None of the four missense mutations is associated with a severe disease or the development of amyloidosis in Turkish FMF patients living in Turkey. The influence of unknown environmental factors and/or the presence of other genetic changes are necessary to explain the phenotypic variation of the disease and the development of amyloidosis.

Infantile acute hemorrhagic edema (IAHE) is a leukocytoclastic vasculitis that is confined to the skin without visceral involvement. Edema and purpuric lesions characterize the disease. The disorder has a dramatic onset, with a short, benign course and spontaneous resolution within several weeks. The clinical similarities between IAHE and Henoch-Shönlein purpura have been discussed in the literature. We report three infants with IAHE and discuss the clinical, laboratory, and histopathologic features of the disease. We suggest that it should be regarded as a separate entity for appropriate diagnostic investigations and therapy.

In order to obtain data on blood pressure (BP) distribution in Turkish children, a total of 5,599 Turkish children from birth to 18 years were studied. BP rises with age, and both systolic and diastolic BP showed a positive correlation with height and weight in both sexes. As the sampling was representative of Turkish children at different ages, the mean systolic and diastolic BP levels were compared for each age with the results reported in the study of the Second Task Force. The mean systolic and diastolic BP of Turkish children and the increase with growth and development were different from the Second Task Force study. Genetic, ethnic, and environmental factors were suggested to be responsible for this variation. In conclusion, normal BP curves should be applied with caution in childhood, and every population should use their own normal standards to define a measured BP level in children.

Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by recurrent self‐limited attacks of fever accompanied by peritonitis, pleuritis and arthritis. Approximately 5% of individuals with FMF have been reported to have Henoch‐Schonlein purpura (HSP) and about 1% have polyarteritis nodosa (PAN). Protracted febrile myalgia is another vasculitis‐associated clinical entity among patients with FMF. Recently, the gene responsible for FMF, MEFV, has been cloned and four missense mutations (M680I, M694V, V726A and M694I) have been described. In this report, we present clinical and laboratory findings and mutation results of 23 children with FMF‐associated vasculitis. HSP, PAN and protracted febrile attacks have been diagnosed in 11, 2 and 10 children, respectively. Mutation analysis shows that 3 children are homozygotes for the M694V mutation and 11 are compound heterozygotes for 2 of the studied mutations. M694V/V726A mutations were identified in 8, M694V/M694I in 2 and M680I/M694V in 1 of these children. In six children only one mutation was found and in three none of the studied mutations were identified. This study confirms that most children with FMF‐associated vasculitis have identifiable mutations in the MEFV gene. Environmental and/or other genetic factors are possibly involved in the pathogenesis of vasculitis in FMF; elucidation of these mechanisms will help to understand pathogenesis of childhood vasculitides. ?Children, Familial Mediterranean Fever, MEFV mutations, vasculitis

We suggest that FMF, perhaps as a consequence of impaired control of inflammatory responses, predisposes to vasculitis with renal involvement.

Familial Mediterranean fever (FMF) is an autosomal recessive disease. It is characterized by recurrent febrile episodes in association with peritonitis, pleuritis, and arthritis. Progressive systemic amyloidosis is the most important complication of FMF that inevitably leads to chronic renal failure. Recently, the gene for FMF, MEFV, has been cloned and four missense mutations have been described: M694V, M680I, V726A, and M694I. Initial studies have suggested that the presence of the M694V mutation carries a significant risk for the development of amyloidosis. In this study, we present seven families, in which at least two individuals have been diagnosed with FMF and at least one with amyloidosis. Among 18 individuals, in whom molecular testing was performed for the four aforementioned mutations, ten had amyloidosis. None of these ten individuals was found to be homozygous for the M694V mutation. In three families, there were two sibs with amyloidosis. None of the sib-pairs with amyloidosis was found to have the same genotype. There were two or more sibs with the same genotype in four families. Only one sib from each family developed amyloidosis in these families. These results provide evidence that FMF patients without the M694V mutation are also at risk for the development of amyloidosis. Particular mutations themselves do not appear to be sufficient to explain the occurrence of amyloidosis in all cases with FMF.

No abstract

This study demonstrates that the predominant association of AA amyloidosis is with FMF. It also suggests that the routine immunohistochemical study of patients with amyloidosis who are of certain ethnic backgrounds suffices for classifying the subtype of amyloid fibril protein and the related disease.