Colitis Risk Increase In Inflammatory Eye Disease Patients
Overview
Microscopic colitis (MC) is an inflammatory condition affecting the colon, but its association with inflammatory eye diseases remains unclear. This study aimed to determine if inflammatory eye diseases, specifically iridocyclitis and episcleritis, are risk factors for developing MC.
Using the ESPRESSO database, which includes data on gastrointestinal tract biopsies from 1965 to 2017, we conducted a nationwide matched case-control study in Sweden. We identified 14,338 patients with biopsy-confirmed MC diagnosed between 1981 and 2017. These patients were matched by age, sex, county, and year of birth with 68,753 controls from the general population. We compared the incidence of inflammatory eye diseases in both groups.
Our analysis showed that 1.6% of MC patients had a history of inflammatory eye disease, compared to 0.9% in the control group. This resulted in an adjusted odds ratio (aOR) of 1.77 (95% CI = 1.52–2.07) for inflammatory eye diseases among MC patients. The aOR for these conditions was 1.52 (95% CI = 1.17–1.98) when compared to siblings, indicating a significant association. Additionally, patients treated with budesonide, indicative of more severe disease, had a slightly higher aOR for previous inflammatory eye diseases.
In conclusion, our study finds that inflammatory eye diseases are more prevalent among individuals who later develop MC. This suggests potential shared etiological factors and inflammatory pathways between these conditions, which is important for both gastroenterologists and ophthalmologists to consider.
Introduction
Microscopic colitis (MC) is an inflammatory condition of the colon, typically presenting as watery diarrhea in middle-aged women. Unlike classical inflammatory bowel diseases (IBD) such as Crohn’s disease or ulcerative colitis, MC does not cause macroscopic changes in the colonic mucosa and features milder inflammation. Diagnosis relies on histopathological examination of a colonic biopsy, classifying MC into two main subtypes: collagenous colitis (CC) or lymphocytic colitis (LC). Recent studies from Sweden, the U.S., and Denmark have reported rising incidence rates of MC, which now approach or exceed those of ulcerative colitis and Crohn’s disease.
Research into extraintestinal manifestations of MC is limited and primarily based on smaller studies. However, emerging evidence suggests significant associations between MC and conditions such as rheumatoid arthritis, acute pancreatitis, and major adverse cardiovascular events. Additionally, MC is linked with autoimmune disorders, though its relationship with inflammatory eye diseases remains unexplored.
Inflammatory eye diseases, such as iridocyclitis and episcleritis, are commonly associated with IBD and celiac disease, often occurring simultaneously or even preceding the onset of these conditions. Both MC and iridocyclitis involve inflammatory processes linked to elevated levels of TH-17, and a notable proportion of patients with episcleritis have underlying inflammatory diseases. Given these connections, this study aimed to investigate the potential association between inflammatory eye diseases and microscopic colitis using a large nationwide histopathology cohort. Understanding this relationship could reduce diagnostic delays for microscopic colitis and enhance the scientific knowledge of extraintestinal inflammation associated with the disease.
Method
Healthcare in Sweden is predominantly publicly funded, aiming to provide equitable access to all citizens. This study utilized data from nationwide Swedish healthcare registers and government-maintained population records. Each Swedish citizen receives a unique personal identification number at birth or upon immigration, facilitating comprehensive data collection with minimal missing information.
Data Sources
– Swedish National Patient Register (NPR): Contains diagnoses and medical procedures coded using International Classification of Diseases (ICD). It has been nationwide since 1987 and includes specialized outpatient care data from 2001.
– Prescribed Drug Register: Provides nearly complete coverage of dispensed medications in Sweden since July 2005.
– Total Population Register: Records personal identity numbers, vital status, migration, and residence data since 1968.
– Multigeneration Register: Part of the Total Population Register, this archive includes data on Swedish citizens born from 1932 to present, along with their siblings and biological parents.
