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Objectives: This report presents a case of pseudoephedrine-induced nonpigmented bullous fixed drug eruption (NBFDE) manifesting as recurrent palmoplantar exfoliation in a scuba diver. It emphasizes the importance of considering drug allergies in the differential diagnosis when divers present with peeling hands and soles. Methods: A 38-year-old female scuba diver experiencing recurrent palmoplantar exfoliation underwent a clinical evaluation, patch testing, an interferon-gamma enzyme-linked immunospot (ELISpot) assay, and graded drug challenges with pseudoephedrine and phenylephrine. Results: Patch testing yielded negative results; however, the ELISpot assay indicated a strong immune response to pseudoephedrine. A graded challenge involving pseudoephedrine successfully reproduced the symptoms, confirming a diagnosis of pseudoephedrine-induced NBFDE. Subsequently, a challenge with phenylephrine elicited a milder reaction, suggesting it as a potential alternative medication for the patient. Conclusions: This case highlights NBFDE as a potential cause of skin peeling in scuba divers who are allergic to pseudoephedrine. It emphasizes the importance of considering drug allergies when diagnosing palmoplantar exfoliation in divers and underscores the need for a thorough evaluation of medication use in this group. Alternative medications and management strategies should be considered for divers with a pseudoephedrine allergy to prevent ear barotrauma while minimizing the risk of adverse skin reactions.
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BACKGROUND: Allopurinol has been causing substantial morbidity and mortality particularly in Asian population by producing cutaneous adverse drug reactions (cADRs). Nonetheless, there are no data describing whether other genetics are a valid marker for prediction of allopurinol-induced cADRs patients in addition to HLA-B*58:01 allele. The goal of this study was to identify suitable single nucleotide polymorphisms (SNPs) for allopurinol induced cADRs among Thai patients. METHODS: We conducted a case-control association study after enrolling 57 Thai patients with allopurinol induced cADRs and 101 allopurinol-tolerant controls. The genetic biomarkers and associated SNPs located on chromosome 6p21 were examined by TaqMan® SNP genotyping assays in both the cases and the controls. RESULTS: Out of fifteen SNPs in nine genes, we found four combined SNPs (rs3099844 of HCP5, rs9263726 of PSORS1C1, rs9263733 of POLR2LP, and rs9263745 of CCHCR1) were significantly associated with allopurinol-induced cADRs compared to the tolerant controls (OR 73.2; 95% CI 24.2-266.8; P = 1.9 × 10- 24). The overall sensitivity, specificity, positive predictive value and negative predictive value of these combinations were 84%, 94%, 9%, and 100%, respectively. However, the variant alleles of these SNP combinations were detected in 89.5% (51/57) of the cases. Moreover, the HLA-B*58:01 allele was observed in 86.0% of patients with allopurinol-induced cADRs, but only in 4.0% of tolerant controls (OR: 137.2; 95% CI: 38.3-670.5 and p-value = 1.7 × 10- 27). CONCLUSIONS: Thus, this research confirms the association between the specific HLA-B*58:01 allele and all phenotypes of allopurinol-induced cADRs in Thais. Furthermore, there was found the combined four SNPs (rs3099844, rs9263726, rs9263733, and rs9263745) could be used as alternative novel biomarkers for predicting cADRs in patients taking allopurinol.
