Detecting Lesional Granulysin Levels for Rapid Diagnosis of Cytotoxic T lymphocyte-Mediated Bullous Skin Disorders
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Chun-Bing Chen1, Kang-Ling Kuo2, Chuang-Wei Wang3
1Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, Keelung, Taoyuan, Taiwan; Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan.
Background:
Bullous skin disorders are induced by different pathomechanisms and several are emergent, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Rapid diagnostic methods for SJS/TEN or cytotoxic T-lymphocyte (CTL)-mediated bullous disorders are crucial for early treatment. Granulysin, primarily expressed by CTLs, is a specific cytotoxic protein responsible for SJS/TEN and similar skin reactions.
Objective:
To assess granulysin levels in blister fluids to differentiate SJS/TEN and similar CTL-mediated bullous reactions from other autoimmune bullous disorders.
Methods:
Using ELISA, we measured granulysin in blister fluids from patients with bullous skin disorders, including SJS/TEN, erythema multiforme major, bullous fixed-drug eruption, bullous lupus erythematosus, paraneoplastic pemphigus, pemphigus vulgaris, bullous pemphigoid, purpura fulminans-related bullae, and hand-foot syndrome/hand-foot-skin reactions. We compared serum and blister granulysin levels in patients with SJS/TEN presenting varying severity, monitoring serial granulysin levels from acute to late stages.
Results:
Overall, 144 patients presenting with bullous skin disorders were enrolled. Blister granulysin levels (mean ± SD) in CTL-mediated disorders, including TEN (n = 28; 3938.7 ± 3475.7), SJS-TEN overlapping (n = 22; 1440.4 ± 1179.6), SJS (n = 14; 542.0 ± 503.2), erythema multiforme major (n = 7; 766.3 ± 1073.7), generalized bullous fixed-drug eruption (n = 10; 720.4 ± 858.3), and localized bullous fixed-drug eruption (n = 16; 69.0 ± 56.4), were significantly higher than in non-CTL-mediated bullous disorders (P < .0001), including bullous lupus erythematosus (n = 3; 22.7 ± 20.1), paraneoplastic pemphigus (n = 3; 20.3 ± 8.6), pemphigus vulgaris (n = 3; 4.4 ± 2.8), bullous pemphigoid (n = 18; 4.0 ± 2.7), purpura fulminans (n = 4; 5.9 ± 5.5), and hand-foot syndrome/hand-foot-skin reactions (n = 6; 4.6 ± 3.5). Blister granulysin levels correlated with clinical severity of SJS/TEN (P < .0001).
Conclusions:
Determination of blister granulysin levels is a noninvasive and useful tool for rapid differential diagnosis of SJS/TEN and other similar CTL-mediated bullous skin disorders for treatment selection.
