FIXED DRUG ERUPTION CAUSED BY ETORICOXIB • ANDRADE & GONCALO

Fixed drug eruption caused by etoricoxib – 2 cases confirmed by patchtesting

Pedro Andrade and Margarida Goncalo

Department of Dermatology and Venereology, Coimbra University Hospital, 3000-075 Coimbra, Portugal

doi:10.1111/j.1600-0536.2010.01847.x

Key words: celecoxib; etoricoxib; fixed drug eruption; NSAID; patch tests.

Non-steroidal anti-inflammatory drugs (NSAIDs) areresponsible for most fixed drug eruptions (FDEs), whichare uncommon forms of cutaneous adverse drug reaction.In our experience, nimesulide and piroxicam are mostfrequently responsible for this adverse effect (1, 2). Wepresent two cases of FDE caused by etoricoxib, a recentlydeveloped but widely used selective cyclo-oxygenase(COX) isoenzyme 2 inhibitor, which has rarely beendescribed as a cause of FDE.

Correspondence: Pedro Andrade, MD, Servico de Dermatologia eVenereologia, Hospitais da Universidade de Coimbra, Praceta Mota Pinto,3000-075 Coimbra, Portugal. Tel: +351239400420; Fax: +351239400490.E-mail: pedro.andrade@portugalmail.com

Conflicts of interest: The authors have no conflicts of interest to declare.

Case Report

The first patient, a 69-year-old female, had multiple sharpround erythematous pruriginous patches of diameter1–4 cm on her face, upper limbs, and trunk. All lesionsoccurred simultaneously, 24 hr after oral intake of 60 mgof etoricoxib for treatment of a febrile syndrome. This wasthe first episode, although the patient had used etoricoxib3 years before with no cutaneous reaction.

The second patient, a 63-year-old female withosteoarthritis who used several NSAIDs for pain control,presented similar lesions on her face, upper limbs, andlower limbs. This patient reported a previous eruption inthe same location in the past month, following intakeof an NSAID, showing spontaneous regression withhyperpigmentation.

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FIXED DRUG ERUPTION CAUSED BY ETORICOXIB • ANDRADE & GONCALO

In both patients inflammatory lesions regressed aftersuspension of the suspected drugs and the use of mild topi-cal steroids, resulting in multiple hyperpigmented residuallesions.

Six weeks after the resolution of the acute erup-tions, patch tests were performed on dorsal non-involvedskin with the European baseline series and a series ofanti-inflammatory drugs in 1–10% pet., including thesuspected drugs and related molecules (allergen occlusionfor 2 days in Finn Chambers® on Scanpor® tape; EpitestLtd Oy, Tuusula, Finland). All allergens were provided byChemotechnique Diagnostics® (Chemotechnique Diag-nostics, Vellinge, Sweden), apart from etoricoxib andcelecoxib, which were obtained by preparation of the pow-der of commercial pills (Exxiv® and Celebrex®) in pet.(active drug at 10%), as pure drugs could not be obtained.Suspected drugs and related chemicals were also appliedon residual pigmented lesions under occlusion for 1 day:etoricoxib (10% pet.) in the first case; and nimesulide (5%pet.), diclofenac sodium (10% pet.), ibuprofen (5% pet.),etoricoxib (10% pet.) and celecoxib (10% pet.) in the sec-ond case. Readings were performed at D1/D2 on lesionalskin and at D2/D3 on normal skin. In both cases, a pos-itive reaction was observed only to etoricoxib (10% pet.)

Fig. 1. Case 1: positive patch test reaction to etoricoxib 10% pet. ona hyperpigmented residual lesion on D1.

on lesional skin on D1 and D2 (Figs. 1 and 2). In thesecond case, there was no reaction to celecoxib (Fig. 2)or any other NSAID tested on lesional skin. No positivereactions were observed on normal skin.

No flares of FDE occurred after withdrawal of etoricoxib.The second patient recognized having taken etoricoxibamong the several NSAIDs used and, when she furtherused celecoxib after patch testing, she developed noadverse reaction.

Discussion

Despite being a recent drug, etoricoxib [CAS 202409-33-4, or 5-chloro-2-(6-methylpyridin-3-yl)-3-(4-methylsulfonylphenyl)pyridine] is widely used in many coun-tries. Because of its high level of COX2/COX1 selectivity,it combines high anti-inflammatory activity (equivalentor superior to that of conventional NSAIDs) with a lowerincidence of side effects (3, 4). Specifically, cutaneousadverse events are quite rare (5, 6). Some cases of induc-tion or aggravation of urticaria and angio-oedema have

Fig. 2. Case 2: positive patch test reaction to etoricoxib 10% pet.on a hyperpigmented residual lesion on D1 (on the right), with anegative patch test reaction to celecoxib 10% pet. (on the left).

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FIXED DRUG ERUPTION CAUSED BY ETORICOXIB • ANDRADE & GONCALO

been described (7, 8), as well as sporadic cases of ery-thema multiforme (9), Stevens–Johnson syndrome (6),and acute generalized exanthematous pustulosis (10). Toour knowledge, only two cases of FDE caused by etoricoxibhave been described (11, 12).

In our cases, drug imputability was promptly con-firmed by patch testing on residual lesions, as describedfor several NSAIDs (1, 2, 11, 12), including cele-coxib (13–15). Despite the pharmacological similarity

between etoricoxib and celecoxib, no cross-reaction wasobserved between these molecules, as only the latteris a sulfonamide-related drug. Other than confirmingthe culprit drug, patch testing can also be useful tostudy cross-reactions (2). In this case, a negative patchtest result with celecoxib was followed by a nega-tive oral rechallenge result, reinforcing the place ofpatch testing in the study of this type of adverse drugreaction.

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