Portal de Periódicos da CAPES

Intertriginous drug eruption: report of a case and proposed pathogenetic mechanism

2008; Wiley; Volume: 47; Issue: 12 Linguagem: Inglês

10.1111/j.1365-4632.2008.03638.x

1365-4632

Vikram K. Mahajan, Nand Lal Sharma, Rashmi Jindal,

Eosinophilic Disorders and Syndromes

The clinical appearance of a drug eruption does not help in determining the offending drug or the pathogenetic mechanism involved. Routine laboratory investigations, intradermal or patch testing, drug re-challenge, and other in vitro tests either have limited diagnostic value or are open to misinterpretation.1 A temporal correlation between drug administration and onset of rash provides strong circumstantial evidence for diagnosis which is often an assessment of probability. Intertriginous drug eruption or drug rash confined to intertriginous areas are uncommon or perhaps remain misdiagnosed. As presentations of such unusual drug eruptions of acute nature are often baffling, their documentation is of practical importance for appropriate management. A 5-year-old boy presented with fever (38.5 °C), chaffed lips, erythematous, edematous, confluent at places, scaly plaques with mild burning sensation over perilabial, periocular, and neckfold skin, axillae, genitocrural, and perianal folds, and cubital and popliteal fossa. There was mild palmoplantar erythema and pharyngeal congestion. He also had generalized, exanthematous, nonpustular, mildy pruritic rash. He had received one dose of amoxicillin the previous night. There was no personal/family history of drug allergy or atopy in the past. Systemic examination and investigative profile were normal. Suspecting drug eruption, amoxicillin was stopped. Antihistamines and topical emollients were prescribed. However, the rash became severe, erosive, painful, and toxic epidermal necrolysis (TEN)-like (Fig. 1). Oral prednisolone in tapering doses cleared the rash during next week. Patch testing 2 weeks later with amoxicillin (5, 10, and 20% in petrolatum) was negative. Severe, TEN-like skin rash involving face, neck fold, axillary vault, and chest wall. Also note wide spread erythematous, exanthematous rash Amoxicillin happens to be the common cause of intertriginous drug eruption in our and previous reports.1–6 Clindamycin, ceftriaxone, cephalexin, and cefuroxime, percodan (combination of oxycodone HCl, oxycodone terephthalate, and aspirin), naproxen, and celecoxib are implicated infrequently.4,5,7 Interestingly, localization of intertriginous drug eruption is suggested to be a type of systemic contact dermatitis involving buttocks, upper-inner thighs, and axillae (baboon syndrome) which characteristically occurs after ingestion/inhalation of a contact allergen (e.g. amoxicillin, ampicillin, nickel, heparin, mercury) in individuals previously sensitized by topical exposure to same allergen in the same areas.6 Clinicopathologically it is indistinguishable from contact dermatitis and has positive patch testing. According to Wolf et al.4 this seems unlikely for drugs (penicillins, cephalosporins, analgesics, and chemotherapeutics) commonly reported to cause intertriginous drug eruptions as they are not used topically. Their concept of intertriginous drug eruption being a “recall phenomenon”– recall of past dermatitis; a severe diaper rash in infancy, typical intertrigo, allergic or irritant contact dermatitis (unrelated to the drug in question) involving same areas as the new drug eruption4 also does not appear reasonable. As in that case intertriginous drug eruption will perhaps occur more often in patients with infantile/atopic dermatitis and have histology of dermatitis rather than EM- or TEN-like as observed in most cases.1,4,5,7 Negative patch testing with offending drugs in most patients also contradicts this concept. We propose another more plausible pathogenetic mechanism for this bizarre drug eruption. Amoxicillin, codeine, other β-lactam antibiotics (benzylpenicillin, phenoxymethylpenicillin, ceftriaxone, cefuroxime, and ceftazidine) and doxorubicin get concentrated and secreted in apoeccrine sweat.8–10 As apoeccrine glands secrete sweat at a seven-fold higher rate than the eccrine glands do10 a significant amount of offending drug/metabolites appears to be delivered to the skin surface particularly in axillary, breast, pubic, inguino-crural and perianal folds where apoeccrine glands are concentrated. Thus amoxicillin/metabolites first concentrate in the sweat and produce a direct toxicity to sweat glands which then get excreted on the skin surface in a gradient fashion, highest concentration in the upper epidermal layers than in the deeper layers, inflicting nonimmunologic direct toxicity to keratinocytes in outer layers manifesting as EM- or TEN-like clinically while local friction, occlusion and heat evidently contribute towards its severity. The concept is also substantiated by negative patch testing, macrophage migration or indirect rat mast cell degranulation tests, EM- or TEN-like histology and subsidence of rash after withdrawal of the offending drug in most cases.1,2,4,5 We feel that until the exact nature of such cutaneous adverse drug reaction gets established, it should be accepted and documented as “intertriginous drug eruption” and evaluated as such.