478 results on '"Monoclonal Gammopathy of Undetermined Significance complications"'
Search Results
2. Monoclonal Gammopathy of Undetermined Significance and Associated Cardiovascular Outcomes in a Hospital Setting-A Fresh Perspective.
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Mustafa A, Wei C, Araji G, Niazi MRK, Grovu R, Weinberg M, and Lafferty J
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- Humans, Female, Male, Aged, Middle Aged, Comorbidity, Hospitalization statistics & numerical data, Aged, 80 and over, Monoclonal Gammopathy of Undetermined Significance complications, Cardiovascular Diseases epidemiology
- Abstract
There is a paucity of data on the cardiovascular implications of monoclonal gammopathy of undetermined significance, especially among hospitalized patients. Our study aimed to investigate the association between MGUS and cardiovascular outcomes in a hospital setting using the National Inpatient Sample database. MGUS patients were sampled using ICD-10 codes. The patients were stratified into two cohorts based on the presence or absence of MGUS. Comorbidities and cardiovascular outcomes were collected using ICD 10 DM codes. CV outcomes were evaluated before and after 1:1 matching for age, gender, and race. Furthermore, a sensitivity analysis was performed on the matched population, which excluded patients with diabetes mellitus, prior myocardial infarction, chronic kidney disease (stages 3-5), dialysis, hypertension, obesity, metabolic syndrome, cancer, antiplatelets, and oral anticoagulant use and was adjusted for smoking, dyslipidemia, and aspirin use to evaluate the cardiovascular outcomes. MGUS patients had more heart failure, atrial fibrillation, venous thromboembolism, aortic aneurysm, aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, conduction disorder, cor pulmonale, peripheral vascular disease, and acute myocardial infarction. After matching, MGUS was associated with heart failure, atrial fibrillation, venous thromboembolism, aortic stenosis, mitral regurgitation, conduction disorder, cor pulmonale, and peripheral vascular disease. MGUS was linked to a wide spectrum of cardiovascular diseases in an inpatient setting. Further studies are needed to formulate appropriate recommendations for the screening and management of cardiovascular complications in individuals with MGUS.
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- 2024
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3. Plasma cells with Auer-rod-like inclusions in a patient with MGUS and acute myeloid leukaemia with NPM1 mutation.
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Glanzmann J, Kalberer C, Bonadies N, and Colucci G
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- Humans, Male, Inclusion Bodies pathology, Female, Middle Aged, Nucleophosmin, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute pathology, Mutation, Nuclear Proteins genetics, Monoclonal Gammopathy of Undetermined Significance genetics, Monoclonal Gammopathy of Undetermined Significance pathology, Monoclonal Gammopathy of Undetermined Significance complications, Plasma Cells pathology, Plasma Cells metabolism
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- 2024
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4. Gammopathic dermopathy: characterization of cutaneous MGUS.
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Gordon ER, Chen C, Trager MH, Adeuyan O, Lapolla BA, Fahmy LM, Schreidah CM, Wetter DA, and Geskin LJ
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- Humans, Female, Male, Aged, Middle Aged, Aged, 80 and over, Adult, Skin pathology, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance pathology, Skin Diseases etiology, Skin Diseases diagnosis, Skin Diseases pathology
- Abstract
Monoclonal Gammopathy of Undetermined Significance (MGUS) is a clonal plasma cell disorder that is considered preneoplastic, asymptomatic, and only requiring observation. However, MGUS may result in cutaneous complications, which are poorly understood, causing treatment delays and patient suffering. We present 30 patients with cutaneous findings associated with MGUS, characterizing clinical presentations, isoforms, treatments, and outcomes. These included: MGUS-associated 'rashes' (pruritic eczematous rashes), reactive and mucin-depositional conditions (pyoderma gangrenosum, scleromyxedema), M-protein-related deposition disorders (POEMS syndrome, Waldenstrom macroglobulinemia), and cutaneous lymphomas. Twelve of 30 (40%) patients received multiple myeloma drugs (MMDs). Eleven (92%) patients improved, and those not receiving MMDs rarely improved, suggesting that MMDs have efficacy for cutaneous manifestations of MGUS. Therefore, trialing MMDs may be warranted for patients with MGUS not responding to other therapies. Moreover, evaluation for monoclonal gammopathy in elderly patients with intractable pruritus or other chronic skin conditions that are non-responsive to skin-directed therapies should be considered.
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- 2024
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5. [Latest updates on immunotactoid glomerulopathy and fibrillary glomerulonephritis].
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Lafargue MC and Cohen C
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- Humans, Multiple Myeloma complications, Multiple Myeloma pathology, Multiple Myeloma therapy, Paraproteinemias complications, Paraproteinemias therapy, Paraproteinemias pathology, Leukemia, Lymphocytic, Chronic, B-Cell complications, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance therapy, Monoclonal Gammopathy of Undetermined Significance pathology, Glomerulonephritis pathology, Glomerulonephritis etiology, Glomerulonephritis therapy
- Abstract
Various hematologic malignancies can lead to renal complications. The most common of these hemopathies to affect the kidney is multiple myeloma, however an increasing number of kidney diseases are associated with other monoclonal gammopathies. It is recognized that clones in small abundance can be responsible for severe organ damage, thus the concept of monoclonal gammopathy of renal significance (MGRS) has emerged. Although the hemopathy in these patients is more consistent with monoclonal gammopathy of undetermined significance (MGUS) than with multiple myeloma, the diagnosis of a renal complication changes the therapeutic management. Preservation and restoration of renal function is possible with treatment targeting the responsible clone. In this article, we take as an example immunotactoid and fibrillary glomerulopathies, two distinct entities with different etiologies and consequently different management. Immunotactoid glomerulopathy is most often associated with monoclonal gammopathy or chronic lymphocytic leukemia, the deposits on renal biopsy are monotypic, and treatment is therefore based on clone targeting. Fibrillary glomerulonephritis, on the other hand, is caused by autoimmune diseases or solid cancers. Deposits on renal biopsy are in the vast majority polyclonal. There is a specific immunohistochemical marker, DNAJB9, and treatment is less well established., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
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- 2024
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6. Association Between Autoimmune Diseases and Monoclonal Gammopathy of Undetermined Significance : An Analysis From a Population-Based Screening Study.
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Sverrisdottir I, Thorsteinsdottir S, Rognvaldsson S, Aspelund T, Vidarsson B, Onundarson PT, Agnarsson BA, Sigurdardottir M, Thorsteinsdóttir I, Sveinsdottir SV, Palmason R, Olafsson I, Sigurdsson F, Thordardóttir AR, Eythorsson E, Jonsson A, Palsson R, Indridason OS, Gislason GK, Olafsson A, Sigurdsson J, Steingrímsdóttir H, Einarsson Long T, Hultcrantz M, Durie BGM, Harding S, Landgren O, Kristinsson SY, and Love TJ
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- Humans, Male, Female, Iceland epidemiology, Middle Aged, Cross-Sectional Studies, Aged, Adult, Prevalence, Prospective Studies, Autoimmune Diseases epidemiology, Autoimmune Diseases complications, Autoimmune Diseases diagnosis, Monoclonal Gammopathy of Undetermined Significance epidemiology, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance complications, Mass Screening methods
- Abstract
Background: Monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. In previous registry-based, retrospective studies, autoimmune diseases have been associated with MGUS. However, these studies were not based on a screened population and are therefore prone to ascertainment bias., Objective: To examine whether MGUS is associated with autoimmune diseases., Design: A cross-sectional study within iStopMM (Iceland Screens, Treats, or Prevents MM), a prospective, population-based screening study of MGUS., Setting: Icelandic population of adults aged 40 years or older., Patients: 75 422 persons screened for MGUS., Measurements: Poisson regression for prevalence ratios (PRs) of MGUS among persons with or without an autoimmune disease, adjusted for age and sex., Results: A total of 10 818 participants had an autoimmune disorder, of whom 599 had MGUS (61 with a prior clinical diagnosis and 538 diagnosed at study screening or evaluation). A diagnosis of an autoimmune disease was not associated with MGUS (PR, 1.05 [95% CI, 0.97 to 1.15]). However, autoimmune disease diagnoses were associated with a prior clinical diagnosis of MGUS (PR, 2.11 [CI, 1.64 to 2.70])., Limitation: Registry data were used to gather information on autoimmune diseases, and the homogeneity of the Icelandic population may limit the generalizability of these results., Conclusion: The study did not find an association between autoimmune disease and MGUS in a systematically screened population. Previous studies not done in systematically screened populations have likely been subject to ascertainment bias. The findings indicate that recommendations to routinely screen patients with autoimmune disease for MGUS may not be warranted., Primary Funding Source: The International Myeloma Foundation and the European Research Council., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2867.
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- 2024
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7. Mass spectrometry-detected MGUS is associated with obesity and other novel modifiable risk factors in a high-risk population.
