Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis.

BACKGROUND: Gastrointestinal tract (GIT) involvement is a common cause of debilitating symptoms in patients with systemic sclerosis (SSc). There are no disease modifying therapies for this condition and the treatment remains symptomatic, largely owing to the lack of a clear understanding of its pathogenesis. AIMS: To investigate novel aspects of the pathogenesis of gastrointestinal involvement in SSc. To summarise existing knowledge regarding the cardinal clinical gastrointestinal manifestations of SSc and its pathogenesis, emphasising recent investigations that may be valuable in identifying potentially novel therapeutic targets. METHODS: Electronic (PubMed/Medline) and manual Google search. RESULTS: The GIT is the most common internal organ involved in SSc. Any part of the GIT from the mouth to the anus can be affected. There is substantial variability in clinical manifestations and disease course and symptoms are nonspecific and overlapping for a particular anatomical site. Gastrointestinal involvement can occur in the absence of cutaneous disease. Up to 8% of SSc patients develop severe GIT symptoms. This subset of patients display increased mortality with only 15% survival at 9 years. Dysmotiity of the GIT causes the majority of symptoms. Recent investigations have identified a novel mechanism in the pathogenesis of GIT dysmotility mediated by functional anti-muscarinic receptor autoantibodies. CONCLUSIONS: Despite extensive investigation, the pathogenesis of gastrointestinal involvement in systemic sclerosis remains elusive. Although treatment currently remains symptomatic, an improved understanding of novel pathogenic mechanisms may allow the development of potentially highly effective approaches including intravenous immunoglobulin and microRNA based therapeutic interventions

A physiological study of the anorectal reflex in patients with functional anorectal and defecation disorders

OBJECTIVE: The symptoms of fecal incontinence and constipation can arise from a variety of alterations of anorectal function. The aim of this study was to investigate components of the anorecal reflex in patients with these symptoms, to determine the functional significance of the various physiological parameters. METHODS: 21 healthy volunteers (controls), 78 incontinent and 74 constipated patients were recruited and symptom burden determined using the Wexner incontinence and constipation questionnaires. All participants underwent standardised anorectal physiology including anorectal manometry, anorectal distension and electrosensitivity thresholds, rectal mucosal blood flow and rectoanal inhibitory reflex measurement. RESULTS: Patients with passive incontinence had lower resting sphincter pressures than controls (38 vs 87cmH2 O, p < 0.05), while those with urge incontinence had lower squeeze pressures than controls (37 vs 119cmH2 O, p < 0.05). Patients with urge incontinence had lower maximal tolerable volumes (100 vs 166mL, p < 0.05). Patients with slow transit constipation had elevated rectal electrosensitivity thresholds compared to controls (31.4 vs 20.2, p < 0.05), and also showed lower mucosal blood flow than patients with evacuation difficult and controls (107 vs 162 (evacuation difficult) vs 169 (controls), p < 0.05). Only patients with passive incontinence were associated with reflex abnormalities (prolonged recovery phase (1.2 vs 0.5 msec, p < 0.05) and total duration of reflex (6.3 vs 4.3 msec, p < 0.05)). CONCLUSION: Anorectal motor, sensory and reflex abnormalities are seen in distinct patterns in patients with fecal incontinence and constipation. This would suggest distinct physiological differences which may predict the potential for different treatment neuromodulation and behavioural modalities in these conditions