Role of E148Q in familial Mediterranean fever with an exon 10 mutation in MEFV.

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease caused by mutations in the MEFV gene. Mutations in exon 10 are associated with typical FMF. Most Japanese patients with typical FMF are compound heterozygotes of M694I in exon 10 and E148Q in exon 2. However, the pathogenic role of E148Q remains controversial. METHODS: We assessed symptoms and serum cytokines among patients with FMF and their family members. They were divided into three subgroups, based on MEFV mutations: individuals carrying M694I and E148Q (group A, n = 14), individuals carrying M694I, but not E148Q (group B, n = 10), and individuals carrying E148Q, but not M694I (group C, n = 11). RESULTS: All but one individual in group A had typical FMF phenotypes, whereas no individual in groups B and C exhibited any episodes of fever or serositis. The serum levels of interleukin-18 during the afebrile phase were significantly elevated in group A (2,806 ± 2,107 pg/mL), compared to those in groups B (499 ± 369 pg/mL) and C (427 ± 410 pg/mL). No difference in interleukin-6 levels was observed among the three groups. CONCLUSIONS: These findings indicated that E148Q may contribute to disease development of FMF in Japanese patients carrying the heterozygous M694I mutation in MEFV and that genetic testing of both parents would lead to better counseling for their children.

Clinical Characteristics of Pediatric Pyelonephritis Without Pyuria or Bacteriuria.

BACKGROUND: The gold standard for the diagnosis of acute pyelonephritis (APN) in children is the finding of both pyuria (P) and bacteriuria (B); however, some APN patients have neither of these findings [APN(P(-);B(-))]. METHODS: In this study, we investigated APN patients who visited our hospital over 14 years to identify specific clinical characteristics of APN(P(-);B(-)). RESULTS: A total of 171 APN patients were included in the study, and of these 29 were APN(P(-);B(-)). Of the APN(P(-);B(-)) patients, 25.9% had vesicoureteral reflux (VUR), the same percentage as the APN(P(+);B(+)) patients, and 69.0% of APN(P(-);B(-)) patients had already taken antibiotics before diagnosis. APN(P(-);B(-)) patients were older and had a longer duration between onset of fever and diagnosis than the patients with pyuria and/or bacteriuria. In addition, they showed higher C-reactive protein levels. APN(P(-);B(-)) patients had high levels of urinary α-1 microglobulin and urinary ß-2 microglobulin. CONCLUSIONS: APN is difficult to diagnose in febrile patients who display neither pyuria nor bacteriuria, but as these patients have the same risk for VUR as APN patients with pyuria and bacteriuria, a detailed history establishing the clinical course as well as urinary chemistry investigations, may assist in diagnosis.

Amniotic membrane transplantation in acute phase of toxic epidermal necrolysis with severe corneal involvement.

OBJECTIVE: To report successful management of acute stage toxic epidermal necrolysis (TEN) by amniotic membrane transplantation. DESIGN: Interventional case report. METHOD/INTERVENTION: A 6-year-old boy who had convulsions and fever due to encephalitis was treated by oral phenobarbital. Two weeks later, he developed a high fever and skin rashes involving >40% of the body, with a positive Nikolsky sign and oral blisters. Examination under general anesthesia performed 5 days after the onset of eye symptoms showed severe inflammation and ulceration on the lid margin and the tarsal conjunctiva in both eyes, a total corneal epithelial defect in the right eye, and a geographical corneal epithelial defect in the left eye. Amniotic membrane was transplanted in both eyes as a patch to cover the entire ocular surface, including upper and lower lid margins. RESULTS: Fourteen days after amniotic membrane transplantation, complete corneal and conjunctival epithelialization was observed in the left eye. However, a second amniotic membrane transplantation was performed in the right eye, which still had a total corneal and conjunctival epithelial defect, and resulted in complete epithelialization 14 days later. Corrected visual acuity improved to 20/16 without any superficial punctate keratitis in both eyes 6 months postoperatively. Minimal symblepharon and peripheral scarring were observed only in the right eye. CONCLUSIONS: Amniotic membrane transplantation performed at the acute phase of TEN is highly effective not only in reducing inflammation and preventing scarring in the conjunctival surface, but also in restoring corneal epithelial integrity in eyes with both corneal and conjunctival ulceration. As a result, in this case it prevented sight-threatening cicatricial complications at the chronic stage.