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Lee DJ, El-Khoury H, Tramontano AC, Alberge JB, Perry J, Davis MI, Horowitz E, Redd R, Sakrikar D, Barnidge D, Perkins MC, Harding S, Mucci L, Rebbeck TR, Ghobrial IM, and Marinac CR
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- Humans, Obesity complications, Obesity diagnosis, Obesity epidemiology, Risk Factors, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance epidemiology, Monoclonal Gammopathy of Undetermined Significance complications, Multiple Myeloma diagnosis, Multiple Myeloma epidemiology, Multiple Myeloma etiology
- Abstract
Abstract: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition of multiple myeloma with few known risk factors. The emergence of mass spectrometry (MS) for the detection of MGUS has provided new opportunities to evaluate its risk factors. In total, 2628 individuals at elevated risk for multiple myeloma were enrolled in a screening study and completed an exposure survey (PROMISE trial). Participant samples were screened by MS, and monoclonal proteins (M-proteins) with concentrations of ≥0.2 g/L were categorized as MS-MGUS. Multivariable logistic models evaluated associations between exposures and MS outcomes. Compared with normal weight (body mass index [BMI] of 18.5 to <25 kg/m2), obesity (BMI of ≥30 kg/m2) was associated with MS-MGUS, adjusting for age, sex, Black race, education, and income (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.21-2.47; P = .003). High physical activity (≥73.5 metabolic equivalent of task (MET)-hours per week vs <10.5 MET-hours per week) had a decreased likelihood of MS-MGUS (OR, 0.45, 95% CI, 0.24-0.80; P = .009), whereas heavy smoking and short sleep had increased likelihood of MS-MGUS (>30 pack-years vs never smoker: OR, 2.19; 95% CI, 1.24-3.74; P = .005, and sleep <6 vs ≥6 hours per day: OR, 2.11; 95% CI, 1.26-3.42; P = .003). In the analysis of all MS-detected monoclonal gammopathies, which are inclusive of M-proteins with concentrations of <0.2 g/L, elevated BMI and smoking were associated with all MS-positive cases. Findings suggest MS-detected monoclonal gammopathies are associated with a broader range of modifiable risk factors than what has been previously identified. This trial was registered at www.clinicaltrials.gov as #NCT03689595., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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8. Clinicopathological characteristics and prognosis in patients with monoclonal gammopathy and renal damage in central China: a multicenter retrospective cohort study.
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He H, Wang Z, Xu J, Liu Y, Shao Y, Hou Y, Gu J, Hu R, and Xing G
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- Humans, Retrospective Studies, Prognosis, Kidney Diseases diagnosis, Kidney Diseases etiology, Kidney Diseases pathology, Paraproteinemias complications, Paraproteinemias diagnosis, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Hematologic Neoplasms complications
- Abstract
Renal involvement is common in monoclonal gammopathy (MG); however, the same patient may have both MG and non-paraprotein-associated renal damage. Accordingly, distinguishing the cause of renal damage is necessary because of the different clinical characteristics and associated treatments. In this multicenter retrospective cohort study, we described the clinicopathological characteristics and prognosis of 703 patients with MG and renal damage in central China. Patients were classified as having MG of renal significance (MGRS), MG of undetermined significance (MGUS), or hematological malignancy. 260 (36.98%), 259 (36.84%), and 184 (26.17%) had MGRS, MGUS, and hematological malignancies, respectively. Amyloidosis was the leading pattern of MGRS (74.23%), followed by thrombotic microangiopathy (8.85%) and monoclonal immunoglobulin deposition disease (8.46%). Membranous nephropathy was the leading diagnosis of MGUS (39.38%). Renal pathological findings of patients with hematological malignancies included paraprotein-associated lesions (84.78%) and non-paraprotein-associated lesions (15.22%). The presence of nephrotic syndrome and an abnormal free light chain (FLC) ratio were independently associated with MGRS. The overall survival was better in patients with MGUS than in those with MGRS or hematological malignancies., (© 2024. The Author(s).)
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- 2024
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9. Surgical Approach for Monoclonal Gammopathy of Undetermined Significance-Related Ocular Copper Deposition.
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Dai X, Lee MJ, Schein OD, Wenick AS, Oboh-Weilke AM, and Woreta FA
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- Male, Humans, Adult, Copper, Trypan Blue, Visual Acuity, Vitrectomy methods, Cataract complications, Monoclonal Gammopathy of Undetermined Significance complications, Phacoemulsification methods
- Abstract
Purpose: The aim of this study was to present the surgical management of a patient with ocular copper deposition associated with monoclonal gammopathy of undetermined significance (MGUS)., Methods: This is a case report of a 44-year-old man with MGUS who presented to us with bilateral diffuse deposition of copper in the cornea and lens., Results: Despite initiating systemic therapy for MGUS, no corneal clearing was observed. A decision was made to proceed with cataract extraction in the left eye given worsening vision. Despite trypan blue staining and a central descemetorhexis, visualization remained too poor to complete phacoemulsification. Pars plana lensectomy and vitrectomy to remove the residual lens material and placement of a posterior chamber intraocular lens in the sulcus with endoillumination was subsequently performed. As vision in the left eye steadily improved postoperatively, cataract surgery was then performed in the right eye. With use of trypan blue, creation of a 6-mm central descemetorhexis, and a retinal light pipe for endoillumination anteriorly to augment visualization, capsulorhexis, phacoemulsification, and insertion of intraocular lens in the bag were completed without difficulty. The patient's vision improved at subsequent follow-ups, reaching a final best-corrected visual acuity of 20/20-1 in the right eye and 20/25-1 in the left eye., Conclusions: Ocular copper deposition is a rare manifestation of MGUS. Cataract extraction is challenging, often requiring advanced techniques. Endoillumination is useful to improve visualization through the dense corneal copper deposition., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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10. The Case | A patient with skin rash, monoclonal gammopathy, and proteinuria.
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Fryc J and Naumnik B
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- Humans, Proteinuria diagnosis, Proteinuria etiology, Paraproteinemias complications, Paraproteinemias diagnosis, Paraproteinemias therapy, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Exanthema diagnosis, Exanthema etiology
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- 2024
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11. Retinopathy in a Patient With IgM MGUS: Causal Association or an Epiphenomenon?
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Ntanasis-Stathopoulos I, Kastritis E, Tzartos J, Terpos E, Dimopoulos MA, and Gavriatopoulou M
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- Humans, Cyclophosphamide, Immunoglobulin M, Cell Transformation, Neoplastic, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Retinal Diseases
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Background/aim: The presence of a monoclonal gammopathy of undetermined significance (MGUS) even in small amounts may trigger tissue damage through immunological or other mechanisms, irrespective of the potential for malignant transformation. The aim of the study was to present a case of monoclonal gammopathy of clinical significance with ocular manifestations and discuss relevant literature., Case Report: In our case, a patient presented with vision disturbances that was eventually attributed to the underlying IgM MGUS after extensive workup to exclude other potential etiologies. The patient showed a clinical response with the fixed-duration DRC (dexamethasone, rituximab, cyclophosphamide) regimen that persisted for at least 1.5 years. Herein, we present, in detail, the patient management and discuss the underlying pathophysiology of this rare entity with few available published data in this field., Conclusion: A high level of clinical suspicion is necessary in order to detect the association between MGUS and a clinical sign or symptom that cannot be attributed elsewhere., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2024
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12. Sjögren's disease activity associates with cardiovascular disease and monoclonal gammopathy: a university cohort study of disease activity and comorbidities.
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Bohman BR, Dowds HS, Blagogee TE, Ike RW, Hansen KE, and McCoy SS
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- Humans, Cohort Studies, Universities, Severity of Illness Index, Comorbidity, Sjogren's Syndrome complications, Sjogren's Syndrome epidemiology, Sjogren's Syndrome diagnosis, Cardiovascular Diseases complications, Cardiovascular Diseases epidemiology, Paraproteinemias complications, Paraproteinemias epidemiology, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance epidemiology, Myocardial Infarction, Peripheral Vascular Diseases
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Background: We used the University of Wisconsin cohort to determine the extent to which the EULAR Sjögren's syndrome disease activity index (ESSDAI) was associated with comorbidities that contribute to mortality., Methods: Our University of Wisconsin, Madison cohort had 111 patients with Sjögren's Disease (SjD) by 2016 ACR/EULAR criteria and 194 control patients with sicca. Our study was performed from March 1st, 2020 through April 1st, 2023. We collected data using a standardized collection tool, including components of the Charlson Comorbidity Index (CCI). Stratifying our SjD patients by ESSDAI < 5 and ESSDAI ≥ 5, we assessed differences in comorbidities associated with mortality., Results: At time of SjD diagnosis, the ESSDAI ≥ 5 group had increased odds of peripheral vascular disease compared to controls (OR 10.17; 95% CI 1.18-87.87). Patients with a current ESSDAI ≥ 5 were more likely to have a myocardial infarction compared to controls (OR 9.87; 95% CI 1.17-83.49). SjD patients had increased prevalence of monoclonal gammopathy compared to controls (9.3% vs 0.5%, p < 0.001). SjD patients with high ESSDAI at diagnosis had greater prevalence of monoclonal gammopathy compared to the SjD patients with a low ESSDAI (16% vs 5%, p = .04). As reported elsewhere, the ESSDAI ≥ 5 group had increased odds of chronic pulmonary disease (OR 4.37; 95% CI 1.59-11.97)., Conclusion: We found high ESSDAI scores were associated with worse cardiovascular outcomes, specifically peripheral vascular disease and myocardial infarction. Furthermore, monoclonal gammopathy was more frequent in SjD patients compared to sicca controls, supporting screening for monoclonal gammopathy in the appropriate clinical scenario. Key Points • High ESSDAI scores are associated with worse cardiovascular outcomes, specifically peripheral vascular disease and myocardial infarction. • Monoclonal gammopathy is more frequent in SjD patients than sicca controls, supporting screening for monoclonal gammopathy in the appropriate clinical scenario., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)
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- 2024
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13. Monoclonal Gammopathy and Its Association with Progression to Kidney Failure and Mortality in Patients with CKD.
