POEMS Syndrome

POEMS Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report POEMS Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Shimpo syndrome
  • Crow-Fukase syndrome
  • Takatsuki syndrome
  • PEP syndrome
  • polyneuropathy-organomegaly-endocrinopathy-M protein-skin lesions
  • osteosclerotic myeloma

Disorder Subdivisions

  • None

General Discussion

Summary

POEMS syndrome is an extremely rare multisystem disorder. POEMS is an acronym that stands for (P)olyneuropathy, disease affecting many nerves; (O)rganomegaly, abnormal enlargement of an organ; (E)ndocrinopathy, disease affecting certain hormone-producing glands that help to regulate sexual function, and certain metabolic functions; (M)onoclonal gammopathy or M proteins; and (S)kin abnormalities. Common symptoms include progressive weakness of the nerves in the legs and arms, an abnormally enlarged liver and/or spleen (hepatosplenomegaly), enlarged lymph nodes, abnormally darkening of the skin (hyperpigmentation), thickening of the skin and excessive hair growth (hypertrichosis). Endocrine abnormalities such as failure of the ovaries and testes (gonads) to function properly (primary gonadal failure) and diabetes mellitus may be present. Specific endocrine abnormalities associated with POEMS syndrome vary from case to case. Other important features of the disease include swelling around the optic nerve (papilledema), abnormal fluid retention, which may occur in the ankles (edema), the abdominal cavity (ascites), or around the lungs (pleural effusions), painless scars on bone x-ray (osteosclerosis), and an elevated platelet count (a blood cell responsible for clotting). Some patients may also have abnormalities in the lung function tests, which may not be noticed because of their inability to walk well due to their neuropathy.



Introduction

POEMS syndrome is associated with a group of disorders known as monoclonal gammopathies or plasma cell dyscrasias. These disorders are characterized the uncontrolled growth of a single clone (monoclonal) of plasma cells, which results in the abnormal accumulation of M-proteins (also known as immunoglobulins) in the blood. Immunoglobulins in health fight infection. However, the specific role M-proteins play and the exact cause of POEMS syndrome is unknown. Research would suggest that a chemical called VEGF (vascular endothelial growth factor) plays an important role in this disease.

Symptoms

POEMS syndrome affects multiple organ systems of the body. The specific symptoms present will vary from case to case. The acronym POEMS highlights the most significant features of this syndrome.



P=Polyneuropathy

In many cases, the first apparent symptom of POEMS syndrome is disease affecting many nerves (polyneuropathy). Individuals with POEMS syndrome experience chronic, progressive disease affecting the peripheral nervous system. The peripheral nervous system consists of all the motor and sensory (sensorimotor) nerves that connect the brain and spinal cord to the rest of the body (i.e., the nerves outside the central nervous system). Affected individuals experience weakness, pain, numbness, or tingling in affected areas usually starting in the toes and feet with the symptoms progressively working their way upwards. The feet and legs are most often affected by peripheral neuropathy, but as time progresses without treatment the hands may become affected as well.



O=Organomegaly

Approximately two thirds of individuals with POEMS syndrome will have an abnormally enlarged liver (hepatomegaly). One third of affected individuals have an abnormally enlarged spleen (splenomegaly). In some cases, affected individuals will exhibit swelling and disease affecting the lymph nodes (lymphadenopathy). When a biopsy is done, these swollen lymph nodes may show Castleman's Disease (angiofollicular lymph node hyperplasia) or Castleman-like features.



E=Endocrine abnormalities

Individuals with POEMS syndrome may exhibit various abnormalities affecting the endocrine system (i.e., the system of glands that secrete hormones into the blood system). Approximately 70 percent of individuals with POEMS syndrome experience primary gonadal failure, a condition characterized by improper function the ovaries in females or testes in males (i.e., gonads).



According to the medical literature, as many as 50 percent of affected individuals will develop diabetes mellitus. In addition, affected individuals will experience deficient functioning of the thyroid gland (hypothyroidism), impaired tolerance of sugar (glucose), insufficient functioning of the adrenal glands. Males with POEMS syndrome may experience abnormal enlargement of their breasts (gynecomastia) and impotence. Females with the disorder may experience stoppage of their menstrual cycle (amenorrhea) or even abnormal discharge of milk from the nipples (galactorrhea).



M=Monoclonal gammopathy or M protein

Monoclonal gammopathies, also known as plasma cell dyscrasias, are a group of disorders characterized by the uncontrolled growth of a single clone (monoclonal) of a certain type of cell (plasma cell). Overproduction of plasma cells may lead to the formation of masses (tumors) consisting of plasma cells (plasmacytomas). Typically these plasmacytomas appear like scars (sclerotic lesions) on bone x-ray.



