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INTRODUCTION & OBJECTIVES: This study aimed to characterize the whole phenotype of Systemic sclerosis (SSc) patients with sicca symptoms, using major salivary glands Ultrasound (SGUS) parameters, minor salivary glands biopsies (mSGB) and clinical findings, and to compare these characteristics with those from patients with Sjogren's Disease (SjD), and patients with sicca manifestations from other causes. METHODS: Sixty SSc patients fulfilling the 2013 ACR/EULAR classification criteria and with subjective self-declared sicca symptoms were consecutively recruited and had SGUS and mSGB. Fifteen SSc patients without subjective sicca symptoms and 65 patients with sicca symptoms from other causes (including 37 SjD with no SSc). RESULTS: SSc patients with subjective sicca symptoms had frequent objective clinical (up to 83 %), histological (44 % of Focus score≥1/ mm2) and US anomalies (63 % of OMERACT ≥2). 53 % patients without subjective clinical complaint also had abnormal objective tests, suggesting the existence of a sub clinical involvement of salivary glands in SSc. SjD-SSc patients had more severe glandular involvement as compared to patients with isolated SjD and isolated Sicca-SSc patients (70%, 48,6 % and 38% of patients with OMERACT ≥2 respectively) suggesting additive impact of both diseases on glandular physiology and structure. CONCLUSION: SjD-SSc overlap have more severe sicca features as compared to isolated sicca-SSc and isolated SjD, suggesting a specific impact of SSc on salivary gland physiology. Further translational studies are needed to identify the underlying pathways that could serve as therapeutic targets.
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SSc is an auto-immune disease characterized by life-threatening manifestations such as lung fibrosis or pulmonary arterial hypertension. Symptoms with a detrimental impact on quality of life are also reported and sicca syndrome (xerostomia, xeropthalmia) is present in up to 80% of patients with SSc. Sicca syndrome can occur in the absence of overlap with Sjögren's disease and recent studies highlight that fibrosis of minor and major salivary glands, directly linked to the pathogenesis of SSc, could be a major contributor of xerostomia in SSc. This narrative review provides an overview of the clinical presentation, diagnostic strategies, management and future perspectives on sicca syndrome in patients with SSc.
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Esclerodermia Sistémica , Síndrome de Sjögren , Xerostomía , Humanos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Calidad de Vida , Xerostomía/etiología , Glándulas Salivales/patologíaRESUMEN
OBJECTIVE: To define a semiquantitative classification of finger pulp blood flow (FPBF) and to evaluate whether this classification could be used to assess FPBF in healthy controls and in systemic sclerosis (SSc) patients. METHODS: Thirty controls and 86 SSc patients were consecutively included. A classification of FPBF including 5 grades (from grade 0 [no signal] to 4 [signal detected on the entire finger pulp, including the subepidermal vascular network]) was evaluated. This classification was explored in basal conditions and after hand baths in hot and cold water in controls. Its relevance was also assessed at room temperature in SSc patients. RESULTS: In controls, power Doppler ultrasonography (PDUS) of FPBF was improved after hot challenge (P = 0.024), whereas cold challenge decreased FPBF (P = 0.001). FPBF correlated with the vasodilation status assessed by the resistivity index of radial arteries (Spearman's correlation coefficient = -0.50, P = 0.0049). Grade 0 was more frequent in SSc patients than in controls (22.1% versus 3.3%; P < 0.05). In SSc patients, grade 0 was associated with severity markers of the digital vasculopathy such as digital ulcers (DUs) (current or past) (P < 0.05) or ulnar artery occlusion (P < 0.05). On the other hand, DUs were less frequent in patients with grade 4 (P < 0.05). A pathologic threshold of <2 (grade 0 or 1) was significantly associated with DUs (odds ratio 6.67 [95% confidence interval 2.31-19.21], P < 0.0001). CONCLUSION: PDUS allowed a semiquantitative evaluation of FBPF in SSc patients and controls. Further studies are warranted to validate these results in independent SSc populations and to compare PDUS to existing tools assessing digital blood flow.
