Background/Purpose: Despite the fact that up to 90% of scleroderma (SSc) patients are affected by gastrointestinal (GI) dysmotility, features associated with severe GI disease are not well-defined. We sought to identify such features by studying a large cohort of SSc patients requiring parenteral nutrition (TPN) for severe GI dysmotility and SSc controls with mild or no GI symptoms.

Methods: Patients were selected from the Johns Hopkins Scleroderma Center cohort database (clinic visits from 1991-2015) and met either 1980 American College of Rheumatology criteria or at least three of five features of the CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome for SSc. All patients with SSc who required TPN for SSc GI dysmotility, and all patients with SSc and mild or no GI symptoms (modified GI Medsger score of 0 or 1) were included in this study. Demographic and clinical data were obtained on each patient at the time of the clinical visit when they were first assigned their maximum GI score. Myopathy was defined by the presence of abnormal muscle enzymes (CK, aldolase), an irritable myopathy on EMG, and/or muscle biopsy findings associated with SSc. In the cross-sectional analysis, associations between dichotomous variables were assessed using Chi-square or Fischer’s exact tests. T-tests were applied to parametric data to evaluate for significant differences in the means of continuous variables between two groups. Univariate logistic regression analyses further explored associations between disease characteristics and severe GI dysmotility. Significant findings from the univariate analyses and potential confounders were then included in a multivariable model to determine whether associations remained significant after adjusting for relevant covariates.

Results: There were 59 TPN dependent SSc patients, and 1,744 SSc patients with mild or no GI symptoms. 1,456 (81%) of patients were female and 347 (19%) of patients were male. In the univariate analysis, we identified male sex (OR 2.2, CI 1.28, 3.86; p = 0.005), diffuse cutaneous disease (OR 2.62, CI 1.53, 4.45; p = <0.001), and black race (OR 2.5, CI 1.42, 4.39; p = 0.001), as features associated with severe GI dysmotility in SSc. Myopathy was also found to associate with severe SSc GI dysmotility (OR 4.5, CI 2.61, 7.79; p = <0.001). After adjusting for potential confounders (age, disease duration, and history of diabetes), male gender (OR 2.6, CI 1.17, 5.90; p=0.02), diffuse disease (OR 2.79, CI 1.20, 6.47; p = 0.017), and myopathy (OR 3.6, CI 1.54, 8.33; p = 0.003), all remained significantly associated with severe GI dysmotility.

Conclusion:  We utilized the largest reported cohort to date of TPN-dependent SSc patients to define phenotypic features associated with severe GI dysmotility. Our results demonstrate that male sex, diffuse cutaneous disease, and myopathy are significantly associated with severe SSc GI dysmotility. As myopathy is a complication associated with severe SSc GI dysmotility, defining autoantigens common among smooth and skeletal muscle may provide insight into disease pathogenesis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/diffuse-scleroderma-male-sex-and-myopathy-are-associated-with-severe-gastrointestinal-dysmotility-in-scleroderma/