POEMS syndrome

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).

• Vkin 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).

Diagnos¹

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

Major criteria

• Polyneuropati.

• 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.

Epidemiologi³

• 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.

Aetiology and pathogenesis¹⁴

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

Clinical features and complications¹

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.

  • Lymfadenopati.

  • 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.

Utredningar³

Blodprov

• 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.

Andra tester

• Nerve conduction studies and electromyography.

• ECG, echocardiogram and lung function tests for cardiorespiratory symptoms.

Biopsi

• 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.

Differentialdiagnos³

• Chronic inflammatory demyelinating polyneuropathy.

• Monoclonal gammopathy of undetermined significance with associated peripheral neuropathy.

• Multiple myelom - 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.

• Waldenströms makroglobulinemi.

Associerade sjukdomar²

• 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.

Ledning¹³

• 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.⁹Possible 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

Prognos

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