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Arteriopatías Oclusivas , Esclerodermia Sistémica , Úlcera Cutánea , Humanos , Proyectos Piloto , Ultrasonografía , Esclerodermia Sistémica/complicaciones , Dedos/diagnóstico por imagen , Dedos/irrigación sanguíneaRESUMEN
BACKGROUND: to compare three existing screening algorithms of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) with the results of a multidisciplinary team (MDT) meeting from a tertiary center. METHODS: we conducted a monocentric longitudinal study from 2015 to 2018. All patients with SSc according to LeRoy's classification were eligible. Patients were excluded in the case of missing data required by any of the three screening algorithms. The algorithms were applied for each patient at inclusion. Right heart catheterization (RHC) was performed based on the MDT decision. MDT members were all blinded from the results of the three algorithms regarding RHC recommendations. The RHC recommendations of each algorithm were compared with the MDT decision, and the impact on diagnosis and management was evaluated. RESULTS: 117 SSc patients were consecutively included in the study, and 99 had follow-up data over the three-year duration of the study (10 deaths). Among the 117 patients, the MDT suggested RHC for 16 patients (14%), DETECT algorithm for 28 (24%), ASIG for 48 (41%) and ESC/ERS 2015 for 20 (17%). Among the 16 patients who had RHC, SSc-PAH was diagnosed in seven. Among patients with an initial recommendation of RHC based on at least one algorithm but not according to the MDT meeting, no SSc-PAH was diagnosed during the three-year follow-up. Results were unchanged when the new 2018 definition of PAH was applied instead of the previous definition. CONCLUSION: a MDT approach appears interesting for the screening of SSc-PAH, with a significant reduction of RHC performed in comparison with dedicated algorithms. The specific relevance of a MDT for the management and follow-up of patients with RHC recommended by existing algorithms but with no PAH warrants further studies.
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OBJECTIVES: To evaluate the diagnostic value of hand ultrasound (US) in systemic sclerosis (SSc) and to explore its relevance within a combined diagnostic approach. METHODS: 224 patients with suspected SSc were consecutively included. They all had US evaluation assessing the presence of fibrotic tenosynovitis (fibrotic TS) and ulnar artery occlusion (UAO). The final diagnosis of SSc was based on the clinical evaluation of a board of experts independently of any pre-established classification criteria. RESULTS: 166 patients were finally diagnosed as SSc according to the experts as reference standard. 62 SSc and 8 non-SSc patients had UAO (uni or bilateral) (p=0.001). 23 SSc patients and 1 non-SSc patient had US fibrotic TS (p=0.007). A US SSc-pattern (presence of UAO and/or fibrotic TS) was reported in 73 SSc patients and 9 non-SSc patients (p<0.001). UAO had an area under ROC curve (AUC) for the diagnosis of SSc of 0.618 (95%CI 0.539- 0.697); with Se=0.373 (0.304-0.449) and Sp=0.862 (0.751-0.928). Fibrotic TS had an AUC of 0.561 (0.480-0.643); with Se=0.139 (0.094-0.199) and Sp=0.983 (0.909-0.997). The US-SSc pattern had a AUC of 0.641 (0.563- 0.695), with Se=0.440 (0.367-0.516) and Sp=0.845 (0.731-0.916). A scoring system including these US parameters and items from ACR/EULAR classification criteria had an AUC of 0.979 (0.962-0.996)) and allows the substitution of capillaroscopy by US parameters with similar performances. CONCLUSIONS: The use of hand US parameters may help to refine the diagnostic strategy of SSc and their inclusion in a combined diagnostic approach could be discussed.
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Esclerodermia Localizada , Esclerodermia Sistémica , Humanos , Angioscopía Microscópica , Arteria Cubital , UltrasonografíaRESUMEN
CONTEXT: Thoracic lymphadenopathy (LA) has been identified as a key prognostic factor in interstitial lung disease (ILD) of all-cause. Crystalline silica is a risk factor of systemic sclerosis (SSc). The association of a history of crystalline silica exposure with chest high-resolution computed tomography (HRCT) features and thoracic LA are still to be determined in SSc patients. OBJECTIVES: We performed an observational study to assess the association of lifetime exposure to silica, with chest HRCT characteristics in a population of SSc patients fulfilling the 2013 ACR/EULAR classification criteria for SSc. METHODS: A specific questionnaire based on a multidisciplinary approach was used to assess occupational and non-occupational exposure to silica in 100 consecutive SSc patients. Clinical characteristics and chest HRCT at diagnosis and at the latest visit were evaluated to assess the association of silica exposure with disease characteristics. RESULTS: 16% of the overall population and 58% of men had an occupation with specific high silica exposure. A higher silica exposure score was associated with the combination of mediastinal and hilar LA on HRCT (OR=8.09, 95%CI=2.01-32.52, P = 0.002). More than 12% of the patients had a combination of mediastinal and hilar LA on HRCT. This marker of silica exposure was predictive of worsening of pulmonary involvement in univariate analysis (OR=5.86, 95%CI=1.64-20.89, P = 0.007) and multivariate analysis (OR=4.57, 95%CI =1.12-18.60, P = 0.034). CONCLUSIONS: In patients with SSc, the combination of mediastinal and hilar LA on HRCT was associated with exposure to silica and was also significantly associated with a more severe evolution of ILD.
