POEMS syndrome (ORPHA:2905)
POEMS syndrome is a paraneoplastic syndrome characterized by polyradiculoneuropathy (P), organomegaly (O), endocrinopathy (E), clonal plasma cell disorder (M), and skin changes (S). Other features include papilledema, extravascular volume overload, sclerotic bone lesions, thrombocytosis/erythrocytosis, and elevated VEGF levels.
Epidemiology
Exact prevalence and incidence rates are not known. The only estimates are from Japan. In this country, prevalence has been reported to be about 1/330,000. Male predilection has been reported (2.5:1).
Clinical description
The average age of onset is in the 5th or 6th decade. The disease covers a wide clinical spectrum depending on the systems involved. Neuropathy is the primary manifestation and is usually peripheral, ascending, and symmetrical with distal weakness and paresthesia. It is both sensory and motor and may cause pain, hyperesthesia, and areflexia. A clonal plasma cell disorder (PCD) is the second major feature. Organomegaly mainly includes hepatomegaly, splenomegaly, and/or lymphadenopathy (Castleman disease; see this term). Various and extensive endocrine disorders may be found causing hypogonadism, thyroid abnormalities, adrenal insufficiency, and/or erectile dysfunction and gynecomastia in men. The skin is commonly affected with development of hyperpigmentation, hemangiomas, hypertrichosis, leukonychia or nail clubbing, sclerodermoid changes, lipodystrophy, and flushing. The main ocular manifestation is papilledema. Extravascular overload mainly manifests as peripheral edema, and sometimes as pleural effusion, ascites, and pericardial effusions. An increased risk of arterial and/or venous thrombosis is reported (up to 20% of patients). Disease severity depends on the systems involved and the course is chronic. Some patients have a mild presentation while others have debilitating disease. 25% have respiratory manifestations including restrictive lung disease, pulmonary hypertension, and respiratory muscle weakness.
Etiology
The pathogenesis has not been clearly elucidated. Vascular endothelial growth factor (VEGF) appears to play a significant role in this plasma cell disorder.
Diagnostic methods
All of the clinical features are not required for diagnosis. Patients with three of the major criteria necessarily including polyradiculoneuropathy and clonal PCD (plus possibly Castleman, sclerotic bone lesions, VEGF elevation), plus at least one minor criterion can be diagnosed with POEMS. Minor criteria are organomegaly, endocrinopathy, papilledema, extravascular overload, and skin changes. Patient with POEMS features who do not have both peripheral neuropathy and PCD are considered as having the Castleman disease variant of POEMS. Radiographic assessment of bones, elevated VEGF, and bone marrow biopsy aid in confirming the diagnosis. VEGF levels correlate with disease activity.
Differential diagnosis
The main differential diagnoses are chronic inflammatory demyelinating polyneuropathy, AL amyloidosis and Guillain-Barré syndrome (see these terms). Monoclonal gammopathy of undetermined significance (MGUS) and should also be considered.
Management and treatment
Patients with dominant sclerotic plasmacytoma are treated with radiotherapy. Radiation is also used in patients with diffuse sclerotic lesions or disseminated bone marrow involvement. Some patients progress after radiation therapy and require systemic treatment. Alkylators are the main treatment, along with lenalidomide and to a lesser extent thalidomide and bortezomib. High-dose chemotherapy with peripheral blood stem cell transplant may be successful. Supportive care should also be provided (orthotics, physical therapy, and continuous positive airway pressure (CPAP)).
Prognosis
The prognosis is generally good if diagnosis is early and appropriate treatment is provided. Causes of death include progressive anasarca, thrombosis, and inanition.

                            Last update: 
                            March 2015


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