POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes)
Published Web Locationhttps://doi.org/10.5070/D390m0423p
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes)Department of Dermatology, New York University
Christine Liang MD, Mercedes Gonzalez MD, Rishi Patel MD, Shane Meehan MD, Hideko Kamino MD, Andrew G Franks Jr MD
Dermatology Online Journal 15 (8): 9
A 62-year-old woman with hypothyroidism presented with a seven-year history of paresthesias, itching, and edema of the skin. Physical examination showed indurated, edematous plaques on the lower extremities. A biopsy specimen showed increased mucin deposition that was consistent with myxedema, and monoclonal IgM was observed on immunofixation. The constellation of findings, which included paresthesias, endocrinopathy, monoclonal gammopathy, and skin changes was consistent with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, which is a rare multisystemic disease that is associated with an underlying plasma-cell dyscrasia.
|Figure 1||Figure 2|
A 62-year-old woman presented to the Charles C. Harris Skin and Cancer Unit in June, 2008, with a seven-year history of generalized itching, pain, and stretching of her skin. The symptoms initially began as periodic episodes but progressed to a continuous sensation. A review of systems showed occasional shortness of breath, generalized fatigue and weakness, paresthesias, left eyelid ptosis, hyperhidrosis, and peripheral edema. The patient had been to nine dermatologists prior to her visit and had four previous biopsies.
Past medical history includes breast cancer status post mastectomy and chemotherapy, idiopathic thrombocytopenic purpura status post splenectomy, Hashimoto's thyroiditis, Hodgkin lymphoma, and depression. Medications include levothyroxine, prednisone, folic acid, nortriptyline, phenelzine, gabapentin, and lithium.
A punch biopsy was obtained from an indurated area of the thigh.
On the lower extremities were non-pitting edema and diffuse induration, which were more prominent on the thighs. Scattered, excoriated, erythematous papules were present over the upper and lower extremities. No lymphadenopathy or hepatomegaly was noted. A colonoscopy showed diverticulae.
An antinuclear antibody titer was 1:320, with a diffuse pattern. Serum immunofixation showed trace monoclonal IgM kappa in gamma region. Anti-SSA, anti-SSB, anti-thyroglobulin, and anti-thyroid peroxidase antibodies as well as a total protein level were normal. A chest radiograph was normal.
There is a sparse, superficial, perivascular lymphocytic infiltrate. Increased deposition of connective-tissue mucin in the papillary and reticular dermis is highlighted by a colloidal iron stain.
Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare, multisystemic disease that is associated with an underlying plasma-cell dyscrasia. There are no criteria that define the syndrome, but most authors agree that a monoclonal plasma-proliferative disorder and polyneuropathy are the two major criteria. Other important features include elevated levels of vascular endothelial growth factor (VEGF), sclerotic bone lesions, Castleman disease, papilledema, peripheral edema, ascites, effusions, thrombocytosis, polycythemia, fatigue, and clubbing [1, 2, 3]. Synonyms include osteosclerotic myeloma, Crow-Fukase syndrome, and Takatsuki syndrome.
The pathophysiology by which plasma cells lead to POEMS syndrome is poorly understood, but elevations in VEGF, interleukin-6, tumor necrosis factor-alpha, and interleukin-1 beta have been implicated. Serum levels of VEGF are markedly elevated in POEMS syndrome patients and correlate with disease activity . Because VEGF increases vascular permeability and angiogenesis, it is proposed that this may account for the organomegaly, edema, and skin hemangiomas .
Several hundred cases of POEMS syndrome have been reported, but the incidence may be underreported because the syndrome can go unrecognized. Peak incidence occurs during the fifth to sixth decades of life, and peripheral neuropathy is the major clinical finding . Common skin manifestations include edema of the lower extremities with diffuse hyperpigmentation, hypertrichosis, and thick skin, with tightening and sclerodermoid changes. Angiomas, in particular glomeruloid hemangiomas, are characteristic. Whitening of the proximal nail, clubbing, hyperhidrosis, and Raynaud phenomenon also may be associated.
The plasma-cell dyscrasias most commonly observed in POEMS patients are osteosclerotic myeloma or a monoclonal gammopathy of unknown relevance [1, 2]. Classic multiple myeloma has never been reported in association with POEMS. Immunoglobulin A-lambda and immunoglobin G-lambda chains are the proteins most frequently found. Endocrinopathy is a central feature of POEMS, with hypogonadism as the most common endocrine abnormality . Hypothyroidism, diabetes mellitus, adrenal insufficiency, hyperprolactinemia, and hypoparathyroidism also are observed. Many patients have more than one abnormality. A case report of POEMS developing during the course of idiopathic thrombocytopenic purpura (ITP) has been reported, which is of note since our patient also had a history of ITP .
Prognosis varies, but typically the course is chronic; in one study the median survival was 13.8 years . The number of POEMS features does not affect prognosis although respiratory symptoms are predictive of an adverse outcome . Within two years of diagnosis, approximately one-quarter of patients develop respiratory symptoms, which include restrictive lung disease and pulmonary hypertension. Acute ischemic strokes and myocardial infarcts occasionally have been reported in association with POEMS .
Treatment of the underlying plasma-cell disorder is the major therapeutic approach. No randomized controlled trials have been performed on POEMS patients, and information on therapy is primarily retrospective. Mainstays of treatment include radiation therapy in osteosclerotic lesions, glucocorticoids, and alkylating agents. High-dose chemotherapy followed by stem-cell transplantation has been successful in some patients [1, 2, 3]. Bevacizumab, which is a monoclonal antibody directed against VEGF, has had variable results; some patients have developed improvement in neuropathy, edema, and respiratory symptoms while others have developed capillary leak syndrome . A multidisciplinary approach is important due to the extent of systems that may be involved in these patients. Future studies need to further examine the role of cytokines in the pathogenesis of this poorly understood disease.
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