Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease with autosomal recessive inheritance [
1]. The main clinical findings of FMF are recurrent and self-limited fever attacks lasting between 12 to 72 h. Severe abdominal, articular and/or chest pain, due to inflammation of the peritoneum, synovia or pleura usually accompany fever [
2]. The most important factor determining the prognosis of FMF is the development of amyloidosis, which could lead to renal failure [
3]. FMF is the most common hereditary recurrent fever syndrome [
1]. Approximately 150,000 people worldwide are estimated to have this condition. FMF has been report all around the world, but its prevalence is very high among certain ethnic groups such as Jewish, Turkish, Armenian and Arabs, reaching figures as high as 1/500 individuals [
4].FMF result from a mutation of the Mediterranean fever (MEFV) gene, located on chromosome 16 [
5] and is inherited in an autosomal recessive manner. Nearly 30% of documented FMF patients carry only one mutation, and up to 20% of patients do not have detectable mutations [
6,
7]. More than 50 FMF-associated mutations in MEFV have been reported [
8]. The most frequent are: M694V, V726A, M694I, and M680I located at exon 10 and E148Q located at exon 2 [
1]. The MEFV gene encodes the protein pyrin, that has an important role in the inflammatory response by regulating caspase-1 activation and processing mature IL-1β [
9]. The diagnosis of FMF relies mainly on clinical findings, and molecular analysis of the
MEFV gene provides genetic confirmation [
10]. There are different sets criteria for FMF diagnosis. The first set criteria was created for adults by a group of experts [
11]. In 2009 Yalcikaya et al. validated a set criteria for paediatric patients [
12]. Recently, the Eurofever group proposed a new set criteria for autoinflammatory recurrent fevers (these sets criteria are compared in Table
1) [
13] . Colchicine is the standard treatment for FMF. However, it could be ineffective or associated with side effects in 5 to 10% of patients [
13]. Interleukin-1(IL-1) inhibition could be useful in colchicine resistant FMF patients [
14‐
16] . Canakinumab is the only biologic agent approved by the U.S. FDA for the treatment of FMF [
17].
Table 1
Comparison of Tel-Hashomer, Yalcinkaya Ozen and Eurofer/Printo set criteria (modified from references 11,12,13). Tek-Hashomer is a writing error, it should be changed in Tel-Hashomer
Major Criteria 1.Recurrent febrile episodes with serosi- tis (peritonitis, synovitis or pleuritis) 2- Amyloidosis of AA type without a predisposing disease 3- Favorable response to regular colchi- cine treatment Minor Criteria 1- episodes 2- FMF in a first-degree relative 3- Erysipelas-like erythema | 1- Fever (Axillary temperature of > 38 °C, 6 72 h of duration, > 3 attacks) 2- Abdominal pain (6 72 h of duration, > 3 attacks) 3- Chest pain (6 72 h of duration, > 3 attacks) 4- Arthritis (6 72 h of duration, > 3 attacks, oligoarthritis) 5- Family history of FMF | Presence of confirmatory MEFV genotype and at least one among the following 1-Duration of episodes 1–3 days 2-Arthritis 3- Chest pain 4- Abdominal pain OR Presence of not confirmatory MEFV genotype and at least two among the following 1-Duration of episodes 1–3 days 2-Arthritis 3-Chest pain 4- Abdominal pain | Presence of 1-Eastern Mediterranean ethnicity 2-Duration of episodes 1–3 days 3- Arthritis 4- Chest pain 5- Abdominal pain Absence of 1-Aphthous stomatitis 2- Urticarial rash 3- Maculopapular rash 4- Painful lymph nodes |
2 major criteria or 1 major + 2 minor criteria | > 2 criteria | > 6 criteria |
FMF could be associated with other autoimmune diseases such as ankylosing spondylitis, rheumatoid arthritis, polyarteritis nodosa, Behcet,, and Systemic Lupus, and Hashimoto’s thyroiditis [
18,
19]. Association of type 1 diabetes mellitus (T1D) and FMF has been newly reported in the medical literature [
20,
21]. We report a case of a boy suffering from T1D, who developed FMF. This is the third association of these two diseases described in the medical literature.