What's new in allergy and immunology

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

ASTHMA AND COPD

Approval of albuterol-budesonide for asthma in the United States (January 2023)

International guidelines have increasingly embraced concomitant use of as-needed inhaled glucocorticoid and a short-acting beta-agonist (SABA) as a therapeutic option for asthma, but combination inhalers have limited availability. A combination inhaler (albuterol-budesonide) has now been approved by the US Food and Drug Administration (FDA) for as-needed therapy in patients ≥18 years with asthma [1]. Although use of as-needed albuterol-budesonide is a reasonable approach for patients with mild persistent asthma or for those with intermittent asthma at high risk for serious exacerbations, it may not be widely available until early 2024. (See "Treatment of intermittent and mild persistent asthma in adolescents and adults", section on 'Combination inhaled glucocorticoid and short-acting beta-agonist as needed'.)

Persistence of asthma control after stopping omalizumab therapy (November 2022)

Omalizumab, an anti-IgE monoclonal antibody, is an effective add-on therapy for uncontrolled moderate-to-severe asthma but the optimal duration of therapy and the persistence of benefit after discontinuation are unclear. In an analysis of the French national healthcare database that included over 19,000 patients with asthma (over 2000 children) who received omalizumab for a median duration of approximately 4.5 years, rates of asthma hospitalizations were reduced by 75 percent and the need for oral corticosteroids by 30 percent after two years of treatment [2]. Among patients with asthma control during treatment, symptoms remained controlled in a significant percentage one, two, and three years after discontinuation (76, 44, and 33 percent in children and 70, 39, and 24 percent in adults, respectively). These findings indicate a lasting benefit after discontinuation of omalizumab in patients with controlled asthma and provide a basis for anticipatory guidance for those who discontinue treatment. (See "Anti-IgE therapy", section on 'Observations post-treatment'.)

Insulin resistance in severe asthma (November 2022)

Several studies have identified an increased prevalence of asthma and difficult-to-control asthma among obese individuals, although the exact reason for the association is not known. A recent study of patients with severe asthma included extensive metabolic phenotyping as well as long-term follow-up [3]. Patients with insulin resistance demonstrated more rapid decline in lung function and increased resistance to beta-agonist and oral glucocorticoid therapies compared with patients having normal insulin sensitivity. Whether targeting insulin resistance can impact these severe asthma features requires further investigation. (See "Severe asthma phenotypes", section on 'Asthma associated with obesity'.)

COVID-19 and asthma control in children (November 2022)

Initial data suggested that COVID-19 did not increase asthma morbidity in children, contrary to that expected for a viral respiratory infection. However, asthma control may have improved during the early waves of the pandemic due to an overall decrease in viral respiratory infections. A comparison of nearly 62,000 children with asthma from 108 health care systems in the United States from March 2020 through February 2021 found that a SARS CoV-2 polymerase chain reaction-positive test was associated with increased rates of emergency department visits, hospitalizations, and use of short-acting beta agonist and oral glucocorticoids in the six months following the positive test compared with those who tested negative [4]. This reinforces the importance of patients continuing medications necessary to maintain optimal asthma control so as to better weather COVID-19 and other viral respiratory infections. (See "Asthma in children younger than 12 years: Management of persistent asthma with controller therapies", section on 'Advice related to Covid-19'.)

Mepolizumab for childhood asthma in urban under-served populations (October 2022)

Among adults and adolescents with severe eosinophilic asthma, treatment with mepolizumab (a monoclonal antibody to interleukin-5) reduces exacerbation rates; however, data in children are limited. Mepolizumab was compared with placebo in a trial of children and adolescents recruited from low-income, primarily urban environments in the United States who presented with poorly controlled asthma and elevated blood eosinophils. Mepolizumab reduced asthma exacerbation rates compared with placebo in this population (1.0 versus 1.3 per year, relative risk 0.73), but the improvement was less than that observed in prior trials of adults and adolescents (relative risk approximately 0.50) [5]. Whether this lesser performance is due to ongoing environmental exposure, higher levels of noneosinophilic inflammation, biologic changes between childhood and adult asthma, or other differences in the overall study populations is not well understood. (See "Treatment of severe asthma in adolescents and adults", section on 'Mepolizumab'.)

