Oral manifestations of immune‐related adverse events in cancer patients treated with immune checkpoint inhibitors

Abstract

Immunotherapy with immune checkpoint inhibitors (ICIs) has transformed cancer treatment over the past decade, improving survival rates in numerous advanced cancers. Immune-related adverse events (irAEs) are common and can affect any organ system, with many of these toxicities being well-characterized with clear grading criteria and management approaches. There has been less emphasis on oral manifestations of irAEs. This review provides an overview of oral manifestations of irAEs, including mucosal and salivary gland toxicities, and proposes a grading system and management guidelines. irAEs are common treatment-related toxicities in patients treated with ICIs. Oral irAEs can range from asymptomatic white reticulations to life-threatening mucocutaneous reactions requiring aggressive management with corticosteroids and/or permanent discontinuation of ICIs. Oral healthcare providers should be prepared to identify and manage oral irAEs in collaboration with oncologists and other specialists.

Checkpoint Inhibitors and the Gut

“…Cutaneous lichenoid reaction is the most common ICI event in the oral cavity, having an incidence of up to 17% [36]. Histopathologic findings are largely non-specific, typically involving mucositis with dense lymphocytic and eosinophilic infiltration and small amounts of clefting without fulminant ulcer [37].…”

“…Apart from superficial lichenoid lesions, 1% of all patients treated with immunomodulators develop superficial oral mucosal blisters, also known as mucous membrane pemphigoid [40]. Mucous membrane pemphigoid typically involves relatively deep infiltrates and histopathologic immunofluorescence findings that typically indicate subepithelial cleavage and linear immunoglobulin deposits at basement membrane [36].…”

“…Another lesion, erythema multiform major, has been associated with the use of PDL-1 antagonist and CTLA-4 antagonist [36]. These lesions are usually more serious and extensive than superficial blisters.…”

“…Stevens-Johnson syndrome-like reactions, toxic epidermal necrolysis-like reactions, and Sjogren syndrome are amongst oral cavity immune modulator-induced adverse events with systemic features. The presence of these conditions is usually an indication to discontinue immunomodulators [36,42].…”

“…Stevens-Johnson syndrome and toxic epidermal necrolysis are well-feared complications of immunomodulators. Although rare (<1% incidence among patients treated with ICI therapy), they are usually associated with PDL-1 and PD-1 antagonist treatment [36]. Lesions are usually not limited to the oral cavity, and are characterized by widespread dusky macules or flat, atypical targetoid lesions involving a high index of body surface area, usually with signs of systemic inflammatory response syndrome [43].…”