uveitis in some anti-TNF–treated patients (3). The annual (1998) incidence of uveitis caused by herpes zoster, herpes simplex, and toxoplasma in the general population may be up to 3.6 per 100,000 person-years (4). However, and somehow inconsistent with their conclu- sion that infliximab is far more effective than etanercept, the authors finally state that these registry-collected data do not support the use of infliximab over etanercept in the treatment of patients with inflammatory diseases that may be associated with uveitis (1). We would like to remind them that in Behc ¸et’s disease, a chronic inflammatory disease frequently compli- cated with uveitis, infliximab is efficacious in rapidly control- ling acute panuveitis relapses in patients already treated with maximum doses of conventional immunosuppressive therapy (5). Currently, more than 200 patients with uveoretinitis associated with Behc ¸et’s disease are treated with repeated infliximab infusions in Japan (Ohno S: personal communica- tion), where a formal approval for this indication was granted to infliximab in January 2007. Petros P. Sfikakis, MD Laikon Hospital Athens University Medical School Athens, Greece Nikos Markomichelakis, MD General Hospital of Athens Athens, Greece 1. Lim LL, Fraunfelder FW, Rosenbaum JT. Do tumor necrosis factor inhibitors cause uveitis? A registry-based study. Arthritis Rheum 2007;56:3248–52. 2. Theodossiadis PG, Markomichelakis N, Sfikakis PP. Tumor necro- sis factor antagonists: preliminary evidence for an emerging ap- proach in the treatment of ocular inflammation [review]. Retina 2007;27:399–413. 3. Paivonsalo-Hietanen T, Tuominen J, Vaahtoranta-Lehtonen H, Saari KM. Incidence and prevalence of different uveitis entities in Finland. Act Ophthalmol Scand 1997;75:76–81. 4. Fonollosa A, Segura A, Giralt J, Garcia-Arumi J. Tuberculous uveitis after treatment with etanercept. Graefes Arch Clin Exp Ophthalmol 2007;245:1397–9. 5. Sfikakis PP, Markomichelakis N, Alpsoy E, Assaad-Khalil S, Bod- aghi B, Gul A, et al. Anti-TNF therapy in the management of Behcet’s disease: review and basis for recommendations [review]. Rheumatology (Oxford) 2007;46:736–41. DOI 10.1002/art.23440 Uveitis following the use of tumor necrosis factor  inhibitors: comment on the article by Lim et al To the Editor: We read with interest the article by Lim et al on the possible relationship between the use of tumor necrosis factor  (TNF) inhibitors and uveitis (1). The results from this registry-based study revealed that etanercept was associated with a greater number of uveitis cases than was infliximab or adalimumab, whereas no disparity was found when comparing these monoclonal antibodies. However, the authors denied a clear propensity for etanercept to cause uveitis compared with infliximab in view of the paucity of the cases observed. Indeed, although a large study indicated that TNF inhibitors reduce the incidence of uveitis (2), the onset or recurrence of uveitis following the use of TNF inhibitors, especially etanercept, has been signaled in retrospective (3) and anecdotal reports, inducing the hypothesis of a causative role for etanercept in uveitis flares. Beginning in 2000, a total of 655 patients attending our rheumatology unit received at least 1 TNF inhibitor. In 4 of the 350 patients treated with etanercept, acute anterior uveitis (as diagnosed by an ophthalmologist) developed: 2 patients had ankylosing spondylitis, 1 patient had psoriatic arthritis, and 1 patient had juvenile idiopathic arthritis (JIA) (Table 1). We are aware that the scarce number of uveitis cases in our series demands caution and not hasty judgments, particularly consid- ering that uveitis may be part of the natural history of ankylosing spondylitis, psoriatic arthritis, and JIA. Moreover, after resolution of uveitis, patient 1 continued to receive etanercept and experienced no further ocular flare. Nonetheless, we cannot ignore some peculiar aspects of this series. All of the patients were receiving etanercept at the time when uveitis appeared, and only 1 of them (patient 3) had already had an episode of uveitis, 6 years before anti- TNF treatment. This patient had 2 relapses subsequent to the commencement of etanercept treatment. Furthermore, all of the patients were complete responders to etanercept (they were not receiving any other concomitant treatment), and uveitis appeared at a time during which their rheumatic disease manifestations were fully controlled. In our series, uveitis has not developed in any patient treated with either infliximab or adalimumab. Thus, our experience corroborates prior obser- vations in which the appearance of ocular inflammation fol- lowed etanercept treatment and resembles the difference in efficacy already demonstrated between the soluble TNF receptor and the anti-TNF antibodies in inflammatory bowel disease, which is an additional extraarticular expression of spondylarthropathy. In this regard, we were interested in the recent study showing that ocular infiltrating T cells from patients with active uveitis stimulated in vitro with soluble TNF receptors began to synthesize TNF (4). These findings testify to a peculiar ocular immune microenvironment, which may explain the poor effect of etanercept compared with that of the anti-TNF antibodies in controlling uveitis. This observation, together with the “challenge-rechallenge” setting described in some reports (5,6), suggests that etanercept may trigger uveitis in some patients. In addition, the results from the registry described by Lim et al are intriguing in terms of showing that uveitis following etanercept treatment may also occur in patients with rheumatoid arthritis (RA), even if this particular ocular involvement is not recognized as part of the clinical spectrum of the disease. Indeed, we did not observe a uveitis flare in any of our 250 patients with RA who were treated with etanercept. In conclusion, we believe that etanercept is different from the anti-TNF monoclonal antibodies in terms of treat- ing the extraarticular manifestations of chronic rheumatic diseases and suggest that anti-TNF antibody treatment is preferable to treatment with the soluble TNF receptor agent in patients with spondylarthropathy experiencing recurrent uveitis flares. LETTERS 1555