POEMS syndrome

Overview

POEMS syndrome is a rare multisystem disorder caused by an underlying plasma cell proliferative disease. The acronym "POEMS" stands for Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, and Skin changes—the five hallmark features that characterize the condition. It is considered a paraneoplastic syndrome and often overlaps with other plasma cell disorders such as multiple myeloma or Castleman disease. The disease is chronic, progressive, and can be life-threatening if not treated, though early diagnosis and intervention can significantly improve outcomes.

Causes

POEMS syndrome is caused by an underlying plasma cell neoplasm, typically a monoclonal proliferation of lambda light chain–producing plasma cells. The exact mechanism through which these cells cause the diverse symptoms of POEMS is not fully understood. However, overproduction of certain cytokines, particularly vascular endothelial growth factor (VEGF), is thought to play a major role in the pathogenesis by increasing vascular permeability and promoting inflammation.

While the cause of the initial plasma cell abnormality is unknown, it is clear that the resulting abnormal immune and inflammatory responses lead to the multisystem manifestations seen in POEMS syndrome.

Symptoms

Symptoms of POEMS syndrome are broad and often affect multiple organ systems. The condition typically progresses slowly, and not all features may be present at once. Major symptoms include:

• Polyneuropathy: Symmetrical, progressive peripheral neuropathy is often the first and most prominent symptom. It typically starts in the legs and leads to muscle weakness, numbness, and difficulty walking.

• Organomegaly: Enlargement of organs such as the liver (hepatomegaly), spleen (splenomegaly), and lymph nodes (lymphadenopathy).

• Endocrinopathy: Involves hormonal disturbances such as hypothyroidism, diabetes mellitus, adrenal insufficiency, and gynecomastia. Hypogonadism is particularly common.

• Monoclonal plasma cell disorder: Detection of an M-protein (monoclonal immunoglobulin) in the blood or urine, usually of the IgA or IgG type, with lambda light chains.

• Skin changes: Includes hyperpigmentation, hypertrichosis (excess hair growth), sclerodermoid changes, and hemangiomas.

Additional features may include:

• Edema (swelling) and effusions (fluid accumulation in pleural or pericardial cavities)

• Papilledema (swelling of the optic disc)

• Thrombocytosis or polycythemia

• Weight loss and fatigue

Diagnosis

Diagnosis of POEMS syndrome is based on a combination of clinical features, laboratory results, and imaging findings. There are established diagnostic criteria that must be met, which include:

• Mandatory criteria:

  • Polyneuropathy

  • Monoclonal plasma cell disorder (usually lambda light chain)

• Major criteria:

  • Sclerotic bone lesions

  • Castleman disease

  • Elevated VEGF levels

• Minor criteria:

  • Organomegaly

  • Endocrinopathy

  • Skin changes

  • Papilledema

  • Extravascular fluid overload

  • Thrombocytosis/polycythemia

Diagnostic investigations include:

• Serum protein electrophoresis (SPEP) and immunofixation: To detect monoclonal proteins.

• Electromyography (EMG): To confirm peripheral neuropathy.

• Imaging: PET or CT scans to detect bone lesions and organ enlargement.

• VEGF levels: Elevated levels support the diagnosis.

• Bone marrow biopsy: To identify abnormal plasma cells.

Treatment

Treatment of POEMS syndrome aims to control the underlying plasma cell disorder and manage the associated symptoms. Options include:

• Radiation therapy: Used when disease is localized, especially in cases with isolated sclerotic bone lesions.

• Systemic therapy: Required for widespread disease and includes:

  • Corticosteroids and alkylating agents like melphalan

  • Immunomodulatory drugs: Thalidomide or lenalidomide, often combined with dexamethasone

  • Proteasome inhibitors: Bortezomib has shown benefit in some patients

• Autologous stem cell transplantation (ASCT): Considered the most effective treatment for eligible patients, especially those with more severe or systemic disease.

• Supportive care: Includes physical therapy for neuropathy, hormone replacement for endocrinopathies, and treatment of fluid overload.

Regular follow-up and multidisciplinary care are essential for managing the complex manifestations of the syndrome.

Prognosis

The prognosis of POEMS syndrome varies depending on the extent of disease and response to treatment. With appropriate therapy, especially autologous stem cell transplantation, many patients achieve long-term remission. However, the condition is chronic and requires continuous monitoring. Early diagnosis and treatment can significantly improve quality of life and survival. Without intervention, the disease can lead to progressive organ failure and severe disability due to neuropathy.

Regular follow-up with specialists in hematology, neurology, endocrinology, and rehabilitation is crucial for optimal management and monitoring of complications.