Proposed Mechanism of the Inflammatory Attacks in Familial Mediterranean Fever

The carotid-femoral (aortic) pulse wave velocity as a marker of arterial stiffness in familial Mediterranean fever

“…Although the role of the Mediterranean fever gene in the development of FMF attacks is not yet clearly understood, its malfunction eventually results in inflammation. It has also been proposed that in FMF, any minor stimulus leads to an uncontrolled inflammatory reaction with complement activation, due to an absence of an inhibitor of C5a and excessive tumour necrosis factor release (19)(20)(21). The inflammatory process of FMF is also caused by leukotriene B 4 , a potent lipid chemoattractant and mediator of acute inflammation (22,23).…”

Exclusion of linkage between familial Mediterranean fever and the human serum amyloid A (SAA) gene cluster

“…The Haldane formulation suggests exclusion of FMF from a 10.4 cM region including and surrounding the SAA gene cluster on chromosome 11. Several other hypotheses have been developed to explain FMF including a defect in lipocortin proteins leading to abnormal prostaglandirdleukotriene biosynthesis ) and reduced complement-derived C5a inhibitor activity (Matzner et al 1990). Neither possibility has been formally excluded.…”

Can Allergen Specific Immunotherapy Induce Familial Mediterranean Fever Attacks?

“…The emergence of attacks due to stress, the onset of attacks with metaraminol infusion and the response to colchicine treatment suggest that a defect in the metabolism of catecholamines may be involved in the pathogenesis of FMF (29). Today, the most widely accepted opinion on the pathogenesis of the disease is that a deficiency of C5a inhibitor, which is a inhibitor quite strong granulocyte chemoattractant C5a, may cause an acute inflammatory attack (30). It is also thought that the presence of wild type pyrin increases the synthesis of C5a/IL-8 inhibitory factor, while in patients with FMF the C5a/IL-8 inhibitory factors are deficient (31).…”