Information on the following diseases can be found in the Related Disorders section of this report:

• Scleroderma
• Chronic inflammatory demyelinating polyneuropathy (CIDP)
• Castleman’s disease
• Osteosclerotic myeloma
• .

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. In addition, individuals may experience a loss of general reflexes and motor function. The feet and legs are most often affected by peripheral neuropathy, but as time progresses without treatment the hands and feet 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, approximately 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 and eventually enter the blood stream. They are a key component of the immune system and secrete a substance known as M-proteins, a type of antibody. Antibodies, also known as immunoglobulins, are produced by the body to combat invading microorganisms, toxins, or other foreign substances. Antibodies can contain a light chain called kappa or lambda; however, the abnormal antibody (M protein) in patients with POEMS virtually always contains the 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 defects
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 leakage of cerebrospinal fluid into the optic disk of the eye may cause swelling of the disk (papilledema). Papilledema may result in progressive loss of clarity of vision (visual acuity).

Additional symptoms associated with POEMS syndrome include fever, clubbing of the fingers, 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). 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.)

The exact cause of POEMS syndrome is not known.

Some researchers suspect that POEMS syndrome may be an autoimmune disorder due to the elevated levels of M-proteins in the blood. In autoimmune disorders, the body’s natural defenses (e.g., M-proteins) against "foreign" or invading organisms mistakenly attack healthy tissue for unknown reasons. However, despite the abnormally elevated levels of M-proteins in the blood, no evidence of them attacking healthy tissue has been found in relation to POEMS syndrome.

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.

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 appears to be more common in Japan than in the United States and Europe.

The exact frequency of POEMS syndrome is unknown because the disorder often goes unrecognized making it making it difficult to determine the true frequency POEMS syndrome in the general population.

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.)

Scleroderma is a rare connective tissue disorder characterized by abnormally increased production and accumulation of collagen, the body's major structural protein, in skin and other organs of the body. There are systemic and localized forms of scleroderma. Systemic scleroderma is characterized by hardening (induration) and thickening of the skin and abnormal degenerative changes and formation of fibrous tissue (fibrosis) in certain organs of the body including the lungs, heart, kidneys, and gastrointestinal tract. Associated symptoms, which may vary widely from case to case, may include abnormal discoloration of and pain affecting the skin of the hands and feet upon exposure to cold temperatures (Raynaud's Phenomenon); abnormal tightness, thickening, "waxiness," and loss of elasticity of the skin; shortness of breath; difficulty swallowing; muscle weakness; joint pain; heart abnormalities including irregular heart beats (palpitations); kidney (renal) abnormalities; and/or other symptoms and findings. In individuals with localized scleroderma, involvement is restricted to the skin, tissue under the skin (subcutaneous tissue), and, in some cases, underlying muscle and bone. Although the exact cause of scleroderma is unknown, some researchers suggest that the disorder represents an abnormal autoimmune response in which the immune system reacts against part of the affected individual's own body. (For more information on this disorder, choose "scleroderma" 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 "osteosclerotic myeloma" as your search term in the Rare Disease Database.)

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, therapy with certain anticancer drugs (chemotherapy), like corticosteroids with cyclophosphamide or melphalan may temporarily alleviate symptoms associated with POEMS syndrome. Some patients may be offered high-dose chemotherapy with peripheral blood stem cell transplant.

Other treatment is symptomatic and supportive.

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 there 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 effects for several of these new drugs is peripheral neuropathy, which is the dominant symptom in patients with POEMS syndrome.

Additional therapies that have been used to treat POEMS syndrome include lenalidomide, anti-VEGF antibodies, interferon, intravenous immunoglobulin, plasmapheresis, and all-trans-retinoic acid.

This disease entry is based upon medical information available through February 2008. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder.

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JOURNAL ARTICLES
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Michel JL, et al. POEMS syndrome: imaging of skeletal manifestations, a study of 8 cases. J Radiol. 2003;84:393-7.

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

Hogan WJ, et al. Successful treatment of POEMS syndrome with autologous hematopoietic progenitor cell transplantation. Bone Marrow Transplant. 2001;28:305-09.

Barry JC, et al. Bilateral optic disk edema in polyneuropathy, organomegaly, endocrinopathy, monoclonal proteins and skin changes. Klin Monatsbl Augenheilkd. 1999;215:59-63.

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

Weichenthal M, et al. POEMS syndrome: cicatricial alopecia as an unusual cutaneous manifestation associated with an underlying plasmacytoma. J Am Acad Dermatol. 1999;40:808-12.

Ayala-Hernadez I, et al. POEMS syndrome. Report of a case. Gac Med Mex. 1999;135:311-15.

Erbsloh-Moller B, et al. POEMS syndrome with chronic renal failure. Med Klin. 1999;94:159-64.

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

Siegel EG, et al. 46-year-old patient with polyneuropathy, hepatosplenomegaly, endocrinopathy, M-gradient, skin manifestations, sclerotic bone changes and therapy refractory ascites. Z Gastroenterol. 1999;37:283-6.

Ako S, et al. Crow-Fukase syndromeÑimmunoadsorption plasmapheresis effectively lowers elevated interleukin-6 concentration. Nephrol Dial Transplant. 1999;14:419-22.

Miret C, et al. The role of plasmapheresis in the POEMS syndrome. Case report. Rev Clin Esp. 1998;198:189-90.

Gatinel D, et al. Papillary edema and the POEMS syndrome. J Fr Ophtalmol. 1998;21:133-41.

Cohnen M, et al. POEMS syndrome. A rare variant of osteosclerotic multiple myeloma with polyneuropathy, organomegaly, endocrinopathy, M-gradient and skin lesions. Med Klin. 1998;93:678-82.

Storstein A, et al. The POEMS syndrome--a rare multiorgan disease. Tidsskr Nor Laegeforen. 1998;118:3274-7.