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

Revised diagnostic criteria for allergic bronchopulmonary aspergillosis (May 2024)

Allergic bronchopulmonary aspergillosis (ABPA), a complex hypersensitivity reaction to airway colonization with Aspergillus fumigatus, can be hard to distinguish from difficult-to-treat asthma or cystic fibrosis. The International Society for Human and Animal Mycology (ISHAM) working group for ABPA recently published revised diagnostic criteria (table 1) that make some key changes to improve the sensitivity and specificity of the diagnosis [1]:

●Total serum immunoglobulin (Ig) E levels of ≥500 international units/mL are sufficient for the diagnosis, rather than the previously higher threshold of 1000 international units/mL.

●Elevated Aspergillus IgG levels by enzyme immunoassay or lateral flow assay are more sensitive for detecting sensitivity to Aspergillus antigens and should be used preferentially over Aspergillus serum precipitins.

We agree with the revised ISHAM diagnostic approach. (See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis", section on 'Diagnostic criteria'.)

Pro-inflammatory airway phenotype associated with asthma susceptibility locus 17q21 (April 2024)

Multiple genome-wide association studies have identified the 17q21 locus as strongly associated with asthma susceptibility, but the mechanism of this association has been uncertain. In recent transcriptome-wide analyses of respiratory epithelium from three separate asthma cohorts, a strong genotype-phenotype link has been identified between the expression of Gasdermin B (GSDMB) and a pro-inflammatory cell-lytic type 1 immune transcriptome signature [2,3]. Higher GSDMB expression was associated with enhanced airway inflammation after respiratory viral infection both in cultured epithelial cells and in mice expressing human GSDMB in their airways. Mechanistically, GSDMB was shown to bind (virally produced) double-stranded RNA and subsequently activate pro-inflammatory signaling cascades. (See "Genetics of asthma", section on 'Expression quantitative trait (eQTL) mapping'.)

Association between gut bacteriophage abundance and asthma risk (April 2024)

The abundance and diversity of gut flora and their interaction with the immune system have been associated with a predisposition to childhood asthma. A recent study examined the role of the fecal virome, predominantly comprising temperate bacteriophages, in a Danish birth cohort of 647 one-year-old children who were subsequently longitudinally assessed for asthma [4]. The relative abundance of certain viral families was associated with subsequent asthma development, and the viromes in turn were associated with early life exposures (eg, siblings and season of birth). The association between virome and asthma was not mediated by the impact on gut bacteria, suggesting independent effects on the developing immune system. (See "Risk factors for asthma", section on 'Influence of microbiome'.)

Tapering inhaled corticosteroids in asthma patients responding to biologics (December 2023)

Strategies for tapering other asthma therapies, such as inhaled corticosteroids (ICS), for patients who achieve good asthma control with biologics has not been well studied. In an open-label, randomized trial of 168 adults with a history of severe eosinophilic asthma and good control on benralizumab and high-dose ICS, 43 patients were assigned to an ongoing high-dose ICS-formoterol regimen and 125 patients were assigned to a 32-week taper protocol (medium-, low-, and as-needed dosing of ICS-formoterol) [5]. In the tapering arm, 92 percent of patients achieved lower doses of ICS, with only 9 percent experiencing exacerbations. However, significant decreases in FEV₁ and increases in fraction of exhaled nitric oxide occurred in patients using the least amount of as-needed ICS-formoterol after their taper. These data suggest that most patients well-controlled on biologics may be successfully tapered to regimens containing medium- or low-dose ICS with long-acting bronchodilators. However, the safety and efficacy of tapering to as-needed ICS-formoterol requires further study. (See "Treatment of severe asthma in adolescents and adults", section on 'Tapering therapy'.)

FOOD ALLERGY AND INTOLERANCE

Omalizumab for food allergy (March 2024)

Most food allergy reactions can be prevented with careful avoidance, but accidental exposures and reactions can still occur. There are also substantial burdens associated with avoidance. In a multicenter, placebo-controlled randomized trial in 177 children aged 1 to 17 years with multiple food allergies, patients assigned to omalizumab, an anti-immunoglobulin E (anti-IgE) monoclonal antibody, plus allergen avoidance had an increased reaction threshold on oral food challenge, compared with avoidance alone [6]. These findings suggest that omalizumab may offer some protection from accidental food exposures and contributed to US Food and Drug Administration approval for this indication [7]. However, its ability to induce permanent tolerance is untested, its use is costly, and administration requires subcutaneous injections at regular intervals indefinitely. For most patients with food allergy, we suggest allergen avoidance alone rather than avoidance plus omalizumab. (See "Food allergy management: Allergen-nonspecific therapies", section on 'Efficacy' and "Management of IgE-mediated food allergy: An overview", section on 'Choice of strategy'.)

IMMUNODEFICIENCY

Anti-IL-23 antibodies and acquired autoimmunity (April 2024)

Autoantibodies to cytokines or other components of the immune system can cause susceptibility to severe infection and mimic inborn errors of immunity or adult onset immunodeficiency due to human immunodeficiency virus infection. In a series of studies primarily in adults with thymoma, anti-interleukin 23 (anti-IL-23) occurred in up to 80 percent of patients with persistent invasive mycobacterial, fungal, or bacterial infections [8]. The degree of neutralizing activity of anti-IL-23 correlated with the severity of infection, with higher neutralization capacity seen in patients with disseminated or unusual cerebral or pulmonary infections. Management approaches, such as exogenous cytokine supplementation or autoantibody depletion, remain to be explored. (See "Inborn errors of immunity (primary immunodeficiencies): Classification", section on 'X. Phenocopies of inborn errors of immunity'.)

