The Relationship Between Autonomic Dysfunction of the Gastrointestinal Tract and Emotional Distress in Patients With Systemic Sclerosis.

We hypothesized that emotional distress in systemic sclerosis (SSc) patients with moderate to severe gastrointestinal (GI) dysfunction is associated with dysautonomia. We sought to determine (1) the clinical characteristics associated with emotional distress in SSc, (2) the odds of having dysautonomia in those with emotional distress, and (3) whether GI dysautonomia, as measured by the Survey of Autonomic Symptoms (SAS), correlates with GI dysautonomia on the Composite Autonomic Symptom Score-31 (COMPASS-31). Clinical and demographic features from our prospective cohort study were compared among SSc patients with and without GI-associated emotional distress (University of California at Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 well-being subscale >0.5 or ≤0.5) in cross-sectional analysis. Covariates/confounders independently associated with emotional distress were used to construct multivariable logistic regression models. The COMPASS-31 and SAS GI subdomains were compared with Spearman correlation. Forty-six patients with SSc were enrolled in the study. In univariate analyses, age (odds ratio [OR], 1.06; p = 0.026), severity of GI dysautonomia (COMPASS-31: OR, 1.41; p = 0.003), anti-centromere (A/B) antibodies (OR, 3.60; p = 0.044), and anti-PM-Scl (75/100) antibodies (OR, 0.15; p = 0.035) were associated with emotional distress. In the adjusted model, those with more severe GI dysautonomia remained more likely to have emotional distress (OR, 1.85; p = 0.026); those with anti-PM-Scl (75/100) antibodies were less likely to have emotional distress (OR, 0.03; p = 0.031). The SAS and COMPASS-31 GI subdomains moderately correlated (ρ = 0.68, p < 0.001). In SSc, increased symptom burden related to GI dysautonomia is associated with emotional distress. Multidisciplinary approaches addressing both the physical and emotional needs of the SSc patient may be warranted to optimize patient care.

DiRenzo D ，Russell J ，Bingham CO 3rd ，McMahan Z ... -  《-》

Symptoms of Autonomic Dysfunction in Systemic Sclerosis Assessed by the COMPASS-31 Questionnaire.

Adler BL ，Russell JW ，Hummers LK ，McMahan ZH ... -  《-》

Clinical and serologic correlates of anti-PM/Scl antibodies in systemic sclerosis: a multicenter study of 763 patients.

Anti-PM/Scl autoantibodies are found in polymyositis, dermatomyositis, systemic sclerosis (SSc), and systemic autoimmune disease overlap syndromes. PM-1α is a major epitope of the PM/Scl complex, and antibodies against PM-1α can be detected using a validated enzyme-linked immunosorbent assay (ELISA). This study was undertaken to determine the prevalence and identify the clinical correlates of anti-PM-1α antibodies in a large cohort of patients with SSc. Serum samples were obtained from 763 patients with SSc enrolled in a multicenter Canadian cohort. The sera were analyzed by ELISA for the presence of antibodies against PM-1α. Associations between the presence of anti-PM-1α antibodies and demographic, clinical, and other serologic manifestations of SSc were investigated. Anti-PM-1α antibodies were present in 55 patients with SSc (7.2%), of whom almost 50% (26 of 55; 3.4% of the overall cohort) had no other SSc-specific antibodies, namely anticentromere, anti-topoisomerase I, and anti-RNA polymerase III. Features positively associated with the presence of anti-PM-1α antibodies included younger age at disease onset, skeletal muscle involvement, calcinosis, inflammatory arthritis, and overlap disease. Interstitial lung disease was less frequent and there were fewer gastrointestinal symptoms present in patients with anti-PM-1α antibodies compared to patients without these antibodies. Anti-PM-1α antibodies are relatively common in SSc and are associated with a distinct clinical phenotype, consistent with that described in association with other anti-PM/Scl autoantibodies. Although anti-PM-1α antibodies are not exclusive of other SSc-specific antibodies, they can be present in the absence thereof. Thus, anti-PM-1α antibodies may have considerable diagnostic and prognostic relevance in SSc.

