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PROPOSE The purpose of this study was to investigate panels of enzyme-linked immunospot assays (ELISpot) to detect drug-specific mediator releasing cells for confirming culprit drugs in severe cutaneous adverse reactions (SCARs). METHODS Frequencies of drug-induced interleukin-22 (IL-22)-, interferon-gamma (IFN-γ)-, and granzyme-B (GrB)-releasing cells were measured by incubating peripheral blood mononuclear cells (PBMCs) from SCAR patients with the culprit drugs. Potential immunoadjuvants were supplemented to enhance drug-induced mediator responses. RESULTS Twenty-seven patients, including 9 acute generalized exanthematous pustulosis (AGEP), 10 drug reactions with eosinophilia and systemic symptoms, and 8 Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) were recruited. The average frequencies of drug-induced IL-22-, IFN-γ-, and GrB-releasing cells were 35.5±16.3, 33.0±7.1, and 164.8±43.1 cells/million PBMCs, respectively. The sensitivity of combined IFN-γ/IL-22/GrB ELISpot was higher than that of IFN-γ ELISpot alone for culprit drug detection in all SCAR subjects (77.8% vs 51.9%, P < 0.01). The measurement of drug-induced IL-22- and IFN-γ releasing cells confirmed the culprit drugs in 77.8% of AGEP. The measurement of drug-induced IFN-γ- and GrB-releasing cells confirmed the culprit drugs in 62.5% of SJS/TEN. Alpha-galactosylceramide supplementation significantly increased the frequencies of drug-induced IFN-γ releasing cells. CONCLUSION The measurement of drug-induced IFN-γ-releasing cells is the key for identifying culprit drugs. The additional measurement of drug-induced IL-22-releasing cells enhances ELISpot sensitivity to identify drug-induced AGEP, while the measurement of drug-induced GrB-releasing cells could have a role in SJS/TEN. ELISpot sensitivity might be improved by supplementary alpha-galactosylceramide. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02574988.

Drug hypersensitivity reactions (DHR) are heterogeneous in their pathomechanisms, clinical presentation, severity, and outcomes. Novel DHR mechanisms, phenotypes, and endotypes have been described. The key to prevention from further exposure to the culprit drugs involves correct identification of the putative drug through a combination of in vitro and/or in vivo tests, accurate drug allergy labeling and reporting, and electronic decision support systems within electronic medical records to prevent future accidental prescribing. Prescreening and premedication, the focus of this review, may be a useful adjunct to preventive measures in certain situations. After an index immediate drug hypersensitivity reaction, prescreening may be useful in perioperative anaphylaxis, and iodinated (ICM) and gadolinium-based contrast media (GCM) where the culprit and potential alternative agents are skin tested. In certain nonimmediate DHR, pharmacogenomic prescreening may be used before prescribing high-risk drugs (eg, carbamazepine and allopurinol) where specific human-leukocyte antigen genotypes are associated with severe cutaneous adverse reactions. Premedication with antihistamine and systemic corticosteroids is another therapeutic strategy to prevent infusion reactions for certain biologicals and chemotherapeutic agents, in cases of perioperative anaphylaxis, ICM and GCM DHR, and clonal mast cell disorders. Rapid drug desensitization may also be used to induce temporary tolerance in situations where there are limited alternative drugs. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE vol:9 issue:8 pages:2958-2966 ispartof: location:United States status: published

Aromatic antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) add up to the limited use of the AEDs in the treatment and prevention of seizures. Human leukocyte antigen-B (HLA-B) alleles have been linked to AEDs-induced cADRs. We investigated the association between cADRs (including Stevens–Johnson syndrome; SJS/toxic epidermal necrolysis; TEN, drug reaction with eosinophilia and systemic symptoms; DRESS, and Maculopapular eruption; MPE) caused by AEDs (phenytoin, carbamazepine, lamotrigine, phenobarbital and oxcarbazepine) and HLA-B alleles in Thai population. Through the case-control study, 166 patients with AEDs-induced cADRs, 426 AEDs-tolerant patients (AEDs-tolerant controls), and 470 healthy subjects (Thai population) were collected. The HLA genotypes were detected using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. We also performed a meta-analysis with these data and other populations. The carrier rate of HLA-B*15:02 was significantly different between AEDs-induced cADRs group and AEDs-tolerant group (Odds ratio; OR 4.28, 95% Confidence interval; CI 2.64–6.95, p p HLA-B*15:02 with AEDs-induced cADRs (OR 4.77, 95%CI 1.79–12.73, p HLA-B*15:02 was associated with SJS/TEN induced by AEDs (OR 10.28, 95%CI 6.50–16.28, p p = 0.001) and carbamazepine (OR 137.69, 95%CI 50.97–371.98, p HLA-B*15:02 and AEDs-induced SJS/TEN was demonstrated with an OR of 10.79 (95%CI 5.50–21.16, p HLA-B*08:01, HLA-B*13:01, and HLA-B*56:02 were significantly higher in the DRESS group compared with the AEDs-tolerant group (p = 0.029, 0.007, and 0.017, respectively). The HLA-B*15:02 allele may represent a risk factor for AEDs-induced cADRs.

Background Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reaction (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The pathomechanism of co-trimoxazole–induced SCAR remains unclear. Objective We aimed to investigate the genetic predisposition of co-trimoxazole–induced SCAR. Methods We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole–induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia. Results The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole–induced SCAR (P = 8.2 × 10−9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole–related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole–induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10−21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10−5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole–induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10−23; OR = 40.1). Conclusion This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole–induced SCAR in Asians.

The multidisciplinary experts in Thailand developed an asthma management recommendation that was relevant to low-middle income countries (LMICS). Populations level consideration about asthma management is emphasized. The healthcare systems, access to and availability of treatments as well as the asthma populations vary from country to country in LMICS. The feasibility in clinical practice for implementation is also a major issue. For these reasons, the practice guidelines that are relevant to local contexts are essential to improve better asthma control. Furthermore, integrative and collaboration between asthma experts and the public health sector to implement and discriminate such guidelines will help to achieve these challenging goals. The topics covered include the current asthma situation in Thailand and the Asia-Pacific region, the definition of asthma, asthma diagnosis, assessment of asthma patients, asthma treatment - both pharmacological and non-pharmacological, management of asthma exacerbation, management of asthma comorbidities, treatment of asthma in special conditions, severe and uncontrolled asthma, Thai alternative medicine and asthma, and asthma and coronavirus disease-19 (COVID-19).

