Improvement in Sjo ¨ gren’s Syndrome Following Therapy With Rituximab for Marginal Zone Lymphoma BRADLEY G. SOMER, DONALD E. TSAI, LISA DOWNS, BARRY WEINSTEIN, AND STEPHEN J. SCHUSTER Introduction Sjo ¨ gren’s syndrome (SS) is a chronic lymphocytic inflam- matory disorder characterized by xerostomia and kerato- conjunctivitis sicca (1). Besides the glandular and extra- glandular features of this disorder, the underlying lymphoproliferative process results in a 44-fold increase in the risk of developing lymphoma for patients with SS compared with the general population (2). The patient that we report here had severe SS for nearly 20 years charac- terized by profound parotid and salivary gland swelling, xeropthalmia, and xerostomia. His symptoms were refrac- tory to supportive measures and hydroxychloroquine. He then developed marginal zone lymphoma that was treated with rituximab, a chimeric monoclonal antibody that re- acts with the CD20 antigen, present on more than 90% of B cells, with complete resolution of his SS-related symp- toms. This case suggests that SS may be, in part, B cell mediated and that therapy with rituximab may be useful in the management of SS. The incidence of SS is estimated between 0.5% and 5% of the population, with an estimated worldwide preva- lence of 500,000 –2,000,000, yet SS is believed to be under diagnosed (3). Primary SS may involve extraglandular sites causing arthritis, pneumonitis, nephritis, nervous system manifestations, and vasculitis of skin and other organs. Secondary SS is defined by the occurrence of the syndrome in association with another known autoimmune disease. There are a number of objective tests and clinical features that are used to establish the diagnosis, including the Schirmer test, the tear break up time, corneal staining, the van Bijsterveld score, secretory sialography, salivary scintigraphy, whole mouth unstimulated collected sali- vary flow rate, and minor salivary gland biopsy. Serologic markers of autoimmune disease, including antinuclear an- tibodies (ANA), anti-SSA, anti-SSB, rheumatoid factor (RF), and cryoglobulins, are frequently present in SS. Currently, there is no consensus treatment for SS. The treatment is generally aimed at alleviating the dryness symptoms and related morbidities. More recent ap- proaches to therapy for SS have included therapies that increase glandular excretion using muscarinic (M3) recep- tor agonists. Systemic manifestations are treated with ste- roids, nonsteroidal antiinflammatory drugs (NSAIDs), hy- droxychloroquine, or cytotoxic agents, but, in general, these therapies are marginally effective and have poten- tially serious side effects. Safer and more efficacious ther- apy directed at modifying the underlying disease process is needed. The present case report suggests that monoclo- nal antibody therapy targeting B lymphocytes may be a novel therapeutic approach to SS deserving further study. Case report A 46-year-old man with a long history of SS was referred for the management of marginal zone lymphoma. More than 10 years ago, he reported difficulty eating dry foods, and occasional ocular crust formation. Physical examina- tion at that time showed mouth dryness with no sublin- gual salivary pool. A magnetic resonance image (MRI) showed enlarged multicystic parotid glands bilaterally. Laboratory studies were remarkable for ANA 1:80, speck- led pattern, and positive SSB antibody. RF and human immunodeficiency virus test results were negative. Fine- needle biopsy of a parotid gland showed lymphoid cells consistent with reactive hyperplasia. The patient was treated for presumed suppurative parotitis and was thought to have SS. Nine years ago, he had a second episode of parotitis and soon afterwards, noted the onset of xeropthalmia with chronic redness of both eyes. Five years ago, his Schirmer test with anesthesia showed an 8-mm right eye and an 8-mm left eye (normal), his tear break up time was 0.5 seconds (abnormal), and rose ben- Bradley G. Somer, MD, Donald E. Tsai, MD, PhD, Lisa Downs, CRNP, Barry Weinstein, DDS, Stephen J. Schuster, MD: University of Pennsylvania Cancer Center, Philadel- phia. Address correspondence to Bradley G. Somer, MD, Hos- pital of the University of Pennsylvania, 16 Penn Tower, 34th and Spruce Street, Philadelphia, PA 19104. E-mail: somerb@ mail.med.upenn.edu. Submitted for publication December 26, 2001; accepted in revised form May 31, 2002. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 49, No. 3, June 15, 2003, pp 394 –398 DOI 10.1002/art.11109 © 2003, American College of Rheumatology CASE REPORT 394