nature publishing group ORIGINAL CONTRIBUTIONS FUNCTIONAL GI DISORDERS 597 © 2012 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY INTRODUCTION Systemic Sclerosis (SSc) is a multisystem disorder characterized by excess connective tissue deposition in the skin and internal organs, including the lungs, heart, kidneys, and gastrointestinal tract (GIT) (1,2). Te GIT is afected in up to 90% of patients, with the esophagus being the most commonly afected site (3). Upper GI symptoms such as heartburn, dysphagia, and abdominal dis- tension are the most commonly reported symptoms (4,5). Lower GI symptoms such as diarrhea, constipation, evacuation difculty, and fecal incontinence, although common and with a major efect on quality of life, are ofen under-reported (6,7). Te exact pathophysiology of GIT involvement is not known, but it is related to both neurogenic and myogenic abnormalities (8,9). Histologically the main changes seen in the GIT are patchy atrophy of the muscularis propria and varying degrees of fbrosis as the disease progresses (10). Te smooth muscle atrophy seen is thought to be secondary to vascular ischemia and neural plexus dysfunctions (11,12). Physiologically, the typical resulting abnor- mality is dysmotility, such as low amplitude contraction in the distal esophagus, and decreased or absent migrating motor com- plexes in the intestine (4,8,13). Reduced blood fow has also been demonstrated in the stomach and duodenum (14,15). Anatomical changes such as intestinal dilatation usually occur as the disease progresses and are thought to relate to severe dysmotility. A number of observational studies have investigated anorectal problems in SSc. Te anorectum is afected in 50–70% of patients (16,17). Fecal incontinence has been reported in up to 38% of patients, although in view of the embarrassing nature of this symptom, it is widely believed that this is an underestimate (6). Te under- lying mechanisms have not been systematically addressed though, and are still unclear, although there is evidence of neural dysfunc- tion, smooth muscle atrophy, and fbrosis. Most studies have shown Fecal Incontinence in Systemic Sclerosis Is Secondary to Neuropathy Nora M. Thoua, BSc, MBBS, MRCP 1 , Mostafa Abdel-Halim, MSc, MRCS 1 , Alastair Forbes, BSc, MD, FRCP, FHEA 2 , Chris P. Denton, PhD, FRCP 3 and Anton V. Emmanuel, BSc, MD, FRCP 1 OBJECTIVES: Systemic sclerosis (SSc) is a chronic multi-system autoimmune disorder with gastrointestinal tract (GIT) involvement in up to 90% of patients and anorectal involvement occurs in up to 50% of patients. The pathogenesis of gastrointestinal abnormalities may be both myogenic and neurogenic. We aimed to identify which anorectal physiological abnormalities correlate with clinical symptoms and thus understand the pathophysiology of anorectal involvement in SSc. METHODS: In total, 44 SSc patients (24 symptomatic (Sx) (fecal incontinence) and 20 asymptomatic (ASx)) and 20 incontinent controls (ICs) were studied. Patients underwent anorectal manometry, rectal mucosal blood flow (RMBF), rectal compliance (barostat), and rectoanal inhibitory reflex assessment (RAIR). RESULTS: Anal squeeze pressure was lower in the IC group compared with both the ASx and Sx groups (IC: 46.95 (30–63.9)) vs. ASx: 104.6 (81–128.3) vs. (Sx: 121.4 (101.3–141.6); P < 0.05). Resting pressure was lower in the IC group. RMBF and rectal compliance did not differ between groups. Anal, but not rectal, sensory threshold, was significantly attenuated in Sx patients (Sx: 10.4 (8.8–11.4) vs. ASx: 6.7 (5.7–7.7) vs. IC: 8.5 (6.5–10.4); P < 0.05). There was a positive correlation between anal sensory thresholds and incontinence score in SSc patients ( r = 0.54; P < 0.05). RAIR was absent in 11/24 Sx patients but only in 2/20 ASx and in 1/20 IC patients. CONCLUSIONS: Fecal incontinence in SSc is related to neuropathy as suggested by absent RAIR and higher anal sensory threshold and is related less so to sphincter atrophy and rectal fibrosis. Am J Gastroenterol 2012; 107:597–603; doi:10.1038/ajg.2011.399; published online 15 November 2011 1 GI Physiology Unit, University College London Hospital, London, UK; 2 Gastroenterology Department, University College London Hospital, London, UK; 3 Centre for Rheumatology, Royal Free Hospital, London, UK. Correspondence: Nora M. Thoua, BSc, MBBS, MRCP, GI Physiology Unit, University College London Hospital, 250 Euston Road, NW1 2BU, London, UK. E-mail: norathoua@hotmail.com Received 26 July 2011; accepted 19 October 2011