Acute generalized exanthematous pustulosis (AGEP)
- Alexis Sidoroff, MD
Alexis Sidoroff, MD
- Professor of Dermatology and Venereology
- Medical University of Innsbruck, Austria
- Chia-Yu Chu, MD, PhD
Chia-Yu Chu, MD, PhD
- Associate Professor - Department of Dermatology
- National Taiwan University Hospital
- Section Editors
- Jean-Claude Roujeau, MD
Jean-Claude Roujeau, MD
- Section Editor — Drug Eruptions
- Emeritus Professor of Dermatology
- Université Paris-Est Créteil (UPEC), Créteil, France
- Maja Mockenhaupt, MD, PhD
Maja Mockenhaupt, MD, PhD
- Section Editor — Drug Eruptions
- Professor of Dermatology
- Medical Center - University of Freiburg, Germany
Acute generalized exanthematous pustulosis (AGEP) is a rare, acute eruption characterized by the development of numerous nonfollicular sterile pustules on a background of edematous erythema (picture 1A) [1,2]. Fever and peripheral blood leukocytosis are usually present.
In approximately 90 percent of cases, AGEP is caused by drugs, most often antibiotics (eg, aminopenicillins and macrolides), antifungals, the calcium channel blocker diltiazem, and antimalarials . The eruption develops within hours or days of drug exposure and resolves spontaneously in one to two weeks after drug discontinuation.
AGEP will be discussed in this topic. Other types of cutaneous drug reactions and pustular eruptions are discussed separately.
●(See "Drug eruptions".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Sidoroff A, Halevy S, Bavinck JN, et al. Acute generalized exanthematous pustulosis (AGEP)--a clinical reaction pattern. J Cutan Pathol 2001; 28:113.
- Speeckaert MM, Speeckaert R, Lambert J, Brochez L. Acute generalized exanthematous pustulosis: an overview of the clinical, immunological and diagnostic concepts. Eur J Dermatol 2010; 20:425.
- Roujeau JC, Bioulac-Sage P, Bourseau C, et al. Acute generalized exanthematous pustulosis. Analysis of 63 cases. Arch Dermatol 1991; 127:1333.
- Ji YZ, Geng L, Qu HM, et al. Acute generalized exanthematous pustulosis induced by docetaxel. Int J Dermatol 2011; 50:763.
- Nakamizo S, Kobayashi S, Usui T, et al. Clopidogrel-induced acute generalized exanthematous pustulosis with elevated Th17 cytokine levels as determined by a drug lymphocyte stimulation test. Br J Dermatol 2010; 162:1402.
- Son CH, Lee CU, Roh MS, et al. Acute generalized exanthematous pustulosis as a manifestation of carbamazepine hypersensitivity syndrome. J Investig Allergol Clin Immunol 2008; 18:461.
- Sidoroff A, Dunant A, Viboud C, et al. Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR). Br J Dermatol 2007; 157:989.
- Birnie AJ, Litlewood SM. Acute generalized exanthematous pustulosis does not always have a drug-related cause. Br J Dermatol 2008; 159:492.
- Manzano S, Guggisberg D, Hammann C, Laubscher B. [Acute generalized exanthematous pustulosis: first case associated with a Chlamydia pneumoniae infection]. Arch Pediatr 2006; 13:1230.
- Ofuji S, Yamamoto O. Acute generalized exanthematous pustulosis associated with a human parvovirus B19 infection. J Dermatol 2007; 34:121.
- Cannistraci C, Parola IL, RiganO R, et al. Acute generalized exanthematous pustulosis in cystic echinococcosis: immunological characterization. Br J Dermatol 2003; 148:1245.
- Makris M, Spanoudaki N, Giannoula F, et al. Acute generalized exanthematous pustulosis (AGEP) triggered by a spider bite. Allergol Int 2009; 58:301.
- Davidovici BB, Pavel D, Cagnano E, et al. Acute generalized exanthematous pustulosis following a spider bite: report of 3 cases. J Am Acad Dermatol 2006; 55:525.
