Speaker- Robert Artur Dahmen

Melasma is a chronic and recurrent condition that is frequently misunderstood, largely due to misleading online images and experiences with ineffective treatments. Patients may have attempted to manage their condition with over-the-counter creams, which can carry health risks and contribute to unrealistic expectations and frustration. Melasma treatment is not just about lasers and peels but also sunscreens and topical agents. Effective melasma treatment requires targeting all skin layers and combining multiple therapeutic approaches. The underlying mechanism of melasma on a hyperactive melanocyte. Various other factors like genetics, sun exposure, medication, pregnancy and associated conditions contribute to melanocyte activity but could not be eliminated. While pregnancy, a known trigger, could be avoided. Sun exposure, another contributing factor, could be mitigated by applying Sun Protection Factor (SPF) 50 sunscreen daily. However, patients often applied sunscreen incorrectly, failing to protect against other components of solar radiation, particularly visible light, including blue light. A study comparing regular sunscreen patients with sunscreen specifically formulated to block visible light revealed a significantly greater reduction in pigmentation in the group treated with the latter. 

Visible light sunscreens, such as iron oxide, were originally used for painting. However, they have since evolved to include transparent iron oxides with smaller, less pigmented particles, making them suitable for cosmetic applications. A popular example is the Cantabria Labs tinted sunscreen, known for its aesthetic appeal on the skin. A study in the Blue Journal suggests that combining tinted sunscreen with makeup is not recommended for adequate sun protection, as it is ineffective and should be used separately. To treat melasma with tinted sunscreen, a skin lightener was necessary to target the condition actively. Several pathways could be targeted to inhibit melanin production, including blocking the transfer of melanosomes to keratinocytes and promoting increased epidermal cell turnover. Among the active ingredients, 4% hydroquinone was the most extensively studied. It had become the gold standard for melasma treatment due to its significant reduction in the Melasma Area and Severity Index (MASI) score. The treatment achieved up to a 70% improvement in patients but needed to be used with caution, especially in individuals with darker skin tones, as prolonged use could induce exogenous ochronosis. The most effective form of hydroquinone treatment was in combination with a topical steroid and some tretinoin, known as a triple combination therapy. This approach targeted multiple pathways involved in the pathogenesis of melasma and was superior to hydroquinone alone. Despite its efficacy, the triple combination therapy was difficult to obtain in Europe and was only available in Switzerland. Treatment duration must be carefully monitored, as extended use could lead to exogenous ochronosis, a paradoxical worsening of pigmentation. If no significant improvement was observed after eight weeks, treatment could be extended for another eight weeks. However, if no substantial changes occurred, a preferred approach was to reduce the treatment to twice weekly for six months and introduce an additional skin lightener to prevent recurrence and manage the condition safely.

Azelaic acid, which may not be the first treatment option that comes to mind, has been extensively researched. Notably, a 20% concentration of azelaic acid has demonstrated comparable efficacy to 4% hydroquinone in treating melasma. It is particularly beneficial for use during pregnancy. Thiamidol, the main ingredient in the Eucerin Anti-Pigment line, has been compared to 4% hydroquinone and is effective without side effects. The active ingredient has been discreetly incorporated into budget-friendly and premium skincare products. A compound known as Melasyl (2- Mercaptonicotinoyl Glycine) interacts with melanin precursors, effectively inhibiting the formation of melanin pigments. A study published in the Journal of the European Academy of Dermatology and Venereology (JEADV) compared Melasyl with 13 other common skin-lightening agents, demonstrating that the active ingredient, 2-methyl-1-naphthol-5-glucoside (2MNG), showed superior efficacy.