The study focused on inflammatory eye diseases, specifically episcleritis and iridocyclitis, with the latter often associated with inflammatory bowel disease (IBD). Uveitis, an umbrella term including anterior, intermediate, and posterior types, was used as the primary exposure. The positive predictive value (PPV) of uveitis in the NPR is approximately 93%.
MC was identified using SNOMED codes for collagenous colitis (M40600) and lymphocytic colitis (M47170). Previous studies have shown a PPV of 95% for these diagnoses, and 96% of patients had diarrhea before diagnosis, confirming the accuracy of the MC definition. The ESPRESSO study, which includes data on all gastrointestinal biopsies from 1965 to 2017, was used to identify individuals with MC and matched controls.
Baseline characteristics such as sex, age, county of residence, date of death, emigration, and country of birth were obtained from the Total Population Register. Socioeconomic status was approximated by educational attainment, categorized into compulsory school (≤9 years), upper secondary school (10–12 years), and college (≥13 years). In cases of missing educational data, parental education levels were used. The study also considered dispensed budesonide as an indicator of clinically significant disease.
The study was approved by the Stockholm Ethics Review Board, and because it was register-based, informed consent was not required. All statistical analyses were conducted using Stata/IC 17.0 for Mac.
Exclusion Criteria
Participants with data inconsistencies (e.g., emigration, death) or those who underwent colectomy before the matching date were excluded.
Sensitivity Analyses
Several analyses were performed to account for potential confounders:
- Socioeconomic Status: Adjusted for educational attainment.
- Inflammatory Comorbidities: Included in the model to control for other inflammatory conditions.
- Familial Factors: Used full siblings as controls to assess familial confounding.
Statistical Analysis
Odds ratios (ORs) and confidence intervals (CIs) were calculated using conditional logistic regression. The model accounted for matching variables (sex, birth year, county of residence) and adjusted for comorbidities occurring before the diagnosis of inflammatory eye disease. Subgroup analyses were conducted based on sex, age at diagnosis, calendar year, country of birth, and educational attainment. Sibling-controlled analyses compared patients with MC to their siblings.
Result
Between 1981 and 2017, a comprehensive study investigated 14,338 patients diagnosed with macular chorioretinopathy (MC), comparing their health data with 68,753 matched controls from the general population. Additionally, the study included 14,656 full siblings of the patients, who did not have MC, to further refine the analysis.
The majority of MC patients were women (71.9%), with a median age of 63.3 years at diagnosis (interquartile range [IQR] = 50.7–72.6). Most patients (94%) were born in Nordic countries, and 30% had achieved an educational level equivalent to university or college (≥13 years of schooling).
Among the cohort, 839 cases of earlier inflammatory eye diseases were identified. Of these, 225 occurred in MC patients, representing 1.6% of the group, while 614 cases (0.9%) were observed in the control group. Notably, the median age at diagnosis for iridocyclitis was younger in microscopic colitis patients (56.9 years, IQR = 43.4–68.3) compared to the controls (60.6 years, IQR = 48.4–70.1). This suggests that inflammatory eye diseases may occur earlier in patients who later develop microscopic colitis.
For those with microscopic colitis, the median time between the first diagnosis of an inflammatory eye disease and microscopic colitis was 4.9 years (IQR = 2.0–7.7). This time interval was comparable for other related conditions, such as chorioretinopathy and late chorioretinopathy.
When adjusting for matching variables—such as birth year, sex, county, calendar year, and educational attainment, which serves as a proxy for socioeconomic status—the study found an adjusted odds ratio (aOR) of 1.77 (95% CI = 1.52–2.07) for the association between inflammatory eye diseases and microscopic colitis. This indicates a significantly higher likelihood of MC among patients with a history of inflammatory eye diseases compared to controls. The aOR was similar across genders, though the confidence interval was broader for males, reflecting the higher prevalence of MC among females.
