Issue: 2017 > July > photo quiz

Answer to Photo Quiz: Cutaneous adverse effects of immunotherapy

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Histopathological examination of skin biopsies taken from squamous papules located on the flank and on the hand both revealed a lichenoid interface dermatitis with vacuolar degeneration of the epidermis and presence of Civatte bodies (figure 2). We made a diagnosis of lichenoid mucocutaneous eruption and vitiligo due to the use of nivolumab. These cutaneous adverse events reflect T-cell mediated immunity towards keratinocytes and melanocytes, activated by immune checkpoint inhibition. In the development of vitiligo due to immunotherapy specific T-cells against MART-1, gp100 and tyrosinase seem to play a role. But also MART-1 reactive antibody responses are suggested to be important. The mechanisms of breaking tolerance to MART-1, which lead to antibody responses, may be dependent on T-cell help, but deserve further investigation.2 More than 15% of patients treated with anti-PD1 antibodies experience cutaneous adverse effects.3 In 82 patients treated with nivolumab at an institution in Australia, 17% of patients developed a lichenoid eruption and 17% developed vitiligo.4
Development of vitiligo or skin eruption in patients receiving anti-PD1 antibody therapy for melanoma is associated with better survival.5 In patients treated with ipilimumab or adoptive T-cell transfer the occurrence of vitiligo has been reported, but not of lichenoid skin eruption. Treatment with topical and systemic corticosteroids resulted in significant improvement. The patient’s melanoma has already been in remission for 17 months.


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  2. Teulings HE, Willemsen KJ, Glykofridis I, et al. The antibody response against MART-1 differs in patients with melanoma-associated leucoderma and vitiligo. Pigment Cell Melanoma Res. 2014;27:1086-96. 
  3. Belum VR, Benhuri B, Postow MA, et al. Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor. Eur J Cancer. 2016;60:12-25. 
  4. Hwang SJ, Carlos G, Wakade D, et al. Cutaneous adverse events (AEs) of anti-programmed cell death(PD)-1 therapy in patients with metastatic melanoma: A single-institution cohort. J Am Acad Dermatol. 2016;74:455-61. 
  5. Freeman-Keller M, Kim Y, Cronin H, Richards A, Gibney G, Weber JS. Nivolumab in resected and unresectable metastatic melanoma: characteristics of immune-related adverse events and association with outcomes. Clin Cancer Res. 2016;22:886-94.