RESUMEN
Systemic sclerosis (SSc) is a clinically heterogeneous autoimmune disease characterized by mutually exclusive autoantibodies directed against distinct nuclear antigens. We examined HLA associations in SSc and its autoantibody subsets in a large, newly recruited African American (AA) cohort and among European Americans (EA). In the AA population, the African ancestry-predominant HLA-DRB1*08:04 and HLA-DRB1*11:02 alleles were associated with overall SSc risk, and the HLA-DRB1*08:04 allele was strongly associated with the severe antifibrillarin (AFA) antibody subset of SSc (odds ratio = 7.4). These African ancestry-predominant alleles may help explain the increased frequency and severity of SSc among the AA population. In the EA population, the HLA-DPB1*13:01 and HLA-DRB1*07:01 alleles were more strongly associated with antitopoisomerase (ATA) and anticentromere antibody-positive subsets of SSc, respectively, than with overall SSc risk, emphasizing the importance of HLA in defining autoantibody subtypes. The association of the HLA-DPB1*13:01 allele with the ATA+ subset of SSc in both AA and EA patients demonstrated a transancestry effect. A direct correlation between SSc prevalence and HLA-DPB1*13:01 allele frequency in multiple populations was observed (r = 0.98, P = 3 × 10-6). Conditional analysis in the autoantibody subsets of SSc revealed several associated amino acid residues, mostly in the peptide-binding groove of the class II HLA molecules. Using HLA α/ß allelic heterodimers, we bioinformatically predicted immunodominant peptides of topoisomerase 1, fibrillarin, and centromere protein A and discovered that they are homologous to viral protein sequences from the Mimiviridae and Phycodnaviridae families. Taken together, these data suggest a possible link between HLA alleles, autoantibodies, and environmental triggers in the pathogenesis of SSc.
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Autoanticuerpos/inmunología , Autoantígenos/genética , Antígenos HLA/genética , Imitación Molecular/inmunología , Esclerodermia Sistémica/genética , Negro o Afroamericano/genética , Alelos , Secuencia de Aminoácidos/genética , Antígenos Virales/genética , Antígenos Virales/inmunología , Autoantígenos/inmunología , Biología Computacional , Conjuntos de Datos como Asunto , Femenino , Predisposición Genética a la Enfermedad , Antígenos HLA/inmunología , Humanos , Masculino , Mimiviridae/inmunología , Phycodnaviridae/inmunología , Estructura Secundaria de Proteína/genética , Medición de Riesgo , Esclerodermia Sistémica/epidemiología , Esclerodermia Sistémica/inmunología , Homología de Secuencia de Aminoácido , Población Blanca/genéticaRESUMEN
PURPOSE OF REVIEW: Systemic sclerosis is a debilitating rheumatic disease with high morbidity and mortality. This review attempts to provide the most recent update on mortality and survival and their determinants in systemic sclerosis (SSc). RECENT FINDINGS: SSc remains an uncommon rheumatic disease with high mortality. There have been attempts to devise more comprehensive but simpler scoring systems to prognosticate survival in SSc, which will influence triaging of patients and guide the utilization of aggressive treatment strategies. SUMMARY: Updated literature review on mortality and survival in SSc has confirmed its high-case fatality but a slowly improving survival profile over time. It identifies some gaps in knowledge, especially in regards to ethnic differences.
