Chronic Eosinophilic Leukemia Presenting as Treatment-Refractory Nodular Scleritis: A Paraneoplastic Autoimmune Syndrome With Multisystem Inflammatory Manifestations.

We report the first documented case of chronic eosinophilic leukemia (CEL) with ETV6-SYK gene rearrangement manifesting as refractory bilateral nodular scleritis within a broader paraneoplastic autoimmune syndrome. A 25-year-old woman with pre-existing Hashimoto's thyroiditis developed progressive bilateral nodular scleritis with anterior uveitis that proved completely refractory to high-dose corticosteroids, methotrexate, and conventional disease-modifying antirheumatic drugs, along with papilledema and granulomatous rosacea, suggesting systemic inflammation. Comprehensive evaluation revealed persistent marked eosinophilia (peak 15,000/μL), prompting hematological investigation, including a bone marrow biopsy and cytogenetic analysis that confirmed CEL harboring the ETV6-SYK fusion oncogene. Recognition of this molecular target enabled precision therapy with fostamatinib, a spleen tyrosine kinase (Syk) inhibitor, combined with adalimumab, a tumor necrosis factor-alpha (TNF-α) inhibitor, resulting in complete and sustained remission of all inflammatory manifestations over 18 months of follow-up. This case underscores the critical importance of maintaining high clinical suspicion for paraneoplastic autoimmune syndromes in patients with treatment-refractory inflammatory conditions, particularly when accompanied by atypical systemic or unexplained laboratory findings, and demonstrates that molecularly targeted precision medicine approaches can transform treatment outcomes in complex paraneoplastic rheumatic disorders.