Clinical updates in inborn errors of immunity: a focus on the noninfectious clinical manifestations.

PURPOSE OF REVIEW: In the last 5 years, several new inborn errors of immunity (IEI) have been described, especially in the areas of immune dysregulation and autoinflammation. As a result, the clinical presentation of IEIs has broadened. We review the heterogeneous presentation of IEIs and detail several of the recently described IEIs with a focus on the noninfectious manifestations commonly seen. RECENT FINDINGS: IEIs may present with early onset and/or multiple autoimmune manifestations, increased risk for malignancy, lymphoproliferation, severe atopy, autoinflammation and/or hyperinflammation. Because of this, patients can present to a wide array of providers ranging from primary care to various pediatric subspecialists. The International Union of Immunological Societies (IUIS) expert committee has created a phenotypic classification of IEIs in order to help clinicians narrow their evaluation based on the laboratory and clinical findings. SUMMARY: Both primary care pediatricians and pediatric subspecialists need to be aware of the common clinical features associated with IEI and recognize when to refer to allergy-immunology for further evaluation. Early diagnosis can lead to earlier treatment initiation and improve clinical outcomes for our patients.

Pearls for practice from the 2023 allergy immunology joint task force on practice parameters GRADE and institute of medicine based atopic dermatitis guidelines.

PURPOSE OF REVIEW: To review the updated 2023 Allergy Immunology Joint Task Force on Practice Parameters (JTFPP) GRADE and Institute of Medicine (IOM) Based Guidelines for the management of atopic dermatitis. RECENT FINDINGS: Topical corticosteroids and/or calcineurin inhibitors are recommended in individuals with atopic dermatitis refractory to moisturizer alone and may be used to maintain remission after acute flare control is achieved. Calcineurin inhibitors are a class of immunosuppressants used to effectively manage different autoimmune disorders. Bleach baths and allergen immunotherapy may be beneficial for individuals with moderate-to-severe disease, while elimination diets, azathioprine, methotrexate, mycophenolate, and systemic corticosteroids are not recommended. Dupilumab is strongly recommended for refractory atopic dermatitis. Oral Janus kinase (JAK) inhibitors carry significant risks; however, this class of medicines may be considered in cases of severe or refractory atopic dermatitis with intolerance to dupilumab. Patient preferences regarding cost, availability, feasibility, and tolerability should be integrated into all treatment plans using a shared decision-making approach. SUMMARY: The 2023 JTFPP Atopic Dermatitis Guidelines offer up-to-date guidance for the management of atopic dermatitis of varying severity in infants, children, and adults.

Serologic measurements for peanut allergy: Predicting clinical severity is complex.

Allergist-immunologists use serologic peanut allergy testing to maximize test sensitivity and specificity while minimizing cost and inconvenience. Recent advances toward this goal include a better understanding of specific IgE (sIgE) and component testing, epitope-sIgE assays, and basophil activation testing. Predicting reaction severity with serologic testing is challenged by a range of co-factors that influence reaction severity, such as the amount and form of any allergen consumed and comorbid disease. In 2020, the Allergy Immunology Joint Task Force on Practice Parameters recommended Ara h 2-sIgE as the most cost-effective diagnostic test for peanut allergy because of its superior performance, when compared with skin prick testing and serum IgE. Basophil activation testing, a functional test of allergic response not evaluated in the Joint Task Force on Practice Parameters guideline, is a promising option for both allergy diagnosis and prognosis. Similarly, epitope-sIgE testing may improve prediction of reaction thresholds, but further validation is needed. Despite advances in food allergy testing, many of these tools remain limited by cost, accessibility, and feasibility. In addition, there is a need for further research on how atopic dermatitis may be modifying serologic food allergy severity assessments. Given these limitations, allergy test selection requires a shared decision-making approach so that a patient's values and preferences regarding financial impact, inconvenience, and psychological effects are considered in the context of clinician expertise on the timing and use of optimized testing.

