Acute generalized exanthematous pustulosis due to clindamycin

Acute generalized exanthematous pustulosis (AGEP) is a rare skin eruption most commonly caused by medications. It is characterized by fever and the acute eruption of non-follicular pustules overlying erythrodermic skin. Histopathology shows subcorneal pustules with a background of dermal edema and spongiosis, leukocytoclastic vasculitis, perivascular eosinophils, and focal necrosis of keratinocytes. Three cases of clindamycin induced AGEP have been reported in the literature. A case of AGEP due to clindamycin is reported in a patient with numerous other drug allergies and without history of psoriasis. Presentation and treatment of AGEP are reviewed.     

Acute generalized exanthematous pustulosis induced by the essential oil of Pistacia lentiscus

Acute generalized exanthematous pustulosis (AGEP) is an uncommon pustular eruption characterized by small nonfollicular pustules on an erythematous background, sometimes associated with fever and neutrophilia. Over 90% of cases are drug-induced; however, it can be caused in rare cases by other agents. We report two cases of AGEP secondary to ingestion of Pistacia lentiscus essential oil, the first two such cases to our knowledge. The cutaneous morphology, disease course and histological findings were consistent with a definite diagnosis of AGEP, based on the criteria of the EuroSCAR study group. These two cases highlight the need to consider herbal extracts as a potential rare cause of AGEP and to ensure the safety of herbal medicines.     

Acute generalized exanthematous pustulosis following a spider bite: report of 3 cases

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction caused mostly by drugs. Three of 22 AGEP cases (13.6%), recruited by us as part of two prospective multinational studies, occurred 24 to 48 hours after a spider bite. We suggest that a spider bite is a possible trigger for AGEP.     

Rapid clearing of acute generalized exanthematous pustulosis after administration of ciclosporin

Acute generalized exanthematous pustulosis (AGEP) is a rare disorder, usually drug‐induced, and is clinically characterized by widespread, non‐follicular aseptic pustules. Although spontaneous resolution usually occurs once the causative drug has been withdrawn, more severe cases often require treatment with systemic corticosteroids. We report a 63‐year‐old woman who developed AGEP after a 30‐day course of hydroxychloroquine. Extensive re‐exacerbation of AGEP after an 18‐day course of methylprednisolone led us to switch the treatment to oral ciclosporin with a prompt and satisfactory improvement. Ciclosporin has many inhibitory effects on the main cell population (T cells) involved in AGEP. In particular, a significant reduction in producton of interleukin‐8 by T cells is a possible explanation of the rapid remission observed in this case. To our knowledge, this is the first reported case of AGEP successfully treated with ciclosporin.     

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

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

Acute generalized exanthematous pustulosis and polyarthritis associated with a novel CARD14 mutation

Acute generalised exanthematous pustulosis (AGEP) is a rare toxicoderma characterised by an acute onset rash, with many sterile pustules on the surface, high fever and increased acute phase reactants. We report the case of a patient who presented to the dermatology department with an AGEP and polyarthritis, in which a novel CARD14 mutation was identified. The pathophysiological mechanism of AGEP remains unclear, although mutations in the IL36RN gene have been identified in a small subset of AGEP patients. Similarly, mutations in the CARD14 gene have been linked to pustular types of psoriasis and familiar cases of pityriasis rubra pilaris; however, there are no reports associating mutations in the CARD14 gene with AGEP.     

Acute localised exanthematous pustulosis (ALEP) induced by clindamycin in pregnancy

Acute generalised exanthematous pustulosis (AGEP) or toxic pustuloderma (TP) is an uncommon though well‐recognised cutaneous hypersensitivity reaction that is usually drug‐induced. It presents with a triad of scattered sterile pustules, fever and malaise. Acute localised exanthematous pustulosis (ALEP) is a rare and unusual variant of AGEP. We describe a case of ALEP triggered by oral clindamycin that occurred during pregnancy.     

