Medicosnext
Vitiligo, an acquired depigmenting disorder, affects up to two percent of the general population. It is beyond a mere cosmetic problem, associated with social stigma and lowered self-esteem. Conventionally, vitiligo has been treated with medicines, surgery, and phototherapy.
Topical treatment with corticosteroid and calcineurin inhibitors were the mainstay for treating localized vitiligo; whereas oral steroid, particularly oral mini pulse therapy, is resorted to, to halt actively progressing vitiligo. Oral antioxidants are often considered an adjunctive to the main treatment, as they supposedly curtail the oxidative stress part of the pathogenesis. Other immunosuppressives, such as oral azathioprine and methotrexate, have variable success in stopping the progression and repigmentation.
Overall available vitiligo treatment has been far from satisfactory for both patient and physician. The success of the treatment lies in a better understanding of its pathogenesis. The pathogenesis of vitiligo is complex, and many theories have been postulated, such as oxidative stress, neural, viral, and autoimmune. Amongst the many genes identified in vitiligo, the majority are immune-susceptibility genes. Oxidative stress might be the primary event in the initiation of the immune dysfunction that leads to vitiligo. Alterations in the body’s innate ability to protect against oxidative damage may play a role in releasing autoantigens and neoantigens, which leads to an influx of cytotoxic CD8 T lymphocytes. Sequential upregulation of interferon-gamma, activation of the Janus Kinase (JAK) signaling pathway, and mobilization of the cytokine CXCL10 results in the activation of T-cells that attack the melanocyte. These findings are now being translated into new drug development, which is already in phase II and phase III clinical trials.
Spotlight is now on JAK inhibitors, such as tofacitinib and ruxolitinib, which block the IFNγ-CXCL10 pathway. These medicines reduce autoimmunity and look promising. As with any other oral immunosuppressive, these are not free of side effects. So, a topical preparation of these is under trial. As of now, these are considered off label by the FDA for the treatment of vitiligo. Again, the problem here is a relapse after the medicine is discontinued. Relapses are attributed to resident memory T-cells.
To offer longer-lasting therapy, the new treatment is focusing on targeting the cytokine interleukin -15 (IL-15). Results of a mouse study reveal that these antibodies turn off the signaling cascade, besides removing memory T-cells from the skin, eliminating the possibility of relapse. According to Dr. Harris, an expert researcher in vitiligo, “Repigmentation has occurred more rapidly with anti-IL-15 therapy than with any other treatment tested to date, but more importantly, the treated area didn’t relapse for the extended period.” Hopefully, a biologic, IL-15 antibody could be a great addition to the armamentarium of the dermatologist treating vitiligo in few years.
Another drug under trial is Afamelanotide, an analog of α-MSH. Vitiligo patients are known to have melanocortin system defects, including reduced serum and cutaneous lesion alpha-melanocyte-stimulating hormone (α-MSH). It helps repigmentation by stimulating melanoblast differentiation, increased melanin production, and melanocyte proliferation. Discovered accidentally as periorbital hyperpigmentation in patients treated with prostaglandin F2a analogs (latanoprost, bimatoprost) for glaucoma, it is now under trial to see its efficacy in treating vitiligo patients. The preliminary work shows it is well tolerated and effective. Its topical preparation is also in the pipeline.
Surgical interventions are preferred for treating vitiligo patients with stable disease. Vitiligo is often considered stable if there is no new lesion, or lesions haven’t expanded for at least two years. Easy as it may sound, establishing disease stability is rather tricky and difficult, where proper photographic documentation is unavailable and patient recall has poor reliability. Disease stability is critical to limit the likelihood of autoimmune destruction of the transplanted melanocytes. Confetti-like lesion, trichrome vitiligo, and koebnerization are indicators of unstable vitiligo. In doubtful cases, a mini punch test graft can be done. A patient can be considered candidate for surgical intervention, if after eight weeks, there exists a halo of repigmentation that extends at least one millimeter beyond the original mini punch graft. Surgical intervention includes punch graft, suction blister graft, needling, and melanocyte keratinocyte transplantation (MKTP). MKTP is a rather new procedure, available in Nepal for the last seven–eight years. It allows the treatment of larger depigmented areas with less donor tissue and results in 70% to 90% successful repigmentation with better cosmesis. A repigmentation usually occurs as early as six weeks and continues over a year, so requiring less frequent repeat procedure.
Phototherapy is a light-based treatment modality, with or without photosensitizers such as psoralen with sun exposure (PUVAsol), psoralen with UVA, narrow band UVB, and excimer laser. It can either be solo or adjunctive to medical or surgical treatment. Except for the PUVAsol, it requires the patient to visit the dermatologist office at regular intervals for a very long time. Many patients opt out of treatment before a significant repigmentation appears, either due to the hassle of traveling and visiting the dermatologist office several times a week, or the side effects of psoralen.
In a nutshell, though many clinical studies are on the frontline in the making of new drugs for treating vitiligo, it is a long waiting period for it to be approved by the FDA and then making its way into our market. Another concern is the cost of these medicines. So, we continue with the clinical acumen we gathered over the years in treating vitiligo patients with what we already have.
