Familial Mediterranean Fever in Armenian women: Investigation of endocrine – related factors’ role in frequency and duration of paroxysms

Abstract

Familial Mediterranean fever (FMF) is a genetic disease predominantly affecting ethnic groups such as Armenians, Jews, Arabs and Turks. Signs of the disease are recurrent self-limited attacks of fever and polyserositis, considerably affecting quality of life of the diseased people. A life-threatening complication of the disease is amyloidosis. In affected regions, the prevalence of the disease and carrier rates among the population is high. Although the genetic etiology of the disease is well established, various investigations indicate the influence of some non-genetic factors on the disease pathways. Further research on the influence of these factors could lead to improved management of FMF and reduction of frequency and severity of attacks. The proposed study aims to investigate the impact of endocrine changes (pregnancy, lactation periods, menstruation and oral contraceptive use) on the frequency and duration of FMF attacks in women. The design of the proposed study is retrospective cohort. The study population includes women with genetically verified diagnosis of FMF in the age range 20-40 years. Participants who never were pregnant will constitute the first group of comparison (unexposed); those who have had pregnancy within the last three years with duration of at least 4 months or are at fourth month of pregnancy and over during the study will comprise the second group of comparison (exposed). The calculated sample size is 214 women. The study team will conduct telephone interviews with participants. The study questionnaire includes 87 close-ended questions with the following sections: socio-demographic information, disease history, FMF treatment, reproductive health, disease course in the last six months and disease course during the pregnancy period in the last 3 years. The student investigator conducted a pilot study to pretest and improve the study protocol and the instrument. The main outcome variables of interest are FMF attacks’ frequency and duration; adherence to treatment during pregnancy. The main explanatory variables of interest include: period of pregnancy, period of lactation, and oral contraceptive use. Data collection will be followed by double entry and data cleaning. The study will use Chi-square test to compare categorical variables and t-test to compare continuous variables. Binary logistic regression and multiple logistic regressions will be utilized to control for confounders. The estimated budget of the study is 2,014,070 AMD. The personnel of the study include project coordinator, data collection and entry staff. The anticipated duration is three months. The Institutional Review Board (IRB)/ Committee on Human Research of the American University of Armenia approved the study protocols. During the pilot study one of the participants reported complete symptomatic remission of regular monthly attacks during separate six-month and two three-month periods of oral contraceptive use prior to diagnosis of FMF. Along with a very limited number of similar reported cases in the literature, this case supports the hypothesis of the proposed study on the relation between female hormonal changes and the course and severity of FMF and is reported as part of this proposal.