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Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Masculino , Esclerodermia Sistémica/diagnóstico por imagen , Dióxido de Silicio/toxicidad , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To evaluate the association of ulnar artery occlusion (UAO) assessed using Doppler ultrasound (DUS) with the severity markers of systemic sclerosis (SSc). METHODS: Two hundred four unselected patients fulfilling the American College of Rheumatology/European League Against Rheumatism 2013 classification criteria for SSc were included in this cross-sectional multicenter study. All patients underwent bilateral hand DUS to evaluate the presence of UAO and clinical/paraclinical visceral evaluation according to current guidelines. Univariable and multivariable ordinal regression models were applied, grading the severity of UAO as "no UAO," "only one UAO," and "UAO on both hands," and assessing its association with clinical features of SSc. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: UAO was found in 76 patients (37.3%) and was bilateral in 49 patients (24%). UAO as an ordinal event was significantly associated with disease duration, history of fingertip ulcers, telangiectasia, higher modified Rodnan skin thickness score (MRSS), worse diffusing capacity for carbon monoxide (DLco) values, higher tricuspid jet velocity, late capillaroscopic pattern, and positivity for anticentromere antibodies (ACAs) (univariable analysis). In the adjusted multivariable ordinal model, UAO was less frequent in women (OR 0.35 [95% CI 0.15-0.83], P = 0.017) and in patients receiving steroids (OR 0.24 [95% CI 0.09-0.62], P = 0.0034). In multivariable analyses, significant association with UAO was retained for history of fingertip ulcers (OR 2.55 [95% CI 1.24-5.21], P = 0.011), higher MRSS (OR 1.65 [95% CI 1.06-2.56], P =0.025), lower DLco values (OR 0.85 [95% CI 0.78-0.94], P = 0.0015), and ACA positivity (OR 2.89 [95% CI 1.36-6.11], P = 0.0056). CONCLUSION: UAO may represent a relevant severity marker of vasculopathy in SSc. Its predictive value for the onset of severe vascular manifestations such as pulmonary arterial hypertension, and its association with mortality, remain to be determined in longitudinal studies.
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Arteriopatías Oclusivas/diagnóstico por imagen , Esclerodermia Sistémica/diagnóstico por imagen , Arteria Cubital/diagnóstico por imagen , Anciano , Anticuerpos Antinucleares/inmunología , Arteriopatías Oclusivas/etiología , Estudios Transversales , Femenino , Dedos , Humanos , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Capacidad de Difusión Pulmonar , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/inmunología , Esclerodermia Sistémica/fisiopatología , Índice de Severidad de la Enfermedad , Úlcera Cutánea/etiología , Telangiectasia/etiología , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/etiología , Ultrasonografía DopplerRESUMEN
A defect in the apoptotic cell clearance (efferocytosis) by phagocytic cells may participate in autoimmunity and chronic inflammation. The mechanisms leading to the emergence of autoimmunity in systemic sclerosis (SSc) are still to be determined. In this study, the efferocytosis capacities of blood monocyte-derived macrophages (MDM) from patients with SSc were evaluated. Blood monocytes obtained from patients with SSc and healthy donors (HD) were differentiated in vitro into macrophages. The capacities of MDM to engulf CFSE+ apoptotic Jurkat human T lymphocytes were compared between SSc MDM and HD using flow cytometry. The expression of classical engulfing receptors in SSc MDM and HD MDM was also evaluated and their involvement in the modulation of efferocytosis was confirmed using a siRNA approach. The mean phagocytic index (PI) reflecting efferocytosis capacities of SSc MDM (PI = 19.3 ± 3.0; n = 21) was significantly decreased in comparison with the PI of HD MDM (PI = 35.9 ± 3.0; n = 31; P < 0.001). In comparison with HD, SSc MDM exhibited a downregulated expression of scavenger receptor (SR)-B1, SR-A1 and integrin ß5 (ITGß5). In HD MDM, the extinction of these receptors was followed by a reduction of efferocytosis only for the repression of ITGß5, suggesting a possible selective role of this integrin in the impaired efferocytosis observed in SSc. As efferocytosis may be at the crossroads of inflammation, autoimmunity and fibrosis, in showing impaired efferocytosis capacities of blood MDM in SSc, our study offers new pathogenesis considerations for the involvement of macrophages in the autoimmune processes driving this disorder.