Vitamin C has been a widely discussed topic in skin care, and a study comparing hydroquinone with 5% ascorbic acid revealed no significant differences in colorimetry. However, there was a notable difference in subjective improvement, high in hydroquinone group. However, the incidence of side effects, such as burning and scaling, was higher in the hydroquinone group compared to the ascorbic acid group. Skinceuticals C E Ferulic acid brand and a small Hungarian brand offering 15% white ascorbic acid was recommended for its effectiveness. Cysteamine although the product had not yet fully penetrated the market, it was proven highly effective and has shown equivalent results to hydroquinone. The only concern about cysteamine is its unpleasant odour. A dermatologist suggested applying it to unwashed skin, then rinsing it off and using it as a mask. Another well-studied ingredient, niacinamide, inhibits melanosome transfer. Niacinamide showed almost no difference to hydroquinone in colorimetry during a split-phase study, with similar results in the MASI reduction. Niacinamide could cause slight burning, although it was far less severe than the burning associated with hydroquinone. After eight weeks of use, niacinamide produced a noticeable improvement in the skin’s appearance. Retinoids and hydroxy acids were employed to increase cell turnover, though they were rarely used in isolation for treating melasma. Instead, they were almost exclusively utilized in combination treatments, highlighting that different approaches often yield similar results. For instance, retinoids and hydroxy acids were seldom used alone in managing melasma, but they were frequently part of combination therapies. 

The treatment protocol includes a triple combination therapy for managing both acne and melasma, alongside the use of a alpha hydroxy acid cleanser and tinted sunscreen. Patient management is tailored to the individual's skin appearance, incorporating anti-inflammatory agents for acne and retinoids to address aging concerns. Special attention is required for patients with darker skin types, as inflammation can lead to post-inflammatory hyperpigmentation, which must be avoided. Agents such as vitamin C, niacinamide and thiamidol can be used in Skin type IV to VI. Additionally, the inclusion of vitamin C and retinoids is recommended for patients experiencing signs of aging. For pregnant patients, azelaic acid could be used throughout pregnancy. However, tranexamic acid was advised as an additional option, and tranexamic acid was advised as an extra option if tinted sunscreen and skin lightener proved ineffective. Tranexamic acid, an enzyme that activates melanocytes and angiogenesis through Vascular Endothelial Growth Factor (VEGF), also inhibits the conversion of plasminogen to plasmin, which is responsible for fibrin degradation, posing potential risks for some patients. A systematic review of 22 randomized controlled trials found no increased venous or arterial thrombosis risk in non-surgical patients treated with tranexamic acid. However, patients with a known risk of venous thrombosis were excluded from the study. The optimal use of tranexamic acid was identified as a dosage of 250 milligrams twice daily for two to six months. Screening for thrombotic risk and excluding high-risk venous thrombosis patients was deemed essential. Dermatologist were also advised to inform patients about possible side effects, including headache, abdominal pain, back pain, and menstrual irregularities. Topical tranexamic acid, while popular, showed evidence of working best when combined with other treatments. The additional interventions should only be incorporated if the patient requires further treatment for residual melasma or fails to respond adequately. Medium depth and deep Chemical peels were not recommended for melasma due to the risk of inflammatory or post-inflammatory hyperpigmentation. Instead, superficial peels like glycolic acid, mandelic acid. lactic acid, or tretinoin acid were suggested to enhance cellular turnover in the superficial skin layer. 

It was crucial to prime the skin with hydroquinone before peeling to achieve optimal results. The treatment regimen recommended discontinuing tretinoin seven days before the procedure, with five to six sessions performed every two to four weeks. A robust and blinded study on laser treatments presents significant challenges. The most extensively researched laser modalities are fractional ablative and non-ablative lasers and Q-switched nanosecond and picosecond lasers. All these options have demonstrated efficacy in reducing melasma scores; however, there was a high risk of recurrence and of post-inflammatory hyperpigmentation. Fractional ablative lasers were not recommended for melasma due to their heightened risk of complications. In contrast, fractional non-ablative lasers exhibited a lower recurrence risk but still posed a significant risk of post-inflammatory hyperpigmentation. Nonetheless, recurrence remained common since these lasers did not provide a cure, merely targeting pigment in the skin without impacting hyperactive melanocytes. A prevalent practice in laser toning involved utilizing low fluencies to prevent over-exertion, with treatments scheduled weekly. The method proved effective for treating melasma. 

In summary, the treatment of melasma necessitated a multifaceted approach that combined various techniques and layers of support. It involved thoroughly understanding potential consequences and the need to adjust treatment components accordingly. The analogy could be likened to enhancing a sandwich with tomato by incorporating additional protein and cheese for improved nutrition. The overarching goal was to provide patients with the most effective treatment possible, ensuring they were aware of the challenges ahead and prepared to invest their best efforts. The comprehensive strategy aimed to guarantee that patients received optimal treatment and support throughout their care journey. 

33, European Academy of Dermatology and Venereology Congress, 25-28 September 2024, Amsterdam