Serum Level of Granulocyte-macrophage Colony-stimulating Factor in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
DOI:
https://doi.org/10.3889/oamjms.2023.11180Keywords:
Steven-Johnson syndrome, Toxic Epidermal Necrolysis, Severe cutaneous adverse drug reactions, Granulocyte-macrophage colony-stimulating factor, Fluorescence covalent microbead immunosorbent assayAbstract
BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Activated T-cells secrete high amounts of cytokines that increase the expression and activity of keratinocytes, including granulocyte-macrophage colony-stimulating factor (GM-CSF).
AIMS: The aims of this study were to evaluate the serum level of GM-CSF in SJS and TEN as well as the relationship between it and the progress of SJS and 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. GM-CSF 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 SJS/TEN 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: There were 19 SJS patients (39.5%) and 29 TEN patients (60.5%). The mean age was 49.3 years, range of 19–77 years. The male patients were 47.9%. The most common causative drugs were traditional medicine (29.1%), followed by carbamazepine (12.5%), and allopurinol (12.5%). On the day of hospitalization, the mean serum level of GM-CSF in the SJS/TEN group was 10.6 pg/mL, which was significantly higher than that of the EM group (p < 0.05) but not higher than that of the HCs group and was higher than that on the day of re-epithelialization (3.6 pg/mL) and the difference was statistically significant with p < 0.05.
CONCLUSION: Serum GM-CSF level can be a good biomarker to evaluate the progress of SJS/TEN.
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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
SchwartzRA,McDonoughPH,LeeBW.Toxicepidermalnecrolysis: Part I. Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad Dermatol. 2013;69(2):173:e1- 13. 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 BC 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 C, 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 CW, 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. 2014;6(1):194 210. https://doi.org/10.3390/toxins6010194 PMid:24394640 DOI: https://doi.org/10.3390/toxins6010194
Shi Y, Liu CH, Roberts AI, Das J, Xu G, Ren G, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: What we do and don’t know. Cell Res. 2006;16(2):126-33. https://doi.org/10.1038/sj.cr.7310017 PMid:16474424 DOI: https://doi.org/10.1038/sj.cr.7310017
Gurumurthy S, Iyer G, Srinivasan B, Agarwal S, Angayarkanni N. Ocular surface cytokine profile in chronic Stevens-Johnson syndrome and its response to mucous membrane grafting for lid margin keratinisation. Br J Ophthalmol. 2018;102(2):169-76. https://doi.org/10.1136/bjophthalmol-2017-310373 PMid:28689166 DOI: https://doi.org/10.1136/bjophthalmol-2017-310373
Auquier-Dunant A, Mockenhaupt M, Naldi L, Correia O, Schröder W, Roujeau JC. Correlations between clinical patterns and causes of erythema multiforme major, 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
Ang CC, Tay YK. Hematological abnormalities and the use of granulocyte-colony-stimulating factor in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. Int J Dermatol. 2011;50(12):1570-8. https://doi.org/10.1111/j.1365-4632.2011.05007.x PMid:22098009 DOI: https://doi.org/10.1111/j.1365-4632.2011.05007.x
Pallesen KA, Robinson S, Toft P, Andersen KE. Successful treatment of toxic epidermal necrolysis/Stevens-Johnson syndrome overlap with human granulocyte colony stimulating factor: A case report. Acta Derm Venereol. 2021;92(2):212-3. https://doi.org/10.2340/00015555-1238 DOI: https://doi.org/10.2340/00015555-1238
Hamilton JA. GM-CSF in inflammation and autoimmunity. Trends Immunol. 2002;23(8):403-8. https://doi.org/10.1016/s1471-4906(02)02260-3 PMid:12133803 DOI: https://doi.org/10.1016/S1471-4906(02)02260-3
Campbell IK, Rich MJ, Bischof RJ, Dunn AR, Grail D, Hamilton JA. Protection from collagen-induced arthritis in granulocyte-macrophage colony-stimulating factor-deficient mice. J Immunol. 1998;161(7):3639-44. PMid:9759887 DOI: https://doi.org/10.4049/jimmunol.161.7.3639
Gonzalez-Juarrero M, Hattle JM, Izzo A, Junqueira-Kipnis AP, Shim TS, Trapnell BC, et al. Disruption of granulocyte macrophage-colony stimulating factor production in the lungs severely affects the ability of mice to control Mycobacterium tuberculosis infection. J Leukoc Biol. 2005;77(6):914-22. https://doi.org/10.1189/jlb.1204723 PMid:15767289 DOI: https://doi.org/10.1189/jlb.1204723
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
Lerch M, Pichler WJ. The immunological and clinical spectrum of delayed drug-induced exanthems. Curr Opin Allergy Clin Immunol. 2004;4(5):411-9. https://doi.org/10.1097/00130832-200410000-00013 PMid:15349041 DOI: https://doi.org/10.1097/00130832-200410000-00013
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