Exanthematous Pustulosis Research Articles

Parasetamole Bağlı Gelişen Bir Akut Jeneralize Ekzantematöz Püstülozis Olgusu

Acute generalized exanthematous pustulosis is an exanthematous disease characterized by a great number of pustules on an acutely erythematous and edematous surface on the skin. These pustules are smaller than 5 mm, have non-follicular localization, and are sterile and superficial. Drugs are held responsible for 90% of the cases and antibiotics are the main culprits. Viral infections, mercury exposure, spider bite and radiation have also been rarely reported as the causative agent. The mortality of AGEP, which is considered to be one of the Severe Cutaneous Adverse Reactions (SCAR), is 5%. Many of the cases reported are adults. Since AGEP is rare in children, we present a ten-month-old boy who developed AGEP after paracetamol use.

Immunosuppressed cutaneous District: The finale of the fascinating farrago of confounding responses?

Immunosuppressed cutaneous District: The finale of the fascinating farrago of confounding responses?

A clinical study of severe cutaneous adverse drug reactions and role of corticosteroids in their management

Background: Various medications are used for the treatment of various diseases. Ironically, adverse drug reactions (ADRs) also accompany the use of these medications and are as old as the medicine itself. These drug reactions can range from mild transient erythema at one end of the spectrum to severe cutaneous ADRs (SCADRS) that include Steven–Johnson syndrome (SJS), toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms complex (DRESS). Aim: This study aims to study the clinical and epidemiological aspects of severe cutaneous adverse drug reactions (SCADRS) at a referral center of Jammu region, with special reference to the role of corticosteroids in the management. Materials and Methods: The study was carried out between July 2015 and December 2015, at a tertiary hospital after permission from Ethical Committee of the institution. A total of 44 patients were included in the study which included outpatients as well as inpatients admitted after written informed consent. The Naranjo ADR probability scale was applied to indicate the causality of the drug with the SCADRS. Results: In the study, a total of 44 patients were included in the study. Males outnumbered the females, and maximum patients were in the age group of 21–40 years. SJS was the most common SCARD found followed by DRESS. Antiepileptic class of drug was found to be most commonly implicated. Immediate withdrawal of the culprit drug and administration of systemic steroids reverted the SCARD in maximum patients. Conclusion: Severe cutaneous adverse drug reactions can be associated with serious morbidity as well as mortality. Their knowledge and prompt recognition are essential for clinicians as early recognition, and immediate withdrawal of the culprit drug/drugs with adequate management can be lifesaving.

Treatments for Severe Cutaneous Adverse Reactions.

Severe cutaneous adverse reaction (SCAR) is life-threatening. It consists of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed drug eruptions (GBFDE). In the past years, emerging studies have provided better understandings regarding the pathogenesis of these diseases. These diseases have unique presentations and distinct pathomechanisms. Therefore, theoretically, the options of treatments might be different among various SCARs. However, due to the rarity of these diseases, sufficient evidence is still lacking to support the best choice of treatment for patients with SCAR. Herein, we will provide a concise review with an emphasis on the characteristics and treatments of each SCAR. It may serve as a guidance based on the current best of knowledge and may shed light on the directions for further investigations.

Immunohistopathological Findings of Severe Cutaneous Adverse Drug Reactions.

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.

Epidemiology of cutaneous adverse drug reactions.

Epidemiologic investigation of cutaneous adverse drug reactions (cADRs) is important in order to evaluate their impact on dermatology and health care in general as well as their burden on affected patients. Few epidemiologic studies have been performed on frequent non-life-threatening cADR, including reactions of both delayed and immediate hypersensitivity, such as maculopapular exanthema (MPE), fixed drug eruption, and urticaria. Concerning rare but life-threatening severe cutaneous adverse reactions, e.g., toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS), several epidemiologic studies have been performed to date, some of which are still ongoing. Such studies enable the calculation of reliable incidence rates and demographic data, and also allow researchers to perform risk estimation for drugs. The spectrum of drugs causing cADR differs substantially when separating the various clinical conditions. Whereas antibiotics are by far the most frequent inducers of milder cADRs, like MPE, they have a much lower risk of inducing SJS/TEN, for which “high-risk” drugs are anti-infective sulfonamides, allopurinol, certain anti-epileptic drugs, nevirapine, and non-steroidal anti-inflammatory drugs (NSAIDs) of the oxicam-type. In contrast, AGEP is predominantly caused by the antibiotics pristinamycin and aminopenicillins, followed by quinolones, (hydroxy-)chloroquine, and sulfonamides. DRESS can be induced by a number of drugs known to cause SJS/TEN, such as certain antiepileptics and allopurinol, but also other medications (e.g., minocyclin).