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Sy-Go JPT, Moubarak S, Vaughan LE, Klomjit N, Viehman JK, Fervenza FC, and Zand L
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- Humans, Retrospective Studies, Paraproteinemias complications, Monoclonal Gammopathy of Undetermined Significance complications, Renal Insufficiency complications, Renal Insufficiency, Chronic complications
- Abstract
Background: Little is known about the prognostic significance of monoclonal gammopathy of undetermined and renal significance (MGUS and MGRS) in patients with CKD. The objective of this study was to determine the clinical and kidney outcomes of patients with CKD with either MGUS or MGRS compared with those with CKD without MGUS or MGRS., Methods: We conducted a retrospective cohort study from 2013 to 2018. Patients who had both CKD diagnosis and monoclonal testing were identified. Patients were divided into MGRS, MGUS, and no monoclonal gammopathy groups. Cumulative incidence functions and Cox proportional hazards regression were used to model time to event data and to evaluate the association between monoclonal gammopathy status and risk of kidney failure, with death treated as a competing risk., Results: Among 1535 patients, 59 (4%) had MGRS, 648 (42%) had MGUS, and 828 (54%) had no monoclonal gammopathy. Unadjusted analysis showed that compared with no monoclonal gammopathy patients, patients with MGRS were at higher risk of kidney failure (hazard ratio [HR] [95% confidence interval]: 2.5 [1.5 to 4.2] but not patients with MGUS (HR [95% confidence interval]: 1.3 [0.97 to 1.6]), after taking death into account as a competing risk. However, in the multivariable analysis, after adjusting for age, sex, eGFR, proteinuria, and Charlson Comorbidity Index, the risk of progression to kidney failure (with death as competing risk) in the MGRS group was no longer statistically significant (HR: 0.9 [0.5 to 1.8]). The same was also true for the MGUS group compared with the group with no monoclonal gammopathy (HR: 1.3 [0.95 to 1.6]). When evaluating the association between MGUS/MGRS status and overall survival, MGRS was significantly associated with mortality in fully adjusted models compared with the group with no monoclonal gammopathy, while MGUS was not., Conclusions: After adjusting for traditional risk factors, MGUS/MGRS status was not associated with a greater risk of kidney failure, but MGRS was associated with a higher risk of mortality compared with patients with no monoclonal gammopathy., (Copyright © 2023 by the American Society of Nephrology.)
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- 2024
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14. Type 1 Cryoglobulinemic Vasculitis Due to Monoclonal Gammopathy of Undetermined Significance Successfully Treated by Bortezomib Plus Dexamethasone.
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Kikuchi R, Onozawa M, Nagai J, Okada S, Hasegawa Y, Ohigashi H, Mitamura S, Maeda T, Takakuwa E, Fujieda Y, Goto H, Hashimoto D, Matsuno Y, and Teshima T
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- Female, Humans, Middle Aged, Bortezomib therapeutic use, Cryoglobulins, Dexamethasone therapeutic use, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance drug therapy, Monoclonal Gammopathy of Undetermined Significance diagnosis, Paraproteinemias complications, Cryoglobulinemia complications, Cryoglobulinemia drug therapy, Vasculitis complications, Vasculitis drug therapy
- Abstract
Cryoglobulins are immunoglobulins that precipitate in cold conditions. Type I cryoglobulinemic vasculitis is associated with hematological malignancies. We herein report a case of steroid-resistant type 1 cryoglobulinemic vasculitis associated with monoclonal gammopathy of undetermined significance (MGUS) in a 47-year-old woman. By immunofixation of cryoglobulin, we found that the main component of cryoglobulin was the M protein due to MGUS, so treatment of MGUS was needed. Bortezomib+dexamethasone therapy resulted in a rapid decrease in cryoglobulin and improvement in the symptoms of cryoglobulinemic vasculitis. In refractory type I cryoglobulinemic vasculitis, treatment of the underlying gammaglobulinopathy should be considered.
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- 2024
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15. Oligoclonal gammopathy: An analysis of 253 cases.
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Karaszewski K, Jasiński M, Waszczuk-Gajda A, Rodziewicz-Lurzyńska A, Ciepiela O, and Jędrzejczak WW
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- Male, Humans, Diagnosis, Differential, Multiple Myeloma diagnosis, Paraproteinemias diagnosis, Paraproteinemias complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance complications
- Abstract
Background: Oligoclonal gammopathy (OG) is a rare disorder of the lymphoid system that is characterized by the presence of at least 2 distinct monoclonal proteins in a patient's serum or urine. The biological and clinical characteristics of this disease are as yet poorly understood., Objectives: The study aimed to assess whether there are significant differences between patients with OG regarding the developmental history (i.e., OG diagnosed at the first presentation compared to OG that has developed in patients with an original monoclonal gammopathy) and the number of monoclonal proteins (2 compared to 3). Moreover, we attempted to determine when secondary oligoclonality develops following the original diagnosis of monoclonal gammopathy., Material and Methods: Patients were analyzed with regard to their age at diagnosis, sex, serum monoclonal proteins, and underlying hematological disorders. Multiple myeloma (MM) patients were additionally evaluated for their Durie-Salmon stage and cytogenetic alterations., Results: Patients with triclonal gammopathy (TG: n = 29) did not differ significantly from patients with biclonal gammopathy (BG: n = 223) (p = 0.81) in terms of age at diagnosis and the dominant diagnosis (MM was the most common diagnosis (65.0% and 64.7%, respectively)). In both cohorts, myeloma patients were mainly classified to the Durie-Salmon stage III. In the TG cohort, there was a higher proportion of males (69.0%) than among patients with BG (52.5%). Oligoclonality developed at various times after diagnosis (up to 80 months in the investigated cohort). However, the occurrence of new cases was higher during the initial 30-month period following the diagnosis of monoclonal gammopathy., Conclusions: There are only small differences between patients with primary compared to secondary OG, between BG and TG, and most patients have a combination of IgGκ+IgGλ. Oligoclonality could develop at any time after the diagnosis of monoclonal gammopathy, but it happens more frequently during the first 30 months, with advanced myeloma being the most prevalent underlying disorder.
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- 2024
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16. Vitamin D and monoclonal gammopathy of undetermined significance (MGUS) among U.S. Black women.
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Ruiz Lopez JN, McNeil GE, Zirpoli G, Palmer JR, Kataria Y, and Bertrand KA
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- Humans, Female, Risk Factors, Calcifediol, Monoclonal Gammopathy of Undetermined Significance epidemiology, Monoclonal Gammopathy of Undetermined Significance complications, Multiple Myeloma, Vitamin D Deficiency epidemiology
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Purpose: Risk factors for monoclonal gammopathy of undetermined significance (MGUS), the asymptomatic precursor to multiple myeloma, are largely unknown. We hypothesized that low vitamin D levels might be associated with higher MGUS prevalence in a national cohort of U.S. Black women., Methods: We screened archived serum samples (collected 2014-2017) from 3896 randomly selected participants in the Black Women's Health Study ages 50-79 for evidence of MGUS; samples had been assayed for 25-hydroxyvitamin D [25(OH)D] shortly after blood draw. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between 25(OH)D level and MGUS status, adjusting for age, body mass index, and season of blood draw., Results: We identified 334 MGUS cases (8.6%) in the study population. The adjusted OR comparing women with vitamin D deficiency (25(OH)D < 20 ng/mL) to those with 25(OH)D levels ≥ 30 ng/mL was 1.27 (95% CI: 0.95, 1.72)., Conclusion: MGUS was more prevalent among Black women with vitamin D deficiency compared to those with 25(OH)D ≥ 30 ng/mL; however, the association was not statistically significant. Future prospective studies are warranted to clarify the possible association between vitamin D and MGUS., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2024
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17. Systematic review and meta-analysis of the clinical features of MGRS.
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Du J and Hu Z
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- Humans, Kidney pathology, Immunoglobulin Light Chains, Paraproteinemias complications, Monoclonal Gammopathy of Undetermined Significance complications, Kidney Diseases pathology
- Abstract
Background: It is crucial to identify patients with monoclonal gammopathy of renal significance (MGRS) from those without MGRS but with monoclonal gammopathy and concomitant kidney diseases. However, there have been few studies with large sample sizes, and their findings were inconsistent. This study aimed to conduct a meta-analysis of MGRS to describe the general characteristics of MGRS and its predictive factors., Methods: Cohort or case-control studies published through December 2022 and related to clinicopathological features of MGRS were retrieved from the PubMed, Cochrane Library, Web of Science, Scopus, and Embase databases. Two researchers searched for studies that met the inclusion criteria. In the univariate analysis, fixed- or random- effects models were used to obtain pooled estimates of the weighted mean difference (WMD) and odds ratio (OR) for risk factors. In the multivariate analysis, the ORs of the independent risk factors from each study were pooled after transforming the original estimates., Results: The meta-analysis included six studies. Univariate analysis showed that the following variables were statistically significant in MGRS: age (WMD = 1.78, 95%CI 0.21-3.35), hypertension (OR = 0.54, 95%CI 0.4-0.73), diabetes (OR = 0.42, 95%CI 0.29-0.59), albumin (WMD = - 0.26, 95%CI - 0.38--0.14), urinary protein level (WMD = 0.76, 95%CI 0.31-1.2), urinary protein ≥ 1.5 g/d (OR = 1.98, 95%CI 1.46-2.68), lambda-chain value (WMD = 29.02, 95%CI 16.55-41.49), abnormal free light-chain ratio (OR = 4.16, 95%CI 1.65-10.47), bone marrow puncture rate (OR = 5.11, 95% CI 1.31-19.95), and abnormal bone marrow outcome rate (OR = 9.63, 95%CI 1.98-46.88). Multivariate analysis showed urinary protein ≥ 1.5 g/d (OR = 2.80, 95%CI 1.53-5.15) and an abnormal free light-chain ratio (OR = 6.98, 95%CI 4.10-11.91) were associated with predictors of MGRS., Conclusions: Compared with non-MGRS patients with monoclonal gammopathy and concomitant kidney diseases, patients with MGRS were older, had fewer underlying diseases, more urinary protein, more abnormal free light-chain ratio, and more abnormal bone marrow results. Urinary protein ≥ 1.5 g/d and an abnormal free light-chain ratio were independent risk factors for MGRS., (© 2024. The Author(s).)
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- 2024
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18. Single monoclonal spike characterized as double monoclonal gammopathy in a patient with multiple myeloma: A rare finding.
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Saijpaul R, Khurana V, Verma R, and Kaushik S
- Subjects
- Humans, Reproducibility of Results, Antibodies, Monoclonal, Multiple Myeloma complications, Multiple Myeloma diagnosis, Multiple Myeloma pathology, Paraproteinemias complications, Paraproteinemias diagnosis, Paraproteinemias pathology, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis
- Abstract
Multiple myeloma (MM) is associated with the secretion of a unique monoclonal protein (M-protein) due to overproduction of immunoglobulin (Ig) by a clone of abnormally proliferating plasma cells. However, in 4% of the cases more than one M-protein can be found. This category of gammopathies is called "double monoclonal gammopathies." Here, we present a rare case of MM with double monoclonal gammopathy, where the presence of both M-proteins was observed in the single sharp peak on capillary zone electrophoresis (CZE). Further the interference of Hook effect is also discussed. Double monoclonal gammopathies need to be identified to increase diagnostic accuracy and reliability, and to get a better understanding of the disease pathogenesis and progression.
