized pustular psoriasis. PMID:29226159

Demodex folliculitis mimicking acute graft-vs-host disease.

PubMed

Cotliar, Jonathan; Frankfurt, Olga

2013-12-01

Acute graft-vs-host disease (GVHD) typically requires high-dose systemic steroids as first-line treatment. Like drug eruptions, viral exanthema, and toxic erythema of chemotherapy, Demodex folliculitis is a clinical mimicker of acute GVHD and requires nonimmunosuppressive therapy. This case of Demodex folliculitis mimicking acute GVHD highlights the need for skin biopsy in patients who have undergone a stem cell transplant with eruptions on the head and neck. A 46-year-old white woman with a history of Fms-like tyrosine kinase 3 acute myeloid leukemia presented to the dermatology clinic with a 5-day history of a nonpruritic eruption on her face and neck 28 days after undergoing a double umbilical cord blood hematopoietic stem cell transplant (HSCT). Findings from the skin biopsy demonstrated a deep dermal lymphocytic infiltrate adjacent to follicular units along with an abundance of Demodex mites noted within the hair follicles consistent with Demodex folliculitis. Oral ivermectin, 12 mg, was given, and the eruption cleared within 24 hours. To our knowledge, this is only the fifth reported case of Demodex folliculitis following HSCT, but the first ever reported to be successfully treated with oral ivermectin. Demodex folliculitis should be added to the differential diagnosis of skin eruptions that arise after HSCT.

Detection of human parvovirus B19 DNA in 22% of 1815 cutaneous biopsies of a wide variety of dermatological conditions suggests viral persistence after primary infection and casts doubts on its pathogenic significance.

PubMed

Santonja, C; Santos-Briz, A; Palmedo, G; Kutzner, H; Requena, L

2017-10-01

Human parvovirus B19 (B19V) has been associated with a number of dermatological and systemic conditions, including myocarditis and autoimmune syndromes. To determine the frequency of B19V DNA detection in a large dermatopathology practice, and to characterize the histopathological patterns involved. We selected for polymerase chain reaction (PCR) detection of B19V a total of 1815 skin biopsies pertaining to entities allegedly related to B19V, as well as cases suspected clinically of representing paraviral exanthemas. Immunohistochemical detection of B19V viral protein 2 (VP2) was performed in 92 PCR-positive cases. B19V DNA was found by PCR in 402 out of 1825 biopsy specimens (22%). VP2 protein was identified by immunohistochemistry in only three instances of papular purpuric 'gloves-and-socks' syndrome. As the virus has the capacity to persist in different tissues (including the skin) for long periods, it could represent merely an innocent bystander, so no pathogenetic significance can be inferred from the PCR positivity for B19V in the vast majority of dermatological conditions studied. © 2017 British Association of Dermatologists.

[Chickenpox case estimation in acyclovir pharmacy survey and early bioterrorism detection].

PubMed

Sugawara, Tamie; Ohkusa, Yasushi; Kawanohara, Hirokazu; Taniguchi, Kiyosu; Okabe, Nobuhiko

2011-11-01

Early potential health hazards and bioterrorism threats require early detection. Smallpox cases caused by terrorist could, for example, be treated by prescribing acyclovir to those having fever and vesicle exanthema diagnosed as chicken pox. We have constructed real-time pharmacy surveillance scenarios using information technology (IT) to monitor acyclovir prescription. We collected the number of acyclovir prescriptions from 5138 pharmacies using the Application Server Provider System (ASP) to estimate the number of cases. We then compared the number of those given acyclovir under 15 years old from pharmacy surveillance and sentinel surveillance for chickenpox under the Infection Disease Control Law. The estimated number of under 15 years old prescribed acyclovir in pharmacy surveillance resembled sentinel surveillance results and showed a similar seasonal chickenpox pattern. The correlation coefficient was 0.8575. The estimated numbers of adults, older than 15 but under 65 years old, and elderly, older than 65, prescribed acyclovir showed no clear seasonal pattern. Pharmacy surveillance for acyclovir identified the baseline and can be used to detect unusual chickenpox outbreak. Bioterrorism attack could potentially be detected using smallpox virus when acyclovir prescription for adults suddenly increases without outbreaks in children or the elderly. This acyclovir prescription monitoring such as an application is, to our knowledge, the first of its kind anywhre.

Immediate and delayed cutaneous reactions to radiocontrast media.

PubMed

Brockow, Knut

2012-01-01

Hypersensitivity reactions to contrast media (CM) are frequent causes of anaphylaxis and drug exanthemas. Adverse events after CM exposure are classified into immediate (≤1 h) and non-immediate reactions (>1 h), with differing mechanisms. In the majority of patients with immediate reactions, IgE-mediated allergy cannot be demonstrated, and the underlying mechanism remains unknown. However, recent data have provided evidence for skin test positivity and/or specific IgE in some patients. T cell-mediated hypersensitivity is the responsible mechanism for the majority of non-immediate skin eruptions. These insights have consequences for diagnosis and prevention. Skin testing evolves to be a useful tool for diagnosis of CM allergy. Skin tests have been employed to confirm this hypersensitivity. Previous reactors have an increased risk to develop new reactions upon repeated exposure; however, other risk factors are poorly defined. The use of skin tests for the selection of a 'safe' CM is under investigation with promising results. In vitro tests to search for CM-specific cell activation include flow cytometric approaches, lymphocyte cultures and construction of cell lines and hybridomas. Premedication of previous reactors is common practice among radiologists; however, breakthrough reactions are a concern, and physicians should not rely on the efficacy of pharmacological premedication. Copyright © 2012 S. Karger AG, Basel.

Monitoring non-immediate allergic reactions to iodine contrast media

PubMed Central

Torres, M J; Mayorga, C; Cornejo-Garcia, J A; Lopez, S; Chaves, P; Rondon, C; Fernandez, T; Blanca, M

2008-01-01

Non-immediate reactions to iodine contrast media (ICM) affect 2–5% of patients receiving these agents. We studied the immunological mechanisms involved in patients with a confirmed non-immediate reaction, maculopapular exanthema, after administration of ICM. The diagnosis was carried out by skin testing or drug provocation test. The immunological study was performed in sequential peripheral blood mononuclear cells taken from the onset of the reaction by flow cytometry and in skin biopsy by immunohistochemistry, with specific recognition by the lymphocyte transformation test (LTT) with different ICM. Flow cytometry showed an increase in the different activation markers [CD69, CD25 and human leucocyte antigen D-related (HLA-DR)] and the skin homing receptor [cutaneous lymphocyte-associated antigen (CLA)] in CD4 lymphocytes, whereas perforin was higher in the CD8 lymphocytes. The skin biopsy showed a perivascular mononuclear infiltrate composed of CD4 lymphocytes, expressing CD25, HLA-DR and CLA, with eosinophils. Intradermal skin tests and the LTT were positive to several ICM, including the culprit agent in four and three patients, respectively, with negative results in all 10 tolerant controls. We showed that a specific immunological mechanism was implicated in patients with non-immediate reactions to ICM. Moreover, the positive results in skin tests and lymphocyte proliferation tests indicated that an important cross-reactivity exists. PMID:18341616

Different patterns of skin manifestations associated with parvovirus B19 primary infection in adults.

PubMed

Mage, Valentia; Lipsker, Dan; Barbarot, Sébastien; Bessis, Didier; Chosidow, Olivier; Del Giudice, Pascal; Aractingi, Sélim; Avouac, Jérôme; Bernier, Claire; Descamps, Vincent; Dupin, Nicolas

2014-07-01

Skin involvement is reported during primary parvovirus B19 infection in adults. We sought to describe the cutaneous presentations associated with parvovirus B19 primary infection in adults. We conducted a descriptive, retrospective, multicenter study. The patients included (>18 years old) had well-established primary infections with parvovirus B19. Twenty-nine patients were identified between 1992 and 2013 (17 women, 12 men). The elementary dermatologic lesions were mostly erythematous (86%) and often purpuric (69%). Pruritus was reported in 48% of cases. The rash predominated on the legs (93%), trunk (55%), and arms (45%), with a lower frequency of facial involvement (20%). Four different but sometimes overlapping patterns were identified (45%): exanthema, which was reticulated and annular in some cases (80%); the gloves-and-socks pattern (24%); the periflexural pattern (28%); and palpable purpura (24%). The limitations of this study were its retrospective design and possible recruitment bias in tertiary care centers. Our findings suggest that primary parvovirus B19 infection is associated with polymorphous skin manifestations with 4 predominant, sometimes overlapping, patterns. The acral or periflexural distribution of the rash and the presence of purpuric or annular/reticulate lesions are highly suggestive of parvovirus B19 infection. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Immunophenotypic characterization of the cutaneous exanthem of SIV-infected rhesus monkeys. Apposition of degenerative Langerhans cells and cytotoxic lymphocytes during the development of acquired immunodeficiency syndrome.

PubMed Central

Ringler, D. J.; Hancock, W. W.; King, N. W.; Letvin, N. L.; Daniel, M. D.; Desrosiers, R. C.; Murphy, G. F.

1987-01-01

A T-cell tropic retrovirus, simian immunodeficiency virus (SIV), has recently been isolated from immunodeficient rhesus monkeys. This virus has remarkable similarities to human immunodeficiency virus (HIV), the etiologic agent of acquired immunodeficiency syndrome. Subsequent studies of simian infection with SIV have shown it to be a relevant animal model for studying the pathogenesis of AIDS in man. In both HIV-infected humans and SIV-infected monkeys, a cutaneous maculopapular eruption has been described. To date, the pathogenesis and possible relationship of these exanthema to the evolution of systemic immunosuppression have remained obscure. In this study, the mononuclear cell infiltrates that characterize skin rashes of SIV-infected rhesus monkeys were found to be composed predominantly of cells with phenotypic characteristics of cytotoxic/suppressor (T8+) lymphocytes and natural killer cells. Many of these cells expressed membrane-bound interleukin-2 receptor molecules. Double labeling and immunoelectron microscopy revealed these cells in direct contact with degenerative Langerhans cells within the epidermis and dermis. These observations suggest that the cutaneous rash associated with SIV infection may be the consequence of target cell injury of Langerhans cells by effector cells with cytotoxic potential. Images Figure 1 Figure 2 Figure 3 PMID:3030113

[Cutaneous adverse drug reaction: prospective study of 118 cases].

PubMed

Chaabane, Hend; Masmoudi, Abderrahmen; Amouri, Meriem; Ghorbel, Sonda; Boudaya, Sonia; Hammami, Serriya; Zghal, Khaled; Turki, Hamida

2013-01-01

Few prospective studies are available on the incidence and analysis of the characteristics of adverse cutaneous drug reactions. To describe the adverse cutaneous reactions, their epidemiologic characteristics as well as the different causative drugs through a prospective hospital study. A 12-month prospective study was managed in our department of dermatology of the teaching hospital Hedi Chaker of Sfax. Requested information included patient characteristics (associated disorders), drug intake (list and chronology of the drug intake during the 3 weeks preceding the adverse reaction) and characteristics of the skin reaction (type, course). The diagnosis was based on a beam of clinical and anamnestic arguments. The drug imputability was evaluated according to the Begaud's French method. One hundred eighteen cases were collected. A prevalence of 1.08/100 among patients consulting in dermatology department was estimated. The macular and papular exanthema represented the most frequent clinical aspects (42 cases) followed by acute urticaria (23 cases), photosensitivity (19 cases) and fixed drug eruption (15 cases). Principal imputable drugs were antibiotics, mainly penicillins followed by analgesics and non-steroidal anti-inflammatory. Although it was monocentric, this study revealed a high frequency of drug-induced dermatitis with different clinical presentation. The high incidence of drug-induced dermatitis induced by antibiotics, analgesics and anti-inflammatory is due to their widespread use, often in self-medication.

Isolation of infectious Zika virus from a urine sample cultured in SIRC cells from a patient suspected of having rubella virus.

PubMed

Oliveira, Maria Isabel de; Namiyama, Gislene Mitsue; Cabral, Gabriela Bastos; Ferreira, João Leandro; Taniwaki, Noemi; Afonso, Ana Maria Sardinha; Lima, Isabella Rillo; Brigido, Luís Fernando Macedo de

2018-01-01

A great variety of viruses which cause exanthema share other clinical manifestations, making the etiologic identification a very difficult task, relying exclusively on the clinical examination. Rubella virus (RV) infection during the early stages of pregnancy can lead to serious birth defects, known as congenital rubella syndrome (CRS). In the present report, we described the presence of Zika virus (ZIKV) particles in urine samples and also ZIKV isolation in SIRC cells from the urine of a patient in acute phase of suspected rubella disease. The 50-year-old unvaccinated woman living in Sao Paulo, Brazil, was admitted to the emergency room with fever, headache, rash, arthralgia and prostration. Urine samples were collected for virus isolation and RT-qPCR. SIRC and Vero cells were inoculated with urine samples during 7 days. RT-qPCR was performed using measles virus (MV) and RV primers and both were found to be negative. After this result, RT-qPCR was performed for parvovirus B19, herpes virus 6 and ZIKV. The urine sample and the isolate were positive by Real Time PCR for ZIKV and negative for all other viruses tested. The sequences isolated are from the Asiatic lineage.

[Comparison of serological procedures used for the diagnosis of viral exanthema in laboratories participating in the measles elimination plan].

