POEMS Syndrome: 2019 Update on diagnosis, risk‐stratification, and management

Abstract

Disease Overview: Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. Diagnosis: The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal PCD, and at least one of the minor criteria. Risk Stratification: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. Risk factors include low serum albumin, age, pleural effusion, pulmonary hypertension, and reduced eGFR. Risk-Adapted Therapy: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3 to 6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes syndrome: Diagnosis, treatment and the current status in Japan

“…Monoclonal plasma cell proliferation is also an essential feature of POEMS syndrome . Plasma cell clonality is confirmed by the assessment of serum or urine M‐protein, serum immunoglobulin light chain ratio, flow cytometry and histopathology of bone marrow specimens.…”

“…Hyperpigmentation, hemangioma and hypertrichosis are frequent lesions . Other skin lesions, including plethora, cyanosis and white nails, are also observed …”

“…The diagnosis of POEMS syndrome is made based on the diagnostic criteria, which consist of characteristic clinical features and laboratory abnormalities . Dispenzieri’s criteria have been used internationally; in contrast, in Japan, modified criteria proposed by Misawa and Kuwabara have been used .…”

“…Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome is a rare multisystemic disease associated with plasma cell dyscrasia, and is a cause of demyelinating polyneuropathy . Although the pathogenesis of POEMS syndrome remains unclear, the proliferation of plasma cells and overproduction of vascular endothelial growth factor (VEGF) seem to play a fundamental role in the pathophysiology of this disease . Additionally, the involvement of other pro‐inflammatory cytokines, such as tumor necrosis factor‐α, interleukin‐6 and interleukin‐12, is also upregulated, and complicates its pathophysiology …”

“…Massive pleural effusions and ascites result in progressive circulatory and respiratory failure, and their average survival time was 2–3 years in the 1980s and 1990s . Since the 2000s, treatments for multiple myeloma, such as high‐dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT), immunomodulatory drugs and proteasome inhibitors, have been applied to POEMS and considered to improve its prognosis dramatically . In contrast, some patients might not recover sufficiently, mainly due to delayed diagnosis, which results in poor outcomes …”