Downloaded from http://journals.lww.com/jclinrheum by BhDMf5ePHKbH4TTImqenVJua3JJgqHHlFvglVyI8Nff3gk3zlXR++TJlKKWmlI7lq3ixuzDzMUE= on 06/24/2020 Frequency of Cytomegalovirus Seropositivity and Viremia in a Midwestern University Lupus Population Alexa Meara, MD, MS, Brian Lamoreaux, MD, Holly Steigleman, MACPR, Julliette Yedimenko, MD, Wael Jarjour, MD, Brad Rovin, MD, Samir Parikh, MD, Isabelle Ayoub, MD, and Stacy Payne Ardoin, MD, MS S ystemic lupus erythematous (SLE) is a clinically heterogeneous autoimmune disease occurring predominantly in women of childbearing age, affecting 20 to 150 per 100,000 people in North America. 1 Morbidity and mortality remain unacceptably high in SLE, and treatment is tailored to specific organ involvement, typ- ically involving immunosuppressive therapy. Treatments include Food and Drug Administration–approved therapies (hydroxy- chloroquine, corticosteroids, and belimumab) and off-label use of immunosuppressive medications (including mycophenolate mofetil, azathioprine, methotrexate, leflunomide, cyclosporine, cyclophosphamide, and rituximab). Due to both the immune dys- regulation inherent to SLE and immunosuppressive therapy, pa- tients with SLE are at increased risk of developing infections. In fact, infection is one of the most common reasons for hospitaliza- tion in SLE patients and is a leading cause of death especially within the first 5 years of diagnosis. 2 Cytomegalovirus (CMV) is a ubiquitous herpes virus, which infects up to 60% to 90% of people, usually within the first 2 de- cades of life. 3 After primary CMV infection, the virus has a life- long latency in the host. 4 Robust host cell-mediated immunity is required to prevent CMV reactivation. Cytomegalovirus infection can be detected by several methods, including viral culture, rapid viral assay, histopathology, p65 antigen detection, and quantitative assessment of CMV nucleic acid amplification. 5 Given its sensi- tivity and rapid turnaround time, the latter method is widely used. 5 In 2010, the World Health Organization recommended interna- tional standardization of methods to detect CMV by nucleic acid amplification. 5 Cytomegalovirus reactivation is of particular concern in solid organ transplant (SOT) recipients whose cell-mediated immunity is impaired by posttransplant immunosuppression. 6 Without CMV prophylaxis, up to 80% of SOT recipients experience CMV infec- tion, with individual risk dependent upon age, transplanted organ, immunosuppression, and donor and recipient CMV serostatus. 6 Consequently, SOT transplant recommendations include routine as- sessment of donor and recipient serostatus and surveillance for CMV reactivation posttransplant. 6 Similar chronic immunosuppression is used in SLE patients and SOT recipients, particularly after initial high-intensity immu- nosuppression give in immediately posttransplant. Cytomegalovirus reactivation is anecdotally infrequent in SLE patients with multiple case reports or series describing SLE patientswith CMV, including colitis and alveolitis. 7–9 It is standard of care to monitor CMV seropositivity and viremia in SOT, and to treat viremia when present due to reactivation of the virus. 10–12 Few studies have examined the frequency of CMV seropositivity or viremia in SLE patients, and there are no specific recommendations for monitoring CMV status in SLE pa- tients. 13 The aim of this study was to determine the frequency of CMV seropositivity and viremia in immunosuppressed SLE patients. METHODS This is an approved study by the Ohio State University Insti- tutional Review Board. Participants were recruited from the Lupus-Vasculitis-Glomerulonephritis clinic at Ohio State Univer- sity Wexner Medical Center from February 2015 to May 2016. Se- quential eligible patients seen during this period were invited participate. The inclusion criteria included age older than 18 years, diagnosis of SLE according to 1997 ACR criteria, treatment with immunosuppressive medication, and/or prednisone greater than 5 mg daily (any disease-modifying antirheumatic drug or biologic medication except hydroxychloroquine). Hydroxychloroquine is not considered an immunosuppressant agent. 13 The Systemic Lupus Erythematous Disease Activity Index (SLEDAI) score was mea- sured by treating clinician. 1 At enrollment, demographic informa- tion, recent laboratory data, SLE history, and current medications were obtained. The serum CMV immunoglobulin G (IgG) anti- body titer was measured using Immulite 2000 XPi. If the CMV IgG antibody titer was positive, a CMV polymerase chain reaction viral load was measured by NucliSens easyMAG and amplified on ABI 7500 using Abbott CMVASR reagents to determine ac- tivity. The viral load was considered to be positive if more than 119 copies were present. 5 If the CMV IgG was negative, no fur- ther testing was performed. If the CMV viral load was positive, participants were referred to an infectious disease consultant for further evaluation and treatment (Figure). RESULTS Table summarizes the demographic characteristics of the 75 SLE patients included in these analyses. The mean SLEDAI score was 2.2 ± 2.7 with the majority having SLEDAI less than 4. Of the 75 subjects enrolled, 50 (67%) were CMV IgG positive. The CMV viral load was undetectable for all participants, as shown in Table. DISCUSSION In this cross-sectional study of SLE patients, 67% were CMV IgG positive, which is similar to the rate observed in the general population. 14,15 None of the patients had a detectable CMV viral load, despite use of immunosuppressive agents (78.6% were taking mycophenolate mofetil, azathioprine, beli- mumab, or cyclophosphamide; see Table). These therapies impair immune system functioning by various mechanisms, including re- ducing lymphocyte proliferation, T-cell function, and cytokine production, and thus place these patients at increased risk for in- fections including reactivation of CMV. 14 However, data from this From the Department of Internal Medicine, and Division of Rheumatology and Immunology, Ohio State University Wexner Medical Center, Columbus, OH. This is funded by the Columbus Medical Research Foundation. Correspondence: Alexa Meara, MD, MS, The Division of Rheumatology and Immunology, The Ohio State University Wexner Medical Center, 480 Medical Center Dr, Davis Bldg, Suite 2056 Columbus, OH 4310. E‐mail: Alexa.meara@osumc.edu. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-1608 DOI: 10.1097/RHU.0000000000001390 CONCISE REPORT JCR: Journal of Clinical Rheumatology • Volume 26, Number 4, June 2020 www.jclinrheum.com 157 Copyright © 2020 Wolters Kluwer Health, Inc. 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