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Alopurinol , Polimorfismo de Nucleótido Simple , Humanos , Alopurinol/efectos adversos , Masculino , Femenino , Tailandia , Persona de Mediana Edad , Estudios de Casos y Controles , Anciano , Adulto , Farmacogenética , Antígenos HLA-B/genética , Predisposición Genética a la Enfermedad , Variantes Farmacogenómicas , Pueblos del Sudeste AsiáticoRESUMEN
BACKGROUND: Diagnosing drug-induced allergy, especially nonimmediate phenotypes, is challenging. Incorrect classifications have unwanted consequences. OBJECTIVE: We sought to evaluate the diagnostic utility of IFN-γ ELISpot and clinical parameters in predicting drug-induced nonimmediate hypersensitivity using machine learning. METHODS: The study recruited 393 patients. A positive patch test or drug provocation test (DPT) was used to define positive drug hypersensitivity. Various clinical factors were considered in developing random forest (RF) and logistic regression (LR) models. Performances were compared against the IFN-γ ELISpot-only model. RESULTS: Among the 102 patients who had 164 DPTs, most patients had severe cutaneous adverse reactions (35/102, 34.3%) and maculopapular exanthems (33/102, 32.4%). Common suspected drugs were antituberculosis drugs (46/164, 28.1%) and ß-lactams (42/164, 25.6%). Mean (SD) age of patients with DPT was 52.7 (20.8) years. IFN-γ ELISpot, fixed drug eruption, Naranjo categories, and nonsteroidal anti-inflammatory drugs were the most important features in all developed models. The RF and LR models had higher discriminating abilities. An IFN-γ ELISpot cutoff value of 16.0 spot-forming cells/106 PBMCs achieved 94.8% specificity and 57.1% sensitivity. Depending on clinical needs, optimal cutoff values for RF and LR models can be chosen to achieve either high specificity (0.41 for 96.1% specificity and 0.52 for 97.4% specificity, respectively) or high sensitivity (0.26 for 78.6% sensitivity and 0.37 for 71.4% sensitivity, respectively). CONCLUSIONS: IFN-γ ELISpot assay was valuable in identifying culprit drugs, whether used individually or incorporated in a prediction model. Performances of RF and LR models were comparable. Additional test datasets with DPT would be helpful to validate the model further.
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Hipersensibilidad a las Drogas , Humanos , Persona de Mediana Edad , Hipersensibilidad a las Drogas/diagnóstico , beta-Lactamas/efectos adversos , Pruebas Inmunológicas , Ensayo de Immunospot Ligado a Enzimas , Pruebas del ParcheRESUMEN
Vitamin D deficiency has been reported to be associated with allergic diseases and dermatological disorders. We investigated the role of vitamin D in drug-induced non-immediate hypersensitivity reactions by measuring serum vitamin D levels in 60 patients diagnosed with non-immediate drug hypersensitivity reactions and in 60 patients who tolerated the same medication without any allergic reactions. The results showed that serum vitamin D levels were significantly lower in patients with severe cutaneous adverse reactions (SCARs) (13.56 ± 6.23 ng/mL) compared to patients with mild reactions (17.50 ± 7.49 ng/mL) and the drug-tolerant control group (17.42 ± 7.28 ng/mL), with p values of 0.031 and 0.015, respectively. The proportion of severe vitamin D deficiency (< 10 ng/mL) was much higher in SCAR patients compared to drug-tolerant subjects (36.7% vs. 11.7%, p value = 0.005). After adjusting for age, gender, region of residence, and concurrent illnesses, patients with severe vitamin D deficiency had significantly increased in-hospital mortality (odds ratio 16.04; 95% CI, 1.25-206.12, p value = 0.03). In conclusion, the risk of developing SCARs and in-hospital mortality was increased in patients with severe vitamin D deficiency. Further investigations should be conducted to elucidate the role of vitamin D in the development of SCARs.
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Hipersensibilidad , Deficiencia de Vitamina D , Humanos , Cicatriz , Deficiencia de Vitamina D/complicaciones , Vitamina D , Vitaminas , Hipersensibilidad/complicacionesAsunto(s)
Hipersensibilidad a las Drogas , Hipersensibilidad , Humanos , Cefalosporinas/efectos adversos , Antibacterianos , Penicilinas , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/tratamiento farmacológico , Monobactamas , Hipersensibilidad/tratamiento farmacológico , Reacciones Cruzadas , Pruebas CutáneasRESUMEN
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatological emergencies. The role of cytokines and chemokines in the pathogenesis, progression of the disease, and histopathologic features is not fully elucidated. To address this gap, we conducted a retrospective study examining the associations between 42 serum biomarkers, histopathologic findings, and clinical outcomes in SJS/TEN patients. We reviewed the medical records of 23 patients diagnosed with SJS/TEN. Regarding histopathology, our study did not reveal any significant associations between the degree of epidermal necrosis, dermal mononuclear cell infiltration, and clinical outcomes. However, an intriguing observation was made regarding the degree of dermal infiltration of CD8 + cells, which showed a negative correlation with the severity of acute ocular complications. Notably, serum levels of IFN-γ positively correlated with the number of CD8 + cells in dermal infiltration. Additionally, higher serum levels of myeloperoxidase were associated with greater degrees of epidermal necrosis, while serum Fas ligand and stem cell factor levels were elevated in individuals with increased dermal mononuclear cell infiltration. Furthermore, the levels of S100A8/A9 were significantly correlated with the SCORTEN and mortality rate. These findings provide insights into the intricate pathogenesis of the disease.
