SSc, or scleroderma, is a serious multi-system disorder of connective tissue disease characterized clinically by thickening and fibrosis of the skin and involvement of internal organs, most commonly the lungs, gastrointestinal tract and heart. SSc affects predominantly women in the prime of their life and is associated with increased morbidity and mortality. SSc is a rare disease with prevalence estimates varying from 30-443/million population1,2 which at the upper bound of 4.43/10,000 is less than 5/10,000 (500/million), the definition used by most funders for a rare disease.
The gastrointestinal tract (GIT) is the most commonly involved internal organ in SSc. GIT involvement is the presenting feature in 10%, occurs during disease course in up to 95%, and is responsible in 6-12% of all deaths in SSc patients3-9. Hypomotility of the bowel in SSc leads to small intestinal bacterial overgrowth (SIBO) in 30–62% of patients10-13. The most carefully performed study of the relationship of symptoms to the presence of SIBO found that symptoms occurring more commonly in patients with SIBO compared to other SSc patients are: abdominal pain/discomfort (86.4 vs 31%), bloating (77.3 vs 44.8%), diarrhea (50 vs 10.3%), constipation (59.1 vs 3.4%) and abdominal tenderness (54.5 vs. 6.9%)10.
There is reason to believe that GI symptoms contribute significantly to quality life in SSc. We found that GI symptoms are an important independent predictor of global pain in SSc4 as well as fatigue5. We also found that the number of GI symptoms was a significant contributor to global health related quality of life (HRQoL) as measured by the SF-366 and the World Health Organization Disability Assessment Schedule II7, both patient-reported generic HRQoL instruments. Also, depression is common in SSc and the number of GI symptoms are significantly associated with that9. We also noted that malnutrition occurs in 18% of our patients and that GI symptoms, especially those often associated with small intestinal bacterial overgrowth (SIBO) such as abdominal bloating and diarrhea, are significantly associated with malnutrition8.
As such, it seems possible that the appropriate treatment of SIBO in SSc could substantially improve not only GI symptoms but also HRQoL, global pain, fatigue and depression. There are 2 major problems that must be addressed. The first is the lack of adequate recognition of the symptoms of SIBO and the need to treat these patients. We will address that challenge with a novel approach to detecting and flagging such symptoms. The second major problem this application addresses is the lack of evidence based treatment algorithms. We will address that challenge by developing an expert based consensus algorithm of therapy which will take the clinician through a sequence of steps in assigning drugs, assessing the response and then making further decisions based on the initial response and its durability.