Background: Asthmatic children on corticosteroids can develop hypothalamic-pituitary-adrenal axis suppression (HPAS). Single nucleotide polymorphisms (SNPs) rs242941 and rs1876828 of the corticotrophin-releasing hormone receptor 1 (CRHR1) gene were associated with lower stimulated cortisol (F) levels, whereas rs41423247 of the glucocorticoid receptor (NR3C1) gene was associated with higher basal F levels. The objective of the current study was to confirm whether these three SNPs are associated with HPAS in asthmatic children. Methods: DNA was extracted from saliva obtained from 95 asthmatic children, who had previously undergone basal F and metyrapone testing. Thirty-six children were classified as suppressed. Non-suppressed children were sub-classified according to their post-metyrapone ACTH (PMTP ACTH) level into a middle (106-319 pg/ml) and a high (>319 pg/ml) ACTH response group. TaqMan® polymerase chain reaction assays were utilized. Results: Only rs41423247 was inversely associated with HPAS (OR = 0.27 [95% CI 0.06-0.90]). Its GC genotype was inversely associated with HPAS (log odds = - 1.28, p = 0.021). √PMTP ACTH was associated with CC (effect size = 10.85, p = 0.005) and GC genotypes (effect size = 4.06, p = 0.023). The C allele is inherited as a dominant trait (effect size = -1.31 (95% CI -2.39 – -0.33; p = 0.012). In the high ACTH response group, both genotypes affected the PMTP ACTH (effect sizes 1.41 and 15.46; p-values 0.023 and < 2x10-26 for GC and CC respectively). Conclusions: The C allele of rs41423247 was found to be protective against HPAS. CC genotype is associated with the highest PMTP ACTH response.

This review highlights the novelties in understanding the underlying immunological mechanisms of drug hypersensitivity reactions (DHRs) as well as tiny changes in clinical classification and diagnosis of DHRs with special reference to beta-lactams (BLs) in the pediatric population, in the last couple of years. Viral infections are very often in children and they can provoke skin rashes which is difficult to differentiate from DHRs. Because of that allergy to BLs in children is overdiagnosed. The correct diagnosis of BLs allergy in children is still an important and hot topic. In this review has been outlined the need for correct diagnosis of BLs allergy in children as well as needed to change the paradigm.

Comment on Matricardi PM et al.: The first, holistic immunological model of COVID-19: implications for prevention, diagnosis, and public health measuresTO THE EDITOR:We read with great interest the review article by Matricardi and colleagues [1] depicting mechanisms of disease for COVID-19 and analyzing both viral and host factors influencing its course. We particularly agree with Authors on the pivotal role of innate immunity in the very early phase of disease, being crucial for the subsequent evolution. Most known weapons of innate immune system are represented by natural antibodies, non-specific antimicrobial proteins, interferons, cytokines and cellular elements (i.e. natural killer cells).[1] However, innate immunity could be influenced by other, still underrecognized, factors.At present, a solid proof of evidence is available on the ability of vitamin D in modulating immune response.[2] Most of data are available from the field of bacterial infections and sepsis,[3] being low vitamin D levels associated with a higher risk of infection and mortality.[4]In addition, vitamin D could play a role against viruses by maintaining physical barriers (i.e. tight junctions, gap junctions, etc.), enhancing natural immunity (i.e. production of cathelicidin, defensins, etc.) and modulating adaptive immune response (i.e. modulation of TH1/TH2 response and inflammation).[5] On this connection, emerging data support the role of vitamin D supplementation in reducing the risk and severity of influenza.[5] Both influenza and COVID-19 show their maximum spread in winter season and the highest severity in elderly people. Reduced vitamin D levels could represent a possible pathophysiological explanation, among others, in both cases.[5,6] With this regard, it has been hypothesized that variations in vitamin D status across countries and latitudes could, at least in part, explain variations of mortality from COVID-19.[6,7]However, at present the exact vitamin D status among COVID-19 patients is unknown.[7] Moreover, the role and mechanisms of vitamin D in the treatment of COVID-19 are still unexplored and several interventional trials are ongoing. Should these hypotheses be confirmed, universal vitamin D supplementation would represent a possible and inexpensive strategy to enhance natural immunity against COVID-19.Antonio Mirijello, MDMaria Maddalena D’Errico, MDAntonella Lamarca, MDPamela Piscitelli, MDSalvatore De Cosmo, MDDepartment of Medical Sciences, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy