A study of gastrointestinal disease in systemic sclerosis and the effect on anorectal function and nutrition

This thesis investigates the prevalence and pathophysiology of gastrointestinal involvement in systemic sclerosis (SSc). The primary pathologies within the gastrointestinal tract affect the mucosa, vasculature, smooth muscle and enteric nervous system. The aim of this thesis was to conduct experiments to assess these pathologies within a well-characterised SSc patient cohort. Introduction: A review of the current understanding of the pathophysiology of gastrointestinal disease in systemic sclerosis. Prevalence of GI symptoms: A prospective questionnaire study of 400 patients in order to assess gut disease burden and review of patient disease characteristics. Anorectal involvement: Extensive anorectal physiological assessment of symptomatic and asymptomatic systemic sclerosis patients compared with incontinent controls in order to assess aspects of neuropathy and myopathy. Nutritional effect as an assessment of mucosal involvement: Nutritional assessment of patients with and without gastrointestinal symptoms through anthropometric assessment, indirect calorimetry and bioelectrical impedance. The pathophysiology of gastrointestinal involvement in systemic sclerosis was further investigated in an established mouse model of scleroderma. This transgenic mouse model expresses a kinase deficient type II TGFβ receptor (TβRIIΔk) in fibroblasts and the mice develop skin fibrosis as well as pulmonary fibrosis and a structural vasculopathy. Gastrointestinal tissue from these mice was examined histologically and the contractile activity of gut tissue was examined in vitro

Current management of the gastrointestinal complications of systemic sclerosis.

Systemic sclerosis is a multisystem autoimmune disorder that involves the gastrointestinal tract in more than 90% of patients. This involvement can extend from the mouth to the anus, with the oesophagus and anorectum most frequently affected. Gut complications result in a plethora of presentations that impair oral intake and faecal continence and, consequently, have an adverse effect on patient quality of life, resulting in referral to gastroenterologists. The cornerstones of gastrointestinal symptom management are to optimize symptom relief and monitor for complications, in particular anaemia and malabsorption. Early intervention in patients who develop these complications is critical to minimize disease progression and improve prognosis. In the future, enhanced therapeutic strategies should be developed, based on an ever-improving understanding of the intestinal pathophysiology of systemic sclerosis. This Review describes the most commonly occurring clinical scenarios of gastrointestinal involvement in patients with systemic sclerosis as they present to the gastroenterologist, with recommendations for the suggested assessment protocol and therapy in each situation