Introduction: The gastrointestinal tract (GI) is the second most affected organ system in systemic sclerosis or systemic/localized scleroderma (SSc) and is an important topic for research. Approximately 90% of patients with scleroderma exhibit pathology of the GI tract. The systemic scleroderma has the potential to impact any part of the gastrointestinal tract, between the oral cavity and anorectum. The pathological complications of scleroderma adversely impact the health-related quality of life of the affected patients and increase the treatment burden of patients and medical professionals. Study Aim: We summarized the epidemiology, commonly reported clinical manifestations, complications, and available therapies for treating the GI pathology in systemic scleroderma patients. Methodology: We performed a literature review using the keywords "systemic sclerosis," "scleroderma," "GI manifestations in scleroderma," and "GI complications of scleroderma" across databases, including Google Scholar, Medline, Embase, and PubMed. We also analyzed a range of case reports concerning scleroderma manifestations and treatment modalities. Results: Our research revealed the annual incidence of SSc attributing to19.3 cases per million adults in the United States. We found the highest incidence of systemic scleroderma in patients within the age range of 44-55 years. Our results affirmed 5:1 incidence of systemic scleroderma that confirmed the higher impact of this disease condition in females than male populations. We found that the gastrointestinal manifestations of systemic scleroderma predominantly elevate the morbidity and mortality incidence among the affected patients. Esophageal and intestinal manifestations impact 90% and 40-70% of patients with systemic scleroderma. The small bowel hypomotility and small intestinal bacterial overgrowth (SIBO) in systemic scleroderma cases trigger the episodes of malabsorption and malnutrition that eventually add to 50% of the mortality rate. Systemic sclerosis is associated with the high incidence of fecal incontinence that triggers depression and its deleterious mental health manifestations in many clinical scenarios. Conclusion: The gastrointestinal complications in systemic sclerosis potentially deteriorate the daily living activities of the affected patients. The systematic management of the gastrointestinal complications of systemic scleroderma warrants multidisciplinary approaches. Prospective studies should focus on developing targeted therapies for improving the recovery patterns and prognostic outcomes in systemic scleroderma cases.

Regulatory T cells are key immune cells to initiate tolerable immune responses. TGFβ is the key cytokine of regulatory T cells. TGFβ is also the master cytokine to stimulate tissue fibrosis. Systemic sclerosis is an autoimmune disease related to overt organ fibrosis. Thus, systemic sclerosis is a disease related to regulatory T cell over-representation. Besides, many end stage organ failures including heart failure, liver cirrhosis, uremia, and pulmonary fibrosis also related to tissue fibrosis. Thus, TGFβ producing regulatory T cells are also involved in the pathogenesis of these end stage organ failure. Once we know the significance of TGFβ and it induced tolerable immune reactions in the pathophysiology of end organ failure, we can develop better prevention or therapeutic strategies to combat these detrimental disorders.

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by pathological processes involving autoimmunity, vasculopathy, and resultant extensive skin and organ fibrosis. Recent studies have demonstrated activation and aberrant wound healing responses in the epithelial layer of the skin in this disease, implicating the epithelial keratinocytes as a source of pro-fibrotic and inflammatory mediators. In this paper we investigated the role of Immunoglobulin G (IgG) autoantibodies directed against epithelial cells, as potential initiators and propagators of pathological keratocyte activation and the ensuing SSc fibrotic cascade. A keratinocyte cell-based ELISA is used to evaluation binding of SSc IgG. SSc skin biopsies were stained by immunofluorescence for the presence of IgG in the keratinocyte layer. Moreover, IgG purified from SSc sera is evaluated for the potential to activate keratinocytes in tissue culture and to induce signaling in TLR2 & 3 reporter cell lines. We demonstrate enhanced binding of SSc IgG to keratinocytes, and activation of these cells leading to release of IL-1α, representing a potential initiating pathway in this disease.