Serum Levels of Interleukin-1 Beta are Decreased in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis at the Time of Hospitalization

Authors

  • Tran Thi Huyen 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
  • Pham Thi Minh Phuong Department of Outpatient, National Hospital of Dermatology and Venereology, Hanoi, Vietnam https://orcid.org/0000-0003-1509-599X
  • Pham Thi Lan Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; Department of Outpatient, National Hospital of Dermatology and Venereology, Hanoi, Vietnam
  • Le Huyen My Department of Outpatient, National Hospital of Dermatology and Venereology, Hanoi, Vietnam
  • 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
  • Le Huu Doanh Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; Department of Outpatient, National Hospital of Dermatology and Venereology, Hanoi, Vietnam

DOI:

https://doi.org/10.3889/oamjms.2024.11800

Keywords:

Steven-Johnson syndrome, Toxic epidermal necrolysis, Severe cutaneous adverse drug reactions, Interleukin-1 beta, Fluorescence covalent microbead immunosorbent assay

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 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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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Schroder K, Tschopp J. The inflammasomes. Cell. 2010;140(6):821-832. https://doi.org/10.1016/j.cell.2010.01.040 PMid:20303873

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

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

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

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

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

Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996;87(6):2095-147. PMid:8630372

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

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

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

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

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

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

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

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Published

2024-02-10

How to Cite

1.
Huyen TT, Phuong PTM, Lan PT, My LH, Vinh NTH, Doanh LH. Serum Levels of Interleukin-1 Beta are Decreased in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis at the Time of Hospitalization. Open Access Maced J Med Sci [Internet]. 2024 Feb. 10 [cited 2026 Oct. 19];12(1):93-7. Available from: https://oamjms.eu/index.php/mjms/article/view/11800