Plasma cells are produced in the bone marrow. They are a key component of the immune system and secrete substances called immunoglobulins or antibodies whose function is to combat invading microorganisms, toxins, or other foreign substances. Each antibody protein contains two types of sub-units: heavy chains and light chains. There are only two types of light chains - kappa and lamba - and the abnormal immunoglobulin (or M-protein) associated with this condition virtually always lambda light chain. Overproduction of plasma cells in individuals with POEMS syndromes may result in the formation of sclerotic bone lesions and an overabundance of M-proteins in the blood. (For more information on M-proteins, see the Causes section of this report.)



In most cases, the specific type of plasma cell dyscrasia associated with POEMS syndrome is osteosclerotic myeloma, a variant of multiple myeloma. (For information on osteosclerotic myeloma, see the Related Disorders section of this report.)



S=Skin abnormalities

Abnormalities affecting the skin may be present in individuals with POEMS syndrome including abnormal darkening of the skin (hyperpigmentation), excessive hair growth (hypertrichosis), hardening and thickening of the skin (sclerosis), excessive sweating (hyperhidrosis), and dusky appearing extremities.



In addition to the classic physical abnormalities associated with POEMS syndrome, affected individuals may also experience swelling of the optic disk (papilledema). Papilledema may result in progressive loss of clarity of vision (visual acuity).



Additional symptoms associated with POEMS syndrome include fluid buildup in the lungs (pleural effusion), and abnormal accumulation of fluid in the skin of the arms and legs and in the space (peritoneal cavity) between the two layers of the membrane that lines the stomach (ascites), fever, and clubbing of the fingers. In some cases, affected individuals may have kidney (renal) abnormalities. In rare cases, increased blood pressure of the arteries within the lungs (pulmonary hypertension) may also be present.



In addition, some cases of POEMS syndrome are associated with a lymphoproliferative disorder, such as Castleman's disease. (For more information on this disorder, see the Related Disorders section of this report.)

Causes

The exact cause of POEMS syndrome is not known.



Studies have demonstrated abnormally high levels of vascular endothelial growth factor (VEGF) in the serum of individuals with POEMS syndrome. More research is needed to determine the exact role cytokines and VEGF play in the development of POEMS syndrome.



Other cytokines (non-antibody chemical that the body's cells to communicate with each other) have been showed to be elevated in patients with the disease, like interleukin-6, interleukin-1 and TNF-alpha.

Affected Populations

POEMS syndrome affects men more often than women and usually occurs during the forties or fifties, although it has been reported in individuals in their twenties. The disorder was originally thought to be more common in Japan than in the United States and Europe. POEMS syndrome often goes unrecognized, making it difficult to determine the true frequency in the general population.

Standard Therapies

Diagnosis

In most cases, POEMS syndrome is diagnosed based upon a thorough clinical evaluation, identification of characteristic symptoms and physical findings, a detailed patient and family history, and laboratory testing.



Confirmation of certain immunologic abnormalities plays an essential role in establishing the diagnosis of POEMS syndrome. Laboratory tests conducted on the liquid portion of the blood (serum) or cerebrospinal fluid (CSF) may reveal elevated levels of M-proteins. Study of the blood plasma may show high levels of vascular endothelial growth factor. In many cases, surgical removal (biopsy) and microscopic examination of small samples of tissue from an osteosclerotic lesion or sometimes a simple bone marrow biopsy will reveal the abnormal presence of monoclonal plasma cells. Skeletal imaging may be performed to detect osteosclerotic lesions characteristic of POEMS syndrome.



Treatment

The treatment of POEMS syndrome is two pronged. The first is directed at treating the underlying plasma cell disorder (e.g. the osteosclerotic myeloma). The second is directed toward ameliorating the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists.



The use of ionizing radiation (radiotherapy) or surgical removal (excision) or of osteosclerotic lesions that are localized (i.e., not widespread throughout the body) may temporarily (and sometimes permanently) lead to a remission of symptoms associated with POEMS syndrome.



In many cases, including those with widespread osteosclerotic lesions or diffuse bone marrow involvement, therapy with certain anticancer drugs (chemotherapy), like corticosteroids with cyclophosphamide or melphalan may alleviate symptoms associated with POEMS syndrome. Many patients may be offered high-dose chemotherapy with peripheral blood stem cell transplant.



Other treatment is symptomatic and supportive.

Investigational Therapies

Because POEMS syndrome is a plasma cell disorder (i.e. due to an overgrowth of plasma cells), it is a cousin disease to multiple myeloma. In the 2000s, there have been several new drugs to treat myeloma. These may be tried only with extreme caution in patients with POEMS syndrome, because the major side effect of several of these new drugs is peripheral neuropathy, the dominant symptom in patients with POEMS syndrome.