Acute generalized exanthematous pustulosis presumed to be caused by acetaminophen

Acute generalized exanthematous pustulosis presumed to be caused by acetaminophen

Acute Generalized Exanthematous Pustulosis Due to Pyrazinamide in a Patient Receiving Antituberculous Treatment: A Case Report

Acute Generalized Exanthematous Pustulosis Due to Pyrazinamide in a Patient Receiving Antituberculous Treatment: A Case Report

First case of DRESS syndrome attributed to a spider bite

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a hypersensitivity reaction that is usually drug induced. The acronym VRESS (V for viral)1 was proposed in cases of proven viral reactivations. We describe a case that was unrelated to any drug or viral reactivation, but was triggered by a spider bite instead. Spider bites have been recently reported to cause acute generalized exanthematous pustulosis (AGEP) and other cutaneous reactions, but not DRESS.

Bullous, pseudobullous, & pustular dermatoses.

Several dermatoses are typified by the formation of spaces (blisters; bullae) within or beneath the epidermis. These may be acellular or filled with particular species of inflammatory cells. Etiological categories include infectious, immune-mediated, genetic, drug-related, and idiopathic lesions. Examples of such disorders include impetigo, Herpes virus infections, pemphigus, bullous pemphigoid and pemphigoid gestationis, epidermolysis bullosa acquisita, IgA-related dermatoses, inherited epidermolysis bullosa variants, Hailey-Hailey disease, and porphyria cutanea tarda. Other conditions manifest microscopic acantholysis within the surface epithelium but are not associated with clinical bullae, such as Darier disease and Grover disease. Finally, both infectious and non-infectious causes exist for the development of neutrophilic pustules in the epidermis, as seen in pustular psoriasis, Sneddon-Wilkinson disease (subcorneal pustular dermatosis), and acute generalized exanthematous pustulosis. This review considers the clinical and histological features of all of these diseases.

Long-term reproducibility of positive patch test reactions in patients with non-immediate cutaneous adverse drug reactions to antibiotics.

As in contact allergy, T cell-mediated hypersensitivity in non-immediate (NI) cutaneous adverse drug reactions (CADRs) to antibiotics is considered to be lifelong, but, in this setting, patch tests have rarely been repeated after long time intervals. To evaluate the long-term reproducibility of positive patch test reactions to antibiotics in patients with NI CADRs. Fifty-six patients with NI CADRs to antibiotics who had relevant positive reactions during patch testing were invited to repeat patch tests with a similar antibiotic series 2-15 years thereafter. Twenty patients were included (9 males and 11 females; mean age 54.6 years): 18 with maculopapular exanthema, 1 with drug hypersensitivity syndrome, and 1 with acute generalized exanthematous pustulosis. Results were reproducible in 17 of 20 patients after a mean interval of 6.0 years (range 2-14.7 years). Concerning β-lactams, 7 of 8 patients remained positive for aminopenicillins, 4 of 4 for isoxazolyl penicillins, and 1 for cefoxitin. Patch test results were also reproducible for clindamycin in 5 of 7 patients, for vancomycin in 1 patient, and for spiramycin in 1 patient. Reproducibility was not affected by the time interval between tests, sex, or age at testing. In the context of NI CADRs, we showed high reproducibility of positive patch test reactions to various antibiotics, even after several years.

Severe Cutaneous Adverse Drug Reactions in Bangladesh: A Review in a Tertiary Level Hospital

Introduction: The Severe Cutaneous Adverse Drug Reactions (SCADRs) are rare but life-threatening as these encompass drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP).
 Objective: To estimate the incidence of SCADRs and to find out the cause in Bangladesh.
 Materials and Methods: 50 patients with SCADRs were studied over a period of 1 year from January 2015 to December 2015 in the Department of Dermatology, Combined Military Hospital, Dhaka. Data were collected from the informant and recorded in structured Case Report Form. Quantitative data were expressed as mean and standard deviation and qualitative data as frequency and percentage.
 Results: Clinical diagnosis of the study subjects recognized 46.0% cases as SJS, 28(19.0%) as TEN, 16.0% as DRESS and 10.0% as AGEP. The maximum incidence (46%) was seen in the age group of 31-50 years; mean age of the patient was 37.42+5.3 years. Male and female ratio was 2.84:1. Anticonvulsant group of drugs could give rise to maximum incidence of SCADRs. Carbamazepine was responsible in 22.0% cases of SCADRs, followed by Phenytoin in 16.0% patients and Phenobarbital in 14.0% cases.
 Conclusion: SCADRs were seen mostly with the anticonvulsant drugs belonging to Carbamazepine and Phenytoin group. SCADRs deserve continuous monitoring to plan preventive strategies.
 Journal of Armed Forces Medical College Bangladesh Vol.12(2) 2016: 71-75

