Methotrexate in Linear Scleroderma: Long-Term Efficacy in Fifty Children From a Single Pediatric Rheumatology Center.

OBJECTIVE: To study disease course and long-term outcome in children with linear scleroderma (SSc) treated with methotrexate (MTX) since diagnosis. METHODS: The present study was retrospective and cross-sectional and included consecutive children with linear SSc who were treated with MTX for >1 year and were followed up for at least 2 years. Disease course was analyzed by the number of relapses and treatment changes. Relapse-free survival was examined by Kaplan-Meier analysis, comparing patients with linear SSc and those with other juvenile localized scleroderma (JLS) disease subtypes. Disease activity and damage were assessed by the Localized Scleroderma Cutaneous Assessment Tool and thermography. RESULTS: Fifty patients with a mean follow-up duration of 7.8 years and a mean MTX treatment duration of 3.1 years were included. Sixteen percent of patients did not respond to the first course of MTX, and 16% had at least 1 flare. Complete remission was observed in 18.2% of patients who were followed up for 2-5 years, in 80.0% of patients followed up for 10 years, and in 87.5% of patients followed up for >10 years. No significant difference in relapse-free survival between patients with linear SSc and in 17 patients with other JLS disease subtypes was observed. Tissue damage was mild in 42% of patients, moderate in 32%, and severe in 26%. The correlations between severity of tissue damage and linear SSc subtype, disease duration, relapses, and remission were not significant. The relationships between treatment duration and disease relapses (P < 0.05) and severity of tissue damage (P < 0.005) were significant. CONCLUSION: Most patients with linear SSc who are treated with MTX achieve complete and long-lasting remission. Overall aesthetic and functional sequelae are moderate, most likely because tissue damage is established early and treatment likely stabilizes the damage. Early diagnosis and MTX treatment, as well as long-term monitoring, are crucial to improve outcome and promptly identify flares.

Determinants of mortality in systemic sclerosis: a focused review.

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.

Pediatric scleroderma: systemic or localized forms.

Pediatric scleroderma includes 2 major groups of clinical entities, systemic sclerosis (SSc) and localized scleroderma (LS). Although both share a common pathophysiology, their clinical manifestations differ. LS is typically confined to the skin and underlying subcutis, with up to a quarter of patients showing extracutaneous disease manifestations such as arthritis and uveitis. Vascular, cutaneous, gastrointestinal, pulmonary, and musculoskeletal involvement are most commonly seen in children with SSc. Treatment of both forms targets the active inflammatory stage and halts disease progression; however, progress needs to be made toward the development of more effective antifibrotic therapy to help reverse disease damage.

Adult outcomes of childhood-onset rheumatic diseases.

A number of studies published over the past 10 years have examined the long-term health, functional and quality of life outcomes of adults with childhood-onset rheumatic diseases such as juvenile idiopathic arthritis, systemic lupus erythematosus, juvenile dermatomyositis and localized scleroderma. As increasing numbers of patients with these conditions survive into adulthood, understanding the adult outcomes of these pediatric conditions has become ever-more important. Identifying modifiable risk factors for poor outcomes is vital to improving care for these patients. In addition, as these conditions and their treatments can affect cardiovascular health, bone health and fertility, particular attention needs to be paid to these outcomes. Preparing patients and their families for a successful transition from pediatric to adult rheumatology care is an important first-step in the long-term management strategy for this expanding patient population.

Acute kidney injury in patients with systemic sclerosis participating in hematopoietic cell transplantation trials in the United States.

Recipients of hematopoietic cell transplantation may be at risk for developing acute kidney injury (AKI), and this risk may be increased in patients who undergo transplantation for severe systemic sclerosis (SSc) due to underlying scleroderma renal disease. AKI after transplantation can increase treatment-related mortality. To better define these risks, we analyzed 91 patients with SSc who were enrolled in 3 clinical trials in the United States of autologous or allogeneic hematopoietic cell transplantation (HCT). Eleven (12%) of the 91 patients with SSc in these studies (8 undergoing autologous HCT, 1 undergoing allogeneic HCT, 1 pretransplantation, 1 given i.v. cyclophosphamide on a transplantation trial) experienced AKI, of whom 8 required dialysis and/or therapeutic plasma exchange. AKI injury in the 9 HCT recipients developed a median of 35 days (range, 0-90 days) after transplantation. Ten of 11 patients with AKI received angiotensin-converting enzyme inhibitor (ACE-I) therapy. The etiology of AKI was attributed to scleroderma renal crisis in 6 patients (including 2 with normotensive renal crisis), to AKI of uncertain etiology in 2 patients, and to AKI superimposed on scleroderma kidney disease in 3 patients. Eight of the 11 patients died, one each because of progression of SSc, multiorgan failure, gastrointestinal and pulmonary bleeding, pericardial tamponade and pulmonary complications, diffuse alveolar hemorrhage, pulmonary embolism, graft-versus-host disease, and malignancy. Limiting nephrotoxins, cautious use of corticosteroids, renal shielding during total body irradiation, strict control of blood pressure, and aggressive use of ACE-Is may be of importance in preventing renal complications after HCT for SSc.

