Recurrent hereditary polyserositis (RHP), also known as
familial Mediterranean fever, is a genetically-determined disease characterized by paroxysmal attacks of
peritonitis,
pleuritis,
arthritis or
inflammation of other serous membranes. We have previously suggested that the pathogenesis of this disease seems to be related to abnormal
catecholamine metabolism. This study compares the plasma and urine
catecholamine profile in patients with RHP during different clinical states to that in controls. In RHP there were lower plasma and higher urine
dopamine levels in the
asymptomatic state and during attacks, while
norepinephrine levels remain unchanged. However, plasma
epinephrine was significantly lower in the
asymptomatic state but markedly higher during attacks. The urine
epinephrine values in both situations were similar but significantly lower than in controls, suggesting abnormal renal excretion of
epinephrine. The urine
metanephrine was markedly elevated in the
asymptomatic state compared to controls, but remained unchanged during the attacks, again suggesting defective renal clearance of
metanephrine.
Metaraminol infusion, which induces attacks in RHP patients, was associated with an increase in plasma
dopamine and
epinephrine (but not
norepinephrine); yet the urinary levels of
dopamine,
epinephrine and
metanephrine remained the same, confirming the dissociation between the plasma and urinary levels of these
catecholamines, probably due to abnormalities in the renal clearance mechanism. We postulate that this dissociation leads to retention of these
amines in the plasma which may subsequently leak through the serous membranes (the target organs) and incite an acute inflammatory process.
Colchicine, the only known
drug that protects against disease attacks, reduces the plasma levels of these
amines, and thus may act by preventing retention that leads to leakage and subsequent
inflammation.