POEMS Syndrome

Authored by Dr Colin Tidy, 11 Mar 2016

Reviewed by:
Dr John Cox, 11 Mar 2016

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Synonyms: osteosclerotic myeloma, Crow-Fukase syndrome, Takatsuki syndrome

POEMS syndrome is defined as the presence of a peripheral neuropathy, a monoclonal plasma cell disorder, and other paraneoplastic features.[1] The acronym stands for:

  • Peripheral neuropathy: the main symptom.
  • Organomegaly.
  • Endocrinopathy.
  • M protein (or monoclonal gammopathy).
  • Skin changes.

Not all these features are required for diagnosis.

Other possible features not represented in the acronym are: sclerotic bone lesions, papilloedema, pleural effusion, oedema, ascites, thrombocytosis and Castleman's disease (giant lymph node hyperplasia).

Both major criteria and at least one minor criterion are required for diagnosis:[2]

Major criteria

  • Polyneuropathy.
  • Monoclonal plasma-proliferative disorder.

Minor criteria

  • Sclerotic bone lesions.
  • Castleman's disease.
  • Organomegaly (splenomegaly, hepatomegaly or lymphadenopathy).
  • Oedema (peripheral oedema, pleural effusion or ascites).
  • Endocrinopathy (adrenal, thyroid, pituitary, gonadal, parathyroid or pancreatic - but diabetes mellitus or hypothyroidism alone are insufficient, as they are common in the general population).
  • Skin changes (hyperpigmentation, hypertrichosis, plethora, haemangiomata, white nails).
  • Papilloedema.
  • POEMS syndrome is probably rare (of the order of hundreds of cases are reported) but may be under-diagnosed and the incidence is unknown.
  • Peak incidence is age 40-60.

The cause is unknown. Increased levels of cytokines, particularly vascular endothelial growth factor (VEGF), may play a role.

These are listed in order of the most common at diagnosis:

  • The defining symptom is a chronic peripheral neuropathy, with motor features predominating:
    • It starts in the feet with paraesthesia.
    • There is symmetrical and proximal spread.
    • Progression is usually gradual but can be rapid.
    • Respiratory muscles may be affected.
    • Some patients also have pain.
  • Osteosclerotic lesions:
    • Occur in 95% of patients.
    • May be solitary or multiple; there may be mixed sclerotic and lytic lesions.
  • Skin changes:
    • Hyperpigmentation and hypertrichosis are common; coarse black hair may occur on the extremities.
    • Other skin changes are: thickening, haemangiomata, plethora, clubbing, white nails.
  • Endocrinopathy:[5]
    • Most commonly, hypogonadism.
    • Diabetes and hypothyroidism are also common.
    • Adrenal insufficiency and hypocalcaemia can occur.
    • There may be multiple endocrine axes affected.
  • Thrombocytosis.
  • Organomegaly - may be:
    • Hepatomegaly.
    • Splenomegaly.
    • Lymphadenopathy.
    • Castleman's disease.
  • Papilloedema:
    • Affects up to half of patients.
    • May be asymptomatic, or may cause headache and visual symptoms.
  • Extravascular volume overload - pitting oedema, ascites or pleural effusions.
  • Uncommon features or complications are:
    • Respiratory - pulmonary hypertension, restrictive lung disease.
    • Thrombosis - arterial or venous.
    • Renal impairment (rare).
    • Congestive cardiac failure.
    • A capillary leak-like syndrome.

Blood tests

  • Serum proteins investigations:[1]
    • By definition, all patients have a monoclonal plasma-proliferative disorder.
    • The monoclonal protein is typically small; it may be missed on electrophoresis unless immunofixation is done on both serum and 24-hour urine.
  • VEGF levels are nearly always raised in patients with active POEMS syndrome. Other cytokine levels may be raised.
  • FBC: there may be thrombocytosis with or without polycythaemia.
  • Liver function and renal function.
  • A full endocrine assessment is advised if POEMS is strongly suspected.[5]

Radiology

  • Skeletal survey may show sclerotic or lytic bone lesions.
  • CXR if there are cardiovascular/respiratory symptoms.

