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Anterior uveitis is the commonest extra-articular manifestation of ankylosing spondylitis (AS) and occurs in up to 40% of patients during the course of their disease.1 Uveitis associated with AS is typically anterior, unilateral and responsive to topical treatment.2 Tumour necrosis factor (TNF) blocking agents have been used in the treatment of uveitis refractory to conventional therapies but etanercept may be less effective in the treatment of uveitis in spondyloarthropathy (SpA) patients,3 possibly related to its alternative mode of action as a receptor blocker rather than antibody to TNF. Paradoxically they also seem to induce new ocular inflammation in some patients with new episodes of uveitis described in previously asymptomatic SpA patients after treatment with etanercept.3–6 More recently there has been one case of new onset uveitis in a patient with JIA treated with infliximab,7 but to our knowledge no cases have been described in SpA.
In the last decade we have treated over 130 AS patients with TNF blocking agents (49% infliximab, 48% etanercept, 3% adalimumab) and have seen new onset uveitis in five previously asymptomatic patients as specified in table 1. These cases show a strong temporal link between uveitis and anti-TNF therapy, particularly case 1 where cessation of therapy resulted in full resolution of the uveitis, but it recurred on re-challenge with etanercept.
All the patients reported here had a diagnosis of AS. Clearly uveitis is more common in patients with AS than other forms of SpA, although this phenomena has also been reported in at least one PsA patient treated with etanercept.8 Interestingly, most of the patients reported here were female and there is only one other case of new uveitis in a male SpA patient on anti-TNF.4 This contrasts significantly with the typical demographic profile of AS, which has a male preponderance.
In all cases, the presentation of uveitis is atypical for AS. Whilst the patients initially had unilateral anterior uveitis, all of them progressed to have involvement in both eyes concurrently. Another observation is that the severity of the uveitis and poor response to treatment in four of our cases was such that it required discontinuation of the drug. Patients 1, 3 and 4 all sustained permanent damage to their sight before the drug was stopped and uveitis resolved. These highly atypical features for AS-related uveitis increase the likelihood that the uveitis is related to their therapy and not simply a chance occurrence of extra-articular disease features.
Whilst anti-TNF drugs offer a new and exciting treatment option for refractory uveitis, it is clear that their mechanism of action in the eye is not fully understood and may relate to the unique immunological environment that exists in the uvea. Further prospective follow-up of patients treated with these drugs may lead to identification of predictors in the development of uveitis in these patients.
Competing interests: None declared.
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