Date of Award

January 2025

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Chung Sang Tse

Second Advisor

Jill Gaidos

Abstract

Inflammatory Bowel Diseases (IBD) are chronic gastrointestinal disorders, namely Crohn's disease (CD) and ulcerative colitis (UC), affecting ~1.6 million people in the U.S. Gastrointestinal (GI) symptoms such as abdominal pain, diarrhea, and rectal bleeding may persist even when endoscopic and histologic findings appear normal (i.e., endoscopic-histologic remission). However, the prevalence of GI symptoms despite endoscopic-histologic mucosal healing remains unclear. Additionally, there is limited research on the impact of non-clinical factors, such as social determinants of health (SDOH), on persistent GI symptoms in patients with endoscopic remission. SDOH refers to conditions in environments—including, but not limited to, housing, transportation, neighborhoods, income, and education—that can significantly impact health outcomes. This thesis aims to address three key gaps in the understanding of IBD: (1) investigate the prevalence of GI symptoms and endoscopic/histologic mucosal healing, particularly in UC; (2) examine the associations between SDOH and persistent symptoms in patients with endoscopic-histologic remission; and (3) assess patients’ preferences for self-help tools to manage IBD.

For Aims 1 and 2, we conducted a secondary analysis of data from a cohort of patients enrolled in the IBD biobank at UC San Diego, where participants underwent colonoscopy and histologic assessments. Endoscopic inflammation was measured using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and the Simple Endoscopic Score for Crohn's Disease (SES-CD). GI symptoms were evaluated using a validated two-item patient-reported outcome measure (PRO-2), based on stool frequency and rectal bleeding for UC, or stool frequency and abdominal pain for CD. SDOH were quantified using the ZIP code-based California Healthy Places Index. We calculated associations between endoscopic-histologic inflammation and GI symptoms using sensitivity, specificity, and predictive values. Univariate logistic regression was used to analyze associations between SDOH and GI symptoms. For Aim 3, we conducted semi-structured focus groups with a separate cohort of patients with IBD and their healthcare providers, using thematic analysis and grounded theory to explore perspectives on self-help interventions.

In our cohort, 25% (18/72) of adults with UC in endoscopic-histologic remission experienced persistent GI symptoms. The Spearman’s rank correlation between endoscopic and clinical disease activity was moderate-to-strongly positive (0.57, 95% CI 0.54-0.60; p<0.0001), while the correlation between histologic and clinical activity was moderate (0.49, 95% CI 0.45-0.53; p<0.0001). Endoscopic- histologic inflammation had the highest sensitivity (87%) for detecting diarrhea or rectal bleeding, compared to endoscopic (77%) or histologic (80%) assessments alone. Lower SDOH was associated with GI symptoms despite endoscopic remission (OR 2.70; 95% CI 1.12, 6.50; p=0.024) in patients with CD, but not in patients with UC. Specifically, poor economic conditions, low educational attainment, poor neighborhood conditions, and limited healthcare access were associated with persistent GI symptoms despite the absence of objective inflammation. Although self-help tools may supplement IBD management, opinions on their use varied. Providers found the variety of tools—helpline, peer mentorship, smart device applications, and workbooks—useful but emphasized the need for tutorials to guide patients. Patients had mixed preferences, with 4/8 using the workbook, 3/8 using apps, and fewer using the helpline or engaging with a peer mentor. Common concerns included cost, convenience, and relevance to individual patients’ needs.

In conclusion, a quarter of UC patients in endoscopic-histologic remission continue to experience GI symptoms. Compared to endoscopic or histologic inflammation alone, combined endoscopic-histologic inflammation has the highest sensitivity for GI symptoms. While SDOH were not associated with diarrhea and rectal bleeding in endoscopically inactive UC, they were linked to abdominal pain and diarrhea in Crohn's patients despite endoscopic remission. Self-help tools are valued by both providers and patients, though patient preferences vary based on accessibility, cost, and perceived relevance to their individual needs.

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This is an Open Access Thesis.

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