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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
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|Original Author: Dr Naomi Hartree||Current Version: Dr Colin Tidy||Peer Reviewer: Dr John Cox|
|Last Checked: 16/10/2012||Document ID: 1019 Version: 23||© EMIS|