POEMS Syndrome

Variant form of multiple myeloma (malignant proliferation of plasma cell in bone marrow causing skeletal destruction leading to bone pain and pathological fractures). The underlying pathology is usually an osteosclerotic myeloma. The acronym stands for:

• P - polyneuropathy: slow onset of mixed motor and sensory polyneuropathy; peripheral nerve demyelination with some axonal degeneration
• O - organomegaly: hepatosplenomegaly
• E - endocrinopathy: gynaecomastia, secondary amenorrhoea, diabetes mellitus, hypothyroidism
• M - monoclonal protein
• S - skin changes: hyperpigmentation, hypertrichosis, skin thickening

Not represented in the acronym are several important features, including sclerotic bone lesions, Castleman disease (giant angiofollicular hyperplasia, multicentric plasma cell variant), papilloedema, pleural effusion, oedema, ascites, and thrombocytosis¹.

Two major criteria and at least 1 minor criterion are required for diagnosis¹:

• Major criteria
  • Polyneuropathy
  • Monoclonal plasmaproliferative disorder
• Minor criteria
  • Sclerotic bone lesions
  • Castleman disease
  • Organomegaly (splenomegaly, hepatomegaly, or lymphadenopathy)
  • Oedema (peripheral oedema, pleural effusion, or ascites)
  • Endocrinopathy (adrenal, thyroid, pituitary, gonadal, parathyroid, pancreatic)
  • Skin changes (hyperpigmentation, hypertrichosis, plethora, haemangiomata, white nails)
  • Papilloedema

POEMS syndrome is rare. Several hundred cases have been described in the literature; however, the true incidence may be higher because the syndrome may go unrecognized.

• Characteristic feature is a chronic inflammatory demyelinating neuropathy causing mainly motor disability.
• Hepatomegaly is found in approximately half of patients.
• Hyperpigmentation and hypertrichosis are common.
• Clubbing, fever, diarrhoea and weight loss may also occur.
• May be angiomatous lesions of trunk.
• Gynaecomastia and atrophic testes.

• Full blood count: thrombocytosis with or without polycythaemia.
• Serum protein immunoelectrophoresis: is used to define the nature and the extent of the monoclonal gammopathy. The M protein is IgG-gamma or IgA-gamma and small in size (median, 1.1 g/dL).
• TSH, fasting blood glucose, a glucose tolerance test, and oestrogen levels to screen for endocrinopathy.
• Plain x-rays: useful for locating lytic bone lesions caused by osteosclerotic myeloma. X-ray surveys often reveal a single osteosclerotic lesion in the spine or proximal long bones. At least 95% of patients have osteosclerotic lesions, with more than half the patients having multiple lesions. Both osteosclerotic and osteolytic lesions may be present and may be of modest size.
• Bone marrow biopsy: may show marrow involvement with plasma cells.
• Lymph node biopsy: if lymphadenopathy; demonstrates findings of Castleman disease.
• Electromyelogram: findings consistent with polyneuropathy, prominent demyelination, and features of axonal degeneration.
• Nerve biopsies: usually reveal evidence of axonal degeneration and demyelination.

• The interconnections between POEMS syndrome, osteosclerotic myeloma, and Castleman disease are still under investigation¹.
• Possible associations include pulmonary hypertension, restrictive lung disease, thrombotic diatheses, arthralgias, cardiomyopathy (systolic dysfunction) and low vitamin B12¹.

• If osteosclerotic lesions are restricted to a limited area: radiotherapy.
• If osteosclerotic lesions are widespread: chemotherapy or autologous stem cell transplantation².
• Clinical responses to prednisone and a combination of melphalan and prednisone occur in approximately 22% to 56% of patients¹.
• Surgical excision of isolated plasmacytomas may result in complete resolution of the syndrome.

• Pulmonary hypertension
• Renal failure
• Thrombotic events
• Congestive heart failure¹.

• Median survival of patients with POEMS syndrome is about 14 years¹.
• The prognosis depends on the extent of the underlying plasma cell disorder and its response to treatment:
  • The prognosis is best for patients with a single lytic lesion and worst for patients with a plasma cell disorder involving the bone marrow.
  • Patients with multiple lytic bone lesions have an intermediate prognosis.
  • When the plasma cell disorder responds to treatment, all other symptoms usually improve or resolve completely.