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Successful treatment of refractory anterior scleritis in primary Sjögren’s syndrome with rituximab
  1. K Ahmadi-Simab1,
  2. P Lamprecht1,
  3. B Nölle2,
  4. M Ai1,
  5. W L Gross1
  1. 1Department of Rheumatology, University Hospital of Schleswig-Holstein, Campus Luebeck, and Rheumaklinik Bad Bramstedt, Ratzeburger Allee 160, 23538 Luebeck, Germany
  2. 2Department of Ophthalmology, University Hospital of Schleswig-Holstein, Campus Kiel, Hegewischstr. 2, 24105 Kiel, Germany
  1. Correspondence to:
    Dr K Ahmadi-Simab

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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.

Figure 1

 (A) Anterior scleritis and flow cytometric analysis of B cell population in primary Sjögren’s syndrome before treatment with the monoclonal anti-CD20 antibody rituximab. (B) Induction of remission with rituximab. For flow cytometric analysis peripheral blood mononuclear cells were stained with fluorochrome conjugated monoclonal antibodies for cell surface antigens or appropriate negative (isotype) controls. Four colour flow cytometric analysis was performed using a FACSCalibur flow cytometer (Becton Dickinson) and CELL-Quest software (Becton Dickinson). Lymphocytes were gated for analysis based on light scattering properties. A second gate was set based on light scattering properties and CD45 perCP staining properties. Positively and negatively stained populations were calculated by quadrant dot plot analysis determined by isotype controls. Quadrant markers were positioned to include >99% of control (isotype) immunoglobulin stained cells in the lower left quadrant. The numbers given in the upper right quadrant of the FACS refer to the fraction of cells detected in each quadrant. B cells display CD19 expression. Before treatment about 10% of the circulating CD19+ B cell population belong to the CD5+ (B1) B cell fraction. After successful treatment with rituximab no circulating CD19+ B cells can be detected.


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.