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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, 4092 (34.1%) had high‐risk HLA alleles, 4583 (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% versus 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. [ABSTRACT FROM AUTHOR]

Purpose: Desensitization is a safe alternative for patients with hypersensitivity reactions (HSRs) to platinum-based chemotherapeutic agents and widely used in real practice by employing stepwise administration of multiple serial dilutions of the culprit drugs. However, its labor-intensive nature has required a simpler protocol that is easier to prepare and perform.Methods: We performed an observational study of patients with platinum HSR who underwent a new non-dilution one-bag desensitization protocol. Premedication consisted of Montelukast as well as H1 and H2 blockers. The outcomes and safety profiles of a new protocol were assessed.Results: A total of 36 patients were recruited (oxaliplatin 23, carboplatin 9, and cisplatin 4) and the most common grade of HSR presented was grade 2 (61.1%), followed by grade 3 (25%), and grade 1 (13.9%). Of 175 desensitization procedures, all cases were successfully completed in re-administration of culprit chemotherapeutic platinum agents; 146 (83.4%) had no breakthrough reactions (BTRs) while 29 (16.6%) did. Most BTRs were mild reactions (grade 1, 51.7%) or moderate reactions (grade 2, 44.8%) of Brown's Scale. Although there was one case of asymptomatic mild hypotension (grade 3, 3.5%), categorized as severe reaction, dyspnea, desaturation, and anaphylaxis did not occur. The proportion of severe HSRs was significantly lower than that of initial HSRs (3.5% vs. 25%, P = 0.0167).Conclusions: The new non-dilution desensitization protocol was safe and effective for re-administration of culprit platinum agents in patients with a history of HSRs. Therefore, this new protocol can be used as an alternative to existing protocols using multiple serial dilutions. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prevalence of biphasic and protracted anaphylaxis to iodinated contrast media (ICM), their risk factors and practical observation duration for detecting biphasic reaction.Methods: 145 patients with ICM anaphylaxis from January 2005-February 2016 were retrospectively categorised into uniphasic, biphasic (anaphylaxis recurrence within 72 h after resolution of initial anaphylaxis) and protracted (anaphylaxis >5 h) reaction groups. Multivariate regression analyses of potential risk factors were performed. We calculated negative predictive value (NPV) for biphasic reactions and additional person-hours required to detect one case during post-anaphylaxis observation.Results: Fifteen patients had biphasic reactions with secondary reactions with similar or milder severity and six had protracted reactions. Most significant risk factors were anaphylaxis duration >40 min for biphasic reactions (odds ratio (OR), 8.65 [95 % CI, 1.05-70.71]; P=0.044), and additional epinephrine administration within 1 h of initial dosing for protracted reactions (OR, 102.0 [95 % CI, 3.40-3057.25]; P=0.008). A 6-h post-anaphylaxis observation produced NPV of 96.4 %, while requiring a minimum of 65.5 additional person-hours to detect one additional case.Conclusion: Biphasic and protracted ICM anaphylaxis developed in 10.3 % and 4.1 %, respectively, with revealing risk factors. Six hours could be practical for post-anaphylaxis observation to detect biphasic reaction.Key Points: • Incidence of biphasic anaphylaxis in iodinated contrast media anaphylaxis is 10.3 %. • Incidence of protracted anaphylaxis in iodinated contrast media anaphylaxis is 4.1 %. • Initial anaphylaxis >40 min can predict for biphasic anaphylaxis development. • A 6-h post-anaphylactic observation in ICM-related anaphylaxis seems practical. [ABSTRACT FROM AUTHOR]

Children with complex chronic conditions (CCC) are presumed to be vulnerable to adverse drug reactions (ADRs). The clinical profiles of ADRs in CCC are not well known. Herein, we aim to describe the ADR profiles in CCC with regard to typical presentations and vulnerable groups. We accessed the ADR yearly reports at a tertiary children's hospital whose practice is mainly dedicated to CCC and descriptively analyzed their clinical profiles according to the presence of a complex chronic condition, ADR severity, and age groups. A total of 1841 cases were analyzed, among which 1258 (68.3%) were mild, 493 (26.8%) moderate, and 90 (4.9%) cases were severe. A total of 1581 (85.9%) cases of complex chronic condition were reported. The proportion of CCC in each severity group increased as the ADR becomes more severe. In CCC, ADRs were most frequently reported by nurses in the adolescent group and in cases where the symptoms involved the gastrointestinal system. The class of antineoplastic and immunomodulating drugs was the most commonly suspected of causing an ADR, followed by one of the antibiotics. When we focus on the trend across the age groups, the ratio of severe-to-total ADRs decreased with older age. Among severe cases, the ratio of off-label prescription-related cases was the highest in the infant/toddler group and decreased as the groups aged. In conclusion, ADRs of CCCs admitted to a tertiary children’s hospital have a unique profile. These groups are vulnerable to ADRs and thus they should be monitored closely, especially when they are infants or toddlers, so that severe ADRs can be identified and treated immediately. [ABSTRACT FROM AUTHOR]

