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Blood Oct 2018
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias
PubMed: 30287466
DOI: 10.1182/blood-2018-07-865642 -
Kidney International Feb 2016
Topics: Aged; Glomerulonephritis, Membranoproliferative; Histiocytosis; Humans; Immunoglobulin kappa-Chains; Kidney Glomerulus; Male; Paraproteinemias
PubMed: 26806837
DOI: 10.1016/j.kint.2015.12.012 -
Muscle & Nerve Jan 2015The paraproteinemias are a heterogeneous group of disorders in which monoclonal plasma cells cause the proliferation of monoclonal proteins. They are of importance to... (Review)
Review
The paraproteinemias are a heterogeneous group of disorders in which monoclonal plasma cells cause the proliferation of monoclonal proteins. They are of importance to clinicians because they often occur in association with neuropathies. Neurologists play a particularly important role when the neuropathy is the presenting feature, in which case they may uncover clinical, laboratory, radiologic, electrodiagnostic, or biopsy findings that lead to identification of the underlying paraproteinemia. The frequency of neuropathies in these patients, and the extent to which such neuropathies dominate the clinical picture, varies significantly between the different paraproteinemias. Treatments may be aimed specifically at the neuropathy, or against the underlying hematologic disorder. In all patients with paraproteinemias, the neurologist can work collaboratively with the hematologist to formulate therapeutic plans and goals and can provide follow-up and monitoring to determine the response of the neuropathy to treatment.
Topics: Humans; Immunoglobulin M; Immunoglobulins; Myelin-Associated Glycoprotein; Paraproteinemias; Peripheral Nervous System Diseases
PubMed: 25288371
DOI: 10.1002/mus.24471 -
British Journal of Hospital Medicine... Jun 2015
Topics: Asymptomatic Diseases; Diagnosis, Differential; Disease Management; Electrophoresis; Humans; Immunoglobulin Light Chains; Multiple Myeloma; Paraproteinemias; Prognosis
PubMed: 26053916
DOI: 10.12968/hmed.2015.76.6.C82 -
Nature Reviews. Nephrology Oct 2015IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition that involves almost every organ system. In this Review, we summarize current knowledge of... (Review)
Review
IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition that involves almost every organ system. In this Review, we summarize current knowledge of IgG4-RD and its most frequent manifestations in the kidney—IgG4-related tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy (MGN). Diagnosis of IgG4-RD relies on histopathology: the typical features are a dense lymphoplasmacytic infiltrate and storiform fibrosis. A high percentage of plasma cells observed within lesions stain positively for IgG4. IgG4-related TIN bears the hallmark pathological findings of IgG4-RD; distinctive radiographic characteristics are also frequently observed with use of contrast-enhanced CT. MGN secondary to IgG4-RD seems to be distinct from idiopathic MGN. Humoral and cell-mediated immunity seem to have roles in the pathophysiology of IgG4-RD, but the details of these roles remain unclear. The IgG4 molecule itself is unlikely to be the primary driver of inflammation; rather, it probably downregulates the immune response. Fibrosis might be caused by activation of innate immune cells by polarized CD4(+) T cells. Glucocorticoids are the standard initial treatment for IgG4-RD, but their long-term adverse effects and the high frequency of relapse and renal damage associated with use of this treatment has prompted a search for more effective options. B-cell depletion and the targeting of plasmablasts are both promising approaches.
Topics: Humans; Immunoglobulin G; Kidney Diseases; Paraproteinemias
PubMed: 26122730
DOI: 10.1038/nrneph.2015.95 -
Deutsches Arzteblatt International Nov 20173.2-3.5% of persons over age 50 have a monoclonal gammopathy. Monoclonal gammopathies have many causes, including cancer. 10-20% of monoclonal gammopathies are of... (Review)
Review
BACKGROUND
3.2-3.5% of persons over age 50 have a monoclonal gammopathy. Monoclonal gammopathies have many causes, including cancer. 10-20% of monoclonal gammopathies are of isotype IgM. A systematic approach to the differential diagnosis of IgM gammopathies is essential because of the different therapeutic implications of the various underlying conditions.
METHODS
This review is based on pertinent publications retrieved by a selective search in PubMed and current guidelines from Germany and abroad.
RESULTS
The diagnosis of a monoclonal IgM gammopathy is established by serum electrophoresis in combination with immune fixation. Further evaluation enables the identification of the underlying condition: the differential diagnosis includes IgM-MGUS (monoclonal gammopathy of unclear significance), Waldenström's disease, and IgM myeloma. The therapeutic implications of the under - lying condition vary from watchful waiting in IgM-MGUS to combined rituximab and antineoplastic chemotherapy (off-label first-line use of rituximab) in symptomatic Waldenström's macroglobulinemia. Ibrutinib has been approved for the treatment of patients with recurrences, or of those for whom first-line treatment with rituximab and chemotherapy is not suitable. The current treatment options do not result in cure. In symptomatic Waldenström's disease, the goal of treatment is to keep the disease under control for as long as possible without impairing the patient's quality of life.
