POEMS syndrome is a rare condition related to a plasma cell dyscrasia, which frequently follows an indolent course. However, a minority of patients present with rapidly progressive disease, often dominated by the polyneuropathy, as illustrated in this case. POEMS is characterised by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes, and presents at an earlier age than multiple myeloma. Clinical features are protean, but patients frequently exhibit papilloedema, volume overload, sclerotic bone lesions () and thrombocytosis.
Approximately 50% of patients may present with thrombocytosis.1
Not infrequently this is mistaken for a myeloproliferative disorder, in the context of characteristic bone marrow findings, namely an increase in megakaryocytes (). Equally, ischaemic complications are well-recognised, with one series reporting 18 of 99 patients suffering from arterial events such as stroke, myocardial infarction and Budd Chiari Syndrome.2
Another study reported 20% of patients suffering with arterial occlusion,3
while an individual suffering with recurrent ischaemic strokes, in the absence of risk factors and despite anticoagulation, has also been reported.4
Bone marrow trephine showing increased megakaryocytes.
The pathogenesis of POEMS is poorly understood but cytokines are believed to play an important role.5
VEGF in particular is often elevated at diagnosis and frequently normalises following successful treatment.6,7
VEGF is known to increase vascular permeability and plays an important role in angiogenesis. It has been postulated that VEGF is secreted from plasmacytomas,8
possibly resulting in arterial obliteration. Indeed, VEGF is released from aggregated platelets in patients with POEMS9
and descriptions of closed lumina of endoneurial blood vessels raise the possibility of microthrombosis contributing to the polyneuropathy.6
Currently treatment options include radiotherapy to solitary plasmacytomas, which has been shown to be effective in approximately 50% of patients.2
Approximately 40% of patients will respond to alkylator treatment in combination with corticosteroids, while 15% may gain some benefit from corticostertoids alone.2
However, observational data strongly suggest that peripheral blood ASCT is the definitive treatment, with up to 87% of patients objectively reporting neurological improvement at 10.8 months in one study.2
Other authors cite continued improvement in neurological symptoms beyond 6 months following treatment.10
ASCT enables high-dose melphalan to be administered, followed by stem cell rescue, while allogeneic stem cell transplantation has not been reported in POEMS syndrome due to unacceptable transplant related mortality. An earlier report suggests the procedure related mortality of ASCT in POEMS patients is similar to those with multiple myeloma11
but more recently it has been recognised that there may be considerable peritransplant morbidity.12
Most notably, approximately 50% of patients are reported to experience engraftment syndrome, which manifests as fever, rash, diarrhoea, non-cardiogenic pulmonary oedema and weight gain within 96 h of neutrophil engraftment. It has been postulated that the clinical sequelae of engraftment syndrome are secondary to a cytokine burst with splenomegaly best predicting a complicated peritransplant course.12
It has been suggested that earlier and more aggressive use of corticosteroids may modulate this effect.12
Few patients have reported to have disease relapse following ASCT, with the exception of one individual we treated who developed marrow dysplasia 5 years following a reduced dose melphalan autologous stem cell transplant (110 mg/m2
) and another individual who had a recurrence of sclerotic bony lesions some 7 years following transplantation.13
- POEMS syndrome is a rare haematological condition that can present with a myriad of clinical features.
- Increasingly cytokine levels, particularly vascular endothelial growth factor, are being employed to monitor the disease activity.
- A proportion of patients develop fulminant POEMS syndrome, with the clinical picture often being dominated by a rapidly progressive peripheral neuropathy.
- Treatment options include radiotherapy, alkylator treatment and peripheral blood stem cell transplantation but need to be tailored to each individual’s disease.