POEMS Syndrome: Symptoms, Causes, Diagnosis, Treatment

POEMS Syndrome: Symptoms, Causes, Diagnosis, Treatment


POEMS syndrome is a very rare multisystem condition where the body’s immune system attacks cells in the nervous system. This attack from the immune system is caused by an abnormal immune response to a cancerous tumor.

POEMS syndrome symptoms include weakness of the arms and legs, darkening of the skin, and an abnormal increase in the size of lymph nodes and internal organs like the spleen or liver.

POEMS syndrome is a chronic (long-term) disorder with no cure. In the United States, POEMS syndrome affects approximately 5,000 people. The disease occurs 1.5 times more often in people assigned male at birth. Researchers don’t know the exact cause of POEMS syndrome, but research suggests that a protein called vascular endothelial growth factor (VEGF) plays a role in the development of the disease.

POEMS syndrome does not have a cure, but treatments like chemotherapy and blood cell transplants can help manage the disease.

POEMS is an acronym for the disorder’s five common symptom types: polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin abnormalities. The type and severity of symptoms vary from person to person.

Polyneuropathy

Polyneuropathy symptoms include limb weakness and numbness due to nerve damage. Polyneuropathies are the main and most common symptoms of POEMS syndrome. They develop over a period of weeks to months. Almost every person diagnosed with POEMS presents with neuropathy symptoms.

Polyneuropathy affects nerves throughout the body and includes the following symptoms:

  • Weakness, pain, and numbness of feet, legs, arms, and hands
  • Burning and prickly skin
  • General muscle weakness that impairs doing everyday tasks like standing up from a chair, grabbing objects, and going up the stairs
  • Blurry vision as a result of ocular nerves being affected

Monoclonal Gammopathy

Monoclonal gammopathy is caused when the immune system’s plasma cells or white blood cells abnormally overproduce proteins. These cells typically produce antibodies that help the immune system fight diseases. Abnormal behavior of these cells is one of the most common symptoms of POEMS. Monoclonal gammopathy affects all individuals diagnosed with POEMS.

Monoclonal gammopathy causes the following symptoms:

  • Overabundance (too many) of proteins in the blood
  • Plasma cell (white blood cell) tumors
  • Thickening and hardening of bones

Organomegaly

Organomegaly is the abnormal enlarging of one or multiple organs in the body. In POEMS syndrome, organomegaly can cause enlarged spleen, liver, and lymph nodes. Enlarged or swollen lymph nodes are also known as Castleman disease.

The most common form of organomegaly is an enlarged liver. Up to 78% of people with POEMS syndrome are diagnosed with this symptom.

Endocrinopathy

Endocrinopathy is caused when normal hormone levels are affected by problems in the endocrine system. Individuals with POEMS syndrome might experience some of the following endocrinopathy symptoms:

  • Difficulty regulating blood sugar
  • Infertility
  • Enlargement of breasts and erectile dysfunction in men
  • Abnormal or absent menstrual cycle
  • Increased breast milk production or breast discharge

Endocrinopathies can affect up to 84% of people diagnosed with POEMS syndrome.

Skin Abnormalities

Skin abnormalities affecting individuals with POEMS syndrome vary widely. Examples include:

  • Darkening of skin
  • Sudden and excessive hair growth
  • Thickening of the skin
  • Excessive sweating
  • Blue pigmented limbs
  • Discoloration of nails
  • Clubbed nails

The cause of POEMS syndrome is not well defined. However, research suggests a protein called vascular endothelial growth factor (VEGF) plays a key role in the development of the disease. People with POEMS syndrome have abnormally high levels of VEGF protein in their blood. This is one of the major signs that a person has POEMS syndrome.

VEGF is a protein produced by plasma cells that plays a role in the formation of blood vessels. While increased levels of VEGF in the blood predict POEMS diagnosis, VEGF alone does not cause the disease. Studies and treatments developed to decrease VEGF levels in POEMS syndrome have produced mixed results.

Another potential cause of POEMS is the abnormally increased production of inflammatory molecules known as cytokines. Cytokines are molecules the body’s immune system produces to kick-start your body to fight off disease. People with POEMS syndrome demonstrate abnormally high blood levels of various cytokines, including interleukin 6 (IL6), interleukin 1(IL1), and tumor necrosis factor alpha (TNF-alpha).

More research is needed to determine why elevated levels of cytokines and VEGF cause POEMS syndrome.

Diagnosing POEMS involves identifying the two major symptoms of the condition: neuropathy and monoclonal gammopathy. These two symptom types are “mandatory major criteria” for diagnosing the condition.

