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Clinical Journal of the American... Jan 2018Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of... (Review)
Review
Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of the entire Ig or its components. Monoclonal proteins are increasingly recognized as a contributor to kidney disease. They can cause injury in all areas of the kidney, including the glomerular, tubular, and vascular compartments. In the glomerulus, the major mechanism of injury is deposition. Examples of this include Ig amyloidosis, monoclonal Ig deposition disease, immunotactoid glomerulopathy, and cryoglobulinemic GN specifically from types 1 and 2 cryoglobulins. Mechanisms that do not involve Ig deposition include the activation of the complement system, which causes complement deposition in C3 glomerulopathy, and cytokines/growth factors as seen in thrombotic microangiopathy and precipitation, which is involved with cryoglobulinemia. It is important to recognize that nephrotoxic monoclonal proteins can be produced by clones from any of the B cell lineages and that a malignant state is not required for the development of kidney disease. The nephrotoxic clones that do not meet requirement for a malignant condition are now called monoclonal gammopathy of renal significance. Whether it is a malignancy or monoclonal gammopathy of renal significance, preservation of renal function requires substantial reduction of the monoclonal protein. With better understanding of the pathogenesis, clone-directed strategies, such as rituximab against CD20 expressing B cell and bortezomib against plasma cell clones, have been used in the treatment of these diseases. These clone-directed therapies been found to be more effective than immunosuppressive regimens used in nonmonoclonal protein-related kidney diseases.
Topics: Animals; Autoimmunity; B-Lymphocytes; Cell Lineage; Complement Activation; Cytotoxicity, Immunologic; Humans; Immunoglobulin G; Kidney Diseases; Kidney Glomerulus; Paraproteinemias; Prognosis; Risk Factors
PubMed: 29114004
DOI: 10.2215/CJN.00560117 -
European Journal of Ophthalmology Sep 2023Plasma cell dyscrasias are a wide range of severe monoclonal gammopathies caused by pre-malignant or malignant plasma cells that over-secrete an abnormal monoclonal... (Review)
Review
Plasma cell dyscrasias are a wide range of severe monoclonal gammopathies caused by pre-malignant or malignant plasma cells that over-secrete an abnormal monoclonal antibody. These disorders are associated with various systemic findings, including ophthalmological disorders. A search of PubMed, EMBASE, Scopus and Cochrane databases was performed in March 2021 to examine evidence pertaining to ocular complications in patients diagnosed with plasma cell dyscrasias. This review outlines the ocular complications associated with smoldering multiple myeloma and monoclonal gammopathy of undetermined significance, plasmacytomas, multiple myeloma, Waldenström's macroglobulinemia, systemic amyloidosis, Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes (POEMS) syndrome, and cryoglobulinemia. Although, the pathological mechanisms are not completely elucidated yet, wide-ranging ocular presentations have been identified over the years, evolving both the anterior and posterior segments of the eye. Moreover, the presenting symptoms also help in early diagnosis in asymptomatic patients. Therefore, it is imperative for the treating ophthalmologist and oncologist to maintain a high clinical suspicion for identifying the ophthalmological signs and diagnosing the underlying disease, preventing its progression through efficacious treatment strategies.
Topics: Humans; Paraproteinemias; Eye; Eye Diseases; Treatment Outcome
PubMed: 36760117
DOI: 10.1177/11206721231155974 -
Practical Neurology Aug 2018POEMS syndrome is a rare and disabling autoinflammatory condition characterised by a typical peripheral neuropathy and the presence of a monoclonal plasma cell disorder.... (Review)
Review
POEMS syndrome is a rare and disabling autoinflammatory condition characterised by a typical peripheral neuropathy and the presence of a monoclonal plasma cell disorder. The acronym 'POEMS' represents the complex and multisystem features of the disease, including polyneuropathy, organomegaly, endocrinopathy, a monoclonal plasma cell disorder and skin disease. The diagnosis of POEMS is a significant challenge because of the heterogeneity of clinical presentations and variation of POEMS features. Patients are often misdiagnosed with another cause of inflammatory neuropathy and receive one or more ineffective immunomodulatory medications, resulting in delayed diagnosis and further clinical deterioration before a diagnosis is made. University College London Hospitals sees one of the largest reported POEMS cohorts in Europe, and runs a multispecialist clinic to assist with diagnosis, treatment and ongoing support. This review draws upon our experience to present the typical features of POEMS syndrome and highlight diagnostic conundrums commonly experienced, supplemented with clinical cases. We provide an investigative guide for clinicians when considering POEMS as the diagnosis, and propose a treatment algorithm that centres on the site and degree of monoclonal cell proliferation.
