Tolerance induction through early feeding to prevent food allergy in infants and children with sensitization against food allergens (TIFFANI): rationale, study design, and methods of a randomized controlled trial.

BACKGROUND: Children with sensitization against foods have to be orally food-challenged before eating these foods for the first time. However, the waiting time for an oral food challenge (OFC) in Germany is about 3-6 months. In contrast, there are hints that an early introduction of allergenic foods might be protective regarding the development of food allergy. The aim of this clinical trial is therefore to investigate, whether an introduction and regular consumption of small amounts of food allergens is safe and will result in an increase of tolerance in children with sensitization against food allergens with unknown clinical relevance. METHODS: In this randomized, placebo-controlled, double-blind, single-center trial, 138 children (8 months to 4 years of age) sensitized to the target allergen(s) hen's egg, cow's milk, peanuts, and/or hazelnuts with unknown clinical relevance will be randomized in a 1:1 ratio to either an active or a placebo group, daily receiving a rusk-like biscuit powder with or without the target allergen(s) for 3-6 months until an OFC will be performed in routine diagnostics. The primary endpoint is an IgE-mediated food allergy to the primary target allergen, after the interventional period. DISCUSSION: Children with sensitization against food allergens with unknown clinical relevance often have to avoid the corresponding foods for several months until an OFC is performed. Therefore, the "window of opportunity" for an early preventive introduction of allergenic foods might be missed. This trial will assess whether an introduction of small allergen amounts will favor tolerance development in these children. TRIAL REGISTRATION: German Clinical Trials Register DRKS00032769. Registered on 02 October 2023.

Patch Testing in Allergic Contact Dermatitis.

BACKGROUND: Allergic contact dermatitis is one of the most common forms of skin diseases that require medical intervention. Appropriate detection of allergens by patch test and accurate avoidance of them is the key to management. The objective of this study is to determine the types and frequency of allergens responsible for Allergic contact dermatitis in a tertiary hospital of Nepal. METHODS: Altogether 120 patients with Allergic contact dermatitis were enrolled in the study. Patch test was performed to find out the most common inciting allergen, utilizing the Indian Standard Series of allergens approved by The Contact and Occupational Dermatoses Forum of India. Results were read at 48 and 96 hours. Grading of the reactions was done based on the criteria of the International Contact Dermatitis Research Group. Pattern of reactivity of different allergens was assessed. RESULTS: Of all the patients, 63 (53%) showed positivity to at least one allergen. Nickel sulfate was the most frequent sensitizing agent in 22 (18%) cases, followed by Fragrance mix in 11(9%) and Paraphenylenediamine in 7 (6%) cases. Out of all positive results, Grade 1 positivity was seen in 44 (51%), Grade 2 positivity in 41(47%) and only 2 (2%) cases showed Grade 3 positivity. Mercaptobenzothiazole, Balsam of Peru, Nitrofurazone and Wool Alcohol did not show positive results in any of our patients. CONCLUSIONS: Patch testing helps in the treatment, long term remission, and patient counseling for prevention. Larger scale studies are required to know the sensitivity to allergens in Nepalese population.

Contact Allergy to Allergens in the Swedish Baseline Series Overrepresented in Diabetes Patients with Skin Reactions to Medical Devices - A Retrospective Study from Southern Sweden.

Allergic contact dermatitis is reported among individuals using continuous glucose monitoring systems and insulin pumps. The aim of this study was to describe contact allergy patterns for allergens in the Swedish baseline series and medical device-related allergens among users. Contact allergy to baseline series allergens and isobornyl acrylate was compared between diabetes patients and dermatitis patients patch-tested at the Department of Occupational and Environmental Dermatology during 2017 to 2020. Fifty- four diabetes patients and 2,567 dermatitis patients were included. The prevalence of contact allergy to fragrance mix II and sesquiterpene lactone mix was significantly higher in diabetes patients compared with dermatitis patients. Of the diabetes patients 13.0% and of the dermatitis patients 0.5% tested positive to sesquiterpene lactone mix (p < 0.001). Of the diabetes patients 7.4% and of the dermatitis patients 2.3% tested positive to fragrance mix II (p = 0.041). Of the diabetes patients 70.4% tested positive to medical device-related allergens. Of the diabetes patients 63.0% and of the dermatitis patients 0.2% were allergic to isobornyl acrylate (p < 0.001). In conclusion, not only medical device-related contact allergies, but also contact allergy to baseline series allergens (fragrance mix II and sesquiterpene lactone mix), is overrepresented in diabetes patients who use medical devices.

