SDRIFE-like reaction induced by an intradermal skin test with clindamycin: A case report

Systemic contact dermatitis (SCD) occurs when an individual sensitized to a contact allergen is exposed to that same allergen or a cross-reacting molecule through a systemic route (transcutaneous, transmucosal, oral, intravenous, intramuscular, or inhalated). Baboon syndrome is the most pathognomonic form of SCD, which consists of delayed exanthema affecting intertriginous surfaces (buttocks, upper inner thighs, axillae, etc.). It was described for the first time in 1984, and its name is due to the erythema that occurs in intergluteal folds and thighs, reminiscent of the red bottoms of baboons. Despite the most frequent location being upper inner thighs and buttocks, it can also involve other intertriginous parts of the body. The first cases were observed after exposure to mercury, nickel, and ampicillin. Since then, over 100 cases of similar eruptions under different names have been described. In 2004, the acronym SDRIFE (symmetric drug-related intertriginous and flexural exanthema) was accepted to refer to those cases associated with systemic drugs with typical lesions of baboon syndrome with unknown history of previous skin sensitization. Five clinical criteria were established for diagnosis: (1) occurrence after exposure to systemic drugs, (2) sharply demarcated erythema in the buttocks and/or V-shaped erythema of the thighs, (3) involvement of at least one other flexural fold, (4) symmetry, and (5) the absence of systemic symptoms. Most frequently, it is caused by antibiotics, especially b-lactams. A 72-year-old woman, without atopic history, was referred to our unit to be studied. She developed a generalized pruritic maculopapular rash without systemic symptoms 6 hours after the intake of ibuprofen and clindamycin for arm cellulitis. Treatment was administered with antihistamines and systemic corticosteroids with improvement of the lesions. The condition resolved completely within a few weeks, with a scaly rash and desquamation, but without residual lesions. She had previously tolerated ibuprofen, but it was the first time she was treated with clindamycin. We performed the patch test (PT) on her upper back with ibuprofen (5% in petrolatum) with readings on day 2 (D2) and day 4 (D4) with negative results. An intradermal (ID) test with 0.03 c.c. of clindamycin (30 mg/mL) was carried out with positive readings on D2. In addition, the patient had erythema in antecubital folds, and retroauricular and occipital regions with generalized pruritus (Figure 1). ID tests in 10 healthy controls were negative. To investigate the sensitivity of the PT versus ID test, we asked our patient for permission to perform a PT with clindamycin, even after the positive ID test with the drug, and she accepted. We performed the PT with clindamycin (1% in petrolatum) with positive readings on D2 and D4. A skin biopsy of the ID lesion was taken (Figure 2) in which preserved thickness, foci of spongiosis, and some necrotic keratinocytes were found in the epidermis. In the dermis, edema, blood extravasation, and a perivascular inflammatory infiltrate, predominantly lymphocytic with some eosinophils, were seen. After written informed consent, a single-blind oral challenge test (OCT) was performed with ibuprofen at gradually increasing doses, at 1-hour intervals up to 600 mg, following the protocol of the European Academy of Allergy and Clinical Immunology drugs committee, with negative result. We describe a case of SDRIFE-like reaction as a complication of an ID test. Usually skin testing is an essential and safe tool for the diagnosis, but the risk of inducing a systemic reaction exists. Although the PT was positive in our patient, it can be negative in one-third to one-half of the patients with SDRIFE. Perhaps this could be due to reduced absorption of systemically administered drugs when applied to the skin by PT. We thought ID with delayed reading would be more accurate for diagnosis than PT, but it may have more risks for patients. The OCT or re-challenge test is positive in almost all reported cases of SDRIFE and at this time is the most reliable way to confirm the diagnosis. There are a few reports in the literature that document SDRIFE due to clindamycin, but we have not found any reports of positive delayed prick or ID tests with clindamycin in patients with SDRIFE. Delayed rashes after the OCT with clindamycin have also been described. Histopathology most commonly demonstrates a superficial perivascular lymphohistiocytic infiltrate sometimes including neutrophils, eosinophils, or mast cells with or without epidermal spongiosis, and necrotic keratinocytes can also be observed, compatible with the findings in the biopsy of the ID test of our patient. The pathogenesis of SDRIFE is not yet known with certainty, although the clinical manifestations and results of skin tests suggest that it could be due to a type IV hypersensitivity mechanism. In our patient, the observed clinical manifestations as well as the results of skin tests and the morphological findings of the