A Prospective Observational Study of Disease Severity and Mortality in Hispanic American Patients With Systemic Sclerosis.

OBJECTIVE: To characterize disease manifestations in Hispanic American patients with systemic sclerosis (SSc) in comparison with non-Hispanic White and Black patients. METHODS: Longitudinal clinical characteristics were collected prospectively in the Genetics versus Environment in Scleroderma Outcome Study cohort. All patients fulfilled the classification criteria for SSc and had a disease duration less than five years at enrollment. RESULTS: A cohort of 427 patients, consisting of 124 Hispanic, 220 non-Hispanic White, and 83 non-Hispanic Black participants were examined. At enrollment, Hispanic patients were significantly younger but had longer disease duration, higher frequency of U1-RNP positivity as well as concurrent systemic lupus erythematosus (SLE) diagnosis, and lower income and educational levels in comparison to non-Hispanic White patients. Compared with non-Hispanic Black patients, Hispanic patients had more frequently limited cutaneous involvement and anticentromere antibodies. In the longitudinal analysis, Hispanic patients had significantly lower forced vital capacity percents predicted (point estimate, -9.3%; P < 0.001) than non-Hispanic White but not Black patients. Hispanic patients had similar longitudinal modified Rodnan Skin Scores like non-Hispanic White patients but lower measurements than non-Hispanic Black patients (point estimate, -3.2; P = 0.029). Hispanic patients had significantly higher serially obtained perceived functional disability scores than White patients (point estimate, 0.29; P < 0.001). Hispanic patients also had higher mortality rates than White Americans even after adjustment for age, gender, and socioeconomic statuses. CONCLUSION: Hispanic patients have higher likelihood of having U1-RNP positivity and SLE overlap, more severe restrictive lung disease, as well as higher rate of mortality than non-Hispanic White patients.

Reporting and Representativeness of Race, Ethnicity, and Socioeconomic Status in Systemic Sclerosis Randomized Trials: An Observational Study.

OBJECTIVE: To assess how and to what extent socioeconomic status and ethnicity/race of participants are reported in randomized controlled trials (RCTs) on systemic sclerosis (SSc), and to estimate the representativeness of different ethnic/racial groups in SSc RCTs. METHODS: We searched all published RCTs on SSc indexed in PubMed. We retrieved information on main features of RCTs published from 2000 onward and recorded for each study whether race/ethnicity was reported; how ethnicity/race was defined and assigned; and the number of patients included for each racial/ethnic group. Multivariable logistic regression was used to identify factors associated with race/ethnicity reporting. Proportion of races/ethnicities included in US-based RCTs on SSc was examined and compared with US demographic data. RESULTS: We included 106 studies, mostly conducted in Europe (42%) or North America (25%), published after 2010 (74%), and enrolling a total of 6,693 patients. About one-third of studies provided information about race/ethnicity, with no improved reporting over time. Only 2 papers reported patient's socioeconomic status. Study location (US or intercontinental) was the only significant factor associated with a better reporting of race/ethnicity in multivariable analysis. In studies where race/ethnicity was reported, White patients were mostly represented (79%), followed by Asian (7%), and African American (6%). In the sensitivity analysis limited to studies from the US, underrepresentation of African American patients was observed in the 2000-2010 time period, but not later. CONCLUSION: Documentation of race/ethnicity and socioeconomic status is poor in RCTs on SSc. More effort should be made to document race/ethnicity and socioeconomic status and to promote diversity in SSc RCTs.

Trends in Systemic Sclerosis Mortality Over Forty-Eight Years, 1968-2015: A US Population-Based Study.