- Published
- 2024
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19. Regression of Intermediate-High Risk Monoclonal Gammopathy of Undetermined Significance (MGUS) With Long-term Use of Curcumin: A Case Report.
- Author
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Golombick T, Ramakrishna R, and Manoharan A
- Subjects
- Humans, Disease Progression, Monoclonal Gammopathy of Undetermined Significance drug therapy, Monoclonal Gammopathy of Undetermined Significance complications, Curcumin therapeutic use, Multiple Myeloma drug therapy
- Abstract
Patients with intermediate-high risk MGUS are not offered therapeutic options to date and standard of care remains observation with re-evaluations of the patient every 3 to 6 months. Given the persistent risk of progression as well as potential complications experienced by some, and anxiety experienced by most patients, early intervention with non-toxic curcumin, aimed at potentially slowing down or stopping disease progression might be therapeutic. We present here an intermediate-high risk MGUS patient who has been taking curcumin for 16 years and has shown a decrease in disease markers and an increase in uninvolved immunoglobulins, adding to the body of evidence of benefit of curcumin to MGUS patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
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20. Monoclonal gammopathy of unknown significance in kidney transplanted patients: novel insights into long-term outcomes.
- Author
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Meuleman MS, Mouyabi S, Gueguen J, Vicca S, Divard G, Aubert O, Bienaimé F, Arnulf B, Anglicheau D, Bridoux F, and Cohen C
- Subjects
- Humans, Aged, Immunosuppression Therapy adverse effects, Kidney, Kidney Transplantation adverse effects, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance epidemiology, Multiple Myeloma complications
- Abstract
Background: Because of increased access to kidney transplantation in elderly subjects, the prevalence of monoclonal gammopathies of unknown significance (MGUS) in kidney transplantation (KT) is growing. However, little is known about the consequences of MGUS on long-term outcomes., Methods: We identified 70 recipients with MGUS present at transplantation (KTMG) and 114 patients with MGUS occurring after KT (DNMG), among 3059 patients who underwent a KT in two French kidney transplantation centers. We compared outcomes of KTMG with those of matched controls., Results: Baseline characteristics were similar except for an older age in KTMG compared with the DNMG group (62 vs 57 years, P = .03). Transient MGUS occurred more frequently in DNMG patients (45% vs 24%, P = .007). When compared with matched controls without MGUS, KTMG patients showed higher frequency and earlier post-transplant solid cancers (15% vs 5%, P = .04) and a trend for more bacterial infections (63% vs 48%, P = .08), without difference regarding patient and graft survival, rejection episodes or hematological complications. KTMG patients with an abnormal kappa/lambda ratio and/or severe hypogammaglobulinemia at the time of KT experienced shorter overall survival., Conclusions: MGUS detection at the time of KT is neither associated with a higher occurrence of graft rejection, nor adversely affects graft or overall survival. MGUS should not contraindicate KT. However, MGUS at the time of KT may be associated with higher risk of early neoplastic and infectious complications and warrants prolonged surveillance. Measurement of serum free light chain should be performed before transplant to refine the risk evaluation of KTMG patients and propose personalized follow-up and immunosuppression., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)
- Published
- 2023
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21. Resolution of dysglycaemia after treatment of monoclonal gammopathy of endocrine significance.
- Author
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Grant B, Ratnayake G, Williams CL, Long A, Halsall DJ, Semple RK, Cavenagh JD, Drake WM, and Church DS
- Subjects
- Male, Humans, Aged, Paraproteins, Insulin, Glucose, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance therapy, Paraproteinemias complications, Paraproteinemias therapy, Endocrine System Diseases complications, Hypoglycemia drug therapy, Hypoglycemia complications, Multiple Myeloma complications, Multiple Myeloma diagnosis
- Abstract
In very rare cases of monoclonal gammopathy, insulin-binding paraprotein can cause disabling hypoglycaemia. We report a 67-year-old man re-evaluated for hyperinsulinaemic hypoglycaemia that persisted despite distal pancreatectomy. He had no medical history of diabetes mellitus or autoimmune disease but was being monitored for an IgG kappa monoclonal gammopathy of undetermined significance. On glucose tolerance testing, hyperglycaemia occurred at 60 min (glucose 216 mg/dL) and hypoglycaemia at 300 min (52 mg/dL) concurrent with an apparent plasma insulin concentration of 52 850 pmol/L on immunoassay. Laboratory investigation revealed an IgG2 kappa with very high binding capacity but low affinity (Kd 1.43 × 10-6 mol/L) for insulin. The monoclonal gammopathy was restaged as smouldering myeloma not warranting plasma cell-directed therapy from a haematological standpoint. Plasma exchange reduced paraprotein levels and improved fasting capillary glucose concentrations. Lenalidomide was used to treat disabling hypoglycaemia, successfully depleting paraprotein and leading to resolution of symptoms., Competing Interests: Conflict of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the report. Co-author R.K.S. is on the editorial board of EJE. He was not involved in the review or editorial process for this paper, on which he is listed as an author., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.)
- Published
- 2023
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22. Waldenström's Macroglobulinemia and Cryoglobulinemic Glomerulonephritis: An Unusual Case of Monoclonal Gammopathy of Renal Significance.
- Author
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De La Flor JC, Sulca JM, Rodríguez P, Villa D, Sandoval E, Zamora R, Monroy-Condori M, Lipa R, Perez H, and Cieza M
- Subjects
- Humans, Middle Aged, Cryoglobulins, Glomerulonephritis complications, Glomerulonephritis diagnosis, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Paraproteinemias complications, Paraproteinemias diagnosis, Waldenstrom Macroglobulinemia complications, Waldenstrom Macroglobulinemia diagnosis
- Abstract
Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 °C and dissolve upon reheating. They can induce small-vessel vasculitis with renal involvement. Cryoglobulinemic glomerulonephritis is a rare manifestation that occurs in patients with monoclonal gammopathy, specifically Waldenström's macroglobulinemia. We present the case of a 52-year-old patient with a history of cutaneous vasculitis and hypothyroidism, who presented with generalized edema, moderate anemia, hypercholesterolemia, nephrotic range proteinuria of 12.69 g/day, microhematuria, arterial hypertension, and hypocomplementemia via the classical pathway, without acute kidney injury and with negative serological studies and positive cryoglobulins in the second determination. Serum and urine protein electrophoresis and immunofixation studies showed a monoclonal band of IgM and kappa light chain. Renal biopsy was consistent with cryoglobulinemic glomerulonephritis. In the context of dysproteinemia and cryoglobulinemic glomerulonephritis, bone-marrow aspiration and biopsy were performed, leading to the diagnosis of Waldenström's macroglobulinemia. Monoclonal gammopathies have been described in association with type I cryoglobulinemias. This described association is uncommon, which is why we present this case, along with a review of the literature.
- Published
- 2023
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23. Post-Transplant Monoclonal Gammopathy of Renal Significance: A Case Report.
- Author
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Movilla Echeverri C, Montilla Cosano G, Rivera Garrido C, Suñer Poblet M, and Suarez Benjumea A
- Subjects
- Humans, Kidney, Paraproteinemias complications, Paraproteinemias diagnosis, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance epidemiology, Kidney Transplantation adverse effects, Kidney Diseases etiology
- Abstract
The term monoclonal gammopathy of renal significance has been used to classify the presence of a monoclonal gammopathy or lymphoproliferative disorders that do not meet hematological criteria for myeloma but instead cause kidney damage. Mostly, post-transplant monoclonal gammopathy of renal significance occurs due to recurrent disease. In contrast, the incidence of de novo post-transplant monoclonal gammopathy of renal significance has not been established, as it is considered a rare disease, presenting a unique challenge in terms of diagnosis, management, and potential impact on graft survival. Here, we report a case of de novo monoclonal gammopathy of renal significance diagnosed after kidney transplantation and its complexity due to a concomitant chronic active antibody-mediated rejection., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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24. Gaucher disease prevalence in 600 patients affected by monoclonal gammopathy of undetermined significance.
- Author
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Giuffrida G, Markovic U, Condorelli A, Duminuco A, Calafiore V, Conticello C, Romano A, Grasso S, Riccobene C, Ragusa MTV, Esposito B, Nicolosi D, Calagna M, Nardo A, Consoli U, Uccello G, Di Giacomo V, Neri S, Cingari MR, Rodà F, Innao V, Fiumara A, Duro G, Zizzo C, and Di Raimondo F
- Subjects
- Humans, Aged, Prevalence, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance epidemiology, Gaucher Disease complications, Gaucher Disease diagnosis, Gaucher Disease epidemiology, Paraproteinemias, Anemia
- Abstract
Background: Gaucher disease (GD) is a rare autosomal recessive inherited disorder caused by the lysosomal enzyme acid β-glucosidase deficiency. Many patients experience a critical delay in the diagnosis of up to 8-10 years due to its rarity and variability in signs and symptoms, with the consultation of several specialists., Patients and Methods: This prospective observational study analyzed the prevalence of GD in 600 patients with monoclonal gammopathy of uncertain significance (MGUS) from January 2018 until February 2022., Results: The mean age of participants was 66 years, with a mean monoclonal component of 0.58 g/dL. In 433 MGUS patients with available data, anemia (hemoglobin level < 10 g/dL) was present in 31 patients (7%), and thrombocytopenia (platelet count <100.000/mm
3 ) in 24 (5.5%). Of 600 MGUS patients tested for acid β-glucosidase enzyme activity, 7 patients (1.2%) had activity below 2.5 nmol/h/mL. In comparison, GBA gene analysis was executed in 110 patients. It revealed 4 patients (0.7%) affected by GD (3 patients with compound heterozygous mutation and 1 with homozygous mutation), with a prevalence of 1 every 150 MGUS patients. Furthermore, 12 out of the remaining 106 evaluated patients (11%) were carriers of a single heterozygous mutation while having regular enzyme activity., Conclusions: The clinical heterogeneity of GD and frequent lack of awareness among physicians often lead to diagnostic delays and severe clinical manifestations. The role of MGUS in the presence of at least one clinical sign, such as low platelet count, organomegaly, bone pain, or bleeding tendency, could aid in initiating GD screening with DBS, thus reducing the period between symptom onset and the diagnosis of this rare disease., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)- Published
- 2023
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25. Multiple myeloma and its treatment contribute to increased platelet reactivity.
