Tablet allergen immunotherapy: the anaphylaxis issue.

For the first time 15 years ago, tablet allergen immunotherapy (T-AIT) formulations were approved by regulatory agencies for treating allergic rhinitis caused by grass pollen in adults and children aged >5 years. Extensive evidences existed about effectiveness and safety of AIT. However, the safety profile is particularly compelling in children. Generally, T-AIT causes local reactions, mostly in the oral cavity, that are usually mild-to-moderate and often self-resolving. However, systemic allergic reactions are also observed with T-AIT, anaphylaxis representing the most fearsome adverse event, considering that it occurs in subjects treated for allergic rhinitis. Therefore, we conducted a literature search of patients reporting anaphylaxis because of T-AIT. Nine cases of anaphylactic reactions were reported in literature. Notably, no death was reported using T-AIT. This outcome was very important as it underscored the substantial safety of T-AIT. However, T-AIT deserves careful attention, mainly in the pediatric population. In this regard, after the first report of anaphylactic reaction at the first administration of T-AIT, manufacturers recommended that the first dose should be administered in a medical facility in the presence of staff with experience in managing anaphylaxis and the patient should be observed for at least 30 min. Interestingly, reported anaphylactic reactions were due to grass pollen extracts, with no report concerning other allergen extracts. However, it is relevant to note that anaphylactic reactions because of T-AIT are not reported in recent years.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.).

Contact allergens responsible for eyelid dermatitis in adults.

Allergic contact dermatitis has been established as the most frequent cause of eyelid dermatitis, but it is often misdiagnosed. The purpose of this study was to evaluate the characteristics of patients with eyelid dermatitis who were referred for patch testing. The patients were divided into three subgroups in this retrospective study: patients with only eyelid involvement, patients with involvement of eyelids and other areas, and patients without eyelid involvement. Data was collected on diagnoses, medical history, personal care products and make-up use, occupational dermatitis, and positive allergens. An independent t-test, one-way ANOVA, and chi-squared test were used to analyze the data. A total of 427 patients who referred for patch tests were included in the study. Of these, 139 patients had eyelid dermatitis. Allergic contact dermatitis (ACD) was the most common diagnosis in all three groups referred for patch tests. Use of shaving cream and hair conditioner was significantly higher in patients with only eyelid involvement and nickel sulfate was the most common allergen among them. Patch testing is the gold standard tool in the evaluation of eyelid contact dermatitis, and it is a necessity in the treatment of eyelid dermatitis, for the accurate identification of responsible allergens.

Trends in contact sensitization, results, and implications from a contact dermatitis clinic in Israel.

BACKGROUND: The baseline series includes common allergens, evolves over time, and differs by location. Our study aims to characterize allergen sensitization trends among the Israeli population during the last two decades, compare our results to American and European registries, as well as to highlight significant allergens in additional series outside the European baseline series (OEBS). METHODS: We analysed patch test results of 2086 patients from a designated contact dermatitis clinic in Tel Aviv between 2019 and 2022, compared them to European and North American registries and to 2156 patch test results conducted in Israel two decades ago. RESULTS: 38.6% of patients had at least one positive reaction to an allergen in the European baseline series (EBS), nickel sulphate (14.6%), fragrance mix I (4.6%), and Methylchloroisothiazolinone methylisothiazolinone (MCI/MI; 3.7%) were the most common among them. N-Isopropyl N-Phenyl-4-Phenylenediamine (NIPPD; 0%), Propolis (0.1%), Sesquiterpene lactone mix (0.1%), and Budesonide (0.1%) elicited a sensitization frequency significantly lower than the proposed threshold for baseline inclusion. Chi-square test revealed a statistically significant decrease (p < 0.05) in the sensitization frequency of fragrance mix I, Formaldehyde, Potassium dichromate, Neomycin sulphate, Myroxylon pereirae, Sesquiterpene lactone, and NIPPD during the last two decades. The overall sensitization frequency to the majority of allergens was lower in our cohort in comparison to the North American and European registries. CONCLUSIONS: MCI/MI and 2-hydroxyethyl methacrylate-2 (HEMA) are common, relevant allergens, with high SPIN (significance and prevalence index number) and should be better regulated by the authorities. While among the EBS, NIPPD, Propolis, Sesquiterpene lactone, and Budesonide usually do not elicit a positive reaction and therefore should be reconsidered in baseline series, among the OEBS, Chloramphenicol, Quaternium 15, Propyl gallate, and Amerchol L101 have elicited high SPIN values and should be vigilantly examined in the suitable clinical scenario. Significantly lower sensitization frequency to propolis raises the possibility of a protective effect due to early oral exposure among the Israeli population.

Clinical relevance of doubtful reactions in patch testing: A single-centre retrospective study.

BACKGROUND: Doubtful reactions in patch testing are infrequently reported in the literature; however, recent reports have suggested they be assessed with the same scrutiny as stronger reactions. OBJECTIVE: Assess the clinical relevance of doubtful reactions in patch testing. METHODS: Retrospective study of 1514 patients comprehensively patch tested via the NACDG standard series and additional allergens based on history. The clinical relevance of each reaction was graded based on the NACDG scale: definite, probable, possible, past, unknown and irritant. Reactions were considered 'unique' if an additional mild-to-strong reaction to the same chemical at a different concentration was not observed. RESULTS: 68.9% (1043) of patients demonstrated at least 1 doubtful reaction. Of 4453 total doubtful reactions, 92.2% (4106) were unique. Only 3.3% (137) and 12.2% (500) of these were determined to be of definite or probable clinical relevance respectively. 'Fragrance' was the most common allergen family present among the unique definite doubtful reactions (37). However, 24 (64.9%) of these also had a stronger reaction to another fragrance. Cocamidopropyl betaine was the second most frequent allergen demonstrating definite doubtful reactions (27) and unique in 85.2% (23) of cases. Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) was most prevalent (36) but less frequently unique (58.3%, 21). CONCLUSIONS: Doubtful reactions may not be as impactful to clinical decision making as theorised in the literature. Few demonstrate definite clinical significance, and many have related stronger reactions that capture them for clinical purposes. Identification of doubtful reactions to cocamidopropyl betaine and MCI/MI may be of greatest significance as they most frequently were not supported by stronger reactions.