OBJECTIVE: To identify secular trends associated with systemic sclerosis (SSc) mortality over a 48-year period. METHODS: Using national mortality data compiled by the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research, and population data from the US Census Bureau, we calculated an age-standardized mortality rate (ASMR) for SSc and non-SSc (all other causes), and we also calculated the ratio of the SSc ASMR to the non-SSc ASMR for each year from 1968 to 2015. We then used a joinpoint regression model to evaluate mortality trends overall and by sex and race. RESULTS: From 1968 to 2015, there were 46,798 deaths with SSc recorded as the "underlying" cause of death and 106,058,839 non-SSc deaths. There were an additional 9,063 deaths with SSc recorded as a "contributing" cause of death from 1999 to 2015. Whereas the non-SSc ASMR decreased throughout the 48-year time period, the SSc ASMR increased from 1968 to 2000, followed by decreases each year from 2001 to 2015. The SSc ASMR also decreased for deaths where SSc was a contributing cause from 1999 to 2015. Women and Black persons had higher SSc ASMRs and SSc ASMR to non-SSc ASMR ratios than men and White persons, respectively. Additionally, SSc ASMRs and SSc ASMR to non-SSc ASMR ratios increased at higher rates in women and White persons than in men and Black persons, respectively, during the initial three decades. CONCLUSION: Mortality attributable to SSc increased from 1968 to 2000, followed by a steady decline from 2001 to 2015. However, SSc mortality relative to non-SSc mortality remains high. SSc mortality has disproportionately changed by sex and race over the 48-year period assessed in the present study.

Racial Disparities in Systemic Sclerosis.

Racial and ethnic disparities in systemic sclerosis are abundant. The incidence, severity of end-organ manifestations, functional impairment, quality of life, and mortality of systemic sclerosis vary by ethnic group. This article summarizes such disparities and explores the role of socioeconomic status in their development and persistence.

Clinical and laboratory features of African-Brazilian patients with systemic sclerosis.

OBJECTIVE: African-Brazilians comprise a group of blacks and "pardos." As racial differences can be associated with distinct presentations, we evaluated the clinical and serological associations of African-Brazilians with systemic sclerosis (SSc). METHODS: Sera from 260 adult SSc patients (203 whites and 57 African-Brazilians) were evaluated. Patients with overlap syndromes were excluded. Clinical and demographic data were obtained from an electronic register database. Laboratory analysis included the following: anti-CENP-A/CENP-B, Scl70, RNA polymerase III, Ku, fibrillarin, Th/To, PM-Scl75, and PM-Scl100 by line immunoassay and anti-nuclear antibodies (ANA) by indirect immunofluorescence (IIF) on HEp-2 cells. RESULTS: African-Brazilian SSc patients presented shorter disease duration (12.8 ± 6.5 vs. 15.9 ± 8.1 years, p = 0.009), higher frequency of nucleolar ANA pattern (28% vs. 13%, p = 0.008), and lower frequencies of centromeric ANA pattern (14% vs. 29%, p = 0.026) and CENP-B (18% vs. 34%, p = 0.017), as well as an association with severe interstitial lung disease (58% vs. 43%; p = 0.044). Further comparison of ethnic groups according to subsets revealed that diffuse SSc African-Brazilian patients presented higher frequency of pulmonary hypertension (p = 0.017), heart involvement (p = 0.037), nucleolar ANA pattern (p = 0.036), anti-fibrillarin antibodies (p = 0.037), and higher mortality (48% vs. 19%; p = 0.009). A different pattern was observed for the limited subset with solely a lower frequency of esophageal involvement (p = 0.050) and centromeric ANA pattern (p = 0.049). Survival analysis showed that African-Brazilians had a higher mortality, when adjusted for age, gender, and clinical subset (RR 2.06, CI 95% 1.10-3.83, p = 0.023). CONCLUSION: African-Brazilians have distinct characteristics according to clinical subset and an overall more severe SSc than whites, similar to the blacks from other countries.Key Points • African-Brazilian SSc patients were associated with severe interstitial lung disease and nucleolar ANA pattern when compared to white SSc patients. • When disease subsets were considered, African-Brazilian patients with diffuse SSc presented association with pulmonary hypertension, heart involvement, nucleolar ANA pattern, and anti-fibrillarin antibodies. • White SSc patients were associated with centromeric ANA pattern. • Survival analysis at 5, 10, 15, and 20 years, adjusted for age, gender, and disease subset, was significantly worse in African-Brazilian SSc patients.

