Successful treatment of Wegener’s granulomatosis associated scleritis with rituximab

Rituximab (Rituxan, Genentech, Inc, South San Francisco, CA, USA) is a new anti-CD20 B cell monoclonal antibody that has been used successfully to treat refractory cases of Wegener’s granulomatosis (WG).^1–3 There has been no published report of its effect in Wegener’s associated eye disease. We describe the successful treatment of Wegener’s associated scleritis with rituximab.

Case report

A 21 year old man with WG, proved on renal biopsy and by anti-neutrophil cytoplasm antibody (ANCA) positivity 6 years earlier, presented with bilateral, painful, red eyes. On examination his visual acuities were 6/4 right eye and 6/5 left eye. Anterior segment examination showed subconjunctival haemorrhage, congested scleral vessels, scleral oedema, peripheral corneal infiltrates, and mild anterior chamber inflammation in each eye. Funduscopy revealed bilateral swollen optic discs with scattered retinal haemorrhages in the right eye. A diagnosis of scleritis was made. Oral prednisolone was increased from 5–40 mg daily and maintenance oral mycophenolate mofetil 2 g daily was continued. Topical prednisolone acetate 1% hourly was commenced to both eyes.

Over the next month the scleritis had not improved and his systemic vasculitis had become more active, causing arthralgia, haemoptysis, and new vasculitic skin lesions. His white cell count (WCC) had risen to 13.9×10⁹ compared to 9.6×10⁹ the previous month. His ANCA had become positive by indirect immunofluorescence (titre of 1 in 25), and by proteinase 3 specific ELISA (titre 22 units, normal range <10). A new infiltrate was present in the lower lobe of his right lung on chest x ray.

Owing to concern over the total cumulative dose of cyclophosphamide he had previously received (>25 g), he was given an intravenous infusion of rituximab 1 g. Intravenous cyclophosphamide (12.5 mg/kg, adjusted for renal function) was also given with the rituximab infusion. These infusions were repeated after 2 weeks.

This led to an immediate significant systemic improvement accompanied by reduction of WCC to 9.6×10⁹ and ANCA became undetectable. The pulmonary infiltrate resolved. The scleritis also resolved promptly, evident from completely white eyes, resolution of active scleral vessels, corneal infiltrates, optic disc swelling, and subjective resolution of ocular pain. At 7 months after the infusion, the patient remained in remission. His systemic treatment was slowly reduced to prednisolone 15 mg daily and mycophenolate mofetil 750 mg twice daily.

Comment

Rituximab is a humanised monoclonal antibody against the CD20 antigen that is expressed on the cell surface during early pre-B cell development and persists through all stages of B cell differentiation.⁴ It results in rapid depletion of CD20 positive B lymphocytes from the circulating blood and is well tolerated. The precise role of B cells in the pathogenesis of WG remains elusive at present, but several possibilities exist. B cells can act as antigen presenting cells to T cells or provide additional co-stimulatory signals for them. Another possibility is that self reactive B cells, derived from unusual B cell subsets,⁵ may follow an alternative maturation process, including the continued expression of CD20 during antibody production.

There has been no report on its effect on WG associated scleritis. Our patient was given rituximab primarily for his generalised vasculitis, but his refractory scleritis also responded promptly. Although he also received cyclophosphamide at the same time, the dose and course were limited to avoid toxicity. Therefore, in this case the prompt improvement was attributed to rituximab, rather than cyclophosphamide.

This is the first case reporting rituximab as an effective treatment for refractory WG associated scleritis.