[Causes of death of patients with systemic sclerosis]. / Analiza przyczyn zgonów chorych na twardzine ukladowa.

UNLABELLED: Systemic sclerosis (SSc) is a chronic, systemic connective tissue disease, characterized by progressive skin fibrosis, internal organs and disfunction blood vessels. THE AIM: of the study was o analyze death causes in patients with SSc and the assessment of relationship between clinical status, immunologic test results and survival/mortality of patients with SSc. MATERIAL AND METHODS: Case histories of all patients with SSc, hospitalized for six years (since 1'" October 1999 to 1It October 2005) in Department of Rheumatology and Internal Diseases, Medical University of Bialystok, were retrospectively analyzed. Current patients status at the end-point of study was estimated during control examination and phone contact in selected cases. The time and cause of death was based on autopsy results. RESULTS: In study group of 76 patients with SSc, 13 deaths were found (17,1%). Death cause analyses revealed that: interstitial lung disease was the main cause of death (4/13 - 30%). As a secondary cause of death in these patients neoplasms were recognized (3/13 - 23,1%). In all patients with neoplasms exudation in pleura was diagnosed. CONCLUSIONS: Pulmonary complications and neoplasms are predominant causes of death in patients with SSc. Risk factors of death are: pulmonary hypertension and myositis. The presence of exudation in pleura in patients with SSc is a bad prognostic symptom and a possible sign of neoplastic disease.

Scleroderma at end stage renal disease in the United States: patient characteristics and survival.

BACKGROUND: The patient characteristics and mortality associated with scleroderma have not been characterized for a national sample of end stage renal disease (ESRD) patients. METHODS: 364,317 patients in the United States Renal Data System initiated on ESRD therapy between 1 January 1992 and 30 June 1997 with valid causes of ESRD were analyzed in an historical cohort study of scleroderma. RESULTS: Of the study population, 820 (0.22%) had scleroderma. The mean age of patients with scleroderma was 56.38 +/- 13.93 years vs. 60.48 +/- 16.51 years for patients with other causes of ESRD (p<0.01 by Student's t-test). In histogram analysis, there were two age peaks: 45-49 and 65-69. In logistic regression, patients with scleroderma, compared to patients with other causes of ESRD, were significantly more likely to be women, Caucasian, younger, and more likely to have congestive heart failure but less likely to have ischemic heart disease, stroke, and receive predialysis erythropoietin. The unadjusted two-year survival of patients with scleroderma during the study period was 49.3% vs. 63.8% in all other patients (adjusted hazard ratio, 1.96, 95% CI 1.70-2.26, p=0.0001 by Cox Regression). CONCLUSIONS: Among patients with ESRD, the demographics of patients with scleroderma were similar to those of patients with scleroderma in the general population. Patients with scleroderma had decreased survival compared to patients with other causes of ESRD, despite being equally likely to be wait listed and receive renal transplantation adjusted for other factors.

Causes of death and poor survival prognostic factors in thai patients with systemic sclerosis.

Causes of death and poor prognostic factors for patients with systemic sclerosis (SSc) were studied in 222 cases. Their mean age at the onset and duration of disease was 48.9 +/- 12.0 years and 23.3 +/- 29.3 months, respectively. Fifty-three per cent were diffuse subtype. Patients with diffuse SSc had more digital pitting scars and more muscle, heart, lung, and esophageal involvement than those with limited subtypes (p < or = 0.02). One hundred and six patients were lost to follow-up. With a median follow-up duration of 25 months, 31 of the remaining 116 patients (26.7%) died. SSc related death occurred in 18 cases, in which the lung, heart and kidney (renal crisis) were the major causes. Infection contributed to the remaining 13 deaths. When compared with living patients, using a univariate analysis, factors associated with a reduced survival rate were age of > 45 years at the onset, diffuse skin thickness, and lung, gastrointestinal tract, heart, kidney and muscle involvement (p < or = 0.001). In the multivariate analysis, only age of > 45 years at onset and cardiac involvement remained poor prognostic factors (p = 0.04 and 0.001, respectively).

Mortality in systemic sclerosis: a comparison with the general population.

OBJECTIVE: To compare the mortality rate in patients with systemic sclerosis (SSc) with that of the general population. METHODS: Standardized mortality ratios (SMR) were calculated for 237 patients with SSc followed prospectively, using age and sex specific mortality rates in Ontario for the period 1976-1990. RESULTS: The overall SMR for the SSc cohort was 4.69. The mortality rate was greater with diffuse than with limited scleroderma (SMR 6.18 and 3.80, respectively), but not different between men and women. CONCLUSION: The mortality rate in SSc is increased compared to that of the general population, especially in the subset with diffuse disease.