Associations of Multiple NOTCH4 Exonic Variants with Systemic Sclerosis.

OBJECTIVE: Findings from previous genome-wide association studies indicated an association of the NOTCH4 gene with systemic sclerosis (SSc). This is a followup study to fine-map exonic variants of NOTCH4 in SSc. METHODS: All exons of NOTCH4 were sequenced and analyzed in a total of 1006 patients with SSc and 1004 controls of US white ancestry with the Ion Torrent system. Identified SSc-associated variants were confirmed with Sanger sequencing, and then examined in a Chinese Han cohort consisting of 576 patients with SSc and 574 controls. The NOTCH4 variants were analyzed for association with SSc as a whole and with SSc clinical and autoantibody subtypes with and without the influence of specific HLA-class II alleles that had been previously identified as major genetic factors in SSc. RESULTS: A total of 12 SSc-associated and SSc subtype-associated exonic variants of NOTCH4 were identified in the US cohort. Three of them are nonsynonymous single-nucleotide polymorphisms and 1 is a CTG tandem repeat that encodes for a poly-leucine, all of which are located in the NOTCH4 extracellular domain (NECD). Conditional logistic regression analysis on SSc-associated HLA-class II alleles indicated an independent association of the NOTCH4 variants with SSc autoantibody subtypes. Analysis of the Chinese cohort supported a genetic contribution of NOTCH4 to SSc and its subtypes. CONCLUSION: Multiple NOTCH4 exonic variants were associated with SSc and/or SSc subtypes. Several of these variants encode nonsynonymous sequence changes occurring in the NECD, which implicates a potentially functional effect of NOTCH4.

Analysis of the genetic component of systemic sclerosis in Iranian and Turkish populations through a genome-wide association study.

Objectives: SSc is an autoimmune disease characterized by alteration of the immune response, vasculopathy and fibrosis. Most genetic studies on SSc have been performed in European-ancestry populations. The aim of this study was to analyse the genetic component of SSc in Middle Eastern patients from Iran and Turkey through a genome-wide association study. Methods: This study analysed data from a total of 834 patients diagnosed with SSc and 1455 healthy controls from Iran and Turkey. DNA was genotyped using high-throughput genotyping platforms. The data generated were imputed using the Michigan Imputation Server, and the Haplotype Reference Consortium as a reference panel. A meta-analysis combining both case-control sets was conducted by the inverse variance method. Results: The highest peak of association belonged to the HLA region in both the Iranian and Turkish populations. Strong and independent associations between the classical alleles HLA-DRB1*11: 04 [P = 2.10 × 10-24, odds ratio (OR) = 3.14] and DPB1*13: 01 (P = 5.37 × 10-14, OR = 5.75) and SSc were observed in the Iranian population. HLA-DRB1*11: 04 (P = 4.90 × 10-11, OR = 2.93) was the only independent signal associated in the Turkish cohort. An omnibus test yielded HLA-DRB1 58 and HLA-DPB1 76 as relevant amino acid positions for this disease. Concerning the meta-analysis, we also identified two associations close to the genome-wide significance level outside the HLA region, corresponding to IRF5-TNPO3 rs17424921-C (P = 1.34 × 10-7, OR = 1.68) and NFKB1 rs4648133-C (P = 3.11 × 10-7, OR = 1.47). Conclusion: We identified significant associations in the HLA region and suggestive associations in IRF5-TNPO3 and NFKB1 loci in Iranian and Turkish patients affected by SSc through a genome-wide association study and an extensive HLA analysis.

