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.