CASE REPORT

Atypical Continuous Keratitis in a Case of Rheumatoid

Arthritis Accompanying Severe Scleritis
Masayuki Hata, MD,*† Takahiro Nakamura, MD, PhD,*†‡ Chie Sotozono, MD, PhD,*†‡
Kyoko Kumagai, MD,*† Shigeru Kinoshita, MD, PhD,‡ and Yasuo Kurimoto, MD, PhD*†

Purpose: Rheumatoid arthritis (RA) often presents with ocular

complications: typically dry eye, peripheral corneal ulcer, and
R heumatoid arthritis (RA) is a chronic progressive autoim-
mune disease characterized by a polyarticular synovitis.
RA often presents with ocular complications caused by
scleritis. We report for the first time a case of severe scleritis with immunocomplex deposits: typically dry eye, peripheral ulcer-
RA, accompanying atypical continuous keratitis, which apparently ative keratitis (PUK), and scleritis. Moreover, RA causes
differs from typical peripheral ulcerative keratitis (PUK). a wide variety of ocular lesions, including uveitis and corneal
Methods: Observational case report. impairment in the clinical course.1
Scleritis is one of the severe ocular manifestations of
Results: A 68-year-old woman with RA presented at our hospital RA and is associated with systemic inflammation.2,3 As com-
complaining of worsening arthritis accompanying ocular injection pared to patients with idiopathic scleritis, RA-associated
and discharge. On examination, nodular scleritis and peripheral scleritis is sometimes resistant to treatments.4 In addition,
corneal infiltration were noted. In addition to administering topical RA presents with various corneal lesions associated with
steroid and antibiotics, cyclosporine and an oral steroid were added the occurrence of scleritis.5,6 PUK is a severe inflammatory
because of the patient’s worsening scleritis. Despite gradual disease that characteristically involves the peripheral cornea.
improvement of the scleritis, the efficacy of the additional treatments The clinical presentation of PUK is characteristically a non-
was limited. Four months after initial treatment, the patient presented infiltrating ulcer at the periphery of the cornea that is often
with uveitis, thought to be caused by a herpetic virus. Antivirus contiguous with adjacent scleritis.7
treatment was effective for the uveitis, but atypical continuous ker- Conventional treatment of RA consists of the adminis-
atitis suddenly appeared. The keratitis was located from 4-o’clock to tration of systemic corticosteroids and immunosuppressants.
10-o’clock positions continuously in the midperipheral cornea and Methotrexate is widely used as the first-line treatment;
apparently differed from herpetic keratitis or PUK as typically seen however, methotrexate monotherapy often fails to reduce or
in RA cases. Immune reaction was suspected, and the keratitis im- eradicate the inflammation. A combination with other immu-
proved within 2 weeks. After that, the introduction of an anti–tumor nosuppressants, such as cyclophosphamide, cyclosporine A,
necrosis factor a drug (infliximab) completely resolved the severe and azathioprine, is often used to lower the disease activity.4,8
scleritis and there was no recurrence of ocular inflammation. In addition, surgical intervention by keratoepithelioplasty is
commonly chosen for treating the severe peripheral corneal
Conclusion: As is shown in this case, RA can present with atypical ulcer.9 However, very little published data exist regarding
continuous keratitis, thought to be a manifestation of an immuno- treatments for RA-related ocular inflammation resistant to
logic reaction other than PUK. In addition, although immunosup- conventional treatments. Tumor necrosis factor a (TNF-a)
pressants are often used for the treatment of RA with scleritis, is an inflammatory cytokine, and agents blocking its action
the efficacy is limited. Infliximab may be a useful treatment for have proven to be effective in treating RA. Reports are few,
treatment-resistant scleritis. but some case studies have reported the effective treatment of
Key Words: rheumatoid arthritis, scleritis, peripheral ulcerative severe scleritis.10,11
keratitis, uvetis, infliximab In this present study, we report for the first time a case of
severe scleritis with RA accompanying atypical continuous
(Cornea 2012;31:1493–1496) keratitis that apparently differs from typical PUK, which
ultimately was effectively treated by the use of an anti-TNF drug.
Received for publication July 27, 2011; revision received August 25, 2011;
accepted October 14, 2011.
From the *Department of Ophthalmology, Kobe City Medical Center General CASE REPORT
Hospital, Kobe, Japan; †Department of Ophthalmology, Institute of Bio- A 68-year-old woman was referred to our hospital presenting with
medical Research and Innovation Hospital, Kobe, Japan; and ‡Depart- conjunctival injection and ocular discharge in her OD and worsening of
ment of Ophthalmology, Kyoto Prefectural University of Medicine, arthralgia. She had been diagnosed with RA over the previous 15 years
Kyoto, Japan.
The authors have no funding or conflicts of interest to disclose. and had been treated with prednisolone (5 mg/d) and methotrexate
Reprints: Takahiro Nakamura, Department of Ophthalmology, Kyoto Prefectural (6 mg/wk). Her best-corrected visual acuity was 20/32 OD and 20/20
University of Medicine, 465 Kajii-cho, Hirokoji-agaru, Kawaramachi-dori, OS. In her OD, nodular scleritis at the upper and lower sclera and
Kamigyo-ku, Kyoto 602-0841, Japan (e-mail: [email protected]). peripheral corneal infiltration at the 3-o’clock and 9-o’clock positions
Copyright © 2012 by Lippincott Williams & Wilkins were noted (Fig. 1). There were no inflammatory cells in the anterior

