Determination of the incidence and predictive characteristics of drug hypersensitivity reactions among children hospitalized at Department of Pediatrics at Mersin University Hospital

Along with the rapid expansion in the global drug consumption rates, drug hypersensitivity reactions (DHR) are increasingly seenboth in hospitalized patients and outpatients. There is no reported study that examined the prospective incidence rate of DHR in hospitaized children in Turkey. On the other hand, the role of biomarkers in predicition and prognosis of DHR is gaining importance in the last few years. In our study, we aimed to determine the incidence of DHR in children hospitalized in pediatric wards of our hospital, the clinical characteristics of reactions, the involved drugs and the relationship between selected biomarkers', namely; high sensitivity C-reactive protein (hs-CRP), S100A8/A9 (calprotectin) and Thymus and activation-regulated chemokine (TARC), levels and the clinical characteristics and prognosis. Drug hypersensitivity development was prospectively tracked by daily visits in all hospitalized pediatric patients between 01.05.2022- 01.05.2023 in Mersin University Hospital pediatric wards and all DHRs were recorded and followed up. On the 1st and 7th day of the reaction, blood samples for hs-CRP, calprotectin and TARC were taken from the patients and their levels were measured in the serum. A total of 62 reactions in 58 patients were encountered during prospective follow-up of one year. A total of 62 DHRs were observed in a total of 7330 hospitalized patients in pediatric wards, resulting in an annual incidence rate of 8 per 1000 patient. The departments with the highest incidence of DHR development were pediatric intensive care, pediatric infection and general pediatrics. Although betalactams had the highest total number of reactions among 62 recorded reactions antiepileptics, chemotherapeutics and other antibiotics, had the first three highest incidence rates, respectively when the drug-specific incidence rates were calculated. Among a total of 7330 patients SCAR developed in two patients, giving an annual SCAR incidence rate of 0.27 per 1000 patients.The age of the patients ranged between 0.2 and 18 years, and the average age was 7.7 (7.79±5.30 years). When the phenotypes of DHRs were examined; 9.6% (n=6) had anaphylaxis, 32.2% (n=20) maculopapular eruption (MPE), 3% (n=2) severe cutaneous adverse reactions (SCAR), and 54.8% (n=34) had urticaria. There were concurrent infection findings in 42 of the patients with DHR, while there was no accompanying infection in 20 patients. When the demographic and clinical features of 0-12 years old and > 12 years old children, a significant difference was found only in terms of the diseases that caused hospitalization/treatment and the person who first noticed the reaction. The mean levels of serum hs-CRP, calprotectin and TARC levels taken at the first day of DHR were significantly higher than that of healthy children, both for the entire patient group and also for both immediate (IR) and non-immediate (NIR) type reactions when chronologically classified. The mean hs-CRP level of the NIRs was significiantly higher than the IRs. There was no significant difference between mean calprotectin and TARC levels of IRs and NIRs. When cases definitively proven by suitable testing were compared to other groups separately, it was found that calprotectin and TARC levels were significantly higher than healthy patients, but there was no significant difference in terms of hs-CRP levels. Blood absolute neutrophil/lymphocyte ratios (ANC/ALC) did not show any significant difference between groups. In 28 patients whose first and 7th day samples could be studied, there was no statistically significant difference in hs-CRP and calprotectin levels between the two samples, but the 7th day levels were quite lower than the first day levels. In the TARC study, there was no statistically significant difference between the 1st and 7th days, but the 7th day levels were higher. When calprotectin, hs-CRP and TARC levels were compared between 20 MPE and 2 SCAR patients, no statistically significant differences were found, probably due to small number of SCAR cases, but hs-CRP levels were rather higher in SCAR cases than in MPE on both sampling points, whereas calprotectin levels were somewhat higher in MPE than in SCAR cases. When patients with acute infections during the reaction were compared to patients without infection, no statistically significant differences were detected between eosinophil, sedimentation, CRP, absolute ANC/ALC, calprotectin, hs-CRP and TARC levels, but all biomarkers were higher in patients with infection than in those without infection. In conclusion; the annual DHR incidence rate in all pediatric patients hospitalized in Mersin University Faculty of Medicine Pediatrics wards was found to be lower than the rates found in developed countries and severe reactions were rare. It was also shown that high hs-CRP, calprotectin and TARC levels measured in the early period of the reaction may be successful biomarkers in predicting the development of DHR, but accompanying infections may also affect the levels. Keywords: drug hypersensitivity reaction, incidence, , biomarkers, calprotectin, hs-CRP, TARC