CONCLUSION
Evidence-based treatment decisions in Waldenström's macroglobulinemia now rely mainly on small-scale, single-armed trials. Patients with this disease should be treated in the setting of a clinical trial if possible. Trials aimed at improving the quality of treatment for other IgM-associated diseases, such as IgM neuropathies and cold agglutinin disease, would also be desirable.
Topics: Germany; Humans; Immunoglobulin M; Neoplasm Recurrence, Local; Paraproteinemias; Quality of Life; Waldenstrom Macroglobulinemia
PubMed: 29169431
DOI: 10.3238/arztebl.2017.0745 -
Clinical Lymphoma, Myeloma & Leukemia Nov 2018TEMPI (telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal gammopathy, perinephric fluid collections, intrapulmonary shunting) syndrome is a newly... (Review)
Review
TEMPI (telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal gammopathy, perinephric fluid collections, intrapulmonary shunting) syndrome is a newly described clinical entity that is generally considered a plasma cell dyscrasia with multiple system involvement. The etiology and pathophysiology of this condition remains elusive. Nevertheless, clonal plasma cells and monoclonal protein appear to be major contributors. The early diagnosis of TEMPI syndrome is essential because therapies targeting the underlying plasma cells can lead to a dramatic response. Bortezomib-based chemotherapy, daratumumab monotherapy, and autologous hematopoietic stem cell transplantation can result in reversal of most manifestations. Nevertheless, the diagnosis of TEMPI syndrome remains a substantial challenge owing to its rarity and the complexity of clinical presentations. TEMPI syndrome is often misdiagnosed as other causes of erythrocytosis, resulting in a delayed diagnosis and further clinical deterioration. The aim of the present review was to present the clinical and biologic features of TEMPI syndrome, highlighting the differential diagnosis and outlining the present understanding of its pathophysiology and treatment.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Neoplasms, Plasma Cell; Paraproteinemias; Polycythemia; Prognosis; Syndrome; Telangiectasis; Transplantation, Autologous
PubMed: 30100329
DOI: 10.1016/j.clml.2018.07.284 -
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 -
Journal of the American Academy of... Dec 2017Cutaneous manifestations secondary to paraprotein deposits in the skin include a group of different disorders that although rare, may be the first clinical manifestation... (Review)
Review
Cutaneous manifestations secondary to paraprotein deposits in the skin include a group of different disorders that although rare, may be the first clinical manifestation of the underlying hematologic dyscrasia. In this article we review the clinical manifestations and histopathologic findings of the processes that result from specific deposition of the paraprotein in different structures of the skin. Paraneoplastic processes frequently associated with hematologic malignancies will not be covered in this review. Some of the disorders included here result from deposition of the intact paraprotein in the skin, whereas in other cases the lesions are due to deposition of modified paraproteins in the form of amyloid substance, cryoglobulins, or crystalglobulins. Cutaneous amyloidoma refers to nodular dermal deposits of amyloid derived from immunoglobulin light chains produced by local plasma cells in the absence of systemic amyloidosis. Dermatologists and dermatopathologists should be aware of the clinical and histopathologic features of these rare disorders because sometimes the cutaneous lesions are the first sign of an underlying silent hematologic malignancy with paraproteinemia.
Topics: Humans; Paraproteinemias; Paraproteins; Skin; Skin Diseases
PubMed: 28985955
DOI: 10.1016/j.jaad.2017.07.039 -
Frontiers in Endocrinology 2022TEMPI (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) syndrome is... (Review)
Review
TEMPI (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) syndrome is a rare and newly defined multisystemic disease, which belongs to "monoclonal gammopathy of clinical significances". Due to its rarity, the etiology, pathogenesis, and clinical features of this disease remain largely unknown. Owing to its hidden and diverse clinical manifestations, missed diagnosis and misdiagnosis are common. In recent years, as more patients (including three fatal cases) were identified, some special clinical manifestations other than the typical pentad of TEMPI syndrome have been reported. Meanwhile, several studies attempting to identify the pathogenesis of TEMPI syndrome were conducted. In this review, we summarize the reported clinical characteristics of TEMPI syndrome and discuss the current and potential treatment options for patients with TEMPI syndrome, including those with relapsed/refractory disease. Furthermore, we provide an overview of current knowledge on the pathophysiology of TEMPI syndrome.
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Polycythemia; Syndrome; Telangiectasis
PubMed: 35663307
DOI: 10.3389/fendo.2022.886961