Anthrax Vaccine and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus in the U.S. Military: A Case-Control Study.

U.S. military personnel assigned to areas deemed to be at high risk for anthrax attack receive Anthrax Vaccine Adsorbed (AVA). Few cases of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have been reported in persons who received AVA. Using a matched case-control study design, we assessed the relationship of RA and SLE with AVA vaccination using the Defense Medical Surveillance System. We identified potential cases using International Classification of Diseases, 9th Revision, Clinical Modification codes and confirmed cases with medical record review and rheumatologist adjudication. Using conditional logistic regression, we estimated odds ratios (OR) for AVA exposure during time intervals ranging from 90 to 1,095 days before disease onset. Among 77 RA cases, 13 (17%) had ever received AVA. RA cases were no more likely than controls to have received AVA when looking back 1,095 days (OR: 1.03; 95% confidence interval [CI]: 0.48-2.19) but had greater odds of exposure in the prior 90 days (OR: 3.93; 95% CI: 1.08-14.27). Among the 39 SLE cases, 5 (13%) had ever received AVA; no significant difference in receipt of AVA was found when compared with controls (OR: 0.91; 95% CI: 0.26-3.25). AVA was associated with recent onset RA, but did not increase the risk of developing RA in the long term.

Elevated subclinical double-stranded DNA antibodies and future proliferative lupus nephritis.

BACKGROUND AND OBJECTIVES: Elevated anti-double-stranded DNA (dsDNA) antibody and C-reactive protein are associated with proliferative lupus nephritis (PLN). Progression of quantitative anti-dsDNA antibody in patients with PLN has not been compared with that in patients with systemic lupus erythematosus (SLE) without LN before diagnosis. The temporal relationship between anti-dsDNA antibody and C-reactive protein elevation has also not been evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This case-control Department of Defense Serum Repository (established in 1985) study compared longitudinal prediagnostic quantitative anti-dsDNA antibody and C-reactive protein levels in 23 patients with biopsy-proven PLN (Walter Reed Army Medical Center, 1993-2009) with levels in 21 controls with SLE but without LN matched for patient age, sex, race, and age of serum sample. The oldest (median, 2601 days; 25%, 1245 days, 75%, 3075 days), the second to last (368; 212, 635 days), and the last (180; 135, 477 days) serum sample before diagnosis were analyzed. RESULTS: More patients with PLN had an elevated anti-dsDNA antibody level than did the matched controls at any point (78% versus 5%; P<0.001), <1 year (82% versus 8%; P<0.001), 1-4 years (53% versus 0%; P<0.001), and >4 years (33% versus 0%; P=0.04) before diagnosis. A rate of increase >1 IU/ml per year (70% versus 0%; P<0.001) was most specific for PLN. The anti-dsDNA antibody levels increased before C-reactive protein did in most patients with an antecedent elevation (92% versus 8%; P<0.001). CONCLUSIONS: Elevated anti-dsDNA antibody usually precedes both clinical and subclinical evidence of proliferative LN, which suggests direct pathogenicity. Absolute anti-dsDNA antibody level and rate of increase could better establish risk of future PLN in patients with SLE.