Familial Mediterranean fever in children presenting with attacks of fever alone.
OBJECTIVE
Familial Mediterranean fever (FMF) is an inherited disease characterized by attacks of febrile polyserositis. In children, attacks of fever alone, or with headache and malaise, may precede other forms of attacks. Our objective was clinical and genetic characterization of FMF and its development in pediatric patients who first presented with attacks of fever alone.


METHODS
Clinical characterization and MEFV genotype of all FMF patients < 16 years of age at disease onset and first presenting with attacks of fever alone were analyzed and compared for age, sex, and disease duration with matched FMF patients presenting with serositis at the onset of the disease.


RESULTS
There were 814 patients with FMF in our registry. Fifty patients formed the study group and 234 patients the control group. In the study group, the first (febrile) attacks appeared at a younger age than in the control group (1.7 +/- 1.6 yrs vs 5.0 +/- 4.1 yrs, respectively; p < 0.0001), diagnosis was made earlier (4.2 +/- 2.7 yrs vs 6.7 +/- 4.1 yrs; p < 0.0001), despite a trend for a longer delay in diagnosis. In the study group, attacks were shorter (1.6 +/- 0.8 days vs 2.1 +/- 1.0 days; p = 0.023) and homozygosity to the M694V mutation was more prevalent (46% vs 31%; p = 0.03). Attack rate, colchicine dose, and the MEFV mutation carrier rates were comparable between the groups. In 40/50 (80%) of the patients with fever alone, serositis had developed over a course of 2.9 +/- 2.2 years after disease onset.


CONCLUSIONS
FMF in young children may begin with attacks of fever alone, but it progresses to typical FMF disease over the next 2.9 +/- 2.2 years. Our study demonstrates that clinical heterogeneity at presentation is more likely to indicate a feature of a disease in development, rather than to mark distinct phenotypes of FMF.
Padeh
Shai
S
Department of Pediatrics A, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel. Shay.pade@sheba.health.gov.il
Livneh
Avi
A
Pras
Elon
E
Shinar
Yael
Y
Lidar
Merav
M
Feld
Olga
O
Berkun
Yackov
Y
D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D010505:Familial Mediterranean Fever / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005334:Fever / Q000175:diagnosis* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007585:Jews / Q000235:genetics; D008297:Male; D009154:Mutation; D012042:Registries