Prevalence of allergic sensitization with vernal keratoconjunctivitis: A systematic review with meta-analyses.

To determine the prevalence of allergic sensitization in patients with vernal keratoconjunctivitis (VKC) and to provide an overview of published studies on this topic. We systematically searched 11 literature databases on 24 May 2021, for studies with cross-sectional data on the prevalence of positive allergy tests in patients with VKC. Our main outcome of interest was the prevalence of allergic sensitization and the allergens involved. Prevalence meta-analyses were made to provide summary estimates. We identified 33 eligible studies for qualitative review with 2122 patients with VKC. Studies were predominantly based on patients seen in ophthalmology clinics. Overall, studies reported that the most prevalent positive allergen tests were the inhaled allergens house dust mites and pollen. Twenty-nine studies were eligible for the quantitative analysis. Here, we calculated the prevalence of allergen-positive patients to 57.7% (95% confidence interval: 52.5%-62.8%). Subgroup analyses of pooled estimates on sensitization based on specific testing methods found prevalence estimates of 51.4% for conjunctival provocation test, 68.7% for total tear IgE, 58.9% for specific tear IgE, and 58.2% for skin prick test. The prevalence of allergic sensitization in patients with VKC is 57.7%, and mostly towards inhaled allergens. The most frequent positive allergens are house dust mites and pollen. Identifying possible clinically relevant allergens provide information that may aid in managing VKC, such as environmental allergy-avoidance or allergy-specific treatment.

Managing food allergy: GA2LEN guideline 2022.

Food allergy affects approximately 2-4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy.

Preventive Effect of Allergen Immunotherapy on Asthma and New Sensitizations.

Allergen immunotherapy (AIT) is a disease-modifying treatment for some IgE-mediated allergic diseases with the potential to have important preventive effects. Children with allergic rhinitis have a high risk of developing asthma, and treating allergic rhinitis with AIT may interfere with disease progression and prevent onset of asthma. Although the evidence is limited due to relatively few and heterogeneous studies, data nevertheless suggest that AIT has a preventive effect on development of asthma especially in children with rhinitis due to grass pollen allergy. AIT may also affect the development of new sensitizations. Both the degree of sensitization and the specific sensitization pattern may influence future disease severity and development of comorbidities. Hitherto, the indication for AIT for prevention of development of asthma in grass/birch pollen allergic children has been the same as for treatment of allergic rhinitis. Probably, AIT should be applied in the early stage of the allergic disease to have the greatest preventive effect on disease progression. Consequently, in the future, the potential preventive effects should influence the timing of initiating AIT. The window of opportunity to prevent asthma may primarily exist in young children with mild symptoms and a low degree of sensitization.

Prospective study of 5-day challenge with penicillins in children.

OBJECTIVES: To examine if a 5-day challenge with penicillin improves the diagnostic sensitivity compared with a single full dose in children with mild skin reactions. DESIGN: Subjects referred with suspected allergy to penicillin were consecutively included. Irrespectively of the morphology of the index reaction and the result of specific IgE, all subjects underwent a two-step titrated drug provocation test (DPT) with the culprit drug followed by a 5-day challenge at home. PARTICIPANTS: Children and adolescents aged 0-18 years referred to allergic workup for penicillin hypersensitivity at two paediatric Danish centres. Only subjects with non-severe skin reactions were included. RESULTS: A total of 305 subjects were included and 22 (7%) of the DPTs were positive. Three subjects reacted within 1 hour of the first full dose and nine reacted 1-8 hours after the first full dose. Additional 10 positive reactions were observed during the prolonged provocation. Seven subjects reacted after the second full dose and three reacted after 3-6 days. Only mild skin rashes were observed. Eighteen subjects had a specific IgE to a penicillin >0.1 kU/L. Only one of these had a positive DPT. CONCLUSION: In children, a DPT with penicillins should include at least two full doses. In children with mild hypersensitivity reactions it may be safe to perform DPTs despite a low specific IgE. TRIAL REGISTRATION NUMBER: NCT04331522.

