Acral Necrosis After PD-L1 Immune Checkpoint Inhibitor Therapy
Practice Points
- Dermatologists should be aware of acral necrosis as a rare adverse event of treatment with an immune checkpoint inhibitor.
- Delayed immune-related events are sequelae of immune checkpoint inhibitors that can occur months after treatment is discontinued.
Acral necrosis following immune checkpoint inhibitor therapy has been reported as a rare and recalcitrant immune-related adverse event (AE).1-4 However, our patient’s symptoms occurred months after treatment was discontinued, which is consistent with a DIRE.5 The course of acral necrosis begins with acrocyanosis (a Raynaud disease–like phenomenon) of the fingers that progresses to necrosis. A history of Raynaud disease or other autoimmune disorder generally is absent.1 Our patient’s history indicated actively smoking at the time of presentation, similar to a case described by Khaddour et al.1 Similarly, in a case presented by Comont et al,3 the patient also had a history of smoking. In a recent study of acute vascular events associated with immune checkpoint inhibitors, 16 of 31 patients had a history of smoking.6
No definitive diagnostic laboratory or pathologic findings are associated with acral necrosis following immune checkpoint inhibitor therapy. Histopathologic analysis does not demonstrate vasculitis or other overt vascular pathology.2,3
The optimal treatment of immune checkpoint inhibitor–associated digital necrosis is unclear. Corticosteroids and discontinuation of the immune checkpoint inhibitor generally are employed,1-4 though treatment response has been variable. Other therapies such as calcium channel blockers (as in our case), sympathectomy,1 epoprostenol, botulinum injection, rituximab,2 and alprostadil4 have been attempted without clear effect.
We considered a diagnosis of paraneoplastic acral vascular syndrome in our patient, which was ruled out because the syndrome typically occurs in the setting of a worsening underlying malignancy7; our patient’s cancer was stable to improved. Thromboangiitis obliterans was ruled out by the absence of a characteristic thrombus on biopsy, the patient’s older age, and involvement of the nose.
We report an unusual case of acral necrosis occurring as a DIRE in response to administration of an immune checkpoint inhibitor. Further description is needed to clarify the diagnostic criteria for and treatment of this rare autoimmune phenomenon.