PubMed

de Ory, Fernando; Sanz, Juan Carlos; Echevarría, Juan Emilio; Mosquera, María del Mar; Guisasola, María Eulalia

2004-01-01

The comparison of serological methods used by the laboratories participating in the Network for the Elimination of Measles to diagnose measles virus infection as well as differential diagnosis with other exanthematic diseases are compared. One panel of 20 serum samples including measles (12), rubella (4), parvovirus B19 (2) and dengue (2) infections was established. All cases were diagnosed by detection of specific IgM. The panel was sent to the laboratories of the Network. The results were compared with those obtained at the reference laboratory. Regarding measles, IgM response from 20 laboratories (19 by ELISA and 1 by indirect immunofluorescence) was obtained, with an agreement of 91.5%. Related to rubella IgM, replay from 6 laboratories, using ELISA, was received, with an agreement of 98.7%. With respect to parvovirus B19 IgM, response from 10 laboratories (8 by ELISA and 2 by indirect immunofluorescence) was obtained, with an agreement of 94.6%. Results about dengue virus were not reported by any laboratory. Some laboratories from the network should review the methods used for the diagnosis of measles and other exanthematic diseases. The results reassert the need for a reference laboratory to support confirmation of the results.

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.

T-cell involvement in drug-induced acute generalized exanthematous pustulosis

PubMed Central

Britschgi, Markus; Steiner, Urs C.; Schmid, Simone; Depta, Jan P.H.; Senti, Gabriela; Bircher, Andreas; Burkhart, Christoph; Yawalkar, Nikhil; Pichler, Werner J.

2001-01-01

Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption most often provoked by drugs, by acute infections with enteroviruses, or by mercury. It is characterized by acute, extensive formation of nonfollicular sterile pustules on erythematous background, fever, and peripheral blood leukocytosis. We present clinical and immunological data on four patients with this disease, which is caused by different drugs. An involvement of T cells could be implied by positive skin patch tests and lymphocyte transformation tests. Immunohistochemistry revealed a massive cell infiltrate consisting of neutrophils in pustules and T cells in the dermis and epidermis. Expression of the potent neutrophil-attracting chemokine IL-8 was elevated in keratinocytes and infiltrating mononuclear cells. Drug-specific T cells were generated from the blood and skin of three patients, and phenotypic characterization showed a heterogeneous distribution of CD4/CD8 phenotype and of T-cell receptor Vβ-expression. Analysis of cytokine/chemokine profiles revealed that IL-8 is produced significantly more by drug-specific T cells from patients with AGEP compared with drug-specific T cells from patients that had non-AGEP exanthemas. In conclusion, our data demonstrate the involvement of drug-specific T cells in the pathomechanism of this rather rare and peculiar form of drug allergy. In addition, they indicate that even in some neutrophil-rich inflammatory responses specific T cells are engaged and might orchestrate the immune reaction. PMID:11390425

Paediatric Virology in the Hippocratic Corpus

PubMed Central

Mammas, Ioannis N.; Spandidos, Demetrios A.

2016-01-01

Hippocrates (Island of Kos, 460 B.C.-Larissa, 370 B.C.) is the founder of the most famous Medical School of the classical antiquity. In acknowledgement of his pioneering contribution to the new scientific field of Paediatric Virology, this article provides a systematic analysis of the Hippocratic Corpus, with particular focus on viral infections predominating in neonates and children. A mumps epidemic, affecting the island of Thasos in the 5th century B.C., is described in detail. ‘Herpes’, a medical term derived from the ancient Greek word ‘ἕρπειν’, meaning ‘to creep’ or ‘crawl’, is used to describe the spreading of cutaneous lesions in both childhood and adulthood. Cases of children with exanthema ‘resembling mosquito bites’ are presented in reference to varicella or smallpox infection. A variety of upper and lower respiratory tract viral infections are described with impressive accuracy, including rhinitis, pharyngitis, tonsillitis, laryngitis, bronchiolitis and bronchitis. The ‘cough of Perinthos’ epidemic, an influenza-like outbreak in the 5th century B.C., is also recorded and several cases complicated with pneumonia or fatal outcomes are discussed. Hippocrates, moreover, describes conjunctivitis, otitis, lymphadenitis, meningoencephalitis, febrile convulsions, gastroenteritis, hepatitis, poliomyelitis and skin warts, along with proposed treatment directions. Almost 2,400 years later, Hippocrates' systematic approach and methodical innovations can inspire paediatric trainees and future Paediatric Virology subspecialists. PMID:27446241

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

PubMed

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

2018-04-01

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

Systemic Contact Dermatitis.

PubMed

Aquino, Marcella; Rosner, Greg

2018-05-15

Systemic contact dermatitis (SCD) traditionally refers to a skin condition where an individual who is cutaneously sensitized to an allergen will subsequently react to that same allergen or a cross reacting allergen via a different route. It occurs to allergens including metals, medications, and foods. The exact pathophysiology underlying this disease remains unknown, although it appears to be mediated by type 4 hypersensitivity reactions and possibly type 3 hypersensitivity reactions. The p-I concept (pharmacologic interaction with immunoreceptors) hypothesized that drugs are able to bind directly to a T cell receptor without first being presented by MHC (major histocompatibility complex) molecules and without prior metabolism, which would help explain why SCD can be seen on first exposure to medications. Nomenclature remains a challenge as SCD can be subcategorized using terms such as ACDS (allergic contact dermatitis syndrome) and its four clinical stages, Baboon syndrome, and SDRIFE (symmetrical drug-related intertriginous and flexural exanthema), which share many overlapping features. Food allergens may be responsible for uncontrolled or persistent symptoms in patients with contact dermatitis who do not respond to topical avoidance. With medications, symptoms may be induced by topical application versus systemic administration. Patch testing (PT) may be beneficial in diagnosing SCD caused by metals and many topical medications including corticosteroids, antimicrobials (ampicillin, bacitracin, erythromycin, neomycin, nystatin), NSAIDs (diclofenac, ibuprofen), anesthetics, and antihistamines (chlorphenamine, piperazine). Current treatment options include topical steroids and oral antihistamines for symptom relief and dietary avoidance to causative foods or metals.

[Vemurafenib-induced toxic epidermal necrolysis].

PubMed

Wantz, M; Spanoudi-Kitrimi, I; Lasek, A; Lebas, D; Quinchon, J-F; Modiano, P

2014-03-01

Herein we report the first case of toxic epidermal necrolysis (TEN) occurring with use of vemurafenib. A 75-year-old female patient was being treated with vemurafenib for stage IV melanoma with BRAF V600E mutation. She suddenly presented fever, diffuse pruriginous maculopapular erythema, palpebral edema, palmar bulla, conjunctivitis, cheilitis and mucosal ulceration. The condition progressed towards detachment affecting 50% of the skin area. Cutaneous biopsy revealed lichenoid dermatosis, chiefly vesicular with numerous eosinophils. Direct immunofluorescence (IFD) was negative. Vemurafenib was the only drug to which the reaction was ascribable and we concluded on vemurafenib-induced TEN. To our knowledge, this is the first reported case of vemurafenib-induced TEN, but this adverse effect, although already described in the BRIM-3 study, appears rare in clinical practice. Other severe skin reactions have been described in the literature. These include a case of Stevens-Johnson syndrome in a female patient treated with vemurafenib and previously receiving ipilimumab. A more common occurrence is cutaneous reactions involving efflorescence of benign hyperkeratotic lesions, occasionally accompanied by authentic epidermal carcinoma or keratoacanthoma, and requiring regular dermatological monitoring of patients treated with vemurafenib. If maculopapular exanthema occurs under vemurafenib, continuation of this treatment should be reassessed since the risk of progression to a more serious condition such as TEN, as seen in the present case, cannot be ruled out. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

[Lead intoxication in a group of workers in Germany].

PubMed

Willi, R F; Felgenhauer, N; Eyer, F; Buters, J T; Zilker, T

2009-12-01

Seventeen East-European workers with a suspected lead-intoxication presented themselves to the Department of Toxicology. All of them had worked on the renovation of pylons of a high-tension line. The old paint, known to contain lead was removed with needle descalers. The patients had blood lead concentrations between 325 and 1124 microg/l, but no specific symptoms. The workers neglected the protective measures at their working-place. 12 of 17 workers had lead-concentrations above 400 microg/l (Reference < 90 microg/l). 10 of 17 patients showed an increased level of free protoporphyrins and all workers showed a decreased activity of delta-aminolaevulinacid-dehydratase (ALAD). Patients with lead-concentration above 700 microg/l were treated with the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA) 3 x 200 mg/d for nine days. The patients with lead concentrations between 400 and 700 microg/l were treated which DMSA 3 x 100 mg/d. After the DMSA-treatment the lead-concentrations had dropped (p < 0.001). During the DMSA-therapy one patient had to be treated in the hospital because of a generalised allergic exanthema. We report seventeen patients with high lead concentration in their blood due to occupational exposure. The high blood lead levels showed that the workers had not been protected adequately. This examplifies that occupational lead exposure still occurs, also in Germany. By patients with unspecific symptoms connected with lead exposure a biomonitoring for lead is necessary.

Human herpes virus type 6 can cause skin lesions at the BCG inoculation site similar to Kawasaki Disease.

PubMed

Kakisaka, Yosuke; Ohara, Tomoichiro; Katayama, Saori; Suzuki, Tasuku; Sasai, Shu; Hino-Fukuyo, Naomi; Kure, Shigeo

2012-12-01

Kawasaki Disease (KD) is acute, febrile, multisystem vasculitis of early childhood, the detailed mechanism of which is still unclear. Skin symptoms occur in KD, such as edema of the hands and feet with subsequent desquamation and redness at the inoculation site of bacillus Calmette-Guerin (BCG). The change at the BCG inoculation site has been considered as a specific feature of KD, although its mechanism is not fully understood. We present an 11-month-old boy who developed fever with redness of the BCG site due to infection with human herpes virus type 6 (HHV6). At the age of 3 months, the patient received BCG. His fever remitted 7 days after the onset of skin redness, with sequential desquamation at the BCG site and extremities, which is not a common feature of HHV6 infection that typically lasts for 3 days. The final diagnosis was exanthema subitum. Characteristically, the HHV6 infection in our patient appeared to be associated with the invigoration of the T cell system, as represented by the elevated serum levels of soluble interleukin-2 receptor (3,490 U/ml vs. normal range 145-519 U/ml). This patient clearly showed redness and crusting at the BCG inoculation site, suggesting that HHV6 infection might cause skin changes similar to those of KD via an unknown mechanism. In addition, we suggest that the activation of the T cell system may account for the skin lesions in KD, characterized by redness and subsequent crusting of the BCG inoculation site and desquamation of the extremities.

[Detection of rubella virus RNA in clinical material by real time polymerase chain reaction method].

PubMed

Domonova, É A; Shipulina, O Iu; Kuevda, D A; Larichev, V F; Safonova, A P; Burchik, M A; Butenko, A M; Shipulin, G A

2012-01-01

Development of a reagent kit for detection of rubella virus RNA in clinical material by PCR-RT. During development and determination of analytical specificity and sensitivity DNA and RNA of 33 different microorganisms including 4 rubella strains were used. Comparison of analytical sensitivity of virological and molecular-biological methods was performed by using rubella virus strains Wistar RA 27/3, M-33, "Orlov", Judith. Evaluation of diagnostic informativity of rubella virus RNAisolation in various clinical material by PCR-RT method was performed in comparison with determination of virus specific serum antibodies by enzyme immunoassay. A reagent kit for the detection of rubella virus RNA in clinical material by PCR-RT was developed. Analytical specificity was 100%, analytical sensitivity - 400 virus RNA copies per ml. Analytical sensitivity of the developed technique exceeds analytical sensitivity of the Vero E6 cell culture infection method in studies of rubella virus strains Wistar RA 27/3 and "Orlov" by 11g and 31g, and for M-33 and Judith strains is analogous. Diagnostic specificity is 100%. Diagnostic specificity for testing samples obtained within 5 days of rash onset: for peripheral blood sera - 20.9%, saliva - 92.5%, nasopharyngeal swabs - 70.1%, saliva and nasopharyngeal swabs - 97%. Positive and negative predictive values of the results were shown depending on the type of clinical material tested. Application of reagent kit will allow to increase rubella diagnostics effectiveness at the early stages of infectious process development, timely and qualitatively perform differential diagnostics of exanthema diseases, support tactics of anti-epidemic regime.