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Esclerodermia Sistémica/mortalidad , Salud Global , Humanos , Morbilidad/tendencias , Tasa de Supervivencia/tendenciasRESUMEN
Objectives: To evaluate the hospitalizations and define the factors associated with in-hospital mortality, longer length of stay (LOS) and higher hospital costs among SSc hospitalizations. Methods: We used the National Inpatient Sample (2012-13) to identify adult hospitalizations with SSc, excluding patients with concomitant diagnosis of RA and systemic lupus. We calculated rates of hospitalization, in-hospital mortality, LOS and hospital costs. Factors associated with these outcomes were evaluated by univariate and backward stepwise multivariate logistic regression. Results: There were 9731 hospitalizations in the sample representing an estimated 48 655 hospitalizations nationwide with SSc (0.09%), and the inpatient mortality rate was 5%. Patients were predominantly older (mean age 63.2 years), female (82.2%) and Caucasian (71.5%). Infections were the most common primary diagnoses among SSc hospitalizations (17.4%) and among those who died (32.7%). Acute renal failure [adjusted odds ratio (aOR) = 4.3, 95% CI: 3.3, 5.6] and aspiration (aOR= 3.5, 95% CI: 2.5, 4.9) were strongly associated with in-hospital mortality. The median (interquartile range) LOS was 4 days (-2, 7), and the median (interquartile range) cost was $8885 (-5169, 15921). While hospital from the West region, acute renal failure, acute bowel obstruction and aspiration (aOR > 2.0 with P < 0.0001 for all) seem to predict higher cost of hospitalization, pulmonary fibrosis, myositis and any type of infection in addition to the same factors, except the West region (aOR > 2.0 with P < 0.0001 for all), were associated with longer LOS. Conclusion: Infections are currently the most common diagnoses among SSc hospitalizations and in-hospital deaths. This emphasizes the importance of being vigilant in prevention and early treatment of infections in SSc patients.
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Costos de Hospital/tendencias , Hospitalización/economía , Pacientes Internos/estadística & datos numéricos , Tiempo de Internación/tendencias , Sistema de Registros , Esclerodermia Sistémica/mortalidad , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Mortalidad Hospitalaria/tendencias , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Esclerodermia Sistémica/economía , Esclerodermia Sistémica/terapia , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Scleroderma (systemic sclerosis) is an autoimmune rheumatic disorder that is characterized by fibrosis, vascular dysfunction, and autoantibody production that involves most visceral organs. It is characterized by a high morbidity and mortality rate, mainly due to disease-related complications. Epidemiological data describing mortality and survival in this population have been based on both population and observational studies. Multiple clinical and non-clinical factors have been found to predict higher likelihood of death among thepatients. Here, we do an extensive review of the available literature, utilizing the PubMed database, to describe scleroderma and non-scleroderma related determinants of mortality in this population. We found that even though the mortality among the general population has declined, scleroderma continues to carry a very high morbidity and mortality rate, however we have made some slow progress in improving the mortality among scleroderma patients over the last few decades.
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Esclerodermia Sistémica/mortalidad , Fibrosis , Humanos , Morbilidad/tendencias , Esclerodermia Localizada/mortalidad , Esclerodermia Sistémica/complicacionesRESUMEN
OBJECTIVES: To assess the utility of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) in detecting and monitoring pulmonary hypertension (PH) in systemic sclerosis (SSc). METHODS: PHAROS is a multicenter prospective cohort of SSc patients at high risk for developing pulmonary arterial hypertension (SSc-AR-PAH) or with a definitive diagnosis of SSc-PH. We evaluated 1) the sensitivity and specificity of BNP≥64 and NT-proBNP≥210 pg/mL for the detection of SSc-PAH and/ or SSc-PH in the SSc-AR-PAH population; 2) baseline and longitudinal BNP and NT-proBNP levels as predictors of progression to SSc-PAH and/or SSc-PH; 3) baseline BNP≥180, NT-proBNP≥553 pg/mL, and longitudinal changes in BNP and NT-proBNP as predictors of mortality in SSc-PH diagnosed patients. RESULTS: 172 SSc-PH and 157 SSc-AR- PAH patients had natriuretic peptide levels available. Median BNP and NT-proBNP were significantly higher in the SSc-PH versus SSc-AR-PAH group. The sensitivity and specificity for SSc-PAH detection using baseline BNP≥64 pg/mL was 71% and 59%; and for NT-proBNP≥210 pg/mL, 73% and 78%. NT-proBNP showed stronger correlations with haemodynamic indicators of right ventricular dysfunction than BNP. Baseline creatinine, RVSP > 40 mmHg, and FVC%:DLco% ratio ≥1.8 were associated with progression from SSc-AR-PAH to SSc-PH but no association with individual or combined baseline BNP and NT-proBNP levels was observed. Baseline and follow-up BNP or NT-proBNP levels were not predictive of death, however, a composite BNP/NT-proBNP group predicted mortality (HR 3.81 (2.08-6.99), p<.0001). CONCLUSIONS: NT-proBNP may be more useful than BNP in the detection and monitoring of PAH in SSc patients, but additional studies are necessary.
