- 11/2017 cutaneous melanoma of the right foot (Breslow tumor thickness 6 mm)
- initial stage: pT4bN2aM0, IIIC (AJCC 2017), BRAF wild-type, NRAS Q61R-mutation
- 01/2019: disseminated pulmonary, hepatic and lymph node metastases
- 01/2018-01/2019 adjuvant immunotherapy with ipilimumab (1 mg/kg bw) every 6 weeks and nivolumab 240 mg every two weeks (CheckMate-915 clinical trial)
- 02/2019 combined immunotherapy with ipilimumab (3 mg/kg bw) and nivolumab (1 mg/kg bw) due to progressive disease (three cycles)
- 06/2019 - today: dacarbazine (DTIC) every three weeks
Nine weeks after initiation of the combined immunotherapy with ipilimumab (3 mg/kg bw) and nivolumab (1 mg/kg bw) the patient presented to our dermato-oncological ambulance with dizziness, imbalance and an acute bilateral hearing loss due to an immune-mediated bilateral vestibulopathy. Furthermore, she suffered from progressive visual loss in both eyes (0.1 in the right eye; 0.8 in the left eye). ophthalmologic consultation confirmed a papillitis, retinal vasculitis as well as an uveitis. An alopecia areata universalis as well as leukotrichia induced by CPIs was already known. Thus, we diagnosed Vogt-Koyanagi-Harada syndrome (VKH).
Therapy with methylprednisolone (1 g/d) was initiated for three days and was tapered in the following weeks. The bilateral vestibulopathy remained irreversible; the patient still requires hearing aids on both sides. Contrary to that an improvement in vision was achieved in the right eye (0.1 à 0.32).
Immunotherapy was interrupted; instead a chemotherapy with dacarbazine was initiated. Current staging showed stable disease.
VKH is an inflammatory disease syndrome characterized by bilateral uveitis in combination with alopecia, vitiligo or auditory manifestations, as shown in our patient. It is caused by a systemic immune reaction against melanocytes and can possibly be induced by immune checkpoint-inhibitors (Bricout et al., J Immunotherapy, 2017).
Ophthalmic irAEs occur in less than 1% of patients under immunotherapy and include uveitis, episcleritis and scleritis. Only few case reports about VKH exist (Crosson et al. J Immunotherapy, 2016). Wong et al. first reported a case of bilateral ipilimumab induced vitritis, choroiditis and retinal detachments due to VKH. As in our case, high-dose corticosteroids led to a quick improvement (Wong et al., Retin Cases Brief Rep., 2012).
Oncologists should be aware of possible ophthalmic and systemic findings induced by immunotherapy and should consider quick ophthalmologic consultation.