Effect of Topical Steroids on Skin Prick Test: A Randomized Controlled Trial.

INTRODUCTION: Topically applied corticosteroids on the skin can significantly inhibit the wheal response to allergens in skin prick test (SPT). The duration of this effect is unknown. The aim of this study is to investigate the duration of the inhibitory effect of topical corticosteroids on SPT. METHODS: Twenty-two healthy subjects were included in a single-blinded randomized study. All subjects were skin prick tested using a standard inhalant allergen panel. The subjects were randomized to treat either the left or right forearm with Betnovat® cream (group III steroid) once a day for 10 days. Subsequently, the subjects were skin prick tested the following 5 days and at day 8 on both forearms. RESULTS: At baseline, the 22 individuals had positive SPT for a total of 72 allergens. Compared with the untreated arm, the mean size of the wheals was significantly reduced on day 1 (12 h after end of treatment) by 0.56 mm (95 % confidence interval (CI) [0.06; 1.06], p = 0.03) for allergens and 0.70 mm [0.32; 1.09] (p = 0.001) for histamine. On day 2 (36 h after end of treatment), the mean difference between treated and untreated arm was 0.47 mm [-0.08; 0.85] (p = 0.02) for allergen-induced wheals and 0.22 mm [-0.21; 0.64] (p = 0.31) for histamine-induced wheal. On day 3, 4, 5, and 8, there was no significant difference. CONCLUSIONS: Treatment with topical steroid significantly inhibited the response to SPT for 36 h but for less than 3 days. In addition, we demonstrated that topical applied corticosteroids inhibit the mean wheal size of the positive histamine control for a shorter time than for the allergens. Consequently, positive response to histamine control is not a valid marker for reliable skin prick test in steroid-treated patients. Plain language summary available for this article.

Relationship between specific IgE to egg components and natural history of egg allergy in Danish children.

BACKGROUND: The majority of egg-allergic children develop tolerance over time. However, it may take numerous of consecutive egg challenges to get there as no good indices to predict tolerance exist. OBJECTIVE: To investigate whether serial measurements of specific IgE to egg white, ovomucoid, ovalbumin, conalbumin, lysozyme, and egg yolk could improve the specificity of the diagnostic workup and aid in the decision when to rechallenge egg-allergic children. METHODS: The outcome of oral food challenges with hen's egg and corresponding specific IgE levels were evaluated in children referred to The Allergy Center within an 8-year period. The egg-allergic children were rechallenged and had specific IgE levels measured once a year. RESULTS: During a median follow-up of 26 months, 287 challenges and corresponding 287 serum analyses were performed in 130 children. Of the 130 children, 99 were egg allergic and 82 of these were rechallenged. Based on the initial diagnostic challenges only, area under the curve (AUC) estimates of the ability of specific IgE titers to distinguish between egg sensitization and egg allergy were only modest (maximum 0.83) and provided no clinical meaningful decision points. Specific IgE levels at baseline did not differ between tolerant and persistent allergic children. However longitudinally, acquisition of tolerance was associated with a decrease in IgE to egg white and to ovomucoid. In all cases of an increase in IgE to ovomucoid, the rechallenge was positive. CONCLUSION: The decision when to rechallenge egg-allergic children should encounter the course of specific IgE.

A randomized trial of lower leg and height growth in children with asthma treated with inhaled budesonide from a new dry powder inhaler.