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Hipertensión Pulmonar/diagnóstico , Péptido Natriurético Encefálico/sangre , Esclerodermia Sistémica/complicaciones , Anciano , Progresión de la Enfermedad , Femenino , Hemodinámica , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/fisiopatología , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Estudios Prospectivos , Sistema de Registros , Esclerodermia Sistémica/sangreRESUMEN
Anti-P antibodies have been associated with organ involvement in SLE, such as in autoimmune hepatitis, and have been suggested to be directly pathogenic. Neuropsychiatric lupus, lupoid hepatitis, autoimmune hepatitis, lupus nephritis, and Chagas' disease have been associated with the presence of anti-P antibody. This review seeks to look into the current literature on anti-P antibody and the association between SLE and non-SLE autoimmune connective tissue disorder.
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Autoanticuerpos/sangre , Enfermedad de Chagas/inmunología , Nefritis Lúpica/inmunología , Vasculitis por Lupus del Sistema Nervioso Central/inmunología , Proteínas Ribosómicas/inmunología , Enfermedad de Chagas/sangre , Humanos , Nefritis Lúpica/sangre , Vasculitis por Lupus del Sistema Nervioso Central/sangreRESUMEN
OBJECTIVE: To assess patients with SSc who present without circulating ANAs or RP. METHODS: Five thousand three hundred and ninety patients who fulfilled the ACR criteria for SSc and were enrolled in the EULAR Scleroderma Trials and Research (EUSTAR) database were screened for the absence of both RP and circulating ANA. To differentiate SSc from its mimics, additional information was gathered using a standardized questionnaire. RESULTS: Five thousand three hundred and seventy-eight (99.8%) of the 5390 SSc patients in the EUSTAR database had either detectable ANA or a history of RP. Twelve (0.2%) patients lacked both circulating ANA and RP. Details of the medical history could be obtained for seven patients. Three cases were compatible with ANA-negative and RP-negative SSc and were not typical of any known SSc mimic. Four patients had a malignancy: two had breast cancer, one had multiple myeloma with possible scleromyxoedema and one had bladder carcinoma. There was no temporal relationship between the onset of skin fibrosis and that of the tumour. Although no patient with confirmed nephrogenic systemic fibrosis was identified among the cases of ANA-negative and RP-negative SSc, the presentation of one patient could be compatible with that of nephrogenic systemic fibrosis other than for the absence of chronic kidney disease or of known prior gadolinium exposure. CONCLUSION: We have identified a very small subgroup of SSc patients who lack both circulating ANA and RP, none of whom fulfils the diagnostic criteria for any known SSc mimic. Prospective studies are needed to elucidate the clinical presentation, evolution and outcome of such patients.