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Macrófagos/inmunología , Fagocitosis/inmunología , Esclerodermia Sistémica/inmunología , Estudios de Casos y Controles , Humanos , Cadenas beta de Integrinas/metabolismo , Macrófagos/metabolismo , Monocitos/inmunología , Monocitos/metabolismo , Receptores Depuradores de Clase B/metabolismo , Factores de Empalme Serina-Arginina/metabolismoRESUMEN
Systemic sclerosis is a rare connective tissue disease characterised by a wide range of clinical manifestations. Compared with previous sets of criteria, the 2013 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification of systemic sclerosis encompasses a broader and more relevant spectrum of the condition. Nonetheless, clinical and prognostic heterogeneity persists among patients fulfilling these criteria. The next task in the classification of systemic sclerosis is the development of new subset criteria that can successfully identify subgroups of patients with distinct prognostic or pathophysiological features. In this Viewpoint we describe the history of systemic sclerosis over the past century with the objective of highlighting the effect of previous nosological debates on efforts to understand and manage this disorder. Rather than seeking to present a systematic review of possible subgrouping for systemic sclerosis in relation to prognosis, we aim to clarify how nosological considerations have influenced our understanding of the cause and prognosis of this so-called idiopathic rheumatological disorder and how aetiological, prognostic, and pathophysiological hypotheses have helped to describe clusters within the disease. By reflecting on past nosological debates and endeavours, we identify challenges for the current initiative to develop a new subgrouping of systemic sclerosis.
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Objectives: To characterize hand synovial manifestations assessed by power Doppler ultrasonography (PDUS) in a cohort of unselected patients fulfilling the 2013 ACR/EULAR classification criteria for SSc and to evaluate the associations of these synovial manifestations with the main general clinical and biological features of SSc. Methods: One hundred and three SSc patients were consecutively included and underwent PDUS evaluation of both hands assessing synovial and tenosynovial manifestations according to the OMERACT definitions. Clinical, biological and immunological SSc characteristics were recorded at the same time. Results: Thirty-three patients (32%) had ultrasonographic synovial/tenosynovial involvement. The two main PDUS features were Doppler-positive/inflammatory synovitis (n = 18, 17.5%) and sclerosing tenosynovitis (TS) (n = 19, 18.4%). Inflammatory synovitis was more frequent in the wrist and MCP joints. Sclerosing TS was more frequent in men [odds ratio (OR) = 6.32, 95% CI: 2.17, 18.41; P = 0.001] and was associated with anti-RNA polymerase III antibodies (OR = 10.93, 95% CI: 1.84, 65.12; P = 0.01), diffuse SSc (OR = 18.24, 95% CI: 4.80, 69.32; P < 0.0001), interstitial lung disease (OR = 6.09, 95% CI: 1.86, 19.98; P = 0.001) and inflammatory arthralgia (OR = 14.64, 95% CI: 2.58, 83.10; P = 0.002). Inflammatory TS or synovitis were associated with CRP levels >5 mg/l (OR = 5.50, 95% CI: 1.81, 16.70; P = 0.001), pericarditis (OR = 7.81, 95% CI: 1.58, 38.71; P = 0.017) and inflammatory arthralgia (OR = 15.96, 95% CI: 2.80, 91.02; P = 0.002). Inflammatory synovitis and sclerosing TS were not significantly associated within an individual patient (OR = 2.77, 95% CI: 0.88, 8.70; P > 0.05). Conclusions: Ultrasonographic synovial involvement is frequent in patients fulfilling the 2013 ACR/EULAR classification criteria and PDUS may have a part to play in a more accurate and precise description of musculoskeletal manifestations of the disease, especially as the question of a treat-to-target approach is arising for SSc.
