FMF: Familial Mediterranean fever

What is it?

FMF is a periodic fever syndrome characterised by recurrent bouts of fever with accompanying pain. It is typically inherited and the first symptoms of the flare usually occur before the age of 30.[1–5]

How common is it?

FMF is most prevalent in the eastern Mediterranean region and about 2.5 per 100,000 people are affected in Western countries.[6] From a worldwide perspective, it is a rare disease.

What are the symptoms?

FMF flares lasting from a few hours to 3-4 days can involve the following symptoms:[5,7,8]

  • Fever
  • Abdominal and/or chest pain
  • Inflammation of a joint e.g., knee, ankle, wrist
  • Painful, severe skin redness in nearly 50% of patients, often on the feet and/or lower legs
  • Spleen enlargement
  • Swelling of the ends of fingers and/or toes ('digital clubbing')

However, fever may be the only symptom particularly during childhood.[8]

In some cases it is unknown why FMF flares start, but the following have been identified as common triggers:[5]

  • Stress
  • Cold
  • Infections
  • Some medications
  • The menstrual cycle

Possible symptoms of FMF (modified according to [3,4,7,8])

What typically happens over the course of the illness?

If FMF is left untreated, approximately 6-8 out of 10 patients will develop amyloidosis.[4] Amyloidosis is a condition in which a protein called amyloid builds up in the kidneys leading to kidney failure. Improved diagnosis and treatment means that kidney damage caused by amyloidosis occurs less frequently than in the past.

How is it caused?

In FMF, activation of the innate immune system and the inflammatory response occurs due to changes in the Mediterranean fever (MEFV) gene. To date, more than 300 different changes to this gene have been identified as possible causes of FMF.[9]

Status: 2016-01-04

[1] Samuels J, Ozen S. Curr Opin Rheumatol. 2006;18:108–17.
[2] Lachmann HJ, Hawkins PN. Arthritis Res Ther. 2009;11:212.
[3] Savic S, Dickie LJ, Battellino M et al. Curr Opin Rheumatol. 2012;24:103–12.
[4] Gattorno M, Federici S, Pelagatti MA et al. J Clin Immunol. 2008;28(Suppl 1):73–83.
[5] Manna R: Familial Mediterranean fever. (Last accessed on 13.10.2013).
[6] Fujikura K. Mol Genet Genomic Med. 2015;3:272–282.
[7] Ciccarelli F, De Martinis M, Ginaldi L. Curr Med Chem. 2014;21:261–269.
[8] Shohat M, Halpern GJ. Genet Med. 2011;13:487-498.
[9] MEFV sequence variants. Available from: (accessed November 2015).

If you have a child with an autoinflammatory disease…

…you will know there are added pressures and considerations for your family life. Thankfully, you’re not alone.

Life with Periodic Fevers

June 2016 - GLDEIM/ACZ885/0075