Acute generalized exanthematous pustulosis due to ceftriaxone: Report of a pediatric case with recurrence after positive patch test

Acute generalized exanthematous pustulosis (AGEP) is seen uncommonly in children and sometimes shows atypical clinical features in this population. Patch testing can be used effectively in children for the confirmation of the culprit drug in cases of multiple drug use. Here, we report a rare, pediatric case of ceftriaxone‐induced AGEP confirmed by patch testing with subsequent recurrence of the skin eruption.     

Severe flucloxacillin‐induced acute generalized exanthematous pustulosis (AGEP), with toxic epidermal necrolysis (TEN)‐like features: does overlap between AGEP and TEN exist? Clinical report and review of the literature

Acute generalized exanthematous pustulosis (AGEP) and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse drug reactions. Especially in TEN, large areas of the skin and mucosae may become detached. Although AGEP and SJS/TEN are distinct entities with a different clinical picture, pathogenesis, prognosis and treatment, they may share some features, raising the hypothesis of overlap between both entities. We present a severe case of AGEP, caused by flucloxacillin, clinically presenting with TEN‐like features and pronounced systemic symptoms with haemodynamic and respiratory instability. Furthermore, we present a review of the literature on cases of AGEP with features resembling SJS/TEN or a supposed overlap with SJS/TEN.     

Acute generalized exanthematous pustulosis (AGEP)--a clinical reaction pattern

BACKGROUND: A wide range of diseases or reactions can cause pustular eruptions of the skin. In this spectrum there seems to be a subgroup with characteristic clinical features and a typical course which is mostly caused by drugs for which the term acute generalized exanthematous pustulosis (AGEP) has been established. OBJECTIVE: To describe the clinical features of AGEP. METHODS: The authors' experience from a multinational epidemiological study on severe cutaneous adverse reactions and a comprehensive review of the literature were used to provide an overview of the disease and it's possible causes. An algorithm for validating cases which was established for this study is also presented. RESULTS: AGEP typically presents with at least dozens of non follicular sterile pustules occurring on a diffuse, edematous erythema predominantly in the folds and/or on the face. Fever and elevated blood neutrophils are common. Histopathology typically shows spongiform subcorneal and/or intraepidermal pustules, a marked edema of the papillary dermis, and eventually vasculitis, eosinophils and/or focal necrosis of keratinocytes. Onset is acute, most often following drug intake, but viral infections can also trigger the disease. Pustules resolve spontaneously in less than 15 days. CONCLUSION: The diagnosis AGEP should be considered in cases of acute pustular rashes and detection of the causative drug should be strived for. Knowledge of the clinical features and usual course of this disease can often prevent unnecessary therapeutical measures.     

Oral prednisolone induced acute generalized exanthematous pustulosis due to corticosteroids of group A confirmed by epicutaneous testing and lymphocyte transformation tests

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption which is often provoked by drugs. CASE REPORT: We report 2 cases of AGEP which showed rapidly spreading pustular eruptions accompanied by malaise, fever and neutrophilia after the administration of systemic prednisolone (corticosteroid of group A, hydrocortisone type). The histological examination showing neutrophilic subcorneal spongiform pustules was consistent with the diagnosis of AGEP. In both cases the rash cleared within a week upon treatment with topical steroids (corticosteroid of group D1, betamethasonedipropionate type and corticosteroid of group D2, hydrocortisone-17-butyrate type). Three months after recovery, the sensitization to corticosteroids of group A was confirmed by epicutaneous testing and positive lymphocyte transformation tests. CONCLUSION: These cases show that systemic corticosteroids can induce AGEP and demonstrate that epicutaneous testing and lymphocyte transformation tests may be helpful in identifying the causative drug. Our data support previous reports indicating an important role for drug-specific T cells in inducing neutrophil inflammation in this disease.     

Acute generalized exanthematous pustulosis after pemetrexed, and recurrence after re-introduction

Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous reaction, which in most cases, is related to medication. Pemetrexed is an antifolate drug, approved for treatment of metastatic non-small-cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). We present a case of AGEP caused by pemetrexed, and a recurrence of this eruption after re-introduction of pemetrexed despite use of corticosteroids.     

Concurrent acute generalized exanthematous pustulosis in siblings

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction triggered in most cases by drugs. It is characterized by abrupt onset and rapid evolution of fields of sterile pustules on an erythematous background. The role of genetic predisposition in this reactive disorder is being explored. We report the simultaneous occurrence of AGEP in two siblings after being exposed to the same drug.     

