Exanthematous Pustulosis Research Articles

Acute generalized exanthematous pustulosis secondary to Valproate: An uncommon cutaneous reaction of a common drug

Objective: There are various adverse drug reaction (ADR) associated with pharmacological therapy that differ in clinical presentation, prognosis and therapy. Among these, cutaneous eruptions are the most common type of all ADRs.Theclinical presentation of cutaneous drug eruptions ranges from common transient and benign erythema to the most severe forms such as Steven-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN). Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous drug reaction accounting for 1–5 cases/1,000,000 per year. Antibiotics like β‑lactams and macrolides are the usual offending agents. Among anticonvulsants-carbamazepine, phenobarbital and phenytoin are commonly associated with AGEP. Sodium valproate is relatively free from cutaneous drug reaction. Thus, we hereby, report a rare case of AGEP in a 24 years old male, reaction following valproate intake used to control post traumatic seizure. Key words: Acute generalized exanthematous pustulosis, Valproate, Adverse drug reaction.

Severe Cutaneous Drug Reactions: Do Overlapping Forms Exist?

Acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms are all severe hypersensitivity reactions to medications. While each of these reactions is a well-established entity with specific diagnostic criteria, clinicians see cases that fulfill criteria for more than one form, prompting discussion on the possibility of combined forms. Such overlapping clinical pictures meeting the criteria for 2 conditions have thus become a topic of debate in dermatology in recent years. We describe 2 patients with cutaneous drug reactions having the characteristics of both acute generalized exanthematous pustulosis and Stevens-Johnson syndrome -toxic epidermal necrolysis. We also review previously published cases and current thinking on such overlapping conditions.

Toxicodermias graves: ¿existen las formas combinadas?

Acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms are all severe hypersensitivity reactions to medications. While each of these reactions is a well-established entity with specific diagnostic criteria, clinicians see cases that fulfill criteria for more than one form, prompting discussion on the possibility of combined forms. Such overlapping clinical pictures meeting the criteria for 2 conditions have thus become a topic of debate in dermatology in recent years. We describe 2 patients with cutaneous drug reactions having the characteristics of both acute generalized exanthematous pustulosis and Stevens-Johnson syndrome -toxic epidermal necrolysis. We also review previously published cases and current thinking on such overlapping conditions.

Adverse cutaneous drug eruptions: current understanding.

Adverse cutaneous drug reactions are recognized as being major health problems worldwide causing considerable costs for health care systems. Most adverse cutaneous drug reactions follow a benign course; however, up to 2% of all adverse cutaneous drug eruptions are severe and life-threatening. These include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Physicians should be aware of specific red flags to rapidly identify these severe cutaneous drug eruptions and initiate appropriate treatment. Besides significant progress in clinical classification and treatment, recent studies have greatly enhanced our understanding in the pathophysiology of adverse cutaneous drug reactions. Genetic susceptibilities to certain drugs have been identified in SJS/TEN patients, viral reactivation in DRESS has been elucidated, and the discovery of tissue resident memory T cells helps to better understand the recurrent site-specific inflammation in patients with fixed drug eruption.

Analysis of cross-reactivity among radiocontrast media in 97 hypersensitivity reactions

Results Ninety-seven patients were included. CR occurred between ionic monomers (IMs) in 2 cases, between non-ionic monomers (NIMs) in 93 cases, between an ionic dimer (ID) and an IM in 1 case, between NIMs and IMs in 38 cases, between NIMs and IDs in 29 cases, between non-ionic dimers (NIDs) and IMs in 9 cases, between IDs in 13 cases, and between NIMs in 65 cases. Multiple correspondence analyses identified two subgroups of RCM in which CR was frequent: Group A (iodixanol, iopamidol, iomeprol, iohexol, ioversol), which share two identical N-(2, 3-dihydroxypropyl) carbamoyl side chains that could be the antigen determinant (also present in other drugs), and Group B (ioxaglate, iobitridol). Conclusion From this largest study of CR between RCM, we demonstrate that frequent CR between RCM does not follow the current chemical classification. Thus, we propose reclassifying RCM, and also suggest re-challenging sensitized patients with RCM from a different CR subgroup than that of the RCM initially involved.