Brief Report: Whole-Exome Sequencing to Identify Rare Variants and Gene Networks That Increase Susceptibility to Scleroderma in African Americans.

OBJECTIVE: Whole-exome sequencing (WES) studies in systemic sclerosis (SSc) patients of European American (EA) ancestry have identified variants in the ATP8B4 gene and enrichment of variants in genes in the extracellular matrix (ECM)-related pathway that increase SSc susceptibility. This study was undertaken to evaluate the association of the ATP8B4 gene and the ECM-related pathway with SSc in a cohort of African American (AA) patients. METHODS: SSc patients of AA ancestry were enrolled from 23 academic centers across the US under the Genome Research in African American Scleroderma Patients consortium. Unrelated AA individuals without serologic evidence of autoimmunity who were enrolled in the Howard University Family Study were used as unaffected controls. Functional variants in genes reported in the 2 WES studies in EA patients with SSc were selected for gene association testing using the optimized sequence kernel association test (SKAT-O) and pathway analysis by Ingenuity Pathway Analysis in 379 patients and 411 controls. RESULTS: Principal components analysis demonstrated that the patients and controls had similar ancestral backgrounds, with roughly equal proportions of mean European admixture. Using SKAT-O, we examined the association of individual genes that were previously reported in EA patients and none remained significant, including ATP8B4 (P = 0.98). However, we confirmed the previously reported association of the ECM-related pathway with enrichment of variants within the COL13A1, COL18A1, COL22A1, COL4A3, COL4A4, COL5A2, PROK1, and SERPINE1 genes (corrected P = 1.95 × 10-4 ). CONCLUSION: In the largest genetic study in AA patients with SSc to date, our findings corroborate the role of functional variants that aggregate in a fibrotic pathway and increase SSc susceptibility.

Association between the functional PTPN22 G788A (R263Q) polymorphism and susceptibility to autoimmune diseases: A meta-analysis.

This study explored whether the functional protein tyrosine phosphatase nonreceptor 22 (PTPN22) G788A (R263Q) polymorphism is associated with susceptibility to autoimmune diseases. A meta-analysis was conducted using 23 comparative studies with a total of 16,719 patients and 17,783 controls. The meta-analysis showed an association between the A allele of the PTPN22 G788A polymorphism and decreased risk of autoimmune diseases in all subjects (p < 0.001). Analysis after stratification by ethnicity indicated that the PTPN22 788A allele was significantly associated with autoimmune diseases in Europeans (p < 0.001) but not in Latin Americans. Meta-analysis by autoimmune disease type showed a significant negative association between the PTPN22 788A allele and systemic lupus erythematous (SLE) (p = 001), rheumatoid arthritis (RA) (p = 0.008), ulcerative colitis (UC) (p = 0.016), but not Crohn's disease (CD). A single study for each showed no association between the PTPN22 788A allele and systemic sclerosis, giant cell arteritis, Henoch-schonlein purpura, uveitis, and Grave's disease. This meta-analysis demonstrates that the PTPN22 G788A polymorphism confers protection against SLE, RA, and UC, supporting evidence of association of the PTPN22 gene with a subgroup of autoimmune diseases.

Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease characterised by skin and systemic fibrosis culminating in organ damage. Previous genetic studies including genome-wide association studies (GWAS) have identified 12 susceptibility loci satisfying genome-wide significance. Transethnic meta-analyses have successfully expanded the list of susceptibility genes and deepened biological insights for other autoimmune diseases. METHODS: We performed transethnic meta-analysis of GWAS in the Japanese and European populations, followed by a two-staged replication study comprising a total of 4436 cases and 14 751 controls. Associations between significant single nuclear polymorphisms (SNPs) and neighbouring genes were evaluated. Enrichment analysis of H3K4Me3, a representative histone mark for active promoter was conducted with an expanded list of SSc susceptibility genes. RESULTS: We identified two significant SNP in two loci, GSDMA and PRDM1, both of which are related to immune functions and associated with other autoimmune diseases (p=1.4×10-10 and 6.6×10-10, respectively). GSDMA also showed a significant association with limited cutaneous SSc. We also replicated the associations of previously reported loci including a non-GWAS locus, TNFAIP3. PRDM1 encodes BLIMP1, a transcription factor regulating T-cell proliferation and plasma cell differentiation. The top SNP in GSDMA was a missense variant and correlated with gene expression of neighbouring genes, and this could explain the association in this locus. We found different human leukocyte antigen (HLA) association patterns between the two populations. Enrichment analysis suggested the importance of CD4-naïve primary T cell. CONCLUSIONS: GSDMA and PRDM1 are associated with SSc. These findings provide enhanced insight into the genetic and biological basis of SSc.

