Allergic Diseases and Mental Health.

Neuropsychiatric symptoms have long been acknowledged as a common comorbidity for individuals with allergic diseases. Proposed mechanisms for this relationship vary by disease and patient population and may include neuroinflammation and/or the consequent social implications of disease symptoms and management. We review connections between mental health and allergic rhinitis, atopic dermatitis, asthma, vocal cord dysfunction, urticaria, and food allergy. Many uncertainties remain and warrant further research, particularly with regards to how medications interact with pathophysiologic mechanisms of allergic disease in the neuroimmune axis. Proactive screening for mental health challenges, using tools such as the Patient Health Questionnaire (PHQ) and Generalized Anxiety Disorder (GAD) screening instruments among others, can aid providers in identifying patients who may need further psychiatric evaluation and support. Though convenient, symptom screening tools are limited by variable sensitivity and specificity and therefore require providers to remain vigilant for other mental health 'red flags'. Ultimately, understanding the connection between allergic disease and mental health empowers clinicians to both anticipate and serve the diverse physical and mental health needs of their patient populations.

Use of Vaccines in Patients Receiving Dupilumab, A Systematic Review and Expert Delphi Consensus Recommendation: A position paper of the American College of Allergy, Asthma and Immunology.

BACKGROUND: Dupilumab is a monoclonal antibody targeting the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Due to its immune modulatory effects, clinical trials studying dupilumab did not allow for patients to receive live vaccines during the clinical trials out of an abundance of caution, and thus package insert recommends patients being treated with dupilumab avoid live vaccines. As dupilumab is now approved down to 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians. OBJECTIVE: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients receiving dupilumab and to provide expert guidance on the use of vaccines in patients receiving dupilumab. METHODS: A systematic review of the literature was performed, and an expert Delphi Panel was conducted. RESULTS: The available literature on patients who received vaccinations while on dupilumab overall suggests that live vaccines are safe and the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed on the use of vaccines in patients on dupilumab was likely safe and effective. CONCLUSION: Vaccines (including live vaccines) can be administered to patients on dupilumab in a shared decision-making capacity.

Health Promotion of Early and Sustained Allergenic Food Introduction for the Prevention of Food Allergy.

Observational studies and landmark randomized control trials support early and sustained allergenic food introduction in infancy as an effective preventive strategy against food allergy development. Despite a consensus regarding the intended goals of early and sustained allergenic food introduction, there have been myriad policy recommendations among health authorities in how to achieve both individual and population-level health outcomes for food allergy prevention. This clinical management review provides an overview on the data that informs early and sustained allergenic food introduction strategies, suggestions on how to advise allergenic food introduction, principles of prevention programs as they relate to food allergy prevention, and health promotion and systems-level challenges that impede achievement of food allergy prevention goals.

Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent.

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. RESULTS: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. CONCLUSION: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.

Burden of disease of respiratory syncytial virus in infants, young children and pregnant women and people.

Background: Passive immunization products for infants and pregnant women and people have sparked interest in understanding Canada's respiratory syncytial virus (RSV) burden. This rapid review examines RSV burden of disease in infants, young children and pregnant women and people. Methods: Electronic databases were searched to identify studies and systematic reviews reporting data on outpatient visits, hospitalizations, intensive care unit admissions, deaths and preterm labour associated with RSV. We also contacted Canadian respiratory virus surveillance experts for additional data. Results: Overall, 17 studies on infants and young children and 10 studies on pregnant women and people were included, in addition to primary surveillance data from one Canadian territory (Yukon). There were higher rates of medical utilization for infants than older children. Hospitalization rates were highest in infants under six months (more than 1% annually), with 5% needing intensive care unit admission, but mortality was low. Severe outcomes often occurred in healthy full-term infants and burden was higher than influenza. Respiratory syncytial virus attack rate was 10%-13% among pregnant women and people. Only one study found a higher hospitalization rate in pregnant women and people compared to non-pregnant women and people. Limited evidence was found on intensive care unit admission, death and preterm birth for pregnant women and people. Conclusion: While risk of severe outcomes is larger in high-risk infants and children, healthcare burden is greatest in healthy term infants. The RSV severity for pregnant women and people appears to be similar to that for non-pregnant women and people.

Infantile atopic dermatitis - increasing severity predicts negative impacts on maternal and infant sleep: a mixed methods study.

