Background: Nonimmediate (delayed) allergic reactions to penicillins are common and some of them can be life-threatening. The genetic factors influencing these reactions are unknown/poorly known/poorly understood. We assessed the genetic predictors of a delayed penicillin allergy that cover the HLA loci. Methods: Using next-generation sequencing (NGS), we genotyped the MHC region in 24 patients with delayed hypersensitivity compared with 20 patients with documented immediate hypersensitivity to penicillins recruited in Italy. Subsequently, we analyzed in silico Illumina Immunochip genotyping data that covered the HLA loci in 98 Spanish patients with delayed hypersensitivity and 315 with immediate hypersensitivity compared to 1,308 controls. Results: The two alleles DRB3*02:02:01:02 and DRB3*02:02:01:01 were reported in twenty cases with delayed reactions (83%) and ten cases with immediate reactions (50%), but not in the Allele Frequency Net Database. Bearing at least one of the two alleles increased the risk of delayed reactions compared to immediate reactions, with an OR of 8.88 (95% CI, 3.37–23.32; P <0.0001). The haplotype (ACAA) from rs9268835, rs6923504, rs6903608, and rs9268838 genetic variants of the HLA-DRB3 genomic region was significantly associated with an increased risk of delayed hypersensitivity to penicillins (OR, 1.7; 95% CI: 1.06–1.92; P=0.001), but not immediate hypersensitivity. Conclusion: We showed that the HLA-DRB3 locus is strongly associated with an increased risk of delayed penicillin hypersensitivity, at least in Southwestern Europe. The determination of HLA-DRB3*02:02 alleles in the risk management of severe delayed hypersensitivity to penicillins should be evaluated further in larger population samples of different origins.

Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID-19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off-label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off-label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease.

Background: Eosinophilic asthma (EA) is characterized by abnormal production and release of type 2 cytokines, such as interleukin-5 (IL-5), from T helper type 2 (Th2) lymphocytes and type 2 innate lymphoid cells (1). The aim of this study was to evaluate the usefulness of the basophil phenotype assessment and serum IL-5 assay in monitoring a series of severe EA patients treated with anti IL-5 drugs and correlate the results of these tests with baseline patients’ characteristics and clinical response, with particular attention to systemic steroid use and asthma exacerbations. Methods: Blood samples of 19 severe asthma patients were collected at T3 and T6 for evaluation of serum levels of IL-5 and basophil phenotype assessment. Results: All patients experienced an improvement of lung function, with an increase of FEV1 from a mean value of 71.9 to 83.8% of the theoretical value (+12%). Oral corticosteroids were progressively reduced and finally stopped in 14 (73.7%) of the 19 patients after six months of follow-up. Patients who achieved a complete response to anti-IL5 treatment showed a rate of activated basophils CD3negCRTH2posCD203cposCD125pos (4.78 ± 2.26%) at T0 significantly lower than that of patients not achieving the complete response (34.57 ± 14.01%, p=0.05). Conclusions: This pilot study in EA patients shows that the determination of activated basophils, that express CD125 is related to anti IL5/IL5Rα drug mechanism of action and subsequent immune response, proving to be a biomarker that identifies the patient’s phenotype that responds to therapy and that requires the concomitant use of OCS.