HLA-B*13:01-positive patients in Thailand can develop frequent co-trimoxazole hypersensitivity reactions. This study aimed to characterize drug-specific T cells from three co-trimoxazole hypersensitive patients presenting with either Stevens-Johnson syndrome or drug reaction with eosinophilia and systemic symptoms. Two of the patients carried the HLA allele of interest, namely HLA-B*13:01. Sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones were generated from T cell lines of co-trimoxazole hypersensitive HLA-B*13:01-positive patients. Clones were characterized for antigen specificity and cross-reactivity with structurally related compounds by measuring proliferation and cytokine release. Surface marker expression was characterized via flow cytometry. Mechanistic studies were conducted to assess pathways of T cell activation in response to antigen stimulation. Peripheral blood mononuclear cells from all patients were stimulated to proliferate and secrete IFN-γ with nitroso sulfamethoxazole. All sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones expressed the CD4+ phenotype and strongly secreted IL-13 as well as IFN-γ, granzyme B and IL-22. No secretion of IL-17 was observed. A number of nitroso sulfamethoxazole-specific clones cross-reacted with nitroso dapsone but not sulfamethoxazole whereas sulfamethoxazole specific clones cross-reacted with nitroso sulfamethoxazole only. The nitroso sulfamethoxazole specific clones were activated in both antigen processing-dependent and -independent manner, while sulfamethoxazole activated T cell responses via direct HLA binding. Furthermore, activation of nitroso sulfamethoxazole-specific, but not sulfamethoxazole-specific, clones was blocked with glutathione. Sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones from hypersensitive patients were CD4+ which suggests that HLA-B*13:01 is not directly involved in the iatrogenic disease observed in co-trimoxazole hypersensitivity patients.

Atopic dermatitis (AD), a chronic, relapsing dermatitis, is characterized by dry and pruritus skin in patients with a personal or family history of atopy. It affects up to 20% of children and 1-3% of adults in most countries worldwide, and leads to significant treatment costs and morbidity. These guidelines are developed in accordance with evidence-based publications and expert opinions. Following simple algorithms, the guidelines aim to assist adult and pediatric physicians in the better care of patients with AD. As with other diseases, there have been several diagnosis criteria proposed over time. Nonetheless, the classical Hanifin and Rajka criterion with no pathognomonic laboratory biomarkers is still the most widely used worldwide for the diagnosis of AD. The management of AD must be considered case by case to provide suitable care for each patient. Basic therapy is focused on avoiding specific/unspecific provoking factors and hydrating skin. Topical anti-inflammatory treatments such as glucocorticoids and calcineurin inhibitors are suggested for disease flare, and proactive therapy is best for long-term control. Other therapies, including antimicrobial agents, systemic antihistamines, systemic anti-inflammatory agents, immunotherapy, phototherapy, and psychotherapy, are reviewed in these guidelines. Crisaborole, a new topical phosphodiesterase 4 inhibitor, can be used twice daily in AD patients over three months old. Dupilumab, a biological drug for patients with moderate-to-severe AD, may be considered in patients with no improvement from other systemic treatments.

International audience; Background: The issues and challenges in the diagnosis of drug allergy/hypersensitivity among children and adults in Asia are likely to be different from non-Asian countries.Objective: To study the diagnostic modalities used in the evaluation and management of drug allergy/drug hypersensitivity reactions (DHRs) among member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI).Methods: A questionnaire comprising 41 questions was circulated electronically to member societies and individual members of APAAACI between January 23, 2020 and March 6, 2020.Results: Twenty-six respondents from 15 member societies and 1 individual member responded. European DHR guidelines were most commonly used. Skin prick and intradermal testing was used by 100%, with only 60% having access to commercial penicillin skin test reagents. In vitro-specific IgE tests were used by 75%, and basophil activation test by 56.3% for immediate DHR. Patch tests were used by 75% in contrast to lymphocyte transformation tests by 25% for nonimmediate DHR. Drug provocation tests were used by 68.8%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (93.3%). Human leukocyte antigen (HLA) genotype testing was mandatory among 25% respondents before new carbamazepine prescriptions, and 8.3% for allopurinol prescriptions.Conclusions: There was increased use of skin testing for iodinated contrast media hypersensitivity and patch testing for nonimmediate DHR. HLA genotype testing prior to new carbamazepine, allopurinol and abacavir prescriptions remain variable despite strong associations for severe cutaneous adverse reactions with Asian ethnicity. Results of this survey form a useful framework for developing educational and training needs and for improving access to drug allergy diagnostic and treatment modalities across APAAACI member societies.

Co-trimoxazole (CTX) causes various forms of severe cutaneous adverse reactions (SCARs). This case-control study was conducted to investigate the involvement between genetic variants of human leukocyte antigen (HLA) and CYP2C9 in CTX-induced SCARs, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) in Thai patients. Thirty cases of CTX-induced SCARs were enrolled and compared with 91 CTX-tolerant controls and 150 people from the general Thai population. Cases comprised 18 SJS/TEN and 12 DRESS patients. This study demonstrated that genetic association of CTX-induced SCARs was phenotype-specific. HLA-B*15:02 and HLA-C*08:01 alleles were significantly associated with CTX-induced SJS/TEN, whereas the HLA-B*13:01 allele was significantly associated with CTX-induced DRESS. In addition, a significant higher frequency of HLA-A*11:01-B*15:02 and HLA-B*13:01-C*03:04 haplotypes were detected in the group of CTX-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and DRESS cases, respectively. Genetic association of CTX-induced SCARs is phenotype-specific. Interestingly, these association was observed only in HIV-infected patients but not in non-HIV-infected patients.