- Zaraa I, Ben Taazayet S, Trojjet S, et al. Acute generalized exanthematous pustulosis induced by the essential oil of Pistacia lentiscus. Clin Exp Dermatol 2012; 37:361.
- Yoon TY, Lee DY, Kim YJ, et al. Acute generalized exanthematous pustulosis induced by velvet antler. Br J Dermatol 2011; 165:447.
- Choi MJ, Kim HS, Park HJ, et al. Clinicopathologic manifestations of 36 korean patients with acute generalized exanthematous pustulosis: a case series and review of the literature. Ann Dermatol 2010; 22:163.
- Saissi EH, Beau-Salinas F, Jonville-Béra AP, et al. [Drugs associated with acute generalized exanthematic pustulosis]. Ann Dermatol Venereol 2003; 130:612.
- Ueda T, Abe M, Okiyama R, et al. Acute generalized exanthematous pustulosis due to allylisopropylacetylurea: role of IL-17-producing T cells. Eur J Dermatol 2011; 21:140.
- Smith K, Norwood C, Skelton H. Do the physical and histologic features and time course in acute generalized exanthematous pustulosis reflect a pattern of cytokine dysregulation? J Cutan Med Surg 2003; 7:7.
- Britschgi M, Pichler WJ. Acute generalized exanthematous pustulosis, a clue to neutrophil-mediated inflammatory processes orchestrated by T cells. Curr Opin Allergy Clin Immunol 2002; 2:325.
- Britschgi M, Steiner UC, Schmid S, et al. T-cell involvement in drug-induced acute generalized exanthematous pustulosis. J Clin Invest 2001; 107:1433.
- Britschgi M, von Greyerz S, Burkhart C, Pichler WJ. Molecular aspects of drug recognition by specific T cells. Curr Drug Targets 2003; 4:1.
- Pichler WJ. T cells in drug allergy. Curr Allergy Asthma Rep 2002; 2:9.
- Schmid S, Kuechler PC, Britschgi M, et al. Acute generalized exanthematous pustulosis: role of cytotoxic T cells in pustule formation. Am J Pathol 2002; 161:2079.
- Tokura Y, Mori T, Hino R. Psoriasis and other Th17-mediated skin diseases. J UOEH 2010; 32:317.
- Kabashima R, Sugita K, Sawada Y, et al. Increased circulating Th17 frequencies and serum IL-22 levels in patients with acute generalized exanthematous pustulosis. J Eur Acad Dermatol Venereol 2011; 25:485.
- Onoufriadis A, Simpson MA, Pink AE, et al. Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. Am J Hum Genet 2011; 89:432.
- Navarini AA, Valeyrie-Allanore L, Setta-Kaffetzi N, et al. Rare variations in IL36RN in severe adverse drug reactions manifesting as acute generalized exanthematous pustulosis. J Invest Dermatol 2013; 133:1904.
- Nakai N, Sugiura K, Akiyama M, Katoh N. Acute generalized exanthematous pustulosis caused by dihydrocodeine phosphate in a patient with psoriasis vulgaris and a heterozygous IL36RN mutation. JAMA Dermatol 2015; 151:311.
- Navarini AA, Simpson MA, Borradori L, et al. Homozygous missense mutation in IL36RN in generalized pustular dermatosis with intraoral involvement compatible with both AGEP and generalized pustular psoriasis. JAMA Dermatol 2015; 151:452.
- Burrows NP, Russell Jones RR. Pustular drug eruptions: a histopathological spectrum. Histopathology 1993; 22:569.
- Halevy S, Kardaun SH, Davidovici B, et al. The spectrum of histopathological features in acute generalized exanthematous pustulosis: a study of 102 cases. Br J Dermatol 2010; 163:1245.
- Prange B, Marini A, Kalke A, et al. [Acute localized exanthematous pustulosis (ALEP)]. J Dtsch Dermatol Ges 2005; 3:210.
