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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. The acronym stands for:
- P - peripheral neuropathy: the main symptom.
- O - organomegaly.
- E - endocrinopathy.
- M - M protein (or monoclonal gammopathy).
- S - 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:
- Major criteria:
- 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).
- POEMS 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.
Aetiology and pathogenesis
The cause is unknown. Increased levels of cytokines, particularly vascular endothelial growth factor (VEGF), may play a role.
Clinical features and complications
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.
- Most commonly, hypogonadism.
- Diabetes and hypothyroidism are also common.
- Adrenal insufficiency and hypocalcaemia can occur.
- There may be multiple endocrine axes affected.
- Organomegaly - may be:
- Castleman's disease.
- 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.
- Serum proteins investigations:
- 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.
- Vascular endothelial growth factor (VEGF) levels are nearly always raised in patients with active POEMS. 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.
- Skeletal survey may show sclerotic or lytic bone lesions.
- CXR if there are cardiovascular/respiratory symptoms.
- Nerve conduction studies and electromyography.
- ECG, echocardiogram and lung function tests for cardiorespiratory symptoms.
- 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.
- 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.
- 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.
- If osteosclerotic lesions are widespread - chemotherapy or autologous stem cell transplantation. Possible treatments (from small series and case reports) are:
- Melphalan and prednisolone.
- Cyclophosphamide ± prednisolone.
- Corticosteroids alone, which may help stabilise the disease.
- High-dose chemotherapy with stem cell transplantation - although this carries significant risks.
- Lenalidomide or thalidomide. There are concerns that thalidomide also causes peripheral neuropathy and fluid retention. Lenalidomide, which was helpful in one reported case.
- Bevacizumab therapy, which has been reported as beneficial in some cases but fatal in another.
- The median survival is eight years.
- Death is often caused by heart failure, respiratory failure, renal failure or infection.
- Approximately 50% of patients with POEMS syndrome become bedridden.
Further reading & references
- Dispenzieri A; POEMS Syndrome. Hematology Am Soc Hematol Educ Program. 2005:360-7.
- Dispenzieri A, Kyle RA, Lacy MQ, et al; POEMS syndrome: definitions and long-term outcome.; Blood. 2003 Apr 1;101(7):2496-506. Epub 2002 Nov 27.
- Mullen EC; Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Oncol Nurs Forum. 2008 Sep;35(5):763-7.
- Gandhi GY, Basu R, Dispenzieri A, et al; Endocrinopathy in POEMS syndrome: the Mayo Clinic experience. Mayo Clin Proc. 2007 Jul;82(7):836-42.
- 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 13;6:CD006828.
- Jaccard A, Royer B, Bordessoule D, et al; High-dose therapy and autologous blood stem cell transplantation in POEMS syndrome.; Blood. 2002 Apr 15;99(8):3057-9.
- Dispenzieri A, Moreno-Aspitia A, Suarez GA, et al; Peripheral blood stem cell transplantation in 16 patients with POEMS syndrome, and a review of the literature. Blood. 2004 Nov 15;104(10):3400-7. Epub 2004 Jul 27.
- Dispenzieri A, Klein CJ, Mauermann ML; Lenalidomide therapy in a patient with POEMS syndrome. Blood. 2007 Aug 1;110(3):1075-6.
- Dietrich PY, Duchosal MA; Bevacizumab therapy before autologous stem-cell transplantation for POEMS syndrome. Ann Oncol. 2008 Mar;19(3):595. Epub 2008 Jan 21.
- Badros A, Porter N, Zimrin A; Bevacizumab therapy for POEMS syndrome. Blood. 2005 Aug 1;106(3):1135.
- Straume O, Bergheim J, Ernst P; Bevacizumab therapy for POEMS syndrome. Blood. 2006 Jun 15;107(12):4972-3; author reply 4973-4.
- Chan JL et al, POEMS Syndrome, Medscape, Apr 2011
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
Dr Naomi Hartree
Dr Colin Tidy
Dr John Cox