Original article
Risk factors for development of systemic lupus erythematosus: Allergies, infections, and family history

https://doi.org/10.1016/S0895-4356(02)00429-8Get rights and content

Abstract

We examined risk factors for systemic lupus erythematosus (SLE) in 265 recently diagnosed patients in North Carolina and South Carolina and 355 control subjects identified through driver's license records and frequency matched to patients by age, sex, and state. Analyses were limited to exposures before diagnosis (cases) or reference year (control subjects). SLE patients were more likely than control subjects to report a history of allergy to medications (odds ratio [OR] 3.1, 95% confidence interval [CI], 2.1–4.5), particularly to antibiotics. SLE risk increased with history of shingles (OR 2.5, 95% CI 1.1–5.9) and with frequent (more than once per year) cold sores in the 3 years before diagnosis (OR 2.8, 95% CI 1.4–5.4). There was little association with history of mononucleosis, a marker of late infection with Epstein-Barr virus, implanted medical devices, or hepatitis B vaccination. History of lupus in parents or siblings was associated with an increased risk (OR 3.3, 95% CI 1.2–8.6). Further research is needed to clarify whether medication allergies and specific infectious agents are involved in the etiology of SLE. Published by Elsevier Science Inc.

Introduction

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by the production of non-organ–specific autoantibodies including antinuclear, anti-double stranded DNA and antiphospholipid antibodies. Significant health consequences include renal failure, vasculitis, arthritis, seizures and other neurologic complications, and increased risk of infection [1]. Most (85%) SLE patients are female [2], and in the United States the incidence and prevalence of SLE are at least three times higher in African Americans compared with whites [3]. Autoimmune diseases, including SLE, are among the leading causes of death in women under age 65 years [4].

The role of genetics in SLE is suggested by patterns of disease susceptibility in murine models of SLE [5], familial association and linkage studies [6], and by concordance of disease in twins [7]. Little is known, however, about environmental (or nongenetic) risk factors. Few epidemiologic studies of SLE have been conducted, and size and design limitations (e.g., setting in tertiary care centers, control selection) have been noted in many of them [3]. Previous studies have reported associations with allergy to sulfa drugs and other medications 8, 9, history of herpes zoster (shingles) [8], and Epstein-Barr virus infection [10]. Case reports of SLE diagnosis subsequent to hepatitis B vaccination have been reported [11], but this association has not been assessed in an epidemiologic study.

We examined family history and medical-related risk factors, focusing on allergies and selected infectious agents, in a large, population-based, case-controlled study of recently diagnosed SLE. We also explored two issues that could affect the racial disparity seen in the incidence of SLE: (1) whether specific factors were associated with an increased risk of SLE among African Americans but not among whites and (2) whether specific risk factors were more prevalent in the African American population.

Section snippets

Materials and Methods

The Carolina Lupus Study is based in 60 contiguous counties in eastern North Carolina and eastern South Carolina. Cases were identified through community-based rheumatologists, university-based rheumatology practices (Duke University Medical Center, East Carolina University School of Medicine, University of North Carolina School of Medicine, and the Medical University of South Carolina), two public health clinics, and patient support groups. Thirty of the 40 community-based rheumatologists in

Results

Ninety percent of the 265 SLE cases in the Carolina Lupus Study were female, and 60% were African American (Table 1). The mean age at diagnosis was 39 years but was younger among African Americans (37 years) compared with whites (43 years) (P value for t test of racial difference in diagnosis age < 0.001). Because of the age- and sex-matching procedure we used, these characteristics are similar in the control subjects. We did not match by race, and the racial distribution of control subjects is

Discussion

A history of medication allergy was associated with an increased risk of developing SLE in our study. This association was strongest for sulfa medications but was seen to a lesser extent with penicillin and codeine. These results support observations from two previous case-controlled studies: Strom et al. [8] reported an association with medication allergy (OR 1.8, 95% CI 1.1–3.0), and Petri and Allbritton [9] reported an association with sulfonamide (OR 2.4, 95% CI 1.2–4.7) and

Acknowledgments

This study was supported by the Division of Intramural Research of the National Institute of Environmental Health Sciences. We thank the physicians who participated in the Carolina Lupus Study Group in North Carolina (H. Vann Austin, Faye Banks, Franc Barada, George Brothers, Walter Chmelewski, Duncan Fagundus, David Fraser, Stephen G. Gelfand, Helen Harmon, Robert A. Harrell, III, John Harshbarger, G. Wallace Kernodle, Jr, Elliot Kopp, Kara Martin, John L. McCain, Cathleen Melton, Gwenesta

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