Vitiligo:
Vitiligo is a skin disorder categorized by hypopigmented lesions (white spots) on the skin and occurs due to the destruction of functional melanocytes from the epidermis layer. Vitiligo can disturb any area, but it most commonly affects the neck, face, hands, and legs. Vitiligo is classified as generalized or localized vitiligo based upon the spread of the lesions and the appearance of hypopigmented cutaneous areas49.
Pathogenesis: The analysis of blood and skin samples showed increased levels of CXC motif ligand 10 in the blood serum. The pathogenesis of vitiligo involves raised levels of tumor necrosis factor-alpha (TNFα) and interferon-gamma (IFN-γ) and CD8+ T cells mediated skin infiltration expressing CXC motif receptor 3.
Alternatively, vitiligo-like lesions can be caused by microphthalmia-associated transcription factor (MITF) that allows the transcription of many genes, essential for promoting the survival of melanocytes. MITF- associated genes are tumor-specific neoantigens, and genes that may signify melanocyte lineage-specific antigens. Therefore, immune system activation against MITF-associated epitopes with PD-1/PD-L1 blockers could destroy normal melanocytes causing the development of vitiligo-like lesions 50( Figure 4).
Clinical incidence: Ten cases of vitiligo, hypopigmentation, or loss of pigment after the anti-PD-1/PD-L1 therapy have been reported. Six of them were associated with nivolumab therapy 13, 51-53, three of them with pembrolizumab therapy54-56, and one of them with anti-PD-L1 atezolizumab57. The time from initiation of anti-PD-1/PD-L1 therapy to the progression of disease ranges from six days to nine months. Vitiligo was observed in patients with age from 30-75 years. Vitiligo-like hypopigmentation (or melanoma-associated leukoderma) was reported in melanoma patients (3.4 to 28%) and other metastatic cancers. The overall incidence of vitiligo is assessed to be 5.5% respectively with anti-PD-1/ PD-L1 checkpoint inhibitors. The distribution of PD-1/PD-L1 induced vitiligo typically involves the upper body, such as the face, neck, upper torso, and upper limbs. Focal patches may also be seen around scars or sites of skin metastases. Mainly asymptomatic lesions can occur, categorized by hypopigmented macules in the photo exposed areas, which can be headed by pruritis or nonspecific maculopapular rash 58. Hypopigmentation has been reported in a patient with metastatic melanoma resulting in whitening of eyelashes, eyebrows, body hair, and scalp in accumulation to vitiligo, with pembrolizumab immunotherapy 55.
Treatment: Despite the presence of hypopigmentation or vitiligo most of the patients continued to PD-1/PD-L1 immunotherapy. Vitiligo can spontaneously be treated with high potency topical corticosteroids and excimer laser therapy56. Other therapies include intravenous immunoglobulin therapy (IVIg) clobetasol propionate 0.05%59, topical tacrolimus (0.1% ointment) (n=2)53, 60, calcipotriol and calcineurin inhibitors60, 0.05% fluticasone propionate13, triamcinolone 0.1% cream53. Sun protection for the prevention of hypopigmented areas from burning.