Clinical and genetic peculiarities of vasculitis associated with Familial Mediterranean fever in Armenian children

Introduction

Familial Mediterranean fever (FMF) is the most common hereditary disorder among Armenians. It manifests mainly in childhood and represents a significant health care pediatric problem. The clinical picture of FMF and vasculitis have much in common: fever, abdominal pain, arthritis, myalgia, skin lesions. Numerous data indicate a higher incidence of vasculitis in FMF patients, compared with healthy ethnically matched populations.

Objective

To investigate clinical and genetic peculiarities of vasculitis associated with FMF in children in Armenia.

Methods

A group of 715 children with FMF was observed at the National Pediatric Centre for FMF (438 boys, 277 girls, mean age 8.64±0.17). The diagnosis of FMF was confirmed based on the Tel-Hashomer criteria and molecular genetic detection of MEFV mutations. For statistical analysis standard statistical Epi-Info 2000 Program was performed.

Results

Frequency of vasculitis in Armenian children with FMF was rather high - 4.3% (31 children). Henoch-Shonlein Purpura (HSP) was diagnosed in 1.5% (11) patients, Protracted Febrile Myalgia (PFM) - in 2.7% (20). FMF in these patients characterized by early onset (mean age 3 years), high (4 fold) risk of PFM [RR = 3.90 (1.32 ÷ 11.35); χ2 = 5.94; p = 0.015], as well as late diagnosis of FMF (9.42 ± 0.72) and late onset of colchicine treatment. They had also high frequency of severe FMF attacks, prevalence of acute recurrent arthritis and HSP and PFM manifestation after 5-6 year of FMF onset. The risk of HSP was 5-fold increased in children with severe FMF compared with moderate activity of disease. The development of vasculitis was associated with M694V-homozygous and compound-heterozygous genotypes. Particularly, HSP and PFM were observed respectively at 2.9% and 4.6% M694V-homozygous patients (χ2 = 8.27; p <0.02), which confirms the influence of MEFV genotype on the development of vasculitis.

Conclusion

Armenian children with FMF had higher than expected frequency of vasculitis (4.3%). We suppose, that in children with FMF: 1) HSP and PFM vasculitis might be considered as markers of severe FMF and early disease onset 2) M694V homozygous genotype is a risk factor for the development of PFM. These results are consistent with data on the susceptibility of FMF patients in ethnically matched populations in the development of HSP and PFM [Lange-Sperandio B. et al., 2004].MEFV mutation genetic screening is recommended for Armenian children with HSP, PFM vasculitis for early diagnosis of FMF, treatment and prevention of complications.