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.