Journal of Allergy and Clinical Immunology-In Practice最新文献

Primary immune regulatory disorders (PIRDs) are inborn errors of immunity characterized by immune dysregulation and multisystem involvement, whose hepatic manifestations can mimic autoimmune, cholestatic, or microvascular liver disease. Among these, heterozygous signal transducer and activator of transcription 1 gain-of-function pathogenic variants are predominantly associated with autoimmune hepatitis-like liver injury whereas vascular and portal hypertensive phenotypes are rarely reported and likely underrecognized. We describe a young adult with recurrent infections and progressive liver disease who ultimately received the diagnosis of a signal transducer and activator of transcription 1 gain-of-function mutation. The case illustrates the spectrum of hepato-gastrointestinal involvement in PIRDs, emphasizing diagnostic considerations, imaging and histopathologic features, and management strategies including conventional immunosuppression, targeted Janus kinase inhibition, and hematopoietic stem cell transplantation. We also outline infectious complications of Janus kinase inhibition, including progressive multifocal leukoencephalopathy.

Background: Although current treatment options for acute exacerbations of antihistamine refractory chronic spontaneous urticaria (CSU) are generally considered safe and effective, patients have breakthrough symptoms necessitating treatment. Epinephrine injections were once used for the treatment for acute urticaria or acute exacerbations of chronic urticaria or angioedema, but their use has declined. The development of an intranasal epinephrine spray (ARS-2) offers a needle-free alternative for the treatment of CSU exacerbations.

Objective: To assess the efficacy and safety of ARS-2 for the treatment of exacerbations of CSU.

Methods: This was a phase 2, single-dose, randomized, placebo-controlled crossover efficacy study in which adult patients (n = 21) experiencing an acute flare or exacerbation of urticaria symptoms were treated with ARS-2 (1 or 2 mg) or placebo. Urticaria symptoms and severity were assessed based on both patient-reported and investigator-rated assessments.

Results: Relative to placebo, both 1- and 2-mg doses of ARS-2 resulted in lower patient-reported hive and pruritus scores (P < .05) and a lower investigator-reported extent of urticaria and erythema scores (P < .05). Additionally, a greater percentage of patients receiving ARS-2 were considered by investigators to have been effectively treated. Patient-reported satisfaction scores were also significantly higher for both doses of ARS-2 relative to placebo. Only minor adverse events were reported.

Conclusion: ARS-2 may offer a safe and effective treatment option for urticaria exacerbations.

Background: Oral H1-antihistamines (OAHs) are among the most frequently used medications for the treatment of allergic rhinitis (AR).

Objective: To perform a systematic review and network meta-analysis comparing the efficacy and safety of individual OAHs in patients with AR.

Methods: We searched 4 electronic bibliographic databases and 3 clinical trial databases for randomized controlled trials assessing adults with perennial or seasonal AR, and comparing (1) OAH versus placebo or (2) different individual OAHs. We performed a network meta-analysis on the Total Nasal Symptom Score, Total Ocular Symptom Score, Rhinoconjunctivitis Quality-of-Life Questionnaire, development of adverse events, and withdrawals due to adverse events. Certainty of evidence for comparisons involving the most clinically relevant second-generation OAHs was assessed using Grading of Recommendations, Assessment and Evaluation approach to network meta-analysis.

Results: We included 74 randomized controlled trials (21 on perennial AR and 53 on seasonal AR). Cetirizine, ebastine, bilastine, and rupatadine were among the individual medications associated with the highest efficacy for improving nasal symptoms. For other efficacy outcomes, the most efficacious interventions varied. A similar frequency of adverse events was observed among different individual second-generation OAHs, with serious adverse events being rare. For most comparisons, the certainty of evidence was rated as "low" or "very low," indicating substantial uncertainty regarding the treatment effects.

Conclusions: Although some OAHs seem to be more efficacious than others, most of the differences between individual second-generation medications are trivial or small. In addition, we did not find any relevant differences in the safety profiles of second-generation OAHs.

