Treatment of Systemic Sclerosis-Associated Calcinosis: A Case Report of Rituximab-Induced Regression of CREST-Related Calcinosis and Review of the Literature Dimitrios Daoussis, MD, 1 Ioannis Antonopoulos, MD, 1 Stamatis-Nick C. Liossis, MD, Georgios Yiannopoulos, MD, and Andrew P. Andonopoulos, MD, FACP Objectives: Calcinosis is frequently encountered in patients with systemic sclerosis (SSc) and may be associated with significant morbidity. No treatment has shown so far an unequivocal beneficial effect. Methods: We performed an extensive internet search (MEDLINE) using the keywords calcinosis, calcification, scleroderma, systemic sclerosis, and treatment. Results: Our patient had extensive Calcinosis, Raynaud, Esophagitis, Sclerodactyly, telangiectasia (CREST)-related calcinosis, frequently ulcerating and painful. Following 2 rituximab courses (consisting of 4 weekly infusions, 375 mg/m 2 each), calcinosis significantly improved and pain disappeared. Pharmacologic agents used in the treatment of SSc-associated calcinosis include diltiazem, minocycline, warfarin, biphosphonates, and intravenous immunoglobulin. Other ther- apeutic approaches include surgical excision, laser vaporization, and extracorporeal shock wave lithotripsy. Conclusions: Evidence for all existing therapies is weak and therefore larger scale controlled studies are needed. Rituximab appears as a promising treatment especially in view of recent evidence that this therapy may be also effective in the underlying disease. © 2012 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 41:822-829 Keywords: Rituximab, B cells, systemic sclerosis, scleroderma, limited, CREST, calcinosis, calcification, treatment, warfarin, diltiazem, IVIG, minocycline, biphosphonates, laser, lithotripsy C alcinosis, the deposition of calcified material in soft tissues, is frequently seen in patients with systemic sclerosis (SSc), especially those with the limited form of the disease. It has been reported that as many as 40% of patients with limited SSc have calcinosis (1). The lesions are commonly located in pressure areas, usually the extensor surfaces, most frequently of the hands but also of the knees and elbows. They do not solely represent bothersome lumps causing cosmetic issues but are frequently associated with significant morbidity. Cal- cinosis may lead to skin ulceration and local inflamma- tion, which sometimes can be complicated by infection. The resulting significant pain and functional disability lead to distress and impaired quality of life. SSc-associated calcinosis is a form of the so-called dystrophic calcifica- tion, a term describing the deposition of calcified material in damaged tissues in the presence of normal calcium/ phosphorus metabolism. Indeed, patients with SSc are not characterized by an imbalance in calcium/phosphorus metabolism but do have extensive vasculopathy that leads to tissue ischemia and eventually structural damage. However, it is not exactly clear why and how calcinosis develops in patients with SSc. Therapeutic options for SSc-associated calcinosis are rather limited; several drugs as well as a few nonpharma- cologic treatments have been tried with disappointing or modest results. The relevant studies are mainly case re- Division of Rheumatology, Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, Patras, Greece. 1 These authors contributed equally to this article. The authors have no conflicts of interest to disclose. Address reprint requests to D. Daoussis, MD, Department of Internal Medicine, Division of Rheumatology, Patras University Hospital, 26504 Rion, Patras, Greece. E-mail: jimdaoussis@hotmail.com. SYSTEMIC SCLEROSIS 822 0049-0172/12/$-see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.semarthrit.2011.11.007