Available online at www.sciencedirect.com www.jdds.org ScienceDirect

Journal of Dermatology & Dermatologic Surgery xxx (2016) xxx–xxx

Systemic drug related intertriginous and flexural exanthem (SDRIFE) due to clindamycin

Dear Editor, Discussion A 50-year-old male was referred to us for a symmetric, confluent, erythematous, pruritic eruption of a three day Systemic drug-related intertriginous and flexural exan- duration involving the flexures, which appeared two days thema (SDRIFE) is a distinctive typically after starting intravenous clindamycin for chronic involving the flexural folds and gluteal areas, commonly osteomyelitis. There was no past history of any similar observed after exposure to beta-lactam antibiotics, such rash. Cutaneous examination revealed the presence of well as penicillins and cephalosporins, with amoxicillin being defined maculopapular eruption involving the axillae, cubi- implicated in the majority of cases (Ha¨usermann et al., tal fossa, inguinal regions and buttocks (Fig. 1a, b). There 2004). was no associated fever or lymphadenopathy. The mucosae SDRIFE is thought to result from a type IV delayed and other system examination were normal. Blood counts, hypersensitivity immune response to the offending drug. liver and renal function tests were normal as were the chest Occlusion, sweating or frictional injury and recall X-ray and abdominal ultrasound. There was no atypical phenomenon of past have also been presumed lymphocytosis or eosinophilia. A biopsy was advised but to play a role in its pathogenesis (Kardaun and Tupker, was refused by the patient. 2012). Few authors have also postulated recall phe- Causality assessment was carried out using the Naran- nomenon as a cause of SDRIFE. Most cases of SDRIFE jo’s scale and the World Health Organization (WHO)– may represent a recall of any form of dermatitis that has Uppsala Monitoring Centre (UMC) criteria after which occurred in the past in the same area after exposure to a we came to a conclusion that clindamycin was the ‘proba- new drug. Previous dermatitis may have been severe diaper ble’ (Naranjo’s score 6) cause of this adverse drug reaction. rash in infancy, to any allergen or A diagnosis of SDRIFE secondary to intravenous clin- irritant, or other forms of typical (Daito et al., damycin was made, and the medication was changed. 2009). Another novel pathological mechanism, the p-i con- The patient was started on oral prednisolone 20 mg/day cept (pharmacologic interaction with immunoreceptors) with oral anti-histamines which were stopped after one was suggested to be involved in the pathogenesis of week. The eruption resolved three days after withdrawal SDRIFE. According to this new concept, certain drugs of clindamycin without leaving any residual scarring or are able to bind directly and noncovalently to a fitting pigmentary changes but the pruritus persisted for a week. T-cell receptor without first being presented by MHC On follow-up visit, a patch test for clindamycin was per- (major histocompatibility complex) molecules and without formed, both on normal skin and at the affected sites, prior metabolism. The p-i concept may explain several which was negative. An oral re-challenge test was offered aspects of drug reactions including: the ability of an inert but was not accepted by the patient. substance to induce an immune response, the preferential localization of drug reactions in the skin and reactions occurring on first exposure to a drug and the fact that high Peer review under responsibility of King Saud University. drug doses are more often associated with systemic allergic dermatitis (O¨ zkaya, 2009). SDRIFE is characterized by a short latent period and usually appears within hours to two days of drug exposure. Production and hosting by Elsevier Clinically it is characterized by a sharply delineated erythema http://dx.doi.org/10.1016/j.jdds.2016.10.004 2352-2410/Ó 2016 The Author. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Gupta, M., , , Systemic drug related intertriginous and flexural exanthem (SDRIFE) due to clindamycin, Journal of Dermatology & Dermatologic Surgery (2016), http://dx.doi.org/10.1016/j.jdds.2016.10.004 2 M. Gupta / Journal of Dermatology & Dermatologic Surgery xxx (2016) xxx–xxx

Figure 1. Flexural erythematous rash involving the axillae (a), lower abdomen and groins (b). of the perigenital and perianal area and maculopapular Conflict of interest eruption involving the large folds, such as the elbows, axillae, cubital fossae and the knees. Palms, soles, face and mucosae None. are usually spared. Systemic features like fever, lym- phadenopathy and internal organ involvement are usually References not seen (Ha¨usermann et al., 2004; Ha¨usermann and Bircher, 2007; Ozkaya and Babuna, 2011). Daito, J., Hanada, K., Katoh, N., Katoh, S., Sakamoto, K., Asai, J., Ha¨usermann et al. (2004) proposed a set of clinical et al., 2009. Symmetrical drug-related intertriginous and flexural exanthema caused by valacyclovir. Dermatology 21, 60–62. criterion for the diagnosis of SDRIFE which includes the Ha¨usermann, P., Bircher, A.J., 2007. SDRIFE – another acronym for a following: distinct cutaneous drug exanthema: do we really need it? Dermatology 214, 1–2. (1) Exposure to a systemically administered drug either Ha¨usermann, P., Harr, T., Bircher, A.J., 2004. Baboon syndrome resulting at the first or repeated dose (excluding contact from systemic drugs: is there strife between SDRIFE and allergic contact dermatitis syndrome? Contact Dermatitis 51, 297–310. allergens). Kardaun, S.H., Tupker, R.A., 2012. Symmetric drug-related intertrigi- (2) Sharply demarcated erythema of the gluteal/perianal nous and flexural exanthema (Baboon syndrome) induced by omepra- area and/or V-shaped erythema of the inguinal/ zole. Int. J. Dermatol. 51, 1134–1137. perigenital area. O¨ zkaya, E., 2009. Current understanding of Baboon syndrome expert (3) Involvement of at least one other intertriginous/ review of dermatology. 4, 163–175. Ozkaya, E., Babuna, G., 2011. A challenging case: symmetrical drug flexural localization. related intertriginous and flexural exanthem, fixed drug eruption, or (4) Symmetry of affected areas. both? Paediatr. Dermatol. 28 (6), 711–714. (5) Absence of systemic symptoms and signs. Wolf, R., Elman, M., Brenner, S., 1993. Drug-induced intertrigo. Int. J. Dermatol. 32, 515–516. Our patient fulfilled the above criterion, hence was diag- nosed as a case of SDRIFE secondary to clindamycin. Mrinal Gupta Herein we report this case as SDRIFE to clindamycin Sudhaa Skin Centre, 35-A, Lane No-7, Tawi Vihar, has been reported rarely with only one case being docu- Sidhra, Jammu, J&K 180019, India mented till date in the literature (Wolf et al., 1993). E-mail address: [email protected]

Please cite this article in press as: Gupta, M., Systemic drug related intertriginous and flexural exanthem (SDRIFE) due to clindamycin, Journal of Dermatology & Dermatologic Surgery (2016), http://dx.doi.org/10.1016/j.jdds.2016.10.004