FOOD ALLERGY AND INTOLERANCE

Timing of cow's milk protein introduction in infants and risk of allergy (November 2022)

Current guidelines recommend introducing highly allergenic foods, including cow's milk (CM) protein, in infants who are exclusively breast fed, beginning around four to six months of age. A prospective cohort study in 1298 children that examined the timing of receipt of CM-based formula supplementation after delivery and first reported introduction of CM-based formula or other CM products found that introduction at <2 weeks of age followed by continued exposure was associated with the lowest subsequent risk of development of parent-reported adverse reactions to CM (IgE- or non-IgE mediated) between 2 to 13 years of age [6]. This and other accumulating data suggest that very early introduction and continued ingestion of CM protein in some form (other than liquid, whole CM) may reduce the risk of developing CM allergy, although further studies are needed. (See "Introducing highly allergenic foods to infants and children", section on 'Introduction in the general population'.)

Diagnosis of cashew allergy (October 2022)

Traditional approaches to testing for food allergy can result in a high number of supervised food challenges to determine clinical reactivity or tolerance to the food. A systematic review and analysis of six studies demonstrated that use of a combination of skin prick testing, blood testing for whole cashew, and/or blood testing for cashew component protein(s) can minimize the number of food challenges performed and also limit the number of false positives that lead to unnecessary avoidance and false negatives that result in reactions on home reintroduction or supervised challenge [7]. A suggested approach to the diagnosis of cashew allergy is shown in the algorithm (algorithm 1); we agree with this approach. (See "Component testing for pollen-related, plant-derived food allergies", section on 'Cashew'.)

IMMUNODEFICIENCY

Gene therapy for Artemis-deficient SCID (February 2023)

Patients with radiation-sensitive (RS) forms of T-B-NK+ severe combined immunodeficiency (SCID), such as those with defects in the Artemis gene (DCLRE1C), have poorer outcomes after hematopoietic cell transplantation (HCT) than non-RS forms of T-B-NK+ SCID. Thus, alternatives such as gene therapy (GT) are under exploration. Ten newly diagnosed infants have received autologous Artemis GT using a lentiviral vector and low-dose busulfan conditioning [8]. All are making T and B cells, with reconstitution of T cell immunity in six and B cell immunity in four and no adverse events related to the conditioning or gene therapy reported. These initial results suggest that GT may offer an alternative to HCT, particularly in patients without a matched sibling donor. (See "T-B-NK+ SCID: Management", section on 'Gene therapy'.)

New inborn errors of immunity (October 2022)

Fifty-five novel monogenic gene defects that cause inborn errors of immunity (IEI) and one new phenocopy due to autoantibodies have been identified since 2020 in the International Union of Immunological (IUIS) Societies Expert Committee updated IEI classification, bringing the total number of IEI to nearly 500 [9]. Several key points were noted. Different pathogenic variants in a single gene can cause unique phenotypes. Conversely, defects in different genes can have a similar phenotype because they involve a shared pathway. Finally, identification of genetic causes of IEI unequivocally identifies redundant and nonredundant gene functions. (See "Inborn errors of immunity (primary immunodeficiencies): Classification", section on 'Key points'.)

RHINITIS AND RHINOSINUSITIS

Allergen immunotherapy for local allergic rhinitis (November 2022)

Local allergic rhinitis (LAR) describes the subset of patients with rhinitis symptoms who test negative for allergen-specific immunoglobulin E (IgE) on skin testing and in vitro immunoassays, but who react to nasal challenge with allergen. Growing evidence suggests that allergen-specific IgE is produced locally in the nasal tissues but is not detectable systemically for undefined reasons. The utility of allergen immunotherapy (AIT) for LAR was uncertain, but a systematic review and meta-analysis of four randomized trials, which included 156 patients, demonstrated that AIT improved short-term symptom and medication scores and quality of life, and resulted in immunologic changes associated with successful AIT [10]. A standardized approach to nasal challenges would be required before these findings could be widely applied. (See "Subcutaneous immunotherapy (SCIT) for allergic rhinoconjunctivitis and asthma: Indications and efficacy", section on 'Local allergic rhinitis'.)

URTICARIA AND ANGIOEDEMA

New urticaria in the weeks after COVID-19 vaccination (March 2023)

Urticaria with or without angioedema has been reported in association with coronavirus disease 2019 (COVID-19) as well as messenger ribonucleic acid (mRNA) vaccines and boosters, particularly the Moderna mRNA booster. In a study of over 3.5 million adults from two cohorts who received a first booster dose of COVID-19 vaccine, the crude incidence of chronic spontaneous urticaria was approximately 2 cases per 100,000 persons [11]. Of the 800 patients in two cohorts with newly diagnosed urticaria, more than 90 percent of cases were temporally associated with receiving the Moderna vaccine. Urticaria appeared between one and two weeks after vaccination, occurred most days of the week, and, in most patients, resolved in two to six months. This phenomenon is reminiscent of urticaria associated with viral infections, does not constitute an allergy, and is not a reason to avoid future vaccinations or boosters, although affected patients may prefer to choose a different product. (See "New-onset urticaria", section on 'COVID-19 vaccines and boosters'.)