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Síndrome de Stevens-Johnson , Humanos , Calgranulina A , Linfocitos T CD8-positivos , Necrosis , Estudios RetrospectivosRESUMEN
BACKGROUND: At present, no predictive models are available to determine the probability of in-hospital mortality rates (HMRs) in all phenotypes of severe cutaneous adverse reactions (SCARs). OBJECTIVES: Our study explored whether simple clinical and laboratory assessments could help predict the HMRs in any phenotypes of SCAR patients. METHODS: Factors influencing HMRs in 195 adults diagnosed with different SCAR phenotypes were identified, and their optimal cut-offs were determined by Youden's index. Predictive equations for HMRs for all SCAR patients and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) patients were determined using the exact logistic regression models. RESULTS: Acute generalized exanthematous pustulosis (AGEP) patients were significantly older, with a short time from drug exposure to reaction, and higher neutrophil count compared to SJS/TEN and drug reaction with eosinophilia and systemic symptoms (DRESS, p < 0.001). Peripheral blood eosinophilia, atypical lymphocytosis and elevated liver transaminase enzymes were significantly higher in DRESS. SJS/TEN phenotype, age ≥ 71.5 years, neutrophil-to-lymphocyte ratio ≥ 4.08 (high NLR) and systemic infection were factors predicting in-hospital mortality in all SCAR subjects. The ALLSCAR model developed from these factors demonstrated high-diagnostic accuracy for predicting HMRs in all SCAR phenotypes (area under the receiver-operator curve (AUC) = 0.95). The risk of in-hospital death was significantly increased in SCAR patients with high NLR after adjusting for systemic infection. The model derived from high NLR, systemic infection and age yielded higher accuracy than SCORTEN (AUC = 0.77) for predicting the HMRs in SJS/TEN patients (AUC = 0.97). CONCLUSIONS: Being older, having systemic infection, having a high NLR and SJS/TEN phenotype increases ALLSCAR scores, which in turn increases the risk of in-hospital mortality. These basic clinical and laboratory parameters can easily be obtained in any hospital setting. Despite its simple approach, further validation of the model is warranted.
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Pustulosis Exantematosa Generalizada Aguda , Eosinofilia , Síndrome de Stevens-Johnson , Humanos , Mortalidad Hospitalaria , Tailandia/epidemiología , Síndrome de Stevens-Johnson/genética , CicatrizRESUMEN
BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reactions with eosinophilia and systemic symptoms (DRESS) are both severe cutaneous adverse reactions. Keratinocyte death is much more prominent in SJS/TEN compared to DRESS. OBJECTIVE: This study aimed to investigate the role of exosomal miRNAs on keratinocyte death in SJS/TEN. METHODS: Peripheral blood mononuclear cells (PBMCs) from SJS/TEN and DRESS patients were stimulated with the culprit drugs. The exosomes released in cell supernatants were co-incubated with HaCaT cells to study the cytotoxic effects on keratinocytes. Exosomal miRNA sequencing analysis was performed to compare the expression patterns between SJS/TEN and DRESS subjects. HaCaT cells were then transfected with miRNA mimics and inhibitors to explore the functions of miRNAs on keratinocyte cell death. RESULTS: Cytotoxic effects of PBMC-derived exosomes on keratinocytes were demonstrated in SJS/TEN and could be neutralized with exosome inhibitors. Cytotoxic effects of PBMC-derived exosomes from SJS/TEN subjects were higher after incubating PBMCs with the culprit drugs than those incubating with irrelevant drugs and unstimulated controls. The sequencing data revealed differential expressions of 61 exosomal miRNAs between SJS/TEN and DRESS. Exosomal miR-4488 was upregulated while miR-486-5p, miR-96-5p and miR-132-3p were downregulated in SJS/TEN compared to DRESS as determined by quantitative real-time PCR. The increased percentage of apoptotic cells upon transfection of HaCat cells was 36.3% and 34.9% with miR-4488 mimic and miR-96-5p inhibitor, respectively. CONCLUSION: This study illustrated the regulatory functions of exosomal miRNAs in controlling keratinocyte death in SJS/TEN. Exosome inhibitors might have a therapeutic role in SJS/TEN.