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Esclerodermia Sistémica/diagnóstico por imagen , Membrana Sinovial/diagnóstico por imagen , Sinovitis/diagnóstico por imagen , Tenosinovitis/diagnóstico por imagen , Adulto , Anciano , Estudios Transversales , Femenino , Articulaciones de la Mano/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Ultrasonografía Doppler , Articulación de la Muñeca/diagnóstico por imagenRESUMEN
OBJECTIVE: To compare microvascular damages on nailfold capillaroscopy (NFC) with macrovascular manifestations evaluated by hand power Doppler ultrasonography (PDUS) in systemic sclerosis (SSc) patients, and to assess the associations of these damages with the main digital manifestations of the disease: digital ulcers, acroosteolysis, and calcinosis. METHODS: NFC, hand radiographs, and PDUS were systematically performed in 64 unselected SSc patients. PDUS evaluation with assessment of ulnar artery occlusion (UAO) and finger pulp blood flow (FPBF) were performed blinded for the results of radiographs and NFC. RESULTS: UAO and pathologic FPBF were associated with severe capillary loss (<4 capillaries/mm) on NFC (odds ratio [OR] 4.04 [95% confidence interval (95% CI) 1.23-13.29]; P < 0.05, and OR 3.38 [95% CI 1.03-11.05]; P < 0.05, respectively). Digital ulcer history was associated with UAO (OR 10.71 [95% CI 3.36-34.13]; P < 0.0001), pathologic FPBF (OR 7.67 [95% CI 2.52-23.28]; P < 0.0001), late NFC pattern (OR 6.33 [95% CI 2.03-19.68]; P = 0.001), and severe capillary loss (OR 8.52 [95% CI 2.15-33.78]; P = 0.001). Acroosteolysis was also associated with UAO (OR 15.83 [95% CI 3.95-63.54]; P < 0.0001), pathologic FPBF (OR 5.52 [95% CI 1.71-17.90]; P = 0.003), late NFC pattern (OR 6.86 [95% CI 2.18-21.53]; P = 0.001), and severe capillary loss (OR 7.20 [95% CI 2.16-24.02]; P = 0.001). Calcinosis on radiographs was associated with late NFC pattern (OR 5.41 [95% CI 1.82-16.12]; P = 0.002), severe capillary loss (OR 12.69 [95% CI 3.14-51.26]; P < 0.0001), and UAO (OR 3.19 [95% CI 1.14-8.92]; P = 0.025). Combination of UAO and severe capillary loss in the same patient was especially associated with digital ulcer history (OR 18.60 [95% CI 2.24-154.34]; P = 0.001) and acroosteolysis (OR 10.83 [95% CI 2.56-45.88]; P = 0.001). CONCLUSION: Microvascular damages evaluated by NFC and macrovascular features like UAO assessed by PDUS show concordant associations with the main digital manifestations of the disease.
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Angioscopía Microscópica , Esclerodermia Sistémica/diagnóstico por imagen , Ultrasonografía , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: As intravenous immunoglobulins (IVIG) exhibit immunomodulatory and antifibrotic properties, they may be a relevant treatment for systemic sclerosis (SSc). The objectives of this work were thus to report on the efficacy and safety of IVIG in a population of SSc patients and to review the available literature. METHODS: 46 patients from 19 French centers were retrospectively recruited. They were included if they had a diagnosis of SSc and received at least 1 IVIG infusion at a dosage >1g/kg/cycle. Relevant data collected at IVIG discontinuation were compared to those collected at IVIG initiation. A comprehensive literature review was performed. RESULTS: We observed a significant improvement of muscle pain (74% vs. 20%, p<0.0001), muscle weakness (45% vs. 21%, p=0.01), joint pain (44% vs. 19%, p=0.02), CK levels (1069±1552UI vs. 288±449UI, p<0.0001) and CRP levels (13.1±17.6mg/L vs. 9.2±16.6mg/L, p=0.001). We also noted a trend for an improvement of gastro-esophageal reflux disease (68% vs. 53%, p=0.06) and bowel symptoms (42% vs. 27%, p=0.06). Skin and cardiorespiratory involvements remained stable. Finally, corticosteroid daily dose was significantly lower by the end of treatment (13.0±11.6mg/day vs. 8.9±10.4mg/day, p=0.01). Only two severe adverse events were reported (one case of deep vein thrombosis and one case of diffuse edematous syndrome). CONCLUSION: Our work suggests that IVIG are a safe therapeutic option that may be effective in improving musculoskeletal involvement, systemic inflammation, digestive tract symptoms and could be corticosteroid sparing.
