Polyneuropathy and monoclonal gammopathy: unmasking POEMS syndrome in a case series

Abstract

Background: POEMS syndrome is a rare paraneoplastic disorder associated with an underlying plasma cell dyscrasia. It is defined by a constellation of features, with mandatory criteria including polyradiculoneuropathy and a monoclonal plasma cell disorder, in addition to major criteria such as sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, and Castleman disease. Due to its heterogeneous clinical presentation and overlap with other neurological conditions—particularly chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)—the diagnosis is frequently delayed or missed. Recognizing associated systemic manifestations is essential for early diagnosis and appropriate management. Objective: To illustrate the clinical and laboratory heterogeneity of POEMS syndrome through a case series, emphasizing key features that support early recognition and differential diagnosis in patients with polyneuropathy and monoclonal gammopathy. Methods: We conducted a retrospective case series of patients diagnosed with POEMS syndrome at a tertiary care center in Rio de Janeiro, Brazil. Clinical, laboratory, electrophysiological, imaging, and histopathological data were reviewed. Diagnostic criteria were applied based on established definitions, and cases were analyzed to characterize patterns of presentation, associated features, and therapeutic approaches. Results: Patients presented with polyneuropathy associated with systemic involvement. Neuropathy was consistently sensorimotor, with electrophysiological findings ranging from demyelinating to axonal or mixed patterns. Systemic manifestations were heterogeneous and included endocrinopathies, organomegaly, skin changes, edema, and hematological abnormalities. Monoclonal gammopathy was identified in most cases, with variable immunoglobulin subtypes. Imaging and histopathological evaluation revealed plasma cell disorders, including osteosclerotic or lytic bone lesions, as well as lymphoproliferative conditions such as Castleman disease. Initial misdiagnosis as CIDP occurred in several cases, contributing to delays in diagnosis. Therapeutic approaches varied according to the underlying condition and included immunotherapy, radiotherapy, and chemotherapy, with variable clinical outcomes. Conclusion: POEMS syndrome should be considered in patients with polyneuropathy and monoclonal gammopathy, particularly when associated with systemic features. Its heterogeneous presentation often leads to misdiagnosis as CIDP, delaying appropriate management. Early recognition of red flags and targeted investigation are essential, as treatment depends on the underlying plasma cell disorder and may significantly impact outcomes.