Thyroid Disease Linked With Uveitis

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Patients with thyroid disease have increased risk for uveitis, suggesting the two diseases may share a common autoimmune pathophysiology, researchers found.

Compared with the general population, patients with thyroid disease had a 1.7-fold (95% CI 1.03-2.8, P=0.04) higher risk for uveitis, after adjusting for potential confounders including age, sex, race, smoking, and prior autoimmune disease, according to Nisha Acharya, MD, of the University of California San Francisco, and colleagues.

When the investigators compared thyroid disease patients with a more focused control group of ophthalmology clinic patients, they found a nearly identical risk increase for uveitis (HR 1.8, 95% CI 1.1-2.9, P=0.02), Acharya and colleagues reported online in JAMA Ophthalmology.

The population-based, case-control study found that 13% of patients with uveitis also had thyroid disease, compared with only 7% of the general population (P=0.01) and 9% of the ophthalmology clinic patients (P=0.06).

"Although prior case reports, as well as in vitro and animal studies, have suggested an association between thyroid disease and uveitis, to our knowledge, a large, population-based, case-controlled study investigating such an association has not been performed," Acharya and colleagues wrote.

"In our study, patients with a history of thyroid disease had a weak to moderate association with uveitis using both a general Kaiser Permanente population control group and an ophthalmology clinic control group. In addition, this association persisted when considering only noninfectious cases of uveitis," they noted.

In an accompanying editorial, Sunir Garg, MD, of the Wills Eye Hospital at Thomas Jefferson University in Philadelphia, said that the study, while important, should not affect clinical practice.

"The study ... is important for hypothesis generation, and will help guide future research projects," Garg said. "However, it is not designed to change how we manage our patients with uveitis. At this time, ordering tests to evaluate patients with uveitis for autoimmune thyroid disease is not likely to be clinically useful or cost-effective. Similarly, the presence of autoimmune thyroid disease should not influence treatment, particularly systemic immunosuppression, for patients with uveitis."

Garg added, however, that "from a clinician's perspective, knowing that an association exists between uveitis and other conditions such as autoimmune thyroid disease may help to provide a greater understanding as to why a patient develops uveitis."

Patients often want to know why they developed ocular inflammatory disease, and doctors often have to say they don't know. "Although this fact remains true to some degree, we can at least counsel our patients that we are making progress in understanding the complex relationships between our organs, the immune system, and environmental influences," Garg said.

The retrospective study included 217,061 members of the Kaiser Permanente Hawaii health system during 2006-2007. Investigators searched the medial records of these patients to identify those with diagnoses of uveitis and thyroid disease. All uveitis cases were confirmed by a clinical exam.

The study compared uveitis patients with two control groups, which were randomly selected at a 4:1 ratio. The general Kaiser Permanente control group was composed of members who had at least one healthcare visit during the study period, and the ophthalmology control group was composed of members who had at least one visit to an ophthalmology clinic.

The investigators conducted a logistic regression analysis with uveitis as the main outcome variable and thyroid disease as the main predictor variable, while adjusting for age, sex, race, smoking status, and history of autoimmune disease.

The investigators identified 224 cases of uveitis out of the total Kaiser Permanente membership. Most of these patients (72%) had anterior uveitis. The disease course was acute in 96 patients (43%), recurrent in 59 (26%), and chronic in 57 (25%). Forty-seven patients (21% ) had an associated infectious disease. More than half (57%) were female, and their mean age was 54.

The proportion of patients with uveitis who also had an autoimmune disease was 12%, compared with 3% of the general control group (P<0.001) and 5% of the ophthalmology clinic control group (P<0.001), the study found.

"Autoimmunity is a biologically plausible mechanism that may explain the association between uveitis and thyroid disease," Acharya and colleagues wrote. "Autoimmune thyroid disease has been associated with several other autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Similarly, the link between thyroid disease and uveitis may be explained by an underlying predisposition to immune dysregulation in certain individuals.

"These results suggest that thyroid disease has an important association with ocular inflammation and raises questions regarding whether they share common pathophysiological mechanisms. If these results are further corroborated by future studies, this finding may have implications for clinical care, particularly in the laboratory evaluation of patients with uveitis who have signs and symptoms of thyroid dysfunction," the investigators concluded.

One limitation of the study was that the diagnosis codes use to identify patients with thyroid disease may not have been comprehensive. They did not, for example, include the codes for thyroid cancer. In addition, unknown confounding factors could have affected the results, the researchers noted.