The factors considered as trigger for the attacks in patients with familial Mediterranean fever

Rheumatol Int. 2013 Apr;33(4):893-7. doi: 10.1007/s00296-012-2453-x. Epub 2012 Jul 20.


Although the inflammatory cascade of familial Mediterranean fever (FMF) is partially understood, triggering factors of those attacks has not been studied well. It is supposed that physical stresses such as cold exposure, tiredness and emotional stresses could provoke attacks. This study is aimed to survey the factors regarded as triggering the attacks in patients with FMF and their relationship with MEFV gene mutations. Clinical findings and genetic mutations (consist of M694V, M694I, M680I, V726A, E148Q) of patients were recorded. Patients were questioned about cold exposure, emotional stress, tiredness, long-lasting standing, long-duration travel, starvation, high intake of food, trauma, and infection as triggering factors for the attacks with both serositis and musculoskeletal pain. The study is comprised of 275 FMF patients (male/female: 177/98). The most common triggering factors for the attacks with serositis were cold exposure (59.3 %), emotional stress (49.8 %), tiredness (40.0 %) and menstruation (33.7 % in females). Long-lasting standing (78.8 %), long-duration travel (64.1 %) and tiredness (47.8 %) were the triggering factors for the attacks with musculoskeletal symptoms. The relationships between MEFV mutations and triggering factors were found as M694V allele with starvation, E148Q allele with high intake of food and V726A allele with long-duration travel. The attacks with serositis seem to be triggered by those factors to which whole body exposed, whereas the attacks with musculoskeletal complaints seem to be triggered by those factors to which regional or local part of body exposed. Since the number of alleles was small, a clear conclusion for a relationship between a particular gene variant and a specific trigger was not made.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Cold Temperature / adverse effects*
  • Cytoskeletal Proteins / genetics*
  • Familial Mediterranean Fever / etiology*
  • Familial Mediterranean Fever / genetics
  • Fatigue / complications*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Phenotype
  • Pyrin
  • Risk Factors
  • Stress, Psychological / complications*
  • Travel


  • Cytoskeletal Proteins
  • MEFV protein, human
  • Pyrin