Diagnostic evaluation of a multiplexed RT-PCR microsphere array assay for the detection of foot-and-mouth disease virus and look-alike disease viruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hindson, B J; Reid, S M; Baker, B R

2007-07-26

A high-throughput multiplexed assay was developed for the differential laboratory diagnosis of foot-and-mouth disease virus (FMDV) from viruses which cause clinically similar diseases of livestock. This assay simultaneously screens for five RNA and two DNA viruses using multiplexed reverse transcription PCR (mRT-PCR) amplification coupled with a microsphere hybridization array and flow-cytometric detection. Two of the seventeen primer-probe sets included in this multiplex assay were adopted from previously characterized real-time RT-PCR (rRT-PCR) assays for FMDV. The diagnostic accuracy of the mRT-PCR was evaluated using 287 field samples, including 248 (true positive n= 213, true negative n=34) from suspect cases of foot-and-mouthmore » disease collected from 65 countries between 1965 and 2006 and 39 true negative samples collected from healthy animals. The mRT-PCR assay results were compared with two singleplex rRT-PCR assays, using virus isolation with antigen-ELISA as the reference method. The diagnostic sensitivity of the mRT-PCR assay for FMDV was 93.9% [95% C.I. 89.8-96.4%], compared to 98.1% [95% C.I. 95.3-99.3%] for the two singleplex rRT-PCR assays used in combination. In addition, the assay could reliably differentiate between FMDV and other vesicular viruses such as swine vesicular disease virus and vesicular exanthema of swine virus. Interestingly, the mRT-PCR detected parapoxvirus (n=2) and bovine viral diarrhea virus (n=2) in clinical samples, demonstrating the screening potential of this mRT-PCR assay to identify viruses in FMDV-negative material not previously recognized using focused single-target rRT-PCR assays.« less

Diagnostic evaluation of a multiplexed RT-PCR microsphere array assay for the detection of foot-and-mouth and look-alike disease viruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hindson, B J; Baker, B R; Bentley Tammero, L F

2007-09-18

A high-throughput multiplexed assay (Multiplex Version 1.0) was developed for the differential laboratory diagnosis of foot-and-mouth disease virus (FMDV) from viruses which cause clinically similar diseases of livestock. This assay simultaneously screens for five RNA and two DNA viruses using multiplexed reverse transcription PCR (mRT-PCR) amplification coupled with a microsphere hybridization array and flow-cytometric detection. Two of the seventeen primer-probe sets included in this multiplex assay were adopted from previously characterized real-time RT-PCR (rRT-PCR) assays for FMDV. The diagnostic accuracy of the mRT-PCR was evaluated using 287 field samples, including 248 (true positive n= 213, true negative n=34) from suspectmore » cases of foot-and-mouth disease collected from 65 countries between 1965 and 2006 and 39 true negative samples collected from healthy animals. The mRT-PCR assay results were compared with two singleplex rRT-PCR assays, using virus isolation with antigen-ELISA as the reference method. The diagnostic sensitivity of the mRT-PCR assay for FMDV was 93.9% [95% C.I. 89.8-96.4%], compared to 98.1% [95% C.I. 95.3-99.3%] for the two singleplex rRTPCR assays used in combination. In addition, the assay could reliably differentiate between FMDV and other vesicular viruses such as swine vesicular disease virus and vesicular exanthema of swine virus. Interestingly, the mRT-PCR detected parapoxvirus (n=2) and bovine viral diarrhea virus (n=2) in clinical samples, demonstrating the screening potential of this mRT-PCR assay to identify viruses in FMDV-negative material not previously recognized using focused single-target rRT-PCR assays.« less

Secondary pulmonary syphilis: Case report and review of literature.

PubMed

Kassem Youssef, H; Blind, A; Chouta Ngaha, F; Drenou, B; Nojavan, H; Michel, C

2018-04-01

Syphilis is a sexually transmitted disease that can affect numerous organs in its secondary or tertiary stages. We describe a case of secondary syphilis with pulmonary involvement and we present a literature review. A 69-year-old male patient was admitted to hospital for dyspnoea and extended papular exanthema with palmoplantar involvement. The serological test for syphilis was positive. Ocular examination showed bilateral papillitis and retinal haemorrhage. Chest radiography revealed an interstitial alveolar infiltrate predominantly in the upper lobes, mild pleural effusion and hilar adenopathy. These infiltrates were slightly hypermetabolic on PET scan suggesting inflammatory or infectious origin. Treatment with intravenous penicillin G was effective on cutaneous, ocular and pulmonary manifestations. Lung involvement in secondary syphilis is poorly known and rarely described. We found 27 cases of pulmonary syphilis reported in English and the main European languages since 1967. Mean age at diagnosis was 46 years with clear male predominance (89%). HIV co-infection was declared in 5 cases. Treponema pallidum was found in 6 patients using PCR on bronchoalveolar lavage (BAL) (3 patients) or on a lung biopsy (1 patient), immunohistochemistry (IHC) on BAL (1 patient) and Giemsa staining on a pleural fluid sample (1 patient). Chest X-rays may show unilateral or bilateral infiltrates or nodules with or without pleural effusion or hilar adenopathy. Sub-pleural involvement is frequent and penicillin is the treatment of choice. Pulmonary syphilitic involvement should be suspected where pulmonary symptoms or radiological changes occur in secondary syphilis. IHC, special staining or PCR on BAL, pleural fluid or lung tissue are useful for the identification of spirochetes. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

In vitro comparison of acyclovir, ganciclovir and cidofovir against equid alphaherpesvirus 3 and evaluation of their efficacy against six field isolates.

PubMed

Vissani, María A; Zabal, Osvaldo; Tordoya, María S; Parreño, Viviana; Thiry, Etienne; Barrandeguy, María

2018-05-17

Equid alphaherpesvirus 3 (EHV3) is the etiological agent of equine coital exanthema (ECE), which is a venereal, highly contagious disease, characterized by the formation of papules, vesicles, pustules and ulcers on the external genitalia of mares and stallions. EHV3 remains in a latent state after a successful infection and there are latently infected animals in which the virus is reactivated and generally re-excreted subclinically. There are no available vaccines for this condition and prevention is based on the clinical examination of mares prior to mating, which allows to segregate those showing clinical signs. As this approach does not eliminate the risk of contagion in stallions from subclinically infected mares, there is a need for a specific EHV3 treatment. Nowadays, there exist various antiviral compounds of proven effectiveness for other alphaherpesviruses affecting humans and animals. The aim of the present study was to compare the efficacy of three antiviral compounds, acyclovir, ganciclovir and cidofovir against EHV3 in vitro, and to assess their efficacy against six EHV3 Argentinian field isolates. To determine the efficacy of these compounds in vitro, three parameters were analyzed: reduction of plaque number, reduction of plaque size and reduction of viral production. Additionally, the effectiveness of the three compounds at an optimum concentration previously determined in this study was investigated for the EHV3 field isolates. Based on our results, ganciclovir was the most potent antiviral compound to reduce EHV3 replication in vitro and may thus be a valuable candidate for treatment and prevention of ECE in mares and stallions. Copyright © 2018 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Genome-Wide Comparison of Cowpox Viruses Reveals a New Clade Related to Variola Virus

PubMed Central

Kurth, Andreas; Nitsche, Andreas

2013-01-01

Zoonotic infections caused by several orthopoxviruses (OPV) like monkeypox virus or vaccinia virus have a significant impact on human health. In Europe, the number of diagnosed infections with cowpox viruses (CPXV) is increasing in animals as well as in humans. CPXV used to be enzootic in cattle; however, such infections were not being diagnosed over the last decades. Instead, individual cases of cowpox are being found in cats or exotic zoo animals that transmit the infection to humans. Both animals and humans reveal local exanthema on arms and legs or on the face. Although cowpox is generally regarded as a self-limiting disease, immunosuppressed patients can develop a lethal systemic disease resembling smallpox. To date, only limited information on the complex and, compared to other OPV, sparsely conserved CPXV genomes is available. Since CPXV displays the widest host range of all OPV known, it seems important to comprehend the genetic repertoire of CPXV which in turn may help elucidate specific mechanisms of CPXV pathogenesis and origin. Therefore, 22 genomes of independent CPXV strains from clinical cases, involving ten humans, four rats, two cats, two jaguarundis, one beaver, one elephant, one marah and one mongoose, were sequenced by using massive parallel pyrosequencing. The extensive phylogenetic analysis showed that the CPXV strains sequenced clearly cluster into several distinct clades, some of which are closely related to Vaccinia viruses while others represent different clades in a CPXV cluster. Particularly one CPXV clade is more closely related to Camelpox virus, Taterapox virus and Variola virus than to any other known OPV. These results support and extend recent data from other groups who postulate that CPXV does not form a monophyletic clade and should be divided into multiple lineages. PMID:24312452

RASopathic Skin Eruptions during Vemurafenib Therapy

PubMed Central

Rinderknecht, Jeannine D.; Goldinger, Simone M.; Rozati, Sima; Kamarashev, Jivko; Kerl, Katrin; French, Lars E.

2013-01-01

Purpose Vemurafenib is a potent inhibitor of V600 mutant BRAF with significant impact on progression-free and overall survival in advanced melanoma. Cutaneous side effects are frequent. This single-center observational study investigates clinical and histological features of these class-specific cutaneous adverse reactions. Patients and Methods Patients were all treated with Vemurafenib 960 mg b.i.d. within local ethic committees approved clinical trials. All skin reactions were collected and documented prospectively. Cutaneous reactions were classified by reaction pattern as phototoxic and inflammatory, hair and nail changes, keratinocytic proliferations and melanocytic disorders. Results Vemurafenib was well tolerated, only in two patients the dose had to be reduced to 720 mg due to arthralgia. 26/28 patients (93%) experienced cutaneous side effects. Observed side effects included UVA dependent photosensitivity (n = 16), maculopapular exanthema (n = 14), pruritus (n = 8), folliculitis (n = 5), burning feet (n = 3), hair thinning (mild alopecia) (n = 8), curly hair (n = 2) and nail changes (n = 2). Keratosis pilaris and acanthopapilloma were common skin reactions (n = 12/n = 13), as well as plantar hyperkeratosis (n = 4), keratoacanthoma (n = 5) and invasive squamous cell carcinoma (n = 4). One patient developed a second primary melanoma after more than 4 months of therapy (BRAF and RAS wild type). Conclusion Vemurafenib has a broad and peculiar cutaneous side effect profile involving epidermis and adnexa overlapping with the cutaneous manifestations of genetic diseases characterized by activating germ line mutations of RAS (RASopathy). They must be distinguished from allergic drug reaction. Regular skin examination and management by experienced dermatologists as well as continuous prophylactic photo protection including an UVA optimized sun screen is mandatory. PMID:23516541

Clinical features and phylogenetic analysis of Coxsackievirus A9 in Northern Taiwan in 2011

PubMed Central

2013-01-01

Background Coxsackievirus A9 (CA9) was one of the most prevalent serotype of enteroviral infections in Taiwan in 2011. After several patient series were reported in the 1960s and 1970s, few studies have focused on the clinical manifestations of CA9 infections. Our study explores and deepens the current understanding of CA9. Methods We analyzed the clinical presentations of 100 culture-proven CA9-infected patients in 2011 by reviewing their medical records and depicted the CA9 phylogenetic tree. Results Of the 100 patients with culture-proven CA9 infections, the mean (SD) age was 4.6 (3.4) years and the male to female ratio was 1.9. For clinical manifestations, 96 patients (96%) had fever and the mean (SD) duration of fever was 5.9 (3.4) days. Sixty one patients (61%) developed a skin rash, and the predominant pattern was a generalized non-itchy maculopapular rash without vesicular changes. While most patients showed injected throat, oral ulcers were found in only 19 cases (19%), among whom, 6 were diagnosed as herpangina. Complicated cases included: aseptic meningitis (n=8), bronchopneumonia (n=6), acute cerebellitis (n=1), and polio-like syndrome (n=1). Phylogenetic analysis for current CA9 strains is closest to the CA9 isolate 27-YN-2008 from the border area of mainland China and Myanmar. Conclusions The most common feature of CA9 during the 2011 epidemic in Taiwan is generalized febrile exanthema rather than herpangina or hand, foot, and mouth disease. Given that prolonged fever and some complications are possible, caution should be advised in assessing patients as well as in predicting the clinical course. PMID:23347781

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.

Hypersensitivity reactions to non-steroidal anti-inflammatory drugs.

PubMed

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

2009-11-01

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

Schizophrenia or Atypical Lupus Erythematosus with Predominant Psychiatric Manifestations over 25 Years: Case Analysis and Review

PubMed Central

Mack, Axel; Pfeiffer, Christiane; Schneider, E. Marion; Bechter, Karl

2017-01-01

We observed a case over 25 years of relapsing–remitting schizophrenic spectrum disorder, varying regarding the main symptomatology between more depressive or more schizoaffective or rather typical schizophrenic syndrome. Diseased phases were repeatedly accompanied by minor skin lesions, which were initially classified as mixed tissue disorder. Psychotic phases were waxing–waning over years. During one later relapse, skin involvement was severe, classified to likely represent an allergic reaction to psychopharmaca; this generalized exanthema remitted rapidly with cortisone treatment and azathioprine. Under continued azathioprine and low dose neuroleptics, the patient remitted completely, appearing psychiatrically healthy for 16 years. When azathioprine was set off due to pregnancy, an extraordinary severe relapse of schizophrenia like psychosis accompanied by most severe skin lesions developed within a few weeks, then requiring 2 years of psychiatric inpatient treatment. Finally, a diagnosis of systemic lupus erythematodes plus neuropsychiatric lupus was made. A single CSF sample in 2013 showed suspicious biomarkers, matching with CSF cytokine profiling in schizophrenic and affective spectrum disorder patients and indicated mild neuroinflammation. Complex immune suppressive treatment was reinitiated short after relapse, but was only partially successful. However, surprisingly the psychosis and skin lesions remitted (in parallel) when belimumab was given (add-on). The very details of this complicated, long-term disease course are discussed also with regard to general ideas, in particular with respect to the question if this case of seemingly comorbid schizophrenia with minor autoimmunity signs represented a case of one emerging autoimmune disorder with variant manifestations systemically and within the CNS, though atypically with predominant appearance as a schizophrenia spectrum disorder. PMID:28798699

Genome-wide comparison of cowpox viruses reveals a new clade related to Variola virus.

