Consensus best practice pathway of the UK scleroderma study group: gastrointestinal manifestations of systemic sclerosis.

Systemic sclerosis is an autoimmune connective tissue disorder, which can be progressive with multisystem involvement. Guidance on the management of complications is based on a limited data set and practice amongst clinicians can vary. The UK Scleroderma study group set up several working groups to agree some consensus pathways for the management of specific complications. Approximately nine out of ten patients with systemic sclerosis will have involvement of the gastrointestinal system and in this review article we explore the management of these complications in a symptom-based approach. The algorithms are a useful tool for clinicians, which we hope, will be a point of reference and highlight the need for further research in these areas.

Fecal incontinence in systemic sclerosis is secondary to neuropathy.

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.

Gut fibrosis with altered colonic contractility in a mouse model of scleroderma.

OBJECTIVE: Gastrointestinal involvement occurs in up to 90% of patients with SSc. Animal models of SSc mimic some of the pathophysiological disease processes of SSc. The transgenic (TG) mouse strain TßRIIΔk-fib is characterized by ligand-dependent up-regulation of TGF-ß signalling and has been shown to develop skin fibrosis, lung fibrosis and diminished aortic ring contractility and adventitial fibrosis. We investigated if similar changes are observed in the gut tissue in this mouse model. METHODS: Colonic tissue was examined using histology and immunohistochemistry analyses. Tissue architecture was examined by haematoxylin and eosin (H&E), picrosirius red and immunohistochemical markers for α-smooth muscle actin (α-SMA), phospho-Smad 2/3 (pSmad2/3), Ki-67, protein gene product 9.5 and S-100. Fibrosis was quantified using the NIS Elements BR 2.30 system and by Sircol assay. Colonic strip contractile responses to potassium chloride (KCl) and carbachol were assessed in isolated organ baths. Confirmatory gut fibroblast and intestinal tissue biochemical assays, including cellular signalling mechanisms, were performed. RESULTS: H&E staining and staining for α-SMA, Ki-67, pSmad2/3 or neural tissue staining showed no differences between TG and wild-type (WT) mice gut tissue. There was increased collagen deposition in the gut of TG mice. Quantitative PCR results of TG gut fibroblasts showed evidence of up-regulated collagen and CTGF transcription, and non-canonical TGF-ß signalling pathways were also up-regulated. The organ bath studies showed diminished colonic strip contractility in TG mice compared with WT control mice to KCl and carbachol. CONCLUSION: We have shown that this TG mouse model, previously shown to develop skin and lung, develops colonic fibrosis with associated effects on colonic tissue contractility. This may offer further insight in pathological processes leading to the development of gut fibrosis.

Internal anal sphincter atrophy in patients with systemic sclerosis.

OBJECTIVES: SSc is a connective tissue, multisystem disorder of unknown aetiology. The gastrointestinal tract (GIT) is affected in up to 90% of patients. The exact pathophysiology of GIT involvement is not known, but it is related to both neurogenic and myogenic abnormalities as well as possible vascular and ischaemic changes. Thinning of the internal anal sphincter (IAS) has been demonstrated in SSc with faecal incontinence. We aimed to investigate anal sphincter structure in patients with SSc. METHODS: Forty-four SSc patients [24 symptomatic (Sx) and 20 asymptomatic (ASx)] and 20 incontinent controls (ICs) were studied. Patients underwent anorectal manometry and endoanal US. RESULTS: In the ICs, external anal sphincter defects were more common, but the IAS was less atrophic, evident by both atrophy scores and IAS thickness. There was no significant difference in atrophy scores [Sx: 2 (1.5-3) vs ASx: 2 (1-2)] or IAS thickness [Sx: 1.85 (1.5-2.3) vs ASx: 1.8 (1.7-2.25)] between the Sx and ASx SSc patients. CONCLUSION: Patients with SSc (both Sx and ASx) have thin and atrophic IAS, suggesting that IAS atrophy develops even in ASx patients and this may be amenable to treatment with sacral neuromodulation.

Assessment of gastrointestinal symptoms in patients with systemic sclerosis in a UK tertiary referral centre.

OBJECTIVES: The gastrointestinal tract (GIT) is affected in up to 90% of patients with SSc to a variable extent and severity. We aimed to establish the frequency and range of gastrointestinal (GI) symptoms in SSc patients at the Royal Free Hospital, a tertiary referral centre. METHODS: A 52-item, previously validated, questionnaire capturing SSc-related gut dysfunction was given to consecutive patients with SSc attending the rheumatology outpatient department. The questionnaire assesses the 'frequency' of five categories of symptoms and their 'impact' on social functioning and emotional well-being. Patients' notes were reviewed to establish disease subtype, autoantibody profile and other internal organ involvement. RESULTS: We collected 402 completed questionnaires (357 females; mean age 55). Sixty-nine per cent of patients had lcSSc and 30% dcSSc with mean disease duration of 11 years. Mean questionnaire scores showed that patients have a wide range of GI symptoms. Ninety-four per cent of patients reported upper and 79% lower GI symptoms, 3% of patients reported no symptoms and 10% reported daily symptoms. There was no association between disease subtype or autoantibody profile and GI symptoms. There was a positive correlation between diarrhoea scores (high scores = best health) and pulmonary fibrosis (r = 0.134, P = 0.0068). No other association between GI symptoms and other internal organ involvement was found. CONCLUSIONS: GI symptoms, both upper and lower, are common in patients with SSc. Patients should be asked specifically about GI symptoms as they may be under-reported and therefore under-treated. GI focused questionnaire is an effective way to assess gut symptoms and adjust treatment.