Prevalence and Severity of Depression and Anxiety in Patients With Systemic Sclerosis: An Epidemiologic Survey and Investigation of Clinical Correlates.

BACKGROUND: Systemic sclerosis (SSc) is a chronic multisystem connective tissue disorder with detrimental impact on quality of life. Patients with SSc face emotional distress and frequently meet criteria for a psychiatric disorder. However, the pattern of psychiatric manifestations may vary according to socioethnic background. OBJECTIVES: We investigated the prevalence of depressive and anxiety symptoms and examined their association with sociodemographic and clinical factors in Iranian SSc patients. METHODS: Depressive and anxiety symptoms were evaluated by Beck Depression Inventory and Cattell questionnaire in 114 SSc patients. The associations between sociodemographic and clinical factors and depressive/anxiety symptoms were examined via multivariate analysis. RESULTS: The prevalence of depressive symptoms was 68.4%. There was a significant association between depressive symptoms and pulmonary and gastrointestinal manifestations. Also, diffuse SSc patients were more prone to depressive symptoms. Mean Rodnan scores were significantly higher in patients with depressive symptoms in comparison with subjects with no depressive symptoms. The prevalence of anxiety symptoms was 23.6%. Anxiety symptoms were not associated with demographic characteristics, SSc subtype, disease duration, Rodnan score, other clinical features, and previous history of depression in the patients or their family. The coincidence of anxiety and depression was 82.8%. CONCLUSIONS: Depressive and anxiety symptoms are prevalent among Iranian SSc population. The depressive symptoms showed correlation with pulmonary and gastrointestinal involvement, as well as diffuse SSc subtype.

[Efficacy of hyperbaric oxygen therapy in the treatment of ischemic toe ulcer in a patient presenting systemic sclerosis]. / Efficacité de l'oxygénothérapie hyperbare dans le traitement d'un ulcère nécrotique d'orteil au cours d'une sclérodermie systémique.

BACKGROUND: The medical treatment of ischemic ulcers in patients with systemic sclerosis remains difficult. Despite the major help provided by vasodilator treatments, the risk of spontaneous or surgical amputation remains high. OBSERVATION: A 48-year-old female patient from Guadeloupe was treated in our department for diffuse systemic sclerosis present for 15 years complicated by lung, joint and digestive involvement, and associated with severe Raynaud's phenomenon. The clinical course was marked by the occurrence of multiple ischemic ulcers, which were resistant to conventional medical treatment and resulted in two surgical amputations (to the 2nd and 3rd interphalangeal joints of the toes of the left foot). Treatment with an endothelin-receptor antagonist and a calcium inhibitor was then introduced for secondary prevention. Two years later, the patient consulted for a further ischemic ulcer of the left 4th toe. She refused the proposed treatment with iloprost. Because of the unfavorable outcome and the absence of therapeutic alternative to amputation, hyperbaric oxygen therapy was initiated. Thirty 90-minutes sessions of pure oxygen at 2.5 ATA were conducted over a 10-week period. Complete healing was obtained after 8 months. DISCUSSION: We report herein a clinical case illustrating the efficacy of hyperbaric oxygen therapy for the treatment of ischemic ulcers of the toes in systemic sclerosis. It could offer an alternative therapeutic option, in particular for patients presenting resistant ischemic ulcers and a contraindication for or intolerance to the conventional medical treatment.