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Eosinofilia , MicroARNs , Síndrome de Stevens-Johnson , Humanos , Síndrome de Stevens-Johnson/terapia , MicroARNs/metabolismo , Leucocitos Mononucleares/metabolismo , Queratinocitos/metabolismo , Muerte CelularRESUMEN
BACKGROUND: Mislabeling of drug allergic histories causes avoidable negative impacts on patients and healthcare system. Although multidisciplinary adverse drug reaction (ADR) services to verify and de-label drug allergic histories have been operated in particular hospitals in Thailand, their performances have not been reported. This research aimed to examine the effectiveness of verification of drug allergic history and de-labeling (VD) services of the physician-led multidisciplinary ADR clinic. METHODS: This research was a retrospective descriptive study. Medical charts of patients with at least one drug allergic history who received VD services at the multidisciplinary clinic between January 2017 to December 2018, were reviewed. Data on the history of drug allergy, VD services, and results were analyzed and presented using descriptive statistics. RESULTS: Seventy patients' charts were reviewed, and 171 unconfirmed drug allergic histories were identified. 79.53% of the reported reactions involved skin and soft tissues. The most found adverse skin reactions were maculopapular rash, pruritic and erythematous rash, and angioedema. The remaining 20.47% were systemic reactions which included drug reaction with eosinophilia and systemic symptoms (DRESS), anaphylaxis, and nausea/vomiting was the most prevalent. Antituberculosis, beta-lactam antibiotics, and nonsteroidal anti-inflammatory drugs (NSAIDs) were the most reported suspected drugs. Drug allergic history reviewing by physicians or pharmacists could confirm and de-label for 3 and 20 reactions, respectively. Seven and one reactions were confirmed by enzyme-linked immunospot assay and patch test, respectively. The provocation tests with the suspected or alternative drug were conducted in 64 reactions. Twelve reactions were confirmed, and 45 reactions were de-labeled. Totally, 65/171 (38.01%) allergic histories were successfully de-labeled, 23/171 (13.45%) were confirmed, and 83/171 (48.53%) were inconclusive. CONCLUSIONS: More than half of drug allergic histories were successfully confirmed or de-labeled by the multidisciplinary ADR team. The collaborative activities of various healthcare professionals, consisting of physicians, nurse, and pharmacists as presented in the study were effective in VD services and should be implemented in other healthcare settings.
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Clinical applications of skin testing are known to help diagnose IgE-mediated and T-cell-mediated delayed cutaneous reactions. By contrast, drug-induced immune complex-mediated vasculitis is primarily diagnosed based on medical history, clinical setting and laboratory evidence of immune-complex formation, as there are no proven methods to identify the suspect culprit. We report three cases of drug- or biologic-induced immune complex-mediated vasculitis, in which the culprit agents could be confirmed by a positive intradermal test with later reading (between 12 and 24 h after the test), with verification by immunohistochemical or immunofluorescent results. The findings of our study suggest that skin tests with a delayed reading could have a potential role in diagnosing some instances of immune complex-mediated hypersensitivity reactions.
