Silica Dust: Does It Ignite Inflammation In The Gut And Eye

Ulcerative colitis (UC) is a chronic inflammatory ailment of the colon. It is considered a part of the inflammatory bowel disease (IBD) category. It causes inflammation and ulcers in the colon’s lining, usually starting in the rectum and spreading upward. UC can vary in severity and is classified into ulcerative proctitis, left-sided colitis, and extensive colitis based on how much of the colon is affected. In Sweden, UC affects about 17.9 people per 100,000 annually. Symptoms often begin between ages 20 and 30 and include bloody, mucus-filled stools. The disease results from genetic, psychological, and environmental factors. UC also increases the risk of certain eye diseases, including inflammatory conditions like episcleritis and uveitis.

 

THE STUDY BACKGROUND

Ulcerative colitis (UC) is a long-term colonic disease that falls under the broader category of inflammatory bowel disease (IBD). It is characterized by inflammation of the superficial mucosa with ulcerations, primarily affecting the rectum and extending proximally to various extents within the colon [1]. UC can be categorized based on the importance of colon involvement in ulcerative proctitis, left-sided colitis, and extensive colitis [2]. UC’s annual age-standardized incidence rate in Sweden was 17.9 per 100,000 person-years between 2002 and 2014, with a lifetime cumulative incidence of 1.44% for males and 1.35% for females [3]. Symptoms typically manifest between the ages of 20 and 30 but can occur at any age, with women generally being diagnosed at a slightly older age than men [3].

The pathogenesis of UC is multifactorial, involving genetic, psychosocial, and environmental factors. Key contributing elements include damage to the intestinal barrier, an imbalance of the colonic bacterial flora, increased expression of toll-like receptors (TLR) in dendritic cells, and an exaggerated T-cell response [4]. UC also increases the risk of several ophthalmological diseases or ocular extraintestinal manifestations (EIM), such as episcleritis, scleritis, and uveitis, including iritis [5, 6]. The underlying factors contributing to these ocular conditions are poorly understood, but genetic predisposition and intestinal microbial factors are considered significant [4, 6].

Exposure to silica dust has been identified as a risk factor for several lung diseases, such as lung parenchyma cancers, silicosis, chronic obstructive pulmonary disease (COPD), and lung infections, and it also plays a significant role in the development of many inflammatory diseases, including sarcoidosis, rheumatoid arthritis, and IBD [7]. Although systemic conditions associated with increased uveitis risk have been documented, there is limited data linking silica dust exposure directly to inflammatory ophthalmological conditions. Some studies suggest that coal miners exposed to silica dust may exhibit inflammatory changes in the retina and choroid, observable via optical coherence tomography (OCT) imaging [8].

 

This study aims to investigate the risk of ophthalmic diseases in individuals with UC through a case-control approach. Additionally, it seeks to determine whether occupational silica dust exposure contributes to the development of ophthalmological diagnoses, particularly those associated with inflammation. This research could provide insights into the pathogenesis of uveitis and other eye diseases in the context of UC and occupational hazards.

 

THE STUDY METHOD

The study employed a case-control design, adhering to the Declaration of Helsinki guidelines and receiving approval from the regional ethical board in Uppsala. Data were sourced from the Patients’ registers with the National Board of Health and Welfare (NBHW) and Statistics Sweden. The study identified individuals diagnosed with ulcerative colitis (UC) using the International Classification of Diseases, Tenth Revision (ICD-10) code K51, focusing on diagnoses made between 2007 and 2016, with a two-year washout period to ensure only newly diagnosed cases were included.

Participants included individuals aged 20 to 65 diagnosed with UC within the specified timeframe. Each case was matched with two controls based on the same birth year, sex, and county of residence, excluding individuals diagnosed with Crohn’s disease, Ankylosing spondylitis, sarcoidosis, or Rheumatoid arthritis. Controls were also ensured not to be first-degree relatives of the cases. Ophthalmological conditions were defined by diseases in chapter VII of ICD-10 (H00-H59). Case follow-up time began at the year of UC diagnosis, while controls shared the same follow-up start year.

Work-related silica dust exposure was assessed using a job-exposure matrix (JEM). Occupations with at least 5% of workers exposed to 0.02 mg/m³ or more of respirable silica dust were considered exposed. Comparisons were made between exposed and non-exposed individuals on the ICD diagnosis block level. Additionally, specific inflammatory diagnoses, such as sclera inflammation, keratitis, iris and ciliary body inflammation, choroid and retina inflammation, and other retinal diseases, were analyzed to explore their pathogenesis of UC and silica dust exposure.

 

ANALYSIS

The researchers used STATA 14.1 and IBM SPSS® version 29.0 to analyze the study. The scientists compared cases, and controls were made using Cox regression analysis. The results were presented as 95 percent (%) confidence intervals (CI) and Hazard Ratios (HR). Differences in the age of mortality were assessed with independent samples t-tests. A statistically significant difference was defined as an HR value with the lower limit of the CI above 1.

