D2.406 - Severe DRESS in an oncohematological patient: diagnostic and therapeutic challenges

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe adverse drug reaction characterized by systemic involvement, eosinophilia and viral reactivation, with potential late complications. Diagnosis and management are challenging in patients exposed to multiple drugs.

A 60-year-old woman with IgA multiple myeloma started first-line therapy with daratumumab, bortezomib, lenalidomide and dexamethasone, with trimethoprim–sulfamethoxazole, acyclovir and allopurinol prophylaxis. She was admitted to ICU with suspected sepsis and treated with piperacillin–tazobactam. Despite clinical improvement and negative cultures, on day 4 she developed liver and renal dysfunction, fever, lymphadenopathy, extensive maculopapular rash and progressive eosinophilia. DRESS was diagnosed (RegiSCAR score 5) and methylprednisolone initiated. Benralizumab was considered but not administered.

Clinical improvement occurred within 48 hours. On day 7, 20 minutes after trimethoprim–sulfamethoxazole administration, she developed acute systemic symptoms with bronchospasm, hypoxemia, rash worsening and marked eosinophilia, with normal serum tryptase. Corticosteroids were intensified and suspected drugs withdrawn. Despite subsequent clinical and analytical improvement with eosinophil normalization, 72 hours later she developed severe neurological deterioration requiring intubation. HHV-6 reactivation was detected, evolving to encephalitis and refractory epilepsy. Pharmacogenetic testing revealed HLA-B*58:01, associated with allopurinol hypersensitivity. Patch tests with acyclovir and allopurinol were negative.

This case illustrates severe DRESS in an oncohematological patient with marked eosinophilia, tissue damage, HHV-6 reactivation and serious neurological sequelae. It highlights diagnostic and therapeutic complexity in critically ill patients and supports consideration of eosinophil-targeted therapies in selected cases.