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      Patologías cutáneas asociadas a gammapatías monoclonales: ¿qué sabemos hasta ahora? Translated title: Dermatological manifestations of monoclonal gammopathies

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          Translated abstract

          Monoclonal gammopathies of uncertain significance (MGUS) correspond to pre-malignant hematological disorders characterized by the production of a monoclonal protein and infiltration of less than 10% of the bone marrow by plasma cells. Its importance lies in the risk of progression to malignant disorders and in the association with different renal, neurological and skin manifestations. There are pathophysiological mechanisms that support a causal relationship between monoclonal gammopathies (MGs) and different skin diseases, such as type I cryoglobulinemia (CG), primary systemic amyloidosis (PSA) or necrobiotic xanthogranuloma (NXG). However, there is a group of skin diseases associated with MGs whose pathogenesis has not been elucidated. In this context, the role of the dermatologist is crucial in the suspicion of different haematological disorders based on skin manifestations and in the multidisciplinary treatment of these patients. In this article, we carry out an exhaustive review of the literature published in this area and propose a screening algorithm for MGs in patients with specific skin diseases.

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          Most cited references56

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          International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma.

          This International Myeloma Working Group consensus updates the disease definition of multiple myeloma to include validated biomarkers in addition to existing requirements of attributable CRAB features (hypercalcaemia, renal failure, anaemia, and bone lesions). These changes are based on the identification of biomarkers associated with near inevitable development of CRAB features in patients who would otherwise be regarded as having smouldering multiple myeloma. A delay in application of the label of multiple myeloma and postponement of therapy could be detrimental to these patients. In addition to this change, we clarify and update the underlying laboratory and radiographic variables that fulfil the criteria for the presence of myeloma-defining CRAB features, and the histological and monoclonal protein requirements for the disease diagnosis. Finally, we provide specific metrics that new biomarkers should meet for inclusion in the disease definition. The International Myeloma Working Group recommends the implementation of these criteria in routine practice and in future clinical trials, and recommends that future studies analyse any differences in outcome that might occur as a result of the new disease definition.
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            Systemic amyloidosis.

            Tissue deposition of protein fibrils causes a group of rare diseases called systemic amyloidoses. This Seminar focuses on changes in their epidemiology, the current approach to diagnosis, and advances in treatment. Systemic light chain (AL) amyloidosis is the most common of these conditions, but wild-type transthyretin cardiac amyloidosis (ATTRwt) is increasingly being diagnosed. Typing of amyloid fibrils, a critical determinant of therapy, has improved with the wide availability of laser capture and mass spectrometry from fixed histological tissue sections. Specific and accurate evaluation of cardiac amyloidosis is now possible using cardiac magnetic resonance imaging and cardiac repurposing of bone scintigraphy tracers. Survival in AL amyloidosis has improved markedly as novel chemotherapy agents have become available, but challenges remain in advanced disease. Early diagnosis, a key to better outcomes, still remains elusive. Broadening the amyloid-specific therapeutic landscape to include RNA inhibitors, fibril formation stabilisers and inhibitors, and immunotherapeutic targeting of amyloid deposits holds promise to transform outcomes in systemic amyloidoses.
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              Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance

              BACKGROUND Monoclonal gammopathy of undetermined significance (MGUS) occurs in approximately 3% of persons 50 years of age or older. METHODS We studied 1384 patients who were residing in southeastern Minnesota and in whom MGUS was diagnosed at the Mayo Clinic in the period from 1960 through 1994; the median follow-up was 34.1 years (range, 0.0 to 43.6). The primary end point was progression to multiple myeloma or another plasma-cell or lymphoid disorder. RESULTS During 14,130 person-years of follow-up, MGUS progressed in 147 patients (11%), a rate that was 6.5 times (95% confidence interval [CI], 5.5 to 7.7) as high as the rate in the control population. The risk of progression without accounting for death due to competing causes was 10% at 10 years, 18% at 20 years, 28% at 30 years, 36% at 35 years, and 36% at 40 years. Among patients with IgM MGUS, the presence of two adverse risk factors — namely, an abnormal serum free light-chain ratio (ratio of kappa to lambda free light chains) and a high serum monoclonal protein (M protein) level (≥1.5 g per deciliter) — was associated with a risk of progression at 20 years of 55%, as compared with 41% among patients who had one adverse risk factor and 19% among patients who had neither risk factor. Among patients with non-IgM MGUS, the risk of progression at 20 years was 30% among those who had the two risk factors, 20% among those who had one risk factor, and 7% among those who had neither risk factor. Patients with MGUS had shorter survival than was expected in the control population of Minnesota residents of matched age and sex (median, 8.1 vs. 12.4 years; P<0.001). CONCLUSIONS Significant differences were noted in the risk of progression between patients with IgM MGUS and those with non-IgM MGUS. Overall survival was shorter among patients with MGUS than was expected in a matched control population. (Funded by the National Cancer Institute.)
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                Author and article information

                Journal
                rmc
                Revista médica de Chile
                Rev. méd. Chile
                Sociedad Médica de Santiago (Santiago, , Chile )
                0034-9887
                May 2021
                : 149
                : 5
                : 747-757
                Affiliations
                [1] Santiago Santiago de Chile orgnamePontificia Universidad Católica de Chile orgdiv1Escuela de Medicina orgdiv2Departamento de Dermatología Chile
                [2] Santiago Santiago de Chile orgnamePontificia Universidad Católica de Chile orgdiv1Escuela de Medicina orgdiv2Departamento de Hematología-Oncología Chile
                [4] Santiago Santiago de Chile orgnamePontificia Universidad Católica de Chile orgdiv1Escuela de Medicina Chile
                [3] Santiago Santiago de Chile orgnamePontificia Universidad Católica de Chile orgdiv1Escuela de Medicina orgdiv2Departamento de Medicina Interna Chile
                Article
                S0034-98872021000500747 S0034-9887(21)14900500747
                10.4067/s0034-98872021000500747
                2dc2951e-838b-4827-96ad-c977aaaed406

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 23 November 2021
                : 06 September 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 56, Pages: 11
                Product

                SciELO Chile

                Categories
                ARTICULOS DE REVISION

                Skin Diseases,Paraproteinemias,Monoclonal Gammopathy of Undetermined Significance

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