OTHER GENERAL ALLERGY AND IMMUNOLOGY

Trial of lebrikizumab for atopic dermatitis (March 2023)

Lebrikizumab is a monoclonal antibody that selectively binds to soluble IL-13. In a phase 3 randomized trial that included 211 adults and adolescents with moderate to severe atopic dermatitis (AD), more patients receiving subcutaneous lebrikizumab plus topical corticosteroids achieved an IGA score of clear/almost clear at 16 weeks, compared with those receiving placebo plus topical corticosteroids (41 versus 22 percent, respectively) [12]. Lebrikizumab-related adverse events included conjunctivitis and injection site reaction. Larger and longer-term trials are needed to further evaluate the efficacy and safety of lebrikizumab for AD. (See "Treatment of atopic dermatitis (eczema)", section on 'Anti-IL-13 antibodies (lebrikizumab)'.)

Trial of topical brepocitinib for atopic dermatitis (March 2023)

Brepocitinib is an investigative small molecule tyrosine kinase 2/janus kinase 1 (JAK1) inhibitor that blocks the interleukin (IL) 12 and IL-23 pathways. In a six-week randomized trial that included 292 adolescent and adults with mild to moderate atopic dermatitis, topical brepocitinib 1% once or twice daily induced a greater reduction of the Eczema Area and Severity Index score from baseline, compared with vehicle (-70 and -75 percent versus -44 and -47 percent, respectively) [13]. Adverse events, most frequently nasopharyngitis and worsening of atopic dermatitis, occurred in 34 percent of patients. Although topical brepocitinib appears promising for the rapid improvement of mild to moderate atopic dermatitis, more data on long-term efficacy and safety are needed. (See "Treatment of atopic dermatitis (eczema)", section on 'JAK inhibitors'.)

Monitoring patients with eosinophilic esophagitis (February 2023)

Eosinophilic esophagitis (EoE) is a chronic condition; however, the optimal strategy for long-term monitoring is unclear. A panel of international experts recently published recommendations for monitoring patients with clinically stable EoE [14]. The recommendations included follow-up visits every 12 to 24 months and individualizing the decision to perform upper endoscopy based on symptoms, prior esophageal pathology, medication adjustments, and clinician and patient preferences. Our approach to monitoring patients with EoE is consistent with the expert recommendations. (See "Treatment of eosinophilic esophagitis (EoE)", section on 'Introduction'.)

Dupilumab for eosinophilic esophagitis (January 2023)

Therapeutic options for eosinophilic esophagitis (EoE) are expanding. In a two-part trial in patients with EoE that had not responded to proton pump inhibitor therapy, weekly dupilumab resulted in higher rates of histologic improvement after 24 weeks relative to placebo (part A [weekly dupilumab]: 60 versus 5 percent, and part B [dupilumab every 2 weeks]: 59 versus 6 percent) [15]. Dupilumab also improved dysphagia symptom scores. Based on these findings, the US Food and Drug Administration approved dupilumab for EoE in patients ≥12 years of age who weigh ≥40 kg [16]. Future studies will help to inform the role of dupilumab in EoE management. (See "Treatment of eosinophilic esophagitis (EoE)", section on 'Options for nonresponders'.)

Allergen immunotherapy for atopic dermatitis (October 2022)

Allergen immunotherapy (AIT) is a well-established treatment for allergic rhinoconjunctivitis and asthma, but studies of its utility for atopic dermatitis (AD) are mixed. In a new meta-analysis, the addition of AIT (either subcutaneous or sublingual, mostly using house dust mites as the allergen) or placebo was evaluated in 23 randomized trials that enrolled nearly 2000 children and adults with AD who were not controlled with standard therapy (either topical corticosteroids or calcineurin inhibitors) [17]. Patients receiving add-on AIT more often experienced a clinically important decrease in AD severity and improvement in quality of life. Thus, add-on AIT may be beneficial for patients who have eczema that is not controlled with conventional therapies and proven sensitization to house dust mites. AIT may be especially helpful for patients with concomitant allergic rhinoconjunctivitis or asthma. (See "Treatment of atopic dermatitis (eczema)".)