Hymenoptera stings can cause severe systemic reactions, including life-threatening anaphylaxis. Venom immunotherapy (VIT) remains the only disease-modifying treatment for Hymenoptera venom allergy. Conventional outpatient VIT buildup protocols are safe and well-tolerated but require prolonged buildup phases. On the other hand, accelerated inpatient rush and ultra-rush protocols are associated with higher costs due to inpatient hospitalization and may increase the risk of systemic reactions.

Intramuscular (IM) epinephrine administered via manual injection, autoinjector, or as a nasal spray, are the current first-line treatments for anaphylaxis. AQST-109 is a needle- and device-free sublingual alternative epinephrine formulation in late-stage clinical development.

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency disorder seen in clinical medicine. The immune defect occurs in males and females equally, and is characterized by reduced serum levels of immunoglobulin G (IgG) along with deficient immunoglobulin A (IgA) and/ or immunoglobulin M (IgM) levels, along with poor to absent specific antibody responses to infection or vaccinations. Although CVID is considered a primary immune defect, most subjects are diagnosed between the ages of 20 to 40. However, due to the heterogeneous clinical appearance, a diagnostic delay of 5 to 8 years after the first cardinal symptom is common in all countries where this has been investigated. As the genetics of this immune defect have been further clarified, it is clear that the name "CVID" is an umbrella diagnosis, useful clinically for arranging treatment, but it actually includes a very large number of immune defects, many of which are not yet discovered. Due to prevalence, common inflammatory complications, and numbers of medical encounters, the awareness of CVID is critical for pediatricians, internists, and primary care physicians, as well as pulmonologists, otolaryngologists, hematologists and physicians in many other specialties. Here we outline the early history of CVID, the diagnostic criteria and standard workup of subjects, the clinical manifestations, emerging genetic understandings and current treatment modalities for patients with this immune defect.

Penicillin allergy labels affect 1 in 10 people but are uncommonly reflective of true, IgE-mediated allergy. Penicillin allergy labeled patients have increased exposure to broad-spectrum antibiotics that increase the risk for treatment failures, antimicrobial resistance, and adverse events. De-labeling of penicillin allergy is an evidence-based strategy to support access to optimal antibiotics and reduce antimicrobial resistance.

Eosinophilic chronic rhinosinusitis (ECRS), a refractory subtype of chronic rhinosinusitis, frequently coexists with asthma. CRS can exacerbate the asthma burden, contributing to poor disease control. However, how comorbid ECRS influences the clinical efficacy of dupilumab in asthma remains unclear.

Patients commonly present to the Allergist/Immunologist with concerns for mast cell activation disorder with associated gastrointestinal symptoms (MCAD-GI). Currently, there is limited evidence supporting diagnostic utility of staining for MCs on gastrointestinal biopsies.

Chronic urticaria (CU) affects a significant percent of the global population and carries a higher burden of unmet medical need. Current standard-of-care includes antihistamines and omalizumab, but omalizumab is not effective in all patients and has not been shown to induce long-term disease remission. This review examines the diverse therapeutic pipeline spanning IgE-based and non-IgE based mast cell targeting strategies, including recent clinical data. The therapeutic landscape has expanded rapidly with multiple mechanisms under investigation. IgE-targeted approaches include omalizumab biosimilars, with CT-P39 having received FDA approval. Dupilumab received FDA approval for antihistamine refractory chronic spontaneous urticaria (CSU) supporting the targeting of type-2 cytokines, IL-4 and IL-13, in this disease. Bruton's tyrosine kinase (BTK) inhibitors show promise, with remibrutinib receiving FDA approval and demonstrating significant reductions in UAS7 in Phase 3 trials. c-Kit (c-Kit or KIT) inhibition with barzolvolimab shows robust efficacy with sustained effects post-treatment. Finally, JAK inhibitors, MRGPRX2 antagonists and other novel mechanisms are advancing through clinical trials. Although some programs have been discontinued due to safety concerns or lack of efficacy such as fenebrutinib (BTK inhibitor), THB001 (c-Kit inhibitor), EP262 (MRGPRX2 antagonist), tezepelumab (anti- TSLP), as well as lirentelimab and AK006 (Siglec-targeting agents), these studies have informed many of the other positive studies. In summary, over the last year, we have seen the CU pipeline mature with multiple Phase 3 programs and new approvals representing diverse mechanisms of action. Nevertheless, significant therapeutic gaps persist for omalizumab-refractory disease and chronic inducible urticaria.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are major exacerbating factors in approximately one-third of chronic spontaneous urticaria (CSU) patients, contributing to disease chronicity and severity. However, comprehensive comparisons of clinical characteristics and treatment responses remain limited.