Lung function evaluation is a cornerstone in the clinical assessment of patients with asthma. Monitoring lung function decline provides valuable insights into disease progression, the impact of risk factors, and the efficacy of treatments. Accelerated lung function decline often results from the interplay between modifiable risk factors and innate predispositions. Modifiable exposures such as early life respiratory infections, air pollutants, or tobacco smoke can negatively affect lung development and increase the risk of future decline. On the other hand, nonmodifiable factors, including genetic polymorphisms, epigenetic alterations, and congenital conditions such as pulmonary dysplasia or prematurity may determine lower baseline lung function and greater susceptibility to decline. Moreover, in adulthood, persistent airway inflammation, recurrent asthma exacerbations, and progressive airway remodeling further contribute to functional deterioration, particularly in patients with severe asthma. These interacting factors give rise to heterogeneous clinical trajectories of lung function over time, underscoring the need for individualized assessment and management. Clinically, lung function deterioration should be suspected in patients with frequent asthma exacerbations, persistent symptoms, and unsuppressed inflammatory biomarkers despite optimized therapy, or progressive loss of bronchodilator response. The presence of risk factors associated with poor lung function development from childhood may also help identify those at higher risk. In some cases, symptoms alone may not correlate with objective lung function impairment, highlighting the need for serial spirometric assessments during follow-up visits. The challenges for clinicians lie in identifying early functional deterioration, recognizing treatable traits, and implementing tailored therapies within a personalized management approach. In this review we explore the pathophysiologic mechanisms underlying accelerated lung function decline and discuss diagnostic strategies and therapeutic implications aimed at optimizing care for patients with asthma.

Background: neffy (epinephrine nasal spray) is the first needle-free option for the treatment of severe allergic reactions. Seasonal allergic rhinitis with nasal obstruction may alter intranasal drug absorption, but its impact on nasal epinephrine is unclear.

Objective: To compare pharmacokinetics and pharmacodynamics of repeated neffy dosing with intramuscular (IM) epinephrine under normal nasal conditions and following nasal allergen challenge (NAC)-induced allergic rhinitis, and to assess the effect of repeat-dose laterality METHODS: This was a phase 1, open-label, randomized, crossover study in 43 adults with seasonal allergic rhinitis. Subjects underwent 2 treatment periods under normal conditions (neffy 2.0 mg + 2.0 mg; IM 0.3 mg + 0.3 mg) and 3 periods after NAC. Under NAC, neffy was given to the same nostril (R/R) or opposite nostrils (R/L); IM was administered to contralateral thighs. Doses were separated by 10 minutes. Epinephrine concentrations, blood pressure, and heart rate were measured up to 240 minutes. Adverse events were recorded RESULTS: Across normal and NAC conditions, neffy resulted in a higher or comparable maximum plasma concentration, greater early (≤60-minute) partial area under the curves, and a faster time to maximum plasma concentration versus IM. Under NAC, neffy R/R resulted in the highest sustained epinephrine exposure and pharmacodynamic responses, whereas neffy R/L was generally comparable to IM. All adverse events were mild; no serious adverse events occurred.

Conclusions: Repeated dosing of neffy, including during NAC-induced allergic rhinitis, yields pharmacokinetic/pharmacodynamic profiles comparable or greater to IM epinephrine, supports same-nostril repeat dosing, and provides a well-tolerated, needle-free option for patients who may require a second dose.

Background: Vocal cord dysfunction (VCD), or inducible laryngeal obstruction (ILO), is an episodic upper airway disorder that can mimic anaphylaxis.

Objective: To determine the prevalence of VCD/ILO among adults referred to allergy clinic for suspected anaphylaxis and to identify clinical markers that distinguish VCD/ILO from anaphylaxis.

Methods: We conducted a retrospective study of adults referred for suspected anaphylaxis to a tertiary allergy clinic in Newcastle, Australia, in 2023. Patients were classified as confirmed VCD/ILO (laryngoscopy-proven), suspected VCD/ILO (spirometry findings or high clinical suspicion after exclusion of alternate diagnoses), anaphylaxis, or other. Demographics, triggers, comorbidities, clinical features, investigations, and health care utilization were compared between laryngoscopy-confirmed VCD/ILO and anaphylaxis.

