Ruxolitinib-associated dual immune complications: HBV reactivation and warm autoimmune hemolytic anemia in a patient with polycythemia vera

Ruxolitinib is a JAK1/2 inhibitor used in patients with polycythemia vera (PV) who are resistant or intolerant to hydroxyurea. Although it effectively controls hematologic parameters, its immunosuppressive nature may predispose patients to infectious and immune-mediated complications. Here, we report a rare case of concurrent hepatitis B virus (HBV) reactivation and warm autoimmune hemolytic anemia (wAIHA) during ruxolitinib treatment. A 58-year-old male was diagnosed with PV based on erythrocytosis (Hb: 22.9 g/dL), low erythropoietin level (1.3 mIU/mL), splenomegaly (176 mm), and a JAK2 V617F mutation detected in both peripheral blood and bone marrow. Hydroxyurea was initiated due to inadequate hematocrit control despite phlebotomies but was ineffective. Ruxolitinib was introduced and later escalated to 15 mg twice daily, achieving target hematologic response. In the 14th month of therapy, the patient developed anemia, transaminase elevation, hyperbilirubinemia, and HBV reactivation (HBsAg, HBeAg, anti-HBe positive; HBV DNA: 772,066 IU/mL). Further evaluation revealed hemolytic anemia with positive direct Coombs test, low haptoglobin, reticulocytosis, and elevated LDH. Ruxolitinib was discontinued, and entecavir plus oral corticosteroids were initiated. Clinical and laboratory findings improved, allowing ruxolitinib to be safely reintroduced at a lower dose after 1 month. Corticosteroids were tapered without recurrence, and the patient remains clinically stable under maintenance therapy. This case highlights the potential for dual immune complications, HBV reactivation and wAIHA, during ruxolitinib therapy in PV. Careful pre-treatment screening and close monitoring are essential for early detection and management of such adverse events. This case underscores the importance of pre-treatment HBV screening and vigilant monitoring for immune complications during ruxolitinib therapy.