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Anticuerpos Antinucleares/análisis , Enfermedad de Raynaud/inmunología , Esclerodermia Difusa/inmunología , Adulto , Anciano , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Esclerodermia Difusa/diagnósticoRESUMEN
INTRODUCTION: Clinically significant pericardial effusions and cardiac tamponade in systemic sclerosis (SSc) patients is uncommon and the factors that contribute to progression of pericardial involvement in SSc patients have not been well established. METHODS: A review of the national inpatient sample database was performed looking SSc related hospitalizations between 2002 and 2019. Data was collected on patients with pericardial effusions and cardiac tamponade and analyzed to identify and describe patient characteristics and comorbidities. RESULTS: Out of a total of 523,410 SSc hospitalizations, with an overall inpatient mortality rate of 4.7% (24,764 patients), pericardial effusion was identified in 3.1% of all hospitalizations (16,141 patients) out of which 0.2% (838 patients) had a diagnosis of cardiac tamponade. Patients with pericardial effusion were significantly more likely to have pulmonary circulatory disease (p = < 0.0001), congestive heart failure (p = < 0.0001) end stage renal disease (p = < 0.0001), diabetes (p = 0.015), and hypothyroidism (p = 0.025). Patients with cardiac tamponade were significantly more likely to have a history of coronary artery bypass graft surgery (p = 0.001) or atrial fibrillation (p = < 0.0001). Hospitalized patients with cardiac tamponade had a significantly increased mortality rate of 17.7% compared to 8.8% in patients with pericardial effusions without a tamponade physiology, with an odds ratio of 2.3 (1.97-2.86), p = < 0.0001. CONCLUSION: Pericardial effusion and tamponade are associated with increased morbidity and mortality in SSc patients. Further studies are required to explore the role of patient comorbidities and characteristics in development into pericardial effusions or tamponade.
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BACKGROUND: Patients with normal (mean pulmonary arterial pressure (mPAP) ≤20 mm Hg) and borderline mean pulmonary pressures (21-24 mm Hg) are "at risk" of developing pulmonary hypertension (PH). The objectives of this analysis were to examine the baseline characteristics in systemic sclerosis (SSc) with normal and borderline mPAP and to explore long-term outcomes in SSc patients with borderline mPAP versus normal haemodynamics. METHODS: PHAROS is a multicentre prospective longitudinal cohort of patients with SSc "at risk" or recently diagnosed with resting PH on right heart catheterisation (RHC). Baseline clinical characteristics, pulmonary function tests, high-resolution CT, 2-dimensional echocardiogram and RHC results were analysed in normal and borderline mPAP groups. RESULTS: 206 patients underwent RHC (results showed 35 normal, 28 borderline mPAP, 143 resting PH). There were no differences in the baseline demographics. Patients in the borderline mPAP group were more likely to have restrictive lung disease (67% vs 30%), fibrosis on high-resolution CT and a higher estimated right ventricular systolic pressure on echocardiogram (46.3 vs 36.2 mm Hg; p<0.05) than patients with normal haemodynamics. RHC revealed higher pulmonary vascular resistance and more elevated mPAP on exercise (≥30; 88% vs 56%) in the borderline mPAP group (p<0.05 for both). Patients were followed for a mean of 25.7 months and 24 patients had a repeat RHC during this period. During follow-up, 55% of the borderline mPAP group and 32% of the normal group developed resting PH (p=NS). CONCLUSIONS: Patients with borderline mPAP have a greater prevalence of abnormal lung physiology, pulmonary fibrosis and the presence of exercise mPAP ≥30 mm Hg.
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Presión Sanguínea/fisiología , Hipertensión Pulmonar/fisiopatología , Arteria Pulmonar/fisiopatología , Esclerodermia Sistémica/fisiopatología , Cateterismo Cardíaco , Femenino , Estudios de Seguimiento , Hemodinámica , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/fisiopatología , Pruebas de Función Respiratoria , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnósticoRESUMEN
To compare the characteristics of patients with systemic sclerosis who died within 2 years of diagnosis to those who died after 2 years of diagnosis. A retrospective chart review of all medical records of deceased systemic sclerosis (SSc) patients who had been followed at our institution from 1985 to 2007 was performed. We identified 87 deceased SSc patients within this period. From the 87 deceased individuals, 20 had died within 2 years after they were diagnosed, and 67 had died after 2 years of their diagnosis. Patients who died within 2 years of diagnosis were more likely to be anticentromere antibody negative when compared to the patients who died after 2 years (17/20 vs. 48/67, P = 0.03). The time from the first appearance of non-Raynaud's symptoms to diagnosis was significantly shorter in the group who died within 2 years than in the group who died after 2 years of diagnosis (11.8 ± 10.3 vs. 60.7 ± 64.9 months, P = 0.002). According to the Medsger severity score, there was more severe muscle (0.82 ± 1.13 vs. 1.8 ± 1.28, P = 0.0014) and heart (0.86 ± 1.37 vs. 2.1 ± 1.71, P = 0.0013) involvement at the initial evaluation in patients who died before 2 years of diagnosis when compared to the group of patients who died after 2 years of diagnosis. The time from the first symptoms to treatment initiation was significantly shorter in patients who died early (9.43 ± 6.3 vs. 38.3 ± 54.4 months, P = 0.05). The interval between treatment initiation and death was also significantly shorter (15.1 ± 9.48 vs. 60.7 ± 49.7 months, P = 0.001), reflecting greater severity of disease. Patients who died within the first 2 years of SSc diagnosis were typically anticentromere negative and had significant muscle and cardiac involvement. The time from the first appearance of non-Raynaud phenomenon symptoms to death was much shorter in the patients who died within 2 years of diagnosis, suggesting a very fulminant form of systemic sclerosis.