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Mitchell JL, Khan D, Rana RH, Kriek N, Unsworth AJ, Sage T, Bye AP, Laffan M, Shapiro S, Thakurta A, Grech H, Ramasamy K, and Gibbins JM
- Subjects
- Humans, Lenalidomide pharmacology, Lenalidomide therapeutic use, Pilot Projects, Multiple Myeloma drug therapy, Multiple Myeloma complications, Thrombosis complications, Monoclonal Gammopathy of Undetermined Significance complications
- Abstract
Multiple myeloma (MM) and its precursor states, smoldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased incidence of thrombosis, however the cause of this is unknown. Lenalidomide treatment of MM substantially improves patient survival, although significantly increases thrombotic risk by an unknown mechanism. This pilot study aimed to establish the impact of MM and its treatment with Lenalidomide on platelet function. We analyzed platelet function in MGUS, SM and MM compared to healthy controls. We report an increase in platelet reactivity in MGUS, SM, and MM where increases in fibrinogen binding, P-selectin exposure, altered receptor expression, elevated levels of aggregation and enhanced sensitivity to agonist stimulation were observed. We also demonstrate an increase in patient platelet reactivity post Lenalidomide treatment compared to pre-treatment. We show Lenalidomide treatment of platelets ex vivo increased reactivity that was associated with formation of larger thrombi at arterial shear rates but not venous shear rates. This study demonstrates a clear increase in platelet reactivity and prothrombotic potential in patients with MGUS, SM and MM which is elevated further upon treatment with Lenalidomide. Our observations suggest that more detailed studies are warranted to determine mechanisms of thrombotic complications to enable the development of new preventative strategies that specifically target platelets.
- Published
- 2023
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26. Sporadic Late-Onset Nemaline Myopathy: Current Landscape.
- Author
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Nicolau S and Milone M
- Subjects
- Adult, Humans, Delayed Diagnosis, Proteomics, Muscle, Skeletal, Myopathies, Nemaline diagnosis, Myopathies, Nemaline genetics, Myopathies, Nemaline therapy, HIV Infections complications, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance drug therapy, Monoclonal Gammopathy of Undetermined Significance pathology
- Abstract
Purpose of Review: Sporadic late-onset nemaline myopathy (SLONM) is a rare adult-onset, acquired, muscle disease that can be associated with monoclonal gammopathy or HIV infection. The pathological hallmark of SLONM is the accumulation of nemaline rods in muscle fibers. We review here current knowledge about its presentation, pathophysiology, and management., Recent Findings: SLONM usually manifests with subacutely progressive proximal and axial weakness, but it can also present with chronic progressive weakness mimicking muscular dystrophy. The pathophysiology of the disease remains poorly understood, with evidence pointing to both autoimmune mechanisms and hematological neoplasia. Recent studies have identified histological, proteomic, and transcriptomic alterations that shed light on disease mechanisms and distinguish SLONM from inherited nemaline myopathies. A majority of SLONM patients respond to intravenous immunoglobulins, chemotherapy, or hematopoietic stem cell transplant. SLONM is a treatable myopathy, although its underlying etiology and pathomechanisms remain unclear. A high degree of suspicion should be maintained for this disease to reduce diagnostic delay and treatment in SLONM and facilitate its distinction from inherited nemaline myopathies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
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27. Treatment-responsive glycogen storage myopathy in a patient with POEMS syndrome: A new monoclonal gammopathy-associated myopathy.
- Author
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Soontrapa P, Tracy JA, Gonsalves WI, and Liewluck T
- Subjects
- Female, Humans, Middle Aged, Glycogen, Vascular Endothelial Growth Factor A, POEMS Syndrome complications, POEMS Syndrome diagnosis, POEMS Syndrome therapy, Monoclonal Gammopathy of Undetermined Significance complications, Paraproteinemias complications, Muscular Diseases complications
- Abstract
Background: Myopathies associated with monoclonal gammopathy are relatively uncommon and underrecognized, treatable myopathies, and include sporadic late onset nemaline myopathy, light chain amyloid myopathy, and a recently described vacuolar myopathy with monoclonal gammopathy and stiffness (VAMGS). Herein, we report a new subtype of monoclonal gammopathy-associated myopathy (MGAM) in a polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) patient., Method: Case report., Results: A 51-year-old woman presented with a 6-month history of progressive bilateral foot drop, lower limb edema, and a 15-lb weight loss. She denied muscle stiffness. Neurologic exam showed severe distal weakness, mild proximal weakness, and length-dependent sensory deficits. Laboratory studies revealed biclonal gammopathy (IgG kappa and IgA lambda), thrombocytosis, and elevated vascular endothelial growth factor. Creatine kinase was normal. Electrodiagnostic studies identified mixed demyelinating and axonal polyradiculoneuropathy and a superimposed proximal myopathy. Gluteus medius biopsy demonstrated scattered fibers with glycogen-filled vacuoles, similar to VAMGS, with additional rare myofibers containing polyglucosan bodies. She was diagnosed with POEMS syndrome and concomitant glycogen storage myopathy. Next-generation sequencing of glycogen storage and polyglucosan body myopathy-related genes was unrevealing. Proximal weakness resolved after autologous stem cell transplant., Conclusions: This patient expands a spectrum of MGAM. Recognition of this condition and other subtypes of MGAM is of utmost important because they are treatable., (© 2023 European Academy of Neurology.)
- Published
- 2023
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28. [Monoclonal gammopathy of uncertain significance].
- Author
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Alejo E, Puertas B, and Mateos MV
- Subjects
- Humans, Middle Aged, Paraproteinemias complications, Paraproteinemias diagnosis, Paraproteinemias epidemiology, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance epidemiology, Multiple Myeloma complications
- Abstract
Monoclonal gammopathy of uncertain significance is a premalignant plasma cell neoplasm with a high prevalence in the population over 50 years of age and an annual risk of progression of 1%. Multiple recent studies have led to advances in understanding both the pathogenesis of these disorders and their risk of progression to other diseases. Patients require lifelong follow-up, and a multidisciplinary and risk-adapted approach is essential. In recent years, an increasing number of entities associated with a paraprotein, known as clinically significant monoclonal gammopathies, have been recognized., (Copyright © 2023. Published by Elsevier España, S.L.U.)
- Published
- 2023
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29. Association of monoclonal gammopathy of undetermined significance and C3 glomerulopathy.
- Author
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Ekladious A, Bhandari R, and Javaid MM
- Subjects
- Humans, Bortezomib therapeutic use, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Glomerulonephritis diagnosis, Glomerulonephritis drug therapy, Kidney Diseases, Kidney Failure, Chronic
- Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is usually an asymptomatic pre-malignant condition caused by the proliferation of clonal plasma cells. Often considered a benign condition, it has the potential to progress to malignant plasma cell or lymphoproliferative disorders. Moreover, MGUS can rarely cause glomerular disease by activating the alternative complement pathway resulting in immunoglobulin-negative C3-positive glomerulonephritis called C3 glomerulopathy. Because of its rarity, the diagnosis might not be considered by the treating physicians, leading to delayed diagnosis or misdiagnosis. Untreated C3 glomerulopathy can lead to irreversible glomerular damage and end-stage renal failure, and a high index of suspicion is essential for timely diagnosis and management. Here, we present the case of a patient with a prior diagnosis of MGUS who presented with proteinuria and microscopic haematuria and was diagnosed with C3 glomerulopathy. The patient had complete resolution of the disease after receiving treatment with a combination of dexamethasone, lenalidomide and bortezomib for the underlying MGUS., (© 2023 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)
- Published
- 2023
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30. Risk and Severity of COVID-19 Infection in Monoclonal Gammopathy of Undetermined Significance: A 3-Year Propensity Matched Cohort Study.
- Author
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Ashruf OS, Orozco Z, and Kaelber DC
- Subjects
- Humans, Cohort Studies, Retrospective Studies, Disease Progression, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance epidemiology, COVID-19 complications, COVID-19 epidemiology, Multiple Myeloma complications, Multiple Myeloma epidemiology
- Abstract
Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant disorder causing monoclonal plasma cell proliferation in bone marrow. This population is at risk of developing multiple myeloma (MM) and severe viral infections; risk factors of severe COVID-19 infection. Using TriNetX, a global platform providing data of 120 million patients, we aimed to quantify the risk and severity of COVID-19 in MGUS patients., Patients and Methods: A retrospective cohort analysis was performed using the TriNetX Global Collaborative Network. From January 20, 2020, to January 20, 2023, we identified a cohort of 58,859 MGUS patients and compared to non-MGUS patients, determined by relevant diagnosis/LOINC test codes. After 1:1 propensity score-matching, we identified COVID-19 cases to quantify risk and identify patients who had been hospitalized, ventilated/intubated, and deceased to quantify severity. Measures of association and Kaplan-Meier analysis were conducted., Results: After propensity-score matching, there were 58,668 patients in both cohorts. MGUS patients were found to be at a reduced risk of contracting COVID-19 (RR 0.88, 95% CI 0.85-0.91). MGUS patients with COVID-19 showed higher mortality risk and decreased survival time compared to the general population (HR 1.14, 95% CI 1.01-1.27). MGUS patients with COVID-19 who were hospitalized exhibited significantly decreased survival time (log-rank test, P = 0.04)., Conclusion: As COVID-19 remains a looming health concern, especially amongst vulnerable populations, our analysis emphasizes the need for adequate vaccination and treatment regimens as well as an understanding of the severity of infection in MGUS patients and justification for precautionary measures., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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31. Cryoglobulinemic Vasculitis Associated with Monoclonal Gammopathy of Undetermined Significance Developed after Sustained Virologic Response of Hepatitis C.