Residents'corner October 2015. DeRmpath&Clinic: Acute generalised exanthematous pustulosis.

Case 1: A 55 year-old lady presented with diffuse oedematous erythema infiltrated with numerous small non-follicular pustules. This initially appeared over her face and axillae but subsequently spread to involve much of her torso and proximal limbs. There was associated fever and general malaise. Laboratory investigations also demonstrated an accompanying neutrophilia. Five days previously she had started oral flucloxacillin for a recurrent facial cyst.Case 2: A 48 year-old lady presented with multiple [...]

Akut generalizált exanthemás pustulosis két eset kapcsán

Akut generalizált exanthemás pustulosis két eset kapcsán

Research on Susceptible Genes and Immunological Pathogenesis of Cutaneous Adverse Drug Reactions in Chinese Hans.

Cutaneous adverse drug reactions (cADRs) include mild maculopapular exanthems (MPE), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). We used HLA high-resolution genotyping and genome wide association analysis (GWAS) to identify the genetic markers for cADRs induced by common culprit drugs in Han Chinese population. To further understand the immunopathogenesis of cADRs, and with the goal of developing treatment strategies, we compared the expression of cytoxic cytokines between the patients with cADRs and normal controls. Our data suggested that the carbamazepine induced SJS/TEN, allopurinol induced CADRs, methazolamide induced SJS/TEN and SASP induced DRESS were respectively strongly associated with HLA-B*15:02, HLA-B*58:01, HLA-B*59:01 and HLA-B*13:01. In addition, increased expression of cytotoxic cytokines in sera and tissues of cADRs patients were found, compared with healthy controls. Our findings may shed light on prediction and prevention of cADRs, provide clues to pathogenesis, and guide treatment strategies of these reactions.

Severe drug-induced skin reactions: clinical features, diagnosis, etiology, and therapy.

Drugs can induce severe skin reactions that differ in clinical presentation, prognosis, and therapy. The spectrum of these reactions not only includes bullous reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and generalized bullous fixed drug eruption (GBFDE) but also acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). If AGEP or DRESS is suspected, the diagnosis should be confirmed by thorough clinical examination, a skin biopsy, and specific laboratory tests. Crucial for the patient's prognosis, the causative agent should be rapidly identified and discontinued. It is therefore important to know the most frequent triggers of severe drug reactions, some of which may induce various reaction patterns. Depending on the clinical diagnosis, symptomatic and adequate supportive therapy, as well as systemic immunomodulatory treatments are used. The prognosis in SJS/TEN is often poor and depends on the patient's age and underlying conditions as well as the extent of skin detachment. The prognosis of GBFDE is somewhat better, but recurrences may lead to more severe disease manifestations. In DRESS, protracted and recurrent courses have been described, whereas AGEP usually resolves without problems.

Targeted Exome Resequencing: Adme Pharmacogenetics In Human Liver

August 2015 e71 Stevens-Johnson Syndrome, toxic epidermal necrolysis (SJS/TEN), DRESS (drug reaction with eosinophilia and systemic symptoms), and acute generalized exanthematous pustulosis (AGEP). Objective: To identify serious cases of (CADR) and the main suspected drugs. Materials and Methods: Retrospective observational, between 2008 and 2014 at the Clinical Pharmacology Service of Hospital Universitario de la Princesa (Madrid) have identified 28 cases of severe skin reactions induced by drugs. Results: Twenty-eight (CADR), 18 women and 10 men, mean age 43.1 years, (35.7%) in dermatology services, UCI, internal medicine. The main identified toxicodermia was AGEP (35.71%), followed by DRESS syndrome and SJS / TEN (25%), erythema multiforme (7.14%), leukocytoclastic vasculitis and linear IgA bullous dermatitis (3.57%). Main identified drug was phenytoin (28.75%), followed by amoxicillin/clavulanate (14.28%), carbapenems, antiretroviral treatment, piperacillin/tazobactam and magnesium metamizol (7.14%), and allopurinol, tramadol, NSAIDs, vancomycin, clindamycin, ranitidine, and simvastatin a (3.57%). Mortality rate was: 28.57% (n = 8), of which 4 by SJS/TEN, 2 by DRESS, and 2 by AGEP total of 8 patients. Conclusions: Serious toxicodermies in the Hospital de la Princesa have a low frequency but are associated with high mortality, risk of complications and sequelae; Very similar to that found in other studies, the most frequent is acute generalized exanthematous pustulosis.

