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Neurological Sciences : Official... Nov 2021Paraproteinemia is associated with different peripheral neuropathies. The major causes of neuropathy correlated with paraproteinemia are the deposition of immunoglobulin... (Review)
Review
Paraproteinemia is associated with different peripheral neuropathies. The major causes of neuropathy correlated with paraproteinemia are the deposition of immunoglobulin in the myelin, represented by anti-myelin-associated glycoprotein (MAG) neuropathy; deposition of immunoglobulin or its fragment in the interstitium, represented by immunoglobulin light chain amyloidosis (AL amyloidosis); and paraneoplastic mechanisms that cannot be solely attributed to the deposition of immunoglobulin or its fragment, represented by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin change (POEMS) syndrome. Patients with anti-MAG neuropathy and POEMS syndrome present with slowing of nerve conduction parameters. This characteristic fulfills the electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) defined by the European Academy of Neurology and Peripheral Nerve Society (EAN/PNS). Although direct damage caused by the deposition of amyloid can induce axonal damage in AL amyloidosis, some patients with this condition have features fulfilling the EAN/PNS electrodiagnostic criteria for CIDP. Conventional immunotherapies for CIDP, such as steroids, intravenous immunoglobulin, and plasma exchange, offer no or only minimal-to-modest benefit. Although rituximab can reduce the level of circulating autoantibodies, it may only be effective in some patients with anti-MAG neuropathy. Drugs including melphalan, thalidomide, lenalidomide, and bortezomib for POEMS syndrome and those including melphalan, thalidomide, lenalidomide, pomalidomide, bortezomib, ixazomib, and daratumumab for AL amyloidosis are considered. Since there will be more therapeutic options in the future, thereby enabling appropriate treatments for individual neuropathies, there is an increasing need for early diagnosis.
Topics: Humans; Neural Conduction; POEMS Syndrome; Paraproteinemias; Peripheral Nerves; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
PubMed: 34529193
DOI: 10.1007/s10072-021-05583-7 -
Annals of Allergy, Asthma & Immunology... Jan 2019
Review
Topics: Blood Proteins; Electrophoresis; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Inflammation; Paraproteinemias
PubMed: 30579431
DOI: 10.1016/j.anai.2018.08.004 -
Current Opinion in Neurology Oct 1999Paraprotein-associated neuropathies are a diverse group of disorders. The pathogenesis of many of them is poorly understood. Treatments have usually consisted of plasma... (Review)
Review
Paraprotein-associated neuropathies are a diverse group of disorders. The pathogenesis of many of them is poorly understood. Treatments have usually consisted of plasma exchange, corticosteroids, intravenous immunoglobulin, and other immunosuppressive therapies. Response to treatment has varied from good to very poor. Most recent work in this field has had two goals: achieving a better understanding of pathogenesis and developing better treatments. Such diverse entities as hepatitis C virus, vascular endothelial growth factor, and cytokines now appear to play a role in pathogenesis. More aggressive therapies such a bone marrow transplantation, interferon-alpha, and Rituximab have shown some promise.
Topics: Amyloidosis; Cryoglobulinemia; Humans; Multiple Myeloma; Nervous System Diseases; POEMS Syndrome; Paraproteinemias
PubMed: 10590896
DOI: 10.1097/00019052-199910000-00013 -
Blut Jun 1985Indications, results, techniques, laboratory monitoring and complications of therapeutic plasmapheresis in patients with symptomatic paraproteinemia are reviewed. In... (Review)
Review
Indications, results, techniques, laboratory monitoring and complications of therapeutic plasmapheresis in patients with symptomatic paraproteinemia are reviewed. In paraproteinemia associated with severe complications plasma-pheresis has been used successfully as an emergency treatment, as a treatment that reduces temporarily the paraprotein level until reduction of resynthesis is reached by cytotoxic therapy, or as a longterm adjuvant therapy in cases of slowly proliferating plasmacytoma or lymphoma. Plasmapheresis has not been shown to influence the underlying malignant process. Paraprotein-related complications that can be reduced by plasmapheresis are hyperviscosity, hypervolemia, haemorrhagic diathesis, cryoglobulinemic symptoms, rapidly deteriorating renal insufficiency, visual impairment, and neurologic disturbances. Technically, large-pored plasma filters have some advantage as compared to centrifugation techniques. Paraprotein-specific complications of therapeutic plasmapheresis are rare. As an ancillary treatment, therapeutic plasmapheresis has expanded the therapeutic tools in the management of paraproteinemia.
Topics: Acute Kidney Injury; Blood Viscosity; Blood Volume; Corneal Opacity; Cryoglobulinemia; Hemorrhagic Disorders; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Male; Neurologic Manifestations; Paraproteinemias; Paraproteins; Plasma Exchange; Plasmapheresis; Priapism
PubMed: 3890984
DOI: 10.1007/BF00320925 -
Advances in Medical Sciences Mar 2017Amyloidosis is the general term describing the extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins. There are... (Review)
Review
Amyloidosis is the general term describing the extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins. There are multiple different human protein precursors of amyloid fibrils. Amyloid deposits are stained using Congo Red and show typical apple-green birefringence in polarized microscopy. Nowadays, a novel technique LMD/MS technique or laser microdissection combined with mass spectrometry help to diagnose amyloidosis. Amyloidosis of the kidney is typically classified as being either one of two types: AL or AA. Less common is the hereditary amyloidosis. Clinical manifestations are usually determined by the type of precursor protein, the tissue distribution, and the amount of amyloid deposition. Renal manifestation is usually present as asymptomatic proteinuria or clinically apparent nephrotic syndrome. In some patients clinical presentation include impaired kidney function with no or mild proteinuria. Patients with renal amyloidosis who progress to end-stage renal disease (ESRD) can be treated with either dialysis or renal transplantation. Diagnosis of amyloidosis is prerequisite to consider treatment options to avoid unnecessary chemotherapy. Treatment of amyloidosis is aimed at decreasing the precursors of fibrillary proteins and/or decrease in synthesis/deposition of amyloid fibrils. It depends upon the type of amyloidosis and cause of excess fibril production.
