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        The Role of In Vitro Detection of Drug- Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions

        Klaewsongkram Jettanong,Buranapraditkun Supranee,Thantiworasit Pattarawat,Rerknimitr Pawinee,Tuchinda Papapit,Chularojanamontri Leena,Rerkpattanapipat Ticha,Chanprapaph Kumutnart,Disphanurat Wareeporn 대한천식알레르기학회 2021 Allergy, Asthma & Immunology Research Vol.13 No.6

        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 druginduced IFN-γ- and GrB-releasing cells confirmed the culprit drugs in 62.5% of SJS/TEN. Alpha-galactosylceramide supplementation significantly increased the frequencies of druginduced 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.

      • KCI등재

        Clinical Characteristics, Urinary Leukotriene E4 Levels, and Aspirin Desensitization Results in Patients With NSAID-Induced Blended Reactions

        Klaewsongkram Jettanong,Buranapraditkun Supranee,Mongkolpathumrat Pungjai,Palapinyo Sirinoot,Chantaphakul Hiroshi 대한천식알레르기학회 2021 Allergy, Asthma & Immunology Research Vol.13 No.2

        Purpose: Data on non-steroidal anti-inflammatory drug (NSAID) hypersensitivity in Southeast Asia are scarce. Increased urinary leukotriene E4 (uLTE4) levels have been suggested as a biomarker of NSAID-exacerbated respiratory disease (NERD). This study investigated clinical patterns of NSAID sensitivity in Thailand and the diagnostic roles of uLTE4 measurement in various phenotypes. Methods: The clinical phenotypes in 92 Thai adults with cross-reactive NSAID hypersensitivity were characterized based on the clinical history and drug provocation. The uLTE4 levels were measured at baseline, after aspirin provocation and after desensitization. Results: More than half of the patients (56.5%) presented with cutaneous symptoms (NSAID-exacerbated cutaneous disease), while one-third (33.7%) developed symptoms in at least 2 systems (NSAID-induced blended reactions; NIBR). Fifty-two patients underwent drug provocation and 59.6% of them yielded positive results. After drug provocation, a significant number of patients with confirmed NSAID cross-reactivity experienced clinical symptoms in more than one organ system. The uLTE4 levels at baseline were comparable between the NSAID-tolerant and NSAID-sensitive groups, but were substantially increased after aspirin provocation predominantly in NERD (983.4 pg/mg creatinine) and NIBR (501.0 pg/mg creatinine) compared to NSAID-tolerant subjects (122.1 pg/mg creatinine, P < 0.01 and 0.05, respectively). The uLTE4 levels were elevated after aspirin desensitization, although nasal polyposis and asthma were under control in 3 NERD and 3 NIBR subjects. Conclusions: NIBR is not uncommon among NSAID-sensitive patients in Thailand. The diagnostic value of basal uLTE4 levels was limited, but increased uLTE4 levels upon aspirin provocation suggest NSAID cross-reactivity with respiratory components. This study indicates that aspirin desensitization, if necessary, might be effective in both NERD and NIBR.

      • KCI등재

        A Case of Sulfasalazine-Induced Hypersensitivity Syndrome Confirmed by Enzyme-Linked Immunospot Assay

        Parkpoom Phatharacharukul,Jettanong Klaewsongkram 대한천식알레르기학회 2013 Allergy, Asthma & Immunology Research Vol.5 No.6

        A 24-year-old male with a history of spondyloarthropathy presented with high fever, cervical lymphadenopathy and generalized maculopapular rash. He was treated with prednisolone for chronic uveitis before being switched to sulfasalazine 3 weeks prior to admission. Laboratory findings revealedmarked leukocytosis with frequent atypical lymphocytes. Sulfasalazine was discontinued and the etiology of mononucleosis syndrome explored. During admission, he developed acalculous cholecystitis and hypotension. All symptoms quickly improved following administration of systemic corticosteroids. The investigation for infectious mononucleosis yielded negative results and a diagnosis of sulfasalazine-induced hypersensitivity syndromewas confirmed using enzyme-linked immunospot assays.

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