Mucous Membrane Pemphigoid, Bullous Pemphigoid, and Anti-programmed Death-1/ Programmed Death-Ligand 1: A Case Report of an Elderly Woman With Mucous Membrane Pemphigoid Developing After Pembrolizumab Therapy for Metastatic Melanoma and Review of the Literature

Abstract

An 83-year-old patient developed erosions and a blister of the gingival mucous membrane, 6 months after discontinuation of the anti-programmed death-1 (anti PD-1) pembrolizumab therapy administered for 10 months for a metastatic melanoma. A diagnosis of mild mucous membrane pemphigoid (MMP) was made. Complete remission of MMP was rapidly obtained with minimal therapy (doxycycline). MMP remained in complete remission after a 3-month follow-up since discontinuation of the doxycycline therapy and no evidence of relapse of the melanoma was observed after a 14-month follow-up since discontinuation of the pembrolizumab therapy. The widespread use of anti PD-1 and anti-programmed death-ligand-1 (PD-L1) in several malignancies reveals new adverse events. MMP describes a group of chronic, inflammatory, mucous membrane-predominant, subepithelial auto-immune blistering diseases. It is clinically distinct from bullous pemphigoid another autoimmune blistering disease but shares some immunological similarities with it. Twenty-nine cases of bullous pemphigoid associated with anti PD-1/PD-L1 have been reported in the literature and one of MMP. Here, we described the case of a MMP developed after pembrolizumab and discussed the accountability of anti PD-1/PD-L1 in our case and the previous reported bullous pemphigoid and MMP cases using the Begaud system scoring.

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“…3 Skin lesions, which are found in 25% of cases, are often limited and confined to the face and scalp, as in our second patient. [4][5][6] Our first case was striking, since he developed oral MMP in combination with lichenoid cutaneous lesions. [4][5][6] Our first case was striking, since he developed oral MMP in combination with lichenoid cutaneous lesions.…”

“…[4][5][6] Our first case was striking, since he developed oral MMP in combination with lichenoid cutaneous lesions. 2,5 The interval between start of ICIs and BP onset was highly variable with a median of 6 months, as in our cases. 2,5 In a review of 27 ICB-triggered BP cases, the median age was 68 years.…”

“…1 However, it causes adverse effects, including lichenoid reactions. [2][3][4][5][6] We describe two new cases of pembrolizumab-triggered MMP; one of which was associated with cutaneous lichenoid lesions. [2][3][4][5][6] We describe two new cases of pembrolizumab-triggered MMP; one of which was associated with cutaneous lichenoid lesions.…”

“…3 Only three cases of MMP linked to ICI therapy have been described so far: while two cases had only mild oral involvement as in our two observations, the third case developed severe stenosis of the larynx (Table 1). 2,5 In a review of 27 ICB-triggered BP cases, the median age was 68 years. Lichenoid reactions with rarely mucosal involvement are observed in approximately 25% of cases during ICI therapy, but BP has also been increasingly reported.…”

“…Lichenoid reactions with rarely mucosal involvement are observed in approximately 25% of cases during ICI therapy, but BP has also been increasingly reported. 5 Immune checkpoint inhibitor therapy with anti-programmed death-1/ programmed death-ligand 1 results in a breakdown of tolerance, reduces activity of regulatory T cells (Tregs) and activates B cells and autoreactive T cells. 2,5 The interval between start of ICIs and BP onset was highly variable with a median of 6 months, as in our cases.…”