Enhanced early skin treatment for atopic dermatitis in infants reduces food allergy.

BACKGROUND: Early-onset atopic dermatitis is a strong risk factor for food allergy, suggesting that early effective treatment may prevent transcutaneous sensitization. OBJECTIVES: This study tested whether enhanced treatment of atopic dermatitis to clinically affected and unaffected skin is more effective in preventing hen's egg allergy than reactive treatment to clinically affected skin only. METHODS: This was a multicenter, parallel-group, open-label, assessor-blind, randomized controlled trial (PACI [Prevention of Allergy via Cutaneous Intervention] study). This study enrolled infants 7-13 weeks old with atopic dermatitis and randomly assigned infants in a 1:1 ratio to enhanced early skin treatment or conventional reactive treatment using topical corticosteroids (TCSs). The primary outcome was the proportion of immediate hen's egg allergy confirmed by oral food challenge at 28 weeks of age. RESULTS: This study enrolled 650 infants and analyzed 640 infants (enhanced [n = 318] or conventional [n = 322] treatment). Enhanced treatment significantly reduced hen's egg allergy compared with the conventional treatment (31.4% vs 41.9%, P = .0028; risk difference: -10.5%, upper bound of a 1-sided CI: -3.0%), while it lowered body weight (mean difference: -422 g, 95% CI: -553 to -292 g) and height (mean difference: -0.8 cm, 95% CI: -1.22 to -0.33 cm) at 28 weeks of age. CONCLUSIONS: This study highlighted the potential of well-controlled atopic dermatitis management as a component of a hen's egg allergy prevention strategy. The enhanced treatment protocol of this trial should be modified before it can be considered as an approach to prevent hen's egg allergy in daily practice to avoid the adverse effects of TCSs. After remission induction by TCSs, maintenance therapy with lower potency TCSs or other topical therapies might be considered as alternative proactive treatments to overcome the safety concerns of TCSs.

House Dust Mite Subcutaneous Immunotherapy and Lung Function Trajectory in Children and Adolescents with Asthma.

Background: Allergen-specific immunotherapy is currently the only disease-modifying treatment for allergic asthma, and it has been shown to improve control of asthma while reducing both drug use and asthma exacerbations. However, its effects on lung function­especially its long-term effects­remain controversial. We aimed to identify factors associated with a possible beneficial effect of allergen-specific immunotherapy on lung function in asthma by retrospectively evaluating the long-term changes in lung function in children with asthma who received house dust mite subcutaneous immunotherapy (HDM-SCIT). Methods: We enrolled children with asthma who had undergone HDM-SCIT for more than 1 year. Clinical information and lung function measurements were retrieved from the electronic chart system. To characterize the trajectory of lung function change, we performed linear regression analysis to evaluate the maximal expiratory flow at 50% of the forced vital capacity during two periods: before and during HDM-SCIT. Slopes from a least-squares regression line for the two periods, i.e., S1 before HDM-SCIT and S2 during HDM-SCIT, were compared. The subjects were then classified into two groups: an improving group (Group I) defined as S2 − S1 > 0, and a declining group (Group D) defined as S2 − S1 < 0. The clinical factors at the start of HDM-SCIT were compared between the two groups. Results: A total of 16 patients were analyzed. Eight patients were classified into each of Group I and Group D. The mean ages were 10.5 and 11.8 years, and the mean treatment periods were 4.1 and 3.9 years. Group I had a significantly lower blood eosinophil count and a significantly higher HDM-specific IgE level than Group D. Logistic regression showed a strong relationship between those two markers and the lung function trajectory. Conclusion: Control of the blood eosinophil count in highly HDM-sensitized patients may increase the beneficial effect of HDM-SCIT on lung function.

Factors associated with outcome of egg allergy 1 year after oral food challenge: A good baseline quality of life may be beneficial.

