1 Institute of Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
2 Periodic Fevers Research Centre, Università Cattolica Sacro Cuore, Rome, Italy.
3 Institute of Pediatrics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
| This is an Open Access article distributed
under the terms of the Creative Commons Attribution License
(https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
self-limited attacks of fever and short-lived inflammation in the
serosal membranes, joints, and skin are the leading features of
familial Mediterranean fever (FMF), the most common autoinflammatory
disorder in the world, transmitted as autosomal recessive trait caused
by MEFV gene mutations. Their
consequence is an abnormal function of pyrin, a natural repressor of
inflammation, apoptosis, and release of cytokines. FMF-related mutant
pyrins are hypophosphorylated following RhoA GTPases’ impaired activity
and show a propensity to relapsing uncontrolled systemic inflammation
with inappropriate response to inflammatory stimuli and leukocyte
spread to serosal membranes, joints or skin. Typical FMF phenotype 1
consists of brief episodes of inflammation and serositis, synovitis,
and/or erysipelas-like eruption, whereas phenotype 2 is defined by
reactive amyloid-associated (AA) amyloidosis, which is the most ominous
complication of FMF, in otherwise asymptomatic individuals.
The Ancient Heredity of Familial Mediterranean Fever
The Size of a Borderless Disease
Pyrin, an Intracellular Sentinel against Infections
A Host of Genotype Studies
A Kaleidoscopic Disease with Protean Faces
|Table 1. List of the main clinical features of familial Mediterranean fever in the cohort of patients managed in our Centre.|
Searching for Universal Diagnostic Criteria of Familial Mediterranean Fever
|Table 2. Classification Criteria for the Clinical Diagnosis of Familial Mediterranean Fever (FMF) according to the Tel Hashomer criteria. Diagnosis is made when 2 major criteria or 1 major and 2 minor criteria are satisfied, while diagnosis is probable if 1 major and 1 minor criterion are present.|
|Table 3. Classification Criteria for the Clinical Diagnosis of Familial Mediterranean Fever (FMF) according to Livneh et al. Diagnosis of FMF requires ≥1 major criteria, or ≥ 2 minor criteria, or 1 minor criterion plus ≥5 supportive criteria (family history of FMF, appropriate ethnic origin, age less than 20 years at disease onset, severity of attacks requiring bed rest, spontaneous remission of symptoms, presence of symptom-free intervals, transient elevation of inflammatory markers, episodic proteinuria or hematuria, nonproductive laparotomy with removal of a “white” appendix, consanguinity of parents) or 1 minor criterion plus ≥ 4 of the “first” five supportive criteria. “Incomplete” attacks are defined as painful and recurrent flares that differ from typical attacks in 1 or 2 features, as follows: 1) normal temperature or lower than 38°C; 2) attacks longer than 1 week or shorter than 6 hours; 3) no signs of peritonitis recorded during acute abdominal complaint.|
|Table 4. Classification Criteria for the Clinical Diagnosis of Familial Mediterranean Fever (FMF) according to Yalçinkaya and Ozen (Turkish FMF Pediatric Criteria). Diagnosis of FMF requires the presence of 2 out of 5 criteria (in Turkish children).|
Ancient and Modern Treatments
How to Put Patients in Differential Diagnosis