- Betto P, Germi L, Bonoldi E, Bertazzoni M. Acute localized exanthematous pustulosis (ALEP) caused by amoxicillin-clavulanic acid. Int J Dermatol 2008; 47:295.
- Rastogi S, Modi M, Dhawan V. Acute localized exanthematous pustulosis (ALEP) caused by Ibuprofen. A case report. Br J Oral Maxillofac Surg 2009; 47:132.
- Peermohamed S, Haber RM. Acute generalized exanthematous pustulosis simulating toxic epidermal necrolysis: a case report and review of the literature. Arch Dermatol 2011; 147:697.
- Azib S, Florin V, Fourrier F, et al. Severe acute generalized exanthematous pustulosis with blistering mimicking toxic epidermal necrolysis, associated with a primary mumps infection. Clin Exp Dermatol 2014; 39:723.
- van Hattem S, Beerthuizen GI, Kardaun SH. 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. Br J Dermatol 2014; 171:1539.
- Meiss F, Helmbold P, Meykadeh N, et al. Overlap of acute generalized exanthematous pustulosis and toxic epidermal necrolysis: response to antitumour necrosis factor-alpha antibody infliximab: report of three cases. J Eur Acad Dermatol Venereol 2007; 21:717.
- Kardaun SH. Acute generalized exanthematous pustulosis (AGEP), presenting with toxic epidermal necrolysis-like features, due to morphine: a neglected culprit? Eur J Dermatol 2011; 21:427.
- Wensween CA, Bouwes Bavinck JN. [Overlapping acute disseminated exanthematous pustulosis and toxic epidermal necrolysis]. Ned Tijdschr Geneeskd 2001; 145:1525.
- Kostopoulos TC, Krishna SM, Brinster NK, Ortega-Loayza AG. Acute generalized exanthematous pustulosis: atypical presentations and outcomes. J Eur Acad Dermatol Venereol 2015; 29:209.
- Hotz C, Valeyrie-Allanore L, Haddad C, et al. Systemic involvement of acute generalized exanthematous pustulosis: a retrospective study on 58 patients. Br J Dermatol 2013; 169:1223.
- Alniemi DT, Wetter DA, Bridges AG, et al. Acute generalized exanthematous pustulosis: clinical characteristics, etiologic associations, treatments, and outcomes in a series of 28 patients at Mayo Clinic, 1996-2013. Int J Dermatol 2017; 56:405.
- Treudler R, Grunewald S, Gebhardt C, Simon JC. Prolonged course of acute generalized exanthematous pustulosis with liver involvement due to sensitization to amoxicillin and paracetamol. Acta Derm Venereol 2009; 89:314.
- Brandenburg VM, Kurts C, Eitner F, et al. Acute reversible renal failure in acute generalized exanthematous pustulosis. Nephrol Dial Transplant 2002; 17:1857.
- Kardaun SH, Kuiper H, Fidler V, Jonkman MF. The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis. J Cutan Pathol 2010; 37:1220.
- Friedmann PS, Ardern-Jones M. Patch testing in drug allergy. Curr Opin Allergy Clin Immunol 2010; 10:291.
- Barbaud A. Drug patch testing in systemic cutaneous drug allergy. Toxicology 2005; 209:209.
- Whittam LR, Wakelin SH, Barker JN. Generalized pustular psoriasis or drug-induced toxic pustuloderma? The use of patch testing. Clin Exp Dermatol 2000; 25:122.
- Wolkenstein P, Chosidow O, Fléchet ML, et al. Patch testing in severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Contact Dermatitis 1996; 35:234.
- Mashiah J, Brenner S. A systemic reaction to patch testing for the evaluation of acute generalized exanthematous pustulosis. Arch Dermatol 2003; 139:1181.
- Lazarov A, Livni E, Halevy S. Generalized pustular drug eruptions: confirmation by in vitro tests. J Eur Acad Dermatol Venereol 1998; 10:36.