A rare case of lysozyme-induced anaphylaxis in a child with egg allergy.

We report an unusual case of anaphylaxis induced by the lysozyme-containing over-the-counter-drug Lysopaine®, which contains 20 mg lysozyme hydrochloride and 1.5 mg cetylpyridinium chloride, in a 9-year-old child with allergy to hen's egg as well as multiple IgE-mediated food allergies. The involvement of lysozyme was confirmed by positive skin prick tests for Lysopaine® and the presence of specific IgE against lysozyme. Our case highlights the importance of properly educating allergic patients to recognize allergens, even minor ones. Despite the presence of lysozyme in various food and drug products, it is not necessarily perceived as an allergenic protein by patients with egg allergy, and the labeling may be misleading, thereby exposing patients to potentially severe reactions.

Axillary Contact Dermatitis: An Update on Potential Allergens and Management.

The differential diagnosis of dermatoses in the axillae is broad. Contact dermatitis-both irritant and allergic-represents common etiologies. Axillary contact dermatitis can develop following exposure to a variety of irritants and/or allergens. Frequently implicated sources include deodorants, antiperspirants, detergents, soaps, and clothing. Fragrance, a ubiquitous ingredient within these products, as well as metals and dyes, are common causes of contact dermatitis. Clinical assessment, bedside diagnostic techniques, histopathology, and patch testing can aid in the diagnosis and help inform management directions.

The Natural History and Risk Factors for the Development of Food Allergies in Children and Adults.

PURPOSE OF REVIEW: This narrative review explores food allergy prevalence and natural history stratified by life stages, especially in context of evolving knowledge over the last few decades. RECENT FINDINGS: The prevalence of food allergy remains highest in early childhood with common food triggers being cow's milk, soy, hen's egg, wheat, peanut, tree nuts, sesame, fish, and shellfish. This correlates with certain risk factors especially pertinent in the postnatal period which appear to predispose an individual to developing a food allergy. Some allergies (such as milk and egg) were previously thought to be easily outgrown in early life; however, recent studies suggest increasing rates of persistence of these allergies into young adulthood; the reason behind this is unknown. Despite this, there is also evidence demonstrating that food allergies can be outgrown in adolescents and adults. An understanding of the paradigm shifts in the natural history of food allergy allows clinicians to provide updated, age-appropriate, and tailored advice for patients on the management and prognosis of food allergy.

A randomized, double-blind placebo-controlled study on the efficacy of Omalizumab on food allergy threshold in children with severe food allergy.

BACKGROUND: Food allergy is common in childhood with some children having a low threshold and being difficult to protect from accidental ingestion of the offending food. Therapies for this potentially life-threatening condition are highly needed. The aim of this study was to evaluate the efficacy of Omalizumab in food-allergic children. METHODS: This is a single-center, double-blind, placebo-controlled study. Food allergic children with a cumulative threshold ≤443 mg food protein at DBPCFC were randomized to Omalizumab (asthma dose) or placebo (3:1). After 3 months, a second DBPCFC was performed (steps 3, 10, 30, 100, 300, 1000, and 3000 mg food protein), followed by a separate open challenge up to 10,000 and 30,000 mg food protein if negative. Responders were defined as ≥2-step increases in threshold. Non-responders received high-dose Omalizumab. A third DBPCFC was performed after 6 months. Skin testing, blood samples, and the severity of atopic co-morbidity were registered during the study and 3 months after treatment. RESULTS: In total, 20 children were evaluated at 3 months (14 Omalizumab, 6 placebo). All treated with Omalizumab increased their threshold at least two steps and with a significant difference between the Omalizumab and the placebo group (p = .003), although the intended number of included children was not reached. The threshold before Omalizumab treatment was 13-443 mg food protein while the threshold after 3 months of treatment increased up to 44,000 mg (1143-44,000). In the placebo group, two children improved threshold during the study. CONCLUSION: An increase in the threshold level during Omalizumab treatment significantly improve patient safety and protected all children against small amount of allergen.

Omalizumab for the Treatment of Multiple Food Allergies.

BACKGROUND: Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. METHODS: In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension. RESULTS: Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group. CONCLUSIONS: In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.).

Thunderstorm Asthma and Climate Change.

This JAMA Insights in the Climate Change and Health Series defines thunderstorm asthma, describes its effects and increased rate of occurrence, and highlights recommendations for improved response during future events.

