<p>Photodynamic therapy (PDT) using methylene blue (MB) has demonstrated promising efficacy in treating common warts by inducing local cytotoxicity. However, its immunomodulatory potential remains underexplored. This study aimed to evaluate the clinical and immunological impact of MB-mediated PDT in patients with multiple common warts, with particular focus on systemic cytokine modulation. This prospective cohort study enrolled 30 patients with clinically and dermoscopically diagnosed common warts. Each patient received up to five weekly PDT sessions, during which the largest lesions were injected with sterile MB solution and covered with liposomal MB gel. Red light (640 nm, 80 J/cm<sup>2</sup>, 10 min) was applied using the Omega LED Light B system. Serum interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α) levels were measured at baseline, 1 month, and 6 months post-treatment. Both treated and untreated lesions demonstrated significant size reduction at 1 and 6 months (p = 0.01). Percentage improvement in treated lesions reached 32.44% ± 21.31% at 1 month and 44.15% ± 24.12% at 6 months. IL-2 levels declined over time (p = 0.054 and 0.022 at 1 and 6 months, respectively), and TNF-α levels also showed a significant overall reduction during follow-up (p = 0.01). A significant negative correlation was observed between clinical improvement and IL-2 levels, particularly in treated lesions at both follow-up time points and in untreated lesions at six months. In contrast, TNF-α levels showed no significant direct correlation with clinical improvement. However, multivariate analysis identified TNF-α levels at one month as a positive predictor of clinical response, whereas elevated baseline TNF-α was associated with poorer outcomes. In conclusion, MB-PDT was associated with clinical improvement and changes in systemic cytokine profiles. However, because untreated lesions demonstrated comparable clinical improvement, these findings should be interpreted cautiously in the light of natural history of wart regression observed in some clinical scenarios. The observed cytokine changes may reflect immune resolution and warrant confirmation in larger controlled studies. <i>Trial Registration</i>: Pan African Clinical Trials Registry (PACTR), Trial No. PACTR202607875594537, registered on 16 June 2026.</p>

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Photodynamic immune modulation in common warts: the impact of methylene blue therapy

  • Fatma Badr El-koumy,
  • Maha Rafea,
  • Nevien Samy

摘要

Photodynamic therapy (PDT) using methylene blue (MB) has demonstrated promising efficacy in treating common warts by inducing local cytotoxicity. However, its immunomodulatory potential remains underexplored. This study aimed to evaluate the clinical and immunological impact of MB-mediated PDT in patients with multiple common warts, with particular focus on systemic cytokine modulation. This prospective cohort study enrolled 30 patients with clinically and dermoscopically diagnosed common warts. Each patient received up to five weekly PDT sessions, during which the largest lesions were injected with sterile MB solution and covered with liposomal MB gel. Red light (640 nm, 80 J/cm2, 10 min) was applied using the Omega LED Light B system. Serum interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α) levels were measured at baseline, 1 month, and 6 months post-treatment. Both treated and untreated lesions demonstrated significant size reduction at 1 and 6 months (p = 0.01). Percentage improvement in treated lesions reached 32.44% ± 21.31% at 1 month and 44.15% ± 24.12% at 6 months. IL-2 levels declined over time (p = 0.054 and 0.022 at 1 and 6 months, respectively), and TNF-α levels also showed a significant overall reduction during follow-up (p = 0.01). A significant negative correlation was observed between clinical improvement and IL-2 levels, particularly in treated lesions at both follow-up time points and in untreated lesions at six months. In contrast, TNF-α levels showed no significant direct correlation with clinical improvement. However, multivariate analysis identified TNF-α levels at one month as a positive predictor of clinical response, whereas elevated baseline TNF-α was associated with poorer outcomes. In conclusion, MB-PDT was associated with clinical improvement and changes in systemic cytokine profiles. However, because untreated lesions demonstrated comparable clinical improvement, these findings should be interpreted cautiously in the light of natural history of wart regression observed in some clinical scenarios. The observed cytokine changes may reflect immune resolution and warrant confirmation in larger controlled studies. Trial Registration: Pan African Clinical Trials Registry (PACTR), Trial No. PACTR202607875594537, registered on 16 June 2026.