Short-term knemometry is a highly sensitive and accurate method for non-invasive assessment of systemic activity of inhaled corticosteroids in children with asthma. However, there are no randomized data available to elucidate the relation between inhaled corticosteroid suppressed short-term lower leg and height growth. The aim of the present study was to assess the relation between short-term lower leg and 1-yr height growth in children with asthma treated with inhaled budesonide from the new Pulairmax inhaler 200 µg once daily in the morning or montelukast 5 mg once daily. A total of 52 pre-pubertal children with asthma were included in a randomized open-label parallel group study. Length of the lower leg and height were measured by knemometry and stadiometry, respectively, at study entry and after 2, 4, 12, 20, 28, 36, 44 and 52 wks. Lower leg and height growth rates were significantly lower in the budesonide than in the montelukast group (p < 0.0001). Mean 2-wks lower leg growth rate was 0.17 mm/wk in the budesonide and 0.39 mm/wk in the montelukast treated children (p = 0.02). Mean 1-yr height growth rate was 5.51 cm/yr in the budesonide and 6.51 cm/yr in the montelukast group [95% CI: (0.20; 1.79)]. There was a strong linear correlation between lower leg and height growth in both groups, rho = 0.96 (budesonide) and 0.98 (montelukast). In conclusion, 1-yr height growth suppression of budesonide 200 µg administered via the Pulairmax inhaler once daily in the morning was indicated from suppressed short-term lower leg growth providing evidence that short-term knemometry is able to predict 1-yr height growth suppression of inhaled corticosteroids. Short-term knemometry should be performed as part of the safety assessments of new inhaled corticosteroids and inhalation devices in children with asthma before long-term height growth evaluations are initiated.

Suppressive effects of topical mometasone furoate and tacrolimus on skin prick testing in children.

Skin prick tests were performed in 12 children with atopic eczema before and after 2 weeks of treatment with topical mometasone furoate and tacrolimus. Both treatments significantly suppressed the allergen wheal size. Mometasone furoate reduced the histamine wheal size as well. Skin prick testing in children treated with topical glucocorticoids or tacrolimus is associated with a risk of false-negative test results.

A 2-week, crossover study to investigate the effect of fluticasone furoate nasal spray on short-term growth in children with allergic rhinitis.

BACKGROUND: It is essential to assess potential growth effects of any newly developed corticosteroid. Fluticasone furoate is a recently approved, enhanced- affinity intranasal corticosteroid with low systemic bioavailability and proven efficacy in treating allergic rhinitis. OBJECTIVE: The aim of the current study was to assess whether treatment with fluticasone furoate nasal spray affected the short-term lower-leg growth rate in children with allergic rhinitis. METHODS: Prepubertal children with seasonal or perennial allergic rhinitis of at least 1 year's duration were included in this single-center, randomized, double-blind, placebo-controlled, crossover study. The study consisted of 4 periods, each of 2 weeks' duration screening, then 2 treatment periods separated by a washout). Study medications were fluticasone furoate nasal spray 110 microg and placebo nasal spray, both administered QD in the morning. The primary end point, lower-leg growth rate (measured in millimeters per week), was assessed by knemometry. Adverse events were also assessed. RESULTS: Fifty-eight patients were randomized to the study and comprised the intent-to-treat (ITT) population (mean [SD] age, 9.1 [1.4] years; 39 males, 19 females). Five patients were excluded from the ITT group due to protocol violations; thus, 53 patients (mean [SD] age, 9.0 [1.4] years; 35 males, 18 females) comprised the growth population (a de facto per-protocol group). In the growth population, the adjusted mean lower-leg growth rate was 0.40 and 0.42 mm/wk with fluticasone furoate and placebo, respectively. The difference in adjusted mean lower-leg growth rate between fluticasone furoate and placebo was -0.016 mm/wk (95% CI, -0.13 to 0.10). Fluticasone furoate was noninferior to placebo, as the lower boundary of the 95% CI was above the prespecified noninferiority margin of -0.20 mm/wk. These results were supported by the ITT analysis. Fluticasone furoate nasal spray was well tolerated and had an adverse-event profile similar to that of placebo nasal spray. Nasopharyngitis (placebo, 4; fluticasone furoate, 1) and headache (placebo, 3; fluticasone furoate, 1) were the most frequent adverse events during the treatment periods. CONCLUSION: In this study, fluticasone furoate nasal spray 110 microg QD for 2 weeks had no effect on lower-leg growth rate in these prepubertal children with allergic rhinitis.