PubMed

Dabrowski, Piotr Wojtek; Radonić, Aleksandar; Kurth, Andreas; Nitsche, Andreas

2013-01-01

Zoonotic infections caused by several orthopoxviruses (OPV) like monkeypox virus or vaccinia virus have a significant impact on human health. In Europe, the number of diagnosed infections with cowpox viruses (CPXV) is increasing in animals as well as in humans. CPXV used to be enzootic in cattle; however, such infections were not being diagnosed over the last decades. Instead, individual cases of cowpox are being found in cats or exotic zoo animals that transmit the infection to humans. Both animals and humans reveal local exanthema on arms and legs or on the face. Although cowpox is generally regarded as a self-limiting disease, immunosuppressed patients can develop a lethal systemic disease resembling smallpox. To date, only limited information on the complex and, compared to other OPV, sparsely conserved CPXV genomes is available. Since CPXV displays the widest host range of all OPV known, it seems important to comprehend the genetic repertoire of CPXV which in turn may help elucidate specific mechanisms of CPXV pathogenesis and origin. Therefore, 22 genomes of independent CPXV strains from clinical cases, involving ten humans, four rats, two cats, two jaguarundis, one beaver, one elephant, one marah and one mongoose, were sequenced by using massive parallel pyrosequencing. The extensive phylogenetic analysis showed that the CPXV strains sequenced clearly cluster into several distinct clades, some of which are closely related to Vaccinia viruses while others represent different clades in a CPXV cluster. Particularly one CPXV clade is more closely related to Camelpox virus, Taterapox virus and Variola virus than to any other known OPV. These results support and extend recent data from other groups who postulate that CPXV does not form a monophyletic clade and should be divided into multiple lineages.

Clinical characteristics and molecular epidemiology of Enterovirus infection in infants <3 months in a referral paediatric hospital of Barcelona.

PubMed

Rodà, Diana; Pérez-Martínez, Esther; Cabrerizo, María; Trallero, Gloria; Martínez-Planas, Aina; Luaces, Carles; García-García, Juan-José; Muñoz-Almagro, Carmen; Launes, Cristian

2015-11-01

Enterovirus (EV) infection is common in infants, but the information with regard to the molecular epidemiology and the associations between types and clinical variables is very scarce. This study includes 195 children <3 months old with fever, attended from March 2010 to December 2012 in an emergency department of a tertiary paediatric hospital in whom EV infection was confirmed by real-time PCR in blood and/or cerebrospinal fluid. Clinical and epidemiological data was prospectively collected. In 152 (77.9 %) patients, EVs could be typed. The most common type was Echovirus-5 (E5; 32, 21.1 %), followed by Echovirus-11 (E11; 18, 11.8 %), Echovirus-21 and Echovirus-25 (E21, E25; 11 each one, 7.2 %) and Coxsackievirus-B4 (CVB4; 6, 6.6 %). The majority of types appeared in spring, but E5 and E25 were found mainly during summer (p < 0.01). E21 was associated with high-grade fever (p < 0.01); E5 with exanthema (p = 0.03) and CVB4 tended to cause meningitis more often than the other types (p = 0.07). The most common EV types were Echovirus-5 and Echovirus-11. Some significant associations between types and epidemiologic and clinical findings were observed. What is Known-What is New • Enteroviruses cause a normally benign illness in young infants, except in some cases. • The molecular epidemiology of Enterovirus infection is not well known in European countries. • This study describes a large number of infants with Enterovirus infection and shows the seasonality of different types, and their associations with epidemiologic and clinical variables.

The HLA-A*31:01 allele: influence on carbamazepine treatment

PubMed Central

Yip, Vincent Lai Ming; Pirmohamed, Munir

2017-01-01

Carbamazepine (CBZ) is an effective anticonvulsant that can sometimes cause hypersensitivity reactions that vary in frequency and severity. Strong associations have been reported between specific human leukocyte antigen (HLA) alleles and susceptibility to CBZ hypersensitivity reactions. Screening for HLA-B*15:02 is mandated in patients from South East Asia because of a strong association with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). HLA-A*31:01 predisposes to multiple phenotypes of CBZ hypersensitivity including maculopapular exanthema, hypersensitivity syndrome, and SJS/TEN in a range of populations including Europeans, Japanese, South Koreans and Han Chinese, although the effect size varies between the different phenotypes and populations. Between 47 Caucasians and 67 Japanese patients would need to be tested for HLA-A*31:01 in order to avoid a single case of CBZ hypersensitivity. A cost-effectiveness study has demonstrated that HLA-A*31:01 screening would be cost-effective. Patient preference assessment has also revealed that patients prefer pharmacogenetic screening and prescription of alternative anticonvulsants compared to current standard of practice without pharmacogenetic testing. For patients who test positive for HLA-A*31:01, alternative treatments are available. When alternatives have failed or are unavailable, HLA-A*31:01 testing can alert clinicians to 1) patients who are at increased risk of CBZ hypersensitivity who can then be targeted for more intensive monitoring and 2) increase diagnostic certainty in cases where hypersensitivity has already occurred, so patients can be advised to avoid structurally related drugs in the future. On the basis of the current evidence, we would favor screening all patients for HLA-A*31:01 and HLA-B*15:02 prior to starting CBZ therapy. PMID:28203102

Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016: A GeoSentinel Analysis.

PubMed

Hamer, Davidson H; Barbre, Kira A; Chen, Lin H; Grobusch, Martin P; Schlagenhauf, Patricia; Goorhuis, Abraham; van Genderen, Perry J J; Molina, Israel; Asgeirsson, Hilmir; Kozarsky, Phyllis E; Caumes, Eric; Hagmann, Stefan H; Mockenhaupt, Frank P; Eperon, Gilles; Barnett, Elizabeth D; Bottieau, Emmanuel; Boggild, Andrea K; Gautret, Philippe; Hynes, Noreen A; Kuhn, Susan; Lash, R Ryan; Leder, Karin; Libman, Michael; Malvy, Denis J M; Perret, Cecilia; Rothe, Camilla; Schwartz, Eli; Wilder-Smith, Annelies; Cetron, Martin S; Esposito, Douglas H

2017-01-17

Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Descriptive, using GeoSentinel records. 63 travel and tropical medicine clinics in 30 countries. Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. Frequencies of demographic, trip, and clinical characteristics and complications. Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain-Barré syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission. Centers for Disease Control and Prevention, International Society of Travel Medicine, and Public Health Agency of Canada.

Missed opportunities in the diagnosis of human immunodeficiency virus infection in the Region of Aragon. Late diagnosis importance.

PubMed

Gargallo-Bernad, César; Sangrós-González, Francisco Javier; Arazo-Garcés, Piedad; Martínez-Álvarez, Rosa; Malo-Aznar, Carmen; Gargallo-Bernad, Alicia; Ballester-Luna, Alba; Cabrero-Pascual, Luis Eduardo; Gil-Orna, Pablo; Abadía-Gallego, Víctor José; Torres-Peña, Isabel; Ordiz-Suárez, Héctor

2018-04-30

Late Diagnosis (LD) of Human Immunodeficiency Virus (HIV) infection (CD4 lymphocytes <350/μl at diagnosis of the disease), deteriorates the condition of those affected and increases the probability of transmission. The objective of the present study was to analyse the prevalence of LD, to identify missed diagnostic opportunities (MDO) and to find out which level of the health care delivery system they took place. Retrospective, observational and descriptive study of the population diagnosed with infection of HIV/AIDS in the period 2011-2015 in Aragon. MDO were identified during the 3 years prior to diagnosis of the disease in all levels of the health care delivery system as well as frequentation of consultations. The indicator conditions (IC) that generated more MDO were analysed according to the latest recommendations for early diagnosis of HIV in the health care setting. 435 newly diagnosed HIV/AIDS cases were analysed. 45.1% were diagnosed in Primary Healthcare (PH). 49.4% presented criteria of LD and 61.1% were infected through heterosexual contact. The majority of MDO (68.5%) were given in PH. The IC that generated the most MDO were seborrheic dermatitis/exanthema (19.4%) and fever of unknown origin (10.3%). However, the IC that were associated with higher LD were pneumonia acquired in the community and unjustified weight loss. In Aragon, prevalence of LD is high, the main route of infection is heterosexual and most of MDO go unnoticed in PH. The dissemination of current guidelines for requesting IC guided HIV testing and HIV screening across the preoperative period will result in an effective measure to decrease the LD. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Natural History of Benign Nonimmediate Allergy to Beta-Lactams in Children: A Prospective Study in Retreated Patients After a Positive and a Negative Provocation Test.

PubMed

Tonson la Tour, Aude; Michelet, Marine; Eigenmann, Philippe A; Caubet, Jean-Christoph

2017-11-23

The drug provocation test (DPT) is considered as the gold standard to diagnose drug allergy and is particularly important in the diagnosis of nonimmediate beta-lactam (BL) allergy in children. The natural history of BL allergy remains unknown. Our main aim was to evaluate the natural history of nonimmediate BL hypersensitivity and the long-term tolerance acquisition, and our secondary objective was to determine the negative predictive value (NPV) of the DPT following a 2-day protocol. Children developing a benign rash while treated by BL were prospectively recruited at the Emergency Department of the Geneva University Hospital from 2006 to 2011 and challenged with the incriminated BL (initial diagnostic drug provocation test [idDPT]) following a 2-day protocol. In case of a positive idDPT, the patients underwent a follow-up drug provocation test (fuDPT) 3 years later. In case of a negative idDPT, we sent a questionnaire to assess tolerance of a subsequent treatment with the incriminated BL. Among the 18 children with a positive idDPT, 16 children (89%) had a negative fuDPT and 2 children developed a benign exanthema. Among those 16 children, 11 tolerated a subsequent treatment with the incriminated BL without any reaction, suggesting natural antibiotic tolerance acquisition. From another point of view, we found that the NPV of the DPT following a 2-day protocol was excellent at 96.7%. Our data strongly suggest that a fuDPT is safe and useful to assess tolerance acquisition in children with a confirmed benign nonimmediate BL allergy. In addition, our results support the use of a short DPT protocol (2 days), which led to a high NPV of 96.7% in our population, with a favorable benefit-risk balance. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Survival of viral pathogens in animal feed ingredients under transboundary shipping models

PubMed Central

Bauermann, Fernando V.; Niederwerder, Megan C.; Singrey, Aaron; Clement, Travis; de Lima, Marcelo; Long, Craig; Patterson, Gilbert; Sheahan, Maureen A.; Stoian, Ana M. M.; Petrovan, Vlad; Jones, Cassandra K.; De Jong, Jon; Ji, Ju; Spronk, Gordon D.; Minion, Luke; Christopher-Hennings, Jane; Zimmerman, Jeff J.; Rowland, Raymond R. R.; Nelson, Eric; Sundberg, Paul; Diel, Diego G.

2018-01-01

The goal of this study was to evaluate survival of important viral pathogens of livestock in animal feed ingredients imported daily into the United States under simulated transboundary conditions. Eleven viruses were selected based on global significance and impact to the livestock industry, including Foot and Mouth Disease Virus (FMDV), Classical Swine Fever Virus (CSFV), African Swine Fever Virus (ASFV), Influenza A Virus of Swine (IAV-S), Pseudorabies virus (PRV), Nipah Virus (NiV), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), Swine Vesicular Disease Virus (SVDV), Vesicular Stomatitis Virus (VSV), Porcine Circovirus Type 2 (PCV2) and Vesicular Exanthema of Swine Virus (VESV). Surrogate viruses with similar genetic and physical properties were used for 6 viruses. Surrogates belonged to the same virus families as target pathogens, and included Senecavirus A (SVA) for FMDV, Bovine Viral Diarrhea Virus (BVDV) for CSFV, Bovine Herpesvirus Type 1 (BHV-1) for PRV, Canine Distemper Virus (CDV) for NiV, Porcine Sapelovirus (PSV) for SVDV and Feline Calicivirus (FCV) for VESV. For the remaining target viruses, actual pathogens were used. Virus survival was evaluated using Trans-Pacific or Trans-Atlantic transboundary models involving representative feed ingredients, transport times and environmental conditions, with samples tested by PCR, VI and/or swine bioassay. SVA (representing FMDV), FCV (representing VESV), BHV-1 (representing PRV), PRRSV, PSV (representing SVDV), ASFV and PCV2 maintained infectivity during transport, while BVDV (representing CSFV), VSV, CDV (representing NiV) and IAV-S did not. Notably, more viruses survived in conventional soybean meal, lysine hydrochloride, choline chloride, vitamin D and pork sausage casings. These results support published data on transboundary risk of PEDV in feed, demonstrate survival of certain viruses in specific feed ingredients (“high-risk combinations”) under conditions simulating transport between continents and provide further evidence that contaminated feed ingredients may represent a risk for transport of pathogens at domestic and global levels. PMID:29558524

CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

PubMed

Morel, Esther; Escamochero, Salvador; Cabañas, Rosario; Díaz, Rosa; Fiandor, Ana; Bellón, Teresa

2010-03-01

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are severe, bullous cutaneous diseases with uncertain pathogenesis, although cytotoxic T cells seem to be involved. Natural killer (NK)-like activity has been found in blister infiltrates. Cytotoxic T lymphocytes (CTLs) with NK-like activity (NK-CTLs) have been shown to express T-cell receptors restricted by the HLA-Ib molecule HLA-E. Alternatively, the HLA-E-specific activating receptor CD94/NKG2C can trigger T-cell receptor-independent cytotoxicity in CTLs. Our aim was to test whether HLA-E expression sensitizes keratinocytes to killing by CTLs with NK-like activity and to explore the expression of activating receptors specific for HLA-E in blister cytotoxic lymphocytes. We used flow cytometry and immunohistochemistry to analyze HLA-E expression in keratinocytes from affected skin in patients with SJS, TEN, and other less severe drug-induced exanthemas. The expression of CD94/NKG2C was analyzed by means of flow cytometry in PBMCs and blister cells from patients. PBMCs and blister cells were analyzed for their ability to kill HLA-E-expressing cells. Involvement of CD94/NKG2C in triggering degranulation of cytolytic cells was explored by means of CD107a mobilization assays and standard cytotoxicity chromium release assays. We found that keratinocytes from affected skin expressed HLA-E and that cell-surface HLA-E sensitizes keratinocytes to killing by CD94/NKG2C(+) CTLs. Frequencies of CD94/NKG2C(+) peripheral blood T and NK cells were increased in patients with SJS and TEN during the acute phase. Moreover, activated blister T and NK lymphocytes expressed CD94/NKG2C and were able to degranulate in response to HLA-E(+) cells in an NKG2C-dependent manner. CD94/NKG2C might be involved in triggering cytotoxic lymphocytes in patients with SJS and TEN.

