Co-amoxiclav-inducedacute generalizedexanthematouspustulosis confirmed bypatch testing

Contact Dermatitis 2006: 55: 372

Matthew J. Harries1, Sister J. McIntyre2

and T. P. Kingston2

1The Dermatology Centre, The University ofManchester, Hope Hospital, Stott Lane,Salford, Manchester M6 8HD, UK and2Department of Dermatology, MacclesfieldDistrict General Hospital, Victoria Road,Macclesfield, Cheshire SK10 3BL, UK

Key words: acute generalized exanthematouspustulosis (AGEP); co-amoxiclav; patch test.

Case Report

A 34-year-old lady was referred fromthe maternity department with a rap-idly evolving rash that had developed2 days after an elective caesarean sec-tion. Examination showed a general-ized itchy rash mainly involving herchest, back, and proximal limbs.The skin was erythematous, oedema-tous, and slightly scaly and wasstudded with small non-follicularpustules particularly over the groinand thighs. The patient was pyrexialand tachycardic and felt unwell.

An adverse cutaneous drug reactionwas suspected, and all recent medica-tion was reviewed. It is transpired thatshe had received a single intravenousdose of co-amoxiclav (amoxicillinand clavulanic acid—Augmentin�,Uxbridge, UK) during the caesareansection as a prophylactic measurebased on departmental protocol. Shehad also received oral diclofenac as anal-gesia, subcutaneous enoxaparin forthromoembolism prophylaxis, andintravenous granisetron as an antiemeticprior to the rash developing.

A skin biopsy showed acute inflam-mation of both the epidermis and thedermis predominantly with neutrophils,marked papillary oedema, and smallsub-corneal pustule formation. Thediagnosis of acute generalized exanthe-matous pustulosis (AGEP) was made.All medication was stopped, and therash quickly settled over the next 7days with conservative management.

Three months later, she was patchtested to the British Contact Der-

matitis Society standard series, co-amoxiclav (1%, 5%, and 10% pet.),diclofenac (1% and 5% pet.), enoxa-parin (1% and 5% aqueous), and gra-nisetron (1% and 5% aqueous). Shehad þþþ allergic reactions to allthree concentrations of co-amoxiclavtested along with a þþþ reaction tonickel. Diclofenac, enoxaparin, andgranisetron patch tests were negative.The final diagnosis of co-amoxiclav-induced AGEP was made, andappropriate avoidance advice given.

Discussion

AGEP is an acute febrile eruptionfirst described in 1980 by Beylotet al. (1). It is characterized by numer-ous non-follicular pustules arising onerythematous and oedematous skin.Fever and blood neutrophilia are alsocommonly found. Of particular noteis the rapid evolution of the rash afterthe causative drug has been takenalong with the quick resolution ofthe rash when the causative drug iswithdrawn. AGEP is drug inducedin more than 90% of cases withbeta-lactam and macrolide antibiot-ics being the most common causativeagents (2). It has been suggested thatthe cell-bound drug elicits a drug-specific T-cell reaction eventually re-sulting in neutrophil chemotaxis (3).

Wolkenstein et al. reported that59 patients with severe cutaneousadverse drug reactions [includingAGEP, Stevens–Johnson syndrome(SJS), and toxic epidermal necrolysis(TEN)] were patch tested to the sus-pected culprit drug(s). They found thatin 50% patients (n ¼ 7) with AGEP,a relevant positive patch test result wasfound. The proportion of relevant pos-itive tests was significantly higher inAGEP than in SJS or TEN (4). Sincethen, a number of case reports andsmall series have shown positive resultsof patch testing in AGEP leadingWatsky to suggest that the positivepatch test rate may be in fact higherthan the 50%quoted in theWolkensteinstudy (5). He did, however, concede thatthese positive results may reflect publi-cation bias. There has been one previousreport of co-amoxiclav-induced AGEP(6). In this case, the diagnosis was alsoconfirmed with patch testing.

This case highlights the potentialrole of patch testing in AGEP. Itappears that the probability of gettinga relevant positive result is greater inAGEP than in other severe adverse

drug reactions, including SJS orTEN. Patch testing may have a rolein assessing the culpability of a suspectdrug while avoiding the need for po-tentially dangerous provocation tests.It may also be particularly beneficialwhen numerous suspect drugs are con-sidered as the cause of the reaction.

References

1. Beylot C, Bioulac P, Doutre M S.Pustuloses exanthematiques aıguesgeneralisees: a propos de 4 cas. AnnDermatol Venereol 1980: 107: 37–48.

2. Roujeau J-C, Bioulac-Sage P, BourseauC et al. Acute generalized exanthema-tous pustulosis: analysis of 63 cases.Arch Dermatol 1991: 127: 1333–1338.

3. Britschgi M, Steiner U C, Schmid Set al. T-cell involvement in drug-inducedacute generalized exanthematous pustu-losis. J Clin Invest 2001: 107: 1433–1441.

4. Wolkenstein P, Chosidow O, FlechetM-L et al. Patch testing in severe cuta-neous adverse drug reactions, includ-ing Stevens-Johnson syndrome andtoxic epidermal necrolysis. ContactDermatitis 1996: 35: 234–236.

5. Watsky K L. Acute generalized exan-thematous pustulosis induced by met-ronidazole: the role of patch testing.Arch Dermatol 1999: 135: 93–94.

6. de Thier F, Blondeel A, Song M. Acutegeneralized exanthematous pustulosisinduced by amoxicillin with clavulanate.Contact Dermatitis 2001: 44: 114–115.

Address:Matthew Harries, MRCP (UK)The Dermatology CentreThe University of ManchesterHope HospitalStott LaneSalfordManchesterM6 8HDTel: þ44 161 2067373Fax: þ44 161 2061018e-mail: mjharries@doctors.org.uk

372 CONTACT POINTS