Familial mediterranean Fever in the world.

Introduction Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever accompanied by peritonitis, pleuritis, arthritis, or erysipelas-like erythema (1,2). A typical FMF attack lasts approximately 3 days. The frequency of episodes varies from once every week to several times a year. One of the devastating complications of FMF is the development of serum amyloid A (SAA) amyloidosis, which mainly affects the kidneys but may involve other organs. Since 1972, colchicine has been the treatment of choice for FMF (3). It controls the acute attacks and prevents the development of amyloidosis. The disease is prevalent among populations surrounding the Mediterranean Sea. However, in recent years, more and more cases have been reported in countries not related or close to this area, such as the US and Japan. This observation raised the question as to the real prevalence of FMF in countries other than those around the Mediterranean basin and to its clinical characteristics in these countries. Furthermore, it poses a challenge to find out the ethnic origin of these patients and to study whether their disease behaves similarly to that in the countries commonly associated with FMF. FMF may display a different clinical picture among various populations, and these differences reflect the change in the repertoire of mutations among the specific populations. In this review, we will try to look for and explain the origin of FMF in countries far from the Mediterranean and Middle East regions. We will also compare the nature of the disease in these countries and find out whether they differ from the FMF manifestations, treatment, and prognosis in patients surrounding the Mediterranean Sea. Prevalence of FMF in the world FMF is almost always restricted to Turks, Armenians, Arabs, and non-Ashkenazi Jews. It is quite a rare disease in the rest of the world, although patients with FMF have been reported in European countries such as France, Germany, Italy, and Spain, as well as in the US and Australia (2,4). The exact frequency of FMF among the various populations is not always available because formal epidemiologic studies have not been done. Nevertheless, a rough estimate regarding the prevalence of the disease can be obtained by gathering details from different studies and sources (Figure 1). Turkey is probably the country with the highest number of FMF patients in the world. Since the prevalence of FMF is approximately 1:400 to 1:1,000 (highest in the areas of Anatolia) and the population is approximately 70 million, it is estimated that Turkey has more than 100,000 patients with FMF (4–6). In Israel, the prevalence is slightly more than 1:1,000 (depending on the ethnic group), and since the population is approximately 7 million, it is estimated that there are approximately 10,000 patients (7). Armenia is probably the next country with widespread FMF. It is estimated that the prevalence of FMF is approximately 1:500 and with a population of 3 million, the total number of patients is approximately 6,000 (8). Other countries in the Middle East such as Jordan, Syria, and Lebanon have many FMF patients, but their exact number is not known (9,10). In addition to the above countries, FMF is found in significant numbers in North African countries, Greece, Crete, France, Germany, Italy, and the US (11–14). In recent years, approximately 100 cases have been reported in Japan (15, 16, and Tsuchiya-Suzuki A, et al: unpublished observations). On the other hand, there are countries where FMF has not been found or reported. These include sub-Saharan African countries, Ethiopia, Yemen, and Scandinavian states, as well as South Asian and Far Eastern countries such as India and Thailand. The identification of the MEFV gene associated with FMF and the prevalence of its mutations in the different ethnic groups allowed some hypotheses on the phylogeny of the disease (12).