BACKGROUND: Safely liberalizing the diet to include an allergenic food may accelerate resolution of food allergy. The outcome of liberalization, however, varies among patients. METHODS: We conducted a prospective observational study to identify factors associated with outcome for egg allergy 1 year after oral food challenge (OFC). We enrolled children <72 months old who had egg allergy and underwent OFC for determination of the safe intake quantity of egg allergen. Each child's baseline clinical background was recorded. Caregivers used the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) to assess their children's QoL. Dietary advice based on the OFC result was provided to support safe egg consumption. At 1 year after OFC, the quantity of egg each child safely consumed in daily life was surveyed. We classified the outcome as Successful (Group S) if the quantity increased during the 1 year, or as Unsuccessful (Group U) if it did not. Factors associated with the outcome were investigated by multivariate logistic regression analysis. RESULTS: A total of 93 children were enrolled, and after 1 year, 57 finished in Group S and 36 in Group U. The mean FAQLQ-PF score at baseline was significantly lower (ie, a better QoL) in Group S than in Group U. Multivariate logistic regression analysis identified a good QoL and absence of comorbid asthma or atopic dermatitis as factors predicting a favorable outcome. CONCLUSION: QoL may affect food allergy outcome. Intervention focusing on the QoL may promote outgrowing of food allergies.

Three cases of severe adolescent asthma treated with mepolizumab: lung function trajectories.

Real-world experience with mepolizumab for pediatric asthma is still limited. We report 3 patients who were treated with mepolizumab for severe adolescent asthma. Two patients, a 12-year-old boy and a 14-year-old girl, responded well to mepolizumab and showed apparent improvement in lung function from a downward trend over time before treatment. The third patient, a 16-year-old boy, whose treatment was switched from omalizumab to mepolizumab, did not have satisfactory response. The 2 successful cases had eosinophil counts of 440 and 371/µL and multiple comorbid allergic diseases including food allergies. The clinical benefit to them included elimination of both exacerbation and exercise-induced asthma. Interestingly, the boy's food-induced gastrointestinal symptoms disappeared following start of mepolizumab treatment.

A novel homozygous mutation of CLCN2 in a patient with characteristic brain MRI images - A first case of CLCN2-related leukoencephalopathy in Japan.

Chloride channel 2 (ClC-2) is one of nine ClC family proteins and is encoded by CLCN2. We report the first patient with a CLCN2 mutation in Japan. A 22-month-old female had generalized tonic-clonic convulsions at the age of 3 months. Brain MRI showed high signals in the bilateral cerebellar white matter including the dentate nucleus, dorsal midbrain, and posterior limbs of the internal capsules in diffusion-weighted images, and apparent diffusion coefficient values were low in the same areas. Antiepileptic drugs were effective, and she had neither intellectual disabilities nor motor disturbance. A homozygous frameshift mutation (c.61dup, p.Leu21Profs∗27) of CLCN2 was identified in the patient. Homozygous mutations of CLCN2 are known to be associated with CLCN2-related leukoencephalopathy (CC2L). The clinical findings of this patient were different from other patients with CC2L. Therefore, mutations in CLCN2 may cause various phenotypes. Further accumulation of cases with CLCN2-mutations is required to explore the clinical spectrum of CC2L.

Analysis of glutathione and glutathione disulfide in human saliva using hydrophilic interaction chromatography with mass spectrometry.

A sensitive method for the determination of glutathione (GSH) and glutathione disulfide (GSSG) in human saliva was developed and validated. GSH was captured and stabilized by the addition of N-ethylmaleimide (NEM). Solid-phase extraction (SPE) using an Oasis MAX extraction cartridge was employed for sample preparation and analysis was performed on a Shimadzu LCMS-2010 A that was operated in the single ion monitoring mode using positive ion electrospray ionization (ESI) as the interface. The monitored ion for GSH-NEM was m/z 433 and that for GSSG was m/z 613. Chromatography was carried out on an Atlantis HILIC silica column (150 mm x 2.1 mm, 5 microm) with acetonitrile and formate buffer as the mobile phase at the flow rate of 0.2 ml/min. The calibration curve was linear over the range of 0.1-100 microM for GSH-NEM. The extraction recoveries of GSH-NEM spiked at concentrations of 25 and 50 microM were 97.1 and 104.4%, respectively. Similar results were obtained for GSSG. The newly developed hydrophilic interaction chromatography with mass spectrometry (HILIC/MS) method showed superior sensitivity for the determination of GSH and GSSG in human saliva samples.