The use of lamotrigine ( LTG) can be limited by the occurrence of cutaneous adverse drug reactions (c ADRs) that range from maculopapular eruption ( MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis. A few human leukocyte antigen ( HLA)-related genetic risk factors for carbamazepine-induced cADR have been identified. However, the HLA-related genetic risk factors associated with LTG-induced cADR are not yet well known. We performed HLA genotyping in 50 Korean patients with epilepsy, including 21 patients presenting LTG-induced MPE and 29 LTG-tolerant patients. A significant association between the HLA-A*2402 allele and LTG-induced MPE was identified, in comparison with the LTG-tolerant group (odds ratio [ OR] 4.09, p = 0.025) and the general Korean population ( OR 3.949, p = 0.005). The frequencies of the Cw*0102 or Cw*0702 alleles were significantly higher in the LTG- MPE group than in the Korean population, whereas the frequency of the A*3303 allele was lower. The coexistence of the A*2402 and Cw*0102 alleles was significantly associated with the LTG- MPE group when compared to the LTG-tolerant group ( OR 7.88, p = 0.007). In addition, the Cw*0701 allele was more frequent in the LTG-tolerant group than in the Korean population. These findings suggest the presence of HLA-related genetic risk factors for LTG-induced MPE in the Korean population. [ABSTRACT FROM AUTHOR]

Background: Severe cutaneous adverse reactions (SCARs) include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). SJS and TEN (SJS/TEN) and DRESS are thought to be different diseases; however, they share some clinical and laboratory features. Although SCORTEN serves as an excellent prognostic marker for SJS/TEN, there is still a need for development of other prognostic markers for SCARs. Methods: The study population consisted of 88 SCAR patients. Clinical characteristics and clinical manifestations were compared between SJS/TEN and DRESS. Risk factor analyses for prolonged hospitalization were performed. Results: Of the 88 patients, 41 were SJS/TEN and 47 were DRESS. Mortality rates of TEN and DRESS were 9.8 and 2.1%, respectively. Allopurinol and carbamazepine were the most common causes of both SJS/TEN and DRESS (34.7 and 62.9%, respectively). Some of the systemic presentations, such as fever and laboratory abnormalities were common in both phenotypes. Thrombocytopenia tended to be related to prolonged hospitalization (longer than 3 weeks) in SJS/TEN (odds ratio, OR = 5.1, 95% confidence interval, CI 0.8-31.8, p = 0.076). In DRESS patients, leukocytosis at presentation (OR 4.8, 95% CI 1.1-20.3, p = 0.03) was related to prolonged hospitalization. Conclusions: Clinical features of SCARs in a tertiary hospital in Korea were similar to those reported previously. SJS/TEN and DRESS shared some clinical and laboratory features. Thrombocytopenia for SJS/TEN and leukocytosis at presentation for DRESS may be useful prognostic markers for prolonged hospitalization. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the incidence and risk factors of late adverse reactions (ARs) to non-ionic low-osmolar contrast media (LOCM).Methods: The occurrence of late AR was monitored on day 1 and from day 7 to day 28 in all patients who received enhanced computed tomography using LOCM during a 5-week study period in a single tertiary hospital. Patients who experienced late AR were followed up for three years.Results: Among the total 10,540 LOCM exposures, 315 ARs (3.0%) were reported; acute ARs occurred in 108 LOCM exposures (1.0%) and late ARs occurred in 207 LOCM exposures (2.0%) (90.9% within one week, 9.1% developed afterwards by day 20). Previous history of drug allergy (odds ratio [OR] = 4.59; 95% confidence interval [CI] 2.17-9.71) and allergic diseases (OR = 2.54; 95% CI 1.32-4.91) were risk factors of late ARs to LOCM. Although the recurrence rate was lowered with premedication from 8.5% to 1.7% (8/94 vs. 3/178; p = 0.016), LOCM change did not make difference compared to reuse of the culprit LOCM (2/38 vs. 9/234; p = 0.655). In patients with a history of late AR to LOCM, the risk of recurrent reactions decreased with longer time intervals between exposures (OR = 0.86; 95% CI: 0.77-0.97; p = 0.025) and with the use of antihistamine premedication (OR = 0.27; 95% CI: 0.06-0.99; p = 0.049).Conclusions: Late ARs to LOCM occurred mostly within one week. The use of premedication may be helpful in reducing the recurrence of late ARs. [ABSTRACT FROM AUTHOR]

Summary: Background: Although the US FDA recommends screening for HLA-B*1502 allele in most of Asian ancestry before initiating carbamazepine therapy, the HLA associations with carbamazepine hypersensitivity in non-Chinese Asian populations remain unclear. This study investigated the association between the HLA class I genotype and carbamazepine-induced severe cutaneous adverse reaction (SCAR) in Koreans. Methods: Twenty-four patients who had developed carbamazepine-induced SCAR (7 Stevens–Johnson syndrome (SJS), 17 drug hypersensitivity syndrome (HSS)), 50 carbamazepine-tolerant controls from the Korean Pharmacogenetic Adverse Drug Reaction Research Network and data of 485 Korean general population from a previously published study were recruited. HLA-A, -B, and -C genotyping was performed by direct DNA sequence analysis. Results: Only one of the seven SJS patients was positive for the B*1502 allele, but the frequency of B*1511 was much higher in the patients with CBZ-SJS than in the CBZ-tolerant control patients (P =0.011, P c =not significant; OR=18.0(2.3–141.2)). The frequencies of A*3101 in carbamazepine-induced HSS and SCAR were significantly higher than those in carbamazepine-tolerant controls (P c =0.011, OR=8.8(2.5–30.7) and P c =0.013, OR=7.3(2.3–22.5), respectively). The frequencies of B*1511 in carbamazepine-SJS and A*3101 in carbamazepine-HSS/SCAR were significantly higher than those in the general population. Conclusions: HLA-B*1502 does not seem to be an effective predictive marker for carbamazepine-induced SCAR, while HLA-B*1511 and A*3101 was associated with carbamazepine-induced SJS and HSS/SCAR respectively in the Korean population. [ABSTRACT FROM AUTHOR]