Short-term growth in children with eczema during treatment with topical mometasone furoate and tacrolimus.

BACKGROUND: Treatment with topical glucocorticoids in children with atopic eczema may be associated with systemic adverse effects, such as suppression of growth. AIM: To asses if treatment with topical mometasone furoate 0.1% or topical tacrolimus 0.1% affects short-term growth in children with atopic eczema. Primary outcome measures were lower leg growth rates measured by knemometry. METHODS: Twenty 5- to 12-year-old prepubertal children with atopic eczema were included in a randomised, investigator-blind crossover study with five periods: two treatment periods, a run in, a wash out and a run out. All periods were of 2-week duration. The subjects applied mometasone furoate ointment 0.1% once daily during one treatment period and tacrolimus ointment 0.1% twice daily during the other treatment period. RESULTS: As compared to run in mean lower leg growth rate during mometasone furoate and tacrolimus treatment was reduced by 0.09 and 0.06 mm/week, respectively, (F = 1.12, p = 0.35). Consistently, no statistically significant effects on urine levels of eosinophil protein X and crossed-linked N-telopeptides were detected. CONCLUSION: Treatment with mometasone furoate or tacrolimus does not affect short-term growth in children with mild to moderate atopic eczema.

Allergic conjunctivitis in children with asthma, rhinitis and eczema in a secondary outpatient clinic.

Little evidence is available on the prevalence of allergic conjunctivitis in pediatric populations. The objective of this study was to assess the cumulative prevalence of allergic conjunctivitis in children with rhinitis, asthma and eczema in a secondary pediatric outpatient clinic. Children aged 5-15 yr referred during the period of 2002-2004 in whom allergic conjunctivitis, asthma, allergic rhinitis or eczema was diagnosed were included in a retrospective survey. At referral patient characteristics, history, symptoms, signs and results of type 1 allergy tests were entered into an electronic form. Four hundred and fifty-eight children with a mean age of 9.4 yr were studied. Of 316, 324 and 149 children with rhinitis, asthma or eczema, respectively, 133 (42%), 78 (24%) and 45 (30%) had concomitant allergic conjunctivitis. One hundred and thirty-seven (30%) had allergic conjunctivitis, of whom 133 (97%) also had allergic rhinitis, 77 (56%) asthma and 45 (33%) eczema. One hundred and twenty-five (91%) of the children with allergic conjunctivitis had positive allergy tests to one or more allergens, sensitization to house dust mites being more frequent in chronic allergic conjunctivitis than in acute allergic conjunctivitis (95% vs. 53%; p < 0.01). Sensitization to grass was more frequent in children with acute allergic conjunctivitis (78% vs. 57%; p = 0.03). In a secondary pediatric outpatient clinic allergic conjunctivitis is a frequent co-morbidity to allergic rhinitis and to asthma and eczema. Allergic conjunctivitis need to be included as an important co-morbidity in future guidelines on asthma, rhinitis and eczema management.

[Longitudinal growth in children with asthma treated with inhaled glucocorticoids]. / Laengdevaekst hos børn, der har astma og er i behandling med inhalerede glukokortikoider.

Randomised, double-blind studies with a knemometer have shown that the risk of inhaled glucocorticoid-induced growth suppression depends on dose, administration regimen, delivery device and specific glucocorticoid. Dry-powder beclomethasone dipropionate, 300-400 microg daily, and budesonide, 400 microg daily, suppress height growth rate by 20-25% during the first year of treatment, whereas lower doses of budesonide and fluticasone propionate do not affect growth rate. Available assessments of final height are flawed by poor compliance rates. Children with asthma on continuous treatment with inhaled glucocorticoids should have their height measured at six-month intervals. In the case of growth deviation, they should be referred for evaluation.