Lichen planus‐like lesion preceding bullous pemphigoid development after programmed cell death protein‐1 inhibitor treatment

Abstract

Immune checkpoint inhibitors including programmed cell death protein 1 (PD‐1) antibody are used in major breakthrough therapies in cancer, however they cause unique adverse events, termed immune‐related adverse events (irAEs). Among the various dermatological irAEs, an autoimmune bullous disease, bullous pemphigoid (BP), the hallmarks of which are circulating autoantibodies to epidermal basement membrane zone (BMZ) including BP180, have been noted. However, the mechanism and timing of autoantibody production in PD‐1 inhibition remains unclear. Herein we report the case of a lichen planus (LP)‐like lesion in presence of anti‐BMZ antibodies, preceding BP in a patient treated with pembrolizumab, a PD‐1 antibody. A 72‐year‐old Japanese woman with a 3‐month history (6 cycles) of pembrolizumab was referred to our department for pruritic purple‐red papules or plaques. Histological finding revealed LP‐like dermatitis. Although pembrolizumab was stopped because of disease progression, she developed edematous erythematous lesions and tense blisters seven weeks later. Based on histopathological findings, direct immunofluorescence (DIF) assay and positive findings on chemiluminescent enzyme immunoassay (CLEIA) for BP180, she was diagnosed with BP and administered oral prednisolone. The blisters and erythemas improved, whereas her respiratory condition worsened and she died 29 days after the development of BP. We performed DIF of formalin‐fixed, paraffin‐embedded specimens biopsied from the LP‐like lesion and revealed IgG deposition at the epidermal BMZ. This finding showed anti‐BMZ antibodies had already existed at LP‐like lesion preceding development of BP; this suggests that the preceding LP‐like lesion induced anti‐BMZ antibody production, resulting in the development of BP.

Comment on “Toxic epidermal necrolysis during camrelizumab treatment for oesophageal squamous cell carcinoma”

“…The vicious circle could be named epitope spreading. Similar phenomenon was also observed in ICIs-related bullous pemphigoid 10. In conclusion, we provided more evidence that anti-SSA antibody was found in TEN patients triggered by anti-PD1 therapy.…”

Lichen planus pemphigoides with antibodies against the BP180 C‐terminal domain induced by pembrolizumab in a melanoma patient

“…1 Recently, a few cases of LPP induced by pembrolizumab have been reported (Table S1). [2][3][4][5] Antibodies against BP180NC16a were detected in all previous cases, while antibodies against the C-terminal region of BP180 were detected in our case. There were no clinical differences between the above two types, but our patient had a good response to a small dose of oral steroid (PSL 10 mg/day).…”

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

“…Varying severities have been reported following PD‐1 inhibitors depending on concurrent treatment for underlying malignancy. 20 For instance, combinational therapy of radiation and nivolumab has resulted in multiple, erosive LP. The initial eruptions only became erosive after radiation therapy.…”

“…While one previous report does indicate a LPP case following pembrolizumab, a separate study found this conclusion unlikely since clinical and histological findings lacked blisters of LP lesions. 20 In one case, an 87‐year‐old female with NSCLC was diagnosed with LPP following 9 cycles of nivolumab. Another case of a 57‐year‐old male with NSCLC had LPP after 3 months of nivolumab treatment.…”