Dengue, chikungunya, and Zika virus infections imported to Paris between 2009 and 2016: Characteristics and correlation with outbreaks in the French overseas territories of Guadeloupe and Martinique.

PubMed

Vasquez, Victor; Haddad, Elie; Perignon, Alice; Jaureguiberry, Stéphane; Brichler, Ségolène; Leparc-Goffart, Isabelle; Caumes, Eric

2018-07-01

Dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) infections are rapidly expanding across countries and are being diagnosed in returned travellers who represent epidemiological sentinels. The French Territories of America (FTA) such as Guadeloupe and Martinique see high levels of tourism and have experienced three consecutive outbreaks by these viruses in the last decade. This study was performed to evaluate how ill returned travellers could have represented epidemiological sentinels for these three expanding arboviral diseases over eight consecutive years. The degree of correlation between the cases of ill returned travellers arriving at a French tertiary hospital in Paris and the three outbreaks that occurred in the FTA during the study period was estimated. All consecutive ill returned travellers diagnosed at the hospital in Paris with imported DENV, CHIKV, or ZIKV infections from January 2009 to December 2016 were included. Epidemiological and clinical variables were evaluated. Data concerning the incidence of arboviruses in the FTA, as well as the temporal relationship between the occurrence of imported cases and outbreaks in the FTA, were analyzed. Overall, 320 cases of arboviral infection were reported: 216 DENV, 68 CHIKV, and 36 ZIKV. Most of the patients presented with fever and exanthema. One hundred and fifteen patients were exposed in Guadeloupe or Martinique, which were the at-risk destinations in 25% of patients with DENV, 59% of patients with CHIKV, and 58% of patients with ZIKV. The occurrence of cases diagnosed in returning travellers followed the same time pattern as the outbreaks in these areas. A temporal correlation was found between newly diagnosed imported cases of arboviruses and the three corresponding outbreaks that occurred in Martinique and Guadeloupe during 8 consecutive years. Thus, ill returned travellers act as epidemiological sentinels from the beginning up to the end of outbreaks occurring in touristic locations. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prevalence and genotypic characterization of Human Parvovirus B19 in children with measles- and rubella-like illness in Iran.

PubMed

Rezaei, Farhad; Sarshari, Behrang; Ghavami, Nastaran; Meysami, Parisa; Shadab, Azadeh; Salimi, Hamid; Mokhtari-Azad, Talat

2016-06-01

Human Parvovirus B19 (B19V) is a prototype of the Erythroparvovirus genus in Parvoviridae family. B19V infections are often associated with fever and rash, and can be mistakenly reported as measles or rubella. Differential diagnosis of B19V illness is necessary for case management and also for public health control activities, particularly in outbreak situations in which measles or rubella is suspected. To investigate the causative role of B19V infection in children with measles- and rubella-like illness, a total of 583 sera from children with exanthema were tested for presence of B19V by determining anti-B19V IgG and IgM antibodies by ELISA as well as B19V DNA detection by nested PCR. DNA positive samples were assessed further for determination of viral load and sequence analysis by Real-Time PCR and Sanger sequencing method, respectively. Out of 583 patients, 112 (19.21%) patients were positive for B19V-IgM antibody, 110 (18.87%) were positive for B19V-IgG antibody, and 63 (10.81%) were positive for B19V viral DNA. The frequency of B19V-IgG antibodies were increased with age; that is children under 6 year old showed 7.11% seroprevalence for B19V-IgG as compared to 18.39% and 28.91% for age groups 6 to >11 and 11-14 years old, respectively. Phylogenetic analysis of the NS1-VPu1 overlapping region revealed that all sequenced B19V-DNA belonged to genotype 1. The results of this study may aid the surveillance programs aiming at eradicating measles/rubella virus in Iran, as infections with B19V can be mistakenly reported as measles or rubella if laboratory testing is not conducted. © 2015 Wiley Periodicals, Inc.

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

PubMed Central

Bonnafous, Pascale; Gautheret-Dejean, Agnès

2015-01-01

SUMMARY Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like other herpesviruses, induces a lifelong latent infection in humans. As a noticeable difference with respect to other human herpesviruses, genomic HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population. Although it is infrequent, this may be a confounding factor for the diagnosis of active viral infection. The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR. Many active HHV-6 infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. However, the virus may be the cause of serious diseases, particularly in immunocompromised individuals. As emblematic examples of HHV-6 pathogenicity, exanthema subitum, a benign disease of infancy, is associated with primary infection, whereas further virus reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients. Generally speaking, the formal demonstration of the causative role of HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous nature of the virus, chronicity of infection, existence of two distinct species, and limitations of current investigational tools. The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment, as well as the conditions of drug administration, are not formally approved to date. There are still numerous pending questions about HHV-6 which should stimulate future research works on the pathophysiology, diagnosis, and therapy of this remarkable human virus. PMID:25762531

Safety and tolerability of prescription omega-3 fatty acids: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Chang, Cheng-Ho; Tseng, Ping-Tao; Chen, Nai-Yu; Lin, Pei-Chin; Lin, Pao-Yen; Chang, Jane Pei-Chen; Kuo, Feng-Yu; Lin, Jenshinn; Wu, Ming-Chang; Su, Kuan-Pin

2018-02-01

Omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] are widely recommended for health promotion. Over the last decade, prescription omega-3 fatty acid products (RxOME3FAs) have been approved for medical indications. Nonetheless, there is no comprehensive analysis of safety and tolerability of RxOME3FAs so far. A systematic review of randomized controlled trials (RCTs) was carried out based on searches in six electronic databases. The studies involving marketed RxOME3FA products were included, and adverse-effect data were extracted for meta-analysis. Subgroup analysis and meta-regression were conducted to explore the sources of potential heterogeneity. Among the 21 included RCTs (total 24,460 participants; 12,750 from RxOME3FA treatment cohort and 11,710 from control cohort), there was no definite evidence of any RxOME3FA-emerging serious adverse event. Compared with the control group, RxOME3FAs were associated with more treatment-related dysgeusia (fishy taste; p = 0.011) and skin abnormalities (eruption, itching, exanthema, or eczema; p < 0.001). Besides, RxOME3FAs had mild adverse effects upon some non-lipid laboratory measurements [elevated fasting blood sugar (p = 0.005); elevated alanine transaminase (p = 0.022); elevated blood urea nitrogen (p = 0.047); decreased hemoglobin (p = 0.002); decreased hematocrit (p = 0.009)]. Subgroup analysis revealed that EPA/DHA combination products were associated with more treatment-related gastrointestinal adverse events [eructation (belching; p = 0.010); nausea (p = 0.044)] and low-density lipoprotein cholesterol elevation (p = 0.009; difference in means = 4.106mg/dL). RxOME3FAs are generally safe and well tolerated but not free of adverse effects. Post-marketing surveillance and observational studies are still necessary to identify long-term adverse effects and to confirm the safety and tolerability profiles of RxOME3FAs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Molecular epidemiology of enterovirus and parechovirus infections according to patient age over a 4-year period in Spain.

PubMed

Cabrerizo, María; Díaz-Cerio, María; Muñoz-Almagro, Carmen; Rabella, Núria; Tarragó, David; Romero, María Pilar; Pena, María José; Calvo, Cristina; Rey-Cao, Sonia; Moreno-Docón, Antonio; Martínez-Rienda, Inés; Otero, Almudena; Trallero, Gloria

2017-03-01

The epidemiology and clinical association of enterovirus (EV) and parechovirus (HPeV) infections, as well as the type-distribution-according-to-age, were determined during a 4-year study period in Spain. During 2010-2013, a total of 21,832 clinical samples were screened for EV and the detection frequency was 6.5% (1,430). Of the total EV-negative samples, only 1,873 samples from 2011 to 2013 were available for HPeV testing. HPeV was detected in 42 (2%) of them. Positive samples were genotyped using PCR and sequencing. EV infections occurred in all age groups of patients: neonates (17%), children 28 days to 2 years (29%), children 2-14 years (40%), and adults (14%). Thirty-four different EV types were identified. HPeV infections were detected exclusively in infants <8 m (70% neonates, P < 0.05). All but one HPeV were HPeV-3. Differences in type frequency detection were found according to age and clinical manifestation. Coxsackievirus (CV)-B4 (61%), CV-B5 (83%), and HPeV-3 (64%) were more frequent in neonates than in older patients (P < 0.05). Echovirus (E)-3 (60%), E-18 (47%), E-25 (62%), CV-A6 (61%), CV-A16 (72%), and EV-71 (75%) were mainly detected in children 28 days to 2 years (P < 0.05), whereas, E-6 (79%), E-20 (88%), and E-30 (85%) were predominant in children >2 years and adults (P < 0.05). Clinically, meningitis was associated with EV (P < 0.01) whereas, encephalitis was more frequent in HPeV-infected patients. CV-B types were associated with myocarditis (90%; P < 0.05) and EV species A with hand-foot-mouth-disease/atypical exanthema (88%; P < 0.05). J. Med. Virol. 89:435-442, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A retrospective study on sequential desensitization-rechallenge for antituberculosis drug allergy

PubMed Central

Chia, Faith Li-Ann; Tan, Sze-Chin; Tan, Teck-Choon; Leong, Khai-Pang; Tan, Justina Wei-Lyn; Tang, Chwee-Ying; Hou, Jin-Feng; Chan, Grace Yin-Lai; Chng, Hiok-Hee

2014-01-01

Background Antituberculosis (anti-TB) drug allergy often involves multiple concurrently administered drugs which subsequently need to be reinitiated as no better alternatives exist. Objective To describe the results of tailored sequential desensitization-rechallenge (D-R) for anti-TB drug allergy. Methods Consecutive patients who had undergone D-R to anti-TB drugs between 1 September 1997 and 31 January 2012 were recruited. Following resolution of the acute reaction, anti-TB drug was restarted at 1:6,000 to 1:3 of the final daily dose (FDD), with gradual single or multiple step daily dose escalation to the FDD. Subsequent drugs were sequentially added ≥3 days later when the preceding drug was tolerated. Full blood count and liver function tests were monitored prior to addition of each new drug. Results There were 11 patients of whom 10 were male, predominantly Chinese (8 patients). Regimens comprised at least 3 drugs: isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA), or streptomycin. All patients had nonimmediate reactions, with cutaneous eruptions, where maculopapular exanthema (MPE) was the most common (8 patients). Drug-induced hypersensitivity syndrome (DIHS) occurred in 6 patients, and Stevens Johnson syndrome (SJS) in 2 patients. D-R to INH was successful in 7/9 patients (77.8%) and to RIF/EMB/PZA/streptomycin in all. Of the 2 patients who failed INH D-R, 1 developed fever and MPE on day 3, the other MPE on day 8. D-R with INH and RIF respectively was successful in 2 patients with SJS. Among DIHS patients, 1 failed D-R with INH (fever and MPE on day 3). There were 23/25 (92%) successful D-R among the 11 patients. All patients completed TB treatment of ≥5 months' duration with no cases of drug-resistant TB. Conclusion Tailored sequential TB drug D-R is successful where no better alternative therapies are available, with careful dose escalation and close monitoring, and after a careful risk-benefit assessment. PMID:25097851

Absorption and retention of nickel from drinking water in relation to food intake and nickel sensitivity.

