What is POEMS syndrome?
POEMS syndrome is a rare multisystem disorder. POEMS stands for:
- Monoclonal gammopathy
- Skin changes
What causes POEMS syndrome?
The cause of POEMS syndrome is not well understood. It is associated with a chronic overproduction of pro-inflammatory cytokines (small molecules that act as messengers between cells to promote inflammation). These include IL-1b, IL6, TNFα and vascular endothelial growth factor (VEGF – a powerful vasodilator that may cause leaky blood vessels).
Who gets POEMS syndrome?
POEMS syndrome is rare, with only a few hundred cases described in the medical literature. However, it may be underreported due to being under-recognised. Many of thes cases are from Japan.
POEMS syndrome is 2.5 times more common in men than in women. It also presents at a younger age in men, most commonly in their 40s and 50s.
What are the clinical features of POEMS syndrome?
A common initial presentation of POEMS syndrome is with progressive weakness and swelling of the peripheries. Clinical manifestations vary depending on the organ systems involved.
Peripheral neuropathy (disorder of peripheral nerves) is often prominent, causing weakness in the feet and later in the arms. In more than half of patients, the weakness is severe, so that they are unable to climb stairs, get up from a seated position, or grip objects. Patients are often eventually confined to a wheelchair.
POEMS syndrome can also cause reduced sensation. Pinprick, vibration and sense of position (proprioception) are affected the most, whereas temperature and pain sensation usually stay normal.
Cranial and autonomic nerves are not affected in POEMS syndrome. However, vision may be affected because of papilloedema (swelling of the optic disc).
Organomegaly (enlargement of internal organs) is present in up to 50% patients and is generally mild. Most commonly affected organs are:
- Lymph nodes
Most patients with POEMS syndrome have endocrinopathy (disorder of endocrine glands), often with multiple abnormalities.
Hypogonadism is the most common abnormality. Low testosterone and elevated oestrogen levels have been reported, as have impotence and enlarged breasts (gynaecomastia) in men and amenorrhoea (absence of menstrual bleeding) in women.
Other reported endocrine abnormalities in POEMS syndrome include:
- Diabetes and glucose intolerance
The detection of monoclonal immunoglobulins (antibodies) confirm the presence of a monoclonal plasma cell proliferative disorder. Investigations may include serum immunoglobulins and electrophoresis, urinary Bence-Jones proteins, bone or bone marrow biopsy.
Darkened skin colour (hyperpigmentation) has been seen in about 50–90% patients with POEMS syndrome. This is most commonly diffuse but can be localised. It most frequently affects the extensor surfaces, neck, axilla and back. There is an increase in melanin production without an increase in the number of melanocytes, a process similar to that seen in Addison disease.
Scleroderma-like skin thickening and tightening has been reported in 25–80% of patients.
Hypertrichosis (excessive hair growth) has been noted in around 25–80% of patients, most often resulting in coarse black hair over face, limbs and chest.
Other skin problems may include:
- Localised hyperhidrosis (excessive sweating)
- Eruptive glomeruloid haemangiomas on the trunk and distal limbs
- Terry nails: white proximal and red distal nail
- Nail clubbing
- Raynaud phenomenon
- Facial lipotrophy (loss of fat)
- Calciphylaxis (necrosis of skin and fatty tissue associated with abnormal calcium deposition).
POEMS syndrome is not usually associated with mucous membrane involvement.
Other symptoms and signs
POEMS syndrome may also cause:
- Weight loss and fatigue
- Extravascular fluid overload with ascites, peripheral oedema and pleural effusion (accumulation of fluid in the abdominal cavity, limbs and lung lining respectively)
- Arterial and venous thromboses (blood clots)
- Pulmonary disease:
- Restrictive lung disease
- Pulmonary hypertension
- Respiratory muscle weakness.
What is the differential diagnosis of POEMS syndrome?
When a monoclonal gammopathy is found, other diagnoses that should be considered include:
- Multiple myeloma
- Solitary plasmacytoma of bone
- Monoclonal gammopathy of undetermined significance (MGUS)
- Waldenstrom macroglobulinaemia
- Primary amyloidosis
How is POEMS syndrome diagnosed?
The diagnosis of POEMS syndrome should be considered in patients with peripheral neuropathy of unknown cause plus a plasma cell disorder. The Mayo Clinic diagnostic criteria for POEMS syndrome consists of 5 major criteria, and 6 minor criteria. To diagnose POEMS, you need:
- Both mandatory major criteria,
- At least 1 of the other major criteria,
- AND at least 1 of the minor criteria.
|Mandatory major criteria||Major criteria||Minor criteria|
*Due to the common nature of diabetes and hypothyroidism in the general population, these disorders are not sufficient to fulfil minor diagnostic criteria for POEMS.
Suggested investigations depend on the clinical picture and may include the following:
- Blood tests
- Full blood count: which may show thrombcytosis +/-polycythaemia
- Endocrine panels may show abnormalities including deranged thryotropin, glucose, and oestrogen
- Serum or urine electrophoresis to test for the monoclonal immunoglobulin
- X-ray of bones in almost all patients show osteosclerotic lesions, which are often multiple
- Biopsy of an enlarged lymph node may show Castleman disease
- Lumbar puncture in those with neuropathy may show increased protein in the cerebrospinal fluid
- Nerve conduction studies may show changes of demyelination and axonal degeneration
- Bone marrow examination may show involvement with plasma cells
- Lymph node biopsy of enlarged nodes
- Skin biopsy results are usually nonspecific
- Scleroderma-like lesions show nonspecific hyperpigmentation of the basal layer with inflammatory infiltrate or dermal fibrosis. Sweat glands and collagen are normal, which differentiates it from scleroderma.
- Hyperpigmented lesions show nonspecific inflammatory infiltrate of lymphocytes and plasma cells
- Angiomas include strawberry naevus, lobular capillary angioma, and in around 3%, glomeruloid haemangioma (this is especially characteristic of POEMS syndrome and shows enlarged vascular spaces filled with coiled capillaries surrounded by pericytes, which look like kidney glomerulus).
What is the prognosis of POEMS syndrome?
POEMS syndrome is a chronic disease. The median survival is around a decade (8-14 years), which is 3 times longer than patients with multiple myeloma. However, many patients are bedridden due to neuropathy (50%).
Shorter survival is associated with nail clubbing and extravascular fluid overload. The most common causes of death are:
- Cardio-respiratory failure
- Renal failure
- Progressive exhaustion, due to lack of nutrition
- Thrombosis (blood clots)
Treatment and management of POEMS syndrome
As POEMS syndrome is rare, there are no standard treatments or randomised controlled trials to inform us which treatment is most effective. Management depends on treatment of the underlying plasma cell disorder and may include radiation therapy, chemotherapy or haematopoietic cell transplantation.
Around 75% of patients have some response to treatment, and VEGF levels (if available) can be used to follow response.