<unk>  is a rare medical<unk>  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). In 1938, Ilya Mark Scheinker, a Russian neurologist and neuropathologist described a patient with a solitary plasmacytoma, sensorimotor polyneuropathy, and localized patches of thickened and deeply pigmented skin. In 1956, R. S. Crow published two case reports of myelomatosis with peripheral neuritis and other striking features. In 1977, Iwashita et al described a patient who had an osteosclerotic myeloma accompanied by sensorimotor polyneuropathy, skinhyperipigmentation, edema, hypertrichosis, gynecomastia, and white nails. In 1980, Bardwick et al proposed the acronym<unk> ' to represent a<unk>  characterized by polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes.<unk>  is a para-neoplastic<unk>  characterized by multi-organ system dysfunction, monoclonal plasma cell proliferation and demyelinating inflammatory polyneuropathy. The lambda component of immunoglobulin light chains is thought to be overproduced in<unk>  secondary to monoclonal plasma cell proliferation. Bone marrow studies of patients suffering from<unk>  shows lymphoid aggregates rimmed by monotypic or polytypic plasma cells. The monoclonal gammopathy or overproduction of lambda light chain stimulates the monocyte/macrophage system to produce various proinflammatory cytokines. such as interleukin-1, interleukin-6, interleukin-12, vascular endothelial growth factor (VEGF) and TNF-Alpha. Transforming growth factor beta (TGF-beta), an inhbitory cytokine is thought to be underproduced in patients suffering from<unk>  leading to a storm of proinflammatory cytokines which drive the disease process. The overproduction of this IL-6 may be related to some of the clinical features seen in<unk>  such as gammopathy, elevated C-Reactive protein (CRP) and thrombocytosis. The mesangial proliferation and membranoproliferative glomerulonephritis (MPGN) seen in<unk>  is thought to be secondary to increased production of platelet-derived growth factor(PDGF) and fibroblast growth factor beta (FGF-β) have been implicated in mesangial cell proliferation. The neovascularization induced by VEGF leads to increased vascular permeability. Since the increased production of VEGF is unchecked due to the plasma cell dyscrasia, the consequence is an unregulated extravasation of intravascular fluid into the extravascular compartment. resulting in edema.<unk>  is known to be associated multiple myeloma (osteosclerotic type), Castleman's disease, plasmacytoma, monoclonal gammopathy of undetermined significance (MGUS), pulmonary hypertension, restrictive lung disease, thrombophilia, cardiac amyloidosis and papilledema. There are no known and well established causes of<unk> . Marked activation of the pro-inflammatory cytokines and weak or decreased TGF beta 1 action can play a role in the disease pathogenesis. The precise incidence of<unk>  is difficult to determine and we have no well established data to quote. The median age at presentation has been 51 years with the majority of the patients comprising of males. A mediansurvival of 165 months has also been recorded. The precise incidence of<unk>  is difficult to determine due to the complexity of the<unk>  presentation and we have no well established data regarding the incidence. Prevalence of<unk>  in Japan is reported to be about 0.3/100,000. There is no racial predilection to<unk> . There is no well established data regarding the gender predilection of<unk> . Data from Japan shows a male predilection of 2.5:1. The majority of<unk>  cases have been reported in Japan and China. According to the The International Myeloma Working Group, the diagnosis of<unk>  may be established if both mandatory criteria, one major and one minor criteria are fulfilled. Mandatory criteria include presence of polyneuropathy and a monoclonal plasma cell proliferative disorder. Major criteria include presence of sclerotic bone lesions or mixed sclerotic/lytic lesions, presence of Castleman's disease and elevated serum VEGF levels. Minor criteria include presence of organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema, thrombocytosis and polycythemia. Patients suffering from<unk>  may have variable presentation and can present a diagnostic challenge for the clinician due to non-specific symptomology. Common symptoms of<unk>  include numbness, tingling and weakness affecting extremities, fatigue, generalized pain in the body, foot drop, blurred vision, peripheral edema, dyspnea and hyperpigmentation. Less common symptoms include muscle weakness, diplopia, ocular pain and ascites. Laboratory findings consistent with the diagnosis of<unk>  include increased serum VEGF level, increased number of thrombocytes, increased number of erythrocytes, elevated cerebrospinal fluid (CSF) protein content, increased number of leukocytes, low levels of IgG lambda or IgA lambda M-protein in the serum, and increased number of plasma cells in the bone marrow. An x-ray may be helpful in the diagnosis of<unk> . Findings on an x-ray suggestive of<unk>  include osteolytic bone lesions, pleural effusion, increased cardiac silhouette (secondary to pericardial effusion), and ascites. CT scan may be helpful in the diagnosis of<unk> . Findings on CT scan suggestive of<unk>  include bone lesions, lymphadenopathy, hepatomegaly, splenomegaly, pleural effusion, pericardial effusion, and ascites. MRI may be helpful in the diagnosis of<unk> . Findings on MRI suggestive of<unk>  include diffuse lumbosacral nerve root enhancement, bone lesions. Echocardiography/ultrasound may be helpful in the diagnosis of<unk> . Findings on echocardiography/ultrasound suggestive of<unk>  include pericardial effusion, left ventricular hypertrophy with moderately impaired systolic function, pulmonary hypertension, seroperitoneum, and hepatosplenomegaly. CT scan may be helpful in the diagnosis of<unk> . Findings on CT scan suggestive of<unk>  include bone lesions, lymphadenopathy, hepatomegaly, splenomegaly, pleural effusion, pericardial effusion, and ascites. MRI may be helpful in the diagnosis of<unk> . Findings on MRI suggestive of<unk>  include diffuse lumbo-sacral nerve root enhancement and bone lesions. (18)F-FDG PET/CT is an adequate tool for evaluation, diagnosis, and monitoring of the pathology. (18)F-FDG PET/CT may be helpful in the diagnosis of<unk> . Findings suggestive of<unk>  include mixed bone lesions, lymphadenopathy, hepatosplenomegaly, and serous cavity effusions. Fluorescein angiography may reveal unilateral pooling of fluid consistent with cystoid macular edema. Optical coherence tomography (OCT) may show loss of retinal nerve fiber layer thickness. Other diagnostic studies that can help in making the diagnosis of<unk>  include nerve conduction study, electromyograpy, fundoscopy, serum plasma electrophoresis and immunofixation electrophoresis, visual field testing, and pulmonary function test. Patients with isolated bone lesion without bone marrow clonal plasma cells involvement can be treated with radiotherapy. Patients with a disseminated disease (more bone lesions and/or bone marrow plasmacytosis) are the candidates for systemic therapy. Systemic therapy includes corticosteroids, autologous stem cell transplantation (ASCT), induction therapy, alkylator-based therapy, thalidomide, lenalidomide, bortezomib, and bevacizumab. Surgical intervention is not recommended for the management of<unk> . There are no established measures for the primary prevention of<unk> . There are no established measures for the secondary prevention of<unk> .
POEMS syndrome
Monoclonal gammopathy of undetermined significance
Familial amyloidosis
Secondary amyloidosis
Multiple myeloma
Hamman-Rich syndrome
Waldenström's macroglobulinemia
Monoclonal gammopathy of undetermined significance surgery