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Anterior scleritis is an inflammation of the superficial, subconjunctival sclera which may follow infection or occur in rheumatic disease. Anterior scleritis due to secondary immune complex mediated vasculitis is an extremely rare extraglandular manifestation in primary Sjögren’s syndrome.1 Symptoms of anterior scleritis are pain, tearing, and photophobia. If left untreated, anterior scleritis may progress to scleromalacia and, ultimately, threaten eyesight by affecting the uvea.2 Here we report on the successful induction of remission with the B cell directed monoclonal anti-CD20 antibody in a case of refractory anterior scleritis with episcleritis in primary Sjögren’s syndrome.
Primary Sjögren’s syndrome was diagnosed in a 60 year old white woman according to the criteria of the European study group.3 Ocular and oral sicca symptoms included for more than 3 months, a pathological Schirmer test (<5 mm/5 min), and pathological salivary scintigraphy. Antinuclear antibodies and Ro (SSA) were detected and, later on, anti-fodrin antibodies. Complement levels were normal, cryoglobulin was negative. The patient was treated for arthralgia with low dose steroids and hydroxychloroquine.
In 2001 the patient’s illness was complicated by an anterior scleritis. Treatment with steroids and eye drops containing ciclosporin was not effective. Application of different immunosuppressant drugs (methotrexate, ciclosporin, cyclophosphamide, intravenous immunoglobulin, tumour necrosis factor α blockade with infliximab, leflunomide) combined with high doses of steroids did not result in a remission of the anterior scleritis. Based on pathogenetic considerations (see below) we finally applied the monoclonal anti-CD20 antibody rituximab in order to induce remission and prevent the sequelae of anterior scleritis—that is, scleromalacia and uveitis.
Four weeks after stopping the preceding immunosuppression the patient was given rituximab for the first time. Four rituximab infusions (375 mg/m2 intravenously, MabThera) at 4 week intervals induced remission of the anterior scleritis (fig 1). The steroid dose could be tapered. Fluorescence activated cell sorting (FACS) analysis of lymphocyte populations showed a depletion of circulating peripheral B cells (fig 1). Thereafter, the patient received mycophenolate mofetil to maintain remission. She has now remained in remission for 6 months.
Killing of CD20 positive cells mediated by rituximab is caused by several mechanisms, including complement dependent cytotoxicity, antibody dependent cell mediated cytotoxicity, and induction of apoptosis.4 Rituximab induces remission of malignant B cell lymphomas.5 Clinical findings, data from animal models, and in vitro experiments suggest that B cells have a pivotal role in a number of rheumatic conditions such as rheumatoid arthritis and primary Sjögren’s syndrome. Rituximab successfully induced remission in a number of cases of refractory systemic lupus erythematosus, dermatomyositis, and cryoglubulinaemic vasculitis associated with hepatitis C virus.6–8 An immunosuppressive combination treatment with rituximab also induces remission in refractory rheumatoid arthritis.9 B cells may play an important part in primary Sjögren’s syndrome. Ectopic lymphoid tissue formation and lymphoproliferation are a hallmark of primary Sjögren’s syndrome. The risk for malignant B cell lymphoma is increased nearly 40-fold in patients with Sjögren’s syndrome. Alterations in the B cell compartment have been noted in primary Sjögren’s syndrome. A significant reduction in circulating memory CD27+ B cells and accumulation of memory B cells in the salivary glands is seen in primary Sjögren’s syndrome.10
These studies provided the rationale for the use of rituximab in our patient with refractory anterior scleritis in primary Sjögren’s syndrome. We suggested that B cell depletion might favour induction of remission. To our knowledge this is the first report to show successful induction with rituximab in primary Sjögren’s syndrome. We cannot totally rule out the possibility of delayed effects as a result of previous drug treatment, but induction of remission paralleled the complete depletion of circulating B cells induced by rituximab. Remission was subsequently maintained with mycophenolate mofetil in the presence of persistent peripheral B cell depletion.
Our report suggests that specific B cell depletion may be one successful strategy in the treatment of refractory primary Sjögren’s syndrome. However, further studies are needed to determine the place of B cell depletion strategies in the treatment of severe organ manifestations in primary Sjögren’s syndrome.
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