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Background: Beta-lactam (BL) antibiotics hypersensitivity is common in children. Clinical manifestation of BL hypersensitivity varies from mild to severe cutaneous adverse drug reactions (SCARs)., Objective: To determine the association of HLA genotype and BL hypersensitivity and the prevalence of true drug allergy in patients with history of BL hypersensitivity., Methods: A case-control study was performed in 117 children with aged 1-18 years. Children with history of non-SCARs BL hypersensitivity were evaluated for true drug hypersensitivity including skin test and drug provocation test. Tolerant control patients were children who could tolerate BL for at least 7 days without hypersensitivity reaction. HLA genotype (HLA-A, HLA-B, HLA-C and HLA-DRB1) were performed in 24 cases and 93 tolerant controls using PCR-SSO (polymerase chain reaction - sequence specific oligonucleotide probes)., Results: There were association of HLA-C*04:06 (OR = 13.14, 95%CI: 1.3-137.71; p = 0.027), and HLA-C*08:01 (OR = 4.83, 95%CI: 1.93-16.70; p = 0.016) with BL hypersensitivity. HLA-B*48:01 was strongly associated with immediate reaction from BL hypersensitivity (OR = 37.4, 95%CI: 1.69-824.59; p = 0.016) while HLA-C*04:06, HLA-C*08:01 and HLA-DRB1*04:06 were associated with delayed reaction (p < 0.05). Among 71 cases who were newly evaluated for BL hypersensitivity, only 7 cases (9.8%) had true BL hypersensitivity., Conclusions: Less than 10% of children with suspected of BL hypersensitivity have true hypersensitivity. There might be a role of HLA-B, HLA-C and HLA-DRB1 genotype in predicting BL hypersensitivity in Thai children.

Objective: Phenobarbital hypersensitivity is one of the common drug hypersensitivity syndromes in children. Clinical symptoms of phenobarbital hypersensitivity vary from maculopapular rashes (MPs) to severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Drug hypersensitivity has been demonstrated to be associated with variations in the HLA genotypes. This study was to investigate the association between the variations of HLA genotypes and phenobarbital hypersensitivity in Thai children., Methods: The cases were Thai children, between 0 and 18 years of age, who were diagnosed with phenobarbital hypersensitivity, which included SCARs and MPs. The control patients were Thai children of a corresponding age who had taken phenobarbital for at least 12 weeks without any hypersensitivity reaction. Blood samples were collected for HLA genotyping by using a reverse-sequence-specific oligonucleotide (SSO) probes method. The carrier rates of HLA alleles were compared between 47 cases (27 SCARs and 20 MPs) and 54 controls., Results: The carrier rates of HLA-A*01:01 and HLA-B*13:01 were significantly higher in the phenobarbital-induced SCARs than in the tolerant controls (18.5% vs. 1.85%, p = 0.01, odds ratio [OR] 11.66, 95% confidence interval [CI] 1.21-578.19; 37.04% vs. 11.11%, p = 0.009, OR 4.60, 95%CI 1.29-17.98). There was a trend of a higher carrier rate of HLA-C*06:02 in the phenobarbital-induced SCARs when compared with those in the tolerant controls (29.63% vs. 11.11%, p = 0.059, OR 3.31, 95% CI 0.88-13.31). In contrast to the phenobarbital-induced SCARs, only the HLA-A*01:01 carrier rate in the phenobarbital-induced MPs was significantly higher than those in the tolerant controls (20% vs. 1.85%, p = 0.017, OR 12.69, 95% CI 1.15-661.62)., Significance: An association between phenobarbital hypersensitivity and HLA-A*01:01 and HLA-B*13:01 has been demonstrated in Thai children., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Objective: Skin testing with penicilloyl-polylysine (PPL) and a minor determinant mixture (MDM) were previously recommended for evaluating β-lactam hypersensitivity. However, PPL and MDM have not been commercially available. This study was to determine the negative predictive value (NPV) of skin testing with β-lactam antibiotics for the diagnosis of β-lactam hypersensitivity., Method: Patients age 1-18 years old with a history of β-lactam hypersensitivity were evaluated by skin tests (a skin prick test, an intradermal test) with penicillin G, ampicillin, amoxicillin-clavulanic acid, and the suspect βlactam. The patients who had a negative skin test were performed with a drug provocation test (DPT) in a 3-dose-graded challenge. The hypersensitivity reactions were classified into immediate and non-immediate reactions., Results: A total of 126 patients were evaluated for β-lactam hypersensitivity. Twenty two patients (17.4%) were confirmed with a ?-lactam hypersensitivity. 12 (54.54 %) of them were confirmed by a skin test. There was no systemic reaction occurring after the skin tests. Ten patients (9.6%) from 104 patients with a negative skin test showed reactions after a DPT providing the NPV of the skin test with a 91.2% value., Conclusions: Among those children with a history of β-lactam hypersensitivity, skin testing with penicillin G, ampicillin, amoxicillin-clavulanic acid, and the suspect β-lactam was safe and provided a good NPV when PPL and MDM were unavailable. However, a skin test with β-lactam antibiotics alone did not provide a high sensitivity, thus a DPT procedure was necessary in order to confirm the diagnosis of β-lactam hypersensitivity.