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Hipersensibilidad a las Drogas , Hipersensibilidad Tardía , Hipersensibilidad Inmediata , Hipersensibilidad , Vasculitis , Humanos , Hipersensibilidad a las Drogas/diagnóstico , Complejo Antígeno-Anticuerpo/efectos adversos , Pruebas Cutáneas/métodos , Hipersensibilidad/diagnóstico , Hipersensibilidad/etiología , Hipersensibilidad Inmediata/inducido químicamente , Hipersensibilidad Tardía/inducido químicamenteRESUMEN
BACKGROUND: Data on beta-lactam hypersensitivity (BLH) are mainly focused on immediate or mild nonimmediate reactions in the ambulatory setting, but limited in patients with concurrent illness and moderate-to-severe nonimmediate reactions in the hospitalized setting. OBJECTIVE: To investigate the entire spectrum of BLH in Thai tertiary hospital. METHODS: Clinical characteristics of 357 patients with suspected BLH were evaluated in a 7-year period. Culprit drug identification was performed in 335 patients by combined skin testing, in vitro testing, or drug provocation tests. RESULTS: The predominant BLH presentations were non-immunoglobulin (Ig)E-mediated reactions with severe cutaneous adverse reactions of 18.9%, and BLH status was definitively confirmed in 18.1%. The most common verified culprits were cephalosporins (34.8%), particularly in hypersensitivity type IV reactions. Natural penicillins were the main implicated drugs in 48.5% of ambulatory patients. In contrast, cephalosporins and carbapenems were the main implicated drugs in hospitalized patients. Non-IgE-mediated anaphylaxis and serum sickness-like reaction remained diagnostically challenged. New generations of beta-lactams, hospitalized patients, recent allergic history, and underlying malignancies or autoimmune diseases were associated with increased BLH risk. CONCLUSION: At present, cephalosporins are the leading causes of BLH, particularly in non-IgE-mediated reactions. More research on the verification of non-IgE hypersensitivity reactions from new generations of beta-lactams should be better emphasized. CLINICAL TRIAL REGISTRATION: The registry was approved by the Ethics and Research Committee of the Faculty of Medicine, Chulalongkorn University, and listed on ClinicalTrials.gov (Identifier: NCT01667055; https://www. CLINICALTRIALS: gov/ct2/show/NCT01667055).
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Hipersensibilidad a las Drogas , Hipersensibilidad Inmediata , Humanos , Antibacterianos/efectos adversos , beta-Lactamas/efectos adversos , Carbapenémicos/efectos adversos , Cefalosporinas/efectos adversos , Reacciones Cruzadas , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad Inmediata/diagnóstico , Penicilinas/efectos adversos , Pruebas CutáneasRESUMEN
Urticaria is a common cutaneous adverse event from coronavirus disease 2019 vaccination. Previous studies hypothesized that excipients as polyethylene glycol in BNT162b2 vaccine and polysorbate in ChAdOx1 nCoV-19 vaccine are allergens. A 28-year-old woman had urticaria after a booster vaccination with BNT162b2 at the site of previous intradermal injection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) spike protein. This reaction emphasized that delayed urticaria may not be an allergic reaction to excipient but rather to the immunogen as such as SARS-CoV-2 spike protein.
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Background: Oxaliplatin is a third-generation platinum compound that has efficacy against colorectal cancer. Hypersensitivity reactions during oxaliplatin infusion are a key problem during its use, with the varying incidences and deficiencies of clearly identified risk factors. Objective: To determine the incidence, severity and risk factors of oxaliplatin-related hypersensitivity reaction (HSR). Method: This retrospective study investigated 245 colorectal cancer patients (1,690 treatment cycles) receiving care at King Chulalongkorn Memorial Hospital, Thai Red Cross society between January 1, 2015 and December 31, 2019. The patients' demographic data, laboratory data and clinical features suggesting hypersensitivity reactions to oxaliplatin were reviewed. The Fisher's Exact test and unpaired t-test were used to determine the differences among patients with and without oxaliplatin HSR. The potential risk factors for oxaliplatin HSR were analyzed for statistical significance by logistic regression. Results: A total of 245 colorectal cancer patients (1,690 treatment cycles) were included in this study. The incidence of oxaliplatin HSR was 37.96%, according to the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (NTCAE) version 5.0, grade 1, grade 2 and higher grades were 27.35% (67 patients), 6.53% (16 patients) and 4.08% (10 patients), respectively. The proportion of male patients and patients with a history of prior exposure to platinum-based chemotherapy were statistically higher in the HSR group. The eosinophil count and serum creatinine level were also significantly greater in the HSR group. On the contrary, the total lymphocyte count and serum albumin level were significantly lower in the HSR group. The multivariate logistic regression found 5 risk factors with a significant difference. Male gender, prior exposure to platinum-based chemotherapy and elevated eosinophil count were associated with increased risk of oxaliplatin HSR, whereas elevated monocyte count and elevated serum albumin were protective factors for the development of oxaliplatin HSR. Conclusion: Colorectal cancer patients treated with an oxaliplatin-based regimen with male gender, prior exposure to platinum-based chemotherapy and elevated eosinophil count have a greater risk of oxaliplatin related hypersensitivity reactions.
