Serum Levels of Interleukin-1 Beta are Decreased in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis at the Time of Hospitalization
DOI:
https://doi.org/10.3889/oamjms.2024.11800Keywords:
Steven-Johnson syndrome, Toxic epidermal necrolysis, Severe cutaneous adverse drug reactions, Interleukin-1 beta, Fluorescence covalent microbead immunosorbent assayAbstract
BACKGROUND: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Some immunological and genetic factors are believed to be involved in the pathogenesis of the disease, including tumor necrotic factor-alpha, interferon-gamma, and interleukin (IL)-17. IL-1β is one of the most prominent cytokines associated with the innate immune response.
AIMS: The study aimed to evaluate the serum level of IL-1β in SJS/TEN and the relation between it and the progress of SJS/TEN.
METHODS: This was a cross-sectional descriptive study conducted at the National Hospital of Dermatology and Venereology, in Hanoi, Vietnam, from October 2017 to September 2019. 48 SJS/TEN patients, 43 erythema multiforme (EM) patients, and 20 healthy controls (HCs) participated. IL-1β levels were measured using the fluorescence covalent microbead immunosorbent assay (ProcartaPlex Immunoassay Panels kit, Thermo Fisher Scientific, USA). The Mann–Whitney U test was used to compare serum IL-1β levels. The Wilcoxon tests were used to compare quantitative variables before and after the treatment. Differences were considered to be statistically significant at p < 0.05.
RESULTS: 19 SJS patients (39.5%) and 29 TEN patients (60.5%) participated in our study. The mean age was 49.3 years; the range was 19–77 years (47.9% males; 52.1% females). The most common causative drugs were traditional medicine (29.1%), carbamazepine (12.5%), and allopurinol (12.5%). On the day of hospitalization, the mean serum level of IL-1β of the SJS/TEN group was 26.4 ± 81.7 pg/mL, ranging from 0.5 pg/mL to 447 pg/mL. This level was significantly lower than that of the HCs group (p < 0.001) but not lower than that of the EM group. The mean serum level of IL-1β in the SJS/TEN patients on the day of hospitalization was 26.4 ± 81.7 pg/ml, higher than that on the day of re-epithelialization (1.9 ± 5.6 pg/mL) and the difference was statistically significant with p < 0.01.
CONCLUSION: Serum IL-1β level in SJS/TEN patients is lower than in HCs. It is not a good biomarker to differentiate SJS/TEN from EM.
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Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol. 1993;129(1):92-6. PMid:8420497 DOI: https://doi.org/10.1001/archderm.129.1.92
Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: Part I. Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad Dermatol. 2013;69(2):13. e1-13, quiz 185-6. https://doi.org/10.1016/j.jaad.2013.05.003 PMid:23866878 DOI: https://doi.org/10.1016/j.jaad.2013.05.003
Su SC, Mockenhaupt M, Wolkenstein P, Dunant A, Le Gouvello S, Chen CB, et al. Interleukin-15 is associated with severity and mortality in stevens-Johnson syndrome/toxic epidermal necrolysis. J Invest Dermatol. 2017;137(5):1065-73. https://doi.org/10.1016/j.jid.2016.11.034 PMid:280111474 DOI: https://doi.org/10.1016/j.jid.2016.11.034
Wolkenstein P, Latarjet J, Roujeau JC, Duguet C, Boudeau S, Vaillant L, et al. Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis. Lancet. 1998;352(9140):1586-9. https://doi.org/10.1016/S0140-6736(98)02197-7 PMid:9843104 DOI: https://doi.org/10.1016/S0140-6736(98)02197-7
Rzany B, Mockenhaupt M, Baur S, Schröder W, Stocker U, Mueller J, et al. Epidemiology of erythema exsudativum multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis in Germany (1990-1992): Structure and results of a population-based registry. J Clin Epidemiol. 1996;49(7):769-73. https://doi.org/10.1016/0895-4356(96)00035-2 PMid:8691227 DOI: https://doi.org/10.1016/0895-4356(96)00035-2
Sassolas B, Haddad C, Mockenhaupt M, Dunant A, Liss Y, Bork K, et al. ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson syndrome and toxic epidermal necrolysis: Comparison with case-control analysis. Clin Pharmacol Ther 2010;88(1):60-8. https//doi.org/10.1038/clpt.2009.252 PMid:20375998 DOI: https://doi.org/10.1038/clpt.2009.252
Chung WH, Wang CW, Dao RL. Severe cutaneous adverse drug reactions. J Dermatol. 2016;43(7):758-66. https://doi.org/10.1111/1346-8138.13430 PMid:27154258 DOI: https://doi.org/10.1111/1346-8138.13430
Creamer D, Walsh SA, Dziewulski P, Exton LS, Lee HY, Dart JK, et al. U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016. Br J Dermatol. 2016;174(6):1194-227. https://doi.org/10.1111/bjd.14530 PMid:27317286 DOI: https://doi.org/10.1016/j.bjps.2016.01.034
Chung WH, Hung SI, Yang JY, Su SC, Huang SP, Wei CY, et al. Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis. Nat Med. 2008;14(12):1343-50. https://doi.org/10.1038/nm.1884 DOI: https://doi.org/10.1038/nm.1884
Nassif A, Bensussan A, Dorothée G, Mami-Chouaib F, Bachot N, Bagot M, et al. Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal necrolysis. J Invest Dermatol. 2002;118(4):728-33. https://doi.org/10.1046/j.1523-1747.2002.01622.x PMid:11918724 DOI: https://doi.org/10.1046/j.1523-1747.2002.01622.x
Nassif A, Bensussan A, Boumsell L, Deniaud A, Moslehi H, Wolkenstein P, et al. Toxic epidermal necrolysis: Effector cells are drug-specific cytotoxic T cells. J Allergy Clin Immunol. 2004;114(5):1209-15. https://doi.org/10.1016/j.jaci.2004.07.047 PMid:15536433 DOI: https://doi.org/10.1016/j.jaci.2004.07.047
Su SC, Chung WH. Cytotoxic proteins and therapeutic targets in severe cutaneous adverse reactions. Toxins (Basel). 2014;6(1):194-210. https://doi.org/10.3390/toxins6010194 PMid:24394640 DOI: https://doi.org/10.3390/toxins6010194
Downey A, Jackson C, Harun N, Cooper A. Toxic epidermal necrolysis: review of pathogenesis and management. J Am Acad Dermatol. 2012;66(6):995-1003. https://doi.org/10.1016/j.jaad.2011.09.029 PMid:22169256 DOI: https://doi.org/10.1016/j.jaad.2011.09.029
Viard-Leveugle I, Gaide O, Jankovic D, Feldmeyer L, Kerl K, Pickard C, et al. TNF-α and IFN-γ are potential inducers of Fas-mediated keratinocyte apoptosis through activation of inducible nitric oxide synthase in toxic epidermal necrolysis. J Invest Dermatol. 2013;133(2):489-98. https://doi.org/10.1038/jid.2012.330 PMid:22992806 DOI: https://doi.org/10.1038/jid.2012.330
Abe R, Shimizu T, Shibaki A, Nakamura H, Watanabe H, Shimizu H. Toxic epidermal necrolysis and Stevens- Johnson syndrome are induced by soluble Fas ligand. Am J Pathol. 2003;162(5):1515-20. https://doi.org/10.1016/S0002-9440(10)64284-8 PMid:12707034 DOI: https://doi.org/10.1016/S0002-9440(10)64284-8
Posadas SJ, Padial A, Torres MJ, Mayorga C, Leyva L, Sanchez E, et al. Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity. J Allergy Clin Immunol. 2002;109(1):155-161. https://doi.org/10.1067/mai.2002.120563 PMid:11799383 DOI: https://doi.org/10.1067/mai.2002.120563
Schroder K, Tschopp J. The inflammasomes. Cell. 2010;140(6):821-832. https://doi.org/10.1016/j.cell.2010.01.040 PMid:20303873 DOI: https://doi.org/10.1016/j.cell.2010.01.040