Additional therapies that have been used to treat POEMS syndrome include lenalidomide, thalidomide and bortezomib. The role of the following therapies is much less certain: anti-VEGF antibodies, interferon, intravenous immunoglobulin, plasmapheresis, and all-trans-retinoic acid.



Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com



Contact for additional information about POEMS syndrome:



Angela Dispenzieri, M.D.

Consultant, Division of Hematology

Professor of Medicine, Laboratory Medicine, and Pathology

Mayo Clinic

200 First Street SW

Rochester, MN 55905

Phone: 507 266-0792

Fax: 507 266-4972

References

TEXTBOOKS

Mitrani AA. POEMS Syndrome. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:26.



Fauci AS, et al, eds. Harrison's Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:2137-38.



Magalini SI, et al, eds. Dictionary of Medical Syndromes. 4th ed. New York, NY: Lippincott-Raven Publishers; 1997:196.



Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:965.



Frank MM, et al. Samter's Immunologic Diseases, 5th ed. Boston, MA: Little, Brown and Company; 1995:992.



Wilson JD, et al. Textbook of Endocrinology. 8th ed. Philadelphia, PA: W. B. Saunders Co; 1992:1562-63.



JOURNAL ARTICLES

Dispenzieri A. How I treat POEMS syndrome. Blood. 2012;119(24):5650-5658.



Nasu S, Misawa S, et al. Different neurological and physiological profiles in POEMS syndrome and chronic inflammatory demyelinating polyneuropathy. Journal of neurology, neurosurgery, and psychiatry. 2012;83(5):476-479.



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



D'Souza A, Lacy M, et al. Long-term outcomes after autologous stem cell transplantation for patients with POEMS syndrome (osteosclerotic myeloma): a single-center experience. Blood. 2012;120(1):56-62.



Briani C, Fabrizi GM, et al. Vascular endothelial growth factor helps differentiate neuropathies in rare plasma cell dyscrasias. Muscle Nerve. 2012;43(2):164-167.



Li J, Zhang W, et al. Combination of melphalan and dexamethasone for patients with newly diagnosed POEMS syndrome. Blood. 2011;117(24):6445-6449.



Kuwabara S, Misawa S, et al. Neurologic improvement after peripheral blood stem cell transplantation in POEMS syndrome. Neurology. 2008;71(21):1691-1695.



Rovira M, et al. Dramatic improvement of POEMS syndrome following autologous haematopoietic cell transplantation. Br J Haematol. 2001;115:373-75.



Soubrier M, et al. Growth factors and proinflammatory cytokines in the renal involvement of POEMS syndrome. Am J Kidney Dis. 1999;34:633-8.



Arimura K. Increased vascular endothelial growth factor (VEGF) is causative in Crow-Fukase syndrome. Rinsho Shinkeigaku. 1999;39:84-5.

Resources

American Autoimmune Related Diseases Association, Inc.

22100 Gratiot Ave.

Eastpointe, MI 48021

Tel: (586)776-3900

Fax: (586)776-3903

Tel: (800)598-4668

Email: aarda@aarda.org

Internet: http://www.aarda.org/



NIH/Child Health and Human Development - Section on Endocrinology and Genetics

Bldg 31, Room 2A32, MSC 2425

31 Center Drive

Bethesda, MD 20892-2425

Tel: (301)402-1998

Fax: (301)402-2984

Email: stratakc@exchange.nih.gov

Internet: http://segen.nichd.nih.gov/index.html



NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Information Clearinghouse

One AMS Circle

Bethesda, MD 20892-3675

USA

Tel: (301)495-4484

Fax: (301)718-6366

Tel: (877)226-4267

TDD: (301)565-2966

Email: NIAMSinfo@mail.nih.gov

Internet: http://www.niams.nih.gov/



NIH/National Institute of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

Tel: (301)496-5751

Fax: (301)402-2186

Tel: (800)352-9424

TDD: (301)468-5981

Internet: http://www.ninds.nih.gov/



Neuropathy Association

60 East 42nd Street

Suite 942

New York, NY 10165

USA

Tel: (212)692-0662

Fax: (212)692-0668

Email: info@neuropathy.org

Internet: http://www.neuropathy.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Center for Peripheral Neuropathy

University of Chicago

5841 South Maryland Ave, MC 2030

Chicago, IL 60637

Tel: (773)702-5659

Fax: (773)702-5577

Internet: http://peripheralneuropathycenter.uchicago.edu/



AutoImmunity Community

Email: moderator@autoimmunitycommunity.org

Internet: http://www.autoimmunitycommunity.org



For a Complete Report

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