BACKGROUND: While the impacts of atopic dermatitis (AD) on maternal and child sleep outcomes have been previously explored, less is known about the associations between infantile AD and sleep quality and quantity. OBJECTIVE: To describe the perceived causes of AD-associated maternal sleep disturbances and the association between AD severity and infant sleep outcomes. METHODS: Mothers with infants aged < 19 months old with a diagnosis of AD were recruited from social media and medical clinics in Winnipeg, Canada between October 2021 and May 2022. Infant AD severity was classified using maternal-reported data on the Patient-Oriented Scoring Atopic Dermatitis tool (PO-SCORAD). Quantitative data were collected via a series of questionnaires with a subset of mothers subsequently completing semi-structured interviews. Quantitative and qualitative data were integrated in the discussion. RESULTS: Mothers of infants with moderate/severe AD (6/12) were more likely to report their infant suffering from a higher degree of sleeplessness (i.e., ≥ 5 on a scale of 0-10) over the past 48 h compared to mothers of infants with mild AD (0/18). This was supported by qualitative findings where mothers described how their infant's sleep quality and quantity worsened with AD severity. Additionally, 7/32 mothers reported that their child's AD, regardless of severity, disturbed their sleep. Maternal sleep loss was most commonly attributed to infant itching (6/7), followed by worry (4/7). CONCLUSION: Infantile AD severity was associated with worse sleep outcomes for both mothers and infants. We propose that maternal and infantile sleep quality and quantity can be improved by reducing AD severity through adherence to topical treatments.

Patient-Centered Practice Guidelines: GRADEing Evidence to Incorporate Certainty, Balance Between Benefits and Harms, Equity, Feasibility, and Cost-Effectiveness.

The practice of medicine in recent years has emphasized the use of evidence-based clinical guidelines to help inform treatment decisions. Since its development in 2004, the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach has offered a systematic process for reviewing and summarizing the certainty of evidence found in the medical literature regarding various treatment options. To develop truly patient-centered care guidelines, this appraisal of the certainty of evidence must be combined with an understanding of the balance between benefits and harms, patient preferences, equity, feasibility, cost-effectiveness, and policy implications. This review examines each of these domains in detail, exploring the process and benefits of developing relevant, patient-focused guidelines directly applicable to the practice of modern medicine.

Clinical characteristics and management of pediatric egg-induced anaphylaxis: A cross-sectional study.

BACKGROUND: Egg is the third most common food allergy in children; however, data on pediatric egg-induced anaphylaxis are sparse. OBJECTIVE: To describe the clinical characteristics, management, and outcomes of pediatric egg-induced anaphylaxis. METHODS: Children presenting with anaphylaxis were recruited from 13 emergency departments as part of the Cross-Canada Anaphylaxis Registry, from which data on anaphylaxis triggered by egg were extracted. Multivariate logistic regression was used to determine factors associated with prehospital epinephrine autoinjector (EAI) use and to compare anaphylaxis triggered by egg with other triggers of food-induced anaphylaxis (FIA). RESULTS: We recruited 302 children with egg-induced anaphylaxis. The mean age was 2.6 years (SD = 3.6), and 55.3% were male. Only 39.4% had previously been diagnosed with an egg allergy. Prehospital EAI use was 32.1%, but this was not significantly lower than in other triggers of FIA (P = .26). Only 1.4% of patients required hospital admission. Relative to other triggers of FIA, patients with egg-induced anaphylaxis were significantly younger (P < .001) and exhibited more vomiting (P = .0053) and less throat tightness (P = .0015) and angioedema (P < .001). CONCLUSION: To the best of our knowledge, this is the largest published cohort of pediatric egg-induced anaphylaxis. In this cohort, prehospital EAI use was very low. In addition, we identified certain symptoms that distinguish egg-induced from other triggers of FIA. Taken together, high suspicion is crucial in identifying egg-induced anaphylaxis, given the younger patient demographic and frequent lack of FIA history.

Food allergies on a college campus.

