D1.389 - Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis Due to Allopurinol With Subsequent Sensitization to Brentuximab: A Case Report

Toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS) are severe, life-threatening type IV hypersensitivity reactions, most frequently triggered by antibiotics, anticonvulsants, and sulfonamides.

We report the case of a 65-year-old man diagnosed with Sézary syndrome who started treatment in 2021 with brentuximab (every 3 weeks), allopurinol, and omeprazole. Four days after treatment initiation, he developed low-grade fever, followed by a confluent erythematous–purpuric macular exanthema involving the trunk and proximal limbs. Oral corticosteroids were initiated, allopurinol was withdrawn, and a skin biopsy was performed, showing features consistent with drug-induced skin toxicity. After clinical improvement, a second cycle of brentuximab was administered. Four days later, the patient experienced marked clinical deterioration with flaccid bullae, positive Nikolsky sign, coarse desquamation, fever, and poor general condition, despite corticosteroid escalation and omeprazole withdrawal. He was referred to our center, where a repeat biopsy was compatible with erythema multiforme/TEN, and he was included in the Piel en Red registry. Causality assessment was performed using the Spanish Pharmacovigilance System for Medicines for Human Use (SEFV-H) algorithm. Lymphocyte transformation tests (LTT) and skin tests were conducted.

SEFV-H scoring yielded brentuximab (+7, probable) and allopurinol and omeprazole (+4, possible). LTT was positive for allopurinol and oxypurinol, equivocal for omeprazole, and negative for brentuximab. Skin tests for brentuximab were initially negative. A diagnosis of possible SJS/TEN overlap syndrome secondary to allopurinol hypersensitivity was established, with very low probability of omeprazole involvement. The patient evolved favorably with oral corticosteroids and apheresis. Avoidance of allopurinol, omeprazole, and brentuximab was recommended.In 2025, four years later, reintroduction of brentuximab was considered. Skin tests were negative, and a controlled drug challenge was performed, with tolerance of one-quarter of the therapeutic dose. Full-dose administration induced generalized erythema and pruritus, and the subsequent cycle was complicated by hypotension despite premedication. Repeat skin testing revealed a positive intradermal test. A brentuximab desensitization protocol (3 bags, 12 steps) was initiated, allowing successful administration with only mild delayed reactions and full tolerance by the third cycle.

This case illustrates an SJS/TEN overlap syndrome secondary to allopurinol, followed by subsequent IgE-mediated sensitization to brentuximab. It highlights the value of comprehensive allergological evaluation and drug desensitization protocols to safely reintroduce essential oncologic therapies.