Key Points

1-First-ever global randomized, parallel, double-blind controlled clinical trial on ALA-PDT for recalcitrant palmar and plantar warts (ALA-PDT vs. placebo).

      2-Significant efficacy: ALA-PDT demonstrated remarkable wart clearance after six treatment sessions.

    *  One month after six treatments, the median wart area reduction in the ALA-PDT group was  98% (range: 56%-100%), significantly greater than the 46% reduction in the placebo group       (median difference = 46%, p = 0.0006).

    *   Two months after six treatments, the median wart area reduction in the ALA-PDT group was 100% (range: 56%-100%), compared to 29% in the placebo group (median difference = 29%,   p = 0.008).

    *  The number of completely cleared warts in the ALA-PDT group was significantly higher than in the placebo group at week 14 and week 18 (p < 0.05).

      3-No impact from wart size or duration: Wart size and disease duration did not affect ALA-PDT efficacy.

      4-No recurrence: No patients experienced wart recurrence within two months after six treatments.

A randomized double-blind trial published in The Lancet confirms that ALA-PDT effectively eliminates recalcitrant palmar and plantar warts in six treatment sessions, with low recurrence rates and consistent efficacy regardless of wart size or disease duration.

1. Background

Palmar and plantar warts not only affect aesthetics but can also cause functional and social issues, making treatment challenging. Conventional therapies include topical medication combined with curettage, glutaraldehyde application, or cryotherapy, which can achieve a 70% cure rate within three months for common palmar and plantar warts. However, for recalcitrant warts that fail standard treatments, clinicians often turn to immune modulators, laser therapy, and other approaches, yet some warts remain difficult to eradicate.

Aminolevulinic Acid-Photodynamic Therapy (ALA-PDT) involves the topical application of aminolevulinic acid (ALA) followed by red light irradiation. This therapy is widely used for actinic keratosis and superficial basal cell carcinoma, with cure rates ranging from 90% to 100%. ALA-PDT is favored for its short healing time, non-invasiveness, and minimal adverse reactions. It has also shown promise in treating viral infections such as condyloma acuminatum, herpes simplex, molluscum contagiosum, and palmar and plantar warts.

This article presents a randomized, parallel, double-blind clinical trial published in The Lancet, evaluating the efficacy and safety of ALA-PDT for recalcitrant palmar and plantar warts compared to placebo treatment.

2. Methods

Patient Inclusion Criteria

• Diagnosis: Recalcitrant palmar and plantar warts unresponsive to any prior treatments for over three months (excluding mosaic warts).

Randomization

• All wart lesions were assigned treatment groups using computer-generated randomization.

Treatment Protocol

• Debridement: Removal of the wart's stratum corneum until blood vessels were visible.

• ALA Application: 20% ALA or placebo (identical in appearance and odor) was topically applied and occluded for four hours.

• Red Light Irradiation: All lesions received 590 nm-700 nm red light exposure at 70 J/cm².

• Treatment Frequency: Once weekly for three sessions. If warts persisted at week 7, an additional three sessions were performed.

• Additional Measures: Patients twice-weekly debrided warts and applied a keratolytic agent (10% salicylic acid and 11% lactic acid).

Outcome Assessment

• Primary endpoint: Relative wart size reduction compared to baseline.

• Secondary endpoints: Change in wart count and residual wart area.

• Statistical Analysis:

• Wilcoxon rank-sum test for wart size changes.

• Chi-square test for wart clearance rates.

• Two-way ANOVA for residual wart area assessment (p < 0.05 considered statistically significant).

3. Results

Patient and Wart Baseline Characteristics

• * 45 patients enrolled (19 male, 26 female, median age 37 years, range: 20-84 years).

• * 232 warts included (117 in ALA-PDT group, 115 in placebo group).

* 93.1% (216/232) received six PDT treatments.

Wart Area Reduction

 * Week 14 (1 month after six treatments): ALA-PDT group showed 98% median wart area reduction, compared to 46% in the placebo group (p = 0.0006).

 * Week 18 (2 months after six treatments): ALA-PDT group achieved 100% median wart clearance, significantly outperforming the placebo group (p = 0.008).

Wart Count Reduction

• ALA-PDT group exhibited significantly higher wart clearance rates than the placebo group at weeks 14 and 18 (p < 0.05).

Factors Affecting Efficacy

 * Neither wart size nor disease duration significantly impacted ALA-PDT treatment efficacy.

 * Smaller warts had a higher likelihood of complete clearance (p = 0.043).

No Recurrence

No recurrent warts were observed during the two-month post-treatment follow-up period.

Safety Profile

 * No severe local or systemic adverse effects occurred.

 * No scarring, skin abnormalities, or functional impairment were noted.

 * Some patients experienced temporary mild hyperpigmentation on the dorsal hand warts.

 * Pain levels during light exposure were significantly higher in the ALA-PDT group than in the placebo group.

4. Discussion

This randomized, parallel, double-blind clinical trial confirms that ALA-PDT effectively eliminates recalcitrant palmar and plantar warts after six treatment sessions. Importantly, wart size and disease duration did not influence efficacy.

ALA-PDT works by selectively accumulating protoporphyrin IX (PpIX) in HPV-related lesions, making infected cells more susceptible to light-induced destruction. A multicenter phase III trial in China reported a 98.42% clearance rate for condyloma acuminatum one week post-treatment. This study further substantiates ALA-PDT's potential for treating persistent warts.

5. Conclusion

This study demonstrates that ALA-PDT is a safe and effective treatment for recalcitrant palmar and plantar warts. Future randomized clinical trials may explore ALA-PDT's application for other wart types.