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Background: Oxaliplatin is a third-generation platinum compound that has efficacy against colorectal cancer. Hypersensitivity reactions during oxaliplatin infusion are a key problem during its use, with the varying incidences and deficiencies of clearly identified risk factors. Objective: To determine the incidence, severity and risk factors of oxaliplatin-related hypersensitivity reaction (HSR). Method: This retrospective study investigated 245 colorectal cancer patients (1,690 treatment cycles) receiving care at King Chulalongkorn Memorial Hospital, Thai Red Cross society between January 1, 2015 and December 31, 2019. The patients demographic data, laboratory data and clinical features suggesting hypersensitivity reactions to oxaliplatin were reviewed. The Fishers Exact test and unpaired t-test were used to determine the differences among patients with and without oxaliplatin HSR. The potential risk factors for oxaliplatin HSR were analyzed for statistical significance by logistic regression. (AU)
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Hipersensibilidad , Oxaliplatino , Neoplasias Colorrectales , Estudios Retrospectivos , TailandiaRESUMEN
A high prevalence of hepatitis B (HepB) antibody loss after liver transplantation (LT) and de novo HepB infection (DNH) was documented, hence revaccination to prevent DNH is crucial. This study aimed to compare the safety and immunogenicity of two HepB vaccine regimens in liver-transplanted children. Liver-transplanted children who were previously immunised but showed HepB surface antibodies (anti-HBs) ≤ 100 mIU/mL were randomised to receive a standard three-dose (SD) and double three-dose (DD) vaccine intramuscularly in months 0-1-6. Anti-HBs and T-cell-specific response to the HepB antigen were assessed. A total of 61 children (54.1% male, aged 1.32 ± 1.02 years) completed the study without any serious adverse reaction. The seroprotective rate was 69.6% vs. 60% (p = 0.368) and 91.3% vs. 85% (p = 0.431) in SD and DD after the first and third 3-dose vaccinations, respectively. The geometric mean titre (95% confidence interval) of anti-HBs in SD and DD were 443.33 (200.75-979.07) vs. 446.17 (155.58-1279.50) mIU/mL, respectively, at completion. Numbers of interferon-γ-secreting cells were higher in hyporesponders/responders than in nonresponders (p = 0.003). The significant factors for the immunologic response to HepB vaccination were anti-HB levels prevaccination, tacrolimus trough levels, and time from LT to revaccination. SD and DD had comparative immunogenicity and were safe for liver-transplanted children who were previously immunised.
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INTRODUCTION: Allergic rhinitis is an inflammation of the nasal mucosa in response to allergens. There is evidence that yoga can improve personal health and has positive effects on immune function. However, the effects of Hatha yoga training on rhinitis symptoms and cytokines in patients with allergic rhinitis are still unclear. OBJECTIVE: The purpose of this study was to investigate the effects of Hatha yoga training on rhinitis symptoms and cytokines in allergic rhinitis patients. METHODS: Twenty-seven allergic rhinitis patients were randomized into 2 groups: a control group (CON; n = 14) and a yoga group (YOG; n = 13). The CON group continued with normal activities and the YOG group was required to complete a protocol of Hatha yoga training for 60 minutes per session, 3 times per week for 8 weeks. Physiological characteristics, allergic rhinitis symptoms, and cytokine secretions were comparatively analyzed before and after yoga training. RESULTS: After 8 weeks, the YOG group had increased peak nasal inspiratory flow (PNIF) and exhibited significantly decreased rhinitis symptoms and nasal blood flow (NBF) compared to pre-test. Moreover, the YOG group had significantly higher nasal secretion of interleukin (IL)-2 than the CON group. CONCLUSION: The present findings demonstrated that 8 weeks of Hatha yoga training had beneficial effects in allergic rhinitis by improved clinical allergic rhinitis and cytokine profiles.
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Rinitis Alérgica , Rinitis , Yoga , Citocinas , Humanos , Mucosa Nasal , Rinitis Alérgica/terapiaRESUMEN
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.