Drug hypersensitivity reactions (DHRs) occasionally present with severe cutaneous adverse reactions (SCARs) which result in a high risk of morbidity and mortality. Although SCARs are rare, the occurrence could lead to a significant increase in healthcare and economic burden, especially when more than one possible culprit drug is implicated. Therefore, the accurate identification of the culprit drug(s) is important for correct labeling and subsequent patient education and avoidance. To date, clinical evaluation using causality assessment has limitations because the assessment may be inaccurate due to the overlapping timelines when multiple drugs are initiated/continued. Moreover, drug provocation tests (DPTs) which is the gold standard in diagnosis, are contraindicated, and in vivo skin tests may also be associated with risks of triggering SCAR. The European Network for Drug Allergy recommended that in vitro tests, if available, should be performed before any in vivo tests. Basophil activation tests and lymphocyte transformation tests, could serve as reliable in vitro tests for both immediate and delayed-type DHR. Many academic medical centers with affiliated laboratory services offer these tests in the diagnostic evaluation of SCARs in clinical practice. This not only complements identification of the culprit drug(s), but may also be used to test for potentially non cross-reactive alternatives, hence avoiding DPTs. In this review, we summarize the roles of in vitro tests in identifying the culprit drug(s) in SCARs, issues with utilization and interpretation of test results, and our experience in clinical practice.

Objective To adapted the Drug Hypersensitivity Quality of Life (DrHy-Q) Questionnaire from Italian into Thai and assessed its validity and reliability. Design Prospectively recruited during January 2012–May 2017. Setting Multicenter; six Thai tertiary university hospitals. Study Participants Total of 306 patients with physician-diagnosed drug hypersensitivity. Interventions Internal consistency and test–retest reliability were evaluated among 68 participants using Cronbach’s ɑ and intra-class correlation coefficient (ICC). The validity of Thai DrHy-Q was assessed among 306 participants who completed World Health Organization Quality of Life-BREF (WHOQOL-BREF-THAI). Construct and divergent validities were assessed for Thai DrHy-Q. Known-groups validity assessing discriminating ability was conducted in Thai DrHy-Q and WHOQOL-BREF-THAI. Main outcome measures Validity; reliability; single vs. multiple drug allergy; non-severe cutaneous adverse reactions (SCAR) vs. SCAR. Results Thai DrHy-Q showed good reliability (Cronbach’s ɑ = 0.94 and ICC = 0.8). Unidimensional factor structure was established by confirmatory factor analysis (CFI&TLI = 0.999, RMSEA = 0.02). Divergent validity was confirmed by weak correlation between Thai DrHy-Q and WHOQOL-BREF-THAI domains (Pearson’s r = −0.41 to −0.19). Known-groups validity of Thai DrHy-Q was confirmed with significant difference between patients with and without life-threatening SCAR (P = 0.02) and patients with multiple implicated drug classes vs. those with one class (P < 0.01); while WHOQOL-BREF-THAI could differentiate presence of life-threatening SCAR (P < 0.01) but not multiple-drug allergy. Conclusions Thai DrHy-Q was reliable and valid in evaluating quality of life among patients with drug hypersensitivity. Thai DrHy-Q was able to discriminate serious drug allergy phenotypes from non-serious manifestations in clinical practice and capture more specific drug-hypersensitivity aspects than WHOQOL-BREF-THAI.

Allopurinol is one of the most common causes of severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). This study identified the risk factors associated with the development of allopurinol-induced SCARs in a Thai population.Eighty-six allopurinol-induced SCARs (i.e. 19 DRESS and 67 SJS/TEN) and 182 allopurinol-tolerant patients were enrolled in the study. The HLA-B*58:01 allele was determined. Clinical and medicinal data were collected.Results from multivariate analysis showed that only the HLA-B*58:01 and female sex were identified as risk factors of allopurinol-induced SCARs in this Thai population. Patients who carried the HLA-B*58:01 allele were at a higher risk of allopurinol-induced DRESS [odds ratio (OR)=149.2, 95% confidence interval (CI)=24.0-∞, P1.00×10]. Similar results were observed in allopurinol-induced SJS/TEN (OR=175.0, 95% CI=44.3-690.9, P=1.69×10). The risk of allopurinol-induced SCARs in women was higher than that in men (OR=4.6, 95% CI=1.4-15.6, P=1.44×10). The overall mortality rate of allopurinol-induced SCARs was 11.39% and a higher mortality rate was observed in elderly women.Among the risk factors identified, the HLA-B*58:01 allele had the greatest impact on the development of both phenotypes of allopurinol-induced SCARs in this studied Thai population. In case HLA-B*58:01 genotyping cannot be accessed, close monitoring of allopurinol usage, especially in elderly women with impaired renal function, is necessary to reduce the mortality rate of these life-threatening SCARs.

The purpose of this study was to investigate the association of genetic factors including variants in HLA-B and CYP2C genes and non-genetic factors with phenotype-specific phenytoin (PHT)-induced severe cutaneous adverse reactions (SCARs) in Thai patients. Thirty-six PHT-induced SCAR cases (15 Stevens-Johnson syndrome (SJS) and 21 drug rash with eosinophilia and systemic symptoms (DRESS)/drug hypersensitivity syndrome (DHS)) and 100 PHT-tolerant controls were studied. Variants in HLA-B, CYP2C9, and CYP2C19 genes were genotyped. Fisher’s exact test and multiple logistic regression analysis were performed to test the association of genetic and non-genetic factors with specific type of SCARs. Multiple logistic regression models showed that genetic and non-genetic factors associated with PHT-induced SCARs were specified to its phenotype. HLA-B*13:01, HLA-B*56:02/04, CYP2C19*3, and omeprazole co-medication were strong risk factors of DRESS/DHS (adjusted OR = 13.29, p = 0.0001; adjusted OR = 56.23, p = 0.0007; adjusted OR = 6.75, p = 0.0414; and adjusted OR = 9.21, p = 0.0020, respectively). While CYP2C9*3 and having Chinese ancestry were significant risk factors of SJS (adjusted OR = 10.41, p = 0.0042 and adjusted OR = 5.40, p = 0.0097, respectively). Combined genetic and non-genetic risk factors optimized sensitivity and increased specificity for predicting PHT-induced SCARs. This study showed that distinct genetic markers were associated with phenotype-specific PHT-induced SCARs. Non-genetic factor, omeprazole co-medication, was strongly associated with PHT-induced DRESS/DHS in addition to variants in HLA-B and CYP2C genes. Combined markers may be better predictors for PHT-induced SCARs.