Allergic or Not: Final Interpretation of Doubtful Patch Test Reactions From the North American Contact Dermatitis Group, 2019-2020.

Background: Doubtful patch test reactions generally do not meet criterion for positivity in patch testing. However, the North American Contact Dermatitis Group (NACDG) allows for doubtful reactions to be coded with a final determination of "allergic/positive" based on the temporal pattern, appearance, known characteristics of the allergen, and/or other supportive patch test reactions. Objectives: To analyze NACDG data from the 2019-2020 patch test cycle to identify patterns in the interpretation and relevance of doubtful reactions. Methods: The frequency and proportions of doubtful reactions were tabulated and analyzed for patterns. Statistical analyses were limited to allergens with ≥30 doubtful reactions to ensure adequate sample size. Results: Of patch-tested patients, 31.9% (1315/4121) had ≥1 doubtful reaction. Of 2538 total doubtful reactions, 46% (n = 1167) had a final interpretation of "allergic/positive." The allergens with the highest proportion of doubtful reactions at the final visit were hydroperoxides of linalool 1% (4.5%), fragrance mix I 8.0% (3.9%), and cetrimonium chloride 0.5% (3.4%). Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) 0.02% (P < 0.001), MI 0.2% (P < 0.001), nickel sulfate hexahydrate 2.5% (P = 0.001), and neomycin sulfate 20.0% (P = 0.003) doubtful reactions were more likely to be interpreted as allergic than nonallergic. Methyldibromoglutaronitrile/phenoxyethanol 0.2% (P < 0.001), oleamidopropyl dimethylamine 0.1% (P < 0.001), formaldehyde 2.0% (P < 0.001), cetrimonium chloride 0.5% (P < 0.001), benzophenone-4 (sulisobenzone) 10% (P < 0.001), iodopropynyl butylcarbamate 0.5% (P < 0.001), cocamidopropyl betaine 1.0% (P = 0.002), and benzisothiazolinone 0.1% (P = 0.012) doubtful reactions were less likely to be interpreted as allergic. Of the 1167 doubtful reactions interpreted as allergic, 84.9% had current relevance. Conclusions: Doubtful reactions were common and approximately one half were coded with a final interpretation of "allergic/positive." Of those, most were clinically relevant. MCI/MI, MI, nickel, and neomycin were more likely to be interpreted as allergic.

Plain Language Summary: Immunotherapy for Inhalant Allergy.

The plain language summary explains allergen immunotherapy to patients, families, and caregivers. The summary is for patients aged 5 years and older who are experiencing symptoms from inhalant allergies and are considering immunotherapy as a treatment option. It is based on the 2024 "Clinical Practice Guideline: Immunotherapy for Inhalant Allergy." This plain language summary is a companion publication to the full guideline, which provides greater detail for health care providers. Guidelines and their recommendations may not apply to every patient, but they can be used to find best practices and quality improvement opportunities.

New device, 'old' allergens. Allergic contact dermatitis caused by the Dexcom G7 glucose sensor.

BACKGROUND: Allergic contact dermatitis (ACD) has been reported as an adverse effect from the use of several glucose sensors and insulin pumps from different manufacturers. Isobornyl acrylate (IBOA) has been identified as a major culprit sensitizer, but also other acrylates and (modified) colophonium have been reported as causes of ACD. OBJECTIVES: To report the two first cases diagnosed with ACD caused by the Dexcom G7 (DG7) glucose sensor. PATIENTS AND METHODS: Two children with suspected ACD from DG7 were patch tested with our medical device series with an addition of selected test preparations including two variants of modified colophonium - methyl hydrogenated rosinate (MHR) and glyceryl hydrogenated rosinate (GHR). Both patients were also tested with acetone extracts made from different parts of the DG7 sensor. The extracts were analysed by gas chromatography-mass spectrometry (GC-MS). RESULTS: Both patients tested positive to IBOA, hydroabietyl alcohol and GHR. In addition, patient 1 had a positive reaction to MHR and patient 2 had a positive reaction to colophonium. The GC-MS analyses showed the presence of IBOA and colophonium-related substances in the DG7 extracts. CONCLUSIONS: Both patients were diagnosed with contact allergy to well-known medical device-related sensitizers. The presence of IBOA and (modified) colophonium in a newly introduced (on the Swedish market in 2023) glucose sensor is remarkable and indicates an inadequate toxicological assessment of the materials used in the sensor.