- Author
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Ishitoku M, Yoshida Y, Matsubara T, Fujii K, Yorishima A, Oka N, Masuda S, Sugimoto T, Mokuda S, Masaki T, and Hirata S
- Subjects
- Female, Humans, Aged, Sustained Virologic Response, Hepacivirus, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance drug therapy, Hepatitis C, Chronic complications, Hepatitis C, Chronic drug therapy, Hepatitis C complications, Hepatitis C drug therapy, Paraproteinemias complications, Cryoglobulinemia complications, Cryoglobulinemia drug therapy, Vasculitis etiology, Vasculitis complications
- Abstract
A 72-year-old woman had a history of chronic hepatitis C virus (HCV) infection previously treated with interferon to achieve a sustained virologic response. Thereafter, she developed polyarthritis and purpura of the lower extremities as well as progressive renal dysfunction with hypertension and proteinuria that had occurred in the last three months. Laboratory investigations revealed seropositivity for cryoglobulin but negative findings for HCV RNA. She was ultimately diagnosed with cryoglobulinemic glomerulonephritis complicated by monoclonal gammopathy of undetermined significance (MGUS) based on the pathological findings of the kidney and bone marrow, indicating that MGUS-induced cryoglobulinemic vasculitis may occur even after HCV elimination.
- Published
- 2023
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32. Metastatic breast cancer and monoclonal gammopathy of undetermined significance resembling multiple myeloma.
- Author
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Muehlschlegel P, Gillmore R, and Pomplun S
- Subjects
- Female, Humans, Radiography, Monoclonal Gammopathy of Undetermined Significance complications, Multiple Myeloma complications, Breast Neoplasms complications, Paraproteinemias complications
- Abstract
Radiological evidence of lytic bone lesions has a wide differential diagnosis including metastatic bone disease, multiple myeloma, primary bone cancers and infection. Here, we present the case of a woman in her 80s found to have lytic bone lesions associated with an IgA paraproteinaemia who was thus presumed to have a diagnosis of multiple myeloma. However, bone marrow biopsy results were indicative of monoclonal gammopathy of undetermined significance. She was subsequently referred to the 'carcinoma of unknown primary (CUP) team', and ultimately diagnosed with metastatic breast cancer following a repeat trephine biopsy. A range of conditions may present with lytic bone lesions and these differentials must be suitably investigated even in the presence of paraproteinaemia. Early CUP team involvement is pivotal to ensure appropriate clinical management and patient support., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
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33. Multimorbidity in patients with monoclonal gammopathy of undetermined significance.
- Author
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Epstein MM, Zhou Y, Castaneda-Avila MA, and Cohen HJ
- Subjects
- Adult, Humans, Aged, United States epidemiology, Aged, 80 and over, Multimorbidity, Disease Progression, Medicare, Monoclonal Gammopathy of Undetermined Significance epidemiology, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Multiple Myeloma diagnosis, Hypertension epidemiology, Hypertension complications
- Abstract
Monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma, is present in over 5% of adults aged 70 and older, a population with a high prevalence of multimorbidity. MGUS is often diagnosed incidentally when patients seek care for unrelated conditions. Our study sought to examine patterns of multimorbidity among MGUS patients, as overall health may impact patient care and the prioritization of MGUS surveillance. We examined patterns of comorbidities in 429 patients diagnosed with MGUS (2007-2015) and 1287 matched controls. Twenty-seven conditions were defined at diagnosis/index date using algorithms developed by the Centers for Medicare and Medicaid Chronic Conditions Warehouse. Patterns of common comorbidities were identified individually, in dyads and triads, and compared between MGUS cases and controls. We conducted a latent class analysis to identify comorbidity patterns among cases only. We also examined comorbidity patterns among a subset of 32 MGUS cases who progressed to cancer during the study period. The most common comorbidities among both MGUS cases and controls included hypertension and hyperlipidemia. Anemia (cases: 43%; controls: 16%) and chronic kidney disease (CKD; cases: 36%; controls: 18%), and dyads and triads containing those conditions, were more common among cases. Latent class analysis identified three classes of comorbidity among MGUS cases: hypertension-hyperlipidemia plus anemia and CKD (31%); low comorbidity burden (17%); and hypertension-hyperlipidemia alone (52%). The higher prevalence among cases of anemia and CKD, which may be involved in the pathogenesis of, or surveillance for, MGUS, warrants additional investigation., (© 2023 UICC.)
- Published
- 2023
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34. [Rare manifestations of monoclonal gammopathies: About two clinical cases and literature review].
- Author
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Perlot Q, Hermans C, and Vekemans MC
- Subjects
- Humans, Middle Aged, von Willebrand Factor, Paraproteinemias complications, Paraproteinemias diagnosis, von Willebrand Diseases complications, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Angioedema
- Abstract
Introduction: Monoclonal gammopathies are common over the age of 50. Patients are usually asymptomatic. However, some patients present with secondary clinical manifestations, which are now grouped under the entity « Monoclonal Gammopathy of Clinical Significance » (MGCS)., Case Report: Here, we report two rare cases of MGCS: an acquired von Willebrand syndrome (AvWS) and an acquired angioedema (AAE)., Conclusion: The discovery of a decrease in von Willebrand activity (vWF:RCo) or angioedema in a patient over 50 years of age, in the absence of a family history, should prompt a search for a hemopathy and in particular, a monoclonal gammopathy., (Copyright © 2023 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2023
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35. CCL18 promotes migration and invasion of multiple myeloma cells and is associated with poor prognosis.
- Author
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Qiao B, Chen L, Cheng Q, Wang G, Li Q, Zhang B, Li J, Hu Y, and Sun C
- Subjects
- Adult, Humans, Biomarkers, Tumor genetics, Prognosis, Chemokines, CC genetics, Multiple Myeloma genetics, Multiple Myeloma pathology, Monoclonal Gammopathy of Undetermined Significance genetics, Monoclonal Gammopathy of Undetermined Significance complications
- Abstract
CCL18 has recently been implicated in malignancies and is increasingly mentioned as a potential tumoral biomarker and furtherly a molecular target for therapeutic intervention, but its expression and clinical significance in multiple myeloma have not been explored. Serum CCL18 levels were measured by ELISA method in 254 newly diagnosed multiple myeloma (NDMM), 21 monoclonal gammopathy of undetermined significance (MGUS) and 22 healthy adults. The study suggests that the serum CCL18 level in NDMM patients was significantly higher than that in MGUS and healthy adults. High level of CCL18 were associated with advanced ISS and R-ISS stages in MM. Patients with high serum CCL18 displayed a significantly more frequent occurrence of renal impairment and hypercalcemia, while the proportion of achieving complete remission (CR) was lower. More importantly, Cox analysis identified CCL18 and LDH as independent predictors of PFS in MM patients, whereas CCL18, creatinine and LDH were independent predictors of OS. Finally, we show that CCL18 can promote migration and invasion of myeloma cell lines RPMI8226 and MM.1S. CCL18 may play a tumor-promoting role by increasing the migration and invasion abilities of myeloma cells., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2023
- Full Text
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36. Kidney Transplantation in Patients With Monoclonal Gammopathy of Renal Significance.
- Author
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Sprangers B, Hegenbart U, and Wetzels JFM
- Subjects
- Humans, Kidney, Kidney Transplantation adverse effects, Paraproteinemias complications, Kidney Diseases etiology, Kidney Failure, Chronic diagnosis, Kidney Failure, Chronic surgery, Kidney Failure, Chronic complications, Monoclonal Gammopathy of Undetermined Significance complications
- Abstract
Monoclonal gammopathy of renal significance (MGRS) defines disorders characterized by direct or indirect kidney injury caused by a monoclonal immunoglobulin produced by a B-cell or plasma-cell clone that does not meet current hematologic criteria for therapy. MGRS-associated kidney diseases are diverse and can result in the development of end-stage kidney disease. The current paradigm states that the underlying hematologic condition should be treated and in deep remission before kidney transplantation can be performed because recurrence has been reported for all MGRS-associated kidney diseases. However, we suggest that decisions regarding kidney transplantation in MGRS patients should be individualized considering many factors such as the subtype of MGRS-associated kidney disease, patient age and comorbidity, presence and risk of extrarenal complications, estimated waiting time, the availability of a living kidney donor, and previous hematological treatment and response. Thus, kidney transplantation should be considered even in treatment-naive patients, with hematological treatment initiated after successful kidney transplantation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
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37. Acquired von willebrand syndrome secondary to monoclonal gammopathy of undetermined significance: long-term remission after treatment with bortezomib.
- Author
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Saldanha A, Veiga ME, Okazaki E, Rothschild C, Martinez G, Rocha V, Orsi FA, and Villaca P
- Subjects
- Humans, Bortezomib therapeutic use, Myeloma Proteins, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance drug therapy, Multiple Myeloma complications, Multiple Myeloma drug therapy, Paraproteinemias complications, Paraproteinemias drug therapy, von Willebrand Diseases complications, von Willebrand Diseases drug therapy
- Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell disorder that can precede the diagnosis of multiple myeloma. MGUS is characterized by the presence of a monoclonal paraprotein without evidence of multiple myeloma or other lymphoplasmacytic malignancies. Even though MGUS is an asymptomatic condition that does not require management strategies other than periodic follow-up to prevent complications, secondary nonmalignant diseases may arise, requiring control of the plasma cell clone. Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that occurs in patients with no prior personal or family history of bleeding. It is associated with several other disorders, such as neoplasia, mainly hematological (including MGUS and other lymphoproliferative disorders), autoimmune, infectious and cardiac diseases. At diagnosis, patients usually present with cutaneous and mucosal bleeding, including gastrointestinal bleeding. Here, we report a case of a patient with MGUS who developed AVWS after one year of follow-up. The patient was refractory to glucocorticoids and cyclophosphamide and achieved remission only after monoclonal paraprotein was eradicated following treatment with bortezomib and dexamethasone. Our report sdemonstrates that, for refractory cases, eradication of the monoclonal paraprotein may be necessary to treat bleeding complications due to MGUS-associated AVWS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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38. Acute venous thromboembolic events in patients with monoclonal gammopathy of undetermined significance: An analysis of the National Inpatient Sample.
