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Advances in dermatology and venereology Acta Dermato-Venereologica
Lichen Planus in Irradiated Skin During Nivolumab Treatment
Takaya KOMORI , Tetsuya HONDA *, Hiroyuki IRIE , Atsushi OTSUKA and Kenji KABASHIMA Department of Dermatology , Kyoto University Graduate School of Medicine , 54 Kawahara-cho , Shogoin , Sakyo-ku , Kyoto 606-8507 , Japan . * E-mail : hontetsu @ kuhp . kyoto-u . ac . jp and kaba @ kuhp . kyoto-u . ac . jp Accepted Oct 6 , 2016 ; Epub ahead of print Oct 10 , 2016
Lichen planus ( LP ) is a T-cell-mediated chronic inflammatory disease that develops in skin and mucosa ( 1 ). LP is characterized by band-like lymphocyte infiltration in the subepithelium and necrosis of basal keratinocytes ( 1 ). Nivolumab is a monoclonal antibody to programmed death 1 ( PD-1 ), an immune checkpoint molecule . Nivolumab facilitates T-cell activation by cancelling the suppressive effect of PD-1 signalling on T cells . It has been shown to have great efficacy in facilitating T cell activation in various cancers , including , but not limited to , melanoma and breast cancer ( 2 ). In addition , the combination of nivolumab with radiotherapy may have synergistic effects ( 3 ). We report here a case of LP that developed in the irradiated skin area during administration of nivolumab in a patient with breast cancer .
CASE REPORT
A 67-year-old woman diagnosed with breast cancer was referred to our dermatology department because of purple-coloured skin papules on the middle of her back . She had developed breast cancer and had undergone surgery at the age of 63 years . A liver metastasis was found approximately 18 months after the surgery and chemotherapy ( anastrozole and tegafur-uracil ). Nivolumab ( 2 mg / kg ) was then started and administered every 3 weeks . Four months after the nivolumab treatment , the patient reported abdominal pain due to the enlargement of lymph nodes in the hepatic portal region . The liver metastasis also progressed slightly . Nivolumab was discontinued , and fractionated radiation to a total dose of 30 Gy was applied to the enlarged lymph nodes . A week after the radiotherapy , nivolumab was restarted . One month after restarting nivolumab treatment , purple-coloured papules developed on her back ( Fig . 1a , b ). The lesion clearly corresponded to the hepatic portal lymph nodes , which was the area of radiation ( Fig . 1a ). Histological analysis showed band-like lymphocyte infiltration in the upper dermis , with liquefaction and necrotic keratinocytes in the epidermis ( Fig . 1c ). The lesion was diagnosed as LP , and topical difluprednate treatment was started ( 0.05 %); however , the LP lesion persisted . Since the enlarged lymph nodes regressed , nivolumab was discontinued once more . After the cessation of nivolumab , the LP lesion gradually improved by treatment with difluprednate ointment and almost disappeared 8 weeks after the last nivolumab treatment .
DISCUSSION
Both nivolumab and radiation have been reported to trigger LP ( 4 , 5 ). In the current case , the LP did not develop during the first 4 months of nivolumab treatment . However , following radiotherapy , the LP lesion developed one month after restarting nivolumab treatment . The LP lesion was restricted to the irradiated area , and disappeared after the cessation of nivolumab treatment . Therefore , we speculate that both factors were required to fully develop LP in our case .
In LP lesions , the intensive expression of programmed death ligand 1 ( PD-L1 ) on keratinocytes has been reported ( 6 ). In animal models PD-L1 on keratinocytes is suggested to play protective roles in interface dermatitis caused by cytotoxic CD8 + T cells ( 7 , 8 ). The administration of anti-PD-1 antibody significantly increases the production of interferon-γ in patients with oral LP ( 9 ).
Fig . 1 . A 67-year-old woman with breast cancer . ( a ) Purple-coloured papules on the middle of the back . Black square indicates the radiation area . ( b ) Higher magnification image of the lesion . Black dots indicate the biopsy area . ( c ) Haematoxylin and eosin staining ( 20 ×; scale bar 100 µ m ). Subepidermal lymphocyte infiltrations ( black arrows ) and a number of necrotic keratinocyte ( white arrows ) in the epithelium , were seen .
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2017 Acta Dermato-Venereologica . doi : 10.2340 / 00015555-2545 Acta Derm Venereol 2017 ; 97 : 391 – 392