Peripheral ulcerative keratitis – a severe complication of rheumatoid arthritis

Authors: N. Járová 1;  M. Palos 2;  Z. Mazal 1
Authors‘ workplace: Oční oddělení, Oblastní nemocnice Mladá Boleslav, a. s. 1;  Oční klinika Všeobecné fakultní nemocnice 1. LF UK, Praha 2
Published in: Čes. Revmatol., 22, 2014, No. 2, p. 100-106.
Category: Review Article


Rheumatoid arthritis is a systemic inflammatory disease of connective tissue. It can sometimes present itself with extraarticular symptoms, such as eye disorders. Although the most common manifestation is the dry eye disease, there are other severe conditions such as peripheral ulcerative keratitis as well. It is a destructive inflammation at the margin of corneal stroma associated with epithelial defect and progressive stromal degradation and thinning. This potentially devastating disorder can quickly produce necrosis of the corneal stroma, leading to perforation and blindness. In some cases, the peripheral ulcerative keratitis can be the first manifestation of underlying systemic disease. It can also indicate the presence of potentially lethal systemic vasculitis. Therefore, an early diagnose and adequate treatment protocol is key for achievement of satisfactory therapy results. A close cooperation between an ophthalmology and rheumatology specialist is necessary for successful treatment. The role of the rheumatologist is to medically manage patient´s systemic disease with regard to the dynamics of eye impairment. The ophthalmologist´s concern is mainly dealing with local complications and providing feedback for treatment modification. Only effective interdisciplinary cooperation can induce healing process and bring satisfactory treatment results.

Key words:
Rheumatoid arthritis, extraarticular symptoms, peripheral ulcerative keratitis, treatment


1. Svobodová M, Palos M. Periferní ulcerózní keratitida jako komplikace revmatoidní artritidy – výsledky retrospektivní studie. XXI výroční sjezd České oftalmologické společnosti ČLS JEP; Brno: Hanzo production, spol. s r.o.; 2013. p. 104–5.

2. Silva B, Cardozo J, Marback P, Machado F, Galvão V, Santiago M. Peripheral ulcerative keratitis: a serious complication of rheumatoid arthritis. Rheum Int 2010; 30(9): 1267–8.

3. Hogan M AJ, Weddell J. Histology of the Human Eye – An Atlas and Textbook. 2nd ed. Philadelphia: WB Saunders; 1971.

4. Chung G. Phlyctenular keratoconjunctivitis and marginal staphylococcal keratitis. Krachmer J, Mannis M, Holland E (eds). Cornea, 3rd ed. Amsterdam: Elsevier; 2011. p. 1307–10.

5. Mondino BJ. Inflammatory diseases of the peripheral cornea. Ophthalmology 1988; 95(4): 463–72.

6. Foster CS, Forstot SL, Wilson LA. Mortality rate in rheumatoid arthritis patients developing necrotizing scleritis or peripheral ulcerative keratitis. Effects of systemic immunosuppression. Ophthalmology 1984; 91(10): 1253–63.

7. Ali NAM, Mathew R, Joshi N. Peripheral ulcerative keratitis as the initial presentation of rheumatoid arthritis. Brunei Int Med J 2012; 8(6): 353–7.

8. Squirrel DM, Winfield J, Amos RS. Peripheral ulcerative keratitis ‘corneal melt’ and rheumatoid arthritis: a case series. Br J Rheumatol 1999; 38:1245–8.

9. Baldassano VF, Jr. Ocular manifestations of rheumatic diseases. Curr Opin Ophthalmol 1998; 9(6): 85–8.

10. Fox RI, Stern M, Michelson P. Update in Sjögren syndrome. Curr Opin Rheumatol 2000; 12(5): 391–8.

11. Polanska V, Sery O, Fojtik Z, Hlinomazova Z. The presence of dry eye syndrome and corneal complications in patients with rheumatoid arthritis and its association with -174 gene polymorphism for interleukin 6. Cesk Slov Oftalmol 2008; 64(2): 77–80.

12. Galor A, Thorne JE. Scleritis and peripheral ulcerative keratitis. Rheum Dis Clin N Am 2007; 33(4): 835–54.

13. Tauber J, de la Maza MS, Hoang-Xuan T, Foster CS. An analysis of therapeutic decision making regarding immunosuppressive chemotherapy for peripheral ulcerative keratitis. Cornea 1990; 9(1): 66–73.

14. Gregory JK, Foster CS. Peripheral ulcerative keratitis in the collagen vascular diseases. Int Ophthalmol Clin 1996; 36(1): 21–30.

15. Bachmann B, Jacobi C, Cursiefen C. Augenentzündungen bei entzündlichen Systemerkrankungen: Keratitis. Klin Monatsbl Augenheilkd 2011; 228(05): 413–8.

16. Ladas JG, Mondino BJ. Systemic disorders associated with peripheral corneal ulceration. Curr Opin Ophthalmol 2000; 11(6): 468–71.

17. Messmer EM, Foster CS. Vasculitic peripheral ulcerative keratitis. Surv Ophthalmol 1999; 43(5): 379–96.

18. Dana MR, Qian Y, Hamrah P. Twenty-five-year panorama of corneal immunology: emerging concepts in the immunopathogenesis of microbial keratitis, peripheral ulcerative keratitis, and corneal transplant rejection. Cornea 2000; 19(5): 625–43.

19. Jabs DA, Rosenbaum JT. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol 2001; 131(5): 679.

20. Sainz de la Maza M, Foster C, Jabbur NS, Baltatzis S. Ocular characteristics and disease associations in scleritis-associated peripheral keratopathy. Arch Ophthalmol 2002; 120(1): 15–9.