There are limited data on food allergies among college students. In this article, we review the most current available studies. These self-reported surveys and qualitative interviews reported overall poor avoidance of known allergens and low rates of carrying self-injectable epinephrine among students with food allergy. College students may exhibit risk-taking food behaviors due to a number of factors, including age-appropriate risk-taking predilection, strong social influences, and lack of experience in self-advocacy. Having to disclose an otherwise invisible condition repeatedly in a new environment may also lead to "disclosure fatigue," creating an additional barrier to self-advocacy. Common themes in the narrative include hypervigilance, stigma management, and concern about others' misunderstanding of food allergy. Although there is a paucity of data in this area, it is likely that having greater support at the institution level, along with support from peers and faculty, may help improve awareness, self-injectable epinephrine carriage, and allergen avoidance. This review also discusses strategies for preparedness at school, including specific steps to maximize safety.

Addressing common questions on food oral immunotherapy: a practical guide for paediatricians.

Food allergy has been increasing in prevalence in most westernised countries and poses a significant burden to patients and families; dietary and social limitations as well as psychosocial and economic burden affect daily activities, resulting in decreased quality of life. Food oral immunotherapy (food-OIT) has emerged as an active form of treatment, with multiple benefits such as increasing the threshold of reactivity to the allergenic food, decreasing reaction severity on accidental exposures, expanding dietary choices, reducing anxiety and generally improving quality of life. Risks associated with food immunotherapy mostly consist of allergic reactions during therapy. While the therapy is generally considered both safe and effective, patients and families must be informed of the aforementioned risks, understand them, and be willing to accept and hedge these risks as being worthwhile and outweighed by the anticipated benefits through a process of shared decision-making. Food-OIT is a good example of a preference-sensitive care paradigm, given candidates for this therapy must consider multiple trade-offs for what is considered an optional therapy for food allergy compared with avoidance. Additionally, clinicians who discuss OIT should remain increasingly aware of the growing impact of social media on medical decision-making and be prepared to counter misconceptions by providing clear evidence-based information during in-person encounters, on their website, and through printed information that families can take home and review.

Milk-induced anaphylaxis among children presenting to Canadian emergency departments.

BACKGROUND: Cow's milk is one of the most common and burdensome allergens in pediatrics, and it can induce severe anaphylactic reactions in children. However, data on cow's milk-induced anaphylaxis are sparse. OBJECTIVE: To describe the epidemiology of pediatric cow's milk-induced anaphylaxis and to determine risk factors for repeat emergency department (ED) epinephrine administration. METHODS: Between April 2011 and May 2023, data were collected on children with anaphylaxis presenting to 10 Canadian EDs. A standardized form documenting symptoms, triggers, treatment, and outcome was used. Multivariate logistic regression was used. RESULTS: Of 3118 anaphylactic reactions, 319 milk-induced anaphylaxis cases were identified (10%). In the prehospital setting, 54% of patients with milk-induced anaphylaxis received intramuscular epinephrine. In those with milk-induced anaphylaxis, receiving epinephrine before presenting to the ED was associated with a reduced risk of requiring 2 or more epinephrine doses in the ED (adjusted odds ratio, 0.95 [95% CI, 0.90-0.99]). Children younger than 5 years of age were more likely to experience a mild reaction compared with that in older children, who experienced a moderate reaction more often (P < .0001). Compared with other forms of food-induced anaphylaxis, children presenting with milk-induced anaphylaxis were younger; a greater proportion experienced wheezing and vomiting, and less experienced angioedema. CONCLUSION: Prehospital epinephrine in pediatric milk-induced anaphylaxis is underused; however, it may decrease risk of requiring 2 ED epinephrine doses. Milk-induced anaphylaxis in children younger than 5 years of age may be less severe than in older children. Wheezing and vomiting are more prevalent in milk-induced anaphylaxis compared with that of other foods.

Cost-effectiveness of budesonide-formoterol vs inhaled epinephrine in US adults with mild asthma.

