Split-face comparison of hydroquinone 4% plus nitrogen plasma vs. hydroquinone 4% alone in the treatment of melasma

Treatment of skin diseases is important yet challenging. One of the most common skin diseases in women is melasma, which features acquired facial hyperpigmentation. We studied the effect of cold atmospheric nitrogen plasma on this disease. To characterize the nitrogen plasma, we obtained the relative intensity of the species and the plasma temperature and skin temperature during processing at different input powers and gas flows. Patients complaining of melasma were treated with hydroquinone on both sides of the face, and one side was randomly selected for additional nitrogen plasma therapy. Eight treatment sessions of plasma processing were provided 1 week apart, and one follow-up session was scheduled 1 month after the end of treatment. The rate of improvement was scored by a dermatologist in the eighth session and 1 month following the last session using the modified Melasma Area Severity Index (mMASI). Skin biomechanical characteristics such as melanin, cutaneous resonance running time (CRRT), transepidermal water loss (TEWL), and hydration were measured at baseline and during the fourth, eighth, and follow-up sessions. On both sides, we observed a significant decrease in both CRRT and melanin (P < 0.05). TEWL did not change on both sides, while hydration decreased significantly only on the side to which hydroquinone was applied in isolation (P < 0.05). According to clinical scores, on both sides, we had significant improvement. On the side that plasma was not applied, the percentage reduction of pigmentation (mMASI) in the eighth and follow-up sessions in comparison with the baseline was 5.49 ± 8.50% and 33.04 ± 9.17%, respectively, while on the other side, these figures were 20.57 ± 6.64% and 48.11 ± 11%. For melanin, these figures were 13.84 ± 4.84% and 18.23 ± 7.10% on the hydroquinone side and 21.56 ± 3.13% and 23.93 ± 3.02% on the other side. According to these results, nitrogen plasma can safely complement topical hydroquinone to improve clinical outcomes when treating melasma without causing stratum corneum damage or skin discomfort, though confirmatory studies are needed.