21. Messmer EM, Foster CS. Destructive corneal and scleral disease associated with rheumatoid arthritis. Medical and surgical management. Cornea 1995; 14(4): 408–17.

22. McCarthy JM, Dubord PJ, Chalmers A, Kassen BO, Rangno KK. Cyclosporine A for the treatment of necrotizing scleritis and corneal melting in patients with rheumatoid arthritis. J Rheumatol 1992; 19(9): 1358–61.

23. Diaz-Valle D, Benitez del Castillo JM, Castillo A, Sayagues O, Banares A, Garcia-Sanchez J. Immunologic and clinical evaluation of postsurgical necrotizing sclerocorneal ulceration. Cornea 1998; 17(4): 371–5.

24. Galor A, Jabs DA, Leder HA, Kedhar SR, Dunn JP, Peters GB 3rd, et al. Comparison of antimetabolite drugs as corticosteroid-sparing therapy for noninfectious ocular inflammation. Ophthalmology 2008; 115(10): 1826–32.

25. Thorne JE, Jabs DA, Qazi FA, Nguyen QD, Kempen JH, Dunn JP. Mycophenolate mofetil therapy for inflammatory eye disease. Ophthalmology 2005; 112(8): 1472–7.

26. Sobrin L, Christen W, Foster CS. Mycophenolate mofetil after methotrexate failure or intolerance in the treatment of scleritis and uveitis. Ophthalmology 2008; 115(8): 1416–21

27. Robertson SM, Lang LS. Leflunomide: inhibition of S-antigen induced autoimmune uveitis in Lewis rats. Agents Actions 1994; 42(3-4): 167–72.

28. Reinisch W, Sandborn WJ, Hommes DW, D'Haens G, Hanauer S, Schreiber S, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut 2011; 60(6): 780–7.

29. Wiens A, Venson R, Correr CJ, Otuki MF, Pontarolo R. Meta-analysis of the efficacy and safety of adalimumab, etanercept, and infliximab for the treatment of rheumatoid arthritis. Pharmacotherapy 2010; 30(4): 339–53.

30. Sfikakis PP, Theodossiadis PG, Katsiari CG, Kaklamanis P, Markomichelakis NN. Effect of infliximab on sight-threatening panuveitis in Behcet's disease. Lancet 2001; 358(9278): 295–6.

31. Smith JR, Levinson RD, Holland GN, Jabs DA, Robinson MR, Whitcup SM, et al. Differential efficacy of tumor necrosis factor inhibition in the management of inflammatory eye disease and associated rheumatic disease. Arthritis Rheum 2001; 45(3): 252–7.

32. Oh J, Kim M, Wee W. Infliximab for progressive peripheral ulcerative keratitis in a patient with juvenile rheumatoid arthritis. Jpn J Ophthalmol 2011; 55(1): 70–1.

33. Odorcic S, Keystone EC, Ma JJ. Infliximab for the treatment of refractory progressive sterile peripheral ulcerative keratitis associated with late corneal perforation: 3-year follow-up. Cornea 2009; 28(1): 89–92.

34. Pham M, Chow CC, Badawi D, Tu EY. Use of infliximab in the treatment of peripheral ulcerative keratitis in Crohn disease. Am J Ophthalmol 2011; 152(2): 183–8.

35. Thomas JW, Pflugfelder SC. Therapy of progressive rheumatoid arthritis-associated corneal ulceration with infliximab. Cornea 2005; 24(6): 742–4.

36. Tugal-Tutkun I, Ayranci Ö, Kasapcopur Ö, Kir N. Retrospective analysis of children with uveitis treated with infliximab. J AAPOS 2008; 12(6): 611–3.

37. Murphy CC, Ayliffe WH, Booth A, Makanjuola D, Andrews PA, Jayne D. Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis. Ophthalmology 2004; 111(2): 352–6.

38. Tarabishy AB, Schulte M, Papaliodis GN, Hoffman GS. Wegener's granulomatosis: clinical manifestations, differential diagnosis, and management of ocular and systemic disease. Surv Ophthalmol 2010; 55(5): 429–44.

39. Theodossiadis PG, Markomichelakis NN, Sfikakis PP. Tumor necrosis factor antagonists: preliminary evidence for an emerging approach in the treatment of ocular inflammation. Retina 2007; 27(4): 399-413.

40. Hernandez-Illas M, Tozman E, Fulcher SF, Jundt JW, Davis J, Pflugfelder SC. Recombinant human tumor necrosis factor receptor Fc fusion protein (Etanercept): experience as a therapy for sight-threatening scleritis and sterile corneal ulceration. Eye Contact Lens 2004; 30(1): 2–5.

41. Shimmura S, Shimazaki J, Ohashi Y, Tsubota K. Antiinflammatory effects of amniotic membrane transplantation in ocular surface disorders. Cornea 2001; 20(4): 408–13.

42. Houlihan JM, Biro PA, Harper HM, Jenkinson HJ, Holmes CH. The human amnion is a site of MHC class Ib expression: evidence for the expression of HLA-E and HLA-G. J Immunol 1995; 154(11): 5665–74.

43. Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 1995; 270(5239): 1189–92.

44. McGhee CNJ, Patel DV. Mooren's ulcer and amniotic membrane transplant: a simple surgical solution? Clin Exp Ophthalmol 2011; 39(5): 383–5.

45. Maeno A, Naor J, Lee HM, Hunter WS, Rootman DS. Three decades of corneal transplantation: indications and patient characteristics. Cornea 2000; 19(1): 7–11.

Dermatology & STDs Paediatric rheumatology Rheumatology
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