The debate on twitter illustrates the multiple differentials that exist in this situation. Most people pointed out that amyloidosis could cause the symptoms and signs described in the case (hepatomegaly due to infiltration, cardiomyopathy causing peripheral oedema, nephrotic syndrome causing peripheral oedema, peripheral neuropathy due to paraprotein). However we thought we would go for a rarer condition still!
POEMs syndrome is a rare paraprotein disorder. Our patient has several typical features:
- He is the right age and gender – many contributors noted that he is significantly younger than the average MGUS or myeloma patient, which is true.
- He has now developed a number of symptoms and signs of POEMS syndrome:
- POLYNEUROPATHY – on closer questioning he admitted to paresthesia of his finger tips and toes. However examination also revealed distal limb weakness. Distal sensorimotor neuropathy is a cardinal feature of POEMS syndrome, but is similar to alcoholic neuropathy in many ways, confusing the picture in our patient.
- ORGANOMEGALY – Our patient had been noted to have a degree of clinical hepatomegaly, which his GP reasonably attributed to alcohol-induced hepatitis.
- ENDOCRINOPATHY – Gynaecomastia was noted, which can again be seen in both liver disease and POEMS syndrome. He did admit to impotence on further questioning.
- M PROTEIN – as already established, he has an IgG paraprotein, the other cardinal feature of POEMS syndrome.
- SKIN CHANGES – the patient complains of generalised oedema which may have a number of causes, including hypoalbuminaemia and cardiac failure.
Other features not seen in our case, but commonly seen in POEMS syndrome include:
- PULMONARY DISEASE particularly pulmonary hypertension.
- ENDOCRINE – in women amenorrhoea may develop; diabetes, hypothyroidism and adrenal insufficiency are also seen.
- SKIN CHANGES including hyperpigmentation and scleroderma-like appearance may be seen.
- CASTLEMANS DISEASE
- BONE LESIONS – sclerotic in nature
- POLYCYTHAEMIA and THROMBOCYTOSIS
- MYELOMA – co-exists in up to 50% of cases of POEMS.
The other important differential to consider in this case would be amyloidosis, which is also a multisystem paraprotein disorder capable of causing neuropathy, diarrhoea, cardiomyopathy, nephropathy, coagulopathy and organomegaly.
Amyloidosis and POEMS syndrome are both characterised by the presence of a paraprotein. However patients with POEMS syndrome also have elevated levels of serum VEGF, sclerotic bony lesions and characteristic bone marrow changes. The paraprotein in POEMS is usually modest and is almost invariably lambda (IgG or IgA). However there is no absolute diagnostic test – assessment of signs and symptoms is central to establishing the diagnosis.
Management of POEMS syndrome is broadly similar to myeloma and amyloidosis, with the use of a multi-chemotherapy regimen and consideration of autologous transplantation. The end-organ damage may take many months to respond even when biomarkers such as VEGF suggest a meaningful response to therapy. VEGF inhibitors such as Bevacizumab have been tried, but results are mixed. Please see references for further information on e.
Dao LN, Hanson CA, Dispenzieri A, Morice WG, Kurtin PJ, Hoyer JD. Bone marrow
histopathology in POEMS syndrome: a distinctive combination of plasma cell, lymphoid
and myeloid findings in 87 patients. Blood. 2011;117(24):6438-6444.