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Hata et al Cornea  Volume 31, Number 12, December 2012

chamber and vitreous cavity. A fundus examination showed normal DISCUSSION

macula, peripheral retina, disk, and vessels in the OD. The ophthalmologic manifestations of RA are dry eye,
The patient was initially treated with topical betamethasone and PUK, scleritis, and other ocular complications.1 RA also
levofloxacin but was found to be resistant to those treatments. One
month after the initial treatment, oral steroids and cyclosporine (50 mg)
presents with various corneal impairments. It is reported that
were added to the treatment. As a result, the scleritis and peripheral the scleritis is often accompanied by corneal lesions and that
corneal infiltration showed gradual improvement, yet the efficacy was the activity of infiltrative keratitis correlates with that of the
limited. Four months after the initial treatment, she presented with scleritis.5,6 In addition to severe scleritis, this case presented
anterior uveitis with mutton fat keratic precipitates with pigment and for the first time a unique corneal complication, one that is
ocular hypertension (Fig. 2). From these findings, an accompanying clearly different from typical PUK.
herpetic uveitis was highly suspected. Thus, antiherpetic drugs were In the present case, the continuous keratitis suddenly
administered and the anterior uveitis responded well and improved appeared in the midperipheral cornea in the course of treatment
immediately. After that, and most interestingly, an atypical continuous for uveitis, thought to be caused by a herpetic virus.
keratitis appeared, which apparently differs from typical PUK. The Considering the shape and the location of the epithelial lesions,
lesion was located from the 4-o’clock to 10-o’clock positions contin-
uously in the midperipheral cornea, with diffuse superficial punctate
an immunologic mechanism was highly suspected. Although
keratitis (SPK) (Fig. 3), and we continued to administer antivirus drugs the accompanying diffuse SPK, the subsequent hurricane
and topical steroids. Two weeks later, the atypical keratitis gradually keratopathy, and the effect of the reduced antivirus drug may
disappeared, yet conjunctival invasion and hurricane keratopathy were support the indication of a drug-induced mechanism, the shape
temporarily noted. Subsequently, administration of an anti–TNF-a and location of the epithelial lesions were atypical for drug-
drug (infliximab) was initiated because of the persistence of ocular induced corneal damage. Herpetic keratitis was also suspected,
and systemic inflammation. As a result, both scleritis and infiltrative but the SPK surrounding the ulcer and the effect of the reduced
keratitis were completely improved, and there was no recurrence of antivirus drug were incompatible with that hypothesis.
ocular diseases (Fig. 4).

FIGURE 2. A, Slit-lamp photograph of the anterior chamber

FIGURE 1. Slit-lamp photograph of the cornea and sclera in with scleral scattering showing anterior uveitis with mutton fat
diffuse illumination showing nodular scleritis at the upper keratic precipitates with pigment. B, Slit-lamp photograph of
sclera (A) and peripheral corneal infiltration at the 3-o’clock the cornea showing the residual nodular scleritis and periph-
and 9-o’clock positions (white arrow) (B). eral corneal infiltration.

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Cornea  Volume 31, Number 12, December 2012 Atypical Keratitis in a Case of RA

FIGURE 3. A, Slit-lamp photograph of the cornea showing FIGURE 4. A, B, Slit-lamp photograph of the cornea and sclera
continuous corneal epithelial defect, located from the 4-o’clock in diffuse illumination showing the complete improvement
to 10-o’clock positions in the midperipheral cornea. B, Slit- of the scleritis and peripheral corneal infiltration after the
lamp photograph of the cornea with fluorescein stain showing administration of infliximab.
diffuse SPK and the corneal epithelial defect.

