Open Digital Library of Pediatric Rheumatic Disease.

Treatment of anterior uveitis non-responsive to topical steroids

Michael L. Miller and Kelly Rouster-Stevens

From the Department of Pediatrics

Feinberg School of Medicine

Northwestern University, Chicago, IL

millermd@northwestern.edu

INTRODUCTION

We present a child with anterior uveitis unresponsive to topical steroids. After the presentation, with suggested questions for students, we will review our experience with similar patients, and briefly discuss the literature.

CASE PRESENTATION

The patient is an 8-year-old, who was diagnosed at age 7 ½ years with bilateral anterior uveitis after presenting with complaints of blurred vision. He did not have any visual loss, eye pain or injection. He had been started by his ophthalmologist on oral prednisone and also topical steroid drops 4 months before his first visit to the pediatric rheumatology clinic. This treatment did not control of his uveitis. He had no fever, rash, arthralgias or other associated symptoms. Family history was negative for rheumatic disease. Physical examination revealed irregular pupillary borders bilaterally with synechiae (Figure 1). There was full range of motion in all joints with no tenderness or swelling. The

rest of the examination was unremarkable. The ANA and RF were negative.  The UA, ALT, CBC, and ESR were unremarkable. 

Figure 1

QUESTIONS

What treatment would you recommend?

If that did not work, could you recommend any other treatment?

ANSWERS

The patient was begun on oral methotrexate (15 mg/M²) with gradual improvement, and prednisone was tapered and discontinued after 3 months. He had complete resolution of ocular inflammation 6 months after starting methotrexate (MTX). If oral MTX was not effective, subcutaneous MTX could be given. When uveitis is more severe, our center will recommend subcutaneous MTX immediately. We also prescribe folic acid 1 mg po daily to patients receiving MTX. If MTX is ineffective, we will prescribe cyclosporin, 3-5 mg/kg/day, given q 12 hours, adjusting dose according to results of trough cyclosporin levels.

EXPERIENCE WITH SIMILAR PATIENTS

We summarize our patients with similar patients whose anterior uveitis did not respond to topical steroids. All patients had bilateral uveitis, except for patient 8, who had uveitis affecting the right eye only. Patient number 1 in the table below is the patient presented above. Methotrexate (MTX) was given in doses ranging from 10 – 15 mg/M2. Cyclosporin (CsA) was given in doses ranging from 3 – 5 mg/k/g/day, adjusted to obtain therapeutic levels.

Patient (other diagnoses)	ANA	Age at onset of uveitis (years)	Treatment	Outcome
1 (no other diagnoses)	negative	7 6/12	MTX po	Resolved after 6 months
2 (no other diagnoses)	negative	11 5/12	MTX po, then sq	Resolved after 7 months
3 (no other diagnoses)	negative	12 7/12	MTX sq, po prednisone	Resolved after 22 months
4 (oral ulcers, possible Behcet’s)	negative	15 10/12	MTX po, PDN po, i.o. steroid	Persisting after 5 months, to start remicade
5 (JRA, pauci)	1:160 homogeneous	5 6/12	CsA	Resolved after 14 months*
6 (JRA, pauci)	negative	10 9/12	MTX sq x 6 mo, then CsA	Gradually resolved after 4½ years**
7 (JRA, pauci)	1:80 homogeneous	13 2/12	MTX po, Etanercept (for JRA); CsA for flare	Initial resolution (4 years), flare responding after 3 months to CsA
8 (JRA, poly)	1:80 speckled	5	MTX sq	Resolved after 3 months
9 (spondyloartrhopathy)	negative	10 6/12	CsA	Resolved after 9 months***

Notes:

*Methotrexate not given because of twin brother with ALL, patient had transient pre-leukemic changes on bone marrow aspiration.

