Also known as Crow–Fukase syndrome, peculiar progressive polyneuritis syndrome or Takatsuki syndrome, POEMS syndrome is a rare multisystem syndrome associated with plasma cell dyscrasia that consists of the following features: polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. This syndrome was first discovered in 1938 following Scheinker's autopsy of a 39-year-old man with plasmacytoma, sensorimotor polyneuropathy and patches of skin hyperpigmentation.3
The term was later coined by Bardwick et al
Several hundred cases of POEMS syndrome have been reported, but the incidence is thought to be greater. Peak incidence occurs at age 50–60, and progressive peripheral neuropathy is the predominant feature.7
The 5-year survival rate is approximately 60%, which is greater than that of multiple myeloma.8
The number of POEMS features does not correlate with survival, however, and the presence of respiratory symptoms is associated with a poorer outcome.9
Within 2 years of diagnosis, approximately 25% of patients develop respiratory symptoms, including restrictive lung disease, impaired diffusion of carbon monoxide and pulmonary hypertension.9 10
The mechanism by which plasma cells cause POEMS syndrome is not fully understood, but it is thought to involve elevations in vascular endothelial growth factor (VEGF), interleukin 6 (IL6), tumour necrosis factor-α and IL1β.2
There is no definite diagnostic test for POEMS, although a raised vascular VEGF is usually confirmatory and correlates with disease activity.7
VEGF is present in platelets and megakaryocytes and is responsible for increasing vascular permeability and angiogenesis.11
However, other mechanisms may be involved as studies using bevacizumab, a monoclonal antibody directed against VEGF, have had variable results.11
As there are no criteria to define POEMS syndrome, diagnosis can be difficult. Most authors agree that the presence of two major and at least one minor criterion are confirmatory.9
The major criteria are monoclonal plasma cell proliferative disorder and chronic inflammatory demyelinating polyneuropathy.6 10
Minor criteria include sclerotic bone lesions, Castleman's disease, papilloedema, organomegaly, endocrinopathy peripheral oedema and ascites.7 9 12
Castleman's disease is characterised by giant and angiofollicular lymph node hyperplasia.7
Clinical features associated with POEMS include clubbing, weight loss, thrombocytosis and polycythaemia.9
The polyneuropathy typically spreads proximally and motor symptoms predominate.7
Skin changes include haemangiomata, skin thickening, hyperpigmentation, hypertrichosis, white nails and clubbing.13
As POEMS syndrome is a multisystem disorder, a thorough history and full systems examination is required. Aside from baseline blood tests, useful blood tests to identify endocrine anomalies include luteinising hormone, follicle stimulating hormone, prolactin, parathyroid hormone, thyroid function tests, testosterone, oestradiol, cortisol, VEGF and fasting blood glucose.10
Due to the high incidence of respiratory features in POEMS patients, pulmonary function tests should be performed.10
Serum electrophoresis is needed to detect the classical λ-restricted M protein.7
CT and MRI imaging help to differentiate the nature of bony lesions. Bony lesions associated with POEMS syndrome can appear sclerotic, lytic with a sclerotic edge or a have a mixed ‘soap bubble’ appearance.7
A full skeletal survey is required in order to ascertain whether the lesion is solitary.10
The lesion should be biopsied to determine the nature of the lesion as over 95% of patients with POEMS have a monoclonal λ plasmacytoma.7 10
Most patients have multiple endocrine abnormalities.7
Endocrinopathies commonly associated with POEMS include hypogonadism, hypothyroidism, diabetes mellitus, adrenal insufficiency, hyperprolactinaemia and hypoparathyroidism.9
Our patient had a history of erectile dysfunction, hyperprolactinaemia and testosterone deficiency. It is possible that the patient's erectile dysfunction was secondary to hyperprolactinaemia induced hypogonadism.
Treatment of the underlying plasmacytoma is the major therapeutic approach in POEMS. Radiotherapy is indicated if there is a solitary plasmacytoma, and chemotherapy if there are multiple lesions.10
Other treatment options include peripheral blood stem cell transplantation, glucocorticoids and low-dose alkylating agents.7
Autologous peripheral blood stem cell transplantation has been trialled in a small proportion of POEMS patients where it has improved the symptoms of neuropathy, skin changes and lung function tests and reduced VEGF levels.14
Interestingly, patients with lymphadenopathy and splenomegaly were more likely to have post-transplant complications.14
POEMS syndrome is a rare paraneoplastic disorder comprising peripheral neuropathy, organomegaly, endocrinopathy, M protein and skin changes. This is the first reported case of POEMS syndrome presenting with a pathological fracture. The patient had a hip replacement at a specialist orthopaedic hospital and is due to undergo radiotherapy to the femoral lesion.
- Pathological fractures in middle aged men are usually due to bony metastases.
- Taking a detailed medical history and performing a full systems examination make it easier to diagnose paraneoplastic syndromes.
- More research is needed into effective treatments in POEMS syndrome as current management relies on limited studies.