An exploratory factor analysis of the spontaneous reporting of severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCARs) are prominent in pharmacovigilance (PhV). They have some commonalities such as nonimmediate nature and T-cell mediation and rare overlap syndromes have been documented, most commonly involving acute generalized exanthematous pustulosis (AGEP) and drug rash with eosinophilia and systemic symptoms (DRESS), and DRESS and toxic epidermal necrolysis (TEN). However, they display diverse clinical phenotypes and variations in specific T-cell immune response profiles, plus some specific genotype-phenotype associations. A question is whether causation of a given SCAR by a given drug supports causality of the same drug for other SCARs. If so, we might expect significant intercorrelations between SCARs with respect to overall drug-reporting patterns. SCARs with significant intercorrelations may reflect a unified underlying concept. We used exploratory factor analysis (EFA) on data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) to assess reporting intercorrelations between six SCARs [AGEP, DRESS, erythema multiforme (EM), Stevens-Johnson syndrome (SJS), TEN, exfoliative dermatitis (ExfolDerm)]. We screened the data using visual inspection of scatterplot matrices for problematic data patterns. We assessed factorability via Bartlett's test of sphericity, Kaiser-Myer-Olkin (KMO) statistic, initial estimates of communality and the anti-image correlation matrix. We extracted factors via principle axis factoring (PAF). The number of factors was determined by scree plot/Kaiser's rule. We also examined solutions with an additional factor. We applied various oblique rotations. We assessed the strength of the solution by percentage of variance explained, minimum number of factors loading per major factor, the magnitude of the communalities, loadings and crossloadings, and reproduced- and residual correlations. The data were generally adequate for factor analysis but the amount of variance explained, shared variance, and communalities were low, suggesting caution in general against extrapolating causality between SCARs. SJS and TEN displayed most shared variance. AGEP and DRESS, the other SCAR pair most often observed in overlap syndromes, demonstrated modest shared variance, along with maculopapular rash (MPR). DRESS and TEN, another of the more commonly diagnosed pairs in overlap syndromes, did not. EM was uncorrelated with SJS and TEN. The notion that causality of a drug for one SCAR bolsters support for causality of the same drug with other SCARs was generally not supported.

Six-transmembrane epithelial antigens of the prostate comprise a novel inflammatory nexus in patients with pustular skin disorders

Pustular skin disorders are a category of difficult-to-treat and potentially life-threatening conditions that involve the appearance of neutrophil-rich pustules. The molecular basis of most pustular skin conditions has remained unknown. We sought to investigate the molecular basis of 3 pustular skin disorders: generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP), and acute generalized exanthematous pustulosis (AGEP). Microarray analyses were performed to profile genome-wide gene expression of skin biopsy specimens obtained from patients with GPP, PPP, or AGEP and healthy control subjects. Functional enrichment, gene network, and k-means clustering analyses were used to identify molecular pathways dysregulated in patients with these disorders. Immunohistochemistry and immunofluorescence were used to determine protein localization. Quantitative RT-PCR and ELISA were used to determine transcript and secreted cytokine levels. Small interfering RNA was used to decrease transcript levels. Molecules and pathways related to neutrophil chemotaxis emerged as common alterations in patients with GPP, PPP, and AGEP, which is consistent with the pustular phenotypes. Expression of two 6-transmembrane epithelial antigens of the prostate (STEAP) proteins, STEAP1 and STEAP4, was increased in patients' skin and colocalized with IL-36γ around neutrophilic pustules. STEAP1/4 expression clustered with and positively correlated with that of IL-1, the IL-36 family proteins, and CXCL1/8. STEAP4 expression was activated by cytokines and suppressed by inhibition of mitogen-activated protein kinase kinase 1/2, whereas STEAP1 expression appeared less prone to such dynamic regulation. Importantly, STEAP1/4 knockdown resulted in impaired induction of a broad spectrum of proinflammatory cytokines, including IL-1, IL-36, and the neutrophil chemotaxins CXCL1 and CXCL8. STEAP1/4 knockdown also reduced the ability of keratinocytes to induce neutrophil chemotaxis. Transcriptomic changes in 3 pustular skin disorders, GPP, PPP, and AGEP, converged on neutrophil chemotaxis and diapedesis and cytokines known to drive neutrophil-rich inflammatory processes, including IL-1 and members of the IL-36 family. STEAP1 and STEAP4 positively regulate the induction of proinflammatory neutrophil-activating cytokines.

P017 A case of acute generalized exanthematous pustulosis in a patient on hemodialysis

Acute Generalized Exanthematous Pustulosis (AGEP) is a rare skin rash that begins on the face or intertriginous areas and spreads rapidly, with numerous sterile pustules seen on swollen erythema. First described as a subset of pustular psoriasis in a patient with no prior psoriasis history, AGEP typically has acute onset, with an incidence of about one in five million, elicited by drugs about 90% of the time. Most patients also have fevers and leukocytosis, plus mild eosinophilia. Histopathology shows spongiform subcorneal and/or intraepidermal pustule. Skin symptoms usually resolve within two weeks without treatment.

