A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology.

BACKGROUND: Dupilumab is a monoclonal antibody that targets 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. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 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 who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab. METHODS: A systematic review of the literature was performed, and an expert Delphi Panel was assembled. RESULTS: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective. CONCLUSION: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.

Rhinitis 2020: A practice parameter update.

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR.

Deriving individual threshold doses from clinical food challenge data for population risk assessment of food allergens.

BACKGROUND: Food allergies are a significant public health issue, and the only effective management option currently available is strict avoidance of all foods containing the allergen. In view of the practical impossibility of limiting risks to zero, quantitative allergen risk assessment and management strategies are needed. OBJECTIVE: We sought to develop appropriate methods for informing population-based risk assessments and risk management programs to benefit all stakeholders but particularly patients with food allergy. METHODS: Individual thresholds for food allergens (maximum tolerable doses and minimum eliciting doses) can ideally be established through double-blind, placebo-controlled food challenges. If double-blind, placebo-controlled food challenge data are not available, data from widely used open food challenges using predefined objective criteria can also provide useful data regarding minimum eliciting doses. For more than 20 years, the Netherlands Organisation for Applied Scientific Research and the Food Allergy Research and Resource Program at the University of Nebraska-Lincoln have been collecting individual maximum tolerable doses and minimum eliciting doses that produce objective symptoms from published and unpublished clinical data to better refine knowledge regarding the sensitivity of the population to food allergens. RESULTS: In this article we provide in-depth insights into the methodology applied by the Netherlands Organisation for Applied Scientific Research and Food Allergy Research and Resource Program to derive individual maximum tolerable doses and minimum eliciting doses for objective symptoms from clinical food challenge data. More than 90 examples for determining individual allergic thresholds are presented. CONCLUSION: With the methodology presented in this article, we aim to stimulate harmonization and transparency in quantitative food allergen risk assessment and risk management programs, encouraging their wider adoption.

Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Primary Prevention of Food Allergy.

Food allergy is estimated to affect approximately 8% of children in the USA. This is a disease without any known treatment or cure and, for some, a disease that can be quite severe, even life-threatening. While recent advances in potential treatment have made remarkable strides, with two food-targeted immunotherapy products now in phase III trials, perhaps the biggest gains in the field have come in the advent of potential preventative strategies to avoid the development of food allergy in high-risk individuals. There have been multiple, randomized, controlled trials (RCTs) performed in the past 5 years that have demonstrated significant risk reduction from early allergen introduction. These include two trials for early peanut introduction and five trials for early egg introduction in the first year of life. The results indicate that primary prevention of food allergy through early allergen introduction may represent a strategy that could potentially avert tens of thousands of children from becoming food allergic. In support of the data for peanut, the National Institute of Allergy and Infectious Diseases recently sponsored an addendum to the 2010 food allergy guidelines, specifically recommending peanut be introduced in both high- and standard-risk infants to reduce the risk of developing peanut allergy. To date, no formal recommendations have been made for egg, however. This review will focus on the latest evidence supporting early introduction as a strategy to prevent food allergy, as well as on practical aspects for its successful implementation.

Addendum Guidelines for the Prevention of Peanut Allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert Panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides three separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Addendum Guidelines for the Prevention of Peanut Allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert Panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Immune Abnormalities in Fontan Protein-Losing Enteropathy: A Case-Control Study.

OBJECTIVE: To comprehensively characterize the immunologic characteristics of patients with protein-losing enteropathy (PLE) post-Fontan and compare them with patients without PLE post-Fontan. STUDY DESIGN: Patients with PLE post-Fontan and age-matched controls post-Fontan were prospectively studied with laboratory markers of immune function. Infectious history was obtained by interview and chart review. The groups' demographics, cardiac history, immune characteristics, and infection history were compared using appropriate 2-group statistics. RESULTS: A total of 16 patients enrolled (8 patients with PLE and 8 controls). All patients with PLE had lymphopenia compared with 25% of controls (P = .01). All patients with PLE had markedly depressed CD4 T cell counts (median 58 cells/µL) compared with controls (median 450 cells/µL, P = .0002); CD4% was also low in the PLE group (12.3%) and normal in control (36.9%, P = .004). Both groups had mildly depressed CD8 T cells and normal to slightly elevated natural killer and B-cell subsets. A majority of patients with PLE (62.5%) had negative titers to measles, mumps, and rubella vaccination, compared with no control Fontan with a negative titer (P = .03). Despite profoundly low CD4 counts, the frequency of infection was not different between groups with no reported opportunistic infections. CONCLUSIONS: Patients with Fontan-associated PLE have extensive quantitative immune abnormalities, particularly CD4 deficiency. These immune abnormalities are similar to those found in non-Fontan patients with PLE caused by intestinal lymphangiectasia.

