Anti–PD1 Immune Checkpoint Inhibitor–Induced Bullous Pemphigoid in Metastatic Melanoma and Non–Small Cell Lung Cancer

Abstract

Anti-programmed cell death 1 (PD1) targeted immune checkpoint inhibitors such as nivolumab and pembrolizumab are increasingly used to treat advanced malignancies such as melanoma, non-small cell lung cancer, urothelial cancer, and renal cell carcinoma. A rare but increasingly reported adverse effect of anti-PD1 therapy is bullous pemphigoid (BP), an autoimmune blistering disease directed against BP antigen 1 and BP antigen 2 in the basement membrane of the epidermis. We present 3 cases of BP secondary to anti-PD1 immunotherapy in patients with melanoma and non-small cell lung cancer to highlight the diagnosis and treatment of this condition and emphasize the importance of the dermatologist in the care of patients with immunotherapy-related skin disease. Cutis. 2020;105:E9-E12. • Early diagnosis of BP is essential for keeping patients on immunotherapy because its severity often results in temporary or permanent discontinuation of treatment.

European recommendations for management of immune checkpoint inhibitors‐derived dermatologic adverse events. The EADV task force ‘Dermatology for cancer patients’ position statement

“…The overall incidence of bullous dermatoses with anti‐PD‐1/anti‐PD‐L1 agents is estimated about 1%, 59 whereas the reported incidence for anti‐PD‐L1 agents alone ranges from 1.3% to 5%, raising concerns of a higher risk with the use of the latter 68 . Lichen planus pemphigoides, pemphigus, dermatitis herpetiformis, linear IgA bullous dermatosis or mucous membrane pemphigoid have been much more rarely reported in association with ICIs 59,67,69–74 …”

“…68 Lichen planus pemphigoides, pemphigus, dermatitis herpetiformis, linear IgA bullous dermatosis or mucous membrane pemphigoid have been much more rarely reported in association with ICIs. 59,67,[69][70][71][72][73][74] Pathogenesis of ICI-induced BP is vague, but it more likely represents a secondary consequence of both B-and T-cell activation in the context of immune stimulation. PD-1 inhibition may activate antibody-secreting B cells and inhibit immunosuppressive B regulatory cells.…”

“…1,66 The eruption develops from weeks to several months after treatment initiation and manifests with tense bullae and vesicles involving the trunk and extremities. 59,65,67,71,72 A pre-bullous phase, characterised by intractable pruritic and non-specific maculopapular or urticarial plaques may precede bullae formation. 69,73 Mucosal involvement is more common as compared to classic BP, with an incidence close to 40% in the most recent series.…”

Lichen planus pemphigoides: A unique form of bullous and lichenoid eruptions secondary to nivolumab

“…Another study also found renal cell carcinoma to be associated with BP following PD‐1 therapy. Additionally, two 70‐year‐old patients with stage IV melanoma and lung metastases developed BP between 9 and 12 months following the usage of PD‐1 inhibitors 11 …”

“…Additionally, two 70-year-old patients with stage IV melanoma and lung metastases developed BP between 9 and 12 months following the usage of PD-1 inhibitors. 11 Unlike other dermatologic irAEs which occur early in treatment, immunotherapy-induced bullous dermatoses demonstrate latency beyond the first treatment cycle. Often, mild and localized pruritus is the only clinical symptom before quickly progressing to hemorrhagic blisters on the chest, abdomen, thighs, and upper arms.…”