The analysis revealed a significant variation in aOR based on the age at which microscopic colitis was diagnosed. Patients diagnosed at a younger age had a notably higher aOR of 2.76 (95% CI = 1.94–3.92) for having an earlier inflammatory eye disease. This suggests that younger patients with microscopic colitis may have a higher association with prior inflammatory eye conditions. The study also examined the data across different calendar periods. The odds ratios for earlier periods (≤1990 and 1991–2000) were not as informative due to the less frequent diagnosis of MC during those times. However, for the later periods (2001–2010 and 2011–2017), the odds ratios were similar (P for heterogeneity = 0.20), indicating consistent associations in more recent years.
Further analysis confirmed the significant association between microscopic colitis and both episcleritis and iridocyclitis. Sensitivity analyses, including those accounting for dispensation of budesonide—a corticosteroid used for inflammatory conditions—showed a higher aOR among microscopic colitis patients who had been dispensed this medication (2.03, 95% CI = 1.63–2.53) compared to those without such dispensation (1.60, 95% CI = 1.28–2.01). Although the difference was not statistically significant (P for heterogeneity = 0.14), it suggests that budesonide usage may be related to the observed association. Additionally, when adjusting for confounding autoimmune disorders, the elevated aOR for earlier inflammatory eye disease remained significant (aOR = 1.64, 95% CI = 1.40–1.93), indicating that the association is robust even when considering other potential influencing factors.
In summary, this extensive study highlights a significant association between earlier inflammatory eye diseases and the development of microscopic colitis, with variations based on age at diagnosis and calendar period. The findings underscore the need for continued research into the relationships between inflammatory eye conditions and microscopic colitis to better understand these associations and potentially improve diagnostic and therapeutic strategies.
Conclusion
In this nationwide matched case-control study, which included over 14,300 patients with microscopic colitis (MC), it was found that individuals with a history of inflammatory eye diseases such as episcleritis and iridocyclitis had a 77% increased likelihood of developing MC. This association was consistently observed across various sensitivity analyses, with both types of inflammatory eye diseases significantly linked to microscopic colitis. The risk was notably higher for those diagnosed with MC at a younger age.
The study adds new insight into the relationship between inflammatory eye diseases and microscopic colitis, an area previously unexplored in this context. Prior research has explored connections between inflammatory bowel disease (IBD) and episcleritis/iridocyclitis, as well as similar associations with celiac disease.
The study analyzed the association across different age groups, finding that patients diagnosed with microscopic colitis before the age of 50 had a significantly higher risk compared to those diagnosed later. This pattern was consistent for both colonic and lymphocytic subtypes of microscopic colitis. Sensitivity analyses further validated these findings. Adjustments for socioeconomic status, comorbidities, and autoimmune predispositions did not materially alter the association, indicating that shared inflammatory characteristics rather than genetic factors are the primary drivers of the observed relationship.
Biologically, the link between inflammatory eye diseases and microscopic colitis is plausible given the shared inflammatory pathways, specifically the TH-17 pathway, implicated in both conditions. Episcleritis and iridocyclitis in IBD patients are often considered manifestations of systemic immune responses, further supporting the connection between these eye conditions and MC. However, while episcleritis and iridocyclitis are viewed as true extraintestinal manifestations of IBD, other eye conditions like dry eyes and cataracts may occur independently or as side effects of treatment.
The study’s strengths include its nationwide scope, large sample size, and the use of full siblings to address familial confounding. However, limitations include the lack of data on lifestyle factors like BMI and smoking, and potential underreporting of primary care diagnoses. Additionally, as the study relies on Swedish data, its findings may not be fully generalizable to other populations with different lifestyle factors and ethnic backgrounds.
In conclusion, inflammatory eye diseases, specifically episcleritis and iridocyclitis, are significant risk factors for developing microscopic colitis. This association is relevant for both subtypes of microscopic colitis and provides important clinical insights for ophthalmologists and general practitioners. The findings underscore the potential shared underlying causes between these conditions.
Oncology Related Tools
Other
Latest Research
