Neuromuscular Case Vignettes

Case 4: Diagnosis and discussion:

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes).

Further workup: A monoclonal IgA lambda was present with concentration of 0.3 g/dl, accounting for 80% of the IgA level. CT scan of chest, abdomen and pelvis: retroperitoneal and subcarinal multiple enlarged lymph nodes and mild splenomegaly (see A, right column). PET scan showed intense FDG uptake in a lytic lesion in the L.hemipelvis and posterior acetabulum (see B, right column). Serum VEGF level X3 normal.

The diagnosis of POEMS syndrome is made with 3 of the major criteria, two of which must include polyneuropathy and clonal plasma cell disorder (PCD) usually of λ-light chain isotype; and at least one of the minor criteria. Major criteria: polyradiculoneuropathy, clonal PCD, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF), and Castleman disease. Minor criteria: organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. POEMS syndrome is to be differentiated from chronic inflammatory demyelinating polyneuropathy and concomitant monoclonal gammopathy of undetermined significance. Another differential diagnosis is light chain myeloma (in the latter, neuropathy is characteristically small fiber, with significant autonomic failure). POEMS syndrome generally does not respond well to chronic steroid treatment, Intravenous immunoglobulin (IVIG) infusions, and plasma exchange, which are generally effective in CIDP. Clues to the diagnosis of POEMS syndrome include severe neuropathy with demyelinating features, gammopathy (usually IgG or IgA λ) and presence of systemic features (organomegaly, skin changes, edema, pleural effusion, and nephropathy), thrombocytosis and polycythemia (which help differentiating POEMS from myeloma).

Serum VEGF level is usually high in POEMS syndrome, and plays an important role in its pathophysiology. Skeletal survey, MRI and PET-CT scan are commonly used to evaluate for a plasmacytoma. Local radiation therapy could be effective in patients with a solitary sclerotic bone lesion and lack of evidence for significant clonal expansion in bone marrow biopsy. On the other hand, patients who fail radiation therapy or have widespread sclerotic lesions are usually treated with systemic chemotherapy similar to the one administered in multiple myeloma. Autologous stem cell transplantation has been particularly effective. Another potentially effective option is lenalidomide. Although thalidomide and bortezomib may also be effective, their use in POEMS is limited by potential for exacerbating the neuropathy.

Suggested Readings:

1. Dispenzieri A. POEMS syndrome: update on diagnosis, risk-stratification, and management. Am J Hematol. Aug 2012;87(8):804-814.

2. Mauermann ML, Sorenson EJ, Dispenzieri A, et al. Uniform demyelination and more severe axonal loss distinguish POEMS syndrome from CIDP. J Neurol Neurosurg Psychiatry. May 2012;83(5):480-486.