7 Key Signs and Symptoms of POEMS Syndrome You Should Know

POEMS syndrome is a rare, multisystem disorder that affects multiple parts of the body simultaneously. The name POEMS is an acronym that stands for the five major features of the condition: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, and Skin changes. This complex condition is caused by an abnormal proliferation of plasma cells, which produces proteins that damage various organs and tissues throughout the body.

Understanding the symptoms of POEMS syndrome is crucial for early detection and timely medical intervention. Because this condition affects multiple body systems, its symptoms can be diverse and sometimes confusing. Many patients experience symptoms for months or even years before receiving an accurate diagnosis. This article will explore the seven key symptoms of POEMS syndrome to help you recognize the warning signs and seek appropriate medical care.

1. Polyneuropathy (Nerve Damage)

Polyneuropathy is typically the most prominent and often the first noticeable symptom of POEMS syndrome. This condition involves damage to multiple peripheral nerves throughout the body, affecting how signals travel between the brain, spinal cord, and the rest of the body.

The nerve damage usually presents as:

• Numbness and tingling: Patients often experience a “pins and needles” sensation that typically begins in the feet and hands, then gradually progresses upward to the legs and arms
• Muscle weakness: Progressive weakness that starts in the lower extremities and can eventually affect the ability to walk, climb stairs, or perform daily activities
• Loss of reflexes: Diminished or absent deep tendon reflexes, particularly in the ankles and knees
• Sensory changes: Reduced ability to feel temperature, pain, or touch, which can increase the risk of injuries
• Balance problems: Difficulty maintaining balance and coordination due to impaired proprioception (sense of body position)

The polyneuropathy in POEMS syndrome is chronic and progressive, meaning it develops gradually over time and tends to worsen without treatment. Unlike some other forms of neuropathy, this condition typically affects both sides of the body symmetrically.

2. Organomegaly (Enlarged Organs)

Organomegaly refers to the abnormal enlargement of one or more internal organs, which is a hallmark feature of POEMS syndrome. The most commonly affected organs include the liver, spleen, and lymph nodes.

Specific manifestations include:

• Hepatomegaly (enlarged liver): The liver becomes enlarged and may be palpable below the rib cage during physical examination. Patients might experience a feeling of fullness or discomfort in the upper right abdomen
• Splenomegaly (enlarged spleen): An enlarged spleen can cause discomfort or pain in the upper left abdomen and may contribute to early satiety (feeling full quickly when eating)
• Lymphadenopathy (swollen lymph nodes): Lymph nodes, particularly in the neck, armpits, or groin, may become noticeably enlarged and can sometimes be felt as lumps under the skin

The organ enlargement occurs due to the abnormal accumulation of fluid and the effects of the abnormal proteins produced by plasma cells. While not all patients with POEMS syndrome will experience all forms of organomegaly, at least one form of organ enlargement is typically present.

3. Endocrinopathy (Hormonal Imbalances)

Endocrinopathy involves dysfunction of one or more endocrine glands, leading to hormonal imbalances that can affect various body functions. Multiple endocrine systems may be affected simultaneously in POEMS syndrome.

Common endocrine abnormalities include:

• Diabetes or glucose intolerance: Impaired insulin production or insulin resistance leading to elevated blood sugar levels
• Thyroid dysfunction: Hypothyroidism (underactive thyroid) causing fatigue, weight gain, cold intolerance, and depression
• Adrenal insufficiency: Reduced production of cortisol and other adrenal hormones, leading to weakness, fatigue, and low blood pressure
• Gonadal dysfunction: In men, this may manifest as low testosterone levels, reduced libido, and erectile dysfunction. In women, it may cause irregular menstrual periods, amenorrhea (absence of periods), or early menopause
• Growth hormone abnormalities: Can affect metabolism and overall energy levels

These hormonal imbalances can significantly impact quality of life and may cause symptoms such as chronic fatigue, weight changes, mood alterations, decreased bone density, and reproductive issues.

4. Monoclonal Protein and Bone Lesions

The presence of monoclonal protein in the blood is a defining feature of POEMS syndrome. This abnormal protein is produced by the proliferation of plasma cells, which are a type of white blood cell.

