POEMS syndrome

Other Names: Polyneuropathy organomegaly; Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin changes syndrome; Crow-Fukase syndrome

POEMS syndrome is a rare, mulitisystem disorder. POEMS stands for the disorder's features, which may include Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes.

Cause

The cause of POEMS syndrome is not well understood. POEMS syndrome is a paraneoplastic disorder, which means that the signs and symptoms of the syndrome appear as a manifestation of the plasma cell disorder that the patient has (most patients are seen with osteosclerotic myeloma or monoclonal gammopathy of unknown significance); however, the mechanism by which this occurs is unknown. It is associated with a chronic overproduction of some substances known as pro-inflammatory cytokines (small molecules that act as messengers between cells to promote inflammation). These include interleukins (IL-1b, IL6) which are cytokines that help regulate immune responses, TNFα (Tumor Necrosis Factor alfa is a cytokine which is involved in the inflammatory process) and vascular endothelial growth factor (VEGF – a powerful vasodilator that may cause leaky blood vessels) which seem to be important in this disorder.

Signs and symptoms

Signs and symptoms may include progressive sensorimotor polyneuropathy; enlarged liver, spleen, and/or lymph nodes; a disorder of the endocrine glands (often with multiple abnormalities); a monoclonal plasma cell [[]]proliferative disorder; and darkening of the skin (hyperpigmentation). Various other symptoms may also occur and may vary among affected people.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

100% of people have these symptoms

• Polyneuropathy(Peripheral nerve disease)

80%-99% of people have these symptoms

• Abnormality of skin physiology
• Hypogonadism(Decreased activity of gonads)
• Increased circulating antibody level
• Lymphoproliferative disorder
• Visceromegaly

30%-79% of people have these symptoms

• Areflexia(Absent tendon reflexes)
• Ascites(Accumulation of fluid in the abdomen)
• Clubbing of fingers(Clubbed fingers)
• Diabetes mellitus
• Erectile dysfunction(Abnormal erection)
• Fatigue(Tired)
• Gynecomastia(Enlarged male breast)
• [Hemangioma]](Strawberry mark)
• Hyperpigmentationof the skin(Patchy darkened skin)
• Hypertrichosis
• Hypothyroidism(Underactive thyroid)
• Leukonychia(White discoloration of nails)
• Lymphadenopathy(Swollen lymph nodes)
• Metaphyseal sclerosis
• Increased bone density in wide portion of long bone
• Pain
• Papilledema
• Paresthesia(Pins and needles feeling)
• Pericardial effusion(Fluid around heart)
• Pleural effusion(Fluid around lungs)
• Primary adrenal insufficiency
• Pulmonary arterial hypertension
• Increased blood pressure in blood vessels of lungs
• Sclerosis of foot bone(Increased bone density in foot bone)
• Sclerosis of hand bone(Increased bone density in hand bone)
• Sclerosis of skull base(Dense bone of skull base)
• Sclerotic vertebral endplates
• Thickened skin(Thick skin)
• Thrombocytosis(Increased number of platelets in blood)
• Weight loss

Diagnosis

People who are suspected of having POEMS syndrome should first have their medical history evaluated and undergo a complete physical exam. Features suggestive of POEMS syndrome in the history include complaints of neurological symptoms, skin changes, signs of extravascular volume overload, and symptoms suggestive of an endocrine disorder (such as gynecomastia or irregular periods). A detailed physical exam should include an eye exam for papilledema; a neurologic exam; evaluation for enlargement of organs (organomegaly); examination of the skin; and evaluation for the presence of peripheral edema (swelling due to fluid accumulation), pleural or pericardial effusion (fluid build-up around the lungs or heart), ascites, clubbing (enlargement of the fingertips), heart failure, and cardiomyopathy.

A diagnosis of POEMS syndrome requires both the presence of polyneuropathy and a monoclonal plasma cell proliferative disorder, plus the presence of at least one major and one minor criterion on a physical exam, imaging, or laboratory evaluation.

Major criteria include:

• An osteosclerotic or mixed sclerotic/lytic lesion seen on plain films or CT scan measuring at least 0.8 cm in the longest dimension
• Castleman's disease
• Elevated serum or plasma vascular endothelial growth factor (VEGF) levels at least 3 to 4 times the upper limit of normal

Minor criteria include:

• Organomegaly (enlargement of the spleen, liver, or lymph nodes)
• Extravascular volume overload (peripheral edema, ascites, or pleural effusion)
• Endocrinopathy (excluding diabetes mellitus or hypothyroidism)
• Skin changes
• Papilledema
• Thrombocytosis or polycythemia

Many affected people are initially misdiagnosed as having other disorders, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In addition, a number of conditions are associated with a plasma cell disorder and polyneuropathy (with or without osteosclerotic bone lesions), and need to be distinguished from POEMS syndrome.

Treatment

There is no standard treatment; management depends on the underlying plasma cell disorder and may include radiation therapy, chemotherapy, and/or hematopoietic cell transplantation. As reported by Dispenzieri et al. Mayo Clinic treatment regimens are tailored to treat the clinical manifestations and prognosis for the rate of progression of the POEMS syndrome in each patient. Other treatment regiments are being studied. Immunomodulatory imide drugs such as thalidomide and lenalidomide have been used in combination with dexamethasone to treat POEMS syndrome patients. While the mechanism of action of these immunomodulators are not clear, they do inhibit the production of cytokines suspected of contributing to POEMS syndrome such as VEGF, TNFα, and IL-6 and stimulate T cells and NK cells to increase their production of interferon gamma and interleukin 2 (see immunomodulatory imide drug's mechanism of action). A double blind study of 25 POEMS syndrome patients found significantly better results (VEGF reduction, neuromuscular function improvement, quality of life improvement) in patients treated with thalidomide plus dexamethasone compared to patients treated with a thalidomide placebo plus dexamethasone. Since VEGF plays a central role in the symptoms of POEMS syndrome, some have tried bevacizumab, a monoclonal antibody directed against VEGF. While some reports were positive, others have reported capillary leak syndrome suspected to be the result of overly rapid lowering of VEGF levels. It therefore remains doubtful as to whether this will become part of standard treatment for POEMS syndrome.

Prognosis

POEMS syndrome is a chronic condition. In many cases, there is progressive peripheral neuropathy that eventually causes mobility disability. The overall median survival has been estimated to be 13.7 years, while those with clubbing or extravascular volume overload may have median survivals of 2.6 and 6.6 years, respectively. Those who receive radiation therapy with a good response to treatment are thought to have longer survival. Death usually occurs from lack of nourishment or bronchopneumonia.

NIH genetic and rare disease info

• NIH info on POEMS syndrome

POEMS syndrome is a rare disease.

POEMS syndrome Resources
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