High Serum Level of TNF-α in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
DOI:
https://doi.org/10.3889/oamjms.2022.10337Keywords:
Steven-Johnson syndrome, Toxic epidermal necrolysis, Severe cutaneous adverse drug reactions, TNF-α, Fluorescence covalent microbead immunosorbent assayAbstract
BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis are severe cutaneous adverse drug reactions. Some immunological and genetic factors are believed to be involved in the pathogenesis of SJS/TEN, including tumor necrotic factor-alpha (TNF-α). Activated T-cells secrete high amounts of TNF-α and interferon-gamma that both cytokines lead to increased expression and activity of keratinocyte inducible nitric oxide synthase playing an important role in the apoptosis of keratinocytes.
AIM: This study aims to evaluate the serum level of TNF-α in SJS/TEN and the relation between it 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. Forty-eight SJS/TEN patients, 43 erythema multiforme (EM) patients, and 20 healthy controls (HCs) participated. TNF-α levels were measured 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 serum TNF-α levels of 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: Nineteen SJS patients (39.5%) and 29 TEN patients (60.5%) participated in our study. The mean age was 49.3, range 19−77 years (47.9% of males and 52.1% of 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 the SJS/TEN group was 32.6 pg/ml with a range from 1.3 pg/ml to 771.2 pg/ml. This level was significantly higher than that of the HCs group (p < 0.05) but not higher than that of the EM group. The mean serum level of TNF-α in the SJS/TEN patients on the day of hospitalization was 32.6 pg/ml, higher than that on the day of re-epithelialization (2.7 pg/ml) and the difference was statistically significant with p < 0.05.
CONCLUSION: Serum TNF-α levels are a good biomarker to evaluate the progress of SJS/TEN but it is not good to differentiate SJS/TEN from EM.Downloads
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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):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, Gouvello SL, 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, 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 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.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):155-61. https://doi.org/10.1067/mai.2002.120563 PMid:11799383 DOI: https://doi.org/10.1067/mai.2002.120563
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: Result of an international prospective study. Arch Dermatol. 2002;138:1019-24. 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 EM. 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. Soluble mediators of the cutaneous immune system. In: Fitzpatrick’s Dermatology. 9th ed., Vol. 1. New York: McGraw Hill Education; 2019.
Wang F, Ye Y, Luo ZY, Gao Q, Luo DQ, Zhang X. Diverse expression of TNF-α and CCL27 in serum and blister of Stevens-Johnson syndrome/toxic epidermal necrolysis. Clin Transl Allergy. 2018;8:12. https://doi.org/10.1186/s13601-018-0199-6 PMid:29713456 DOI: https://doi.org/10.1186/s13601-018-0199-6
Menter A, Strober BE, Kaplan DH, Kivelevitch D, Prater EF, Stoff B, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019;80(4):1029-72. https://doi.org/10.1016/j.jaad.2018.11.057 PMid:30772098 DOI: https://doi.org/10.1016/j.jaad.2018.11.057
Reynolds KA, Pithadia DJ, Lee EB, Liao W, Wu JJ. Safety and effectiveness of anti-tumor necrosis factor-alpha biosimilar agents in the treatment of psoriasis. Am J Clin Dermatol. https://doi.org/10.1007/s40257-020-00507-1 PMid:32048187 DOI: https://doi.org/10.1007/s40257-020-00507-1
Kerschbaumer A, Sepriano A, Smolen JS, van der Heijde D, Dougados M, van Vollenhoven R, et al. Efficacy of pharmacological treatment in rheumatoid arthritis: A systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-2019-216656 PMid:32033937 DOI: https://doi.org/10.1136/annrheumdis-2019-216656
Smolen JS, Landewé RB, Bijlsma JW, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-2019-216655 PMid:31969328 DOI: https://doi.org/10.1136/annrheumdis-2019-216655
Zhang S, Tang S, Li S, Pan Y, Ding Y. Biologic TNF-alpha inhibitors in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis: A systemic review. J Dermatol Treat. 2020;31(1):66-73. https://doi.org/10.1080/09546634.2019.1577548 PMid:30702955 DOI: https://doi.org/10.1080/09546634.2019.1577548
Gavigan GM, Kanigsberg ND, Ramien ML. Pediatric Stevens-Johnson syndrome/toxic epidermal Necrolysis halted by Etanercept. J Cutan Med Surg. 2018;22(5):514-5. https://doi.org/10.1177/1203475418758989 PMid:29421925 DOI: https://doi.org/10.1177/1203475418758989
Paradisi A, Abeni D, Bergamo F, Ricci F, Didona D, Didona B. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol. 2014;71(2):278-83. https://doi.org/10.1016/j.jaad.2014.04.044 PMid:24928706 DOI: https://doi.org/10.1016/j.jaad.2014.04.044
Hirahara K, Kano Y, Sato Y, Horie C, Okazaki A, Ishida T, et al. Methylprednisolone pulse therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis: Clinical evaluation and analysis of biomarkers. J Am Acad Dermatol. 2013;69(3):496-8. https://doi.org/10.1016/j.jaad.2013.04.007 PMid:23957982 DOI: https://doi.org/10.1016/j.jaad.2013.04.007
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