This manifestation includes:

• M-protein detection: Blood and urine tests reveal the presence of monoclonal protein, typically immunoglobulin A (IgA) or immunoglobulin G (IgG) with lambda light chains
• Bone lesions: Sclerotic (dense, hardened) bone lesions that appear on imaging studies such as X-rays, CT scans, or MRI. These lesions are typically found in the ribs, spine, pelvis, and other bones
• Bone pain: Some patients experience localized bone pain, particularly in areas where lesions are present
• Elevated VEGF levels: Vascular endothelial growth factor (VEGF) levels are characteristically elevated in the blood, contributing to many of the syndrome’s symptoms

While patients may not directly “feel” the presence of monoclonal protein or bone lesions, these findings are crucial for diagnosis and explain many of the other symptoms experienced.

5. Skin Changes (Dermatological Manifestations)

Skin changes are common in POEMS syndrome and can be among the most visible symptoms. These changes result from the effects of elevated VEGF and other factors on blood vessels and skin tissue.

Typical skin manifestations include:

• Hyperpigmentation: Darkening of the skin, particularly in sun-exposed areas or over bony prominences
• Skin thickening: Areas of skin may become thicker, tighter, or appear scleroderma-like (hardened)
• Hypertrichosis: Excessive hair growth, particularly on the extremities, face, or trunk
• Hemangiomas: Small, cherry-red spots or bumps on the skin caused by clusters of blood vessels
• White nails: Leukonychia or whitening of the nail beds
• Acrocyanosis: Bluish discoloration of the fingers, toes, or other extremities due to reduced blood flow
• Flushing: Episodes of skin redness, particularly on the face and neck

These skin changes may develop gradually and can significantly affect a patient’s appearance and self-esteem. They are important diagnostic clues that help differentiate POEMS syndrome from other conditions.

6. Fluid Retention and Swelling (Edema)

Excessive fluid accumulation is a frequent and often debilitating symptom of POEMS syndrome. This occurs due to increased vascular permeability caused by elevated VEGF levels and other factors.

Fluid retention can manifest as:

• Peripheral edema: Swelling of the legs, ankles, and feet that may worsen throughout the day and improve with leg elevation. The swelling may leave an indentation when pressed (pitting edema)
• Ascites: Accumulation of fluid in the abdominal cavity, causing abdominal distension, discomfort, and bloating
• Pleural effusion: Fluid buildup around the lungs, which can cause shortness of breath, chest discomfort, and reduced exercise tolerance
• Pericardial effusion: Fluid accumulation around the heart, potentially affecting heart function and causing chest pain or palpitations
• Facial swelling: Puffiness around the eyes or face, particularly noticeable in the morning

The edema can be severe enough to cause significant weight gain and physical limitation. It may also contribute to skin breakdown and increase the risk of infections.

7. Systemic Symptoms and Fatigue

Beyond the specific organ-related symptoms, POEMS syndrome often causes a range of systemic symptoms that affect overall well-being and quality of life.

These general symptoms include:

• Chronic fatigue: Persistent, overwhelming tiredness that doesn’t improve with rest and interferes with daily activities. This is often one of the most disabling symptoms
• Weakness: Generalized muscle weakness beyond that caused by polyneuropathy alone
• Exercise intolerance: Reduced ability to perform physical activities due to weakness, shortness of breath, or rapid fatigue
• Weight loss or gain: Unintentional changes in body weight due to metabolic changes, edema, or hormonal imbalances
• Fever and night sweats: Low-grade fevers or episodes of sweating, particularly at night
• Clubbing: Enlargement and rounding of the fingertips and nails
• Papilledema: Swelling of the optic disc in the eye, which can cause vision changes or headaches
• Respiratory symptoms: Shortness of breath, particularly with exertion, due to pleural effusion or other factors

These systemic symptoms often develop insidiously and may be attributed to other causes initially, contributing to delays in diagnosis.

What Causes POEMS Syndrome?