A Delayed Presentation of Acute Generalized Exanthematous Pustulosis (AGEP)

Acute Generalized Exanthematous Pustulosis (AGEP) is a Type IVd hypersensitivity reaction that usually occurs within 1-5 days of drug exposure. The diagnosis is clinical and confirmed by skin biopsy. A scoring algorithm has been developed which assigns points to characteristic clinical signs in order to aid in the diagnosis. AGEP is a self-limited disease with a fa- vorable prognosis in most cases. We present an unusual delayed presentation of AGEP secondary to hydroxycholoroquine.

Ticagrelor-induced acute generalized exanthematous pustulosis

Reactions to antiplatelet drugs are not uncommon. With the proliferative use of dual antiplatelet therapy utilizing P2Y12 receptor inhibitors in the current era of medicine, a higher awareness is needed to identify such reactions. Various adverse reactions and side effects including exanthems and other hypersensitivity reactions are known to occur following the use of these agents [1].

Five-year retrospective study of acute generalized exanthematous pustulosis

Five-year retrospective study of acute generalized exanthematous pustulosis

Adverse cutaneous drug reactions--a clinico-demographic study in a tertiary care teaching hospital of the Kashmir Valley, India.

Adverse cutaneous drug reactions (ACDRs) are caused by a wide variety of agents. The aim was to study the incidence and clinico-demographic profile of ACDRs to identify any potential risk factors and compare the results with other studies. A cross-sectional observational study was conducted over a period of one year from October 2012 to October 2013 in the outpatient department (OPD) of a tertiary care teaching hospital of the Kashmir valley in India and various ACDRs were recorded. The incidence of ACDRs was 0.16%. The mean age of patients was 39.36 ± 16.77 years. The male: female ratio was 0.97:1. The most frequently reported cutaneous reactions were with antimicrobials (57.33%) followed by NSAIDs (21.33%) and antiepileptic drugs (17.33%). Less common groups involved were steroids, antipsychotics and bisphosphonates (1.33% each). Fixed drug eruptions (FDEs) were the commonest (45.33%) followed by maculopapular (17.33%), photoallergic (8%), erythema multiforme (6.66%), Stevens-Johnson syndrome (5.33%) and lichenoid eruptions (4%). Less common patterns were urticaria, Drug Reaction with Eosinophilia and systemic symptoms (DRESS syndrome) and acneform eruptions (2.66% each) followed by angioedema, acute generalized exanthematous pustulosis (AGEP), exfoliative dermatitis and toxic epidermal necrolysis (1.33% each). Physicians should have adequate knowledge of adverse drug reactions, especially of newer drugs which are increasing every year in order to minimize such events.

Acute Generalized Exanthematous Pustulosis Caused by Dihydrocodeine Phosphate in a Patient With Psoriasis Vulgaris and a HeterozygousIL36RNMutation

