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      Acute Generalized Exanthematous Pustulosis: Clinical Features, Differential Diagnosis, and Management

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          Abstract

          Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, and drug-induced etiologies. Diagnosis of AGEP depends on both clinical and histologic criteria, as cases of overlap with other disease processes have been reported. Management includes removal of the offending drug or treatment of the underlying cause, if necessary, and supportive care, as AGEP is a self-limited disease. This review aims to provide an overview and update on the epidemiology, pathogenesis, reported precipitating factors, differentials, diagnosis, and management of AGEP.

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

          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. To describe the clinical features of AGEP. 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. 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. 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.
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            Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR).

            Acute generalized exanthematous pustulosis (AGEP) is a disease characterized by the rapid occurrence of many sterile, nonfollicular pustules usually arising on an oedematous erythema often accompanied by leucocytosis and fever. It is usually attributed to drugs. To evaluate the risk for different drugs of causing AGEP. A multinational case-control study (EuroSCAR) conducted to evaluate the risk for different drugs of causing severe cutaneous adverse reactions; the study included 97 validated community cases of AGEP and 1009 controls. Results Strongly associated drugs, i.e. drugs with a lower bound of the 95% confidence interval (CI) of the odds ratio (OR) > 5 were pristinamycin (CI 26-infinity), ampicillin/amoxicillin (CI 10-infinity), quinolones (CI 8.5-infinity), (hydroxy)chloroquine (CI 8-infinity), anti-infective sulphonamides (CI 7.1-infinity), terbinafine (CI 7.1-infinity) and diltiazem (CI 5.0-infinity). No significant risk was found for infections and a personal or family history of psoriasis (CI 0.7-2.2). Medications associated with AGEP differ from those associated with Stevens-Johnson syndrome or toxic epidermal necrolysis. Different timing patterns from drug intake to reaction onset were observed for different drugs. Infections, although possible triggers, played no prominent role in causing AGEP and there was no evidence that AGEP is a variant of pustular psoriasis.
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              Acute generalized exanthematous pustulosis (AGEP): A review and update.

              Acute generalized exanthematous pustulosis is a severe cutaneous adverse reaction characterized by the rapid development of nonfollicular, sterile pustules on an erythematous base. It is attributed to drugs in the majority of cases. Antibiotics are the most common cause of acute generalized exanthematous pustulosis; however, a wide variety of drugs has been associated with this condition. Typically, within 48 hours of ingesting the causative medication, there is acute onset of fever and pustulosis with leukocytosis. In severe cases there can be mucous membrane and systemic organ involvement. Histologic findings include intracorneal, subcorneal, and/or intraepidermal pustules with papillary dermal edema containing neutrophils and eosinophils. Treatment focuses on removal of the causative drug, supportive care, infection prevention, and the often beneficial use of a potent topical steroid.

                Author and article information

                Contributors
                rdodiukgad@gmail.com
                Journal
                Am J Clin Dermatol
                Am J Clin Dermatol
                American Journal of Clinical Dermatology
                Springer International Publishing (Cham )
                1175-0561
                1179-1888
                8 May 2023
                : 1-19
                Affiliations
                [1 ]GRID grid.413558.e, ISNI 0000 0001 0427 8745, Albany Medical College, Albany, ; New York, NY USA
                [2 ]GRID grid.410567.1, Department of Dermatology and Allergy, , University Hospital of Basel, ; Basel, Switzerland
                [3 ]GRID grid.469889.2, ISNI 0000 0004 0497 6510, Department of Dermatology, , Emek Medical Center, ; Afula, Israel
                [4 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Division of Dermatology, Department of Medicine, , University of Toronto, ; Toronto, ON M5S 1A1 Canada
                [5 ]GRID grid.6451.6, ISNI 0000000121102151, Department of Dermatology, Bruce Rappaport Faculty of Medicine, , Technion Institute of Technology, ; Haifa, 3525433 Israel
                Author information
                http://orcid.org/0000-0003-2454-6895
                http://orcid.org/0000-0002-8407-9339
                http://orcid.org/0000-0001-7059-632X
                http://orcid.org/0000-0001-9151-1145
                http://orcid.org/0000-0003-2168-3798
                Article
                779
                10.1007/s40257-023-00779-3
                10166469
                37156992
                82737826-29bd-4dd6-91ec-55b972e238c0
                © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 27 March 2023
                Categories
                Review Article

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