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Enfermedad de Raynaud/diagnóstico , Enfermedad de Raynaud/mortalidad , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/mortalidad , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Fibrosis , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
To describe and compare the diagnosis, demographics and management of systemic lupus erythematosus (SLE) related versus idiopathic acute transverse myelitis during the initial presentation of the disease. We undertook a chart review of the hospital records of patients admitted to our hospital from 1994 until 2007 and had the diagnosis of SLE related and idiopathic acute transverse myelitis. Demographics, laboratory and imaging studies, diagnosis and treatment were recorded in both groups and analyzed in a case control fashion. We identified 15 patients with SLE-related acute transverse myelitis (SLE-ATM) and 39 idiopathic (I-ATM) cases between 1994 and 2007. Patients with SLE were more likely to be African American, have CNS demyelinating lesions on MRI, a high IgG% on their CSF analysis and a higher sedimentation rate on presentation. Treatment with high-dose steroids was instituted in both groups of patients, though SLE patients had a longer hospital stay by an average of 5 days. SLE-ATM patients were more likely to be African American as compared to I-ATM patients, have CNS demyelinating lesions on MRI, a high IgG% on CSF analysis and a higher sedimentation rate on presentation. The hospital stay for SLE patients was 5 days longer than the idiopathic patients. This study underlines the importance of early diagnosis of patients who develop ATM related to SLE.
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Demografía , Manejo de la Enfermedad , Lupus Eritematoso Sistémico/complicaciones , Mielitis Transversa/diagnóstico , Mielitis Transversa/tratamiento farmacológico , Adulto , Negro o Afroamericano/etnología , Anciano , Sedimentación Sanguínea , Enfermedades Desmielinizantes/patología , Diagnóstico Diferencial , Femenino , Humanos , Inmunoglobulina G/líquido cefalorraquídeo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mielitis Transversa/etnología , Estudios Retrospectivos , Esteroides/uso terapéutico , Población Blanca/etnologíaRESUMEN
OBJECTIVE: Hand dysfunction is common in systemic sclerosis (SSc). We undertook this study to evaluate the capacity of autologous adipose-derived regenerative cells (ADRCs) to improve hand function in SSc patients. METHODS: The Scleroderma Treatment with Celution Processed Adipose Derived Regenerative Cells Trial was a prospective, randomized, double-blind trial of ADRCs, in which ADRCs were obtained from patients with SSc by small-volume adipose tissue harvest, and the fingers of each patient were injected with ADRCs. The primary end point was change in hand function at 24 and 48 weeks, assessed using the Cochin Hand Function Scale (CHFS). One of the secondary end points included the change in Health Assessment Questionnaire disability index (HAQ DI) at 48 weeks. Separate prespecified analyses were performed for patients with diffuse cutaneous SSc (dcSSc) and those with limited cutaneous SSc (lcSSc). RESULTS: Eighty-eight patients were randomized to receive ADRCs (n = 48 [32 patients with dcSSc and 16 with lcSSc]) or placebo (n = 40 [19 patients with dcSSc and 21 with lcSSc]). Change in hand function according to CHFS score was numerically higher for the ADRC group compared to the placebo group but did not achieve statistical significance (mean ± SD improvement in the CHFS score at 48 weeks 11.0 ± 12.5 versus 8.9 ± 10.5; P = 0.299). For patients with dcSSc, the between-group difference in the CHFS at 48 weeks was 6.3 points (nominal P = 0.069). For the secondary end point, the dcSSc group exhibited a between-group difference of 0.17 points in the HAQ DI (nominal P = 0.044) at 48 weeks. Of the ADRC-treated patients with dcSSc, 52% reported improvement greater than the minimum clinically important difference for both CHFS and HAQ DI compared to 16% in the placebo group (nominal P = 0.016). Small-volume adipose tissue harvest and ADRC treatment were well tolerated. CONCLUSION: While the primary end point of this trial was not achieved, efficacy trends were observed in patients with dcSSc. Adipose tissue harvest and ADRC injection were demonstrated to be feasible. Further clinical trials of this intervention in the setting of dcSSc are warranted.
