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POEMS Syndrome

  • Author: Joanna L Chan, MD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Oct 22, 2015
 

Background

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare multisystemic disease that occurs in the setting of a plasma cell dyscrasia. The pathophysiologic link between the constellation of symptoms and the underlying disease is not well understood, but the link may be related to changes in the levels of a cytokine or a growth factor. POEMS syndrome was first described by Crow in 1956 and then by Fukase in 1968. The syndrome was termed Crow-Fukase syndrome (by which it is known in Japan) by Nakanishi in a study of 102 cases in Japan.

In 1980, the acronym POEMS was coined by Bardwick et al based on the 5 main features of the disease, namely, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes.

No specific case definition exists for POEMS syndrome; however, most authors agree that patients with POEMS syndrome should have 3 or more of the 5 features. Some authors have proposed that the presence of 2 major criteria, including a monoclonal plasma-proliferative disorder and polyneuropathy, in addition to the existence of 1 minor criterion, is sufficient for diagnosis. The suggested minor criteria include sclerotic bone lesions, organomegaly, edema, endocrinopathy, papilledema, and skin changes. However, the findings of a retrospective analysis of 629 patients using these criteria suggest that this approach may be inadequate for excluding other disease processes that may account for symptoms and that atypical presentations of POEMS may be misdiagnosed.[1, 2]

The polyneuropathy associated with POEMS syndrome is a bilateral symmetric disturbance. It involves both motor and sensory nerves, begins distally, and has a progressive proximal spread. Associated cranial or autonomic nerves are not involved. Both demyelination and axonal degeneration are noted.

The liver, the lymph nodes, and the spleen are the organs most frequently involved. Enlargement of the lymph nodes and spleen is secondary to changes consistent with Castleman disease (giant angiofollicular hyperplasia, multicentric plasma cell variant) in most patients. Approximately 15% of patients with POEMS syndrome have concomitant evidence of Castleman disease. Hepatomegaly is not associated with any defined histologic or pathophysiologic changes.

Multiple endocrinopathies have been associated with POEMS syndrome, and most patients have more than 1 endocrine abnormality. Many of the abnormalities noted can be explained by elevations in estrogen levels. Impotence and gynecomastia are common among men. Amenorrhea is common among women. Diabetes mellitus and glucose intolerance are also noted in many patients. Other associated endocrinopathies include hypothyroidism, hyperprolactinemia, and hypoparathyroidism.

POEMS syndrome is seen in the setting of a plasma cell dyscrasia. Although many plasma cell disorders have been reported in patients with POEMS syndrome, most patients are seen with osteosclerotic myeloma or monoclonal gammopathy of unknown significance.

The M proteins most frequently found are the immunoglobulin A (IgA)–gamma and immunoglobulin G (IgG)–gamma light chains. In a case report of one patient with POEMS syndrome,[3] serum electrophoresis demonstrated an M-band with isolated IgA heavy chain but no abnormal light chain, which could suggest abnormal secretion of monoclonal protein or the rare possibility of coincidental heavy-chain disease in association with POEMS syndrome. A single case of POEMS syndrome in association with Waldenström macroglobulinemia,[4] characterized by immunoglobulin M–kappa paraproteinemia, has been reported. Classic multiple myeloma has not been associated with the disease. The type of plasma cell disorder has not been shown to be correlated with the constellation of symptoms noted in patients with POEMS syndrome.

Multiple dermatologic changes have been associated with POEMS syndrome. The most common changes include hyperpigmentation, skin thickening, sclerodermoid changes, and hypertrichosis. Other skin changes, including whitening of the proximal nail (Terry nails), peripheral edema, hyperhidrosis, clubbing of the fingers, Raynaud phenomenon, and angiomas, have been observed.

Other signs and symptoms associated with POEMS syndrome include papilledema, anasarca, pleural effusions, ascites, fever, thrombosis, renal insufficiency, and diarrhea.