Treatment of allergic reactions and quality of life among caregivers of food-allergic children.

BACKGROUND: Caregivers of food-allergic individuals (FAIs) have decreased quality of life (QoL). The effects of epinephrine administration on QoL are poorly understood. OBJECTIVE: To investigate the relation between QoL and epinephrine use. METHODS: A de-identified 50-question online survey was administered to caregivers of FAIs across the United States through Web site, email, and social media networks of 2 national food allergy advocacy groups. QoL was assessed using the Food Allergy Quality of Life-Parental Burden questionnaire. The effect of prior epinephrine administration on QoL was analyzed using linear regression. RESULTS: Of 3,541 respondents, 35.6% reported their FAIs received epinephrine. Mean Food Allergy Quality of Life-Parental Burden scores were higher (worse QoL) in those reporting FAIs receiving epinephrine (3.07 vs 2.84, P < .001), anaphylaxis (3.01 vs 2.75, P < .001), multiple food allergies (3.16 vs 2.67, P < .001), and multiple food allergies and epinephrine use (3.24 vs 2.57, P < .001) vs those who did not. In a regression model, reported epinephrine use; anaphylaxis; multiple FAIs; multiple food allergies; and egg or milk, wheat or soy, or seafood allergy (vs peanut or tree nut allergy) were significantly associated with an increased (worse) QoL score. Caregiver college education and increasing FAI age were associated with a decreased QoL score (improved QoL). An interaction was noted between reported epinephrine use and anaphylaxis and was associated with a decreased QoL score. CONCLUSION: The effect of epinephrine use on caregiver QoL is conditional and depends on reaction severity. Having multiple FAIs and FAIs with multiple food allergies was associated with worsening QoL. Further studies are needed to better understand the effects of treating an allergic reaction on caregiver QoL.

A 31-year-old pregnant woman with angioedema.

Angioedema is swelling of the deep layers of the dermis and subcutaneous tissue due to an increase in vascular permeability. Angioedema sometimes occurs concomitantly with urticaria and represents an allergic disease. In other cases, angioedema is not associated with an allergic condition. We present the case of a 31-year-old woman with new-onset angioedema in the setting of her first pregnancy. After detailed history, physical examination, and laboratory evaluation, a cause for her angioedema was found that had not been considered previously and had significant implications for future management, particularly in light of her current pregnancy. Because allergists are commonly called on to evaluate and treat angioedema, we should be aware of the many disease processes that can present with this symptom and be well-versed in the workup of new-onset angioedema.

Systemic reactions to inhalant immunotherapy using 1:1 target dosing.

BACKGROUND: The 2007 immunotherapy practice parameters advocate maintenance dosing at 1:1 (1:20 maintenance concentrate). There is limited literature exploring the effect of 1:1 dosing on the rate of systemic reactions to subcutaneous immunotherapy (SRITs). OBJECTIVE: To investigate the effects of 1:1 dosing on SRITs in a large, academic practice. METHODS: We conducted a retrospective cohort study of all nonvenom and noncluster SRITs that occurred between 2005 and 2011. SRITs that occurred from August 2008 through December 2011, postparameter dosing (post-PD) was initiated, were compared to SRITs that occurred from January 2005 to July 2008 with preparameter dosing (pre-PD) using 1:50 as a maintenance concentrate. RESULTS: A total of 269 SRITs occurred in a 7-year period. Significantly more post-PD SRITs (131 of 38,548 injections) occurred than pre-PD SRITs (132 of 52,833 injections) (0.34% vs 0.25%, P = .01). However, when excluding 44 SRITs that occurred in established pre-PD patients transitioned to post-PD, there was no significant difference in SRIT rate (0.25% vs 0.22%), World Allergy Organization (WAO) grade, or SRIT time to onset. Nonred (non-1:1) vials accounted for a significantly larger proportion of all post-PD SRITs compared with all pre-PD SRITs (50.7% vs 31.1%, adjusted P = .009). Prior SRITs were reported less frequently among persons with post-PD SRITs (29.2% vs 70.8%, adjusted P = .009). In an adjusted logistic regression model, male sex (odds ratio, 7.9; 95% CI, 2.4-26) and longer time to reaction onset (odds ratio, 0.94; 95% CI, 0.89-0.99) were associated with higher WAO severity grade reactions. CONCLUSION: Pre-PD vs post-PD SRIT rates were not significantly different, adjusting for patients transitioned from established pre-PD to post-PD. This finding suggests that post-PD is as safe as pre-PD. Male sex and faster time to reaction onset were associated with higher WAO grade reactions.