BACKGROUND: The management of mild asthma has lacked an over-the-counter (OTC) option aside from inhaled epinephrine, which is available in the United States. However, inhaled epinephrine use without an inhaled corticosteroid may increase the risk of asthma death. OBJECTIVE: To compare the cost-effectiveness of OTC as-needed budesonide-formoterol as a plausible alternative to inhaled epinephrine. METHODS: We developed a probabilistic Markov model to compare OTC as-needed budesonide-formoterol inhaler use vs inhaled epinephrine use in adults with mild asthma from a US societal perspective over a lifetime horizon, with a 3% annual discount rate (2022 US dollars). Inputs were derived from the SYmbicort Given as-needed in Mild Asthma (SYGMA) trials, published literature, and commercial costs. Outcomes were quality-adjusted life-years (QALY), costs, incremental net monetary benefit (INMB), severe asthma exacerbations, well-controlled asthma days, and asthma-related deaths. Microsimulation was used to evaluate underinsured Americans living with mild asthma (n = 5,250,000). RESULTS: Inhaled epinephrine was dominated (with lower QALYs gains at a higher cost) by both as-needed budesonide-formoterol (INMB, $15,541 at a willingness-to-pay of $100,000 per QALY) and the no-OTC inhaler option (INMB, $1023). Adults using as-needed budesonide-formoterol had 145 more well-controlled asthma days, 2.79 fewer severe exacerbations, and an absolute risk reduction of 0.23% for asthma-related death compared with inhaled epinephrine over a patient lifetime. As-needed budesonide-formoterol remained dominant in all sensitivity and scenario analyses, with a 100% probability of being cost-effective compared with inhaled epinephrine in probabilistic sensitivity analysis. CONCLUSION: If made available, OTC as-needed budesonide-formoterol for treating mild asthma in underinsured adults without HCP management improves asthma outcomes, prevents fatalities, and is cost-saving.

Housing Insecurity and Asthma Outcomes.

Asthma is a chronic respiratory disease with widespread prevalence that affects children, adolescents, and adults. Asthma morbidity and mortality can be exacerbated in the setting of housing insecurity. In this Grand Rounds Review article, we present a case and discuss the implications that housing insecurity has on asthma outcomes in the United States. We then highlight ways in which providers can advocate for patients with asthma and housing insecurity.

Assessing Pediatric Cephalosporin Allergic Reactions Through Direct Graded Oral Challenges.

BACKGROUND: Cephalosporins, ß-lactam antibiotics, commonly cause allergic reactions. OBJECTIVE: To assess the clinical characteristics and management of pediatric patients with suspected cephalosporin allergy using direct graded oral challenges (GOCs). METHODS: Children referred for suspected cephalosporin allergy at 4 Canadian clinics were recruited over 10 years. Data on demographics, clinical reaction characteristics, and management were collected through a questionnaire. Patients underwent a direct GOC (initially 10% of the treatment dose, then 90% after 20 min), and reactions were monitored 1 week postchallenge. Families were contacted annually for up to 5 years to detect subsequent antibiotic reactions. Logistic regression analysis identified factors associated with positive GOC reactions. RESULTS: Among the 136 patients reporting cephalosporin allergy, 75 (55.1%) were males with a median age of 3.9 years (interquartile range 2.3-8.7). Cefprozil represented the most common cephalosporin linked to the index reaction (67.6% of cases). Of the 136 direct GOCs, 5.1% had an immediate and 4.4% a nonimmediate reaction, respectively. Positive GOCs conducted in children with a history of skin-limited nonsevere rashes were classified as mild, benign skin rashes. Positive GOCs were more likely in children with food allergies (adjusted odds ratio 1.14; 95% confidence interval [95% CI] 1.00-1.29). CONCLUSIONS: Direct GOCs are safe and effective for diagnosing pediatric cases that report nonvesicular skin-limited symptoms while being treated with cephalosporins.

Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations.

BACKGROUND: Guidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology. OBJECTIVE: To produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD. METHODS: A multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group supported guideline development by performing systematic evidence reviews, facilitating guideline processes, and holding focus groups with patient and family partners. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed rating the certainty of evidence and strength of recommendations. Evidence-to-decision frameworks, subjected to public comment, translated evidence to recommendations using trustworthy guideline principles. RESULTS: The panel agreed on 25 recommendations to gain and maintain control of AD for patients with mild, moderate, and severe AD. The eAppendix provides practical information and implementation considerations in 1-2 page patient-friendly handouts. CONCLUSION: These evidence-based recommendations address optimal use of (1) topical treatments (barrier moisturization devices, corticosteroids, calcineurin inhibitors, PDE4 inhibitors [crisaborole], topical JAK inhibitors, occlusive [wet wrap] therapy, adjunctive antimicrobials, application frequency, maintenance therapy), (2) dilute bleach baths, (3) dietary avoidance/elimination, (4) allergen immunotherapy, and (5) systemic treatments (biologics/monoclonal antibodies, small molecule immunosuppressants [cyclosporine, methotrexate, azathioprine, mycophenolate, JAK inhibitors], and systemic corticosteroids) and UV phototherapy (light therapy).