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Inmunoglobulinas Intravenosas/uso terapéutico , Esclerodermia Sistémica/tratamiento farmacológico , Estudios de Cohortes , Femenino , Francia , Humanos , Inmunoglobulinas Intravenosas/farmacología , Persona de Mediana Edad , Estudios Retrospectivos , Esclerodermia Sistémica/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the relevance of power Doppler ultrasonography (PDUS) as a predictive tool of 1-year digital ulcer (DU) occurrence in systemic sclerosis (SSc). METHODS: A total of 55 SSc patients and 19 controls underwent PDUS of both hands to evaluate the prevalence of ulnar artery occlusion (UAO) at baseline. Finger pulp blood flow (FPBF) of the third and fourth fingers was also assessed and considered as pathologic if a defect of the Doppler signal on a finger pulp was observed. All patients were clinically re-evaluated 6 and 12 months later and new ischemic DU occurrences in the meantime were retrospectively recorded. Patients were also asked to call if new DUs occurred between consultations. RESULTS: PDUS parameters were normal in all controls. The prevalence of UAO was 36.4% and was bilateral in 70% of the SSc cases. A total of 56.4% of SSc patients had a pathologic FPBF. UAO and pathologic FPBF were associated with a history of multiple DU episodes (odds ratio [OR] 8.98 [95% confidence interval (95% CI) 2.52-32.01], P < 0.001, and OR 4.69 [95% CI 1.30-16.93], P = 0.014, respectively) and the occurrence of new DUs during the followup in the univariable model (OR 8.73 [95% CI 2.00-38.16], P = 0.005, and OR 12.65 [95% CI 1.50-106.77], P = 0.005, respectively). The association of UAO and pathologic FPBF in the same patient was a predictive factor of new DUs in the multivariable analysis (P = 0.015). CONCLUSION: This study suggests that UAO and pathologic FPBF are associated with a history of multiple DUs and are predictors of new ischemic DUs. These parameters could be used as prognostic factors and considered in further studies evaluating DU treatment strategies.
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Arteriopatías Oclusivas/diagnóstico por imagen , Dedos/irrigación sanguínea , Isquemia/diagnóstico por imagen , Esclerodermia Sistémica/epidemiología , Úlcera/diagnóstico por imagen , Arteria Cubital/diagnóstico por imagen , Ultrasonografía Doppler , Adulto , Anciano , Arteriopatías Oclusivas/epidemiología , Arteriopatías Oclusivas/fisiopatología , Distribución de Chi-Cuadrado , Constricción Patológica , Femenino , Francia/epidemiología , Humanos , Isquemia/epidemiología , Isquemia/fisiopatología , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Proyectos Piloto , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Estudios Prospectivos , Flujo Sanguíneo Regional , Estudios Retrospectivos , Factores de Riesgo , Esclerodermia Sistémica/diagnóstico , Factores de Tiempo , Úlcera/epidemiología , Úlcera/fisiopatología , Arteria Cubital/fisiopatologíaRESUMEN
Systemic manifestations of monoclonal gammopathies (MG) are rare but extremely varied. This general review focuses on the hyperviscosity syndrome, neurological disorders, skin changes, the POEMS syndrome, and biological manifestations, with the exception of amyloidosis AL and cryoglobulinemia. The hyperviscosity syndrome usually involves a combination of general, hemorrhagic, ocular and central neurological disorders. The principal neurological manifestations are peripheral neuropathies, mainly due to IgM with anti-MAG activity. Skin disorders include overload dermatoses (xanthomatosis, mucinosis), neutrophilic dermatosis, urticaria, edema and the AESOP syndrome. The POEMS syndrome classically consists of polyneuropathy, organomegaly, endocrinopathy, monoclonal plasmocyte proliferation, and cutaneous manifestations. MG interference with assay methods can lead to false hyponatremia, hypoglycemia, hyperbilirubinemia, hypercalcemia and hypertransferrinemia. These systemic manifestations can reveal classical MG-related disorders such as monoclonal gammopathy of undetermined significance (MGUS), solitary plasmocytoma, multiple myeloma, and Waldenstrom's disease. They are due either to the chemicophysical properties of the monoclonal immunoglobulin, or to its antibody activity (especially against autoantigens), with potential therapeutic implications.
