Anterior Scleritis and Celiac Disease: A Proposed Association

Dear Sir,

Celiac disease is a prevalent autoimmune disorder related to exposure to gluten, a dietary protein found in wheat, barley, and rye, in susceptible patients.1 Circulating IgA and IgG auto-antibodies directed against tissue transglutaminase, endomisium, and gliadin are frequently elevated. There is an association with HLA antigens DQ2 and DQ8. The most common manifestations are gastrointestinal, with chronic diarrhea, malabsoption syndromes, and abdominal discomfort, but there also is a constellation of rarer systemic findings, including aphthous stomatitis and dermatitis herpetiformis. Celiac disease is associated with other autoimmune diseases such as type 1 diabetes, Hashimoto thyroiditis, and Behçet disease.

Several case reports describing an association of celiac disease with ocular inflammation in the form of recurrent or chronic uveitis have been published.2–5 A connection between both processes was inferred by the remission of uveitis after the introduction of a strict gluten-free diet. A large case-control study of Swedish patients with biopsy-proven celiac disease found a moderate yet significant increase in prevalence of uveitis compared to the general population.6

Scleritis, another form of ocular inflammation, may be associated with systemic conditions in 37–50% of cases, and with several autoimmune conditions in around 25% of cases.7 Scleritis may also be the initial presentation of systemic disease in 36% of patients. However, there are a significant number of cases that remain idiopathic after extensive investigation.

We present an otherwise healthy 37-year-old woman who was referred to our clinic for management of recurrent refractory scleritis in her right eye (OD) of unknown etiology. Her first episode of OD scleritis had happened in 2007 and had settled down with topical steroid treatment. She then experienced a more severe recurrence in July 2008, which required oral prednisone over 10 months and had resulted in ocular hypertension. Extensive screening including inflammatory markers and autoimmunity battery tests were normal.

She was first seen on 17 April 2009 complaining of recurrence of OD redness and ocular pain whenever she tried to reduce the 1% prednisolone drops she had been taking uninterruptedly 3 times per day. Uncorrected visual acuities were 6/6 in either eye, ocular pressures were 25 and 20 mmHg in her right and left eyes, and the rest of the ocular examination was unremarkable. In a self-administered standardized questionnaire the patient reported recurrent gastrointestinal upset, which had been diagnosed as irritable colon syndrome. She was thus referred to the gastroenterology department to explore her symptoms and rule out inflammatory intestinal disease. She underwent examination and extensive testing, including normal digestive endoscopy, colon biopsy, and abdominal magnetic resonance imaging. As she had become asymptomatic, tapered withdrawal of the steroid drops was planned.

In September 2010 she experienced a new recurrence graded as 2+ scleritis8 in her right eye, which necessitated daily 45 mg oral prednisone. However, 1 week after slow tapering and discontinuation she went through a much more severe outbreak graded as 3+ scleritis, which was initially treated with 70 mg oral prednisone. While on high-dose oral prednisone the patient experienced improvement in both ocular and gastrointestinal symptoms. In consultation with the rheumatology department she was successively encouraged to try metothrexate, which had to be withdrawn due to adverse effects, and azathioprine, which was stopped after finding low levels of thiopurine methyltransferase, and was finally given salazopirine. In spite of this, she continued to have low levels of inflammation graded as 1+ scleritis. On 5 July 2011 she was given a sub-Tenon injection of triamcinolone acetonide, which managed to control the inflammation completely but made the intraocular pressure rise again. Topical antihypertensive drugs easily controlled the ocular hypertension and the visual fields returned to within normal limits. As she continued to complain of recurrent gastrointestinal symptoms, she was once again screened for gastrointestinal diseases in July 2011 when high anti-transglutaminase IgA antibodies were found (43.4 U/mL (nl: <20.0) and hydrogen breath test with d-xylose was positive. Subsequently she was found to have duodenal mucosal villous atrophy with leukocyte infiltration. She was prescribed a strict gluten-free diet, which relieved her ocular and gastrointestinal symptoms and restored duodenal mucosal architecture. Systemic steroids were slowly tapered and discontinued and anti-transglutaminase IgA antibodies were lowered significantly by June 2012 (5.0 U/mL).

She experienced one episode of OD nodular 1+ scleritis in July 2012 (Figure 1). The patient thinks she could have inadvertently eaten foods containing gluten. The episode was fully resolved 2 days after sub-Tenon triamcinolone acetonide injection (with topical antihypertensive drugs to avoid ocular hypertension) and she has since been free from recurrences. In January 2013 she was found to be HLA-DQ8 (DQA1* 0301/B1*0302) positive, the ocular examination was normal, and she did not have any gastrointestinal symptoms. At a subsequent visit in April 2013 the patient was found not to have had any further ocular or gastrointestinal symptoms.

FIGURE 1. Mild scleritis recurrence with full response to local treatment.

In this case of recalcitrant scleritis, resolution was achieved only after the introduction of a gluten-free diet. We speculate that an association may be mediated by the intrascleral deposition of immune complexes leading to tissue inflammation, similar to the pathogenesis of dermatitis herpetiformis9 where dermal intrapapillary deposition of IgA leads to neutrophil infiltration.

A recurrence of inflammation was observed after the diet had been introduced and the disease had quieted. This recurrence was quickly managed with local treatment only. We believe that it is possible that this episode may be due to inadvertent gluten exposure as there is great difficulty in achieving strict adherence to diet, in particular when many processed foods contain gluten. Anti-transglutaminase or anti-gliadin antibodies may offer further evidence of a disease association if they are found to be elevated during a flare-up of scleritis.

A significant number of patients with scleritis remain without the identification of an underlying disease and their disease is labeled idiopathic. As celiac disease is often a subclinical condition it may be that a number of patients with scleritis have circulating anti-transglutaminase antibodies.

Although rare, celiac disease should be considered in the differential diagnosis of scleritis associated with gastrointestinal symptoms.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.