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Mortality risk factors associated with familial Mediterranean fever among a cohort of 1.25 million adolescents
  1. Gilad Twig1,2,3,
  2. Avi Livneh1,4,5,
  3. Asaf Vivante2,3,5,6,
  4. Arnon Afek5,7,
  5. Ari Shamiss5,7,
  6. Estela Derazne3,5,
  7. Dorit Tzur3,
  8. Ilan Ben-Zvi1,2,4,5,
  9. Amir Tirosh2,8,
  10. Micha Barchana9,
  11. Tamy Shohat9,
  12. Eliezer Golan5,10,
  13. Howard Amital1,5
  1. 1Department of Medicine, Chaim Sheba Medical Center, Tel Hashomer, Israel
  2. 2The Pinchas Borenstein Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Tel Hashomer, Israel
  3. 3The Israel Defense Forces Medical Corps, Israel
  4. 4Heller Institute of Medical Research, Chaim Sheba Medical Center, Tel Hashomer, Israel
  5. 5Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  6. 6Department of Pediatrics, Chaim Sheba Medical Center, Tel Hashomer, Israel
  7. 7Chaim Sheba Medical Center Management, Chaim Sheba Medical Center, Tel Hashomer, Israel
  8. 8Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  9. 9The National Center for Disease Control, Ministry of Health, Jerusalem, Israel
  10. 10The Israel Renal Registry and Department of Nephrology and Hypertension, Meir Medical Center, Kfar Saba, Israel
  1. Correspondence to Dr Gilad Twig, Department of Medicine ‘B’, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel; Gilad.Twig{at}


Objective There are limited data on long-term comorbidities and mortality among patients with familial Mediterranean fever (FMF). Our objective was to evaluate comorbidities and death rates among individuals with FMF.

Methods We studied a nationwide, population-based, retrospective cohort of 1225 individuals with FMF (59% men) in a database of 1 244 350 adolescents (16–20 years of age) medically evaluated for military service between 1973 and 1997. This cohort was linked with the national mortality, cancer and end-stage renal disease (ESRD) registries in Israel. Study outcomes were all-cause mortality, occurrence of ESRD and malignancy by the age of 50 years.

Results During 30 years of follow-up, death rates were 8.73/104 versus 4.32/104 person-years in the FMF and control groups, respectively (p=0.002). In a multivariable analysis adjusted for age, birth year, socio-economic status, education, ethnicity and body mass index, FMF was associated with increased mortality in men (HR=1.705 (95% CI 1.059 to 2.745), p=0.028) and women (HR=2.48 (1.032 to 5.992), p=0.042). Renal amyloidosis accounted for 35% and 60% of deaths in men and women, respectively. FMF was not associated with an increased incidence of cancer.

Conclusions FMF is associated with increased all-cause mortality that is likely attributed to reduced colchicine compliance or responsiveness. Individuals with FMF do not have an increased incidence of cancer. These results support the awareness among medical community to decrease the higher than average mortality rate among participants with FMF.

  • Amyloidosis
  • Familial Mediterranean Fever
  • Epidemiology

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