**severe uveitis 8 months after onset required left lens implant

***Methotrexate withdrawn after single dose because of development of chills.

DISCUSSION

Experience with treatment of children with anterior uveitis varies, and our results summarized above should be considered anecdotal. With that in mind, it is interesting to observe that patients without any other associated or suspected diagnosis (patients 1-3), tended to do better. However, we are aware of similar patients who have done worse than uveitis patients who also have juvenile rheumatoid arthritis. Patient 4 does not meet formal diagnostic criteria for Behcet’s, but the decision to begin remicade is based upon anecdotal reports of its efficacy in Behcet’s patients with persisting uveitis. Patients 5 through 7 received cyclosporin for reasons listed above, and had good responses.

The uveal tract of the eye is comprised of the choroid, ciliary body, and iris. This continuous, vascular layer can become inflamed resulting in uveitis [1]. The location of the leukocytic infiltration categorizes uveitis as anterior (involving the iris and/or par plicata), intermediate (involving the pars plana and/or adjacent retina), posterior (involving the choroids and/or retina), or panuveitis [2]. Uveitis has been associated with multisystem disease in children including juvenile rheumatoid arthritis (JRA), spondyloarthropathy, Behcet’s disease, sarcoidosis, and Vogt-Koyanagi-Harada syndrome. Up to 80% of children with anterior uveitis have JRA [3]. In particular, 78 to 90% of children with JRA-associated uveitis have pauciarticular disease and among these children 90% have a positive anti-nuclear antibody [3]. Although unusual, uveitis may present prior to the onset of arthritis. Up to half of children with uveitis in the setting of JRA or spondyloarthropathy are asymptomatic, in contrast to patients who present with photophobia, tearing, ocular redness, or blurred vision. Subsequently, screening for uveitis in this patient population is critical to prevent blindness that can occur from persistent, low-grade intraocular inflammation [4].

The management of uveitis can be challenging and is due in part to the paucity of randomized, controlled trials in patients [5]. Treatment varies depending on the anatomic location of the inflammation. Anterior uveitis is generally controlled with topical corticosteroids with or without a mydriatic to prevent synechiae. However, some children respond minimally and require systemic medications, including methotrexate and cyclosporine [5]. More recently, the introduction of tumor necrosis factor (TNF) inhibitors has expanded the repertoire of medications for uveitis. One study reported improvement with etanercept in children with JRA and uveitis [6]. Children refractory to other anti-inflammatory drugs were treated successfully with infliximab in another report [7]. Posterior uveitis, encountered less commonly in children, requires intraocular corticosteroids for unilateral disease and systemic immunosuppression for bilateral disease. For sight-threatening disease a course of systemic corticosteroids is often used. A report by a panel of 12 physicians with expertise in ophthalmology, rheumatology, and pediatrics was recently published in the American Journal of Ophthalmology [8] and reviews various medications utilized in the treatment of inflammatory eye disease.

REFERENCES

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2. Bloch-Michel E, Nussenblatt RB. International Uveitis Study Group Recommendations for the evaluation of intraocular inflammatory disease. Am J Ophthalmol 1987;103:234-5.
   
   
3. Kanskii JJ. Uveitis in juvenile chronic arthritis. Eye. 1988;2:641-5.
   
   
4. Cassidy JT, Petty RE. Juvenile rheumatoid arthritis. In: Cassidy JT, Petty RE. Textbook of Pediatric Rheumatology. Philadelphia, PA: WB Saunders Company; 2001:250-6.
   
   
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6. Lovell DJ, Giannini EH, Reiff A, Cawkwell GD, Silverman ED, Nocton JJ. Etanercept in children with polyarticular juvenile rheumatoid arthritis: Pediatric Rheumatology Collaborative Study Group. N Engl J Med 2000;342:763-9.
   
   
7. Kahn PJ, Weiss M, Imundo LF, Levy DM. Favorable response to higher dose infliximab in refractory uveitis: eleven cases (abstract). Arthritis Rheum 2004;50:S92.
   
   
8. Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol 2000;130:492-513.