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Pathophysiology

The pathophysiology of POEMS syndrome is not well understood. In all patients, a plasma cell disorder underlies the development of the syndrome; however, the mechanism by which this occurs is unknown. Elevations of cytokines, such as interleukin (IL)–1beta, IL-6, and tumor necrosis factor (TNF)–alpha, have all been noted.

Most recently,[5] significant elevations in vascular endothelial growth factor (VEGF) levels have been noted. Increases in VEGF levels have been postulated to lead to enhanced vascular permeability, leading to the associated edema, increased endoneural pressure, and deposition of plasma cell–derived material. As myelin is exposed to serum cytokines and complement, demyelination can occur. In one case report of a patient with POEMS syndrome and bilateral cystoid macular edema, macular thickness varied with serum VEGF levels. After vitrectomy and an intraocular triamcinolone injection, decreased macular thickness was associated with lower intraocular VEGF levels. The authors proposed that elevated VEGF levels may be causally related to cystoid macular edema in persons with POEMS syndrome. Stimulated vascular proliferation has also been postulated to result in some of the skin changes associated with the disease.

VEGF may also play a role in bone metabolism, as suggested by a study of 2 patients who received high-dose therapy (HDT) with autologous stem cell transplantation. In this study by Kastritis et al,[6] decreasing VEGF levels corresponded with both clinical improvement and the normalization of bone metabolism as measured by multiple remodeling indices.

In a study of 22 patients with POEMS, hyperalgesia was correlated with an elevation of proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), in addition to the electrophysiologic reduction of sensory nerve action potentials and the histopathologic loss of myelinated fibers.[7] Serum levels of other growth factors, including epidermal growth factor, fibroblast growth factor, and platelet-derived growth factor, are not increased in patients with POEMS syndrome. Because POEMS syndrome is associated with Castleman disease and angioma formation, a role for human herpesvirus 8 (HHV-8) has been postulated; however, early studies have not demonstrated an association.

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Epidemiology

Frequency

POEMS syndrome is rare. Several hundred cases have been described in the literature; however, the incidence may be underreported because the syndrome may go unrecognized.

Race

No specific racial association has been identified, although a preponderance of cases have been reported in the Japanese literature.

Sex

POEMS syndrome is slightly more prevalent among men than women, with a male-to-female ratio of 2.5:1.

Age

The onset of POEMS syndrome occurs most frequently in the fifth or sixth decade of life, with a mean patient age at onset of 48 years for men and 59 years for women. In 2007 and 2008, however, POEMS syndrome has been reported to occur in two 15-year old patients.[8, 9]

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Contributor Information and Disclosures
Author

Joanna L Chan, MD Mohs Fellow, California Skin Institute

Joanna L Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Coauthor(s)

Matthew N Kubicki Perelman School of Medicine, University of Pennsylvania

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Neil Shear, MD Professor and Chief of Dermatology, Professor of Medicine, Pediatrics and Pharmacology, University of Toronto Faculty of Medicine; Head of Dermatology, Sunnybrook Women's College Health Sciences Center and Women's College Hospital, Canada

Neil Shear, MD is a member of the following medical societies: Canadian Medical Association, Ontario Medical Association, Royal College of Physicians and Surgeons of Canada, Canadian Dermatology Association, American Academy of Dermatology, American Society for Clinical Pharmacology and Therapeutics

Disclosure: Nothing to disclose.

Wingfield Rehmus, MD, MPH Dermatologist, BC Children's Hospital, Vancouver, British Columbia

Wingfield Rehmus, MD, MPH is a member of the following medical societies: American Academy of Dermatology, Society for Pediatric Dermatology

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Abbvie; Valeant Canada<br/> Received honoraria from Valeant Canada for advisory board; Received honoraria from Pierre Fabre for advisory board; Received honoraria from Mustella for advisory board; Received honoraria from Abbvie for advisory board.

Acknowledgements

Alexa F Boer Kimball, MD, MPH Associate Professor of Dermatology, Harvard University School of Medicine; Vice Chair, Department of Dermatology, Massachusetts General Hospital; Director of Clinical Unit for Research Trials in Skin (CURTIS), Department of Dermatology, Massachusetts General Hospital

Alexa F Boer Kimball, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

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