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Esclerodermia Difusa , Esclerodermia Sistémica , Trasplante de Células , Mano , Humanos , Estudios Prospectivos , Esclerodermia Difusa/complicaciones , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/terapiaRESUMEN
OBJECTIVE: Barrett's oesophagus (BE) is the major risk factor for oesophageal adenocarcinoma (EAC). SSc is associated with an increased risk of BE related to chronic reflux. The aim of this study is to determine the outcomes of BE and estimate the EAC risk in SSc patients over a 3-year prospective study. METHODS: SSc patients were recruited through EUSTAR network centres. Inclusion criterion was a recent histological finding of BE. The patients were then prospectively followed and, as recommended, a second oesophageal endoscopy was performed according to the presence of BE-related dysplasia at baseline. RESULTS: A total of 50 SSc patients with BE (40 without and 10 with dysplasia) were included and 46 completed the follow-up (138 patient-years). During the 3-year follow-up, 4 of the 46 BE patients (3% per year) were diagnosed with high-grade dysplasia/EAC, of which one developed cardial EAC. EAC incidence in the BE subgroup with dysplasia increased to 4% per year compared with the absence of EAC cases in the BE subgroup without dysplasia at baseline. CONCLUSION: Our results, in accordance with previous published data suggesting an increased risk of EAC or cardial adenocarcinoma in SSc, highlight the need for accurate follow-up of BE SSc patients at risk of developing adenocarcinoma.
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Esófago de Barrett/patología , Esclerodermia Sistémica/patología , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Esófago de Barrett/epidemiología , Cardias/patología , Comorbilidad , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Factores de Riesgo , Esclerodermia Sistémica/epidemiologíaRESUMEN
Avascular necrosis (AVN) is a pathologic process involving death of bony tissue resulting from loss of blood supply from various causes. Various traumatic and nontraumatic causes of AVN are known, including systemic autoimmune diseases. AVN has been well described in patients with autoimmune diseases such as systemic lupus erythematosus, but in systemic sclerosis (SSc) patients, there have been limited case reports and case series. There have only been three case reports of AVN in multiple anatomic sites (multifocal AVN) reported in SSc patients in the literature. We present a case of multifocal AVN in an SSc patient and a review of literature on the previously reported cases of SSc-related AVN in terms of demographics, clinical presentation, and management. To our knowledge, this is the only literature review of reported AVN cases in SSc patients.
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Lupus Eritematoso Sistémico , Osteonecrosis , Esclerodermia Sistémica , Demografía , Humanos , Lupus Eritematoso Sistémico/complicaciones , Osteonecrosis/diagnóstico por imagen , Osteonecrosis/etiología , Esclerodermia Sistémica/complicacionesRESUMEN
Systemic sclerosis (SSc) is an autoimmune disorder characterized by the involvement of skin and internal organs. With the introduction of angiotensin-converting enzyme inhibitors (ACEIs), scleroderma renal crisis (SRC) is no longer considered a leading cause of death in affected patients. In fact, pulmonary manifestations [interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH)] are currently the major cause of death in patients with SSc. Historically, many centers have been reluctant to offer lung transplantation to patients with SSc due to multiple extrapulmonary manifestations and the assumption of poor post-transplant survival. The purpose of this review is to highlight the recent advances in the evaluation and management of patients with pulmonary manifestations of SSc. We also engage in a systematic literature review to assess all the available data on the survival of patients with SSc after lung transplantation.
