Dynamic cytokine profiles combined with enzyme-linked immunospot assay are useful for immunologically confirming the dapsone hypersensitivity syndrome

To the Editor: Dapsone hypersensitivity syndrome (DHS) is a dapsone-induced T–cell mediated delayed type of hypersensitivity, characterized by fever, rash, lymphadenopathy, and hepatic function abnormalities.1Richardus J.H. Smith T.C. Increased incidence in leprosy reactions to dapsone after introduction multidrug therapy.Lepr Rev. 1989; 60: 267-273PubMed Google Scholar The diagnosis DHS traditionally based on criteria proposed Richardus Smith.1Richardus However, remains challenge clinical practice due difficulty distinguishing from other drug-induced (DHRs), concurrent infections, or underlying diseases. enzyme-linked immunospot (ELISpot) method quantifying release antigen-specific cell cytokines has been widely used DHR culprit drugs coadministered drugs.2Porebski G. Czarnobilska E. Bosak M. Cytotoxicbased assays drug induced antiepileptic drugs.Pol Arch Med Wewn. 2015; 125: 823-834PubMed investigate specific ELISpot assay for diagnosis, we performed comprehensive analysis dynamic cytokine profiles, analyzing 13 (interferon [IFN]-γ, Fas ligand, granzyme B, interleukin [IL] 4, IL-5, IL-6, IL-13, IL-15, IL-17A, IL-21, IL-22, IL-23, tumor necrosis factor-α) peripheral blood mononuclear cells stimulated with without using Luminex (R&D Systems) 4 patients who were tolerant. After stimulation dapsone, index (SI) showed higher levels IFN-γ, B than SI tolerant at day 6 (SI > 2; P < .05) (Fig 1). We further developed applied them examine 16 DHS, tolerant, 12 drugs, healthy donors. In 9 (56.25%), 11 (68.75%), (68.75%) positive IL-5 ELISpot, respectively, whereas combination 3 increased sensitivity 87.5% (14 16). No tested assays, presenting 100% specificity. statistical power more 99.9% 5% significance calculated pwr package R software (The Foundation Statistical Computing, Vienna, Austria). characteristics all results are summarized Table I.1Richardus Additional information available via Mendeley https://data.mendeley.com/datasets/23h5s468c4/draft?a=e9b64699-14b0-464f-be69-e7fda7f38a9a.Table IClinical syndromeNo.Age, ySexInterval,∗Interval, time interval between onset intake appearance symptoms. dClinical manifestation†The was diagnosed Smith.1ELISpot assayFeverGeneralized rashLymphadenopathyHepatic abnormalities‡Hepatic abnormalities defined as 2× upper limit normal aspartate aminotransferase alanine fourth week eighth follow-up.JaundiceIFN-γIL-5Granzyme BCombined142M22√√√−−++241M48√√√√++++334M23√√√√√++++428M21√√√++++544F20√√√−−−−640M30√√√++++754M21√√√+−−+827F20√√√−+++922F30√√√√−+++1041F14√√√√−−−−1142M22√√√√++++1230M28√√√√++++1321M50√√√−+−+1430F26√√√−−++1555M18√√√√++++1622M14√√√++−+Positive, No.(%)9 (56.25)11 (68.75)11 (68.75)14 (87.5)F, Female; IL, interleukin; IFN, interferon; M, male; √, presented this symptom.∗ Interval, symptoms.† Scholar‡ Hepatic follow-up. Open table new tab F, symptom. efficacy previously reported.2Porebski its varied diverse pathogenesis involving initiation progression DHR. Moreover, 1 can elicit different types distinct pathomechanism. For example, pharmacologic interaction model altered peptide repertoire both involved carbamazepine-induced DHR,3Illing P.T. Vivian J.P. Dudek N.L. et al.Immune self-reactivity triggered drug-modified HLA-peptide repertoire.Nature. 2012; 486: 554-558Crossref PubMed Scopus (484) Scholar,4White K.D. Chung W.H. Hung S.I. Mallal S. Phillips E.J. Evolving models immunopathogenesis T cell-mediated allergy: role host, pathogens, response.J Allergy Clin Immunol. 136 (quiz 235): 219-234Abstract Full Text PDF (135) related cytokines, granulysin, perforin establish combined 75%.2Porebski study, our profile that expression specifically upregulated which accordance involvement CD4+ CD8+ DHS.5Zhao Q. Alhilali K. Alzahrani A. al.Dapsone- nitroso dapsone-specific activation hypersensitive expressing risk allele HLA-B∗13:01.Allergy. 2019; 74: 1533-1548PubMed 87.5%, indicating it could be an attractive technique diagnosis. conclusion, confirmed detection good performance immunologically confirming DHS. application profiles promoted development greatly enhanced