Intralesional triamcinolone acetonide injection is indicated for multiple skin conditions such as keloid scars, alopecia areata, and hypertrophic lichen planus. Immediate hypersensitivity reaction remains uncommon. We report on a 24-year-old woman who had received multiple intralesional injections with triamcinolone acetonide (Kenacort) plus lidocaine for keloid scar treatment without any reaction for the previous 10 years. The immediate reaction occurred 15 minutes after injection, with numbness on her face and 5 minutes later with urticaria on her chest wall and upper extremities, together with hypotension (blood pressure of 90/60 mmHg). Allergology workup revealed positive skin prick test for triamcinolone acetonide (Kenacort). Skin tests for other corticosteroids (hydrocortisone, methylprednisolone, and dexamethasone), excipients (carboxymethylcellulose, benzyl alcohol, and polysorbate 80) and lidocaine were negative, including subcutaneous challenge for lidocaine and oral challenge for carboxymethylcellulose. IgE-mediated hypersensitivity reaction must be considered in cases of multiple applications of triamcinolone acetonide injection.

OBJECTIVE This study aimed to describe the genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions (PHT-induced cADRs) in Thai patients. METHOD A retrospective case-control study was conducted among 88 PHT- cADRs (25 SJS/TEN, 37 DRESS/DIHS and 26 MPE) compared to 70 PHT-tolerant controls during 2008-2017. Genotyping was performed by Taqman RT-PCR (EPHX1 337 T > C, EPHX1 416A > G and CYP2C9*3), pyrosequencing (UGT1A1*28, UGT1A1*6) and polymerase chain reaction-sequence-specific oligonucleotide probe (HLA-B). Chi-squared test and binary logistic regression were used to identify factors associated with PHT-cADRs. RESULTS Multivariate analysis showed that HLA-B*46:01 was significantly associated with all PHT-induced cADRs (OR 2.341; 95% CI, 1.078-5.084; P = .032). Age of ≥60 years showed a significant association with PHT-induced SJS/TEN (OR 3.600; 95% CI, 1.214-10.672; P = .021). CYP2C9*3 was almost reaching statistically associated with an increased risk of PHT-induced SJS/TEN (OR 4.800; 95% CI, 0.960-23.990; P = .056). While HLA-B*56:02/04 was found to have a significant association with PHT-induced DRESS/DIHS (OR 29.312; 95% CI, 1.213-707.994; P = .038). Moreover, female gender and HLA-B*40:01 were associated with an increased risk of PHT-induced MPE at OR 5.734; 95% CI, 0.910-58.351; P = .042 and OR 3.647; 95% CI, 1.193-11.147; P = .023, respectively. CONCLUSION Both clinical (advanced age, female gender) and genetic factors (HLA-B*46:01, CYP2C9*3, HLA-B*56:02/04 and HLA-B*40:01) contributed to the risk of PHT-induced cADRs. Further studies with larger sample size may be warranted to confirm these findings and also the influence of EPHX1 gene.

Background: Majority of asthma patients in Thailand suffer from severe uncontrolled disease. National data of severe asthma are lack. The pilot study was performed as a part of Severe Asthma Registry of Thailand (SARP-T). Material and Method: Retrospective cohort of moderate-to-severe asthma patients (>18 years) treated between 2017 and 2018 was performed. Severe asthma was defined by ERS/ATS. Asthma medications, comorbidities, ACT, exacerbation history, spirometry and PEFR were reviewed. Chest CT, FENO, blood eosinophils, and serum IgE were examined. Results: Total 60 moderate-to-severe asthma patients were enrolled, 33 (55%) patients were classified severe asthma. Medium to high dose ICS was noted in 84.9%. Chronic rhinosinusitis and nasal polyps were higher in severe group (33.35 vs 18.5%, p=0.248 and 24.2% vs 7.4%, p=0.162, respectively). Osteoporosis was higher in severe asthma (24.2% vs 3.7%, p=0.033). Atopy was noted in two-third of both groups (p=0.755). ACT, exacerbations and clinic PEFR were similar. However, more severe airflow obstruction (post-BD FEV1/FVC) was noted in severe compared to moderate asthma (73.42 ± 12.7 vs. 79.36 ± 6.8, p= 0.032). High FENO (79.79 ± 57.14 vs. 47.21 ± 15.78 ppb, p= 0.160), high blood eosinophils (260.4 [143.6- 365] vs. 242.1 [81.5- 377.1] cells/µL p =0.68) and high IgE (470 [207-752] vs.138 [46-681.5] IU/ml p =0.159) was noted in severe compared to moderate asthma. Expiratory air trapping and bronchiectasis were more common in severe asthma; 48.5% vs 18.5%, p =0.028 and 27.3% vs 3.7%, p =0.017, respectively. Conclusions: Type 2 biomarkers had limited role for differentiating severe disease in Thai asthma cohort.

Adult onset immunodeficiency associated with anti-interferon-gamma autoantibodiesis an emerging medical issue worldwide especially in South-east Asia. Most patientspresent with disseminated non-tuberculous mycobacteria (NTM) infection and otheropportunistic infections. In addition to standard antimicrobial therapy, immunomodulatoror immunosuppressive drug seem to play a role in some cases. In the present study, we thoroughly reviewed the pathogenesis, clinical features,laboratory diagnosis, modalities of treatment, and clinical outcomes of this condition.