Topics: Amyloidosis; Animals; Humans; Kidney Failure, Chronic; Neoplasms; Paraproteinemias
PubMed: 28153807
DOI: 10.1016/j.advms.2016.06.004 -
Blood Jun 2019Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell dyscrasia that consistently precedes multiple myeloma (MM) with a 1% risk of... (Review)
Review
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell dyscrasia that consistently precedes multiple myeloma (MM) with a 1% risk of progression per year. Recent advances have improved understanding of the complex genetic and immunologic factors that permit progression from the aberrant plasma cell clone to MGUS and overt MM. Additional evidence supports bidirectional interaction of MGUS cells with surrounding cells in the bone marrow niche that regulates malignant transformation. However, there are no robust prognostic biomarkers. Herein we review the current body of literature on the biology of MGUS and provide a rationale for the improved identification of high-risk MGUS patients who may be appropriate for novel clinical interventions to prevent progression or eradicate premalignant clones prior to the development of overt MM.
Topics: Humans; Paraproteinemias
PubMed: 31010848
DOI: 10.1182/blood.2019846782 -
The New England Journal of Medicine May 1998
Review
Topics: Antigens; Female; Glycoconjugates; Humans; Male; Paraproteinemias; Peripheral Nervous System Diseases
PubMed: 9603799
DOI: 10.1056/NEJM199805283382207 -
Annals of Clinical and Laboratory... 2016
Topics: Aged, 80 and over; Humans; Iron; Magnetic Resonance Imaging; Male; Paraproteinemias
PubMed: 27098634
DOI: No ID Found -
Leukemia Dec 1997We have identified by MEDLINE search the cases of gammaglobinopathy and plasma cell malignancy in HIV-positive patients reported in the English language literature. The... (Review)
Review
We have identified by MEDLINE search the cases of gammaglobinopathy and plasma cell malignancy in HIV-positive patients reported in the English language literature. The average age at presentation among HIV-positive patients with plasma cell disorders is 33 years, far younger than the average age of presentation in the general population. Some of these patients present with transient paraproteinemias, while others have persistent paraproteins, which may or may not be associated with true plasma cell malignancies. In most cases in which it has been examined, the paraprotein contains high-titer anti-HIV activity. The presence of high-titer anti-HIV activity in the paraproteins of AIDS patients suggests that an antigen-driven process in response to HIV infection may contribute to the early development of plasma cell disorders in these patients. Recent work in plasma cell tumorigenesis has indicated that transformation at a single point in the B lymphocyte lineage can give rise to either lymphoma or myeloma, dependent upon environmental factors such as T cell function, which may be required for directing transformed lymphocytes from lymphoma and towards plasma cell differentiation. This may explain why B lineage oncogenesis in AIDS patients favors the development of lymphoma over that of myeloma.
Topics: Adult; HIV Infections; Humans; Middle Aged; Multiple Myeloma; Paraproteinemias; Plasmacytoma
PubMed: 9447834
DOI: 10.1038/sj.leu.2400875 -
JAMA Oncology Sep 2021POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare plasma cell disorder characterized by demyelinating... (Review)
Review
IMPORTANCE
POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare plasma cell disorder characterized by demyelinating peripheral neuropathy and clonal plasma cell proliferation. Clinical manifestations are believed to be associated with a surge of inflammatory and angiogenic mediators, including interleukins and vascular endothelial growth factor (VEGF), elicited by clonal and polyclonal plasma cells. The clinical manifestations of POEMS syndrome can be debilitating; therefore, early diagnosis is essential. This review discusses several aspects of POEMS syndrome and includes the most recently published findings, with a special emphasis on diagnosis and treatment strategies.
OBSERVATIONS
POEMS syndrome may be underdiagnosed because of its rarity, and it can be mistaken for chronic inflammatory demyelinating polyneuropathy; this misdiagnosis may lead to delayed therapy and progressive worsening of symptoms, especially neuropathy. Therefore, in addition to measurement of the VEGF level, patients with a monoclonal protein detected in blood and/or urine and neuropathy should be evaluated for POEMS syndrome with use of imaging to assess whether sclerotic bone lesions, effusions, and organomegaly are present. Clinical trials are scant, and treatment is largely based on small case series in which plasma cell-directed therapies, borrowed from the myeloma armamentarium, were used. High-dose melphalan and autologous hematopoietic cell transplantation may be offered to eligible patients. Lenalidomide and dexamethasone can be prescribed for patients who are ineligible for transplants. The main goals of therapy are to attain complete hematologic and VEGF responses and to reduce symptoms, although it may take up to 3 years for neurologic deficits to be ameliorated.
CONCLUSIONS AND RELEVANCE
POEMS syndrome should be considered in the differential diagnosis for patients who have peripheral neuropathy and paraproteinemia among other multisystem manifestations. The syndrome can be debilitating if not recognized early in its course; thus, appropriate diagnosis and treatment are important for optimal clinical outcomes.
Topics: Humans; Lenalidomide; Monoclonal Gammopathy of Undetermined Significance; POEMS Syndrome; Paraproteinemias; Vascular Endothelial Growth Factor A
PubMed: 34081097
DOI: 10.1001/jamaoncol.2021.0586