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      Acute Generalized Exanthematous Pustulosis Induced by Cefepime: A Case Report

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          Abstract

          Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous rash characterized by widespread sterile nonfollicular pustules. Cefepime is a fourth generation cephalosporin, used to treat severe infections. A 67-year-old man was admitted with acute gastroenterocolitis. On the seventh day, the patient developed a nosocomial pneumonia and cefepime was initiated. On the fourth day of cephalosporin treatment, he presented with a maculopapular, pruritic eruption affecting the face, neck, abdomen and limbs. One day later he developed disseminated pustular lesions and his temperature was 37°C. Laboratory analysis evidenced leukocytosis and skin biopsy showed subcorneal pustule, edema in the papillary dermis, perivascular inflammatory infiltrate consisting of neutrophils, leukocytoclasia and red cell extravasation in the epidermis. Cefepime was suspended and within 4 days the non-follicular pustules cleared following a desquamation. AGEP is a disease attributed to a variety of causes, but in 90% of the cases it is due to an adverse drug reaction. Antibiotics are implicated in 80% of these cases, mostly penicillins and macrolides. There are few cases associated with cephalosporins. It is very important to consider AGEP in cases of acute pustular rashes and drugs should be investigated as causative agents.

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

          L Vaillant, J Bouwes Bavinck, S Halevy … (2001)
          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).

            A Dunant, S Halevy, L Naldi … (2007)
            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. Analysis of 63 cases.

              Laura Bernard, A Claudy, C Delavierre … (1991)
              We retrospectively analyzed 63 observations collected in nine French departments of dermatology of an acute pustular dermatosis, recently named in the French literature acute generalized exanthematous pustulosis (AGEP). Even though 11 of these cases occurred in patients with a history of psoriasis, AGEP appeared distinct from pustular psoriasis based on several slight pathologic differences, drug induction in most cases, and a more acute course of fever and pustulosis, with rapid spontaneous healing. We, therefore, suggest that AGEP is a reaction pattern, perhaps favored by a "psoriatic background." The most frequent causes of AGEP seem to be drug reactions, acute infections with enteroviruses, and hypersensitivity to mercury. With 55 (87%) of 63 cases attributed to drugs in this series, AGEP should be added to the list of cutaneous adverse drug reactions. Among drug-induced skin eruptions, AGEP is remarkable by its short time to onset after the administration of the suspected drug (less than 24 hours in half of our cases) and the great predominance (80%) of antibiotics as causative agents. It is suggested that some cases previously reported as "drug-induced pustular psoriasis" were in fact AGEP.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Case Rep Dermatol
                Journal ID (publisher-id): CDE
                Title: Case Reports in Dermatology
                Publisher: S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.ch )
                ISSN (Electronic): 1662-6567
                Publication date Collection: May-Aug 2010
                Publication date (Electronic): 01 June 2010
                Publication date PMC-release: 01 June 2010
                Volume: 2
                Issue: 2
                Pages: 82-87
                Affiliations
                [1] aDepartment of Dermatology, Federal University of São Paulo, São Paulo, Brazil
                [2] bDepartment of Anatomopathology, Federal University of São Paulo, São Paulo, Brazil
                [3] cDepartment of Emergency Medicine, Federal University of São Paulo, São Paulo, Brazil
                Author notes
                *Luciane F.F. Botelho, MD, Dermatology Department, Federal University of São PauloRua Borges Lagoa, 933/44, São Paulo, SP 04038-032 (Brazil), Tel. +55 11 3476 6963, E-Mail lucianebotelho@ 123456hotmail.com
                Article
                Publisher ID: cde0002-0082
                DOI: 10.1159/000314474
                PMC ID: 2988841
                PubMed ID: 21103192
                SO-VID: 829e16c8-fdfb-4866-a37c-3df0dbe900e1
                Copyright © Copyright © 2010 by S. Karger AG, Basel
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial-No-Derivative-Works License ( http://creativecommons.org/licenses/by-nc-nd/3.0/). Users may download, print and share this work on the Internet for noncommercial purposes only, provided the original work is properly cited, and a link to the original work on http://www.karger.com and the terms of this license are included in any shared versions.

                History
                Page count
                Figures: 2, Tables: 2, References: 15, Pages: 6
                Categories
                Subject: Published: June 2010

                ScienceOpen disciplines: Dermatology
                Keywords: cefepime,drug eruption,acute generalized exanthematous pustulosis
                Data availability:
                ScienceOpen disciplines: Dermatology
                Keywords: cefepime, drug eruption, acute generalized exanthematous pustulosis

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