In this installment of Topical Conversations, Naiem Issa, MD, PhD, FAAD, discusses oxidants and antioxidants and their role in the development and resolution of vitiligo. 

Why do oxidants and antioxidants matter in vitiligo? 

Vitiligo starts with an insult that can come in many forms, including sun damage, major stress, traumatic incidents, medications, and other autoimmune disorders that cause inflammatory destruction. This kind of stress manifests in a reduction in the immune privilege of the melanocytes in the skin. 

Melanocytes are typically immune privileged, meaning that the immune system does not recognize the antigens on the melanocytes and do not attack them. 

The stress initiates a reduction in the immune privilege of the melanocytes, which triggers production of CD8+ T cells that cause destruction of the melanocytes, leading to vitiligo. This mechanism is similar to that seen in alopecia areata, in which hair follicle immune privilege becomes decomposed. 

During this destructive stress, there is an increase in oxidants, which causes the formation of reactive oxygen species that affect the cell membrane of melanocytes and the organelles of the cell and cause overall oxidative destruction. This destruction, in turn, causes apoptosis and increased expression of antigens by the dying melanocyte that the immune system recognizes. 

As a compensatory response, antioxidants such as catalase or superoxide dismutase try to act, but with malfunctioning machinery, there is a reduction in the utility of those antioxidants. 

Catalase expression in vitiligo 

A paper by Kassab et al published in the Journal of Clinical Medicine looked specifically at the antioxidant enzyme catalase. The study found that in vitiliginous lesions, when compared to normal lesions, there was a reduction in the catalase expression in the serum of these patients and more so in unstable vitiligo, which showed even less catalase than in stable vitiligo. This demonstrates there is an effect on reducing the amount of antioxidants in the system to allow for compensation. 

However, the study also showed a paradoxical increase in those patients in superoxide dismutase, also known as the anti-aging protein. This could be a compensatory methodology to make up for the lack of catalase and for the increase in the oxidative molecules, representing the interplay present between oxidants and antioxidants to try to prevent the destruction of the melanocyte, thus the antigen presentation. 

The future of antioxidants in vitiligo research 

While the data in this area is still premature, there are studies currently looking into the use of antioxidants like n-acetylcystein and other types of supplements to mop up oxidants and prevent the formation and progression of vitiligo. 

Current knowledge does support that the progression of oxidants leads to the development of vitiligo, and future research is warranted to determine if the use of antioxidants can prevent it.