Rheumatoid corneal melt

A. Sule, C. Balakrishnan, S. Gaitonde, G. Mittal, E. Pathan, N. S. Gokhale1 and V. R. Joshi

Department of Rheumatology, P. D. Hinduja National Hospital, Mumbai and
1 Department of Ophthalmology, Gokhale Nursing Home, Mumbai, India

SIR, Corneal melt, though rare, is a serious complication seen in patients with rheumatoid arthritis (RA). It heralds systemic vasculitis in more than 50% of cases [1, 2], carries a high mortality rate and needs early and aggressive treatment [1, 3]. We report four patients who were treated successfully with a combination of steroid and pulse cyclophosphamide.

Case 1, a female who had had RA for 2 yr, first saw us in April 1996. She complained of pain and swelling of the proximal interphalangeal joints, ankles, knees and left elbow, and early morning stiffness of 1 h. She had had dryness of the eyes for 6 months and was using hydroxypropylmethylcellulose (0.7%) eye drops. Fifteen days before presentation she had developed redness of both eyes with pain and photophobia. There were no systemic complaints. She had been treated all along with non-steroidal anti-inflammatory drugs and Ayurvedic formulations. Examination revealed synovitis of the joints mentioned above. There was bilateral corneal melt with perforation. There were no subcutaneous nodules or any other extra-articular manifestations of RA. Results of investigations were as follows: haemoglobin (Hb) concentration 11.2 g/dl; total leucocyte count (TLC) 9900/mm3 (neutrophils 74, lymphocytes 22, basophils 1, eosinophils 2, monocytes 1); erythrocyte sedimentation rate (ESR) (Westergren) 91 mm/h; rheumatoid factor concentration 160 IU/ml; urine normal, fasting blood sugar concentration 96 mg/dl, serum creatinine concentration 0.9 mg/dl. Her chest X-ray was normal. Hand X-rays showed soft tissue swelling, juxta-articular osteopenia and erosions of the third metacarpal heads bilaterally. She was treated with intravenous (i.v.) pulses of methylprednisolone 1 g/day for 3 days plus i.v. cyclophosphamide 500 mg on day 3. She received six cyclophosphamide pulses at monthly intervals. Oral prednisolone (1 mg/kg) was started on day 4 and was tapered over a period of 6 months. The corneal perforation was treated with cyanoacrylate glue and bandage contact lens together with ciprofloxacin and hydroxypropylmethylcellulose (0.7%) eye drops. At the 6-month follow-up, she had no evidence of active synovitis. There were bilateral corneal opacities but vision was normal. Investigations showed the following: Hb concentration 12.6 g/dl, TLC 5100/mm3 (normal differential count), ESR 25 mm/h and serum albumin concentration 3.48 g/dl. She was started on methotrexate and chloroquine. At her last follow-up, in January 1999, she was doing well.

The main features of the other three cases are shown in Table 1Go.


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TABLE 1.  Salient features of cases 2–4

 
Peripheral ulcerative keratitis (PUK) is characterized by inflammation involving the limbal part of the cornea and adjacent sclera. It is characterized by collagen destruction, cellular infiltration and limbal vascular changes indicative of vasculitis [1, 3]. Several pathogenic mechanisms have been postulated [4, 5]: (i) imbalance between matrix metalloproteinase 1 (MMP-1) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), resulting in rapid corneal keratolysis; (ii) the presence of autoantibodies to specific corneal proteins (such antibodies are present in 91% of cases of PUK, 30% of patients with systemic disease without PUK and in 10% of normal sera, raising doubts about their significance); and (iii) aberrant expression of HLA class II antigens on corneal epithelial cells and keratocytes, with cell-mediated immune destruction.

Severe pain and photophobia are the main symptoms of PUK. There is a sensation of foreign bodies and excessive watering. Slit lamp examination reveals a non-infiltrating ulcer at the periphery of the cornea with surrounding inflammatory infiltrate and conjunctival injection. Keratoconjunctivitis sicca is common. PUK, though classically associated with RA, has been described with primary Sjögren's syndrome, polyarteritis nodosa, Wegener's granulomatosis and relapsing polychondritis. It heralds systemic vasculitis in more than 50% of RA cases. Radiology invariably shows erosive arthritis [1, 2].

Treatment with steroids alone is not adequate. Additional immunosuppression is recommended [4]. Cyclophosphamide is the drug of choice. Concomitant infection needs to be treated. Azathioprine requires at least 3–4 weeks to induce a response, and hence is not an ideal drug [6]. Cyclosporin may be effective [7]. The duration of treatment depends on whether there are associated systemic features.

The usual surgical treatment is scleral or corneal grafting, using autogenous periosteum or sclerotherapy, which gives good results [8, 9]. Cyanoacrylate glue and layering of an amniotic membrane graft is effective for perforations less than 1 mm in size [8, 9]. PUK can recur. It can be reactivated as a result of corneal damage, including that resulting from intraocular surgery. It is advocated that RA patients who have history of PUK should receive immunosuppressive therapy before undergoing intraocular surgery.



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FIG. 1.  Limbal corneal melt with iris prolapse.

 

Notes

Correspondence to: A. Sule, P. D. Hinduja National Hospital & Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai 400016, India. Back

References

  1. Jifi-Bahool H, Saadeh C, O'Connor J. Peripheral ulcerative keratitis in the setting of rheumatoid arthritis: treatment with immunosuppressive therapy. Semin Arthritis Rheum1995;25:67–73.[ISI][Medline]
  2. Foster CS, Forstot SL, Wilson LA. Mortality rate in rheumatoid arthritis patients developing necrotising scleritis or peripheral ulcerative keratitis: effects of systemic immunosuppression. Ophthalmology1984;91:1253–63.[ISI][Medline]
  3. Squirrel DM, Winfield J, Amos RS. Peripheral ulcerative keratitis ‘corneal melt’ and rheumatoid arthritis: a case series. Br J Rheumatol1999;38:1245–8.
  4. Riley GP, Harral RL, Watson PG, Cawston TE, Hazleman BL. Collagenase (MMP-1) and TIMP-1 in destructive corneal disease associated with rheumatoid arthritis. Eye1995;9:703–18.[ISI][Medline]
  5. Michels ML, Lobo M, Cadwell DS, Rice JR, Haynes BF. Rheumatoid arthritis and sterile corneal ulceration: analysis of tissue immune effector cells and ocular epithelial antigens using monoclonal antibodies. Arthritis Rheum1984;27:606–14.[ISI][Medline]
  6. Yu DT, Clemants PJ, Peter JB et al. Lymphocyte characteristics in rheumatic patients and the effect of azathioprine therapy. Arthritis Rheum1974;17:37–45.[ISI][Medline]
  7. Kervick GN, Pflugfelder SC, Haimoviri R, Brown H, Tozman E, Yec R. Paracentral rheumatoid corneal ulceration. Clinical features and cyclosporin therapy. Ophthalmology1992;99:80–8.[ISI][Medline]
  8. Messmes E, Foster S. Destructive corneal and scleral disease associated with rheumatoid arthritis: medical and surgical management. Cornea1995;14:408–17.[ISI][Medline]
  9. Koeniz SB, Sanitato JJ, Kenifman HE. Long term follow up study of scleroplasty using autogenous periosteum. Cornea1990;9:139–43.[ISI][Medline]
Accepted 29 November 2001





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