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We report the case of a pediatric patient with eosinophilic fasciitis, who was successfully treated with early high dose corticosteroids and subsequent use of mycophenolate mofetil. We believe that the early institution of corticosteroids helped to suppress the early inflammatory part of the disease and the subsequent use of mycophenolate mofetil maintained this and may have also helped prevent fibrotic skin changes.
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Corticoesteroides/administración & dosificación , Antiinflamatorios/administración & dosificación , Eosinofilia/tratamiento farmacológico , Fascitis/tratamiento farmacológico , Ácido Micofenólico/análogos & derivados , Niño , Esquema de Medicación , Quimioterapia Combinada , Eosinofilia/patología , Fascitis/patología , Humanos , Masculino , Ácido Micofenólico/administración & dosificaciónRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of mycophenolate mofetil for the treatment of SSc. METHODS: We recruited 15 patients with dcSSc to take part in an open-label study using mycophenolate mofetil to treat their disease over a 12-month period. The primary outcome measure was the modified Rodnan skin score (mRSS), whereas secondary outcomes included the Medsger severity score, pulmonary function studies, 2D echocardiograms and the Short Form Health Survey (SF)-36 questionnaire. RESULTS: The mRSS significantly improved in those patients who tolerated the medication for >3 months (P < 0.0001), and there was a statistically significant improvement in the Medsger severity scores of the general (P = 0.05), peripheral vascular involvement (P = 0.05) and skin (P = 0.0003) scores. The SF-36 scores improved (P = 0.05) and the pulmonary function studies showed a trend towards improvement, though not of statistical significance. The mean pulmonary artery pressure by 2D echocardiography did not change. CONCLUSIONS: In this prospective open-label study of mycophenolate mofetil for the treatment of dcSSc, we observed significant improvements in skin scores, peripheral vascular involvement and patient-perceived health status. Pulmonary function studies did not worsen as expected, but instead showed a trend towards improvement. Controlled trials are needed to further investigate this trend for improved pulmonary function studies.
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Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Esclerodermia Difusa/tratamiento farmacológico , Adulto , Femenino , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/uso terapéutico , Estudios Prospectivos , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: Assessment of systemic sclerosis patients has not directly addressed functioning from the patient's perspective. With this study, we aim to gain our patient's point of view by using a questionnaire to describe their unmet needs and understanding what demographic parameters influence these. METHODS: A computer randomization program selected 50 patients, from 242 systemic sclerosis patients actively followed at our rheumatology clinic, to receive a survey about unmet needs. Twenty-five patients responded to the survey. Of 81 questions, 9 provided demographic data, whereas 72 questions addressed physical, daily living, psychologic, spiritual, existential, health services, health information, social support, and employment issues. A 4-point scale from no need to high need was used to rate all questions. Significant need was considered any issue for which more than 50% of patients reported a high need. The Fisher exact test was used to compare different demographic variables to unmet patient needs. RESULTS: The psychologic/spiritual/existential category had 9 questions reaching significance, the health services category had 5 significant questions, the physical category had 4 significant questions. Patients who had not attended college were more likely to have higher needs than patients who completed a college degree. Unmarried patients reported higher needs in 8 measures as compared with married patients, and patients in rural areas had higher needs in social support needs. CONCLUSIONS: The greatest prevalence of unmet needs in scleroderma patients were in the psychologic/spiritual/existential domain, such as being unable to do things they used to do, fear that the disease will worsen, anxiety and stress, feeling down or depressed, fears of physical disability, uncertainty about the future, change in appearance, keeping a positive outlook, and feeling in control. Significant differences were observed in unmet needs based on education, marital status, location, knowledge of disease, and age. Understanding each patient's specific unmet needs either through direct questioning or by the use of a questionnaire such as the one used for this study can help clinicians to give better care to each of our patients.