Schulte W, Bernhagen J, Bucala R. Cytokines in sepsis: Potent immunoregulators and potential therapeutic targets--an updated view. Mediators Inflamm. 2013;2013:165974. https://doi.org/10.1155/2013/165974 PMid:23853427 DOI: https://doi.org/10.1155/2013/165974
Auquier-Dunant A, Mockenhaupt M, Naldi L, Correia O, Schröder W, Roujeau JC, et al. Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis: Results of an international prospective study. Arch Dermatol. 2002;138(8):1019-24. https://doi.org/10.1001/archderm.138.8.1019 PMid:12164739 DOI: https://doi.org/10.1001/archderm.138.8.1019
Morsy H, Taha EA, Nigm DA, Shahin R, Youssef EMK. Serum IL-17 in patients with erythema multiforme or Stevens- Johnson syndrome/toxic epidermal necrolysis drug reaction, and correlation with disease severity. Clin Exp Dermatol. 2017;42(8):868-73. https://doi.org/10.1111/ced.13213 PMid:28940568 DOI: https://doi.org/10.1111/ced.13213
Iwai S, Sueki H, Watanabe H, Sasaki Y, Suzuki T, Iijima M. Distinguishing between erythema multiforme major and Stevens-Johnson syndrome/toxic epidermal necrolysis immunopathologically. J Dermatol. 2012;39(9):781-6. https://doi.org/10.1111/j.1346-8138.2012.01532.x PMid:22458564 DOI: https://doi.org/10.1111/j.1346-8138.2012.01532.x
Ho AW, Kupper TS. Fitzpatrick’s Dermatology. Soluble Mediators of the Cutaneous Immune System. Vol 1. 9th ed. United States: McGraw Hill Education; 2019.
Kobayashi Y, Yamamoto K, Saido T, Kawasaki H, Oppenheim JJ, Matsushima K. Identification of calcium-activated neutral protease as a processing enzyme of human interleukin 1 alpha. Proc Natl Acad Sci U S A. 1990;87(14):5548-52. http://doi.org/10.1073/pnas.87.14.5548 PMid:2115174 DOI: https://doi.org/10.1073/pnas.87.14.5548
Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996;87(6):2095-147. PMid:8630372 DOI: https://doi.org/10.1182/blood.V87.6.2095.bloodjournal8762095
Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009;27:519-50. http://doi.org/10.1146/annurev.immunol.021908.132612 PMid:19302047 DOI: https://doi.org/10.1146/annurev.immunol.021908.132612
Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7(1):33-42. https://doi.org/10.1038/nrrheum.2010.196 PMid:21119608 DOI: https://doi.org/10.1038/nrrheum.2010.196
Malozowski S, Sahlroot JT. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;357(3):302-3. https://doi.org/10.1056/NEJMc071324 PMid:17634469 DOI: https://doi.org/10.1056/NEJMc071324
Feldmeyer L, Keller M, Niklaus G, Hohl D, Werner S, Beer HD. The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes. Curr Biol. 2007;17(13):1140-5. https://doi.org/10.1016/j.cub.2007.05.074 PMid:17600714 DOI: https://doi.org/10.1016/j.cub.2007.05.074
Feldmeyer L, Werner S, French LE, Beer HD. Interleukin-1, inflammasomes and the skin. Eur J Cell Biol. 2010;89(9):638-644. https://doi.org/10.1016/j.ejcb.2010.04.008 PMid:20605059 DOI: https://doi.org/10.1016/j.ejcb.2010.04.008
Yazdi AS, Drexler SK, Tschopp J. The role of the inflammasome in nonmyeloid cells. J Clin Immunol. 2010;30(5):623-7. https://doi.org/10.1007/s10875-010-9437-y PMid:205824567.y DOI: https://doi.org/10.1007/s10875-010-9437-y
Fenton MJ. Review: Transcriptional and post-transcriptional regulation of interleukin 1 gene expression. Int J Immunopharmacol. 1992;14(3):401-11. https://doi.org/10.1016/0192-0561(92)90170-p PMid:1618594 DOI: https://doi.org/10.1016/0192-0561(92)90170-P
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Copyright (c) 2024 Tran Thi Huyen, Pham Thi Minh Phuong, Pham Thi Lan, Le Huyen My, Nguyen Thi Ha Vinh, Le Huu Doanh (Author)
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