Do the Physical and Histologic Features and Time Course in Acute Generalized Exanthematous Pustulosis Reflect a Pattern of Cytokine Dysregulation?

Background: Acute generalized exanthematous pustulosis (AGEP) is characterized by fever and an indurated erythematous eruption early, with the development of nonfollicular pinhead sterile pustules on an erythematous background. The eruption progresses and resolves relatively rapidly. Although drugs are believed to be the major etiologic agents, other immune modulators, including infections, heavy metals, and radiation, have been implicated. Objective: The purpose of this study was to document underlying diseases in patients with AGEP and to determine if this data and the histologic features suggested an underlying pattern of immune dysregulation. Methods: Twenty-one patients with new or recurrent episodes of AGEP were questioned concerning underlying diseases. The histopathologic features seen in the biopsy sections and the approximate time of biopsy during the course of their eruptions were recorded. Results: Two patients had a history of psoriasis and one patient had a family history of psoriasis, two patients had diagnoses of sarcoid, two patients had inflammatory bowel disease, one had autoimmune thyroiditis, and one patient had multiple sclerosis. Biopsies done at the onset of the eruption showed marked to moderate papillary dermal edema and a mixed dermal inflammatory infiltrate. Shortly thereafter, biopsies showed spongiform pustules within the epidermis and occasional dyskeratotic cells with residual perivascular dermal edema. Although no definitive vasculitis was seen, there was leukocytoclasis within the dermal infiltrate in the majority of biopsy specimens performed more than 48 hours after the onset of the eruption. Conclusion: The histologic features seen in AGEP and the disease associations suggest that patients who develop this eruption may have an underlying tendency for development of a pattern of immune dysregulation characterized by a T helper-1 cytokine pattern.     

Acute generalized exanthematous pustulosis following oral nystatin therapy: a report of three cases

Summary We report three cases of acute generalized exanthematous pustulosis (AGEP) following oral administration of nystatin. All cases showed similar clinical features and hislopathological findings, and a delnyed-type hypersensitivily to nystatin could be demonstrated in patch and prick testing. Drug eruptions to nystatin are extremely rare, and, to our knowledge, AGEP has not been reported previously.     

Schwere Arzneimittelreaktionen der Haut

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are severe drug-induced bullous skin reactions. They are rare, but often life-threatening and have a high mortality rate. Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction, but after the suspected drug is withdrawn, the skin heals rapidly and mortality is low. The clinical pattern, histology and inducing drugs differ substantially between AGEP and the SJS/TEN group.     

Diltiazem-induced acute generalised exanthematous pustulosis

Pustulation is a major feature in several different dermatoses, and it may also occur as a manifestation of drug: hypersensitivity. Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption characterized by acute, extensive formation of sterile pustules, fever and peripheral blood leucucytosis. It shares several clinical and historical features in common with pustular psoriasis. Most reported cases have been triggered by ingestion of broad spectrum antibiotics, particularly betalactams and macrolides. There is usually rapid resolution of the eruption on drug withdrawal. We report the case of a 58 year-old woman who developed AGEP shortly after commencing treatment with the calcium channel binder diltiazem hydro-chloride. The eruption followed a biphasic course, and improved following treatment with systemic corti-costeroids and methotrexate. AGEP appears to be a rare adverse cutaneous reaction to diltiazem, whereas a wide range of other skin eruptions have been reported more commonly with this drug.     

Acute Generalized Exanthematous Pustulosis Associated with Tigecycline

Acute generalized exanthematous pustulosis (AGEP) is a severe and rare eruption that develops mostly from factors related to drugs. It is characterized by a fever and a pustular eruption on the erythematous skin with an acute onset and without follicular localization. Etiopathogenesis has not yet been fully explained. Although it is similar to pustular psoriasis, its clinical, historical and histopathological characteristics are different. In this article, we present a case of AGEP associated with tigecycline that developed in a patient followed up in the intensive care unit for three months with an intra-abdominal injury after a trauma and Acinetobacter baumannii infection.