Acute generalized exanthematous pustulosis (AGEP) is a rare and severe type of drug eruption. Dihydrocodeine phosphate is a semisynthetic opioid analgesic. Recently, recessive mutations in IL36RN have been identified in generalized pustular psoriasis (GPP). To date, 4 cases of AGEP and IL36RN mutation without previous history of psoriasis vulgaris (PV) have been reported. A woman in her 60s with PV presented with diffuse erythema, nonfollicular pustules, and fever. She had been treated with dextromethorphan hydrobromide hydrate, amoxicillin hydrate, clarithromycin, dihydrocodeine phosphate, tipepidine hibenzate, and tulobuterol tape for a cough and common cold. Based on histopathologic results and a positive result in a drug provocation test with dihydrocodeine phosphate, she was diagnosed with AGEP. A heterozygous IL36RN mutation c.28C>T (p.Arg10X) was also confirmed by mutation analysis. This is the first report of dihydrocodeine phosphate-induced AGEP. In this case, helper T cells, type 17, might have been activated because of morphine and underlying PV, followed by increased production of interleukin (IL) 36. However, because of the IL36RN mutation, IL-36 signaling was uncontrolled, which might have resulted in the occurrence of AGEP. An IL36RN mutation might underlie several different pustular skin eruptions, including AGEP and GPP, and further accumulation of patient data is required.

La dermatophytide exanthématique et pustuleuse généralisée (DEPG), une présentation clinique rare de dermatophytide

Dermatophytids are immunologically mediated dermatologic presentations secondary to sensitization to a dermatophyte infection. They are most frequently associated with toe-web intertrigo and usually present as localized, palmar, pruriginous vesicular eruptions. We report three original cases of generalized exanthematous pustular dermatophytid associated with kerions. Two boys aged 11 and 6 years, and one girl aged 6 years initially presented with kerion secondary to Trichophyton tonsurans (case 1), Trichophyton soudanense (case 2) and Trichophyton mentagrophytes (case 3), respectively. Two to three days after initiation of griseofulvin treatment, all patients presented with a pustular eruption extending from the head to the trunk, associated in one case with fever of 39°C and inflammatory chondritis. Samples obtained from the pustular lesions were sterile, serum inflammatory markers were within the normal range and skin lesions resolved on oral corticosteroid treatment (prednisone 0.75 mg/kg, case 1) or high-potency topical steroids (cases 2 and 3) given as an adjunct to griseofulvin treatment (19 to 23 mg/kg/d). Dermatophytids occur during the acute phase of infection or within a few days of treatment initiation. Lesions are remote from the infection site, contain no dermatophyte, and resolve after treatment of the infection. We report three original cases of generalized exanthematous pustular dermatophytid, associated in one case with fever and inflammatory chondritis. The main differential diagnosis is acute generalized exanthematous pustulosis secondary to antifungal drugs. Differences in clinical presentation between the two enable the appropriate diagnosis to be made as well as continued use of the antifungal medication needed to cure the patient. General or topical steroids may also be used in combination.

Antibiotic Allergies in a Birth Cohort from 2007

S U N D A Y 370 The Association of HLA-B* 5101 and Phenobarbital-Induced Severe Cutaneous Adverse Drug Reactions in Thai Children Plernpit Likkasittipan, MD, Wiparat Manuyakorn, MD, Surakameth Mahasirimongkol, Suwat Benjaponpitak, MD, Anannit Visudtibhan, Nuanjun Wichukchinda, Sukanya Wattanapokayakit; Division of Pediatric Allergy/Immunology/Rheumatology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand, Division of Pediatric Allergy/Immunology/Rheumatology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Medical genetic center, Medical Life Science Institute, Department of Medical Science, Ministry of Public Health, Nonthaburi, Thailand, Division of Pediatric Neurology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand. RATIONALE: Adverse drug reactions to phenobarbital (PB), the firstline aromatic anticonvulsant drug, are maculopapular rash (MP) and severe cutaneous adverse drug reactions (SCARs) including drug rash with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These conditions have highmortality rate and are usually unpredictable. This preliminary study aims to investigate the association between variations of HLA genotypes and phenobarbitalinduced SCARs among Thai children. METHODS: Thai children aged between 0-18 years who were diagnosed with phenobarbital hypersensitivity from 2004-2014. Control patients were phenobarbital-tolerant Thai children with corresponding age groups. Their HLA-B locus was genotyped using a PCR technique. RESULTS: A total of 45 Thai children were enrolled. Thirteen children were diagnosed with phenobarbital hypersensitivity (7 with MP and 6 with SCARs). Thirty two phenobarbital-tolerant children were recruited as control. The frequency of HLA-B*5101 in phenobarbital-induced SCARs was 50% (3/6) while only 6% (2/32) was found in the drug-tolerant children (OR515, 95%CI (1.75-128) p5 0.02). No patient with phenobarbital-induced MP was found to carry HLA-B*5101. The frequency of HLA-B*1502 in phenobarbital-induced MP was 14.3%, phenobarbitalinduced SCARs was 16.7% and drug tolerant was 12.5%. We did not find any association between phenobarbital-induced MP and SCARs and HLA-B*1502, a known HLA genotype associated with anticonvulsant hypersensitivity in previous study. CONCLUSIONS: Our preliminary study shows an association between HLA-B*5101 and phenobarbital-induced SCARsamong Thai children.