POEMS syndrome is often diagnosed by a neurologist (doctor specializing in nerve disorders) or hematologist (doctor specializing in blood disorders). To test for neuropathy, your healthcare provider will perform multiple neurological tests to assess how your nervous system is working. One of the tests includes a physical examination, where your healthcare provider will assess:

  • Your muscle weakness
  • Movement of your extremities
  • Whether you can properly feel touch, pressure, and temperature

Electromyography (EMG) might be performed to check nerve function. In particular, it shows slow nerve conduction of action potentials—nerve cell signals allowing proper nerve functioning.

To test for monoclonal gammopathy, your healthcare provider will order a blood test to check for elevated levels of VEGF and cytokines in your blood. Elevated levels of VEGF and cytokines are usually found in blood serum. Plasma levels of VEGF over 200 picograms per milliliter (pg/mL) usually indicate POEMS syndrome. Your healthcare provider will monitor your VEGF plasma levels throughout your disease treatment.

After confirming a POEMS syndrome diagnosis, your healthcare provider will perform various other tests to identify what other POEMS syndromes you are experiencing.

Treatment of POEMS has three major goals:

  1. Eliminate or reduce clonal plasma cells
  2. Reduce levels of VEGF
  3. Stabilize organ function

The treatment team often includes multiple healthcare providers, including neurologists, hematologists, radiologists (specializing in medical imaging), and histopathologists (specializing in studying tissue). These providers use a variety of treatments to accomplish these goals and improve the prognosis.

Effectiveness and response to treatment vary from person to person.

Radiation Therapy

Radiation therapy is the first line of therapy. This type of cancer therapy uses high levels of radiation to kill cancer cells by damaging their DNA.

Radiation therapy targets the plasma cells producing abnormally high levels of VEGF and cytokines. About 50-70% of people treated with radiation therapy demonstrate improvement in neuropathy and organomegaly symptoms and a decrease in VEGF plasma levels.

Chemotherapy

If your POEM syndrome symptoms are more advanced, your healthcare provider might suggest chemotherapy. Chemotherapy involves the use of drugs (without radiation) to target and kill cancer cells. Chemotherapy treatment regimens to treat POEMS syndromes involve some of the following drugs:

  • Lenalidomide
  • Daratumumab
  • Bortezomib
  • Dexamethasone

Some clinical trials support the use of chemotherapy for POEMS syndrome. However, more studies are needed, as these trials had small participant populations.

Autologous Hematopoietic Cell Transplantation 

An autologous hematopoietic cell transplant (auto-HCT) takes a person’s healthy stem cells from the blood or bone marrow before chemotherapy treatment and returns them to the person after radiation or chemotherapy.

Like chemotherapy, some clinical trials with small participant populations have shown promising results for auto-HCT as a treatment for POEMS syndrome. These trials have shown that auto-HCT can drastically improve neuropathy symptoms.

There is no known way to prevent POEMS syndrome.

According to the National Organization for Rare Disorders (NORD), POEMS syndrome has two major co-occurring disorders:

  • Castleman disease: This rare disorder causes enlarged lymph nodes. It can affect a single set of lymph nodes localized to one body part or a large number of lymph nodes throughout the body
  • Osteosclerotic myeloma: Like POEMS, this condition is caused by the abnormal function of plasma cells. Osteosclerotic myeloma causes the hardening of bones, renal (kidney) dysfunction, anemia (reduced number of red blood cells or hemoglobin), and bone lesions.

Conditions With Similar Symptoms

Several conditions share symptoms similar to POEMS syndrome, such as muscle weakness, numbness, and tingling:

  • Chronic inflammatory demyelinating polyneuropathy (CIDP): A rare nerve disorder that causes nerve swelling and destruction of myelin (the protective layer around nerves)
  • Amyloid light chains (AL) amyloidosis: A bone marrow disorder that affects multiple body systems
  • Guillain-Barré syndrome: A disorder in which the body attacks its one peripheral (outside the brain and spinal cord) nervous system
  • Monoclonal gammopathy of undetermined significance (MGUS): Abnormal monoclonal protein in the blood
  • Chronic ataxic neuropathy with ophthalmoplegia (CANOMAD): Neuropathy caused by immunoglobulin M (IgM) antibodies

POEMS syndrome is a very rare multisystem condition where the body’s immune system attacks cells in the nervous system in response to a cancerous tumor. POEMS is an acronym for the disorder’s five common symptom types: polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin abnormalities.

The causes are unclear, but a protein called vascular endothelial growth factor (VEGF) seems to play a key role in the development of POEMS syndrome. Treatment focuses on eliminating or reducing clonal plasma cells, reducing VEGF levels, and stabilizing organ function. It might include radiation, chemotherapy, or cell transplantation.

There’s no cure, but treatment can help manage symptoms.

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