Background Asthma in the elderly is severe and associated with poor treatment outcome. Although atopy has an important role in pathogenesis, its role in the elderly is unclear, partly due to immune senescence. Objective We aimed to examine the associations of Th2-mediated inflammation with asthma severity in the elderly. Methods Consecutive asthmatics older than 60 years without severe exacerbation within 8 weeks were enrolled. Atopic status was determined by positive serum specific IgE or skin prick test to common aeroallergens. Serum total IgE was measured simultaneously to exhaled fractional concentration of nitric oxide (FeNO). Asthma control level was assessed by using Thai Asthma Control Test (ACT) score. Results Total of 44 elderly asthmatic patients were enrolled. The mean age was 68.9 years and mean age of asthma diagnosis was 46.6 years. Seventy-seven percent of patients were female. Atopic status was found in 45.5% of patients. Uncontrolled asthma classified as ACT score < 20 was noted in 25% of elderly asthma, but its association with either high serum total IgE (≥120 IU/mL), high FeNO (≥50 ppb) or atopic status was not detected. Conclusion One-fourth of elderly asthmatics were clinically uncontrolled, while atopy was confirmed in 45.5%. Neither high total IgE, high FeNO nor atopic status was associated with uncontrolled asthma in the elderly. Other factors might play role in asthma severity in the elderly, and has to be further investigated.

Drug hypersensitivity reactions (DHRs) occasionally present with severe cutaneous adverse reactions (SCARs) which result in a high risk of morbidity and mortality. Although SCARs are rare, the occurrence could lead to a significant increase in healthcare and economic burden, especially when more than one possible culprit drug is implicated. Therefore, the accurate identification of the culprit drug(s) is important for correct labeling and subsequent patient education and avoidance. To date, clinical evaluation using causality assessment has limitations because the assessment may be inaccurate due to the overlapping timelines when multiple drugs are initiated/continued. Moreover, drug provocation tests (DPTs) which is the gold standard in diagnosis, are contraindicated, and in vivo skin tests may also be associated with risks of triggering SCAR. The European Network for Drug Allergy recommended that in vitro tests, if available, should be performed before any in vivo tests. Basophil activation tests and lymphocyte transformation tests, could serve as reliable in vitro tests for both immediate and delayed-type DHR. Many academic medical centers with affiliated laboratory services offer these tests in the diagnostic evaluation of SCARs in clinical practice. This not only complements identification of the culprit drug(s), but may also be used to test for potentially non cross-reactive alternatives, hence avoiding DPTs. In this review, we summarize the roles of in vitro tests in identifying the culprit drug(s) in SCARs, issues with utilization and interpretation of test results, and our experience in clinical practice.

All beta-lactam use is associated with a certain rate of adverse reactions. Many of these adverse reactions result in an allergy to the beta-lactam being entered into the patient's medical record. Unfortunately, only a small minority of these recorded allergies are clinically significant immunologically mediated drug hypersensitivity. An unconfirmed allergy to beta-lactams is a significant public health risk, because patients so labeled typically do not receive narrow-spectrum penicillins and cephalosporins when clinically indicated. The alternative antibiotics they receive result in poorer clinical outcomes, increased incidence of serious antibiotic-resistant infections, prolonged hospitalizations, and greater health care utilization. There is a wide variation in beta-lactam allergy incidence and prevalence around the world, based in part on the specific beta-lactams used and overused. There is a wide variation in specific protocols used to confirm current tolerance of beta-lactams and remove these inaccurate allergy reports. Harmonizing testing protocols, when possible, may lead to more widespread use of narrow-spectrum beta-lactams, when clinically indicated, and improve patient safety worldwide. Further research is needed to better understand the regional differences in reporting beta-lactam allergy as this relates to regional differences in beta-lactam use and overuse, the frequency of clinically significant immunologically mediated beta-lactam hypersensitivity, and the optimal testing strategies to confirm current tolerance, based on presenting clinical symptoms.

Background The lymphocyte transformation test (LTT) is a standard laboratory method to identify culprit drugs in patients with a history of drug-induced non-immediate hypersensitivity and is mainly performed during the recovery phase. The measurement of drug-specific interferon γ (IFN-γ)-releasing cells has been introduced to confirm culprit drugs, even during the acute phase of drug allergy. Objectives This study aimed to evaluate the capability of the enzyme-linked immunospot assay (ELISpot) to detect drug-specific IFN-γ-releasing cells during the acute phase and the capability of LTT to identify culprit drugs during the recovery phase in patients presenting with severe cutaneous adverse reactions (SCARs). Methods Peripheral blood mononuclear cells (PBMCs) from 23 SCAR patients were collected during the acute and recovery phases and assayed for drug-specific IFN-γ-releasing cells and lymphocyte proliferation, respectively. Results Drug-specific IFN-γ-releasing cells were detectable in 73.9% of SCAR subjects (55.6% and 85.7% in patients who were and were not taking systemic steroids, respectively), whereas LTT results were positive in 52.2% of SCAR subjects. The frequencies of drug-specific IFN-γ-releasing cells were significantly higher in patients with positive LTT than in those with negative LTT (260.1 ± 110.0 and 46.6 ± 20.7 cells/106 PBMCs, P = 0.01). A significant correlation between the results of the IFN-γ ELISpot assay and LTT was demonstrated (r = 0.65, P value Conclusion The IFN-γ ELISpot assay could be a useful tool to identify culprit drugs in SCAR patients when culprit drug identification is urgently needed during the acute phase of drug allergy.

