Many of the signs and symptoms in POEMS syndrome are due at least in part to the release of an aberrant immunoglobulin, i.e. a myeloma protein, as well as certain cytokines by the malignant plasma cells.
These include a predisposition to forming blood clots, joint pain, cardiomyopathy (systolic dysfunction), fever, low vitamin B12 levels, and diarrhea.
[10] While the main features of this paraneoplastic disease have been described, the exact mechanism behind its development, progression, and manifestations remain elusive.
It is suggested that various other cytokines produced by the clonal plasma cells, perhaps working in concert with each other as well as with VEGF and the myeloma proteins, mediate many of the features of POEMS syndrome.
For example, VEGF, given its ability to stimulate blood vessel formation, would seem likely to be the major contributor to the pathologic hyper-vascularization changes seem in many tissues, such as lymph nodes, affected by POEMS syndrome.
[4] Subacute, distal, symmetrical sensorimotor neuropathy with allodynia and hyperpathia is the most frequent presentation of POEMS syndrome.
Atypical plasma cells invade normal marrow in osteosclerotic lesions, causing sclerosis of the bony lamellae.
[11] Castleman's disease (CD) is a rare heterogeneous lymph node disorder characterized by elevated interleukin-6 levels.
[5] VEGF levels in plasma and serum are significantly higher in POEMS patients and correlate with illness activity.
VEGF normally targets endothelial cells and causes an increase in vascular permeability that is both fast and reversible.
Hypogonadism is the most prevalent endocrine disorder, followed by thyroid anomalies, glucose metabolism defects, and adrenal insufficiency.
Other skin abnormalities include thickening, hypertrichosis, acquired facial lipoatrophy, and infiltrating livedo reticularis with necrosis.
POEMS syndrome can also cause Vascular-type skin changes including acrocyanosis, flushing, hyperaemia, and Raynaud's phenomenon.
[5] Patients tend to be asymptomatic, however, they may report headaches, brief obscurations of vision, scotomata, large blind spots, and gradual visual field constriction.
[5] In addition to tests corresponding to the above findings, such as EMG for neuropathy, CT scan, bone marrow biopsy to detect clonal plasma cells, plasma or serum protein electrophoresis to myeloma proteins, other tests can give abnormal results supporting the diagnosis of POEMS syndrome.
While the mechanism of action of these immunomodulators are not clear, they do inhibit the production of cytokines suspected of contributing to POEMS syndrome such as VEGF, TNFα, and IL-6 and stimulate T cells and NK cells to increase their production of interferon gamma and interleukin 2 (see immunomodulatory imide drug's mechanism of action).
[12] R. S. 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, in 1956.