Consult the medical resource doctors trust

UpToDate is one of the most respected medical information resources in the world, used by over 360,000 doctors and thousands of patients to find answers to medical questions.

  • Content written by a faculty of over 4,000 physicians from leading medical institutions
  • Unbiased: free of advertising or pharmaceutical funding
  • Evidence-based treatment recommendations
  • Continuously updated to incorporate new medical findings

Clinical manifestations and diagnosis of familial Mediterranean fever

INTRODUCTION

Familial Mediterranean fever (FMF) is a disorder characterized by sporadic, paroxysmal attacks of fever and serosal inflammation. It is inherited as an autosomal recessive trait. The cloning of the FMF gene promises to enhance our understanding of the sequence of events leading to the diverse clinical manifestations of this disorder. (See "Pathophysiology of familial Mediterranean fever".)

FMF has been described primarily in several ethnic groups originating in the Mediterranean littoral — Sephardic Jews, Armenians, Turks, North Africans, Arabs, and less commonly Greeks and Italians. However, the disease is not restricted to these groups. In the United States, for example, FMF is frequently encountered in Ashkenazi Jews. Because cases of FMF have been diagnosed in a wide variety of ethnic groups, ancestry should not be used to rule out the diagnosis if other clinical characteristics are present.

The clinical manifestations and diagnosis of FMF will be reviewed here. The management of this disorder is discussed separately. (See "Management of familial Mediterranean fever".)

CLINICAL MANIFESTATIONS

Most patients with FMF experience their first attack in early childhood; in 65 percent of cases, the initial attack occurs before the age of 10, and in 90 percent before the age of 20 [1]. The typical manifestations of the disease are recurrent attacks of severe pain (due to serositis at one or more sites) and fever, lasting one to three days, and then resolving spontaneously. In between attacks, patients feel entirely well. Pain and fever are usually abrupt and reach their peak soon after onset. Many patients have a stereotypic prodrome before their attacks [2].

The frequency of attacks is highly variable, even in a given patient, and it is unusual for a patient to describe a consistent triggering event. Vigorous exercise is regarded as an attack trigger by a few patients. Others may describe exposure to cold, emotional stress, or menstruation as preludes to an attack, but such reports are rare and hard to document with certainty. Attacks tend to abate during the second half of pregnancy, probably because of hormonal changes.
To continue reading this article you need to subscribe.

Read the rest of this article and others like it

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use (click here) ©2010 UpToDate, Inc.
References Top
  1. Sohar, E, Gafni, J, Pras, M, Heller, H. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 1967; 43:227.
  2. Lidar, M, Yaqubov, M, Zaks, N, et al. The prodrome: a prominent yet overlooked pre-attack manifestation of familial Mediterranean fever. J Rheumatol 2006; 33:1089.
  3. Ben-Chetrit, E, Levy, M. Familial Mediterranean Fever. Lancet 1998; 351:659.
  4. Kees, S, Langevitz, P, Zemer, D, et al. Attacks of pericarditis as a manifestation of familial Mediterranean fever (FMF). QJM 1997; 90:643.
  5. Ertekin, V, Selimoglu, MA, Alp, H, Yilmaz, N. Familial Mediterranean fever protracted febrile myalgia in children: report of two cases. Rheumatol Int 2005; 25:398.
  6. Ozen, S, Ben-Chetrit, E, Bakkaloglu, A, et al. Polyarteritis nodosa in patients with Familial Mediterranean Fever (FMF): a concomitant disease or a feature of FMF? Semin Arthritis Rheum 2001; 30:281.
  7. van der Hilst, JC, Simon, A, Drenth, JP. Hereditary periodic fever and reactive amyloidosis. Clin Exp Med 2005; 5:87.
  8. Pras, M. Amyloidosis of familial Mediterranean fever and the MEFV gene. Amyloid 2000; 7:289.
  9. Tunca, M, Akar, S, Onen, F, et al. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore) 2005; 84:1.
  10. Heller, H, Sohar, E, Gafni, J, Heller, J. Amyloidosis in familial Mediterranean fever. An independent genetically determined character. Arch Intern Med 1961; 107:539.
  11. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The International FMF Consortium. Cell 1997; 90:797.
  12. Medlej-Hashim, M, Delague, V, Chouery, E, Salem, N. Amyloidosis in familial Mediterranean fever patients: correlation with MEFV genotype and SAA1 and MICA polymorphisms effects. BMC Med Genet 2004; 5:4.
  13. Sungur, C, Sungur, A, Ruacan, S, et al. Diagnostic value of bone marrow biopsy in patients with renal disease secondary to familial Mediterranean fever. Kidney Int 1993; 44:834.
  14. Rozenbaum, M, Naschitz, JE, Yudashkin, M, et al. Cardiovascular autonomic dysfunction in familial Mediterranean fever. J Rheumatol 2002; 29:987.
  15. Babior, BM, Matzner, Y. The familial Mediterranean fever gene--cloned at last. N Engl J Med 1997; 337:1548.
  16. Eisenberg, S, Aksentijevich, I, Deng, Z, et al. Diagnosis of familial Mediterranean fever by a molecular genetics method. Ann Intern Med 1998; 129:539.
  17. Samuels, J, Aksentijevich, I, Torosyan, Y, et al. Familial Mediterranean fever at the millennium. Clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes of Health. Medicine (Baltimore) 1998; 77:268.
  18. Padeh, S, Shinar, Y, Pras, E, et al. Clinical and diagnostic value of genetic testing in 216 Israeli children with familial Mediterranean fever. J Rheumatol 2003; 30:185.
  19. Livneh, A, Langevitz, P, Zemer, D, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 1997; 40:1879.
  20. Drenth, JP, van der Meer, JW. Hereditary periodic fever. N Engl J Med 2001; 345:1748.
white circle LOG IN
white circle DEMO