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Abdelhay A, Mahmoud AA, Mostafa M, Al Ali O, Gill S, and Jamshed S
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- Humans, Adolescent, Inpatients, Risk Factors, Venous Thromboembolism epidemiology, Venous Thromboembolism etiology, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance epidemiology, Venous Thrombosis epidemiology, Pulmonary Embolism
- Abstract
Background: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a premalignant plasma cell disorder which despite being clinically silent carries an increased risk of venous thromboembolism (VTE). We conducted a population-based study to investigate the risk of VTE in these patients., Methods: We utilized the National Inpatient Sample (NIS) for the year 2016 to compare the incidence of acute VTE between patients who carry the diagnosis of MGUS and those who don't. We excluded hospitalizations with age < 18 years and those that had a diagnosed lymphoma, leukemia, solid malignancy, or other plasma cell dyscrasia. We utilized the ICD-10-CM coding system to search the database for codes of VTE, MGUS, and other comorbid conditions. Multivariate logistic regression models were used for comparative analysis adjusting for demographic characteristics and comorbidities. Baseline comorbidities were described as frequencies and proportions for categorical variables and as medians with interquartile ranges for continuous variables., Results: A total of 33,115 weighted hospitalizations were included in the MGUS group. These were compared to 27,418,403 weighted hospitalizations without the diagnosis of MGUS. The MGUS group had higher odds of composite venous thromboembolism (adjusted OR 1.33, 95 % CI 1.22-1.44), deep vein thrombosis (adjusted OR 1.46, 95 % CI 1.29-1.65), and pulmonary embolism (adjusted OR 1.22, 95 % CI 1.09-1.37)., Conclusion: Patients with MGUS had increased odds of developing acute venous thromboembolism compared to patients with no history of MGUS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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39. Monoclonal gammopathy of thrombotic/thrombocytopenic significance.
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Kanack AJ, Schaefer JK, Sridharan M, Splinter NP, Kohlhagen MC, Singh B, De Lorenzo SB, Mauch EE, Hussein MA, Shaikh M, Kumar S, Wen R, Wang D, Murray D, and Padmanabhan A
- Subjects
- Humans, Monoclonal Gammopathy of Undetermined Significance complications, Paraproteinemias complications, Thrombosis etiology
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- 2023
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40. Monoclonal gammopathy of renal significance: Multidisciplinary approach to diagnosis and treatment.
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Karam S, Haidous M, Dalle IA, Dendooven A, Moukalled N, Van Craenenbroeck A, Bazarbachi A, and Sprangers B
- Subjects
- Humans, Kidney pathology, Paraproteinemias pathology, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance pathology, Kidney Diseases, Kidney Failure, Chronic
- Abstract
Monoclonal gammopathy of renal significance (MGRS) is a hemato-nephrological term referring to a heterogeneous group of kidney disorders characterized by direct or indirect kidney injury caused by a monoclonal immunoglobulin (MIg) produced by a B cell or plasma cell clone that does not meet current hematologic criteria for therapy. MGRS-associated kidney diseases are diverse and can result in the development of end stage kidney disease (ESKD). The diagnosis is typically made by nephrologists through a kidney biopsy. Many distinct pathologies have been identified and they are classified based on the site or composition of the deposited Mig, or according to histological and ultrastructural findings. Therapy is directed towards the identified underlying clonal population and treatment decisions should be coordinated between hematologists and nephrologists in a multidisciplinary fashion, depend on the type of MGRS, the degree of kidney function impairment and the risk of progression to ESKD., Competing Interests: Disclosures The authors have no conflicts of interest to report., (Copyright © 2023. Published by Elsevier B.V.)
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- 2023
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41. Obesity and myeloma: Clinical and mechanistic contributions to disease progression.
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Marques-Mourlet C, Di Iorio R, Fairfield H, and Reagan MR
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- Humans, Obesity complications, Bone Marrow pathology, Disease Progression, Tumor Microenvironment, Multiple Myeloma complications, Multiple Myeloma pathology, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance pathology
- Abstract
Obesity and obesogenic behaviors are positively associated with both monoclonal gammopathy of unknown significance (MGUS) and multiple myeloma (MM). As the only known modifiable risk factor, this association has emerged as a new potential target for MM prevention, but little is known about the mechanistic relationship of body weight with MM progression. Here we summarize epidemiological correlations between weight, body composition, and the various stages of myeloma disease progression and treatments, as well as the current understanding of the molecular contributions of obesity-induced changes in myeloma cell phenotype and signaling. Finally, we outline groundwork for the future characterization of the relationship between body weight patterns, the bone marrow microenvironment, and MM pathogenesis in animal models, which have the potential to impact our understanding of disease pathogenesis and inform MM prevention messages., Competing Interests: Author MR has research funding for the lab from SynDevRx Inc. and Oncopeptides Inc. for research projects that do not affect the research described herein. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marques-Mourlet, Di Iorio, Fairfield and Reagan.)
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- 2023
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42. Artificial intelligence-enabled screening strategy for drug repurposing in monoclonal gammopathy of undetermined significance.
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Ryu AJ, Kumar S, Dispenzieri A, Kyle RA, Rajkumar SV, and Kingsley TC
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- Humans, Artificial Intelligence, Prospective Studies, Drug Repositioning, Disease Progression, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance drug therapy, Monoclonal Gammopathy of Undetermined Significance complications, Paraproteinemias, Multiple Myeloma diagnosis
- Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is a benign hematological condition with the potential to progress to malignant conditions including multiple myeloma and Waldenstrom macroglobulinemia. Medications that modify progression risk have yet to be identified. To investigate, we leveraged machine-learning and electronic health record (EHR) data to screen for drug repurposing candidates. We extracted clinical and laboratory data from a manually curated MGUS database, containing 16,752 MGUS patients diagnosed from January 1, 2000 through December 31, 2021, prospectively maintained at Mayo Clinic. We merged this with comorbidity and medication data from the EHR. Medications were mapped to 21 drug classes of interest. The XGBoost module was then used to train a primary Cox survival model; sensitivity analyses were also performed limiting the study group to those with non-IgM MGUS and those with M-spikes >0.3 g/dl. The impact of explanatory features was quantified as hazard ratios after generating distributions using bootstrapping. Medication data were available for 12,253 patients; those without medications data were excluded. Our model achieved a good fit of the data with inverse probability of censoring weights concordance index of 0.883. The presence of multivitamins, immunosuppression, non-coronary NSAIDS, proton pump inhibitors, vitamin D supplementation, opioids, statins and beta-blockers were associated with significantly lower hazard ratio for MGUS progression in our primary model; multivitamins and non-coronary NSAIDs remained significant across both sensitivity analyses. This work could inform subsequent prospective studies, or similar studies in other disease states., (© 2023. The Author(s).)
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- 2023
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43. Surgical revascularization for quasi-moyamoya disease associated with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome: a case report and literature review.
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Kubota Y, Hanaoka Y, Koyama JI, Takahashi Y, Katoh N, Iwaya M, Fujii Y, Ogiwara T, and Horiuchi T
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- Female, Humans, Adult, Vascular Endothelial Growth Factor A, Moyamoya Disease surgery, POEMS Syndrome surgery, POEMS Syndrome complications, Monoclonal Gammopathy of Undetermined Significance complications, Stroke complications, Ischemic Stroke complications
- Abstract
POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare multisystem disease characterized by plasma cell dyscrasia and overproduction of vascular endothelial growth factor, which is related to disease activity. Recent treatment strategies have improved survival of patients suffering from this disorder; however, ischemic stroke remains a poor prognostic factor. POEMS patients with ischemic stroke frequently develop cerebral large artery stenosis/occlusion, followed by progressive stroke. Post literature review, we present an ischemic stroke case of quasi-moyamoya disease linked with this syndrome that was successfully treated with surgical revascularization. A 41-year-old woman diagnosed with POEMS syndrome developed progressive ischemic stroke due to quasi-moyamoya disease, despite decreased vascular endothelial growth factor level with lenalidomide and dexamethasone treatment. She underwent superficial temporal artery to middle cerebral artery bypass with encephalo-duro-myo-synangiosis bilaterally. The postoperative course was uneventful. Two years and five months after the stroke, neuroimaging demonstrated bypass patency, neovascularization after encephalo-duro-myo-synangiosis, and no recurrence of stroke. Our case is the first to report successful surgical revascularization for a POEMS patient. Surgical revascularization may be a useful treatment option for patients with quasi-moyamoya disease associated with POEMS syndrome, especially for those who develop refractory ischemic stroke despite reduced vascular endothelial growth factor level., Competing Interests: The authors have no conflicts of interest to disclose.
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- 2023
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44. Acquired von Willebrand syndrome in patients with monoclonal gammopathy of undetermined significance investigated using a mechanistic approach.
