Mucous membrane pemphigoid related to nivolumab immunotherapy: report of a rare case and review of the literature

Background

Immune-checkpoint inhibitors (ICIs) have been successfully used in the management of patients suffering from various malignancies; however, these agents have been also blamed for a wide spectrum of adverse events involving several anatomic sites, including the oral mucosa. Herein, we describe a rare case of mucous membrane pemphigoid (MMP) related to PD-1 inhibitor nivolumab and review the English-language literature on immunotherapy-associated MMP.

Case Description

A 74-year-old female presented for the evaluation of widespread painful ulcerations affecting the buccal mucosae, lower lip, and tongue. Nine months ago, the patient was diagnosed with lung adenocarcinoma and underwent 4 cycles of chemotherapy followed by radiation therapy; she was concurrently receiving nivolumab, which was also continued as monotherapy. The oral lesions developed after the last nivolumab injection, approximately 8 months after diagnosis and initiation of immunotherapy. With a clinical provisional diagnosis of a vesiculobullous disease of autoimmune or immunotherapy-associated origin, a perilesional diagnostic oral biopsy was performed. Microscopically, subepithelial clefting was observed, while direct immunofluorescence showed linear deposition of immunoreactants at the basement membrane zone. No circulating autoantibodies in patient’s serum were detected by ELISA and a final diagnosis of MMP was rendered. Considering the temporal relationship between the onset of the symptoms and nivolumab administration, an etiologic correlation between immunotherapy and MMP was considered very likely. Systemic prednisolone treatment, along with nivolumab withdrawal following consultation with patient’s oncologist, resulted in rapid remission of oral lesions.

Conclusions

Although ICIs have an established role in treatment of several cancers, they have also been associated with side effects of variable severity. Especially, ICI-related MMP seems to be quite rare with only a few cases reported in the English-language literature. Oral health care professionals should be aware of such adverse events, as their prompt recognition, accurate diagnosis, and appropriate management improves patients’ quality of life.