Leveraging learning systems to improve quality and patient safety in allergen immunotherapy.

Adverse events occur in all fields of medicine, including allergy-immunology, in which allergen immunotherapy medical errors can cause significant harm. Although difficult to experience, such errors constitute opportunities for improvement. Identifying system vulnerabilities can allow resolution of latent errors before they become active problems. We review key aspects and frameworks of the medical error response, acknowledging the fundamental responsibility of clinical teams to learn from harm. Adverse event response comprises 4 major phases: (1) event recognition and reporting, (2) investigation (for which root cause analysis can be helpful), (3) improvement (inclusive of the plan-do-study-act cycle), and (4) communication and resolution. Throughout the process, clinician wellness must be maintained. Adverse event prevention should be prioritized, and a human factors engineering approach can be useful. Quality improvement tools and approaches complement one another and together offer a meaningful avenue for error recovery and prevention.

Anaphylaxis: A 2023 practice parameter update.

This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.

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.

The Joint Task Force on Practice Parameters GRADE guidelines for the medical management of chronic rhinosinusitis with nasal polyposis.

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence). (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence). (3) In people with aspirin (nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline.

Media Influence on Anxiety, Health Utility, and Health Beliefs Early in the SARS-CoV-2 Pandemic-a Survey Study.

BACKGROUND: The psychological effects from the COVID-19 pandemic and response are poorly understood. OBJECTIVE: To understand the effects of the pandemic and response on anxiety and health utility in a nationally representative sample of US adults. DESIGN: A de-identified, cross-sectional survey was administered at the end of April 2020. Probability weights were assigned using estimates from the 2018 American Community Survey and Integrated Public Use Microdata Series Estimates. PARTICIPANTS: US adults 18-85 years of age with landline, texting-enabled cellphone, or internet access. INTERVENTION: Seven split-half survey blocks of 30 questions, assessing demographics, COVID-19-related health attitudes, and standardized measures of generalized self-efficacy, anxiety, depression, personality, and generic health utility. MAIN MEASURES: State/Trait anxiety scores, EQ-5D-3L Visual Analog Scale (VAS) score, and demographic predictors of these scores. KEY RESULTS: Among 4855 respondents, 56.7% checked COVID-19-related news several times daily, and 84.4% at least once daily. Only 65.7% desired SARS-CoV-2 vaccination for themselves, and 70.1% for their child. Mean state anxiety (S-anxiety) score was significantly higher than mean trait anxiety (T-anxiety) score (44.9, 95%CI 43.5-46.3 vs. 41.6, 95%CI 38.7-44.5; p = 0.03), with both scores significantly higher than previously published norms. In an adjusted regression model, less frequent news viewing was associated with significantly lower S-anxiety score. Mean EQ-5D-3L VAS score for the population was significantly lower vs. established US normative data (71.4 CI 67.4-75.5, std. error 2 vs. societal mean 80, std. error 0.1; p < 0.001). EQ-5D-3L VAS score was bimodal (highest with hourly and no viewing) and significantly reduced with less media viewership in an adjusted model. CONCLUSIONS: Among a nationally representative sample, there were higher S-anxiety and lower EQ-5D-3L VAS scores compared to non-pandemic normative data, indicative of a potential detrimental acute effect of the pandemic. More frequent daily media viewership was significantly associated with higher S-anxiety but also predictive of higher health utility, as measured by EQ-5D-3L VAS scores.

Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis.

Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care.

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.

Achieving the Quadruple Aim to deliver value-based allergy care in an ever-evolving health care system.