PubMed

Nielsen, G D; Søderberg, U; Jørgensen, P J; Templeton, D M; Rasmussen, S N; Andersen, K E; Grandjean, P

1999-01-01

Two studies were performed to examine the influence of fasting and food intake on the absorption and retention of nickel added to drinking water and to determine if nickel sensitization played any role in this regard. First, eight nonallergic male volunteers fasted overnight before being given nickel in drinking water (12 micrograms Ni/kg) and, at different time intervals, standardized 1400-kJ portions of scrambled eggs. When nickel was ingested in water 30 min or 1 h prior to the meal, peak nickel concentrations in serum occurred 1 h after the water intake, and the peak was 13-fold higher than the one seen 1 h after simultaneous intake of nickel-containing water and scrambled eggs. In the latter case, a smaller, delayed peak occurred 3 h after the meal. Median urinary nickel excretion half-times varied between 19.9 and 26.7 h. Within 3 days, the amount of nickel excreted corresponded to 2.5% of the nickel ingested when it was mixed into the scrambled eggs. Increasing amounts were excreted as the interval between the water and the meal increased, with 25.8% of the administered dose being excreted when the eggs were served 4 h prior to the nickel-containing drinking water. In the second experiment, a stable nickel isotope, 61Ni, was given in drinking water to 20 nickel-sensitized women and 20 age-matched controls, both groups having vesicular hand eczema of the pompholyx type. Nine of 20 nickel allergic eczema patients experienced aggravation of hand eczema after nickel administration, and three also developed a maculopapular exanthema. No exacerbation was seen in the control group. The course of nickel absorption and excretion in the allergic groups did not differ and was similar to the pattern seen in the first study, although the absorption in the women was less. A sex-related difference in gastric emptying rates may play a role. Thus, food intake and gastric emptying are of substantial significance for the bioavailability of nickel from aqueous solutions. Copyright 1999 Academic Press.

Clinical characteristics and treatment of severe encephalitis associated with neurogenic pulmonary edema caused by enterovirus 71 in China

PubMed Central

Zhang, Yu-cai; Li, Xing-wang; Zhu, Xiao-dong; Qian, Su-yun; Shang, Yun-xiao; Li, Bi-ru; Liu, Xiao-lin

2010-01-01

BACKGROUND: Hand-foot-mouth disease has become a major public health issue in children in China. In the present prospective study we investigated the clinical characteristics and emergency management of children with severe encephalitis associated with NPE caused by enterovirus 71. METHODS: The study was conducted in 2 pediatric intensive care units (PICUs) over a 2-month period. Clinical records were reviewed of critically ill children with severe encephalitis associated with NPE caused by EV71 who were admitted to PICUs during the period of May to June 2008 in Fuyang. RESULTS: We reviewed the complete records of 36 children, of whom 23 (63.9%) were male and 13 (36.1%) female. Their age ranged from 4 to 48 months, with an average of 15.8 months. All children except one were under 3 years of age. The overall mortality in these children was 19.4%. The average duration of critical life threatening signs and symptoms was 2.1 days (12 hours-5 days). Nervous system diseases included brainstem encephalitis in 27 children (75%), brainstem encephalitis associated with myelitis in 6 children (16.7%), and general encephalitis in 3 chidren (8.3%), respectively. In 12 patients of NPE (33.3%) pink or bloody bubble sputum and asymmetric pulmonary edema or hemorrhage was the primary manifestation but no typical exanthema was observed. Five children died of acute onset of NPE and / or pulmonary hemorrhage with rapid progression of cardiopulmonary failure within hours after admission. Therapeutic management consisted of mechanical ventilation and administration of mannitol, methylprednisolone, intravenous immunoglobulin (IVIG) and vasoactive drugs, associated with the need of fluid volume resuscitation in 9 (25%) of the 36 children. CONCLUSIONS: In children less than 3 years of age found to be affected by severe EV71 encephalitis associated with NPE, one fifth may die. The major organ systems infected by severe EV71 include the central nervous system, the respiratory system, and the cardiovascular system. Early diagnosis and evaluation, respiratory support, treatment of intracranial hypertension, and mainttenance of function of the cardiovascular system are the most important therapeutic measures. PMID:25214951

Imported Zika Virus in a European City: How to Prevent Local Transmission?

PubMed

Millet, Joan-Pau; Montalvo, Tomàs; Bueno-Marí, Ruben; Romero-Tamarit, Arancha; Prats-Uribe, Albert; Fernández, Lidia; Camprubí, Esteve; Del Baño, Lucía; Peracho, Victor; Figuerola, Jordi; Sulleiro, Elena; Martínez, Miguel J; Caylà, Joan A

2017-01-01

Background: On February 1st 2016 the WHO declared the Zika Virus (ZIKV) infection a worldwide public health emergency because of its rapid expansion and severe complications, such as Guillain-Barré Syndrome or microcephaly in newborn. The huge amount of people traveling to endemic areas and the presence of Aedes albopictus in Barcelona increase the risk of autochtonous transmission. The objective of this study was to describe the first ZIKV cases diagnosed in our city and to analyze the surveillance, prevention, and control measures implemented to avoid autochthonous transmission. Methods: An observational cross-sectional population-based study in Barcelona, Spain was performed.An analysis of the socio-demographic, epidemiological, clinical characteristics, and mosquito control activities of the ZIKV cases detected between January 1st and December 2016 was carried out using a specific ZIKV epidemiological survey of the Barcelona Public Health Agency. Results: A total of 118 notifications of possible ZIKV infections were received, and 44 corresponded to confirmed cases in Barcelona residents.Amongst these, the median age was 35 years and 57% were women. All cases were imported, 48% were Spanish-born and 52% foreign-born. Dominican Republic was the most visited country amongst foreign-born patients and Nicaragua amongst Spanish-born. The most frequent symptoms were exanthema, fever, and arthralgia. Among the 24 diagnosed women, 6 (25%) were pregnant. There was one case of microcephaly outside Barcelona city. Entomological inspections were done at the homes of 19 cases (43.2% of the total) and in 34 (77.3%) public spaces. Vector activity was found in one case of the 44 confirmed cases, and 134 surveillance and vector control were carried out associated to imported ZIKV cases. In all cases prevention measures were recommended to avoid mosquito bites on infected cases. Conclusion: Epidemiological and entomological surveillance are essential for the prevention of autochthonous transmission of arbovirosis that may have a great impact on Public Health.The good coordination between epidemiologists, entomologists, microbiologists, and clinicians is a priority in a touristic city with an intense relationship with endemic countries to minimize the risk of local transmission by competent vectors.

Imported Zika Virus in a European City: How to Prevent Local Transmission?

PubMed Central

Millet, Joan-Pau; Montalvo, Tomàs; Bueno-Marí, Ruben; Romero-Tamarit, Arancha; Prats-Uribe, Albert; Fernández, Lidia; Camprubí, Esteve; del Baño, Lucía; Peracho, Victor; Figuerola, Jordi; Sulleiro, Elena; Martínez, Miguel J.; Caylà, Joan A.; Álamo-Junquera, Dolores

2017-01-01

Background: On February 1st 2016 the WHO declared the Zika Virus (ZIKV) infection a worldwide public health emergency because of its rapid expansion and severe complications, such as Guillain-Barré Syndrome or microcephaly in newborn. The huge amount of people traveling to endemic areas and the presence of Aedes albopictus in Barcelona increase the risk of autochtonous transmission. The objective of this study was to describe the first ZIKV cases diagnosed in our city and to analyze the surveillance, prevention, and control measures implemented to avoid autochthonous transmission. Methods: An observational cross-sectional population-based study in Barcelona, Spain was performed.An analysis of the socio-demographic, epidemiological, clinical characteristics, and mosquito control activities of the ZIKV cases detected between January 1st and December 2016 was carried out using a specific ZIKV epidemiological survey of the Barcelona Public Health Agency. Results: A total of 118 notifications of possible ZIKV infections were received, and 44 corresponded to confirmed cases in Barcelona residents.Amongst these, the median age was 35 years and 57% were women. All cases were imported, 48% were Spanish-born and 52% foreign-born. Dominican Republic was the most visited country amongst foreign-born patients and Nicaragua amongst Spanish-born. The most frequent symptoms were exanthema, fever, and arthralgia. Among the 24 diagnosed women, 6 (25%) were pregnant. There was one case of microcephaly outside Barcelona city. Entomological inspections were done at the homes of 19 cases (43.2% of the total) and in 34 (77.3%) public spaces. Vector activity was found in one case of the 44 confirmed cases, and 134 surveillance and vector control were carried out associated to imported ZIKV cases. In all cases prevention measures were recommended to avoid mosquito bites on infected cases. Conclusion: Epidemiological and entomological surveillance are essential for the prevention of autochthonous transmission of arbovirosis that may have a great impact on Public Health.The good coordination between epidemiologists, entomologists, microbiologists, and clinicians is a priority in a touristic city with an intense relationship with endemic countries to minimize the risk of local transmission by competent vectors. PMID:28769893

Association of HLA-A and HLA-B Alleles with Lamotrigine-Induced Cutaneous Adverse Drug Reactions in the Thai Population

PubMed Central

Koomdee, Napatrupron; Pratoomwun, Jirawat; Jantararoungtong, Thawinee; Theeramoke, Voralaksana; Tassaneeyakul, Wichittra; Klaewsongkram, Jettanong; Rerkpattanapipat, Ticha; Santon, Siwalee; Puangpetch, Apichaya; Intusoma, Utcharee; Tempark, Therdpong; Deesudchit, Tayard; Satapornpong, Patompong; Visudtibhan, Anannit; Sukasem, Chonlaphat

2017-01-01

Background: Lamotrigine (LTG) is commonly used for treatment of epilepsy and bipolar disorder. It is one of the common cause of cutaneous adverse drug reactions (CADR). Clinical symptoms of LTG-induced CADR range from maculopapular exanthema (MPE) to severe cutaneous adverse reactions (SCAR). This study aimed to determine the association of the LTG-induced CADR with human leukocyte antigen (HLA) alleles in Thai patients. Methods: Fifteen patients with LTG-induced CADR [10 MPE; 4 Stevens–Johnson syndrome; and 1 drug reaction with eosinophilia and systemic symptoms] and 50 LTG-tolerant controls were included in the study. HLA-A and HLA-B genotyping was performed using polymerase chain reaction-sequence-specific oligonucleotides probes. Results: The proportion of HLA-A∗02:07 and HLA-B∗15:02 allele carriers were significantly higher in the LTG-induced CADR group than in the tolerant controls [odds ratio (OR): 7.83; 95% confidence interval (CI): 1.60–38.25; P = 0.013, and OR: 4.89; 95% CI: 1.28–18.67; P = 0.014]. In addition, subjects with HLA-A∗33:03, HLA-B∗15:02, and HLA-B∗44:03 were significantly higher in the LTG-induced MPE group than in the tolerant controls (OR: 8.27; 95% CI: 1.83–37.41; P = 0.005, OR: 7.33; 95% CI: 1.63–33.02; P = 0.005; and OR: 10.29; 95% CI: 1.45–72.81; P = 0.029). In contrast to the LTG-induced MPE group, there were no significant differences between HLA alleles and LTG-induced SCAR group. Conclusion: HLA-A∗02:07 and HLA-B∗15:02 were associated with LTG-induced CADR in Thai patients. We also identified an association between HLA-A∗33:03, HLA-B∗15:02, and HLA-B∗44:03 and LTG-induced MPE in this population. These results suggest that these alleles could be useful screening markers for preventing CADR before LTG treatment in Thai patients, but further replication studies with larger sample sizes are needed. PMID:29238301

The complete genome sequence of Yersinia pseudotuberculosis IP31758, the causative agent of Far East scarlet-like fever.

PubMed

Eppinger, Mark; Rosovitz, M J; Fricke, Wolfgang Florian; Rasko, David A; Kokorina, Galina; Fayolle, Corinne; Lindler, Luther E; Carniel, Elisabeth; Ravel, Jacques

2007-08-01

The first reported Far East scarlet-like fever (FESLF) epidemic swept the Pacific coastal region of Russia in the late 1950s. Symptoms of the severe infection included erythematous skin rash and desquamation, exanthema, hyperhemic tongue, and a toxic shock syndrome. The term FESLF was coined for the infection because it shares clinical presentations with scarlet fever caused by group A streptococci. The causative agent was later identified as Yersinia pseudotuberculosis, although the range of morbidities was vastly different from classical pseudotuberculosis symptoms. To understand the origin and emergence of the peculiar clinical features of FESLF, we have sequenced the genome of the FESLF-causing strain Y. pseudotuberculosis IP31758 and compared it with that of another Y. pseudotuberculosis strain, IP32953, which causes classical gastrointestinal symptoms. The unique gene pool of Y pseudotuberculosis IP31758 accounts for more than 260 strain-specific genes and introduces individual physiological capabilities and virulence determinants, with a significant proportion horizontally acquired that likely originated from Enterobacteriaceae and other soil-dwelling bacteria that persist in the same ecological niche. The mobile genome pool includes two novel plasmids phylogenetically unrelated to all currently reported Yersinia plasmids. An icm/dot type IVB secretion system, shared only with the intracellular persisting pathogens of the order Legionellales, was found on the larger plasmid and could contribute to scarlatinoid fever symptoms in patients due to the introduction of immunomodulatory and immunosuppressive capabilities. We determined the common and unique traits resulting from genome evolution and speciation within the genus Yersinia and drew a more accurate species border between Y. pseudotuberculosis and Y. pestis. In contrast to the lack of genetic diversity observed in the evolutionary young descending Y. pestis lineage, the population genetics of Y. pseudotuberculosis is more heterogenous. Both Y. pseudotuberculosis strains IP31758 and the previously sequenced Y. pseudotuberculosis strain IP32953 have evolved by the acquisition of specific plasmids and by the horizontal acquisition and incorporation of different genetic information into the chromosome, which all together or independently seems to potentially impact the phenotypic adaptation of these two strains.

A multiplex reverse transcription PCR and automated electronic microarray assay for detection and differentiation of seven viruses affecting swine.

