Triggers for Attacks in Familial Mediterranean Fever: Application of the Case-Crossover Design

The etiology of recurrent attacks of serositis in familial Mediterranean fever (FMF) is not completely understood. Uncontrolled clinical case series have reported that factors associated with emotional, physiological, or physical stress precede and might trigger the attacks. This case-crossover study, conducted between July 2007 and May 2008, aimed to estimate the role of precipitating factors in attacks in a sample of Armenian FMF patients in Yerevan, Armenia, where 104 patients contributed 55 case and 189 control time periods. The authors used conditional logistic regression to compare frequency of exposure to stressful events, strenuous physical activity, menstrual periods, and high-fat food consumption prior to FMF attacks and on attack-free random days. Multiple stressful life events predicted FMF attacks 2 days following the event. After adjustment for treatment, an additional stressful event was associated with an estimated 70% increase in the odds of having an FMF attack on the second day (95% confidence interval: 1.04, 2.79). High levels of perceived stress were also associated with FMF attacks. Physical exertion and high-fat diet did not increase the likelihood of FMF attacks. The possibility of prevention of attacks in FMF needs to be tested through stress-reduction interventions.