Abstract
Chronic erythroderma with persistent hypereosinophilia presents significant diagnostic and therapeutic challenges. We report the case of a 26-year-old man with a 6-year history of refractory erythroderma and eosinophilia. Extensive workup excluded malignancy, autoimmune disease, and secondary causes of eosinophilia. Genetic testing revealed no pathogenic variants but identified a variant of uncertain significance in HTRA2. High-dose mepolizumab monotherapy significantly reduced eosinophil counts but yielded modest clinical improvement. The addition of abrocitinib, previously ineffective alone, led to rapid and sustained symptomatic and biochemical remission. The patient experienced marked improvement in pruritus, scaling, and quality of life; subsequent withdrawal of mepolizumab led to symptom recurrence. This case highlights the complexity of managing erythroderma with hypereosinophilia and suggests that eosinophilia may be a disease marker rather than the primary symptom driver. Combined targeting of eosinophils and broader cytokine pathways via anti-interleukin-5 and JAK1 inhibition may be necessary for effective disease control in refractory cases.