Reacciones adversas cutáneas severas a medicamentos: estado del conocimiento

Las reacciones adversas a medicamentos afectan de manera global entre el 10% y el 20% de los pacientes hospitalizados y el 7% de los pacientes ambulatorios. Aproximadamente, uno de cada mil pacientes hospitalizados sufren reacciones adversas que amenazan la vida. Las reacciones adversas a medicamentos, denominadas como reacciones alérgicas (inmunológicas), se pueden agrupar según la clasificación de Gell y Coombs en: tipo I (mediada por IgE), tipo II (citotóxica), tipo III (por inmunocomplejos) y tipo IV (hipersensibilidad retardada o celular). Actualmente, las reacciones tipo IV se subclasifican según la célula efectora involucrada y sus correspondientes citoquinas. Estos subgrupos se definen como: tipo IVa (con activación del perfil Th1, los macrófagos como células efectoras y liberación de INF-γ y TNF-α), tipo IVb (con activación del perfil Th2, los eosinófilos como células efectoras y liberación de citoquinas como la IL-5, la IL-4 y la IL-13), tipo IVc (con los linfocitos T citotóxicos como células efectoras y liberación de granzimas B y perforinas) y tipo IVd (con los neutrófilos como células efectoras y liberación de CXCL8 y factor estimulante de colonias de granulocitos y macrófagos). La presente revisión se centra en la epidemiología, etiología, fisiopatología y manifestaciones clínicas de las reacciones adversas cutáneas severas a medicamentos como el síndrome de Stevens Johnson, la necrólisis epidérmica tóxica, el síndrome DRESS y la pustulosis exantemática generalizada aguda (PEGA); además de un abordaje terapéutico en cada una de estas enfermedades.

An Acute Generalized Exanthematous Pustulosis Induced by Intravenous Iopromide: A Case Report

An Acute Generalized Exanthematous Pustulosis Induced by Intravenous Iopromide: A Case Report

Histopathological study of six types of adverse cutaneous drug reactions using granulysin expression.

Few studies have been published on the histopathology of cutaneous adverse drug reactions (CADR), and most of these lack information on skin allergological tests. The histopathology of drug reaction with eosinophilia and systemic symptoms (DRESS) is also seldom described. The purpose of our study was to examine six types of well-documented CADR (maculopapular exanthema, DRESS, fixed drug eruption, Stevens-Johnson syndrome, toxic epidermal necrolysis [TEN], and acute generalized exanthematous pustulosis) using histopathology and immunohistochemistry to evaluate the expression of granulysin, a key molecule in TEN. We retrospectively included 106 skin biopsies performed in proven cases of CADR (by chronological investigation, single attributable drug, or/and skin tests). All slides were reviewed, and microscopic changes were analyzed using a standardized form. Granulysin expression was studied by immunohistochemistry. In DRESS, we observed spongiosis, edema, and basal vacuolization, with rare necrotic keratinocytes and constant lymphocytic infiltrate in the superficial dermis. Eosinophils were often present, and pustules were found in 15% of cases. Necrotic keratinocytes are often absent in maculopapular exanthema. Granulysin was expressed in six types of CADR with a trend toward more intense expression in DRESS and TEN. We detailed further about the histopathology of DRESS. Granulysin expression was observed in all CADR with a marked overlap of expression pattern between the six types.

Acute generalized exanthematous pustulosis and generalized pustular psoriasis: Are they distinct pustular disorders?

Acute generalized exanthematous pustulosis and generalized pustular psoriasis: Are they distinct pustular disorders?

Mutation analysis of the IL36RN gene in Japanese patients with palmoplantar pustulosis

The IL36RN gene encodes the interleukin 36-receptor antagonist (IL-36 Ra), which regulates downstream inflammatory signaling provoked by interleukin-36 (α, β, and γ). Some of its mutations leading to deficiency of the IL-36Ra have been reported as the major cause of generalized pustular psoriasis (GPP) without psoriasis vulgaris. The mutation p.L27P caused by a point mutation c.213T>C on the second coding exon in IL36RN gene was originally reported to be associated with cases of familial GPP. Afterward, additional several mutations in IL36RN gene were reported. Recently, it has been reported that similar mutations were detected also in the patients with GPP-related diseases including palmoplantar pustulosis (PPP), acrodermatitis continua of Hallopeau, and acute generalized exanthematous pustulosis. Regarding PPP, which is considered as the localized type of pustular psoriasis, the mutation in IL36RN gene such as homozygous or heterozygous p.S113L has been identified only in very small numbers of patients. In addition, no sizable researches on Japanese patients with PPP have ever been conducted. In this study, we aim to analyze the IL36RN gene mutation in large-scale Japanese patients with PPP.