A previous publication in Chinese leprosy patients showed that the HLA-B*13:01 allele is a strong genetic marker for dapsone-induced drug hypersensitivity reactions, however there are no data describing whether HLA-B*13:01 is a valid marker for prediction of dapsone-induced drug hypersensitivity reactions in other ethnicities or nonleprosy patients. The aim of this study is to investigate whether there is an association between HLA genotypes and dapsone-induced severe cutaneous adverse reactions (SCARs) in Thai nonleprosy patients.HLA-B genotypes of 15 patients with dapsone-induced SCARs (11 drug reaction with eosinophilia and systemic symptoms, 4 Stevens-Johnson syndrome/toxic epidermal necrolysis), 29 control patients, and 986 subjects from the general Thai population were determined by the reverse PCR sequence-specific oligonucleotides probe.The HLA-B*13:01 allele was significantly associated with dapsone-induced SCARs compared with dapsone-tolerant controls (odds ratio: 54.00, 95% confidence interval: 7.96-366.16, P=0.0001) and the general population (odds ratio: 26.11, 95% confidence interval: 7.27-93.75, P=0.0001). In addition, HLA-B*13:01 associated with dapsone-induced SJS-TEN (OR: 40.50, 95% confidence interval: 2.78-591.01, P=0.0070) and DRESS (OR: 60.75, 95% confidence interval: 7.44-496.18, P=0.0001).This study demonstrated an association between HLA-B*13:01 and dapsone-induced SCARs including Stevens-Johnson syndrome/toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms in nonleprosy patients. Moreover, these results suggest that the HLA-B*13:01 allele may be a useful genetic marker for prediction of dapsone-induced SCARs in Thai and Han-Chinese populations.

Background Specific IgE against Solenopsis invicta (imported fire ant) remains the current diagnostic tool for allergy to ants worldwide. However, S. invicta may not be the only cause of ant anaphylaxis in Thai patients. Objective To characterize ant species causing anaphylaxis in Thai patients and to test allergenic reactivity to whole body extracts (WBE) of S. geminata (tropical fire ants) in patients with evidence of IgE-mediated ant anaphylaxis. Methods Thirty-two patients with ant anaphylaxis were identified. The causative ants collected by the patients were subjected to species identification. Twelve patients with ant anaphylaxis and showed positive skin test or serum specific IgE to S. invicta and 14 control subjects were recruited. Whole body extraction from S. geminata was performed for protein characterization using SDS-PAGE and protein staining. IgE-immunoblotting and ELISA-specific IgE binding assays were performed on patients' sera and compared with controls. Results Of 32 patients with ant anaphylaxis, the most common causative ant identified was S. geminata (37.5%). Western blot analysis of crude S. geminata revealed 13 refined protein components that bound to patients' serum IgE. Three major allergens with molecular masses of 26, 55 and 75 kDa were identified. All 12 patients gave positive results for specific IgE to S. geminata with statistically significant higher absorbance units of 0.390 ± 0.044, compared to healthy control group (0.121 ± 0.010), P Conclusions S. geminata is identified as the most common causative ant anaphylaxis in Thai patients. Its WBE comprises of 13 IgE-binding components and 3 major allergens (26, 55 and 75 kDa), which supported possible IgE-mediated mechanism.

Background: Lamotrigine (LTG) is commonly used for treatment of epilepsy and bipolar disorder. It is one of the common cause of cutaneous adverse drug reactions (CADR). Clinical symptoms of LTG-induced CADR range from maculopapular exanthema (MPE) to severe cutaneous adverse reactions (SCAR). This study aimed to determine the association of the LTG-induced CADR with human leukocyte antigen (HLA) alleles in Thai patients. Methods: Fifteen patients with LTG-induced CADR [10 MPE; 4 Stevens–Johnson syndrome; and 1 drug reaction with eosinophilia and systemic symptoms] and 50 LTG-tolerant controls were included in the study. HLA-A and HLA-B genotyping was performed using polymerase chain reaction-sequence-specific oligonucleotides probes. Results: The proportion of HLA-A∗02:07 and HLA-B∗15:02 allele carriers were significantly higher in the LTG-induced CADR group than in the tolerant controls [odds ratio (OR): 7.83; 95% confidence interval (CI): 1.60–38.25; P = 0.013, and OR: 4.89; 95% CI: 1.28–18.67; P = 0.014]. In addition, subjects with HLA-A∗33:03, HLA-B∗15:02, and HLA-B∗44:03 were significantly higher in the LTG-induced MPE group than in the tolerant controls (OR: 8.27; 95% CI: 1.83–37.41; P = 0.005, OR: 7.33; 95% CI: 1.63–33.02; P = 0.005; and OR: 10.29; 95% CI: 1.45–72.81; P = 0.029). In contrast to the LTG-induced MPE group, there were no significant differences between HLA alleles and LTG-induced SCAR group. Conclusion: HLA-A∗02:07 and HLA-B∗15:02 were associated with LTG-induced CADR in Thai patients. We also identified an association between HLA-A∗33:03, HLA-B∗15:02, and HLA-B∗44:03 and LTG-induced MPE in this population. These results suggest that these alleles could be useful screening markers for preventing CADR before LTG treatment in Thai patients, but further replication studies with larger sample sizes are needed.

Background Drug provocation tests (DPT) are commonly performed as part of s-lactam allergy work-up, in case of negative skin tests, and in the absence of contraindications. The recommendations of learned societies have created a frame for DPT performance, but protocols vary widely between centres, generating various hypothesis-driven protocols (i.e., empirical dosing, driven by both safety concerns and practical aspects). Methods The primary objective of this retrospective analysis was to detect eliciting dose thresholds (reactive doses) during s-lactam DPT, using the survival analysis method, in order to suggest optimal step doses. Our secondary objective was to evaluate the safety of our 30-minute incremental one-day protocol. The study included all the patients explored in the Allergy Unit of the University Hospital of Montpellier (France), between September 1996 and July 2015 for a suspicion of drug hypersensitivity reaction to s-lactams, with negative skin tests and positive DPT. Results During the study period, 182 positive DPT (accounting for 171 hypersensitive patients) were analysed. We identified eliciting thresholds and we suggest the following steps for DPT to s-lactams: 5%-15%-30%-50% of daily therapeutic dose (with additional lower steps for index reactions of anaphylaxis). We confirm the safety of one-day protocol for immediate and mild non-immediate reactors, for both children and adults, with a surveillance period of 2h after the last administered dose, and a prolonged surveillance after discharge of 48 hours. Conclusion This data-driven approach in designing DPT protocols is a step forward in improving DPT standardization, starting with the most frequently tested drugs, s-lactam antibiotics. This article is protected by copyright. All rights reserved.

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.