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Paraproteinemias/complicaciones , Paraproteinemias/diagnóstico , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/etiología , Enfermedades Hematológicas/terapia , Humanos , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/terapia , Paraproteinemias/terapia , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/etiología , Enfermedades de la Piel/terapiaRESUMEN
INTRODUCTION: Monoclonal gammopathies of undetermined significance (MGUS) occur in up to 1% of persons aged 50 years or older. The risk of its progression to multiple myeloma or related disorders is also approximately 1% per year. OBJECTIVES: Our study had two aims: to describe the risk of malignant progression of patients examined in our center for MGUS, and to identify predictors of this malignant progression. METHODS: We retrospectively reviewed the medical records of patients with MGUS seen in our center from 1980 through 1995. Information about progression came either from the medical file or from responses to questionnaires sent to patients' general practitioners. RESULTS: The study included 190 patients. Median follow-up was 84 months (range: 12-240 months). MGUS remained stable for 128 patients (67.37%), whose median follow-up was 96 months. Malignant transformations occurred in 41 patients (21.58%). The median interval from diagnosis of MGUS to diagnosis of a lymphoplasma cell proliferative disorder was 49 months. The cumulative probability of progression was 13.05% at 5 years and 25.14% at 10 years. The initial concentration of serum monoclonal protein was a significant predictor of progression (threshold value: 15 g/L). DISCUSSION: The cumulative probability of progression in our study is higher than that observed elsewhere. Our results may well be biased by the short follow-up period and selective referrals. CONCLUSION: The initial concentration of serum monoclonal protein is a significant predictor of malignant progression of MGUS.
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Paraproteinemias/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Neoplasias Hematológicas/epidemiología , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Paraproteinemias/diagnóstico , Paraproteinemias/inmunología , Selección de Paciente , Estudios Retrospectivos , Factores de TiempoRESUMEN
Iron deficiency is the most widespread nutritional disorder in the world, affecting an estimated 1.2 billion people. Its prevalence is particularly high in developing countries (Africa, Asia, South America), but iron deficiency remains a public health problem in industrialised countries. Three successive stages of iron deficiency can be distinguished: iron store depletion, iron-deficient erythropoesis and iron-deficiency anemia. Investigations of iron deficiency should take into account the clinical background. In groups at risk (infants and children, women of childbearing age, pregnant women), management is limited to nutritional inquiries, gynecological examination, and oral iron supplementation. In men and post-menopausal women, iron deficiency is assumed to result from occult gastrointestinal bleeding, and this may necessitate upper and lower gastrointestinal endoscopy. Benign lesions are more frequently found in the upper digestive tract than in the lower digestive tract. When these investigations are negative and iron supplementation is unsuccessful, video-capsule endoscopy is recommended. Oral iron treatment is based on ferrous salts (200 mg/d). The duration of treatment depends on the severity of iron deficiency, ranging from three months for iron store depletion and iron-deficient erythropeisis to six months for iron-deficiency anemia.
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Anemia Ferropénica/etiología , Anemia Ferropénica/terapia , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/epidemiología , HumanosRESUMEN
We report two cases of spinal cord compression by AL amyloid deposits in the setting of multiple myeloma. The first patient, a 57 year old man, had a surgical procedure late in his course, when his neurological status worsened despite medical treatment. The second patient, a 61 year old man, had surgical treatment as soon as vertebral body collapse and epiduritis were diagnosed and spinal amyloidosis revealed a non secretory myeloma. Neurological recovery was significant in both cases and neither developed manifestations of systemic amyloidosis 4 years later.