Itraconazole‐induced Stevens‐Johnson syndrome and toxic epidermal necrolysis overlap: Report of a rare incident

Dear Editor, Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are a group of severe cutaneous adverse reactions. We hereby report a case of SJS-TEN overlap, developing in a young girl who was prescribed oral itraconazole for onychomycosis. A 16-year-old girl presented with fever and reddish rashes over her face, upper limbs, chest, and back, present for the preceding 3 days. She had visited a pediatrician for finger-nail onychomycosis, who prescribed oral itraconazole (400 mg/day for 7 days a month, to be continued for 3-4 cycles). She started to consume the medicine from the next day itself (Day 1). Her parents reported the development of some red lesions on her face and back, in addition to fever and myalgia, from Day 3. When she presented to us on Day 5, cutaneous examination revealed numerous erythematous to purpuric macules coalescing to form patches, distributed over face, upper limbs, chest, abdomen, and back amounting to approximately 25% body surface area involvement (Figure 1). Pseudo-Nikolsky's sign was positive on the back. Erosions were present over oral and genital mucosae. Ocular examination revealed conjunctival redness with mild mucopurulent discharge. She was not taking any other drugs (allopathy, homeopathy, or alternative medicine) apart from itraconazole, which was immediately stopped. She was admitted to the In-Patient Department with a diagnosis of Stevens Johnson syndrome—toxic epidermal necrolysis overlap. Routine investigations were notable for elevated C-reactive protein, serum glucose, and transaminases. Screening for antinuclear antibodies and mycoplasma were negative. Based on SCORTEN (score = 2), mortality risk was estimated to be 12.1%. Histopathology of punch biopsy done from a lesion on the back, showed extensive dyskeratosis of epidermis with blister formation at dermoepidermal junction (Figure 2). Presence of extensive keratinocyte necrosis with paucity of inflammation, was consistent with a diagnosis of SJS-TEN overlap. She was started on cyclosporine at a dose of 4 mg/kg/day for 10 days in conjunction with symptomatic management, to which she responded well. The progression of lesions could be arrested and cutaneous lesions started to heal with post-inflammatory hyperpigmentation. She was discharged on the 11th day of admission. The causal relationship between itraconazole and SJS/TEN was found to be “probable” according to objective causality assessment by the Naranjo probability scale (Naranjo score = 6) and “probable/likely” as per the World Health Organization-Uppsala Monitoring Centre criteria. According to modified Hartwig and Siegel ADR severity assessment scale, we graded the reaction as “Level 3” (moderate). As per algorithm of drug causality for epidermal necrolysis (ALDEN) score, the reaction was labeled as “possible” (score + 3).