Importance Toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS) are rare, acute, life-threatening dermatologic disorders involving the skin and mucous membranes. Research into these conditions is hampered by a lack of standardization of case reporting and data collection. Objective To establish a standardized case report form to facilitate comparisons and maintain data quality based on an international panel of SJS/TEN experts who performed a Delphi consensus-building exercise. Evidence Review The elements presented for committee scrutiny were adapted from previous case report forms and from PubMed literature searches of highly cited manuscripts pertaining to SJS/TEN. The expert opinions and experience of the members of the consensus group were included in the discussion. Findings Overall, 21 out of 29 experts who were invited to participate in the online Delphi exercise agreed to participate. Surveys at each stage were administered via an online survery software tool. For the first 2 Delphi rounds, results were analyzed using the Interpercentile Range Adjusted for Symmetry method and statements that passed consensus formulated a new case report form. For the third Delphi round, the case report form was presented to the committee, who agreed that it was “appropriate and useful” for documenting cases of SJS/TEN, making it more reliable and valuable for future research endeavors. Conclusions and Relevance With the consensus of international experts, a case report form for SJS/TEN has been created to help standardize the collection of patient information in future studies and the documentation of individual cases.

SummaryBackground Allopurinol is a frequent cause of severe cutaneous adverse reactions (SCARs), such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The reactions can potentially be fatal. As drug rechallenge in patients with a history of drug-induced SCARs is contraindicated, in vitro testing may have a diagnostic role as a confirmation test. Objectives To study the diagnostic value of interferon (IFN)-γ enzyme-linked immunospot (ELISpot) assay as a confirmatory test in patients with a history of allopurinol-induced SCARs. Methods Peripheral blood mononuclear cells (PBMCs) from 24 patients with a history of allopurinol-induced SCAR (13 DRESS, 11 SJS/TEN) and 21 control subjects were incubated with allopurinol or oxypurinol in the presence or absence of antiprogrammed death ligand 1 antibody (anti-PD-L1). The numbers of IFN-γ-releasing cells after stimulation in each group were subsequently measured with ELISpot. Results The numbers of IFN-γ-releasing cells in allopurinol-allergic subjects were significantly higher than in control subjects when stimulating PBMCs with oxypurinol 100 μg mL−1, especially when adding anti-PD-L1 supplementation. According to the receiver operating characteristic curve results, the optimal discriminatory power of IFN-γ ELISpot in confirming diagnosis of allopurinol-induced SCARs can be obtained using 16 spot-forming cells per 106 PBMCs as a cut-off value upon oxypurinol/anti-PD-L1 stimulation (79·2% sensitivity and 95·2% specificity). Conclusions The measurement of oxypurinol/anti-PD-L1-inducing IFN-γ-releasing cells yields a high diagnostic value in distinguishing between allopurinol-allergic and control subjects. This technique is beneficial in confirming diagnosis of allopurinol-induced SCARs in patients whose reaction develops while taking multiple drugs.

Aim We aimed to determine the prevalence and characteristics of adverse drug events (ADE) in rheumatoid arthritis (RA) and (osteoarthritis) OA patients. Method A cross-sectional study at rheumatology clinics, was performed by random selection of RA and OA out-patients by a research pharmacist. All suspected ADEs occurring during the last hospital visit and the subjects were identified by retrospective chart review and direct patient interview. ADE characteristics, including causative drug groups, affected organ severity and patient outcomes, were recorded. Results One hundred and forty-three patients consisting of 129 RA and 14 OA were recruited. The patients’ mean ages were 54.3 ± 14.3 years and 121 (84.6%) patients were female. A total of 68 ADEs were detected in 51 patients. The prevalence and rate of ADE were 35.7% and 47.6 events per 100 patients, respectively. Thirty out of 68 ADEs (44.1%) were preventable. Disease-modifying anti-rheumatic drugs and non-steroidal anti-inflammatory drugs resulted in ADEs by 41 (59.4%) and 10 (14.5%) events, respectively. Common affected organs were skin, gastrointestinal tract and eyes which accounted for 20 (29.4%), 18 (26.5%) and eight events (11.6%), respectively. Continuation of the suspected drug was noted in 42 ADEs (61.8%), classified as severity level 1 and 2a-b, and 43 ADEs (63.2%) were completely or partially resolved during the study period. Conclusion ADEs are common in RA and OA patients with prevalence of 35.7%. High exposure to potentially harmful drugs might explain the higher rate of ADE in these patients.

Drug provocation test (DPT) is necessary to diagnose most drug hypersensitivity reactions (HSRs) due to decreased sensitivity of skin testing even when combined with in-vitro tests in immunonologic drug HSR and limited availability of these tests in nonimmunologic reaction. We review the principles and controversial issues of DPT, and recent studies using DPT as a diagnostic tool.DPT is recommended in the diagnosis of HSR to β-lactams, as well as other drug classes [such as acetylsalicylic acid-NSAIDs (ASA-NSAIDs), non-β-lactams antibiotics, heparin, glucocorticoids, and local anesthetic agents]. In view of the decreased sensitivity of skin testing, limited accessibility to new benzylpenicillin polylysine (PPL)/mixture of minor determinant (MDM) test reagents and limited availability of validated sensitive in-vitro tests, individuals who require DPT to β-lactams are increasing. The negative predictive value of allergologic work-up is very high, ranging from 94 to 98% for β-lactams and those reactions after negative tests are mostly nonimmediate and mild. Finally, DPT is recommended to ascertain tolerability of alternative compound when evaluating cross-reactivity among different classes of β-lactams, NSAIDs and glucocorticoids, and possibly iodinated contrast media.DPT is often needed when evaluating patients with suspected drug HSR. More studies regarding standardization of the various protocols are needed in order to increase its acceptance and adoption as a standard practice in the diagnostic algorithm for drug HSR.