Five-Year Retrospective Review of Acute Generalized Exanthematous Pustulosis.

Background. Acute generalized exanthematous pustulosis (AGEP) is an acute pustular eruption characterized by widespread nonfollicular sterile pustules. The aim of this study is to characterize the etiology, clinical features, laboratory findings, management, and outcome of patients with AGEP in Asians. Patient/Methods. A retrospective analysis was performed on patient who presented with AGEP between August 2008 and November 2012 in a tertiary center in Thailand. Results. Nineteen patients with AGEP were included. AGEP was generally distributed in seventeen patients (89.5%) and localized in two (10.5%). Fever and neutrophilia occurred in 52.6% and 68.4%, respectively. Hepatitis was found up to 26.3%. The most common etiology was drugs (94.7%), comprising of antibiotics (73.6%), proton pump inhibitors (10.5%), nonsteroidal anti-inflammatory drugs (5.3%), and herbal medicine (5.3%). Beta-lactams were the most common causal drug, particularly carbapenems and cephalosporins. This is the first report of Andrographis paniculata as an offending agent for AGEP. We found no differences between various treatment regimens (topical corticosteroid, systemic corticosteroid, and supportive treatment) regarding the time from drug cessation to pustules resolution (P = 0.171). Conclusions. We have highlighted the presentation of AGEP among Asians. We found high association with systemic drugs. Carbapenems were one of the leading culprit drugs. Finally, a localized variant was observed.

Acute generalized exanthematous pustulosis secondary to azathioprine

Acute generalized exanthematous pustulosis secondary to azathioprine

Severe cutaneous adverse drug reactions: a clinicoepidemiological study.

Background:Drug eruptions range from transient erythema to the life threatening severe cutaneous adverse reactions (SCAR) that encompass Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms complex (DRESS).Aims and Objectives:To study the clinical and epidemiological aspects of cutaneous adverse drug reactions (CADR).Materials and Methods:Ethical clearance was obtained from the institutional ethics committee. All patients admitted in the Dermatology ward of our tertiary care hospital with CADR (those who fit in the category of probable or possible drug reaction as per WHO casuality assessment) from first September 2011 to 31st August 2012 were included in this cross sectional study after obtaining written informed consent. The drug reaction patterns observed in the study population were determined and the common offending drugs were identified.Results:In the study, population of males outnumbered females and the majority were between 46 and 60 years of age. The commonest reaction pattern observed was SJS- TEN spectrum of illness and aromatic anticonvulsants were the common offending drugs. Prompt withdrawal of the culprit drug and administration of systemic steroids with or without I/V Ig reverted the adverse reaction in all except one.Conclusion:Severe drug reactions predominated as the study population was comprised of inpatients of a tertiary referral centre. Though; previous authors had reported a mortality rate of up to 20% in DRESS, all our patients with this reaction pattern, responded well to treatment. The mortality rate among TEN cases was much lower than the previous reports. Early diagnosis, prompt withdrawal of the suspected drug, careful monitoring for development of complications and immediate intervention can improve the prognosis of CADR.