Background: Aromatic anticonvulsant-induced severe cutaneous adverse drug reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), are fatal immune-mediated adverse drug reactions. CYP2C19, a cytochrome P450 isoform, plays a role in metabolic rate of aromatic anticonvulsant. HLA-B*1502 has also been demonstrated to be associated with carbamazepine-induced SJS-TEN., Methods: Forty case patients who were diagnosed with SCARs after initiation of phenobarbital (PB), phenytoin (PHT), or carbamazepine (CBZ) for 1-8 wk and forty control patients who received PB, PHT, or CBZ at least 2 months with no adverse drug reactions were enrolled in the study. The genotypes of CYP2C19*1, CYP2C19*2, and HLA-B*1502 were analyzed using allele-specific polymerase chain reaction technique. Clinical characteristics of SCARs patients who used different drugs were also analyzed., Results: There was no significant difference in sex, onset of symptoms, laboratory results, treatment, and length of stay among patients with SCARs due to PB, PHT, or CBZ. The patients with CYP2C19*2 variant had a trend to have a likelihood to develop SCARs more than the patients with CYP2C19 wild type (OR = 2.5, 95% CI (0.96-67.3) p = 0.06). In subgroup analysis, the patients with CYP2C19*2 variant were at four times increased risk of SCARs from phenobarbital more than the patients with CYP2C19 wild type (OR = 4.5, 95% CI (1.17-17.37) p < 0.03). There was no association between the HLA-B*1502 and aromatic anticonvulsant-induced severe cutaneous adverse reactions (SCARs)., Conclusion: CYP2C19*2 variant may play a role in the genetic predisposition of SCARs from phenobarbital., (© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Objective: To determine usefulness of basophil activation test [BAT] in diagnosis of immediate betalactam [BL] allergy, and compare the role of diagnosis BAT with standard testing, skin test [ST], and drug provocation test [DPT] in patients with history suspected of drug allergy in Thailand. Materials and Methods: Cross-sectional study of 􀏐ifteen patients with an history of immediate hypersensitivity reactions to common BL drug group, at Ramathibodi Hospital between 2010 and 2012. All subjects underwent ST, and DPT if ST was negative. BAT was done in all patients. Results: Fifteen patients (10 children and 5 adult), including seven male and eight female cases with history of highly indicated immediate type allergic reactions to beta lactam were examined. Five presented with anaphylaxis and 10 with urticarial rash/angioedema. From 􀏐ifteen patients, eight patients were con􀏐irmed allergic to BL, where four had ST positivity, and four had positive DPT. The present study found one patient with severe anaphylaxis that had negative ST, but could not undergo DPT due to underlying diseases. The alternative test BAT yielded positive result. Four of the eight patients were con􀏐irmed as BL allergic patients with positive BAT (50%). None of the patients with negative drug testing had positive BAT. Estimated sensitivity of ST was similar to BAT at 50%, while speci􀏐icity of BAT in the present study was 100%. The result yielded higher sensitivity, such as 62%, when we combined both tests together (ST and BAT). The authors observed BAT positive results in 75% of patients with positive ST, and 25% of patients positive DPT. Conclusion: BAT has an advantage in patients contraindicated to perform DPT. Moreover, BAT can avoid the risk of reproducible reactions from in vivo testing, especially in high-risk patients allergic to BL. BAT is a promising alternate investigation tool ensuring patients' safety. [ABSTRACT FROM AUTHOR]