Each participant contributed person-years from the diagnosis of UC until the development of an ophthalmological disease, emigration, death, or the end of the study period. The Total Population Register and the National Cause of Death Register were utilized to calculate the study’s person-years.

 

RESULTS

Study Population

• The study included 58,989 individuals, 19,663 diagnosed with ulcerative colitis (UC) and 39,326 serving as controls. The gender distribution was nearly equal, with slightly more females than males. Both groups had a mean age of 42 at diagnosis, with males slightly younger than females.

Incidence of Eye Diseases

• People with UC were found to have a higher rate of eye and adnexa diseases compared to the control group. Specifically, 12.8% of UC patients had at least one eye disease diagnosis during the study period, compared to 10.1% of the controls. On average, UC patients were diagnosed with eye conditions about 2.8 years after their UC diagnosis, while controls were diagnosed around 2.9 years after their initial inclusion.

Types of Eye Diseases

• The study identified significant differences in several categories of eye diseases. The most notable increase in risk was seen in conditions affecting the sclera, cornea, iris, and ciliary body, such as episcleritis and anterior uveitis. Other areas with significant findings included conjunctiva disorders, eyelid and lacrimal system issues, visual disturbances, and problems with ocular muscles and refraction.

Gender Differences

• Gender affected the incidence of eye problems in UC patients and healthy participants. For example, increased risks for glaucoma and visual disturbances were significant across the entire study population but were only confirmed in males. Conversely, differences in cataracts and other lens conditions were only significant in females.

Silica Dust Exposure

• About 6.9% of UC patients and 6.2% of controls were exposed to silica dust. UC patients showed a higher risk for certain eye diseases among those exposed. Specifically, the risk of iridocyclitis was notably higher in UC patients exposed to silica dust than those not. This risk was particularly pronounced for those exposed to silica dust.

Overall Findings

• UC patients are more likely to develop eye diseases than controls, with significant increases in certain eye conditions. Silica dust exposure was associated with a higher risk for specific eye diseases, particularly in individuals with UC. The study highlights meaningful connections between UC and various eye conditions and suggests a potential role for environmental factors like silica dust in exacerbating these risks.

 

DISCUSSION

The study explored the incidence of eye diseases in individuals with ulcerative colitis (UC). It focuses on conditions classified under ICD-10 Chapter VII. The analysis revealed that UC patients exhibit a higher prevalence of ocular extraintestinal manifestations than matched controls, with statistically significant differences observed in most eye diseases except for two [1]. This elevated risk for eye diseases in UC patients is consistent with existing literature, which has frequently documented an increased prevalence of inflammatory eye conditions in individuals with inflammatory bowel diseases (IBD) [2, 3]. Specifically, the study identified a significant association between UC and several anterior segment diseases, including anterior uveitis, keratitis, and episcleritis, which were notably more common in the UC cohort.

In addition to anterior segment conditions, the study also found an increased risk for disorders of the sclera, such as episcleritis and scleritis. This observation corroborates previous research suggesting a higher incidence of scleral disorders in UC patients than in the general population [4, 5]. The results also highlighted a significant risk for chorioretinal inflammation, which includes conditions like posterior uveitis. This finding suggests that UC patients are prone to anterior segment eye diseases and more severe conditions affecting the posterior segment, reflecting a broader spectrum of ocular involvement in UC patients [6].

The study’s findings also underscored the prevalence of dry eyes and eyelid problems among UC patients, consistent with previous research indicating that IBD patients are more likely to experience such symptoms [7]. These conditions were predominantly categorized under anterior segment diseases, further supporting that UC patients are at increased risk for ocular manifestations. The study observed some gender-specific differences, with a higher risk of glaucoma in males and lens disorders, such as cataracts, in females. While these findings align with some earlier studies, they also highlight variability in the reported associations between UC and specific ocular conditions [8].

Furthermore, the research examined the role of environmental factors, specifically silica dust exposure, in developing eye diseases among UC patients. The results revealed that silica dust exposure was more prevalent among UC patients than controls and was associated with a heightened risk for certain eye conditions, notably anterior uveitis [9]. This finding suggests a potential link between environmental factors and increased ocular inflammation in UC patients, emphasizing the need for further research to explore how ecological exposures might contribute to ocular manifestations in chronic inflammatory diseases.

Overall, the study provides compelling evidence that individuals with UC are at an increased risk for a range of eye diseases compared to the general population. The heightened risk for conditions such as anterior uveitis, scleral disorders, and chorioretinal inflammation underscores the importance of monitoring and managing ocular symptoms in UC patients. Additionally, the potential role of silica dust exposure in exacerbating ocular inflammation highlights the need for further investigation into environmental risk factors that may influence the development of eye diseases in individuals with UC.

 

STUDY LIMITATIONS

1. Lack of Detailed Clinical Data

   – The study relied on ICD coding, which limits access to detailed information about disease activity, previous surgeries, smoking habits, lifestyle factors, and specific ophthalmological findings.

   – This lack of detailed clinical data may obscure the full extent of the relationship between UC and eye diseases.

2. Unaccounted Pharmacological and Surgical Therapies

   – The study did not analyze the impact of different pharmacological and surgical therapies on eye diseases.