Other tests

  • Nerve conduction studies and electromyography.
  • ECG, echocardiogram and lung function tests for cardiorespiratory symptoms.

Biopsy

  • Biopsy of bone marrow or an osteosclerotic lesion - may show marrow monoclonal plasma cells.
  • Lymph node biopsy - if lymphadenopathy; may demonstrate Castleman's disease.
  • Nerve biopsies - usually reveal evidence of axonal degeneration and demyelination.
  • Chronic inflammatory demyelinating polyneuropathy.
  • Monoclonal gammopathy of undetermined significance with associated peripheral neuropathy.
  • Multiple myeloma - may have polyneuropathy and, rarely, can present with diffuse osteosclerotic bone lesions.[6]
  • Solitary plasmacytoma of bone - may have a small amount of monoclonal protein in serum or urine.
  • Waldenström's macroglobulinaemia.
  • The interconnections between POEMS syndrome, osteosclerotic myeloma and Castleman's disease are still under investigation.
  • Possible associations include pulmonary hypertension, restrictive lung disease, thrombotic diatheses, arthralgias, cardiomyopathy and low vitamin B12.
  • There is currently insufficient evidence regarding the treatment options for POEMS syndrome on which to base practice.[7]
  • Supportive care as required for neurological and respiratory problems - eg, physiotherapy, occupational therapy, respiratory support or multidisciplinary care.
  • Radiotherapy - if the osteosclerotic lesions are single or restricted to a limited area.[8]
  • If osteosclerotic lesions are widespread - chemotherapy or autologous stem cell transplantation.[9]Possible treatments include:
    • Melphalan and prednisolone.
    • Cyclophosphamide ± prednisolone.
    • High-dose chemotherapy with stem cell transplantation.
    • Lenalidomide - has been used with some success.[10]
    • Thalidomide and bortezomib - may be effective but risk exacerbating peripheral neuropathy. The benefit of anti-VEGF antibodies is conflicting.[8]

The median survival of patients with POEMS syndrome is about 14 years.[2]Prompt recognition and institution of supportive care measures and therapy directed against the plasma cell result in the best outcomes.[10]

Further reading and references

  1. Dispenzieri A; POEMS Syndrome. Hematology Am Soc Hematol Educ Program. 2005:360-7.

  2. Dispenzieri A, Kyle RA, Lacy MQ, et al; POEMS syndrome: definitions and long-term outcome. Blood. 2003 Apr 1101(7):2496-506. Epub 2002 Nov 27.

  3. Mullen EC; Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Oncol Nurs Forum. 2008 Sep35(5):763-7.

  4. Dispenzieri A, Buadi FK; A review of POEMS syndrome. Oncology (Williston Park). 2013 Dec27(12):1242-50.

  5. Gandhi GY, Basu R, Dispenzieri A, et al; Endocrinopathy in POEMS syndrome: the Mayo Clinic experience. Mayo Clin Proc. 2007 Jul82(7):836-42.

  6. Delgado Flores G, Robles Cartagena A, Robles Cartagena I, et al; POEMS Syndrome: A Rare Disease With A Challenging Diagnosis. Bol Asoc Med P R. 2015 Jul-Sep107(3):85-8.

  7. Kuwabara S, Dispenzieri A, Arimura K, et al; Treatment for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. Cochrane Database Syst Rev. 2012 Jun 136:CD006828.

  8. Dispenzieri A; POEMS syndrome: update on diagnosis, risk-stratification, and management. Am J Hematol. 2015 Oct90(10):951-62. doi: 10.1002/ajh.24171. Epub 2015 Sep 1.

  9. Arana C, Perez de Leon JA, Gomez-Moreno G, et al; POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) treated with autologous hematopoietic stem cell transplantation: a case report and literature review. Am J Case Rep. 2015 Mar 116:124-9. doi: 10.12659/AJCR.892837.

  10. Dispenzieri A; POEMS syndrome: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol. 2014 Feb89(2):214-23. doi: 10.1002/ajh.23644.

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