POEMS Syndrome is a rare, complex multisystem disorder that affects multiple body systems simultaneously. It is often challenging to diagnose because its wide variety of symptoms can mimic other, more common diseases. This article addresses whether the syndrome is hereditary or acquired, details its characteristics, explains its underlying biological cause, and outlines current management strategies.
Defining POEMS Syndrome
POEMS Syndrome is an acronym summarizing the five main features of the disorder. The “P” stands for Polyneuropathy, a mandatory diagnostic requirement involving chronic, progressive damage to the peripheral nerves, typically causing weakness and numbness in the feet and legs. The “O” represents Organomegaly, the abnormal enlargement of organs like the liver, spleen, or lymph nodes.
The “E” denotes Endocrinopathy, indicating hormonal abnormalities that frequently affect multiple endocrine glands. This often results in hypogonadism or hypothyroidism, leading to symptoms like impotence, amenorrhea, or diabetes-like changes. The “M” is for Monoclonal protein, an abnormal antibody component produced by a clone of plasma cells. The “S” covers Skin changes, which commonly include hyperpigmentation (darkening of the skin) and sometimes thickening or increased body hair.
Diagnosis requires the two mandatory criteria—polyneuropathy and a monoclonal plasma cell-proliferative disorder—along with at least one of the three non-mandatory major criteria and one minor criterion. Other major criteria include sclerotic bone lesions, Castleman disease, and elevated levels of Vascular Endothelial Growth Factor (VEGF).
The Etiology Question: Heredity Versus Acquired
POEMS Syndrome is overwhelmingly considered an acquired condition, not a hereditary one. It develops sporadically over a person’s lifetime, typically presenting in middle age, with the average onset around age 50. The condition is a paraneoplastic syndrome, meaning its symptoms are caused by substances released by a localized, underlying cell disorder.
Reported cases where POEMS Syndrome appears to run in families are extremely small. Experts often re-evaluate these rare familial instances and find them to be misdiagnoses of other hereditary neuropathies, such as Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) or hereditary amyloidosis. The acquired nature of POEMS Syndrome is strongly supported by the underlying cause: a specific, non-inherited proliferation of a single clone of plasma cells.
The Underlying Cause: Monoclonal Plasma Cell Proliferation
The fundamental biological driver of POEMS Syndrome is a monoclonal plasma cell-proliferative disorder. Plasma cells are specialized white blood cells that produce antibodies. In POEMS Syndrome, a single, abnormal clone of these cells multiplies uncontrollably, usually in the bone marrow or a localized bone lesion. This clone produces a specific, abnormal antibody component known as an M-protein, detectable in the blood or urine.
The culprit cell clone is responsible for the massive overproduction of Vascular Endothelial Growth Factor (VEGF). Serum levels of VEGF are significantly elevated in nearly all patients with active POEMS Syndrome and correlate directly with disease activity. VEGF is a potent stimulator of blood vessel formation and increases vascular permeability, causing vessels to become “leaky.”
This increased vascular permeability driven by high VEGF levels is the mechanism behind many of the syndrome’s features, including organ enlargement, extravascular fluid retention, and peripheral edema. The resulting fluid leakage and swelling contribute to the neuropathy and other symptoms. Eliminating the plasma cell clone responsible for the VEGF overproduction is the primary goal of treatment.
Current Treatment Approaches
The management of POEMS Syndrome centers on eliminating the underlying monoclonal plasma cell clone to halt the overproduction of VEGF. Treatment strategy depends heavily on the extent of the disease. For patients with disease localized to a single bone lesion, such as a solitary sclerotic plasmacytoma, localized radiation therapy is the first-line treatment. Radiation effectively destroys the localized clone, reducing VEGF levels and leading to clinical improvement.
Patients with disseminated disease—multiple bone lesions or widespread bone marrow involvement—require systemic therapy. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is often the most effective long-term approach for eligible patients. This intensive treatment aims to eradicate abnormal plasma cells throughout the body, leading to durable remissions.
For patients not candidates for ASCT due to age or other health conditions, systemic chemotherapy is utilized, often combined with corticosteroids. Treatments involving immunomodulatory drugs, such as lenalidomide, or proteasome inhibitors have shown promise in reducing the plasma cell burden and lowering VEGF concentrations.