Factors associated with reported food allergy tolerance among US children.

BACKGROUND: Limited studies exist on predictors of food allergy tolerance. OBJECTIVE: To describe factors associated with tolerance to 9 common food allergens based on caregiver report in a nationally representative survey. METHODS: Data from children with current and outgrown food allergies were identified for analysis from a randomized, cross-sectional survey administered in US households with children from June 2009 through February 2010. Allergies were analyzed based on type of allergy, age at which allergies were outgrown, and reaction history. Adjusted models were formulated to examine the association of child and food allergy characteristics with odds of reporting an allergy as being outgrown. RESULTS: Of 40,104 children surveyed, 1,245 cases of outgrown food allergy were identified. The frequency of tolerance in children with food allergy was 26.6% at a mean age of 5.4 years. Children with milk (41.1%), egg (40.2%), or soy (35.7%) allergy had significantly higher frequencies of tolerance, whereas children with shellfish (13.0%), tree nut (14.3%), and peanut (15.6%) allergies had significantly lower frequencies (P < .05). Factors significantly associated with a report of outgrowing an allergy included a mild to moderate reaction history, being allergic to only 1 food, eczema as the sole allergy symptom, and white compared with black race (P < .05). Probability of tolerance also was significantly higher at younger ages of first reaction and decreased for first reactions occurring later in life, irrespective of allergen, severity, or presentation (P < .05). CONCLUSION: Multiple factors were associated with a report of outgrowing an allergy. Understanding factors associated with outgrowing an allergy can improve disease management and counseling.

Oral and sublingual peanut immunotherapy is not ready for general use.

Food oral immunotherapy (OIT) is an investigational peanut allergy treatment aimed to achieve specific oral tolerance induction. Allergic children are given titrated oral (or sublingual) doses of their allergen on a daily basis, unlike in subcutaneous immunotherapy (SCIT). OIT is theorized to cause a shift from a Th2 to a Th1 regulatory environment, reflected by increases in food-specific IgG4/IgE, and the production of FoxP3. Peanut OIT holds special promise because peanut allergy has an unfavorable natural history and is rarely outgrown. A high percentage of the participants experience symptoms during peanut OIT, including anaphylaxis, warranting epinephrine and/or discontinuation of therapy. This is a concerning fact given that the studies have mostly targeted only older children, with less historical reactivity for enrollment. The handful of peanut OIT studies have shown that some participants can be desensitized to peanut, but none have shown that long-term tolerance can be reestablished. Factors predictive of which patients are most likely to succeed and become desensitized through OIT are unknown. Some private practices have begun offering peanut OIT as a therapy. Such practice is potentially dangerous given the safety and efficacy of OIT in randomized controlled clinical trials is still not well established. Therefore, until further investigation emerges that conclusively demonstrates OIT is safe, intermediate and long-term outcomes are better established, the number of participants that experience symptoms is reduced, and proof of concept established in patients of all ages, (irrespective of past reaction severity), OIT is not ready for use in the general allergy practice.

Recurrent perioperative anaphylaxis in a 54-year-old man.

Reports suggest that perioperative anaphylaxis in patients undergoing general anesthesia range from 1 in 5000 to 1 in 20,000 with mortality rates as high as 9%. Because of the variety of medications that are used for general anesthesia and the rapid succession in which they are administered, it is often difficult to determine the etiology of a severe allergic episode in this setting. Antibiotics and anesthetics are notorious for precipitating allergic reactions and are often implicated. Other perioperative exposures and patient risk factors must also be considered. In this article, we describe the case of a patient who exhibited recurrent anaphylaxis episodes while trying to undergo a vital cardiac surgery.