Sir,

Wegener's granulomatosis (WG) is a rare multisystem granulomatous disease. The ocular presentations of WG include episcleritis, scleritis, peripheral ulcerative keratitis (PUK), obstruction of the nasolacrimal duct, uveitis, and optic nerve involvement. Corneal melting has been reported in 11–16% of patients with WG.1

Case report

A 43-year-old woman presented to our clinic with severe PUK and systemic features of WG. She had multiple negative C and P-ANCA. Clinically, she had a flattened nasal bridge and bilateral dacrocystorhinostomies and on ENT assessment was found to have a septal perforation. A conjunctival biopsy showed a granulomatous inflammation with the histological appearance of WG.

The PUK decompensated and her cornea perforated while on methotrexate 20 mg weekly. Previously she was on cyclophosphamide but had to discontinue as she developed haemorrhagic cystitis. At the time of perforation, she was admitted and treated with pulse intravenous (i.v.) methylprednisone 500 mg/day and eventually required a patch graft as her perforation and thinning worsened. She was discharged on mycophenolate mofetil 500 mg b.d. and prednisone 40 mg o.d. 3 days later she was reviewed in the outpatient clinic with further corneal melting at the edge of the patch graft (Figure 1). She was commenced on i.v. methylprednisone 1 g o.d., but after 3 days the PUK worsened. It was decided to start her on a course of Campath 10 mg i.v. daily (four doses). Her PUK stabilized over the ensuing months and she was kept on a maintenance dose of mycophenolate sodium 1440 mg b.d. and a tapering dose of prednisone to 10 mg o.d., and 18 months after Campath therapy the PUK has remained in remission.

Figure 1
figure 1

Active peripheral ulcerative keratitis (PUK), showing corneal thinning, at the edge of the corneal patch graft (arrow).

Full size image

Comments

WG is a rare disease that usually affects patients in their fourth to sixth decades. It most commonly occurs in Caucasians with a male preponderance. The American College of Rheumatology stipulates that the presence of two or more of the following four criteria is associated with a sensitivity of 88% and a specificity of 92% for WG: abnormal urinary sediment, abnormal chest X-ray, oral ulcers or nasal discharge, and granulomatous inflammation.2 A negative ANCA does not exclude the diagnosis of WG. Pathologically, the finding of a necrotizing granuloma confirms the diagnosis of WG.

Campath is indicated for the treatment of B-cell chronic lymphocytic leukaemia in patients who have been treated with alkylating agents and who have failed fludarabine therapy. Campath has also demonstrated a transient benefit in other conditions such as rheumatoid arthritis and multiple sclerosis.3 Recently, it has been shown to be useful in refractory ocular disease such as non-infectious retinal vasculitis, sympathetic ophthalmia, Behçet's disease as well as recurrent corneal graft rejection.4, 5 Campath is a humanized anti-T-cell monoclonal antibody that recognizes the pan lymphocyte antigen CD52, inducing an antigen-specific unresponsiveness and immunoregulation.6 The main complications of Campath treatment, usually during the first i.v. infusion, include fever, rigor, nausea, vomiting, and hypotension responsive to steroids. Immunosuppression resulting from normal B- and T-lymphocyte depletion is frequent, resulting in an increased risk for opportunistic infections.7 There are many and varied immunosuppressive agents used in the treatment of PUK that usually have good effect. Cyclophosphamide, methotrexate, azathioprine, chlorambucil, and azathioprine have been utilized with good success.8 Cyclophosphamide is the drug of choice for almost all PUK associated with connective tissue disorders. Methotrexate, azathioprine, cyclosporine A, and chlorambucil have been found to be effective.8 To our knowledge, Campath has not been described as a treatment for PUK associated with WG.