Comprehensive assessment of allergic manifestations including drug hypersensitivity in adult patients with inborn errors of immunity

Background: The determination of the prevalence and clinical relevance of allergic manifestations in individuals with human inborn errors of immunity (IEI) remains inadequately established. Here, our objective was to assess the allergic manifestations observed in patients diagnosed with IEI. Method: We evaluated allergic manifestations, including rhinitis, asthma, dermatitis, and venom, drug, and food allergies, in 220 adult patients with IEI. T and B cell subsets, the timing of allergy onset, skin test results, and drug hypersensitivity tests were assessed by using medical records and follow-up data. Results: Antibody deficiencies accounted for 85.9% of the cohort. Allergic rhinitis was the most frequent manifestation (21.8%), followed by asthma (15.9%), atopic dermatitis (12.3%), and drug hypersensitivity (10.9%). Food allergy was rare (0.9%), and no venom allergy was identified. Severe asthma was observed in two patients. Bronchiectasis was more frequent in the patients with asthma versus patients without asthma (28.6% versus 14.4%; p = 0.03). Asthma was more prevalent among patients receiving prophylactic antibiotics (34.1% in those receiving prophylactic antibiotics versus 11.7% in those not receiving prophylactic antibiotics; p = 0.001), and prophylaxis was more common in patients with asthma receiving treatment steps 3-5 than steps 1-2 (57.8% in patients at steps 3-5 versus 18.7% in patients at steps 1-2; p = 0.02). Among 28 drug hypersensitivity reactions in 24 patients (from 47 initially reported cases of patients after exclusion of predictable adverse reactions), immediate-type reactions predominated (78.6%), most commonly urticaria and anaphylaxis (each 21.4%). Among patients with allergic disease, 62% were diagnosed with allergy before IEI. The median (interquartile range) age at the IEI diagnosis was 28 years (18-38 years), and IEI diagnostic delay did not differ by allergy status. The interval between allergy and IEI diagnosis was longer when allergy preceded IEI (median 10 years; p = 0.01). Adult-onset asthma was associated with a higher age at IEI diagnosis (p = 0.004). Aeroallergen sensitization was associated with higher total, memory, and switched memory B cell counts (all p ≤ 0.01) and a higher switched memory B cell proportion (p = 0.04). Conclusion: Allergic manifestations are common in adults with IEI and often occur years before the diagnosis of immunodeficiency. Adult-onset asthma was associated with a higher age at IEI diagnosis, which suggests delayed recognition of underlying immune dysfunction in this subgroup. In addition, aeroallergen sensitization was associated with higher B cell subset counts, which highlights immunologic heterogeneity among adults with allergy and with IEI.