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POEMS Syndrome

NORD is very grateful to Angela Dispenzieri, MD, Consultant, Division of Hematology, Professor of Medicine, Laboratory Medicine, and Pathology, Mayo Clinic, for assistance in the preparation of this report.

Synonyms of POEMS Syndrome

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

Disorder Subdivisions

  • No subdivisions found.

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.

Related Disorders

Symptoms of the following disorders can be similar to those of POEMS syndrome. Comparisons may be useful for a differential diagnosis:

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare disorder in which swelling of nerve roots and destruction of the fatty protective covering (myelin sheath) over the nerves occurs. This disorder causes weakness, paralysis and/or impairment in motor function, especially of the arms and legs. Sensory loss may also be present causing numbness, tingling, or prickling sensations in affected areas. The motor and sensory impairments are usually symmetrical (on both sides of the body), and the degree of severity may vary. The course of CIDP may also vary. Some affected individuals may follow a slow steady pattern of symptoms while others may have symptoms that wax and wane, with the most severe symptoms occurring after many months or a year or more. One feature that distinguishes this disorder from other similar disorders is that there is typically no preceding viral infection at least three months prior to the appearance of the disorder, and no family history of other similar disorders or polyneuropathy. (For more information on this disorder, choose "chronic inflammatory demyelinating polyneuropathy" as your search term in the Rare Disease Database.)

The following disorders may occur in association with the POEMS syndrome:

Castleman's disease is a rare disorder characterized by non-cancerous (benign) growths (tumors) that may develop in the lymph node tissue throughout the body (i.e., systemic disease [plasma cell type]). Most often, they occur in the chest, stomach, and/or neck (i.e., localized disease [hyaline-vascular type]). Less common sites include the armpit (axilla), pelvis, and pancreas. Usually the growths represent abnormal enlargement of the lymph nodes normally found in these areas (lymphoid hamartoma). There are two main types of Castleman's disease: hyaline-vascular type and plasma cell type. The hyaline vascular type accounts for approximately 90 percent of the cases. Most individuals exhibit no symptoms of this form of the disorder (asymptomatic) or they may develop non-cancerous growths in the lymph nodes. The plasma cell type of Castleman's disease may be associated with fever, weight loss, skin rash, early destruction of red blood cells, leading to unusually low levels of circulating red blood cells (hemolytic anemia), and/or abnormally increased amounts of certain immune factors in the blood (hypergammaglobulinemia). The presentation for Castleman's disease can be as one lymph node enlargement (unicentric), which is the most common presentation for the hyaline vascular pathologic variant, or in many lymph node regions (multicentric), with is the more common presentation for the plasma cell variant. Many individuals with multicentric Castleman's disease may exhibit an abnormally large liver and spleen (hepatosplenomegaly). (For more information on this disorder, choose "Castleman’s" as your search term in the Rare Disease Database.)

Osteosclerotic myeloma is a variant of multiple myeloma, a rare condition characterized by excessive production (proliferation) and improper function of certain cells (plasma cells) of the bone marrow. The majority of the cases of osteosclerotic myeloma are associated with POEMS, but there are some patients who have the osteosclerotic bone lesions (hardening and abnormal density of bone), but whose disease acts like typical multiple myeloma. The symptoms of multiple myeloma may include weakness; fatigue; pain in the back and the ribs, worsened by movement; low levels of circulating red blood cells (anemia); and/or renal failure. The exact cause of osteosclerotic myeloma is not known. (For more information on this disorder, choose "multiple myeloma" as your search term in the Rare Disease Database.)

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

POEMS Syndrome Resources

Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder (e.g., polyneuropathy, skin abnormalities, etc.)

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:

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.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2012/09/07 00:00:00 GMT+0

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