Abstract
Background: Although pulsed dye laser (PDL) is the treatment of choice for port-wine stains (PWS), clinical resistance to PDL has been observed in 20-30% of cases. Several alternative treatment modalities have been introduced; however, there is still a lack of definite recommendations regarding the optimal treatment for difficult-to-treat PWS.

Objective: We aimed to systematically review and analyze the comparative effectiveness among treatments for problematic PWS.

Methods & materials: We systematically searched for comparative studies assessing treatments for patients with difficult-to-treat PWS through relevant biomedical databases until August 2022. A Network Meta-Analysis (NMA) was conducted to estimate the odds ratio (OR) for all pairwise comparisons. The primary outcome is the improvement of lesions of more than 25%.

Results: Of the 2498 studies identified, six treatments from five studies were available for NMA. Compared with 585 nm short-pulsed dye laser (SPDL), intense pulsed light (IPL) was the most effective in clearing lesions (OR 11.81, 95% CI 2.15 to 64.89, very low confidence rating), followed by 585 nm long-pulsed dye laser (LPDL) (OR 9.95, 95% CI 1.75 to 56.62, very low confidence rating). The 1064 nm NdYAG, 532 nm NdYAG, and LPDL >585 nm exhibited potential superiority over SPDL 585 nm, although statistical significance was not observed.

Conclusions: IPL and 585 nm LPDL are likely to be more effective than 585 nm SPDL for treating difficult-to-treat PWS. Well-designed clinical trials are warranted to confirm our findings.