PubMed

Erickson, A; Fisher, M; Furukawa-Stoffer, T; Ambagala, A; Hodko, D; Pasick, J; King, D P; Nfon, C; Ortega Polo, R; Lung, O

2018-04-01

Microarray technology can be useful for pathogen detection as it allows simultaneous interrogation of the presence or absence of a large number of genetic signatures. However, most microarray assays are labour-intensive and time-consuming to perform. This study describes the development and initial evaluation of a multiplex reverse transcription (RT)-PCR and novel accompanying automated electronic microarray assay for simultaneous detection and differentiation of seven important viruses that affect swine (foot-and-mouth disease virus [FMDV], swine vesicular disease virus [SVDV], vesicular exanthema of swine virus [VESV], African swine fever virus [ASFV], classical swine fever virus [CSFV], porcine respiratory and reproductive syndrome virus [PRRSV] and porcine circovirus type 2 [PCV2]). The novel electronic microarray assay utilizes a single, user-friendly instrument that integrates and automates capture probe printing, hybridization, washing and reporting on a disposable electronic microarray cartridge with 400 features. This assay accurately detected and identified a total of 68 isolates of the seven targeted virus species including 23 samples of FMDV, representing all seven serotypes, and 10 CSFV strains, representing all three genotypes. The assay successfully detected viruses in clinical samples from the field, experimentally infected animals (as early as 1 day post-infection (dpi) for FMDV and SVDV, 4 dpi for ASFV, 5 dpi for CSFV), as well as in biological material that were spiked with target viruses. The limit of detection was 10 copies/μl for ASFV, PCV2 and PRRSV, 100 copies/μl for SVDV, CSFV, VESV and 1,000 copies/μl for FMDV. The electronic microarray component had reduced analytical sensitivity for several of the target viruses when compared with the multiplex RT-PCR. The integration of capture probe printing allows custom onsite array printing as needed, while electrophoretically driven hybridization generates results faster than conventional microarrays that rely on passive hybridization. With further refinement, this novel, rapid, highly automated microarray technology has potential applications in multipathogen surveillance of livestock diseases. © 2017 Her Majesty the Queen in Right of Canada • Transboundary and Emerging Diseases.

The Complete Genome Sequence of Yersinia pseudotuberculosis IP31758, the Causative Agent of Far East Scarlet-Like Fever

PubMed Central

Eppinger, Mark; Rosovitz, M. J; Fricke, Wolfgang Florian; Rasko, David A; Kokorina, Galina; Fayolle, Corinne; Lindler, Luther E; Carniel, Elisabeth; Ravel, Jacques

2007-01-01

The first reported Far East scarlet-like fever (FESLF) epidemic swept the Pacific coastal region of Russia in the late 1950s. Symptoms of the severe infection included erythematous skin rash and desquamation, exanthema, hyperhemic tongue, and a toxic shock syndrome. The term FESLF was coined for the infection because it shares clinical presentations with scarlet fever caused by group A streptococci. The causative agent was later identified as Yersinia pseudotuberculosis, although the range of morbidities was vastly different from classical pseudotuberculosis symptoms. To understand the origin and emergence of the peculiar clinical features of FESLF, we have sequenced the genome of the FESLF-causing strain Y. pseudotuberculosis IP31758 and compared it with that of another Y. pseudotuberculosis strain, IP32953, which causes classical gastrointestinal symptoms. The unique gene pool of Y pseudotuberculosis IP31758 accounts for more than 260 strain-specific genes and introduces individual physiological capabilities and virulence determinants, with a significant proportion horizontally acquired that likely originated from Enterobacteriaceae and other soil-dwelling bacteria that persist in the same ecological niche. The mobile genome pool includes two novel plasmids phylogenetically unrelated to all currently reported Yersinia plasmids. An icm/dot type IVB secretion system, shared only with the intracellular persisting pathogens of the order Legionellales, was found on the larger plasmid and could contribute to scarlatinoid fever symptoms in patients due to the introduction of immunomodulatory and immunosuppressive capabilities. We determined the common and unique traits resulting from genome evolution and speciation within the genus Yersinia and drew a more accurate species border between Y. pseudotuberculosis and Y. pestis. In contrast to the lack of genetic diversity observed in the evolutionary young descending Y. pestis lineage, the population genetics of Y. pseudotuberculosis is more heterogenous. Both Y. pseudotuberculosis strains IP31758 and the previously sequenced Y. pseudotuberculosis strain IP32953 have evolved by the acquisition of specific plasmids and by the horizontal acquisition and incorporation of different genetic information into the chromosome, which all together or independently seems to potentially impact the phenotypic adaptation of these two strains. PMID:17784789

Canine caliciviruses of four serotypes from military and research dogs recovered in 1963-1978 belong to two phylogenetic clades in the Vesivirus genus.

PubMed

Binn, Leonard N; Norby, Erica A; Marchwicki, Ruth H; Jarman, Richard G; Keiser, Paul B; Hang, Jun

2018-02-23

Vesiviruses (family Caliciviridae) had been shown capable of invading a variety of host species, raising concern of their zoonotic potential. Since the 1980's, several canine caliciviruses (CaCV) isolates have been reported and are phylogenetically related to the vesiviruses with features distinct from both Vesicular exanthema of swine virus (VESV) and Feline calicivirus (FCV) species in phylogeny, serology and cell culture specificities. Etiological studies of canine diseases in dogs used for military services and laboratory studies were conducted in 1963-1978 at the Walter Reed Army Institute of Research. Multiple known and unknown viral pathogens including caliciviruses were recovered. Four unidentified isolates were recovered in Walter Reed Canine Cells (WRCC) from respiratory, fecal and penile specimens. Physicochemical tests, electron microscopy, viral cultivation in human and animal cells, antibody neutralization assays, and recently the genome sequencing were used to characterize the isolates. Sera from these dogs and their cohorts were tested with the isolates to determine origin and prevalence of the infections. The viral isolates were small non-enveloped spherical RNA virions, 27 to 42 nm in diameter with cup-like structures, indicating they are caliciviruses. They propagated in WRCC and MDCK cells, not in either other canine cells or human and other animal cells. Each isolate is antigenically distinct and react with dog sera in respective cohorts. The genomes have nucleotide identities ranging from 70.3% to 90.7% and encode the non-structural polyprotein (1810 amino acids), major capsid protein (691 amino acids) and minor structural protein (134 amino acids). They belong to two different phylogenetic clades in Vesivirus genus with close relation with canine calicivirus (CaCV). These CaCV isolates have restricted cell tropism, antigenic diversity and genetic variation. Further investigation will shed light on antigenic relation to other vesiviruses, and its pathogenicity for dogs and potential infectivity to other animals. Together with the previously reported CaCV strains provides significant evidence to support the formation of a new CaCV species in the Vesivirus genus.

Renaissance mummies in Italy.

PubMed

Fornaciari, G

1999-01-01

The paleopathological study of 40 Italian Renaissance mummies has allowed us to perform about 20 diagnoses, of which 5 concern infectious (smallpox, hepatitis, condyloma, syphilis and pneumonia), 4 metabolic (obesity, atherosclerosis, gallstones and uric acid nephrolithiasis), 2 articular (DISH and rheumatoid arthritis) and 2 neoplastic (skin apithelioma and colon adenocarcinoma) diseases. The mummy of an anonymous child, dated back to the 16th century (C14=1569 +/- 60), presented a diffuse vesiculo-pustular exanthema. Macroscopic aspects and regional distribution suggested smallpox, while EM reavealed many egg-shaped, virus-like particles (250 x 50 nm), with a central dense core. Following incubation with anti-smallpox virus antiserum and protein A-gold complex immunostaining, the particles resulted completely covered with protein A-gold. These results clearly show that this Neapolitan child died of a severe form of smallpox some four centuries ago. The mummy of Maria of Aragon, Marquise of Vasto (1503-1568), reavealed on the left arm an oval, cutaneous ulcer (15x10 nm) with linen dressing. Indirect immunofluorescence with anti-treponema pallidum antibody identified a large number of filaments with the morphological characteristics of fluorescent treponemes. EM evidenced typical spirochetes, with axial fibril. These findings clearly demonstrate a treponemal, probably venereal, infection. The mummy of Ferrante I of Aragon, King of Naples (1431-1494), revealed an adenocarcinoma extensively infiltrating the muscles of the small pelvis. A molecular study of the neoplastic tissue evidenced a typical mutation of the K-ras gene codon 12:the normal sequence GGT (glycine) was altered into GAT (aspartic acid). At present this genetic change is the most frequent mutation of the K-ras gene in sporadic colorectal cancer. The alimentary "environment" of the Neapolitan court of the XV century, with its abundance of natural alimentary alkylating agents, well explains this acquired mutation. These and other diseases as, for example, a fatal puerperal complication, a thyroid goiter, a case of Wilson's cirrhosis, some cases of anthracosis and other peculiar traumatic conditions, such as a mortal stab-wound, can elucidate the pathocenosis of the wealthy classes of the Italian Renaissance.

Clindamycin-induced Maculopapular Exanthema with Preferential Involvement of Striae Distensae: A Koebner phenomenon?

PubMed

Monteagudo, Benigno; Cabanillas, Miguel; Iriarte, Pilar; Ramírez-Santos, Aquilina; León-Muinos, Elvira; González-Vilas, Daniel; Suárez-Amor, Óscar

2018-04-01

Clindamycin is a lincomycin-derived antibiotic useful for the treatment of anaerobic and Gram-positive aerobic bacterial infections. Cutaneous adverse reactions are usually maculopapular exanthemas, although hypersensitivity syndrome, acute generalized exanthematous pustulosis, and Stevens-Johnson syndrome have also been reported (1). We report the case of a patient with a maculopapular rash triggered by clindamycin who developed cutaneous lesions on striae distensae (SD). A 47-year-old woman was referred to our clinic for pruritic cutaneous lesions which had started 6 days earlier. Her past clinical history included hypertension, hypothyroidism, hyperuricemia, cholecystectomy, caesarean section, and endometriosis-related abdominal surgery, and she was taking levothyroxine, allopurinol, imidapril, and omeprazole. The skin rash first developed on her neck and back on the 3rd day of clindamycin oral treatment (300 mg every 6 hours), which was prescribed as antibiotic prophylaxis for a tooth implant. General malaise (but not fever) was also reported. Physical examination revealed an erythematous maculopapular eruption symmetrically distributed on the neck, abdomen, and back (Figure 1, A), with isolated lesions involving the proximal upper and lower limbs (Figure 1, B). There was a striking vertical distribution of skin lesions along the SD on the lateral sides of the abdomen (Figure 1, C). No mucosal involvement was found, and laboratory studies showed no abnormalities. Clindamycin withdrawal was followed by prescription of a course of oral deflazacort, starting at 30 mg daily and tapering down during a 9-day period. On the 5th day of treatment, the rash had almost cleared with minimal desquamation (Figure 1, D). Eight weeks after clearance of the skin rash, informed consent was obtained in order to perform an allergological evaluation of clindamycin, including prick and intradermal (ID) tests on the forearm and patch tests on the upper back (2). For patch testing, powder of the commercial capsules (Dalacin®) was diluted in petrolatum (pet.) and water (aq.), resulting in a final 1% clindamycin dilution. Parenteral clindamycin preparations were used in therapeutic concentrations for prick tests (150 mg/mL) and dilutions in saline of 1/100 and 1/10 for the ID test. Other authors have reported that these concentrations do not seem to irritate the skin (3-6). Prick and ID tests were assessed after 20 min and 24 hours, respectively. Patch tests were removed after the 2nd day, and late reactions were evaluated on day 2 and day 4. Prick and ID test results after 20 min were negative. Late results of ID tests with clindamycin (1.5 and 15 mg/mL) were positive: erythematous infiltrated papules about 7×7 mm and 18×15 mm were observed at 24 hours and lasted until the 8th day. Patch tests with clindamycin 1% in pet. and 1% in aq. were also positive (+ on day 2 and day 4). Positive late skin tests suggested delayed-type non-IgE-mediated allergic clindamycin hypersensitivity. Oral challenge tests are considered to be the gold standard to establish or exclude drug hypersensitivity. Due to the positive result of late skin test to clindamycin, oral challenge was not performed in our patient (3,5). The Koebner isomorphic phenomenon has been described in cutaneous reactions induced by drugs, such as antibiotics and chemotherapy. Chronic pressure on the skin is probably involved in the onset of skin lesions in hand-foot eruptions induced by tyrosine kinase inhibitors (sorafenib and sutinib). Solar exposure and cutaneous trauma also seem to play a role in the location of papulopustular eruptions caused by endothelial growth factor receptor inhibitors (erlotinib) (7). More frequent involvement in traumatized skin and surgical scars has been reported in the context of linear IgA bullous dermatosis and leukocytoclastic vasculitis triggered by vancomycin and cefuroxime (8). SD are produced by non-penetrating physical trauma, similar to friction or pressure. Different dermatoses can develop along SD skin lesions (like plaque psoriasis, pustular psoriasis, lichen planus, vitiligo, discoid lupus erythematosus, lupus vasculitis, urticarial vasculitis, or chronic graft-versus-host disease) (9). Bevacizumab, etretinate, and corticosteroid-induced ulcers, hyperpigmentation caused by bleomycin, and urticariform lesions triggered by diclofenac are examples of different type of drug-induced abnormalities involving SD (10). In summary, we identified clindamycin as the cause of the cutaneous reactions that occurred in our patient on the basis of the results of the skin tests and clinical history. Our findings confirmed a delayed-type hypersensitivity reaction, possibly involving a T-cell-mediated immunologic mechanism. Intradermal and patch tests were found to be useful in order to confirm the diagnosis (4,5). We did not find reports in the literature of drug-induced cutaneous eruptions along the SD as a manifestation of a Koebner phenomenon. Clinical underreporting of this phenomenon could explain the scarce literature on this cutaneous adverse reaction.