   – Potential effects of medications, such as corticosteroids, which could cause cataracts or glaucoma, were not examined.

   – This oversight could affect the interpretation of findings related to the association between UC and ocular conditions.

3. Possible Confounding Factors

   – The absence of data on confounding variables, such as lifestyle factors and specific treatment regimens, limits the ability to account for all potential influences on ocular health.

   – This lack of comprehensive data may lead to an insufficient understanding of the factors contributing to eye diseases in UC patients.

4. Potential Impact of Anti-inflammatory Therapies

   – Anti-inflammatory treatments could influence the prevalence of inflammatory eye conditions.

   – The study did not explore whether these therapies might reduce or underestimate the risk of ocular diseases in UC patients.

5. Limited Investigation of Silica Dust Exposure

   – The association between silica dust exposure and ocular diseases was only briefly analyzed.

   – While the increased risk for anterior uveitis was noted among exposed individuals, the small sample size limits the ability to draw definitive conclusions.

   – Further research is needed to explore the relationship between silica dust exposure and ocular inflammation fully.

 

CONCLUSION

This study highlights the elevated risk of various eye diseases among individuals with ulcerative colitis (UC). The findings confirm that UC is associated with an increased incidence of inflammatory ocular conditions, including anterior and posterior uveitis, episcleritis, and corneal ulceration. Given their susceptibility to such inflammatory eye diseases, these results underscore the need for heightened vigilance in monitoring eye health in UC patients. Additionally, the study suggests that exposure to respirable silica dust may further exacerbate this population’s uveitis risk. This potential link emphasizes the importance of addressing environmental factors, such as silica dust exposure, in managing and preventing ocular complications in individuals with UC. These findings advocate for more research on the eye complications of ulcerative colitis and prevent these complications from developing. They also provide insightful information about the relationship between UC and ocular health.

 

References

1. Algaba, A., Guerra, I., Ricart, E., Iglesias, E., Mañosa, M., Gisbert, JP et al. (2021) Extraintestinal manifestations in patients with inflammatory bowel disease: study based on the ENEIDA registry. Digestive Diseases and Sciences, 66, 2014–2023. (https://link.springer.com/article/10.1007/s10620-020-06455-5)

 

2. Andoh, A., Imaeda, H., Aomatsu, T., Inatomi, O., Bamba, S., Sasaki, M. et al. (2011) Comparison of the fecal microbiota profiles between ulcerative colitis and Crohn’s disease using terminal restriction fragment length polymorphism analysis. Journal of Gastroenterology, 46, 479–486. (https://link.springer.com/article/10.1007/s00535-010-0292-7)

 

3. Ayar, O., Orcun Akdemir, M., Erboy, F., Yazgan, S. & Hayri Ugurbas, S. (2017) Ocular findings in coal miners diagnosed with pneumoconiosis. Cutaneous and Ocular Toxicology, 36, 114–117. (https://www.tandfonline.com/doi/full/10.3109/15569527.2015.1081335)

 

4. Bandyopadhyay, D., Bandyopadhyay, S., Ghosh, P., De, A., Bhattacharya, A., Dhali, G.K. et al. (2015) Extraintestinal manifestations in inflammatory bowel disease: prevalence and predictors in Indian patients. Indian Journal of Gastroenterology, 34, 387–394. (https://link.springer.com/article/10.1007/s12664-015-0607-6)

 

5. Bernstein, C.N., Blanchard, J.F., Rawsthorne, P. & Yu, N. (2001) The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. The American Journal of Gastroenterology, 96, 1116–1122. (https://journals.lww.com/ajg/Abstract/2001/06000/The_Prevalence_of_Extraintestinal_Diseases_in.21.asp)

 

6. Carnahan, M.C. & Goldstein, D.A. (2000) Ocular complications of topical, peri-ocular, and systemic corticosteroids. Current Opinion in Ophthalmology, 11, 478–483. (https://journals.lww.com/co-ophthalmology/Abstract/2000/12000/Ocular_Complications_of_Topical__Peri_Ocular__and.7.aspx)

 

7. Cho, J.H. & Brant, S.R. (2011) Recent insights into the genetics of inflammatory bowel disease. Gastroenterology, 140, 1704–1712. (https://www.gastrojournal.org/article/S0016-5085(11)00238-0/fulltext)

 

8. Christodoulou, D.K., Katsanos, K.H., Kitsanou, M., Stergiopoulou, C., Hatzis, J. & Tsianos, E.V. (2002) Frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece and review of the literature. Digestive and Liver Disease, 34, 781–786. (https://www.dldjournalonline.com/article/S1590-8658(02)00249-1/fulltext)

 

9. Makdoumi, K., Ayoub, L., Bryngelsson, I.-L., Graff, P., Wiebert, P. & Vihlborg, P. (2024) The risk for ophthalmological conditions in ulcerative colitis: A population-based case–control study. Is silica dust-exposure associated with inflammatory eye disease? Acta Ophthalmologica, 00, 1–8. (https://doi.org/10.1111/aos.16708)

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