POEMS Syndrome: Clinical Manifestations, Pathophysiology, and Therapeutic Approaches

POEMS syndrome is a rare paraneoplastic condition associated with an underlying plasma cell neoplasm. The acronym POEMS denotes the cardinal features: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes. While the pathogenesis remains incompletely understood, current evidence suggests that elevated proinflammatory cytokines, particularly vascular endothelial growth factor, coupled with clonal plasma cell proliferation, drive disease progression. Diagnosis presents a significant clinical challenge as it requires identification of multiple major and minor criteria rather than a single definitive test. POEMS is often misdiagnosed given that it shares overlapping features with other conditions, including chronic inflammatory demyelinating polyneuropathy, multiple myeloma, and Castleman disease. For this reason, a multidisciplinary approach for diagnosis is imperative to avoid delay in the diagnosis and treatment of patients. Treatment of POEMS is largely symptom based, including radiation therapy for dominant solitary plasmacytomas, corticosteroids for systemic disease, and agents such as immunomodulatory drugs, proteasome inhibitors, traditional alkylating agents, and/or high dose chemotherapy and autologous stem cell transplantation. Early recognition by clinicians leads to prompt intervention and can substantially alter disease trajectory and improve quality of life. This narrative review provides a comprehensive overview of the diagnostic criteria, pathogenesis, and management of POEMS syndrome.