Background The prevention and confirmation of drug-induced severe cutaneous adverse reactions (SCARs) are difficult. Objective To determine the benefit of HLA-B allele prescreening and the measurement of drug-specific IFN-γ-releasing cells in the prevention and identification of the culprit drug in patients with SCARs. Methods A total of 160 patients with SCARs were recruited from 6 university hospitals in Thailand over a 3-year period. HLA-B alleles were genotypically analyzed. The frequencies of drug-specific IFN-γ-releasing cells in patients with SCARs were also measured. Results The drugs commonly responsible for SCARs were anticonvulsants, allopurinol, beta-lactams, antituberculosis agents, and sulfonamides. If culprit drugs had been withheld in patients carrying known HLA-B alleles at risk, it would have prevented 21.2% of SCAR cases, mainly allopurinol- and carbamazepine-related SCARs. Culprit drug-specific IFN-γ-releasing cells could be identified in 45.7% (53 of 116) of patients with SCARs caused by 5 major drug groups, particularly in patients diagnosed with drug reactions with eosinophilia and systemic symptoms (DRESS) (50.0%), followed by Stevens-Johnson syndrome/toxic epidermal necrolysis (46.0%), and acute generalized exanthematous pustulosis (31.3%). According to our study, high frequencies of drug-specific IFN-γ-releasing cells were significantly demonstrated in patients who suffered from DRESS phenotype, having anticonvulsants or the drugs belonging to the “probable” category based on the Naranjo algorithm scale, as the culprit drugs. Conclusions HLA-B prescreening would succeed in preventing only a minority of SCAR victims. Drug-specific IFN-γ-releasing cells are detectable in almost half of patients. Better strategies are required for better SCAR prevention and culprit drug confirmation.

Background Asthma and chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is an increasingly recognized clinical entity. ACOS significantly impacts on patient outcome compared to isolated asthma or COPD. However, ACOS definition and diagnosis criteria have not been well standardized. ACOS prevalence and clinical features in Thailand has never been studied. Objective: To investigate the prevalence and clinical features of ACOS compared to isolated asthma or COPD among patients with clinician-diagnosis of obstructive airway diseases. Objective To investigate the prevalence and clinical features of ACOS compared to isolated asthma or COPD among patients with clinician-diagnosis of obstructive airway diseases. Methods Spirometry, skin prick test (SPT) and allergens specific IgE (sIgE) were done. Serum total IgE, exhaled nitric oxide (FeNO) and blood eosinophils were measured. High resolution computed tomography (HRCT) was performed. Smoking history, pollution, biomass exposure and symptoms (Asthma Control Test [ACT], COPD assessment test [CAT], Modified Medical Research Council Dyspnea Scale [MMCR]) were assessed. Patients were classified to isolated asthma, COPD or ACOS according to predefined definitions for this study. Results A total 92 patients were enrolled: 58 patients with clinician-diagnosed of late onset asthma and 34 with clinician-diagnosed COPD. The mean age was 67.4 years. Thirty-four asthma patients (58.6%) were considered to have ACOS with postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio

Phenytoin is one of the most common causative drugs of several types of severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS). Genetic polymorphisms of the human leukocyte antigens (HLA) and cytochromes P450 (CYP) have been proposed as key elements for the susceptibility to phenytoin-related SCAR in certain ethnicities. This study investigated the associations between the genetic polymorphisms of HLA class I and CYP2C9 and phenytoin-related SCAR in a Thai population.Sixty phenytoin-related SCAR (i.e. 39 SJS/TEN and 21 DRESS) and 92 phenytoin-tolerant patients were enrolled in the study. The genotypes of HLA class I and CYP2C9 were determined.Six HLA alleles including HLA-A*33:03, HLA-B*38:02, HLA-B*51:01, HLA-B*56:02, HLA-B*58:01, and HLA-C*14:02 were significantly associated with phenytoin-related SJS/TEN, whereas only the HLA-B*51:01 was significantly associated with phenytoin-related DRESS. The odds ratios of phenytoin-related SJS/TEN in the patients who carried one of these alleles ranged from 4- to 10-fold. The frequencies of patients who carried the HLA-B*15:02 in the SJS/TEN (12.82%) or the DRESS (9.52%) groups were not significantly different from that of the controls (14.13%). The higher risk of phenytoin-related SJS/TEN was observed in the patients with CYP2C9*3 (odds ratio=4.30, 95% confidence interval=1.41-13.09, P0.05).Neither SJS/TEN nor DRESS caused by phenytoin was significantly associated with the HLA-B*15:02. The CYP2C9*3 variant was significantly associated with phenytoin-related SJS/TEN, but not DRESS. Certain alleles of HLA, particularly HLA-B*56:02, were significantly associated with phenytoin-related SCAR in the study population.

Background: 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. Objective: To determine the negative predictive value (NPV) of skin testing with β-lactam antibiotics for the diagnosis of β-lactam hypersensitivity. Methods: 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 β-lactam. 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 β-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: The in-depth characterization of the recently identified house dust mite (HDM) major allergen Der p 23 requires the production of its recombinant counterpart because the natural allergen is poorly extractable from fecal pellets. This study aimed to provide a detailed physico-chemical characterization of recombinant Der p 23 (rDer p 23) as well as to investigate its IgE reactivity in a cohort of HDM-allergic patients from Thailand. Methods: Purified rDer p 23, secreted from recombinant Pichia pastoris, was characterized by mass spectrometry and circular dichroism analyses as well as for its chitin-binding activity. The IgE-binding frequency and allergenicity of Der p 23 were determined by ELISA and RBL-SX38 degranulation assays, respectively. Results: Purified intact rDer p 23 carried O-mannosylation and mainly adopted a random coil structure. Polyclonal antibodies to rDer p 23 can detect the corresponding natural allergen (nDer p 23) in aqueous fecal pellet extracts, suggesting that both forms of Der p 23 share common B-cell epitopes. Despite its homologies with chitin-binding proteins, both natural Der p 23 and rDer p 23 were unable to interact in vitro with chitin matrices. Of 222 Thai HDM-allergic patients tested, 54% displayed Der p 23-specific IgE responses. Finally, the allergenicity of rDer p 23 was confirmed by the degranulation of rat basophil leukemia cells. Conclusion: Our findings highlighted important levels of Der p 23 sensitizations in Thailand. Our study clearly suggested that rDer p 23 is likely more appropriate for HDM allergy component-resolved diagnosis than HDM extracts.