Immunological and Inflammatory Characteristics of Severe Cutaneous Adverse Drug Reactions: A Retrospective Study

Qing Luo,1– 3 Xu-Dong Mou,1– 3 Di Cao,1– 3 Wen-Hao Cheng1– 3 1Department of Dermatology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, 222000, People’s Republic of China; 2Department of Dermatology, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu, 222000, People’s Republic of China; 3Department of Dermatology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, 222000, People’s Republic of ChinaCorrespondence: Wen-Hao Cheng, Department of Dermatology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, No. 182, Tongguan North Road, Haizhou District, Lianyungang, Jiangsu, 222000, People’s Republic of China, Tel +86 18961322858, Email [email protected]: Severe cutaneous adverse drug reaction (SCADR) is a life-threatening immune-mediated disorder, yet humoral immune markers and inflammatory biomarkers have not been systematically characterized across major SCADR phenotypes. This study aims to identify the immunological and inflammatory characteristics of SCADR.Methods: We retrospectively enrolled 60 SCADR patients (2015– 2024) and two control cohorts (60 mild drug eruption patients and 60 age- and sex-matched healthy subjects). Baseline serum IgG, IgA, IgM, complement C3/C4, C-reactive protein (CRP), and procalcitonin (PCT) were measured prior to treatment, and between-group comparisons, correlation analyses, and subtype analyses [Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) vs DRESS] were performed.Results: SCADR patients had lower IgG (8.8± 4.1g/L) and complement levels (C3 1.01± 0.37g/L; C4 0.21± 0.12g/L) than controls (P< 0.05), alongside markedly elevated CRP (median: 31.1mg/L) and PCT (0.68μg/L) (P< 0.001). PCT was higher in SJS/TEN than drug reaction with eosinophilia and systemic symptoms (DRESS) (0.85 vs 0.45μg/L, P=0.04), whereas eosinophil counts were higher in DRESS. C3 correlated positively with CRP (r=0.60, P< 0.001). No significant associations were observed between immunoglobulins and PCT, and PCT and CRP were largely independent.Conclusion: SCADR is associated with concurrent alterations in humoral immune markers and acute-phase inflammatory biomarkers. Differences in biomarker patterns between SJS/TEN and DRESS may help with early clinical phenotyping. Prospective multicenter studies are needed to validate these findings and clarify their clinical significance subsequently.Keywords: Stevens–Johnson syndrome, toxic epidermal necrolysis, DRESS, drug-induced hypersensitivity, immunoglobulin, complement, C-reactive protein, procalcitonin, biomarker, severe adverse drug reaction