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

PubMed

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

2014-04-01

To systematically review evidence on genetic risk factors for carbamazepine (CBZ)-induced hypersensitivity reactions (HSRs) and provide practice recommendations addressing the key questions: (1) Should genetic testing for HLA-B*15:02 and HLA-A*31:01 be performed in patients with an indication for CBZ therapy to reduce the occurrence of CBZ-induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLA-B*15:02 or HLA-A*31:01 compared to others? (3) How should patients with an indication for CBZ therapy be managed based on their genetic test results? A systematic literature search was performed for HLA-B*15:02 and HLA-A*31:01 and their association with CBZ-induced HSRs. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus. Patients carrying HLA-B*15:02 are at strongly increased risk for CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in populations where HLA-B*15:02 is common, but not CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE). HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported from Asian countries only, including China, Thailand, Malaysia, and India. HLA-B*15:02 is rare among Caucasians or Japanese; no HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported so far in these groups. HLA-A*31:01-positive patients are at increased risk for CBZ-induced HSS and MPE, and possibly SJS/TEN and acute generalized exanthematous pustulosis (AGEP). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however, HLA-A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop an HSR, resulting in a relatively low positive predictive value of the genetic tests. This review provides the latest update on genetic markers for CBZ HSRs, clinical practice recommendations as a basis for informed decision making regarding the use of HLA-B*15:02 and HLA-A*31:01 genetic testing in patients with an indication for CBZ therapy, and identifies knowledge gaps to guide future research. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Adaptive Immune Responses following Senecavirus A Infection in Pigs.

PubMed

Maggioli, Mayara F; Lawson, Steve; de Lima, Marcelo; Joshi, Lok R; Faccin, Tatiane C; Bauermann, Fernando V; Diel, Diego G

2018-02-01

Senecavirus A (SVA), an emerging picornavirus of swine, causes vesicular disease (VD) that is clinically indistinguishable from foot-and-mouth disease (FMD) in pigs. Many aspects of SVA interactions with the host and the host immune responses to infection, however, remain unknown. In the present study, humoral and cellular immune responses to SVA were evaluated following infection in pigs. We show that SVA infection elicited an early and robust virus-neutralizing (VN) antibody response, which coincided and was strongly correlated with VP2- and VP3-specific IgM responses. Notably, the neutralizing antibody (NA) responses paralleled the reduction of viremia and resolution of the disease. Analysis of the major porcine T-cell subsets revealed that during the acute/clinical phase of SVA infection (14 days postinfection [p.i.]), T-cell responses were characterized by an increased frequency of αβ T cells, especially CD4 + T cells, which were first detected by day 7 p.i. and increased in frequency until day 14 p.i. Additionally, the frequency of CD8 + and double-positive CD4 + CD8 + T cells (effector/memory T cells) expressing interferon gamma (IFN-γ) or proliferating in response to SVA antigen stimulation increased after day 10 p.i. Results presented here show that SVA elicits B- and T-cell activation early upon infection, with IgM antibody levels being correlated with early neutralizing activity against the virus and peak B- and T-cell responses paralleling clinical resolution of the disease. The work provides important insights into the immunological events that follow SVA infection in the natural host. IMPORTANCE Senecavirus A (SVA) has recently emerged in swine, causing outbreaks of vesicular disease (VD) in major swine-producing countries around the world, including the United States, Brazil, China, Thailand, and Colombia. Notably, SVA-induced disease is clinically indistinguishable from other high-consequence VDs of swine, such as FMD, swine vesicular disease, vesicular stomatitis, and vesicular exanthema of swine. Despite the clinical relevance of SVA-induced VD, many aspects of the virus infection biology remain unknown. Here, we assessed host immune responses to SVA infection. The results show that SVA infection elicits early B- and T-cell responses, with the levels of VN antibody and CD4 + T-cell responses paralleling the reduction of viremia and resolution of the disease. SVA-specific CD8 + T cells are detected later during infection. A better understanding of SVA interactions with the host immune system may allow the design and implementation of improved control strategies for this important pathogen of swine. Copyright © 2018 American Society for Microbiology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, S; Danganan, L; Tammero, L

Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed advanced rapid diagnostics that may be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the potential to improve our nation's ability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect animal populations of high economic importance in themore » United States. Under 2005 DHS funding we have developed multiplexed (MUX) nucleic-acid-based PCR assays that combine foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease (SVD) and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1 or Infectious Bovine Rhinotracheitus IBR), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus BPSV, Orf of sheep, and Pseudocowpox). Under 2006 funding we have developed a Multiplexed PCR [MUX] porcine assay for detection of FMDV with rule out tests for VESV and SVD foreign animal diseases in addition to one other domestic vesicular animal disease vesicular stomatitis virus (VSV) and one domestic animal disease of swine porcine reproductive and respiratory syndrome (PRRS). We have also developed a MUX bovine assay for detection of FMDV with rule out tests for the two bovine foreign animal diseases malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV), bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitus virus (BHV-1), bluetongue virus (BTV), and the Parapox viruses which are of two bovine types bovine papular stomatitis virus (BPSV) and psuedocowpox (PCP). This document provides details of signature generation, evaluation, and testing, as well as the specific methods and materials used. A condensed summary of the development, testing and performance of the multiplexed assay panel was presented in a 126 page separate document, entitled 'Development and Characterization of A Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out'. This supplemental document provides additional details of large amount of data collected for signature generation, evaluation, and testing, as well as the specific methods and materials used for all steps in the assay development and utilization processes. In contrast to last years effort, the development of the bovine and porcine panels is pending additional work to complete analytical characterization of FMDV, VESV, VSV, SVD, RPV and MCF. The signature screening process and final panel composition impacts this effort. The unique challenge presented this year was having strict predecessor limitations in completing characterization, where efforts at LLNL must preceed efforts at PIADC, such challenges were alleviated in the 2006 reporting by having characterization data from the interlaboratory comparison and at Plum Island under AgDDAP project. We will present an addendum at a later date with additional data on the characterization of the porcine and bovine multiplex assays when that data is available.« less

Development and Characterization of A Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, S M; Danganan, L; Tammero, L

2007-08-06

Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed candidate multiplexed assays that may potentially be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the ability to improve our nation's capability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect food and agricultural resources with a diagnosticmore » test which could enhance the nation's capabilities for early detection of a foreign animal disease. In FY2005 with funding from the DHS, LLNL developed the first version (Version 1.0) of a multiplexed (MUX) nucleic-acid-based RT-PCR assay that included signatures for foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases (FADs) of swine, Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease Virus (SVDV), and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus [BPSV], Orf of sheep, and Pseudocowpox). In FY06, LLNL has developed Bovine and Porcine species-specific panel which included existing signatures from Version 1.0 panel as well as new signatures. The MUX RT-PCR porcine assay for detection of FMDV includes the FADs, VESV and SVD in addition to vesicular stomatitis virus (VSV) and porcine reproductive and respiratory syndrome (PRRS). LLNL has also developed a MUX RT-PCR bovine assay for detection of FMDV with rule out tests for the two bovine FADs malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV), bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitus virus (BHV-1), bluetongue virus (BTV), and the Parapox viruses (which are of two bovine types) bovine papular stomatitis virus (BPSV) and psuedocowpox (PCP). A timeline for this development is presented in Table 1. The development of the Version 1.0 panel for FMDV rule-out and the most current efforts aimed to designed species specific panels has spanned over 2 1/2 years with multiple collaborative partnerships. This document provides a summary of the development, testing and performance data at OIE Stage 1 Feasibility into Stage 2 Assay Development and Standardization1 (see Table 2), gathered as of June 30th, 2007 for the porcine and bovine MUX assay panels. We present an overview of the identification and selection of candidate genetic signatures, the assay development process, and preliminary performance data for each of the individual signatures as characterized in the multiplexed format for the porcine and bovine panels. The Stage 1 Feasibility data of the multiplexed panels is presented in this report also includes relevant data acquired from the Version 1.0 panel as supporting information where appropriate. In contrast to last years effort, the development of the bovine and porcine panels is pending additional work to complete analytical characterization of FMDV, VESV, SVD, RPV and MCF. The signature screening process and final panel composition impacts this effort. The unique challenge presented this year was having strict predecessor limitations in completing characterization, where efforts at LLNL must precede efforts at PIADC, such challenges were alleviated in the 2006 reporting by having characterization data from the interlaboratory comparison and at Plum Island under AgDDAP project. We will present an addendum at a later date with additional data on the characterization of the porcine and bovine multiplex assays when that data is available. As a summary report, this document does not provide the details of signature generation, evaluation, and testing, nor does it provide specific methods and materials used. This information has been provided in the separate 488 page Supplementary Materials document.« less

Foot & Mouth Disease & Ulcerative/Vesicular Rule-outs: Challenges Encountered in Recent Outbreaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hullinger, P

2008-01-28

Foot and mouth disease (FMD) is a highly infectious and contagious viral disease affecting bovidae (cattle, zebus, domestic buffaloes, yaks), sheep, goats, swine, all wild ruminants and suidae. Camelidae (camels, dromedaries, llamas, vicunas) have low susceptibility. Foot and mouth disease is caused by a RNS virus of the family Picornaviridae, genus Aphthovirus. There are seven immunologically distinct serotypes: A, O, C, SAT1, SAT2, SAT3, Asia 1. Foot and mouth disease causes significant economic loss both to countries who manage it as an endemic disease (with or without vaccination), as well as those FMD free countries which may become infected. Themore » mortality rate is low in adult animals, but often higher in young due to myocarditis. Foot and mouth disease is endemic in parts of Asia, Africa, the Middle East and South America (sporadic outbreaks in free areas). The Office of International Epizootics (OIE), also referred to the World Organization for Animal Health maintains an official list of free countries and zones.1 The OIE Terrestrial Code (Chapter 2.2.10) provides detailed information on the categories of freedom that can be allocated to a country as well as guidelines for the surveillance for foot and mouth disease (Appendix 3.8.7). In short, countries may be completely free of FMD, free with vaccination or infected with foot and mouth disease virus (FMDV). Source of FMDV include incubating and clinically affected animals with virus present in breath, saliva, faeces, urine, milk and semen. In experimental settings virus has been detected in milk several days before the onset of clinical signs2. Additional sources of virus are meat and by-products in which pH has remained above 6.0 as well as persistently infected carrier animals. Carrier animals may include cattle and water buffalo; convalescent animals and exposed vaccinates (virus persists in the oropharynx for up to 30 months in cattle or longer in buffalo, 9 months in sheep). Pigs do not become carriers. It has been shown that the African Cape buffalo are the major maintenance host of SAT serotypes. FMDV transmission can occur by either direct or indirect contact. Indirect transmission can occur via contaminated animate vectors (humans, etc.), inanimate vectors (vehicles, implements) or airborne transmission. Indirect disease transmission via animate or inanimate vectors can play a major role in disease transmission. Good biosecurity can significantly reduce this type of transmission. Airborne transmission is often debated and is known to be serotype and species specific as well as require specific environmental conditions to occur. Airborne transmission is favored in temperate zones and has been postulated to occur over distances of up to 60 km overland and 300 km by sea. Foot and mouth disease virus is an unenveloped virus which is preserved by refrigeration and freezing and progressively inactivated by temperatures above 50 C. FMDV is highly sensitive to pH change and is inactivated by pH < 6.0 or > 9.0. There are many disinfectants which are effective against FMDV including sodium hydroxide (2%), sodium carbonate (4%), and citric acid (0.2%). FMDV is resistant to iodophores, quaternary ammonium compounds, hypochlorite and phenol, especially in the presence of organic matter. The virus can survive in lymph nodes and bone marrow at neutral pH, but is destroyed in muscle when is pH < 6.0 i.e. after rigor mortis. FMDV can persist in contaminated feed/commodities and the environment for over to 1 month, depending on the temperature and pH conditions. The incubation period for FMD is 2-14 days. Animals transition through latent (infected but not infectious), subclinically infected (infectious but lacking clinical signs) clinically infected and recovered disease states. In cattle clinical signs include pyrexia, reluctance to eat, bruxism, drooling, lameness, treading or stamping of the feet and decreased milk production. Most clinical signs are related to the development and subsequent rupturing of vesicles at the coronary band and in the oral cavity. Vesicles and ulcerations can also occur on the mammary gland. Recovery in adult animals usually occurs in 8-15 days. Clinical signs for most serotypes are less dramatic in sheep and goats. Swine can develop very severe coronary band lesions and high mortality in piglets has been observed. One of the challenges of diagnosing FMD is that it may be clinically similar to several other vesicular or ulcerative diseases. FMD is clinically indistinguishable from Vesicular stomatitis, Swine vesicular disease and Vesicular exanthema of swine. It may also resemble Bovine viral diarrhea, Mucosal disease, Infectious bovine rhinotracheitis, Bluetongue, Bovine papular stomatitis, Bovine mammillitis and Rinderpest.« less