Background: Several type B adverse drug reactions (ADRs), especially severe cutaneous adverse reactions (SCARs), are associated with particular human leukocyte antigen (HLA) genotypes. However, pre-stored HLA information obtained from other clinical workups has not been used to prevent ADRs. We aimed to simulate the preemptive use of pre-stored HLA information in electronic medical records to evaluate whether this information can prevent ADRs. Methods: We analyzed the incidence and the risk of ADRs for selected HLA alleles (HLA-B*57:01, HLA-B*58:01, HLA-A*31:01, HLA-B*15:02, HLA-B*15:11, HLA-B*13:01, HLA-B*59:01, and HLA-A*32:01) and seven drugs (abacavir, allopurinol, carbamazepine, oxcarbazepine, dapsone, methazolamide, and vancomycin) using pre-stored HLA information of transplant patients based on the Pharmacogenomics Knowledge Base guidelines and experts’ consensus. Results: Among 11,988 HLA-tested transplant patients, 4,092 (34.1%) had high-risk HLA alleles, 4,583 (38.2%) were prescribed risk drugs, and 580 (4.8%) experienced type B ADRs. Patients with HLA-B*58:01 had a significantly higher incidence of type B ADR and SCARs associated with allopurinol use than that of patients without HLA-B*58:01 (17.2% vs. 11.9%, odds ratio (OR) 1.53 [95% confidence interval (CI) 1.09–2.13], P = 0.001, 2.3% vs. 0.3%, OR 7.13 [95% CI 2.19–22.69], P < 0.001). Higher risks of type B ADR and SCARs were observed in patients taking carbamazepine or oxcarbazepine if they had one of HLA-A*31:01, HLA-B*15:02, or HLA-B*15:11 alleles. Vancomycin and dapsone use in HLA-A*32:01 and HLA-B*13:01 carriers, respectively, showed trends toward increased risk of type B ADRs. Conclusion: Utilization of pre-stored HLA data can prevent type B ADRs including SCARs by screening high-risk patients.

Immediate and non-immediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5-3% of patients receiving non-ionic ICM. The diagnosis and management of these patients is controversial among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and non-immediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Drug provocation test is the gold-standard; although, as it is a risky procedure, the decision for performing it needs to be taken based on a risk-benefit analysis. Another source of controversy is the role of in vitro tests for diagnosis and pretreatment for preventing reactions.

Background: For subjects who had previous hypersensitivity (HSR) to low-osmolar contrast media (LOCM), changing contrast media is recommended. However, determining the safest alternative LOCM is uncertain. We investigated the cross-reactivity among LOCMs and the outcomes of re-exposure in patients with previous immediate HSRs. Methods: The outcomes of re-exposure were assessed in the cohort with previous LOCM-associated HSR by the skin testing results and the presence of a common N-(2,3-dihydropoxypropyl) carbamoyl side chain. Results: Among 431 patients with previous HSR who underwent 482 skin tests, 250 cases (51.9%) showed positivity to intradermal tests, which was positively associated with the severity of HSR. The cross-reactivity among LOCMs was higher between LOCMs sharing common side chain compared to those not sharing (21.5% vs. 13.3%, P = .008). The recurrent HSRs was significantly reduced from 46.6% on re-exposure to culprit LOCM to 12.3% with changing LOCM based on the skin test results (P = .004). The overall recurrence rate was not further reduced when the LOCM was changed based on presence or absence of common side chain (15.1% vs. 11.8%, P = .428). However, for those who had severe index HSRs, skin test non-reactive LOCMs exposures, without the common side chain, resulted in a significant reduction in recurrent HSRs compared to LOCMs with the common side chain (24.0% vs. 7.8%, P = .049). Conclusion: In patients who experienced a severe index HSR to LOCM, avoidance of re-exposure to LOCMs with a common side chain or a positive skin test result is safer.

Aims Lamotrigine is one of the most widely used antiepileptic drugs, but it has a critical issue of a skin rash if the starting dose is too high or the escalation rate is too rapid. We investigated the efficacy and safety of a novel and rapid titration protocol for lamotrigine that takes only 11 days to reach a daily dose of 200 mg. Methods We prospectively enrolled 33 adult patients (age 18-85) who were diagnosed with epilepsy and started lamotrigine administration for the first time at a single tertiary hospital. Our new protocol starts with a subthreshold dose of the drug and then administer a stepwise-incremental dose until reaching the full therapeutic dose within 11 days. Results Of 29 patients analyzed, only two (6.9%) experienced idiosyncratic skin rash before the first follow-up visit at 2 weeks (±3 days). In addition, a therapeutic concentration was reached in more than 75% of studied patients after 2 weeks of lamotrigine administration Conclusion These findings demonstrate the value of the novel tolerance induction protocol for lamotrigine, which could widen the available application of lamotrigine in various situations.