OBJECTIVE: To define the concept of value-based care in allergy, and to review challenges and opportunities in value-based health care delivery for allergists and immunologists. DATA SOURCES: Articles describing practice variation, health care financing and reimbursement, shared decision-making, cost-effective health care delivery, patient-reported outcome measures, social determinants of health, and screening. STUDY SELECTIONS: A narrative review detailing concepts and approaches to improve value-based health care in the context of the Quadruple Aim to address the patient and physician experience, cost, and population health. RESULTS: Efforts to improve cost-effective care can be informed by understanding unwarranted geographic practice variation and benchmarking best practices. Although evidence suggests that shared decision-making and addressing social determinants of health have critical roles in high-quality care, some practices such as routine laboratory screening for urticaria, premedication to prevent recurrent low- or iso-osmolar contrast reactions, extended observation of resolved anaphylaxis, food allergy screening, and penicillin allergy overdiagnosis have high costs in relation to overall societal benefit. Food allergy prevention, newborn screening for severe combined immune deficiency, and penicillin delabeling are examples of population-based opportunities in which allergists and immunologists can assist in creating health care value. Although efforts to incentivize value-based care have emerged in recent years, the degree to which process measures improve patient-important outcomes remain uncertain. Clinician wellness must be made a priority for continued effective practice. CONCLUSION: As health care systems continue to evolve, allergists and immunologists will play a key role in optimizing value by translating emerging evidence into practice and communicating novel approaches to prevent and treat allergic diseases.

Making the GRADE in anaphylaxis management: Toward recommendations integrating values, preferences, context, and shared decision making.

OBJECTIVE: To review GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methods and discuss the clinical application of conditional recommendations in clinical guidelines, specifically in the context of anaphylaxis. DATA SOURCES: Articles that described GRADE, evidence synthesis, evidence to recommendation frameworks, and shared decision making were used to discuss conditional recommendations of the 2020 Anaphylaxis GRADE guideline. STUDY SELECTIONS: A narrative review detailing concepts of GRADE and approaches to translate conditional recommendations to individualized and contextualized patient care. RESULTS: GRADE methods encourage a nuanced relationship between certainty of evidence and strength of recommendations. Strength of recommendation must incorporate key factors, including the balance between benefits and harms, patient values and preferences, and resource allocation (costs), with equity, feasibility, and acceptability also often included as considerations. GRADE guidelines provide recommendations that are characterized by directionality (for or against) and strength (strong or conditional). A conditional recommendation is tailored to context and primarily applied through a lens of patient preferences related to the likelihood of outcomes of importance and a shared decision-making approach. Although the 2020 Anaphylaxis GRADE guideline better informs the practice of anaphylaxis prevention through (1) identification and mitigation of risk factors for biphasic anaphylaxis and (2) evaluation of the use of glucocorticoid and/or antihistamine pretreatment, all GRADE recommendations, although directional, are conditional and as such should not be universally applied to every circumstance. CONCLUSION: Clinical guidelines provide an important opportunity to critically appraise evidence and translate evidence to practice. Patients, practitioners, and policy makers should appreciate the strength of recommendation and certainty of evidence and understand how this affects guideline applicability and implementation.

Preventing iatrogenic gelatin anaphylaxis.

OBJECTIVE: To assess the iatrogenic risks of gelatin allergy and identify resources for patient management. DATA SOURCES: A literature review was performed using PubMed and public databases provided by the National Library of Medicine. STUDY SELECTIONS: Reports of iatrogenic gelatin allergy associated with vaccines, hemostatic agents, intravenous colloids, medicinal capsules, and intraoperative surgical supplies. RESULTS: Gelatin ingredients may not be identified by electronic medical record safeguards, and an exhaustive listing of potential iatrogenic exposures is elusive. The National Library of Medicine AccessGUDID (https://accessgudid.nlm.nih.gov/) can be a useful resource in evaluating medical devices for gelatin content. Unexpected sources of iatrogenic gelatin exposure include hemostatic agents, vascular grafts, intravascular cannulas, bone replacement implants, and emergency resuscitation fluids. CONCLUSION: Vigilance is important within medical systems to avoid inadvertent gelatin exposure when caring for patients with gelatin allergy. Additional safeguards are needed to remove latent health care system errors that fail to prevent gelatin administration in this at-risk population.