The evaluation of cytokine profiles in atopic dermatitis patients treated with dupilumab: association with ocular complications.

BACKGROUND: Dupilumab is an effective treatment for moderate-to-severe atopic dermatitis (AD), yet a substantial proportion of patients develop ocular complications collectively termed dupilumab-associated ocular surface disease (DAOSD). Despite multiple proposed mechanisms - including goblet cell depletion, mucin deficiency, Th1/Th17 immune shifts, and microbiome alterations - no upstream epithelial cytokine marker has been clearly identified. OBJECTIVE: To evaluate whether plasma cytokines differ between AD patients treated with dupilumab who develop ocular complications and those without ocular involvement. METHODS: Complex dermatological examination was performed in adult AD patients receiving dupilumab for ≥24 months. Plasma cytokines (IFN-γ, TNF-α, IL-23, IL-2, IL-31, IL-6, IL-17A, IL-17E, IL-12p70, TSLP, IL-4, IL-5, IL-13, IL-10, IL-33) were quantified under unstimulated and PMA/ionomycin-stimulated conditions in winter and summer seasons. Differences between groups were assessed using non-parametric tests (Mann-Whitney U test and Kolmogorov-Smirnov test). To account for multiple comparisons across the large number of tested cytokines, false discovery rate (FDR) correction was performed using the Benjamini-Hochberg procedure with a significance threshold of q = 0.05. Receiver operating characteristic (ROC) analysis was performed to evaluate biomarker potential to explore potential discriminative performance. AUC values were calculated using empirical (non-parametric) ROC analysis. RESULTS: During the summer period, stimulated thymic stromal lymphopoietin (TSLP) levels were nominally higher in patients with ocular complications compared with those without (p = 0.045). However, this difference did not remain statistically significant after FDR correction. In winter, stimulated TSLP showed a non-significant trend toward higher levels (p = 0.088). No other cytokines differed between groups. ROC analysis demonstrated moderate discriminative ability of stimulated TSLP (AUC 0.81 in summer; 0.70 in winter), although confidence intervals were wide. CONCLUSION: Stimulated TSLP may represent a preliminary observation requiring confirmation in dupilumab-treated AD patients with ocular complications.