Elevated endocan levels and its association with clinical severity in Stevens Johnson syndrome and toxic epidermal necrolysis

Abstract

Purpose: To determine the levels of endocan and inflammatory biomarkers in the systemic circulation of: 1) biopsy confirmed SJS/TEN subjects; 2) patients with allergic skin reactions but biopsy negative for SJS/TEN; and 3) healthy controls. To investigate endocan as a marker of clinical severity by correlating levels with SCORTEN.

Methods: Sixteen patients over the age of 18 years referred to Loyola University Medical Center with severe allergic skin reactions were recruited from May 2012 to May 2014. A diagnosis of SJS or TEN was confirmed in 7 subjects by skin biopsy. Citrated plasma samples were assayed for endocan, tumor necrosis factor-α (TNFα), vascular endothelial growth factor (VEGF), and C-reactive protein (CRP). Differences between SJS/TEN, biopsy negative (B-), and healthy (H) (n=23) subjects were explored using ANOVA and Tukey's post-hoc test. Associations with clinical variables were identified using linear and logistic regression. Data presented as median [IQR].

Results: SJS/TEN and B- subjects had higher endocan levels than normal controls (SJS/TEN: 3.0ng/mL [2.2-8.1]; B-: 4.0ng/mL [1.5-4.9]; H: 1.8ng/mL [1.7-2.0]; p=0.004). Endocan levels were more strongly associated with SCORTEN in SJS/TEN subjects than in B- subjects (r-squared SJS/TEN=0.51; B-=0.03). SJS/TEN subjects exhibited significantly higher levels of TNFα compared to H subjects (p=0.03). SJS/TEN TNFα levels were significantly lower compared to B- subjects (p=0.005). VEGF levels were also elevated among SJS/TEN and B- subjects compared to H subjects (SJS/TEN: 12.0pg/mL [7.6-52.7]; B-: 10.5pg/mL [8.7-12.0]; H: 4.9pg/mL [4.2-6.5]; p<0.0005). There was no significant difference in VEGF levels between SJS/TEN and B- subjects. Similarly, CRP levels were elevated among SJS/TEN and B- compared to H subjects (SJS/TEN: 32.1µg/mL [31.5-52.1]; B-: 83.4µg/mL [44.7-145.4]; H: 1.1µg/mL [0.7-2.0; p<0.0001). There was no significant difference in CRP levels between SJS/TEN and B- subjects.

Conclusions: To our knowledge, this is the first study to evaluate endocan, a marker of endothelial dysfunction, in the systemic circulation of SJS/TEN patients. Elevated endocan levels were more strongly associated with disease severity among SJS/TEN subjects than among less severe allergic reactions with skin involvement.