Serum Concentrations of Thelper2-derived Cytokines in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Authors

  • Thi Huyen Tran Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; Department of Outpatient, National Hospital of Dermatology and Venereology, Hanoi, Vietnam https://orcid.org/0000-0002-9794-5718
  • Nguyen Thi Ha Vinh Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; Department of Outpatient, National Hospital of Dermatology and Venereology, Hanoi, Vietnam https://orcid.org/0000-0001-6066-363X

DOI:

https://doi.org/10.3889/oamjms.2023.11645

Keywords:

Steven-Johnson syndrome, Toxic epidermal necrolysis, Interleukin-4, Interleukin-5, Interleukin-13

Abstract

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 SJS/TEN, including T helper 1 and T helper 2 (Th2)-derived cytokines.

AIM: This study aims to evaluate the serum levels of Th2-derived cytokines in SJS/TEN, compare to those of erythema multiforme (EM) patients, and the relation between them and the progress of SJS/TEN.

METHODS: This was a  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 EM patients, and 20 healthy controls (HCs) participated. Serum interleukin (IL)-4, IL-5, and IL-13 levels were measured by using the fluorescence covalent microbead immunosorbent assay (FCMIA) (ProcartaPlex Immunoassay Panels kit, Thermo Fisher Scientific, USA). The Mann-Whitney U test was used to compare the serum IL levels of the two groups. 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, range of 19–77 years (47.9% males; 52.1% females). The most common causative drugs were traditional medicine (29.1%), and allopurinol (12.5%). On the day of hospitalization, the serum level of IL-4 in the SJS/TEN group was 3 ± 7.5 pg/mL, statistically significantly higher than that in the HCs group (p < 0.05), but not higher than that in the EM group (p > 0.05); serum levels of IL-5 and IL-13 in the SJS/TEN group were 4.5 ± 9.8 pg/mL and 1.6 ± 0.6 pg/mL, respectively, similar to those in the EM and HCs groups. On the day of re-epithelialization, in SJS/TEN patients, the serum level of IL-5 was 1 ± 2.8 pg/ml, statistically significantly lower than that on the day of hospitalization (3 ± 7.5 pg/mL) with p < 0.05. Regarding serum levels of IL-4 and IL-13, there was no difference between the two- time points.

CONCLUSION: The serum concentrations of Th2-derived cytokines (IL-4, IL-5, and IL-13) were not higher in the SJS/TEN group than in the EM group and there was no significant change in the clinical progression of SJS/TEN, except the serum level of IL-5.

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References

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):173. 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:28011147 DOI: https://doi.org/10.1016/j.jid.2016.11.034

Wolkenstein P, Latarjet J, Roujeau JC, Roujeau JC, Duguet C, Boudeau S, 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

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 PMid:19029983 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.org10.1016/j.jaci.2004.07.047 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):155-61. https://doi.org/10.1067/mai.2002.120563 PMid:11799383 DOI: https://doi.org/10.1067/mai.2002.120563

High Serum Level of TNF-α in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. Open Access Macedonian Journal of Medical Sciences; 2021. Available from: https:// oamjms.eu/index.php/mjms/article/view/10337 [Last accessed on 2023 Feb 05].

Huyen TT, Hoa PD, Lan PT. High levels of serum interferon- gamma in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. J Med Res. 2020;127(3): 67-72.

Ho AW, Kupper TS. Fitzpatrick’s Dermatology. Soluble Mediators of the Cutaneous Immune System. Vol. 1. 9 McGraw Hill Education; 2019. ed. United States:

Seder RA, Paul WE, Davis MM, de St Groth BF. The presence of interleukin 4 during in vitro priming determines the lymphokine- producing potential of CD4+ T cells from T cell receptor transgenic mice. J Exp Med. 1992;176(4):1091-8. https://doi.org/10.1084/jem.176.4.1091 PMid:1328464 DOI: https://doi.org/10.1084/jem.176.4.1091

Quaglino P, Caproni M, Osella-Abate S, Torchia D, Comessatti A, Del Bianco E, et al. Serum interleukin-13 levels are increased in patients with Stevens-Johnson syndrome/ toxic epidermal necrolysis but not in those with erythema multiforme. Br J Dermatol. 2008;158(1):184-6. https://doi.org/10.1111/j.1365-2133.2007.08259.x PMid:17941938 DOI: https://doi.org/10.1111/j.1365-2133.2007.08259.x

Nassif A, Moslehi H, Le Gouvello S, Bagot M, Lyonnet L, Michel L, et al. Evaluation of the potential role of cytokines in toxic epidermal necrolysis. J Invest Dermatol. 2004;123(5):850-55. https://doi.org/10.1111/j.0022-202X.2004.23439.x DOI: https://doi.org/10.1111/j.0022-202X.2004.23439.x

Caproni M, Torchia D, Schincaglia E, Volpi W, Frezzolini A, Schena D, et al. Expression of cytokines and chemokine receptors in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis. Br J Dermatol. 2006;155(4):722-8. https://doi.org/10.1111/j.1365-2133.2006.07398.x PMid:16965421 DOI: https://doi.org/10.1111/j.1365-2133.2006.07398.x

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Published

2023-05-04

How to Cite

1.
Tran TH, Vinh NTH. Serum Concentrations of Thelper2-derived Cytokines in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. Open Access Maced J Med Sci [Internet]. 2023 May 4 [cited 2024 Nov. 21];11(B):660-4. Available from: https://oamjms.eu/index.php/mjms/article/view/11645