Meta-analysis of circulating adiponectin, leptin, and resistin levels in systemic sclerosis.

OBJECTIVE: We aimed to evaluate the relationship between circulating blood adipokine levels and systemic sclerosis (SSc). METHODS: We conducted a meta-analysis on serum/plasma adiponectin, leptin, or resistin levels in patients with SSc and controls, and performed a subgroup analysis based on ethnicity and/or disease type. RESULTS: Eleven studies (511 patients with SSc and 341 controls) were included in the meta-analysis. Meta-analysis revealed that adiponectin levels were significantly lower in patients with SSc than in controls (standardized mean differences [SMD] = -0.638; 95 % confidence intervals [CI] = -1.154, -0.122; P = 0.015). Stratification by ethnicity showed a low adiponectin level associated with SSc in Caucasians (SMD = -0.439; 95 % CI = -1.092, -0.213; P = 0.187) and Asians (SMD = -1.006; 95 % CI = -2.031, -0.019; P = 0.055), although this result was not statistically significant. Stratification by disease type revealed that the adiponectin level was significantly lower in the diffuse SSc, but not limited SSc, group than in the control (diffuse: SMD = -1.445; 95 % CI = -2.276, -0.614; P = 0.001; limited: SMD = 0.188; 95 % CI = -0.064, 0.439; P = 0.144). Meta-analysis showed no association between leptin levels and SSc (SMD = -0.029; 95 % CI = -1.362, 1.304; P = 0.966), and no association between resistin levels and SSc (SMD = 0.202; 95 % CI = -0.091, 0.496; P = 0.177). CONCLUSIONS: Our meta-analysis revealed a significantly lower circulating adiponectin level in patients with SSc than in controls. This difference was apparent in the diffuse type of SSc, but not in the limited type. However, circulating leptin and resistin levels were not different between patients with SSc and healthy controls.

Clinical, biochemical, and radiological characterization of the calcinosis in a cohort of Mexican patients with systemic sclerosis.

Calcinosis is a frequent complication of systemic sclerosis (SSc) that is usually located in extremities but may occur across the board. The aim of our study was to identify and quantify the distribution of calcinosis in a cohort of Mexican patients with SSc and its association with clinical features and autoantibodies. A cohort of patients with SSc (2013 ACR/EULAR criteria), classified in diffuse cutaneous (dcSSc) and limited cutaneous (lcSSc) (Le Roy criteria), was studied. For their analysis, patients were allocated into those with and without calcinosis (clinical and/or radiological). The evaluation included the modified Rodnan scale for skin and Medsger disease severity scale (DSS). Calcium, phosphorus, vitamin D, and parathyroid hormone (PTH) and antinuclear antibodies and extractable nuclear antigens were determined in serum. A total of 109 patients were included, 41 (37 %) with and 68 (63 %) without calcinosis. Calcinosis was more frequent in patients with dcSSc (55 vs 27 %). In total, we identified 354 sites with calcinosis and mean per patient of 12.0 ± 9.1; the most common sites affected were the hands (83 %), proximal upper extremity (27 %), and proximal lower extremity (22 %). Patients with calcinosis had a higher score of Rodnan scale, Mesdger DSS, and frequency of anti-nucleolar and anti-Scl-70 antibodies compared to those without calcinosis. Abnormal PTH elevation was found in 35 % of patients with calcinosis and 23 % without it. The prevalence of calcinosis is high in Mexican patients with SSc, especially in diffuse variety, and is associated with increased severity of disease.

Clinical and serological features of systemic sclerosis in a multicenter African American cohort: Analysis of the genome research in African American scleroderma patients clinical database.

Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort).African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987-2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated. Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression analyses.The study population included a total of 1009 African American SSc patients, comprised of 84% women. In total, 945 (94%) patients met the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SSc, with the remaining 64 (6%) meeting the 1980 ACR or CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) criteria. While 43% were actively employed, 33% required disability support. The majority (57%) had the more severe diffuse subtype and a young age at symptom onset (39.1 ±â€Š13.7 years), in marked contrast to that reported in cohorts of predominantly European ancestry. Also, 1 in 10 patients had a severe Medsger cardiac score of 4. Pulmonary fibrosis evident on computed tomography (CT) chest was present in 43% of patients and was significantly associated with anti-topoisomerase I positivity. 38% of patients with CT evidence of pulmonary fibrosis had a severe restrictive ventilator defect, forced vital capacity (FVC) ≤50% predicted. A significant association was noted between longer disease duration and higher odds of pulmonary hypertension, telangiectasia, and calcinosis. The prevalence of potentially fatal scleroderma renal crisis was 7%, 3.5 times higher than the 2% prevalence reported in the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) cohort.Our study emphasizes the unique and severe disease burden of SSc in African Americans compared to those of European ancestry.

Ethnic Differences in Autoantibody Diversity and Hierarchy: More Clues from a US Cohort of Patients with Systemic Sclerosis.

OBJECTIVE: To determine the autoantibody repertoire and clinical associations in a multiethnic cohort of American patients with systemic sclerosis (SSc). METHODS: There were 1000 patients with SSc (196 Hispanic, 228 African American, 555 white, and 21 other) who were screened for antinuclear antibodies (ANA), including anticentromere antibodies (ACA) by indirect immunofluorescence assay, antitopoisomerase-1 (topo-1/Scl-70) by immunodiffusion, and anti-RNA polymerase III (RNAP III) by ELISA. Sera from 160 patients with mainly nucleolar and/or speckled ANA pattern, but negative for ACA, Scl-70, and RNAP III, were further characterized by immunoprecipitation for SSc-specific antibodies. RESULTS: The prevalence of antibodies against RNAP III, Th/To, and PM/Scl did not differ significantly among the ethnic groups. The frequency of anti-Scl-70 was lowest in whites (18.0%) compared with 24.0% and 26.8% in Hispanics and African Americans (p = 0.01), respectively. Compared with African American patients, Hispanic and white subjects had a higher frequency of ACA (p < 0.0001) and lower frequency of U3-RNP (p < 0.0001). U3-RNP antibodies were uniquely higher in African American patients, independent of clinical subset, while Th/To autoantibodies were associated with limited cutaneous SSc in white subjects. Overall, Hispanic and African American patients had an earlier age of onset and a predominance of diffuse cutaneous SSc compared with their white counterparts. CONCLUSION: SSc-specific antibodies may predict disease subset; however, the hierarchy of their prevalence differs across ethnic groups. This study provides the most extensive analysis to date on the relevance of autoantibodies in the diagnosis and clinical manifestations of SSc in Hispanic American patients.

Examination of the association of sex and race/ethnicity with appearance concerns: a Scleroderma Patient-centered Intervention Network (SPIN) Cohort study.