D'Aoust J ，Hudson M ，Tatibouet S ，Wick J ，Canadian Scleroderma Research Group ，Mahler M ，Baron M ，Fritzler MJ ... -  《-》

Anti-RNPC-3 (U11/U12) Antibodies in Systemic Sclerosis in Patients With Moderate-to-Severe Gastrointestinal Dysmotility.

To examine the association of anti-RNPC-3 antibodies in patients with systemic sclerosis (scleroderma or SSc) with selected gastrointestinal (GI) tract complications. Sera from patients with SSc with or without severe GI dysfunction (total parenteral nutrition dependence) from the Johns Hopkins Scleroderma Center were screened for anti-RNPC-3 antibodies. We then examined anti-RNPC-3-positive cases and negative SSc controls from the University of Pittsburgh and the University of Pittsburgh Medical Center (UPMC) scleroderma cohort to confirm our findings and to examine whether specific GI features were associated with anti-RNPC-3 antibodies. In the discovery cohort, patients with SSc with severe GI dysfunction (n = 37) and without GI dysfunction (n = 38) were screened for anti-RNPC-3 antibodies. The former were more likely to have anti-RNPC-3 antibodies (14% versus 3%; P = 0.11). In the Pittsburgh cohort, moderate-to-severe GI dysfunction (Medsger GI score ≥2) was present in 36% of anti-RNPC-3-positive patients versus 15% of anti-RNPC-3-negative patients (P ≤ 0.01). Anti-RNPC-3-positive patients were more likely to be male (31% versus 15%; P = 0.04), African American (18% versus 6%; P = 0.02), have esophageal dysmotility (93% versus 62%; P < 0.01), and interstitial lung disease (ILD) (77% versus 35%; P < 0.01). After adjusting for relevant covariates and potential confounders, moderate-to-severe GI disease was associated with anti-RNPC-3 antibodies (odds ratio [OR] 3.8 [95% confidence interval (95% CI) 1.0-14.3]), and ILD trended toward significance (OR 2.8 [95% CI 1.0-8.2]). Patients with SSc and anti-RNPC-3 antibodies are more likely to be male and African American and to have moderate-to-severe GI disease and ILD. Further studies on larger patient cohorts may be helpful in further defining subsets of patients with SSc at risk for severe GI involvement.

McMahan ZH ，Domsic RT ，Zhu L ，Medsger TA ，Casciola-Rosen L ，Shah AA ... -  《-》

Evaluating the Associations Among Dysautonomia, Gastrointestinal Transit, and Clinical Phenotype in Patients With Systemic Sclerosis.

Our objective was to identify patients with systemic sclerosis (SSc) with a high burden of autonomic symptoms and to determine whether they have a distinct clinical phenotype, gastrointestinal (GI) transit, or extraintestinal features. In a prospective cohort of patients with SSc with GI disease, clinical data were systematically obtained at routine visits. Dysautonomia was identified by the Composite Autonomic Symptom Score (COMPASS)-31questionnaire. GI transit was measured by whole-gut scintigraphy. Associations between total COMPASS-31 scores and clinical features, GI symptoms, and transit were evaluated. Comparisons between patients with global autonomic dysfunction (GAD; ≥5 positive COMPASS-31 subdomains) and those with limited autonomic dysfunction (LAD; <5 positive subdomains) were also studied. A total of 91 patients with SSc and GI involvement were included (mean age 57 years, 90% female, 74% limited cutaneous disease, 83% significant GI disease [Medsger score ≥2]). The mean COMPASS-31 score in patients with SSc was higher than controls (38.8 vs 7.2); 33% had GAD, and 67% had LAD. Patients with GAD were more likely to have limited SSc (93% vs 65%; P < 0.01) and have sicca symptoms (100% vs 77%; P = 0.01). Gastric and colonic transit were faster in patients with GAD (P < 0.05). Upper GI involvement (Medsger GI score of 1 or 2) was associated with higher total COMPASS-31 scores (P = 0.02). Symptoms of global dysautonomia are seen in up to one-third of patients with SSc and GI involvement. Identifying specific clinical characteristics associated with GAD in SSc will help to identify a population that may benefit from therapies that modulate the autonomic nervous system.

Alvarez-Hernandez MP ，Adler B ，Perin J ，Hughes M ，McMahan ZH ... -  《-》