URTICARIA AND ANGIOEDEMA

Investigational gene editing therapy for hereditary angioedema (May 2024)

Hereditary angioedema (HAE) is a genetic disorder caused by pathogenic variants in the gene encoding C1 esterase inhibitor, resulting in excess creation of bradykinin and episodes of debilitating angioedema. An investigational gene editing therapy NTLA-2002 reduces bradykinin production by disrupting the gene for kallikrein B1, an enzyme that catalyzes the generation of bradykinin. In a combined phase I and II trial of 10 adults with HAE, NTLA-2002 was infused once at three different doses [9,10]. Angioedema attacks were reduced by mean of 95 percent over the duration of the 16-week trial. Although potentially curative, and thus exciting, the strategy of knocking down a normal gene rather than correcting a pathogenic variant requires further studies of long-term safety. (See "Hereditary angioedema (due to C1 inhibitor deficiency): General care and long-term prophylaxis", section on 'Investigational therapies'.)

Chronic inducible urticaria (April 2024)

The term chronic inducible urticaria (CIndU) refers to distinct disorders in which urticaria is elicited by identifiable physical triggers (eg, firm pressure, shifts in body temperature, cold, heat, sun, water, or vibration). CIndU can exist in isolation or together with chronic spontaneous urticaria (CSU), but data about CIndU are limited. In a retrospective review of over 400 children and adults with CIndU, those with isolated CIndU had fewer episodes of angioedema, emergency referral, need for systemic glucocorticoids, and coexistent systemic disorders compared with patients with both CIndU and CSU, providing some useful information about the relative severity of these disorders [11]. (See "Physical (inducible) urticaria", section on 'Severity'.)

OTHER GENERAL ALLERGY AND IMMUNOLOGY

Benralizumab in the treatment of eosinophilic granulomatosis with polyangiits (March 2024)

Eosinophilic granulomatosis with polyangiitis (EGPA) is a chronic inflammatory disorder associated with asthma, chronic rhinosinusitis with or without polyposis, and peripheral blood eosinophilia that may be amenable to treatment with biologic agents targeting eosinophilic inflammation via the interleukin-5 (IL-5) pathway. In a randomized trial of 140 patients with relapsing or refractory EGPA, 59 percent of patients receiving benralizumab, an antibody targeting the IL-5 receptors, and 56 percent of patients receiving mepolizumab, an antibody targeting IL-5, achieved remission of disease [12]. Serious adverse events were uncommon and similar in each group. Based upon these findings, we suggest benralizumab or mepolizumab as glucocorticoid-sparing therapeutic options for individuals with non-severe relapsing or refractory EGPA. (See "Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): Treatment and prognosis", section on 'Anti-IL-5 or anti-IL-5R agents'.)

Budesonide oral suspension for eosinophilic esophagitis (March 2024)

In patients with eosinophilic esophagitis (EoE), use of topical glucocorticoids has been limited by lack of regulatory approval and potentially inconsistent drug delivery. Budesonide oral suspension is a formulation that was recently approved by the US Food and Drug Administration for treating EoE in adults and pediatric patients ages 11 years and older [13,14]. Approval was informed by clinical trials showing that topical budesonide resulted in higher rates of histologic remission and symptomatic improvement compared with placebo. We anticipate using budesonide oral suspension as the preferred topical glucocorticoid for treating EoE. (See "Treatment of eosinophilic esophagitis (EoE)", section on 'Topical glucocorticoids'.)

Clinical features of VEXAS syndrome (March 2024)

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a severe, late-adult onset autoinflammatory disease involving the nuclear factor kappa B (NFkB) pathway. The spectrum of clinical manifestations and features of this disease are demonstrated in three recent studies: In a French cohort, patients had an increased risk of serious infections, primarily bacterial and viral but also including invasive fungal and atypical infections despite antimicrobial prophylaxis and may be attributable to intrinsic immunodeficiency in addition to being associated with Janus kinase (JAK) inhibitor therapy [15]. In an Italian cohort, several patients with myelodysplastic syndrome progressed to acute myeloid leukemia [16]. In a Spanish cohort, UBA1 mosaicism was detected in both hematopoietic and nonhematopoietic tissues, indicating that the mutational event occurs during early embryonic development, not adulthood as was previously suspected [17]. The mortality rate was high in all cohorts, ranging from 12 to 40 percent. (See "Autoinflammatory diseases mediated by NFkB and/or aberrant TNF activity", section on 'Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome'.)

Dupilumab for recalcitrant chronic hand eczema (February 2024)

Treatment of severe chronic hand eczema (CHE) is challenging and may require systemic immunosuppressants or oral alitretinoin (a retinoid not available in the United States) or phototherapy. In a small randomized trial, 29 adults with severe CHE were assigned to treatment with dupilumab (an interleukin [IL] 4/IL-13 inhibitor approved for the treatment of atopic dermatitis) or placebo [18]. At week 16, more patients in the dupilumab group than in the placebo group achieved 75 percent improvement in the Hand Eczema Severity index (95 versus 33 percent). Treatment was well tolerated. Ocular pruritus occurred in three patients in the dupilumab group and was the only treatment-associated adverse effect. These findings indicate dupilumab as a valuable option for recalcitrant CHE, although it is not yet approved for this indication. (See "Chronic hand eczema", section on 'Dupilumab'.)