LAUSR

A 76-year-old man with acute myeloid leukemia (AML) presented to the Emergency Department with fever, a pruritic diffuse rash, and worsening painful oral ulcerations. Four days prior, the patient was initiated on low-dose cytarabine (LDAC) and cladribine. Almost 2 weeks prior, for prevention of tumor lysis syndrome with anticipated venetoclax he began oral allopurinol (300 mg daily), and for antimicrobial prophylaxis began oral trimethoprim/sulfamethoxazole (400–80 mg daily), and valacyclovir (500 mg daily). Physical examination revealed a stable, nontoxic appearing patient with scattered erythematous macules and papules coalescing into plaques with admixed petechiae of his face, neck, torso, and upper extremities (Image 1). Oral mucositis with mild hemorrhagic crusting of mucosal lips was present. Laboratory studies were significant for pancytopenia with a downtrending absolute neutrophil count (ANC) and absolute eosinophil count (AEC), both decreasing to zero within four and 2 days of admission, respectively. Respiratory pathogen panel, blood cultures, and hepatitis serologies were negative. Skin biopsy demonstrated vacuolar interface dermatitis, scattered dyskeratotic keratinocytes, and subjacent dermal edema and perivascular and periadnexal lymphohistiocytic inflammation with eosinophils and extravasated erythrocytes (Image 2). These histologic findings are nonspecific and may be seen in exanthematous drug reactions, drug-induced hypersensitivity syndrome (DIHS), and drug-induced erythema multiforme (EM). Timing of rash onset in relation to medication exposure, as well as facial and oral mucosal involvement weighed against morbilliform drug eruption; the lack of targetoid papules and plaques weighed heavily against EM. Clinicopathologic correlation supported a diagnosis of drug-induced hypersensitivity syndrome (DIHS) likely secondary to allopurinol and/or trimethoprim/sulfamethoxazole therapy.