Allergic contact dermatitis due to 1,6-hexanediol diacrylate in ostomy patients.

BACKGROUND: Many people live with ostomies after life-saving surgery. Ostomy patients often suffer from peristomal dermatitis. Allergic contact dermatitis (ACD) has been reported, mostly due to contact allergy (CA) to topical agents. OBJECTIVES: We present three patients with therapy resistant peristomal dermatitis, suggesting ACD caused by different stoma products. METHODS: Patch testing was performed with baseline series, additional series, and selected allergens. They were also tested with their own ostomy products as is and separate extracts of the products. Extracts were analysed using Gas Chromatography-Mass Spectrometry (GC-MS). RESULTS: In all three patients we diagnosed CA to 1,6-hexanediol diacrylate (HDDA), +++ in case (C) 1 and 3, ++ in C 2. HDDA was detected in C 2's ostomy pouch adhesive and in C 1's and 3's flange extenders used to improve the adhesion of the ostomy pouches. CONCLUSION: Therapy resistant peristomal dermatitis should always be suspected of ACD and patch testing, especially with the patient's own products, should be performed.

A comprehensive review on mango allergy: Clinical relevance, causative allergens, cross-reactivity, influence of processing techniques, and management strategies.

Mangoes (Mangifera indica) are widely prized for their abundant nutritional content and variety of beneficial bioactive compounds and are popularly utilized in various foods, pharmaceuticals, and cosmetics industries. However, it is important to note that certain proteins present in mango can trigger various allergic reactions, ranging from mild oral allergy syndrome to severe life-threatening anaphylaxis. The immunoglobulin E-mediated hypersensitivity of mango is mainly associated with three major allergenic proteins: Man i 1 (class IV chitinase), Man i 2 (pathogenesis-related-10 protein; Bet v 1-related protein), and Man i 4 (profilin). Food processing techniques can significantly affect the structure of mango allergens, reducing their potential to cause allergies. However, it is worth mentioning that complete elimination of mango allergen immunoreactivity has not been achieved. The protection of individuals sensitized to mango should be carefully managed through an avoidance diet, immediate medical care, and long-term oral immunotherapy. This review covers various aspects related to mango allergy, including prevalence, pathogenesis, symptoms, and diagnosis. Furthermore, the characterization of mango allergens and their potential cross-reactivity with other fruits, vegetables, plant pollen, and seeds were discussed. The review also highlights the effects of food processing on mango and emphasizes the available strategies for managing mango allergy.

Contact allergy to SIDAPA baseline series allergens in patients with eyelid dermatitis: An Italian multicentre study.

BACKGROUND: Eyelid dermatitis is a frequent reason of dermatological consultation. Its aetiology is not univocal, being contact dermatitis, both allergic and irritant, the most frequent. The primary sources of allergen exposure include cosmetics, metals, and topical medications, from direct, indirect, or airborne contact. OBJECTIVES: To define the frequency of positive patch test reactions to SIDAPA baseline series allergens, to document positive allergens, and to precise the final diagnosis in patients with eyelid involvement. METHODS: A total of 8557 consecutive patients from 12 Italian Dermatology Clinics underwent patch testing with SIDAPA baseline series in 2018 and 2019. Patients were divided into two groups: (i) with eyelid involvement with or without other involved sites (E-Group) and (ii) without eyelid involvement (NE-Group). The final diagnosis and the frequency of positive relevant patch test reactions were evaluated. RESULTS: E-Group consisted of 688 patients (females 78.6%, mean age 45.3 years), 8.0% of 8557 consecutively patch-tested patients. The final diagnosis in E-Group was ADC in 42.4%, ICD in 34.2%, and AD in 30.5%. The highest reaction rates were elicited by nickel sulphate and methylchloroisothiazolinone/methylisothiazolinone in both E-Group and NE-Group, even if these allergens were significantly more frequently positive in NE-Group patients than in E-Group ones. Positive patch test reactions to fragrance Mix II, dimethylaminopropylamine, and sorbitan sesquiolate were significantly more frequent in E-Group patients than in NE-Group ones. CONCLUSIONS: Eyelid dermatitis is a frequent dermatological complaint. Allergic contact dermatitis is the most frequent diagnosis commonly caused by nickel sulphate, isothiazolinones, and fragrances. The surfactants dimethylaminopropylamine and sorbitan sesquioleate are emerging causes of eyelid allergic contact dermatitis.

[Allergies in the light of global environmental changes]. / Allergien im Lichte globaler Umweltveränderungen.