Results: Among 133 adults, 11 (8.3%) had laryngoscopy-confirmed VCD/ILO. Inclusion of suspected cases (n = 21 [15.8%]) increased prevalence of VCD/ILO to 24.1% (n = 32). Compared with anaphylaxis, VCD/ILO was characterized by predominant upper airway symptoms, including throat tightness (100% vs 53.8%, P = .004), stridor (36.4% vs 1.9%, P = .003), dysphonia (72.7% vs 17.3%, P < .001), and cough (54.5% vs 1.9%, P < .001) with fewer systemic symptoms (urticaria 18.2% vs 84.6%, P < .001; gastrointestinal 9.1% vs 44.2%, P = .04; cardiovascular 0% vs 55.8%, P < .01). Multiple triggers were more common in VCD/ILO (72.7% vs 1.9%, P < .001), particularly aerosolized chemicals (36.4% vs 0%, P < .001). IgE sensitization to the proposed trigger was uncommon (9.1% vs 63.5%, P < .008) in VCD/ILO.

Conclusions: VCD/ILO is a frequent differential diagnosis in adults referred for anaphylaxis. Recognition of its characteristic clinical features and trigger profiles may prevent misdiagnosis, reduce health care utilization, and improve patient outcomes.

Background: Allergy-related misinformation proliferates across social media platforms, potentially compromising evidence-based patient care, yet comprehensive analyses remain limited.

Objective: To characterize dominant themes, engagement patterns, and public responses to allergy misinformation across major social media platforms.

Methods: We conducted cross-sectional qualitative content analysis of publicly available posts containing allergy misinformation from TikTok, Instagram, Facebook, and X between January and March 2025. Posts with 500 or more interactions were identified using systematic key word searches and coded for misinformation themes by independent reviewers. Public sentiment was assessed through analysis of top-ranked comments.

Results: Among 347 analyzed posts with 12.3 million combined views, natural cure promotion was most prevalent (31%), followed by IgG testing endorsement (24%), medication fearmongering (18%), food allergy misrepresentation (16%), and pharmaceutical conspiracy theories (11%). Natural cure content generated the highest engagement (median, 2,847 interactions; P < .001). Visual platforms (TikTok and Instagram) favored natural cures whereas text-based platforms emphasized conspiracy content. Of 3,470 analyzed comments, 62% were supportive or neutral toward misinformation, with only 38% providing challenged responses. Among corrective comments, only 23% included scientific evidence.

Conclusions: Allergy misinformation achieves high engagement with limited public correction across social media platforms. Health care providers must anticipate IgG testing and natural remedy narratives, integrate myth-busting into counseling, and leverage society-led digital strategies to counter misinformation's influence on clinical care.

Background: The concept of clinical remission in chronic rhinosinusitis with nasal polyps (CRSwNP) is gaining growing relevance in the era of biologic therapies. However, current definitions remain heterogeneous and lack standardized, operational criteria. This variability limits comparability across studies and hinders the implementation of remission as a therapeutic target in routine practice.

Objective: To develop a multidisciplinary, evidence-based, and clinically applicable definition of clinical remission in CRSwNP, integrating symptom-based, endoscopic, therapeutic, and timing-related criteria, and to evaluate expert consensus on the development of a composite remission score.

Methods: A 3-round Delphi consensus was conducted among experts participating in the Rhinosinusitis Italian Network. Across the 3 rounds, experts rated the statements using a 5-point Likert scale. Positive or negative consensus was defined as ≥70% agreement or disagreement, respectively. Descriptive statistics assessed the convergence and stability of responses.

Results: Experts agreed that remission requires meeting concurrent criteria across 4 domains: timing (≥12 months), absence of systemic corticosteroid use or surgical indication, symptom thresholds (Sino-Nasal Outcome Test-22 <20 plus symptoms and hyposmia visual analog scale ≤3), and endoscopic thresholds (Nasal Polyp Score and modified Lund-Kennedy score, both 0 for complete remission and both ≤2 for partial remission). Consensus emerged on differentiating complete and partial remission, on introducing the concept of sustained remission (≥24 months), and on the need for a composite remission score with weighted components and category thresholds.

Conclusion: This Delphi consensus provides the first operational, multidomain definition of complete and partial clinical remission in CRSwNP, developed independently by a large multidisciplinary panel and informed by patient perspectives. The proposed criteria offer a practical framework to standardize remission assessment and support its adoption as a therapeutic goal.