Anti-U1RNP antibodies are associated with a distinct clinical phenotype and a worse survival in patients with systemic sclerosis.

OBJECTIVES: To clarify the impact of anti-U1RNP antibodies on the clinical features and prognosis of patients with SSc. METHODS: We conducted a monocentric case-control, retrospective, longitudinal study. For each patient with SSc and anti-U1RNP antibodies (SSc-RNP+), one patient with mixed connective tissue disease (MCTD) and 2 SSc patients without anti-U1RNP antibodies (SSc-RNP-) were matched for age, sex, and date of inclusion. RESULTS: Sixty-four SSc-RNP+ patients were compared to 128 SSc-RNP- and 64 MCTD patients. Compared to SSc-RNP-, SSc-RNP+ patients were more often of Afro-Caribbean origin (31.3% vs. 11%, p < 0.01), and more often had an overlap syndrome than SSc-RNP- patients (53.1 % vs. 22.7%, p < 0.0001), overlapping with Sjögren's syndrome (n = 23, 35.9%) and/or systemic lupus erythematosus (n = 19, 29.7%). SSc-RNP+ patients were distinctly different from MCTD patients but less often had joint involvement (p < 0.01). SSc-RNP+ patients more frequently developed interstitial lung disease (ILD) (73.4% vs. 55.5% vs. 31.3%, p < 0.05), pulmonary fibrosis (PF) (60.9% vs. 37.5% vs. 10.9%, p < 0.0001), SSc associated myopathy (29.7% vs. 6.3% vs. 7.8%, p < 0.0001), and kidney involvement (10.9% vs. 2.3% vs. 1.6%, p < 0.05). Over a 200-month follow-up period, SSc-RNP+ patients had worse overall survival (p < 0.05), worse survival without PF occurrence (p < 0.01), ILD or PF progression (p < 0.01 and p < 0.0001). CONCLUSIONS: In SSc patients, anti-U1RNP antibodies are associated with a higher incidence of overlap syndrome, a distinct clinical phenotype, and poorer survival compared to SSc-RNP- and MCTD patients. Our study suggests that SSc-RNP+ patients should be separated from MCTD patients and may constitute an enriched population for progressive lung disease.

Muscle involvement in systemic sclerosis: high mortality not associated with nature of histological lesions.

OBJECTIVES: The aim of this study was to determine the association between different histological patterns and prognosis in patients with SSc and histologically proven muscle involvement. METHODS: A multicentre retrospective study was conducted of a cohort of scleroderma patients who had undergone muscle biopsy. The biopsies were reviewed in a coordinated manner to classify patients based on histological findings. Three different patterns were observed: fibrosing myopathy (FM), inflammatory myopathy (IM) and necrotizing myopathy (NM). Rates of survival, muscle relapse, and cardiac and pulmonary events were compared between these three groups. RESULTS: Among 71 scleroderma patients with muscle biopsy specimens available for review, 33 (46.5%) were classified in the FM group, 18 (25.5%) in the IM group, and 20 (28%) in the NM group. The median follow-up time was 6.4 years (interquartile range, 2.2-10.9 years) and 21 patients died during follow-up, primarily from heart disease and infections. The 10-year survival rate after the first non-Raynaud's disease symptom was 80% and the cumulative incidence of muscle relapse was 25%. Neither factor differed significantly between the three groups. The risk of pulmonary events was lowest in the OM group, significantly lower than in the FM group (hazard ratio, 0.17; 95% CI, 0.04-0.67) and non-significantly lower than in the IMNM group (hazard ratio, 0.28; 95% CI, 0.06-1.24). The risk of cardiac events did not differ significantly between the three groups. CONCLUSION: The mortality rate of scleroderma patients with muscle involvement was not associated with their histological patterns.

Polypharmacy, drug-drug interactions, and adverse drug reactions among systemic sclerosis patients: A cross-sectional risk factor study.

OBJECTIVES: Polypharmacy, drug-drug interactions (DDI) and related adverse drug reaction (ADR) are understudied in SSc. The aim of this work was to determine the prevalence and determinants of DDI and ADR in a real-life prospective cohort of SSc patients. METHODS: We performed a retrospective analysis of the drug prescriptions of SSc patients admitted to the daily scleroderma clinic between January 2020 and April 2022. DDI were identified using 2 prescription analysis applications, and adjudicated related ADRs occurring during a one-year follow-up were reported. Risk factors for DDI and ADR were identified using multivariate analysis. RESULTS: One hundred and eight SSc patients were included. The median number of medications per patient was 6 [4-9]. Seventy-one (65.7 %) patients had 5 or more medications, and 23 (21.3 %) had 10 or more. Seventy-two (66.7 %) patients had DDIs on their prescriptions at inclusion. Patients with DDIs had more medications than patients without DDIs (7 [5-10] versus 3 [2-5], p < 0.0001). Six (8.3) patients experienced ADRs during the one-year follow-up. Patients with ADRs had more medications (14 [10-18] versus 7 [5-10] p < 0.001) and more DDIs (12 [7-32] versus 3 [1-6]; p < 0.001) than patients without ADRs. Multivariate analysis confirmed that the number of prescribed medications was independently positively associated with DDIs (OR: 2.25 [1.52-3.32], p < 0.0001) as well as with ADRs (OR: 1.68 [1.17-2.40], p < 0.01). CONCLUSIONS: SSc patients are significantly exposed to polypharmacy, DDIs and related ADRs, particularly in cases of severe illness, and especially if 5 or more medications are prescribed.

Assessing hand and global disability in a cohort of Algerian patients with systemic sclerosis: Construct validities of the Arab Hand Function Index and the Arabic Health Assessment Questionnaire.

Objective: The study aimed to assess the construct validity of the Arab Hand Function Index and the Arabic Health Assessment Questionnaire in Algerian patients with systemic sclerosis. Methods: Consecutive Algerian patients who fulfilled the American College of Rheumatology/European League Against Rheumatism criteria for systemic sclerosis were included. In addition to disease characteristics, global disability and hand disability were assessed using the Arabic Health Assessment Questionnaire and the Arab Hand Function Index, respectively. Construct validity was assessed by convergent and divergent validity (Spearman's rank correlation coefficient) and factor analysis. The scale reliability was assessed using the Cronbach's alpha. Results: We evaluated 100 systemic sclerosis patients (83 females) of mean ± standard deviation age 46.7 ± 12.3 years, including 59 limited cutaneous systemic sclerosis and 41 diffuse cutaneous systemic sclerosis. Raynaud's phenomenon was detected in 99 patients and digital ulcers in 25. Gastrointestinal tract involvement and interstitial lung disease were detected in 86/100 (86%) and 46/72 (63.9%) patients, respectively. Anti-topoisomerase I and anti-centromere antibodies were detected in 33/76 (43.4%) and 23/76 (30.3%) patients, respectively. The Arab Hand Function Index had a good construct validity with a total score explaining 61% of the variance of the Arabic Health Assessment Questionnaire which also had a good construct validity. Factor analysis of the Arab Hand Function Index and the Arabic Health Assessment Questionnaire items extracted two factors explaining 64% of the variance for the Arab Hand Function Index and one factor explaining 55% of the variance for the Arabic Health Assessment Questionnaire. The Arab Hand Function Index and the Arabic Health Assessment Questionnaire were reliable questionnaires with a Cronbach's alpha >0.8. Conclusion: In Algerian patients with systemic sclerosis, Arab Hand Function Index and Arabic Health Assessment Questionnaire have a good construct validity and reliability.