Presentation

A 90-year-old male with a history of hypertension was diagnosed with metastatic melanoma and treated with pembrolizumab intravenously every 3 weeks. Nine months after treatment with pembrolizumab, the patient developed jaw claudication, temporal headaches, and bilateral vision loss. Inflammation markers (erythrocyte sedimentation rate and C-reactive protein) were significantly elevated. Biopsies of the bilateral temporal arteries demonstrated moderate to severe inflammatory infiltrates and focal mural calcifications consistent with giant cell arteritis (GCA). The patient was started on high-dose prednisone (60 mg) with a taper; however, he was continued on treatment with pembrolizumab for metastatic melanoma as previously outlined.

Three months thereafter, the patient presented as a new patient to our clinic with a recurrence of headache and jaw claudication. The physical exam at this point was notable for frontal-parietal scalp necrosis (Fig. 1). Based on the timing and distribution of his scalp lesions, we made the diagnosis of scalp necrosis secondary to recurrent GCA as a likely result of an immune-related adverse event from his pembrolizumab treatment. Given the severity of the presentation, we recommended holding pembrolizumab indefinitely. Our patient was resumed on high-dose prednisone (60 mg) with a taper and the addition of tocilizumab 162 mg subcutaneously weekly as a disease-modifying and steroid-sparing agent. He had no further progression of scalp necrosis or recurrence of headaches thereafter. Unfortunately, his vision remained permanently impaired bilaterally.

Fig. 1
figure 1

A-10.0 x 8.0 cm right frontal-parietal lesion with central necrosis with smaller surrounding lesions; B-Abnormal temporal artery biopsy with features of severe intimal thickening with luminal compromise (1) and a media expanded by lymphoid infiltrate (2)

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Discussion

Scalp necrosis is a rare but serious complication of GCA. It signifies a severely active disease [1]. In our case, this patient developed GCA and scalp necrosis as an immune-related adverse event (IRAE) after the use of pembrolizumab, a programmed death (PD)-1 inhibitor. IRAEs have been reported in 70% of patients treated with anti-PD1 immunotherapy [2]. By blocking the PD-1 pathway, checkpoint inhibitors increase T cell proliferation, increasing the patient’s susceptibility to autoimmune diseases including GCA. Prophylactic treatment with immunosuppressive agents has not been shown to prevent the incidence of IRAEs [3].

A few cases of GCA have been reported as IRAEs for immunopotentiating treatments such as nivolumab, ipilimumab, and pembrolizumab, but scalp necrosis has only been rarely cited as a complication of GCA associated with immunotherapy. It is important to recognize this unusual cutaneous manifestation of GCA and a possible complication in patients undergoing cancer immunotherapy.