Asunto(s)
Ansiedad/complicaciones , Esclerodermia Sistémica/psicología , Estrés Psicológico/complicaciones , Encuestas y Cuestionarios , Adaptación Psicológica , Adulto , Anciano , Ansiedad/diagnóstico , Actitud Frente a la Salud , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apoyo Social , Estrés Psicológico/diagnóstico , Adulto JovenRESUMEN
OBJECTIVE: We sought to identify predictors of mortality and cardiopulmonary hospitalizations in patients at risk for pulmonary hypertension (PH) and enrolled in PHAROS, a prospective cohort study to investigate the natural history of PH in systemic sclerosis (SSc). METHODS: The at-risk population for PH was defined by the following entry criteria: echocardiogram systolic pulmonary arterial pressure > 40 mmHg, or DLCO < 55% predicted or ratio of % forced vital capacity/%DLCO > 1.6, measured by pulmonary function testing. Baseline clinical measures were evaluated as predictors of hospitalization and death between 2005 and 2014. Cox proportional hazards models were censored at date of PH onset or latest study visit and adjusted for age, sex, race, and disease duration. RESULTS: Of the 236 at-risk subjects who were followed for a median of 4 years (range 0.4-8.5 yrs), 35 developed PH after entering PHAROS (reclassified as PH group). In the at-risk group, higher mortality was strongly associated with male sex, low %DLCO, exercise oxygen desaturation, anemia, abnormal dyspnea scores, and baseline pericardial effusion. Risks for cardiopulmonary hospitalization were associated with increased dyspnea and pericardial effusions, although PH patients with DLCO < 50% had the highest risk of cardiopulmonary hospitalizations. CONCLUSION: Risk factors for poor outcome in patients with SSc who are at risk for PH were similar to others with SSc-PH and SSc-pulmonary arterial hypertension, including male sex, DLCO < 50%, exercise oxygen desaturation, and pericardial effusions. This group should undergo right heart catheterization and receive appropriate intervention if PH is confirmed.
Asunto(s)
Hospitalización , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/mortalidad , Sistema de Registros , Esclerodermia Sistémica/complicaciones , Anciano , Presión Arterial , Ecocardiografía , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales , Tasa de Supervivencia , Capacidad VitalRESUMEN
BACKGROUND: Pericardial effusions in systemic sclerosis (SSc) may present as acute or chronic with or without clinical symptoms. Best treatment is unknown and whether patients receive medical therapy or a surgical procedure is clinician-dependent. OBJECTIVE: To describe the clinical characteristics, treatment, and outcomes of patients with SSc and clinically symptomatic pericardial effusions treated in the inpatient setting. METHODS: We evaluated all SSc admissions over a 10-year period to a tertiary care hospital which has a dedicated SSc clinic. Patients who had a clinically symptomatic pericardial effusion were evaluated based on their demographics, disease pattern, and medical or surgical management. RESULTS: From January 2005 till October 2015, there were 462 SSc admissions with 32 (6.9%) of them being for a clinically symptomatic pericardial effusion in 23 unique patients. Eleven (47%) of these patients had right heart failure, seventeen (74%) had pulmonary arterial hypertension (PAH), and 4 (17%) had tamponade physiology. Five (22%) patients were treated by a surgical procedure, while eighteen (78%) patients had medical therapy. Patients who received medical therapy tended to be older, have a lower serum Cr level, and more likely have right heart failure. CONCLUSION: Clinically symptomatic pericardial effusion is a rare cause for hospital admissions in SSc, with a high percentage of these patients having PAH. Medical therapy tends to be reserved for older patients with right heart failure, while surgical therapy was more likely in patients with higher serum Cr levels.