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Galletta E, Galvanin F, Bertomoro A, Daidone V, and Casonato A
- Subjects
- Humans, von Willebrand Factor chemistry, Phenotype, von Willebrand Diseases complications, Monoclonal Gammopathy of Undetermined Significance complications, Paraproteinemias complications
- Abstract
Background: Acquired von Willebrand syndrome (AVWS) has been reported to occur in association with monoclonal gammopathy, usually of undetermined significance (MGUS). It may present as a type 1 or type 2 von Willebrand factor (VWF) defect depending on the patient's representation of large VWF multimers., Materials and Methods: The mathematical model by Galvanin et al., already employed for studying inherited von Willebrand disease (VWD), was used to explore the pathogenic mechanisms behind MGUS-associated AVWS., Results: The patients studied showed significantly reduced VWF levels and function; an increased VWF propeptide to VWF antigen ratio; and all VWF multimers present but in reduced quantities, with the low-molecular-weight VWF forms being significantly more represented than those of higher molecular weight. Our mathematical model revealed a significantly increased VWF elimination rate constant, with values similar to those of type Vicenza VWD. An even more increased VWF proteolysis rate constant was observed, with values one order of magnitude higher than in type 2A VWD but, in contrast, no loss of large multimers. The model predicted the same elimination rate for high- and low-molecular-weight VWF multimers, but proteolysis of the high-molecular-weight forms also contributes to the pool of low-molecular-weight oligomers, which explains why they were relatively over-represented., Discussion: In MGUS-associated AVWS the increase of both clearance and proteolysis contributes to the circulating levels and multimer pattern of VWF, with a phenotype that appears to be a combination of type Vicenza and type 2A VWD. Hence, the mechanisms behind the onset of AVWS seem to differ from those of inherited VWD.
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- 2023
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45. Refractory adult-onset Still's disease complicated with monoclonal gammopathy of undetermined significance: A case report.
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Saito K, Asano T, Matsumoto H, Fujita Y, Matsuoka N, Ohkawara H, Sumichika Y, Yoshida S, Temmoku J, Yashiro-Furuya M, Sato S, Watanabe H, and Migita K
- Subjects
- Humans, Male, Middle Aged, Cytokines, Methotrexate therapeutic use, Exanthema drug therapy, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance drug therapy, Still's Disease, Adult-Onset complications, Still's Disease, Adult-Onset diagnosis, Still's Disease, Adult-Onset drug therapy
- Abstract
Rationale: Adult-onset Still's disease (AOSD) is a rare inflammatory disease characterized by a classic triad of daily spike fever, arthritis, and a typical salmon-pink rash. The involvement of inflammatory cytokines by various factors such as infection, drug, or neoplasm causes refractory AOSD., Patient Concerns: We report a 63-year-old man with a high fever, rash, hyperferritinemia, and M proteinemia. His serum levels of interleukin-6 and interleukin-18 were remarkably high at 192 and 114,250 pg/mL, respectively., Diagnosis: AOSD complicated with monoclonal gammopathy of undetermined significance was diagnosed., Interventions: After steroid pulse therapy followed by oral prednisolone, cyclosporin, methotrexate, and colchicine, serum ferritin levels temporarily declined, but secondary cytomegalovirus infections exacerbated AOSD's activity., Outcomes: Finally, after tocilizumab induction, AOSD activity was gradually suppressed over a long period., Lessons: The disease activity of AOSD is exacerbated by multiple factors, including comorbidities or infections. Clinicians need to consider that monoclonal gammopathy of undetermined significance complications might become AOSD refractory by an elevation of the inflammatory cytokines. Moreover, further prospective studies are required to confirm this result., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2022
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46. Prevalence of Monoclonal Gammopathy of Undetermined Significance in Black South African Men.
- Author
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Cicero KI, Joffe M, Patel M, Chiuzan C, Pentz A, Ruff P, Lentzsch S, Leng S, Jacobson JS, Rebbeck TR, and Neugut AI
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- Male, Humans, Prevalence, South Africa epidemiology, Immunoglobulin Light Chains, Risk Factors, Monoclonal Gammopathy of Undetermined Significance epidemiology, Monoclonal Gammopathy of Undetermined Significance complications, Paraproteinemias epidemiology, Paraproteinemias complications, Multiple Myeloma
- Abstract
Background: Both multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance (MGUS), occur twice as often within Black compared with White populations, suggesting that racial disparities lie within the development of MGUS. Nonetheless, MGUS has been studied mainly in White cohorts; the study that first described the natural history of MGUS was conducted in 97.3% White Olmsted County, Minnesota., Methods: We determined the prevalence of MGUS among 386 Black South African (SA) men >30 years at Chris Hani Baragwanath Hospital in Johannesburg. We conducted serum protein electrophoresis and free light chain quantification to define MGUS by the same criteria as the Olmsted County studies. We also investigated the association between MGUS and various clinical factors, including human immunodeficiency virus (HIV) infection and smoking., Results: We found the prevalence of MGUS to be 8.03% [95% confidence interval (CI), 5.32-10.74], nearly 1.6-fold higher than in the White Olmsted County male population. In a univariable logistic regression model, MGUS was associated with HIV status (OR, 2.39; 95% CI, 0.95-5.49), but in an adjusted model that included body mass index and cigarette use, the association was not statistically significant. Those who were current (vs. never) cigarette smokers were more likely to have MGUS in both univariable (OR, 5.60; 95% CI, 2.16-17.42) and multivariable models (OR, 4.49; 95% CI, 1.63-14.56)., Conclusions: The prevalence of MGUS in Black SA men is substantially higher than in White populations and may be associated with HIV status and cigarette use., Impact: Racial disparities in MGUS exist and may be associated with potentially modifiable risk factors., (©2022 American Association for Cancer Research.)
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- 2022
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47. Successful use of lenalidomide to treat refractory acquired von Willebrand disease associated with monoclonal gammopathy.
- Author
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Green A, Shen YP, Nelson AT, Sarode R, Ibrahim IF, Cao J, Afraz S, and Yates SG
- Subjects
- Male, Humans, Adult, von Willebrand Factor metabolism, Lenalidomide therapeutic use, von Willebrand Diseases complications, von Willebrand Diseases drug therapy, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance drug therapy, Paraproteinemias complications, Paraproteinemias drug therapy, Paraproteinemias diagnosis
- Abstract
Acquired von Willebrand syndrome (AVWS) is a rare hematologic disorder characterized by quantitative or qualitative defects of von Willebrand factor (vWF), a protein crucial for normal hemostasis. AVWS has been described in association with several pathologic entities with varied mechanisms. Among these, lymphoproliferative disorders are the most common, with monoclonal gammopathy of undetermined significance (MGUS) being the most frequently reported. AVWS in this setting is commonly associated with the development of bleeding that is clinically challenging to manage due to accelerated clearance of vWF, limiting the utility of many conventional treatment modalities such as DDAVP or vWF/FVIII. We report a case of a 43-year-old male who was sent to our institution for new-onset easy bruising and laboratories concerning for von Willebrand disease (vWD). Further diagnostic workup revealed evidence of an IgG monoclonal gammopathy and findings suggestive of vWF inhibition. Ultimately, he was found to have monoclonal gammopathy of clinical significance (MGCS)-associated AVWS refractory to conventional treatment but responsive to lenalidomide and dexamethasone. This case suggests that lenalidomide may be suitable for patients with AVWS secondary to MGCS., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2022
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48. Crystal-storing histiocytosis associated with monoclonal kappa light chain gammopathy.
- Author
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Lesesve JF and Thomas B
- Subjects
- Humans, Immunoglobulin kappa-Chains, Paraproteinemias complications, Monoclonal Gammopathy of Undetermined Significance complications, Histiocytosis etiology, Histiocytosis complications
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- 2022
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49. Monoclonal Gammopathy of Undetermined Significance.
- Author
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Gonsalves WI and Rajkumar SV
- Subjects
- Humans, Disease Progression, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance epidemiology, Paraproteinemias, Multiple Myeloma complications, Multiple Myeloma diagnosis, Multiple Myeloma epidemiology, Waldenstrom Macroglobulinemia complications, Waldenstrom Macroglobulinemia therapy
- Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is of considerable clinical importance to primary care physicians given its high prevalence in the general population. MGUS has a variable but lifelong risk for progression to hematologic cancer, such as multiple myeloma, Waldenström macroglobulinemia, or light-chain amyloidosis. In addition, MGUS has been associated with several nonmalignant yet symptomatic disorders that require therapy directed toward eliminating the monoclonal gammopathy. Thus, it is important not only to understand the essentials of diagnosing and monitoring patients with MGUS but also to recognize when to refer patients with MGUS to a specialist.
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- 2022
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50. Fibronectin glomerulopathy with monoclonal gammopathy responding to bortezomib plus dexamethasone: a case report.
- Author
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Li X, Qi X, Ma Z, and Huang W
- Subjects
- Female, Humans, Adult, Bortezomib therapeutic use, Immunoglobulin A, Antibodies, Monoclonal, Dexamethasone therapeutic use, Fibronectins, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance drug therapy
- Abstract
Background: Fibronectin glomerulopathy is a rare, familial glomerular disease characterized by mesangial fibronectin deposition in the glomeruli. It is caused by the genetic defect in fibronectin and does not involve the activation of the immune system. Therefore, glomerular immunoglobulin and complement staining is generally absent or weak. Monoclonal gammopathy (MG) is an increasing cause of renal lesion, featured by light chain (κ or λ) and/or heavy chain restriction in glomeruli. Herein, we report a case of fibronectin glomerulopathy presenting as strong IgA and C3 immunostaining in renal biopsy, concomitant with monoclonal gammopathy (monoclonal IgA κ)., Case Presentation: A 44-year-old female was admitted to our hospital for one-month pedal edema. The serum albumin of 19.6 g/l, and the 24-h urine protein was 15.092 g. Immunofixation electrophoresis displayed monoclonal IgA. The renal biopsy showed the mesangial deposits positive for IgA (3+) and C3 (3+) and also for IgG (2+), IgM (2+), and C1q (2+) IF microscopy. In addition, the staining intensity of light chain κ was slight greater than that of light chain λ. The glomerular deposits were strongly positive by FN by immuohistochemistry. The patient was treated with bortezomib, dexamethasone in combination with cyclophosphamide and gained partial remission., Conclusion: We present the first FNG patient with strong IgA and C3 immunostaining in the context of monoclonal IgA κ in the circulation. Perhaps FNG, monoclonal IgA κ and immune activation are potentially interplayed and eventually induce renal injuries., (© 2022. The Author(s).)
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- 2022
- Full Text
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