1 Pediatric Rheumatology Clinic and 2 Pediatric Ophthalmology Service, Assaf Harofeh Medical Center, Zerifin, 3 Sackler School of Medicine, Tel Aviv University, Tel Aviv and 4 Pediatric Rheumatology Clinic, Kaplan Hospital, Rehovot, Israel
Correspondence to: T Tauber, Pediatric Rheumatology Clinic, Assaf Harofe Medical Center, Zerifin, 70300, Israel. E-mail: ztauber{at}asaf.health.gov
SIR, Two female patients treated with etanercept for extended oligoarticular juvenile idiopathic (rheumatoid) arthritis (JIA) are presented.
The first case was a 12-yr-old girl who was diagnosed at the age of 15 months with oligoarticular JIA with positive ANA. She progressed to extended oligoarticular disease, treated over the years with NSAIDs, salazopyrin, oral methotrexate, prednisolone, intra-articular steroid injections, physiotherapy and finally etanercept. At the age of 8 yr she developed bilateral anterior uveitis, more severe in her right eye, which was treated with topical as well as sub-Tenon's steroids and oral methotrexate. At the age of 11 she was started on etanercept because of further deterioration in her joint disease. The effect on the joints was excellent, with significant improvement in her daily activities. Two and a half months after commencing etanercept the patient noted deterioration in her vision, with a reduction of visual acuity from 6/12 to 6/60 in the right eye (in which a cataract had developed). Ultrasonography revealed inflammatory cells in the vitreous with a swollen optic disc. Visual evoked potentials (VEP) were reduced in that eye, with prolonged latency. Optic neuritis of the right eye was diagnosed and etanercept was discontinued. She received three intravenous pulses of 1 g methylprednisolone at weekly intervals. At follow-up examination 3 months later vision had improved to 6/24. Follow-up VEP testing revealed improved responses, but latency in the affected eye was still longer than in the other eye. Ultrasound showed a normal appearance of the optic nerve and clearing of the vitreous cells. The child is scheduled for cataract surgery, which will probably improve her vision further.
The second case was a young girl who was diagnosed with ANA-positive oligoarticular JIA at the age of 3 yr. Almost from the onset of her joint disease she also suffered from chronic anterior uveitis of the right eye, which eventually became phthitic. Her joint disease was initially oligoarticular, and then progressed to severe extended polyarthritis. Her treatment regimen included NSAIDs, salazopyrin, systemic and intra-articular corticosteroids and oral methotrexate. At the age of 17, suffering from severe growth retardation, delayed puberty and persistently active joint disease, she started etanercept with striking improvement in her joints, general well-being and growth. The acute-phase proteins returned to normal and ANA became negative for the first time. Eight months after commencement of etanercept, she noted deterioration of vision in her only seeing eye. Fundoscopy revealed optic neuritis. Treatment with etanercept was stopped; she received three pulses of 1 g of intravenous methylprednisolone daily for three consecutive days, followed by oral prednisolone, cyclosporin and topical steroids. Follow-up examination revealed resolution of the optic neuritis and improvement of the visual acuity.
In both cases presented there is an association between etanercept treatment and the appearance of optic neuritis. Initially, only injection site reactions were reported with etanercept [1], but with more widespread use there were reports of other side-effects, such as severe infections as well as eye complications [2, 3]. A recent overview of the drug listed a wide range of side-effects that have been reported in the postmarketing phase of etanercept. These reports include CNS demyelinating disorders, such as multiple sclerosis, transverse myelitis and optic neuritis [4, 5].
The two patients described in this paper developed optic neuritis coinciding with etanercept treatment, which improved upon its discontinuation. In view of this observation and previous reports, there is a high probability that the optic neuritis in these patients was a side-effect of etanercept. Both patients are similar in other aspects of their disease, which started at a young age with oligoarticular JIA and positive ANA and had a persistent, extended oligoarticular course despite aggressive treatment. Both also suffered from severe uveitis, necessitating local and systemic steroids as well as methotrexate. In both patients treatment with etanercept resulted in a striking improvement of their joint disease and general well-being. There is a possibility that children with this type of JIA, and severe eye involvement, are at higher risk of suffering from optic neuritis as a result of etanercept treatment.
In conclusion, patients with JIA, especially those with extended oligoarthritis treated with etanercept, should be closely monitored by an ophthalmologist. Finally, ongoing surveillance for possible side-effects is very important in view of the possibility that there is a subpopulation of JIA patients who are at higher risk of optic neuritis associated with etanercept treatment.
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The authors have declared no conflicts of interest.
References
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