The relationship between vitiligolike depigmentation and melanoma can be explained by the immune activation against antigens associated with melanoma that also are expressed by normal melanocytes. In clinical observations of patients with melanoma and patients with vitiligo, antibodies to human melanocyte antigens were present in 80% (24/30) of patients vs 7% (2/28) in the control group.12 The autoimmune response results from a cross-reaction of melanoma cells that share the same antigens as normal melanocytes, such as melanoma antigen recognized by T cells 1 (MART-1), gp100, and tyrosinase.13,14
Development of vitiligolike depigmentation in patients with metastatic melanoma treated with nivolumab has been reported to occur between 2 and 15 months after the start of PD-1 therapy. This side effect of treatment correlates with favorable clinical outcomes.15,16 Enhancing immune recognition of melanocytes in patients with melanoma confers a survival advantage, as studies by Koh et al17 and Norlund et al18 involving patients who developed vitiligolike hypopigmentation associated with malignant melanoma indicated a better prognosis than for those without hypopigmentation. The 5-year survival rate of patients with both malignant melanoma and vitiligo was reported as 60% to 67% when it was estimated that only 30% to 50% of patients should have survived that duration of time.17,18 Similarly, a systematic review of patients with melanoma stages III and IV reported that those with associated hypopigmentation had a 2- to 4-fold decreased risk of disease progression and death compared to patients without depigmentation.7
Use of traditional treatment therapies for vitiligo is based on the ability of the therapy to suppress the immune system. However, in patients with metastatic melanoma undergoing immune-modulating cancer therapies, traditional treatment options may counter the antitumor effects of the targeted immunotherapies and should be used with caution. Our patient displayed improvement in the appearance of her starkly contrasting hypopigmented patches with the use of hydroquinone cream 4%, which induced necrotic death of melanocytes by inhibiting the conversion of L-3,4-dihydroxyphenylalanine to melanin by tyrosinase.19 The effect achieved by using topical hydroquinone 4% was a lighter skin appearance in areas of application.
There is no cure for vitiligo, and although it is a benign condition, it can negatively impact a patient's quality of life. In some countries, vitiligo is confused with leprosy, resulting in a social stigma attached to the diagnosis. Many patients are frightened or embarrassed by the diagnosis of vitiligo and its effects, and they often experience discrimination.2 Patients with vitiligo also experience more psychological difficulties such as depression.20 The unpredictability of vitiligo is associated with negative emotions including fear of spreading the lesions, shame, insecurity, and sadness.21 Supportive care measures, including psychological support and counseling, are recommended. Additionally, upon initiation of anti–PD-1 therapies, expectations should be discussed with patients concerning the possibilities of depigmentation and associated treatment results. Although the occurrence of vitiligo may cause the patient concern, it should be communicated that its presence is a positive indicator of a vigorous antimelanoma immunity and an increased survival rate.7
Vitiligolike depigmentation is a known rare adverse effect of nivolumab treatment. Although aesthetically unfavorable for the patient, the development of vitiligolike lesions while undergoing immunotherapy for melanoma may be a sign of a promising clinical outcome due to an effective immune response to melanoma antigens. Our patient remains in remission without any evidence of melanoma after 9 months of therapy, which offers support for a promising outcome for melanoma patients who experience vitiligolike depigmentation.