BACKGROUND: The increase in allergies began worldwide with the onset of the Great Acceleration. Environmental pollution and climate change now threaten to cancel out decades of success in health research. OBJECTIVE: A summary of environmental influences is provided, which not only shows the significant increase in the prevalence of allergies worldwide but also that of noncommunicable diseases. The effects of the climate crisis on allergies and the multifactorial and interfunctional relationships with other environmental changes are described in detail. MATERIAL AND METHODS: In order to obtain an overview of the possible effects of global environmental changes on allergies, a wide range of literature was evaluated and the study results were prepared and summarized. RESULTS: A large number of allergens are influencing the human exposome on a daily basis. These allergens are triggered by environmental changes, such as air pollution in the ambient air and indoors, chemicals in everyday objects or residues in food. People are sensitized by the interaction of allergens and pollutants. CONCLUSION: The prevalence of allergies is stagnating in industrialized countries. This is probably just the calm before the storm. The accelerating effects of global warming could make pollen and air pollutants even more aggressive in the future. Urgent action is therefore needed to minimize environmental pollution and mitigate climate change.

The Diagnostic Value of Delayed-Type Reactions to Perennial Aeroallergens for Atopic Disease.

Background: Delayed-type reactions to aeroallergens have been observed, however, their clinical significance continues to be debated. Objective: We assessed the prevalence and significance of delayed-type reactions to aeroallergens in atopic patients. Methods: Retrospective study including 266 patients with history or evidence of atopic disease (atopic dermatitis [AD], allergic rhinitis, and/or allergic asthma) and tested via either the intradermal skin test (IDT) or atopy patch test for common aeroallergens, specifically house dust mites (Dermatophagoides farinae, Dermatophagoides pteronyssinus) and perennial molds (Aspergillus fumigatus, Penicillium notatum). All patients were tested via IDT with both immediate (15 minute) and delayed (2 and 4 days) readings. Delayed reading was considered positive if the IDT injection site demonstrated at least 5 mm induration 48 hours after inoculation. Results: In total, 195 (73.3%) patients demonstrated an immediate-type reaction, whereas 118 (44.4%) had a delayed-type reaction. In total, 75 (28.2%) patients experienced both immediate- and delayed-type reactions, 43 (16.2%) reacted delayed-type only, and 85.3% of delayed-type reactions to individual aeroallergens were associated with eczematous lesions predominantly in air-exposed areas. Conclusion: Delayed-type reactions to aeroallergens are prevalent and clinically significant as a component of extrinsic AD and atopic diseases. The data support delayed reading of the IDT to guide diagnosis and management in these patients.

IgE to common food allergens is associated with cardiovascular mortality in the National Health and Examination Survey and the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: In individuals without symptomatic food allergy, food-specific IgE is considered clinically irrelevant. However, recent studies have suggested that galactose-α-1,3-galactose (alpha-gal) IgE is associated with cardiovascular (CV) disease. OBJECTIVE: We sought to determine whether sensitization to common food allergens is associated with CV mortality. METHODS: The association between IgE sensitization to foods and CV mortality ascertained to 2019 was examined in the National Health and Examination Survey (NHANES) 2005-2006 and the Wake Forest site of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort; MESA enrolled adults without baseline clinical CV diseases between 2000 and 2002. Total and specific IgE was measured to cow's milk, egg, peanut, shrimp, and a panel of aeroallergens (NHANES), and to cow's milk, alpha-gal, peanut, dust mite, and timothy grass (MESA). Cox proportional hazard models were constructed, adjusting for sex, age, race/ethnicity, smoking, education, and asthma. RESULTS: A total of 4414 adults from NHANES (229 CV deaths) and 960 from MESA (56 CV deaths) were included. In NHANES, sensitization to at least 1 food was associated with higher CV mortality (hazard ratio [HR], 1.7 [95% confidence interval (CI), 1.2-2.4], P = .005). Milk sensitization was particularly associated (HR, 2.0 [95% CI, 1.1-3.8], P = .026), a finding replicated in MESA (HR, 3.8 [95% CI, 1.6-9.1], P = .003). Restricting analyses in NHANES to consumers of the relevant allergen strengthened food sensitization relationships, unmasking shrimp and peanut sensitization as additional risk factors for CV mortality. CONCLUSIONS: The finding that food sensitization is associated with increased risk of CV mortality challenges the current paradigm that sensitization without overt allergy is benign. Further research is needed to clarify mechanisms of this association.