Topics: Diagnosis, Differential; Disease Management; Humans; Neuropathology; POEMS Syndrome
PubMed: 29511110
DOI: 10.1136/practneurol-2017-001792 -
Nefrologia : Publicacion Oficial de La... 2017The term monoclonal gammopathy of renal significance (MGRS) comprises a group of diseases pathogenetically characterised by proliferation of a B-cell or plasma cell... (Review)
Review
The term monoclonal gammopathy of renal significance (MGRS) comprises a group of diseases pathogenetically characterised by proliferation of a B-cell or plasma cell clone that synthesises and secretes a monoclonal immunoglobulin or its components (light and/or heavy chains), that may deposit and cause glomerular, tubular, interstitial and/or vascular damage. The importance of differentiating the term MGRS from other monoclonal gammopathies lies in the fact that diagnostic and therapeutic procedures aimed at controlling monoclonal protein synthesis and secretion can be indicated, irrespective of the classic criteria based on malignant tumour expansion. Renal pathology associated with MGRS is highly heterogeneous, and therefore renal biopsy should be considered a key diagnostic tool. A precise diagnostic approach, however, must also identify the monoclonal protein in plasma and/or in urine, together with a complete haematological study in order to determine the nature and extension of cell clones. Recent advances in the understanding of these entities have resulted in significant improvements in clinical course and survival in several forms of MGRS, although more studies and clinical experience are needed in order to delineate more effective therapeutic strategies. In this review, we summarise the main clinical and pathological features of MGRS, highlighting the most appropriate diagnostic approach and current therapeutic options.
Topics: Antibodies, Monoclonal; B-Lymphocytes; Biopsy; Bortezomib; Cyclophosphamide; Humans; Immunoglobulins; Kidney; Melphalan; Paraproteinemias; Paraproteins; Plasma Cells; Renal Insufficiency, Chronic; Rituximab; Thalidomide
PubMed: 28946960
DOI: 10.1016/j.nefro.2017.03.012 -
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 -
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 -
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 -
Frontiers in Bioscience (Elite Edition) Jan 2015Amyloidosis and monoclonal immunoglobulin deposition disease, though rare entities, can wreak havoc on the architecture and functioning of the kidneys. These diseases... (Review)
Review
Amyloidosis and monoclonal immunoglobulin deposition disease, though rare entities, can wreak havoc on the architecture and functioning of the kidneys. These diseases have a predilection to cause severe renal dysfunction leading to end stage renal disease (ESRD). In recent years, the available treatments for these diseases have expanded and afflicted patients are living longer, but with advanced kidney disease. Because of the complex nature of the pathophysiology and treatment of these diseases, it can be very challenging for a clinician to determine whether or not it is appropriate to refer an affected individual for kidney transplantation.
Topics: Amyloidosis; Humans; Kidney Failure, Chronic; Kidney Transplantation; Paraproteinemias
PubMed: 25553370
DOI: 10.2741/724 -
Journal of Medical Case Reports Apr 2023Systemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light... (Review)
Review
BACKGROUND
Systemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light chain amyloidosis, which results from the accumulation of misfolded immunoglobulins. The disease is progressive, with treatment targeted at the underlying plasma cell dyscrasia. Since essentially any organ system can be affected, the presentation is variable and delays in diagnosis are common. Given this diagnostic difficulty, we discuss four different manifestations of light chain amyloidosis.
CASE PRESENTATIONS
In this case series, we discuss four cases of light chain amyloidosis. These include cardiac, hepatic, and gastrointestinal as well as autonomic and peripheral nerve involvement with amyloidosis. The patients in our series are of Caucasian background and include a 69-year-old female, a 29-year-old female, a 68-year-old male, and a 70-year-old male, respectively. The case discussions highlight variability in presentation and diagnostic challenges.
CONCLUSIONS
Amyloidosis is a rare but serious disease that is often complicated by long delays in diagnosis. Morbidity and mortality can sometimes be limited if diagnosed earlier. We hope our real life cases will contribute to understanding and to early suspicion that can lead to early diagnosis and management.
Topics: Male; Female; Humans; Aged; Adult; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Paraproteinemias; Heart
PubMed: 37081462
DOI: 10.1186/s13256-023-03886-1