Nature’s Inflammation Experiment

Autoinflammatory syndromes that are not monogenic and autoinflammatory diseases with complex genetic traits: This spectrum has been growing and is claimed to include diseases such as Behçet Disease, systemic juvenile idiopathic arthritis.¹⁸

Management Principles and Prognosis

The use of colchicine has been a breakthrough in the management of FMF. This is the only periodic fever where an excellent quality of life is possible in the majority of patients—and with a cheap pill. In fact, colchicine has been shown to prevent amyloidosis in compliant patients in series from Israel and Turkey.^19,20 In a large pediatric study (n=809), no manifestations of amyloidosis occurred in 809 treated children during an observation period of up to 13 years.¹⁹ In the Turkish FMF registry, 2.3% developed amyloidosis, all being noncompliant with respect to regular colchicine intake.²⁰ We do not know the genetic factors that determine the development of secondary amyloidosis, although a number of polymorphisms in relevant genes have been associated with the development of secondary amyloidosis in FMF.

A starting dose of 0.5 mg/day colchicine in young children and 1.0 mg/day in older children (older than five years) is sufficient for disease control in approximately half of patients.²¹ This is increased to 1.5­–2 mg/day once the child is more than a square meter. SAA levels might indicate insufficient disease control and thereby require dose adjustment.²²

As physicians, we should warn the families about the risk to other children and follow patients’ siblings closely for any symptoms of unexplained fever or typical attacks. A routine mutation analysis of the FMF gene for siblings is probably not indicated. However, if there is a case of renal amyloidosis in the family, a genetic workup may be informative. SAA levels may need to be checked in patients with one mutation only and in siblings.

Dr. Ozen is professor of pediatrics at Hacettepe University in Ankara, Turkey.

References

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