The standard treatment for RA-associated scleritis is the In conclusion, RA can present with atypical continuous
administration of topical betamethasone, but RA is often keratitis that is thought to be caused by an immunologic
unresponsive to topical treatments. Previous reports have mechanism, as is shown in this case. The pathophysiology is
shown that cyclosporine is effective for treating severe complicated because of the modification of the disease by its
scleritis; however, side effects that limit the effect of that long clinical course and the various drugs that are adminis-
treatment frequently occurred in elderly patients.12–14 In the tered for treatment. In addition, although immunosuppres-
case presented in this study, we added cyclosporine and an sants are often used for the treatment of RA with severe
oral steroid because of the disease’s resistance to topical treat- scleritis, the efficacy of those drugs is limited and side effects
ments. The activity of scleritis and peripheral corneal infiltra- can frequently occur. Infliximab could be considered a treat-
tion improved gradually, but the efficacy was limited. ment choice in patients who are found to be resistant to
The anti–TNF-a monoclonal antibody infliximab is topical or conventional treatments.
widely used for the treatment of RA.15 Previous reports sug-
gested that infliximab is effective for the treatment of ocular
REFERENCES
inflammation associated with RA, especially refractory scleri-
1. Harper SL, Foster CS. The ocular manifestations of rheumatoid disease.
tis.10,16 In this present case, infliximab was initiated after the Int Ophthalmol Clin. 1998;38:1–19.
administration of cyclosporine because ocular activity and sys- 2. Sainz de la Maza M, Foster CS, Jabbur NS. Scleritis associated with
temic inflammation remained. Considering the fact that both the systemic vasculitic diseases. Ophthalmology. 1995;102:687–692.
scleritis and the peripheral corneal infiltration were completely 3. Foster CS, Forstot SL, Wilson LA. Mortality rate in rheumatoid arthritis
patients developing necrotizing scleritis or peripheral ulcerative keratitis.
resolved without any side effects, infliximab may prove to be the Effects of systemic immunosuppression. Ophthalmology. 1984;91:1253–1263.
optimal treatment option in refractory cases of RA-associated 4. Jabs DA, Mudun A, Dunn JP, et al. Episcleritis and scleritis: clinical
scleritis and corneal ulcer, especially in elderly patients. features and treatment results. Am J Ophthalmol. 2000;130:469–476.

Ó 2012 Lippincott Williams & Wilkins www.corneajrnl.com | 1495

Hata et al Cornea  Volume 31, Number 12, December 2012

5. Malik R, Culinane AB, Tole DM, et al. Rheumatoid keratolysis: a series eye disease and associated rheumatic disease. Arthritis Rheum. 2001;
of 40 eyes. Eur J Ophthalmol. 2006;16:791–797. 45:252–257.
6. Messmer EM, Foster CS. Destructive corneal and scleral disease associ- 12. McCarthy JM, Dubord PJ, Chalmers A, et al. Cyclosporine A for the
ated with rheumatoid arthritis. Medical and surgical management. treatment of necrotizing scleritis and corneal melting in patients with
Cornea. 1995;14:408–417. rheumatoid arthritis. J Rheumatol. 1992;19:1358–1361.
7. Galor A, Thorne JE. Scleritis and peripheral ulcerative keratitis. Rheum 13. Kacmaz RO, Kempen JH, Newcomb C, et al. Cyclosporine for ocular
Dis Clin North Am. 2007;33:835–854. vii. inflammatory diseases. Ophthalmology. 2010;117:576–584.
8. Rath T, Rubbert A. Drug combinations with methotrexate to treat rheu- 14. Okada AA. Immunomodulatory therapy for ocular inflammatory disease:
matoid arthritis. Clin Exp Rheumatol. 2010;28(suppl 61):S52–S57. a basic manual and review of the literature. Ocul Immunol Inflamm.
9. Kinoshita S, Ohashi Y, Ohji M, et al. Long-term results of keratoepithe- 2005;13:335–351.
lioplasty in Mooren’s ulcer. Ophthalmology. 1991;98:438–445. 15. Jin J, Chang Y, Wei W. Clinical application and evaluation of anti-TNF-
10. Murphy CC, Ayliffe WH, Booth A, et al. Tumor necrosis factor alpha alpha agents for the treatment of rheumatoid arthritis. Acta Pharmacol
blockade with infliximab for refractory uveitis and scleritis. Ophthalmology. Sin. 2010;31:1133–1140.
2004;111:352–356. 16. Atchia II, Kidd CE, Bell RW. Rheumatoid arthritis-associated necrotiz-
11. Smith JR, Levinson RD, Holland GN, et al. Differential efficacy of ing scleritis and peripheral ulcerative keratitis treated successfully with
tumor necrosis factor inhibition in the management of inflammatory infliximab. J Clin Rheumatol. 2006;12:291–293.

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