- Halevy S, Cohen A, Livni E. Acute generalized exanthematous pustulosis associated with polysensitivity to paracetamol and bromhexine: the diagnostic role of in vitro interferon-gamma release test. Clin Exp Dermatol 2000; 25:652.
- Beltraminelli HS, Lerch M, Arnold A, et al. Acute generalized exanthematous pustulosis induced by the antifungal terbinafine: case report and review of the literature. Br J Dermatol 2005; 152:780.
- Girardi M, Duncan KO, Tigelaar RE, et al. Cross-comparison of patch test and lymphocyte proliferation responses in patients with a history of acute generalized exanthematous pustulosis. Am J Dermatopathol 2005; 27:343.
- Natkunarajah J, Ostlere L. Severe acute generalized exanthematous pustulosis with blistering, mimicking toxic epidermal necrolysis. Clin Exp Dermatol 2012; 37:188.
- Bouvresse S, Valeyrie-Allanore L, Ortonne N, et al. Toxic epidermal necrolysis, DRESS, AGEP: do overlap cases exist? Orphanet J Rare Dis 2012; 7:72.
- Teo WL, Pang SM, Koh HY. Allopurinol hypersensitivity syndrome with acute generalized exanthematous pustulosis manifestations. Cutan Ocul Toxicol 2011; 30:243.
- Ben Salem C, Fathallah N, Saidi W, et al. Acute generalized exanthematous pustulosis as a manifestation of anticonvulsant hypersensitivity syndrome. Ann Pharmacother 2010; 44:1681.
- Cheng S, Edmonds E, Ben-Gashir M, Yu RC. Subcorneal pustular dermatosis: 50 years on. Clin Exp Dermatol 2008; 33:229.
- Kasha EE Jr, Epinette WW. Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) in association with a monoclonal IgA gammopathy: a report and review of the literature. J Am Acad Dermatol 1988; 19:854.
- Butt A, Burge SM. Sneddon-Wilkinson disease in association with rheumatoid arthritis. Br J Dermatol 1995; 132:313.
- Brantley EI, Sheth P. Subcorneal pustular dermatosis in a patient with rheumatoid arthritis and diffuse scleroderma. Dermatol Online J 2009; 15:5.
- Ahmad K, Ramsay B. Pyoderma gangrenosum associated with subcorneal pustular dermatosis and IgA myeloma. Clin Exp Dermatol 2009; 34:46.
- Brown SJ, Barrett PD, Hendrick A, Langtry JA. Subcorneal pustular dermatosis in association with chronic lymphocytic leukaemia. Acta Derm Venereol 2003; 83:306.
- Gréco M, Plantin P. Acute generalized exanthematous pustulosis (AGEP) induced by terbinafine with involuntary positive reintroduction. Eur J Dermatol 2005; 15:116.
- Park JJ, Yun SJ, Lee JB, et al. A case of hydroxychloroquine induced acute generalized exanthematous pustulosis confirmed by accidental oral provocation. Ann Dermatol 2010; 22:102.
- Lee HY, Chou D, Pang SM, Thirumoorthy T. Acute generalized exanthematous pustulosis: analysis of cases managed in a tertiary hospital in Singapore. Int J Dermatol 2010; 49:507.
- Ingen-Housz-Oro S, Hotz C, Valeyrie-Allanore L, et al. Acute generalized exanthematous pustulosis: a retrospective audit of practice between 1994 and 2011 at a single centre. Br J Dermatol 2015; 172:1455.
- Chang SL, Huang YH, Yang CH, et al. Clinical manifestations and characteristics of patients with acute generalized exanthematous pustulosis in Asia. Acta Derm Venereol 2008; 88:363.
- ETIOLOGY AND PATHOGENESIS
- Eliciting factors
- Immunologic mechanisms
- CLINICAL FEATURES
- CLINICAL COURSE
- Clinical and histologic
- Laboratory tests
- DIFFERENTIAL DIAGNOSIS
- Drug withdrawal and supportive measures
- Symptomatic treatment
- SUMMARY AND RECOMMENDATIONS