Rare occurrence of common filaggrin mutations in Turkish children with food allergy and atopic dermatitis

Background/aim: Filaggrin is a protein complex involved in epidermal differentiation and skin barrier formation. Mutations of the filaggrin gene (FLG) are associated with allergen sensitization and allergic diseases like atopic dermatitis (AD), allergic rhinitis, food allergy (FA), and asthma. The aim of the study is to reveal the frequency of change in the FLG gene and determine the association between FLG loss-of-function (LOF) mutations and FA and/or AD in Turkish children. Materials and methods: Four FLG loss-of-function (LOF) mutations known to be common in European populations were analyzed in 128 healthy children, 405 food-allergic children with or without atopic dermatitis, and 61 children with atopic dermatitis. PCR-RFLP was performed for genotyping R501X, 2282del4, and R2447X mutations; S3247Xwas genotyped using a TaqMan-based allelic discrimination assay. Results were confirmed by DNA sequence analysis in 50 randomly chosen patients for all mutations. Results: A total of 466 patients [(67% male, 1 (0.7­2.8) years] and 128 healthy controls [59% male, 2.4 (1.4­3.5) years)] were included in this study. Two patients were heterozygous carriers of wild-type R501X, but none of the controls carried this mutation. Three patients and one healthy control were heterozygous carriers of wild-type 2282del4. Neither patients nor controls carried R2447X or S3247X FLGmutations. There were no combined mutations determined in heterozygous mutation carriers. Conclusions: Although R501X, 2282del4, R2447X, and S3247X mutations are very common in European populations, we found that FLG mutations were infrequent and there is no significant association with food allergy and/or atopic dermatitis in Turkish individuals.

The spectrum of aeroallergen sensitization in children diagnosed with asthma during first 2 years of life.

Aeroallergens may trigger symptoms in sensitized children with asthma. Documentation of sensitization is crucial to enable effective implementation of measures to prevent asthma exacerbations. To document the sensitization patterns of very young children (≤2 years) with asthma, we retrospectively analyzed the skin-prick test (SPT) results of the largest referral center in the country. During a 4-year period, 432 children (median age, 1.21 years; male/female, 2.35) were referred. All patients had recurrent wheezing attacks and good response to inhaled bronchodilators and were diagnosed with asthma by their referring physician. SPT with eight aeroallergens (grass mix, weed mix, tree mix, mold mix, house-dust mite, cockroach, cat, and dog) was performed in 209 patients (full panel group) and the remaining 223 were tested only with a mixture of two house-dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae; house-dust mite group). The sensitization rates in house-dust mite and full panel groups were 3.2% (7/223) and 3.3% (7/209), respectively. Univariate and multivariate modeling was unable to identify a predictor for the presence of aeroallergen sensitization. During first 2 years of life, low rates of aeroallergen sensitization and lack of predictors of sensitization in children with asthma suggest that skin testing for aeroallergens may not be a routine procedure. When there is a high index of suspicion, testing only for indoor aeroallergens including house-dust mites, molds, and pets may identify the majority of sensitized children.

Skin prick testing to aeroallergen extracts: what is the optimal panel in children and adolescents in Turkey?

BACKGROUND/OBJECTIVE: The skin prick test (SPT) is the standard tool for the diagnosis of IgE-mediated allergic diseases. The number and spectrum of allergen extracts to be applied for the diagnosis of sensitized patients in order to achieve the most cost-effective and informative results are critical from both economic and scientific viewpoints. METHODS: In order to determine the minimum test battery panel necessary to cover at least 95% of the cases of SPT sensitization in children and adolescents (2-18 years) with suspected respiratory allergies, we retrospectively analyzed the SPT results of the largest referral center of the country. RESULTS: Over a 2.5-year period, a total of 2,457 children (male/female ratio 1.51) with a median (range) age of 6.8 years (2.0-18.0) were subjected to SPT. Eight hundred and sixty-two (35.1%) children were found to be sensitized to at least one of the 30 aeroallergen extracts tested. The most common sensitizations were to grasses (Festuca pratensis, Phleum pratense, Dactylis glomerata, and Lolium perenne), house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae), cat, weeds (Chenopodium, Plantago, and Artemisia), and moulds (Alternaria and Cladosporium). The sensitization rates increased in conjunction with an increase in age. Testing with 12, 8, and 7 allergens was sufficient to identify over 95% of the sensitized preschool children, school children, and adolescents, respectively. CONCLUSION: An SPT panel covering 12 allergen extracts was sufficient to detect most of the sensitized children and adolescents with recurrent respiratory symptoms. As the patients grow older, a smaller test panel is required compared to the panels used at younger ages.

