POEMS syndrome (also known as Crow-Fukase syndrome, Takatsuki disease, or PEP syndrome) is a rare medical syndrome named for its main clinically recognizable features: Polyneuropathy (peripheral nerve damage), Organomegaly (abnormal enlargement of organs), Endocrinopathy (damage to hormone-producing glands)/Edema, M-protein (an abnormal antibody) and Skin abnormalities (including hyperpigmentation and hypertrichosis).

Signs and symptoms

All patients have polyneuropathy, which usually manifests itself with abnormal and reduced sensation and decreased power in the legs and arms. The condition may be painful and requiring analgesia.

Diagnosis

A 2003 study followed a series of 99 patients and attempted to delineate criteria for the diagnosis of POEMS syndrome. According to their study, both two major criteria and at least one minor criterion are required for the diagnosis:

• Major criteria:
• Polyneuropathy
• Monoclonal plasmaproliferative disorder (a paraprotein of any level)
• Minor criteria:
• Sclerotic bone lesions
• Castleman disease
• Organomegaly (splenomegaly, hepatomegaly or lymphadenopathy)
• Edema (edema, pleural effusion or ascites)
• Endocrinopathy (hormane gland problems involving the adrenals, thyroid, pituitary, gonads, parathyroids, or pancreas)
• Skin changes (hyperpigmentation, hypertrichosis, plethora, hemangiomata, white nails)
• Papilledema

In addition, their study showed a number of associations, the relevance of which to diagnosis was unclear: clubbing, weight loss, thrombocytosis, polycythemia and hyperhidrosis. Possible associations included pulmonary hypertension, restrictive lung disease, a thrombotic diathesis, arthralgia, cardiomyopathy (systolic dysfunction), fever, low vitamin B12 levels and diarrhea.

Pathogenesis

While the main features of the disease have been described, the exact mechanism of the disease has remained elusive. The paraprotein alone is insufficient to explain the multi-organ features, and various cytokines produced by plasmacytoma cells have therefore been linked with the features of POEMS syndrome, specifically interleukin 1β, interleukin 6 and TNFα. There also seems to be a role of vascular endothelial growth factor (VEGF), given the angiogenetic changes in many tissues.

Treatment

Dispenzieri et al list numerous treatments, the effect of many of which is almost anecdotal. Prednisolone and alkylating agents are the most commonly used. The Mayo Clinic group attempted hematopoietic stem cell transplantation in sixteen patients; one patient died during the treatment, and in several others respiratory problems were unmasked in the course of the procedure. The outcome of the treatment, though, was good.

Given that VEGF plays a central role in the symptoms of POEMS syndrome, some have tried bevacizumab (Avastin), a monoclonal antibody directed against VEGF. While some reports were positive, others have reported capillary leak syndrome suspected to be the result of overly rapid lowering of VEGF levels. It therefore remains doubtful as to whether this will become part of standard treatment for POEMS syndrome.

History

Crow, working in Bristol, first described the combination of osteosclerotic myeloma, polyneuropathy and various unusual features (such as pigmentation and clubbing) in two patients aged 54 and 67. The name POEMS syndrome, now the most prevalent, was coined in 1980 by Bardwick et al.

References

External links

• WUSTL neuropathy page
• POEMS syndrome