Refractory Hypereosinophilic Syndrome With Clonal T-Cell Receptor Rearrangement Treated With JAK Inhibition Following Incomplete Response to IL-5 Blockade.

Hypereosinophilic syndrome (HES) comprises a heterogeneous group of disorders characterized by persistent eosinophilia and eosinophil-mediated organ involvement. Although interleukin-5 (IL-5) inhibition is an established treatment strategy, some patients experience persistent or recurrent disease despite therapy. Janus kinase (JAK) inhibition has emerged as a potential therapeutic option in refractory cases. We report a 63-year-old White male who presented with a diffuse pruritic erythematous rash, marked leukocytosis with eosinophils comprising approximately 83% of circulating leukocytes, and markedly elevated serum IgE levels. Bone marrow biopsy demonstrated a hypercellular marrow (approximately 89%) with eosinophils accounting for approximately 75% of nucleated cells. Extensive evaluation, including cytogenetic, fluorescence in situ hybridization, and molecular testing for myeloid neoplasms, was unrevealing, while peripheral blood polymerase chain reaction demonstrated a clonal T-cell receptor gene rearrangement. Despite prior hydroxyurea therapy, prolonged treatment with mepolizumab, and repeated corticosteroid courses, the patient developed recurrent disease with an absolute eosinophil count of 2760/μL. Ruxolitinib was initiated while IL-5 inhibition was continued. Following JAK inhibition, leukocyte and eosinophil counts normalized, corticosteroids were discontinued, and disease control was maintained at 3-month follow-up. This case highlights the potential role of JAK inhibition as adjunctive therapy in refractory HES with clonal T-cell receptor rearrangement. Further studies are needed to define the safety, durability, and optimal integration of JAK inhibition in patients with refractory eosinophilic disorders.