Identifying uncontrolled asthma in children with the childhood asthma control test or exhaled nitric oxide measurement.

BACKGROUND: International guidelines highlight the importance of assessing asthma control status in children with asthma, and research on practical and objective instruments for assessing asthma control is ongoing. OBJECTIVE: To determine the role of the Childhood Asthma Control Test (C-ACT) and fractional concentration of exhaled nitric oxide (FeNO) in identifying children with not well-controlled asthma. METHODS: Children 6 to 11 years of age with asthma were enrolled in the study. They completed C-ACT and underwent FeNO and spirometric measurements during the monthly clinic visits. An asthma specialist assessed asthma control according to the gold standard Global Initiative for Asthma guideline and decided the treatment of the patients. RESULTS: Seventy-six children with a mean (SD) age of 8.7 (1.4) years were evaluated in the first visit, whereas 64 and 51 children were admitted for second and third visits, respectively. A C-ACT score of 22 or less had 69% sensitivity and 77% specificity in determining not well-controlled asthma, whereas an FeNO value of 19 ppb or higher had 61% sensitivity and 59% specificity in patients who completed 3 visits. Receiver operating characteristic curve analysis revealed that the C-ACT was better than FeNO for identifying patients with not well-controlled asthma (area under the curve, 0.79; P < .001 [C-ACT] vs .58, P = .10 [FeNO]) Results of multivariate generalized estimating equation analysis revealed that a C-ACT score of 22 or less (odds ratio, 8.75; 95% confidence interval, 4.35-17.59; P < .001) and an FeNO of 19 ppb or greater (odds ratio, 2.60; 95% confidence interval, 1.07-6.29; P = .03) were significant indicators for the presence of not well-controlled asthma. CONCLUSION: The C-ACT is superior to FeNO in determining the control status of children with asthma and may be used as a complementary tool in clinical practice to detect children with not well-controlled asthma.

Patch testing is an effective method for the diagnosis of carbamazepine-induced drug reaction, eosinophilia and systemic symptoms (DRESS) syndrome in an 8-year-old girl.

Drug reaction, eosinophilia and systemic symptoms (DRESS) is an acute and life-threatening disease, characterised by fever, rash and systemic symptoms, including lymphadenopathy, abnormal liver function, interstitial nephritis, pulmonary and cardiac infiltrates and haematological abnormalities with eosinophilia and atypical lymphocytes. The drugs mostly associated with DRESS are anticonvulsants, allopurinol, minocycline and sulfonamides. This syndrome is rarely seen in childhood even though a large number of children have anticonvulsant treatment. An 8-year-old girl was admitted with fever, lymphadenopathy and skin eruptions on her trunk. Her medical history was notable for epilepsy and carbamazepine treatment had been started 5 weeks previously. Laboratory studies showed a white cell count of 6200/µL (normal, 4100-11 200/µL) with 22% eosinophils and a γ-glutamyl transpeptidase level of 296 U/L (normal, 0-23 U/L). Laboratory tests for infections and collagen diseases were in the normal range. Persistence of fever and maculopapular eruption with generalised desquamation and the appearance of cheilitis and facial angioedema suggested a hypersensitivity reaction to carbamazepine. The carbamazepine was replaced with levetiracetam. All clinical symptoms improved within a week with corticosteroids and antihistamine treatment. Six weeks after complete recovery an epicutaneous patch test with carbamazepine was performed and a carbamazepine-induced positive skin reaction was observed at 48-h. Carbamazepine-induced DRESS syndrome is a rare entity in children. An epicutaneous patch test is a useful tool for identifying the inducing agent for the DRESS syndrome and for identifying a safe anticonvulsant drug.