The exact cause of POEMS syndrome remains not fully understood, but researchers have identified several key factors involved in its development:

Plasma Cell Disorder: The underlying problem in POEMS syndrome is the abnormal proliferation of plasma cells (a type of white blood cell). These cells produce abnormal monoclonal proteins that circulate in the bloodstream and contribute to organ damage.

Elevated Vascular Endothelial Growth Factor (VEGF): Patients with POEMS syndrome have markedly elevated levels of VEGF in their blood. This protein increases blood vessel permeability and stimulates the formation of new blood vessels, contributing to fluid retention, organ enlargement, and many other symptoms.

Inflammatory Cytokines: The abnormal plasma cells produce various inflammatory proteins and cytokines, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α). These contribute to the inflammatory state and multi-organ dysfunction seen in the syndrome.

Unclear Triggers: What triggers the initial plasma cell abnormality is unknown. POEMS syndrome is not inherited and does not appear to have a strong genetic component. There are no known environmental, infectious, or lifestyle factors that have been definitively linked to its development.

Rare Occurrence: POEMS syndrome is extremely rare, affecting fewer than 1 in 100,000 people. It typically occurs in middle-aged adults, with a slight male predominance, and has been reported more frequently in Asian populations, particularly in Japan.

Frequently Asked Questions

How is POEMS syndrome diagnosed?

Diagnosis requires meeting specific criteria including mandatory features (polyneuropathy and monoclonal plasma cell disorder) plus at least one major criterion (sclerotic bone lesions, elevated VEGF, or Castleman disease) and one minor criterion (organomegaly, fluid overload, endocrinopathy, skin changes, papilledema, or thrombocytosis). Blood tests, imaging studies, nerve conduction studies, and bone marrow biopsy are typically needed for confirmation.

Is POEMS syndrome cancer?

POEMS syndrome is not cancer in the traditional sense, but it involves a plasma cell disorder similar to multiple myeloma. The plasma cells multiply abnormally but typically grow more slowly than cancer cells. However, because it involves abnormal cell proliferation and requires similar treatment approaches, it is classified as a plasma cell dyscrasia.

How quickly do POEMS syndrome symptoms progress?

The progression of POEMS syndrome varies among individuals. Most patients experience a gradual onset of symptoms over months to years. Without treatment, symptoms typically worsen progressively. However, the rate of progression can vary, with some patients experiencing more rapid deterioration than others. Early diagnosis and treatment can significantly slow or halt progression.

Can POEMS syndrome symptoms be reversed?

Many symptoms of POEMS syndrome can improve significantly with appropriate medical management. Nerve damage may partially recover, fluid retention often resolves, and organ enlargement typically decreases. However, complete reversal of all symptoms is uncommon, and some degree of residual neuropathy often persists even after successful intervention.

What is the life expectancy with POEMS syndrome?

With modern treatment approaches, the prognosis for POEMS syndrome has improved considerably. Many patients achieve long-term remission and have a life expectancy approaching that of the general population. Without treatment, the condition can be life-threatening. The outcome depends on several factors including the extent of organ involvement, response to treatment, and whether complications develop.

Should I see a doctor if I have some of these symptoms?

Yes, if you experience multiple symptoms described in this article, particularly the combination of progressive numbness and weakness in your limbs along with unexplained swelling or skin changes, you should consult a healthcare provider. Because POEMS syndrome is rare and complex, you may need referral to specialists such as neurologists or hematologists for proper evaluation and diagnosis.

Are there similar conditions that mimic POEMS syndrome?

Yes, several conditions can mimic POEMS syndrome, including chronic inflammatory demyelinating polyneuropathy (CIDP), multiple myeloma, amyloidosis, Castleman disease, and various forms of vasculitis. This is one reason why diagnosis can be challenging and requires careful evaluation of multiple symptoms and test results to distinguish POEMS syndrome from these other conditions.

References:

• Mayo Clinic – POEMS Syndrome
• National Center for Biotechnology Information – POEMS Syndrome
• National Organization for Rare Disorders – POEMS Syndrome
• Johns Hopkins Medicine – POEMS Syndrome
• National Cancer Institute – POEMS Syndrome