PD-1 inhibitors induced bullous lichen planus-like reactions: a rare presentation and report of three cases

Abstract

The introduction of immunotherapy such as antiprogrammed death1 (anti-PD1) monoclonal antibodies has changed the scenario of treatment in cancer. Apart from their impressive efficacy profiles, they are better tolerated than the anticytotoxic T-lymphocyte-associated protein 4 antibodies. Dermatological adverse events such as pruritus and rash have been reported in various clinical trials. We report three cases of anti-PD1-induced bullous lichen planus (LP)-like reactions encountered in our institution. These patients developed LP-like papules and annular plaques with vesicles or crusted centres. Histology showed LP-like changes with negative immunofluorescence. Vesiculobullous lesions in patients treated with anti-PD1 therapies require a careful clinicopathological evaluation.

Pembrolizumab‐induced lichen planus pemphigoides in a patient with metastatic melanoma

“…Erysipel-artige Infl ammation, Vitiligo, Alopezie und Haarwachstum[ 1,2 ] . Es wurden auch Fälle von lichenoiden Hautreaktionen, Lichen planus mucosae, bullösem Lichen planus und bullösem Pemphigoid in Assoziation zur PD-1-Inhibition berichtet[1][2][3][4][5][6] . Ein Anti-PD-1-Antikörper-induzierter LPP wurde nach unserem Wissensstand in der Literatur noch nicht beschrieben.Pembrolizumab induzierte bei unserem Patienten einen schweren LPP und interessanterweise auch eine vollständige Remission des malignen Melanoms.…”

PD‐1 inhibitor‐associated lichenoid inflammation with incidental suprabasilar acantholysis or vesiculation—Report of 4 cases

“…Lichenoid drug reaction secondary to anti-PD1 therapy is becoming well recognized. 12,13,18,19 While blisters or cleftings are not uncommon, these are usually subepidermal and secondary to the intense interface dermatitis. 12 The combination of lichenoid inflammation with suprabasal clefting is very unusual, particularly when the blisters were not clinically apparent.…”

“…12 The vast majority of these blisters were subepidermal and were presumed to be due to the intense lichenoid inflammation etiologically similar to blisters seen in Steven Johnson syndrome or toxic epidermal necrolysis. [12][13][14] The only form of immune-mediated bullous disease unrelated to interface dermatitis that has been described in setting of anti-PD1 therapy is bullous pemphigoid. [14][15][16][17] We present the clinicopathologic features of 4 patients who developed lichenoid inflammation with microscopic suprabasal or intraepidermal clefting while on anti-PD1 agent with or without ipilimumab.…”

Management of the Cutaneous Adverse Effects of Antimelanoma Therapy

“…Vesiculobullous reactions/bullous pemphigoid Multiple reports in the literature describe vesiculobullous reactions such as bullous pemphigoid [53,54], bullous lichenoid reactions and bullous lichen planus-like reactions [55] occurring in patients treated with anti-PD-1 antibodies. Onset of the eruption ranges from 1-month post start of therapy [55] to 18 months after initiation [54]. No formal consensus has been met in regards to standard treatment, and multiple management methods have been described (see Figure 4) including the use of topical or oral corticosteroid and cessation of anti-PD-1 antibody in severe cases [53].…”

“…Methotrexate has been successfully utilized in anti-PD-1-induced bullous pemphigoid [53,56], along with rituxumab [57]. Acitretin has been used in bullous lichen-planus like eruptions [55]. Mucosal erosions have been treated with triamcinolone acetonide [55] as well as oral tacrolimus ointment and dexamethasone mouthwash [58].…”