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

Abstract

SUMMARY Background Gastrointestinal tract involvement is a common cause of debilitating symptoms in patients with systemic sclerosis. 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. Aim To investigate novel aspects of the pathogenesis of gastrointestinal involvement in systemic sclerosis To summarize existing knowledge regarding the cardinal clinical gastrointestinal manifestations of systemic sclerosis and its pathogenesis, emphasizing recent investigations that may be valuable in identifying potentially novel therapeutic targets. Methods Electronic (Pubmed/Medline) and manual Google search Results The gastrointestinal tract is the most common internal organ involved in systemic sclerosis. Any part of the gastrointestinal tract from the mouth to the anus can be affected. There is substantial variability in clinical manifestations and disease course and symptoms are non-specific and overlapping for a particular anatomical site. Gastrointestinal involvement can occur in the in the absence of cutaneous disease. Up to 8% of systemic sclerosis patients develop severe gastrointestinal tract symptoms. This subset of patients display increased mortality with only 15% survival at 9 years. Dysmotiity of the gastrointestinal tract causes the majority of symptoms. Recent investigations have identified a novel mechanism in the pathogenesis of gastrointestinal tract dysmotility mediated by functional anti-muscarinic receptor autoantibodies. Conclusion 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.

Systemic sclerosis – diagnostic and therapeutic recommendations of the Polish Dermatological Society. Part 1: diagnosis and monitoring

“…Oesophageal scintigraphy with oral administration of a technetium-99m labelled agent, followed by the measurement of oesophageal transit time, is a test detecting oesophageal motor disorders such as food retention and gastrointestinal reflux [53]. Ultrasonography is a very sensitive technique for diagnosing primary biliary cirrhosis (PBC) which often accompanies systemic sclerosis, and for evaluating the abdominal cavity in patients with abdominal pain secondary to scleroderma [53]. Oesophageal abnormalities can be assessed by 24-hour pH monitoring in proximal and distal oesophagus.…”

“…Począt-kowo badanie może uwidocznić obniżoną amplitudę skurczów w dystalnych 2/3 przełyku, natomiast w dalszym przebiegu choroby obserwuje się zmniejszenie napięcia dolnego zwieracza przełyku [51]. Scyntygrafia przełyku z doustnym zastosowaniem płynu znakowanego technetem 99mTC, a następnie mierzeniem czasu przechodzenia przez przełyk wykrywa zaburzenia motoryki przełyku -zaleganie pokarmu i refluks żo-łądkowo-jelitowy [53]. Badanie ultrasonograficzne jest bardzo czułą metodą diagnozowania pierwotnej żółcio-wej marskości wątroby (primary biliary cirrhosis -PBC), często związanej z SSc, a także oceny jamy brzusznej u pacjentów z bólami brzucha w przebiegu twardziny [53].…”

“…Scyntygrafia przełyku z doustnym zastosowaniem płynu znakowanego technetem 99mTC, a następnie mierzeniem czasu przechodzenia przez przełyk wykrywa zaburzenia motoryki przełyku -zaleganie pokarmu i refluks żo-łądkowo-jelitowy [53]. Badanie ultrasonograficzne jest bardzo czułą metodą diagnozowania pierwotnej żółcio-wej marskości wątroby (primary biliary cirrhosis -PBC), często związanej z SSc, a także oceny jamy brzusznej u pacjentów z bólami brzucha w przebiegu twardziny [53]. W badaniu zmian w przełyku zastosowanie ma 24-godzinne monitorowanie pH proksymalnej i dystalnej części przełyku.…”

Detecting gastrointestinal manifestations in patients with systemic sclerosis using anti-gAChR antibodies

“…Systemic sclerosis (SSc), a multi-systemic disorder of the connective tissues, is characterized by widespread vascular damage and fibrosis of the skin and visceral organs [13,14] Gastrointestinal (GI) manifestations occur frequently in patients with SSc [15][16][17]. Pseudo-obstruction, malabsorption, gastroesophageal reflux disease (GERD), nausea, vomiting, constipation, and diarrhea are some of the GI complications that can occur in SSc [18][19][20][21][22]. In addition, autonomic dysfunction is also common in SSc, starting early during the disease process and sometimes precedes the development of fibrosis [23][24][25][26][27].…”

“…Anti-RNA polymerase III is also an important biomarker associated with severe dcSSc and a 25% risk of renal crisis [29]. Earlier studies demonstrated that GI dysmotility in SSc was associated with circulating Abs against the muscarinic AChRs and myenteric neurons [19,[29][30][31][32][33][34][35]. Recently, McMahan and colleagues reported patients with SSc and anti-RNPC3 antibodies had moderate-to-severe GI disease and interstitial lung disease [36].…”