Improvement with high-dose infused immune globulin (IVIg) has been transiently effective in half of our cases with typical paraproteinemia and in 20 percent of those with anti-MAG neuropathy but the illness nonetheless progresses in most patients (Gorson et al 2001). In almost all instances, immunosuppression and plasma exchanges or IVIg, if used, must be repeated indefinitely at intervals of 1 to several months as determined by the clinical course. An indwelling catheter is then usually required to allow repeated venous access. This group of neuropathies responds poorly or not at all to corticosteroids.
POEMS Syndrome, Osteosclerotic Myeloma, and Multiple Myeloma
A neuropathy associated with multiple myeloma has already been mentioned; it complicates 13 to 14 percent of cases of multiple myeloma and has a disproportionately high association with the osteosclerotic form of the disease. An abnormal monoclonal globulin (mainly with the kappa light chain component in multiple myeloma but lambda in the osteosclerotic type) is found in the serum of more than 80 percent of patients with myelomatous neuropathy.
In a special and small group of patients with osteosclerotic myeloma, there is a predominantly demyelinating sensorimotor polyneuropathy and systemic disease termed POEMS (i.e., polyneuropathy of moderate severity is associated with organomegaly, endocrinopathy, elevated
M protein, and skin changes, mainly hypertrichosis and skin thickening). The same process has been referred to as the Crow-Fukase syndrome in Japan, where the disease is prevalent. In many cases there is lymphadenopathy attributable to the angiofollicular hyperplasia of Castleman disease. Another characteristic feature of the osteosclerotic-related polyneuropathy is a greatly elevated CSF protein.
The presence of the disease can be suspected from the presence of demyelinating features on the nerve conduction studies, an immunoglobulin spike in the blood, sometimes polyclonal or biclonal rather than monoclonal and, as mentioned, possessing a lambda light chain component. The diagnosis requires the demonstration of one or more osteosclerotic lesions by a radiographic survey of the long bones, pelvis, spine, and skull as well as a PET study, which usually shows the osteosclerotic lesions as highly active (a bone scan is insensitive) and a bone marrow examination, which shows a moderate increase in the number of well-differentiated plasma cells. In most of our patients there have been several discrete bone lesions concentrated in the ribs and spine; the skull and long bones may harbor such lesions as well, or there may be a single lesion, which is often situated in the spinal column. Biopsy of a bone lesion is justified. The organomegaly and skin changes are apparently the result of high levels of circulating VEGF that is produced by the tumor and is useful in confirming the diagnosis.
Treatment of POEMS The neuropathy that complicates a solitary plasmacytoma may improve markedly following irradiation or resection of the bone lesion. Multiple lesions or cases with no apparent bone lesions, including those in the POEMS syndrome, may be treated with chemotherapy (melphalan and prednisone) and may lead to some improvement or stabilization in the neuropathy. Treatment with plasma exchange has yielded uncertain but generally positive short-term results in our patients. The value of plasma exchanged and IVIG have been difficult to affirm in trials. Drugs used to treat multiple myeloma have also been tried, with uncertain results. Autologous stem cell transplantation or bevacizumab (a monoclonal antibody directed against VEGF) have been used, also with mixed results (Kuwabara et al, 2008) and with some positive results in uncontrolled series (Karam et al).