OBJECTIVES: Appearance concerns are common in systemic sclerosis (SSc) and have been linked to younger age and more severe disease. No study has examined their association with sex or race/ethnicity. METHODS: SSc patients were sampled from the Scleroderma Patient-centered Intervention Network Cohort. Presence of appearance concerns was assessed with a single item, and medical and sociodemographic information were collected. RESULTS: Of 644 patients, appearance concerns were present in 72%, including 421 of 565 women (75%), 42 of 79 men (53%), 392 of 550 patients who identified as White (71%), 35 of 41 who identified as Black (85%), and 36 of 53 who identified as another race/ethnicity (68%). In multivariate analysis, women had significantly greater odds of reporting appearance concerns than men (odds ratio (OR)=2.97, 95% confidence interval (CI)=1.78-4.95, p<.001). Black patients had significantly greater odds of appearance concerns than White patients in unadjusted (OR=2.64, 95% CI=1.01-6.34, p=.030), but not multivariate analysis (OR=1.76, 95% CI=0.67-4.60, p=.250). Compared to a general population sample, appearance concerns were substantially more common in SSc, particularly for men across all age groups and for younger women. The most commonly reported features of concern were related to the face and head, followed by the hands and fingers; this did not differ by sex or race/ethnicity. CONCLUSIONS: Appearance concerns were common in SSc. Women were substantially more likely than men to have appearance concerns. Although non-significant in multivariate analysis, Black patients were more likely to have concerns than White patients, likely due to more severe changes in appearance.

A candidate gene study identifies a haplotype of CD2 as novel susceptibility factor for systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is a rare autoimmune disease (AID) with a complex genetic etiology. Evidence for a shared pathogenesis across AIDs is given by the well-known pleiotropism of autoimmune genes. Recently, several unbiased approaches have identified an association between polymorphisms of the CD2 gene, and rheumatoid arthritis (RA) susceptibility. The objective of this study was to investigate whether CD2 polymorphisms are associated with SSc. METHODS: Two SNPs of CD2, rs624988 and rs798036, were genotyped in a total of 1,786 SSc patients and 2,360 healthy individuals from two European populations (France and Italy). Meta-analyses were performed to assess whether an association exists between CD2 polymorphisms or haplotypes and SSc or its main subtypes. RESULTS: The combined analyses revealed an association between the rs624988 A allele and SSc susceptibility: padj=0.023, OR=1.14 (95%CI 1.04-1.25). Single marker analysis did not reveal any association between rs798036 and SSc. Haplotype analysis identified that the A-T haplotype, previously described in RA, was associated with higher susceptibility for SSc (padj=0.029, OR=1.14, 95%CI 1.04-1.25) and with the positive anti-centromere antibody sub-group of SSc patients (padj=0.009, OR=1.19 95%CI 1.07-1.32). Genotype-mRNA expression correlations revealed that the CD2 risk haplotype was associated with decreased CD2 mRNA expression in SSc patients. CONCLUSIONS: Our study establishes CD2 as a new susceptibility factor for SSc, in a European Caucasian population, confirming the sharing of autoimmune risk factors by SSc and RA.

African American race associated with body image dissatisfaction among patients with systemic sclerosis.

OBJECTIVES: Studies have shown a high degree of body image dissatisfaction among patients with systemic sclerosis (SSc). We aimed to identify demographic and phenotypic characteristics that correlate with body image dissatisfaction. METHODS: Ninety-eight patients with SSc were recruited from Georgetown University Medical Center 2003-2004. Anonymous surveys collected demographic information (age, race, gender, duration/type of SSc) and assessed degree of body image dissatisfaction on a scale of 0-3 in relation to phenotypic features of SSc (hand contractures, finger ulcers, pigmentation changes, lip wrinkling/thinning, telangiectasias). A composite total distress score was derived. Parametric and nonparametric T tests were used to compare groups. RESULTS: Of 98 patients, 86 were female and 12 male. The majority of patients were 30-60 years old. The sample was 62% Caucasian, 27% African American, and the rest identified as "other". Twenty-seven percent had limited SSc, 48% diffuse, and 25% "other". African American patients had greater total body image dissatisfaction (p=0.002), specifically with respect to digital ulcers, pruritus, and pigmentation changes, than Caucasian participants. Patients with diffuse SSc had greater body image dissatisfaction than those with limited disease (p=0.002). CONCLUSIONS: Our results suggest that African American patients with SSc and those with diffuse subtype suffer a higher degree of body image dissatisfaction. Screening for and addressing this issue in SSc patients is prudent. Further study is needed to understand racial differences in body image dissatisfaction among patients with SSc.