An Evaluation of the Association of Leukopenia and Severe Infection in Patients With Systemic Lupus Erythematosus Kamoltip Lertchaisataporn, MD, Nuntana Kasitanon, MD, Suparaporn Wangkaew, MD, Saowanee Pantana, BSc, Waraporn Sukitawut, BSc, and Worawit Louthrenoo, MD Background: Leukopenia is a common finding in systemic lupus erythe- matosus (SLE) and may contribute to severe infections. Objectives: The objectives of this study were to determine the prevalence of leukopenia in SLE patients and examine the association between these conditions and severe infections noting the risk factor of severe infections. Methods: This study was a prospective inception lupus cohort of newly diagnosed SLE patients seen between May 2007 and June 2011. Only cases that had been observed for a minimum of 1 year or died during the study were included. Results: There were 89 SLE patients (92% females), with their mean (SD) age and disease duration at the study entry of 31.7 (12.2) years and 2.4 (2.9) months. Leukopenia was found at the diagnosis in 51.6% of the cases. The cumulative prevalence of leukopenia, lymphopenia, and neutropenia was observed in 57.3%, 96.6%, and 60.7%, respectively. Persistent lymphopenia, noted continuously for more than or equal to 75% of the observation period, was found in 41.6%, but there was no persistent neutropenia. The incidence rate of severe infection was 12.4 per 100 patient-years. There was no difference of severe infectionYfree sur- vival rate between patients who ever and never had leukopenia. In the multivariate analysis, using cyclophosphamide was the independent pre- dictor for severe infection in SLE (hazard ratio, 2.73; 95% confidence interval, 1.10Y6.77). Conclusions: Leukopenia was common in SLE but usually not persis- tent. In this study, the presence of leukopenia at any time was not the risk factor for severe infection in SLE. Cyclophosphamide was the im- portant predictor for severe infection in SLE. Key Words: leukopenia, neutropenia, lymphopenia, severe infection, SLE (J Clin Rheumatol 2013;19: 115Y120) S ystemic lupus erythematosus (SLE) is a chronic inflamma- tory autoimmune disease with multiple organ involvement. Hematologic abnormalities, including anemia, thrombocytope- nia, leukopenia, and lymphopenia, are commonly found in SLE patients. 1,2 Leukopenia is common in SLE and is included in both the American College of Rheumatology (ACR) 3 and the Sys- temic Lupus International Collaborating Clinics (SLICC) clas- sification criteria of SLE. 4 Leukopenia in SLE may result from SLE disease activity or bone marrow suppression from immu- nosuppressant(s), comedications, or other medical conditions. As white blood cells (WBCs) have a major role in the immune system in preventing infection, leukopenia may contribute to se- vere infections in SLE. Infection is the most common cause of morbidity and mor- tality in SLE. 2,5 Many previous studies demonstrated that infec- tion is the common risk factor for hospitalizations and death. 2,5,6 The risk factors for infection that had been reported were disease activity, 7,8 immunosuppressive agents, 9Y11 corticosteroids, 2,12 and leukopenia. 13Y15 The association between leukopenia and severe infection remains controversial in SLE. Some studies showed lymphopenia at presentation 13 and neutropenia 14,15 associated with infection in SLE, but other studies do not support the role of leukopenia as a predisposition to severe infection in SLE. 16Y18 The association between leukopenia and infection is a time- dependent relationship. Thus, the number of WBCs at diagnosis or at only 1 time point may not predict an infection in subsequent times. Therefore, the purpose of this study was to examine the association between 3 WBC conditions (leukopenia, lymphopenia, and neutropenia) over a period of time and severe infection in SLE patients from an inception cohort study. PATIENTS AND METHODS Patients The cohort study included all patients with SLE who con- sented for the inception Chiang Mai University Lupus Cohort, a prospective cohort, which included newly diagnosed SLE pa- tients who followed up at the Division of Rheumatology, Chiang Mai University, from May 2007 to June 2011. All patients in an analysis satisfied at least 4 of the 1997 ACR revised criteria for the classification of SLE 3 and had been observed for at least 1 year except patients who died before 1 year of follow-up. The patients who had incomplete data were excluded. Basic demographic characteristics, presenting and cumulative clinical manifestations, Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (M-SLEDAI-2K) scores, 19 the SLICC/ ACR Damage Index 20 for SLE, and immunologic markers (antiY ds-DNA and antiYcardiolipin antibody) were recorded since co- hort entry. Patients were seen at regular intervals of 3 months, or more frequently if medically indicated. At each patient visit, a complete history, physical examination, routine laboratory test- ing, and treatment were performed in a systematic fashion. Also, the admission data, details of severe infection, and causes of death were obtained. This study was approved by our institutional research ethics board, and informed consent was obtained before the study ac- cording to the Declaration of Helsinki. Definition Leukopenia, lymphopenia, and neutropenia were consid- ered when the WBC count was less than 4000/mL, lympho- cytes were less than 1500/mL, and neutrophils were less than 2500/mL, respectively. Severe leukopenia, lymphopenia, and neutropenia were defined when the WBC count was less than ORIGINAL ARTICLE JCR: Journal of Clinical Rheumatology & Volume 19, Number 3, April 2013 www.jclinrheum.com 115 From the Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. The authors declare no conflict of interest. Correspondence: Nuntana Kasitanon, MD, Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. E-mail: nkasitan@med.cmu.ac.th. Copyright * 2013 by Lippincott Williams & Wilkins ISSN: 1076-1608/13/1903Y0115 DOI: 10.1097/RHU.0b013e318289bb9b Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.