Letter to the Editor: The Role of Skin Biopsy in the Management of Immune Checkpoint Inhibitor Toxicity

Re: Fecher LA, Bishu S, Fontana RJ, et al. The role of tissue biopsy in the management of immune checkpoint inhibitor toxicity. J Natl Compr Canc Netw 2022;20(4):417–425.

I read with interest the superlative review by Fecher et al,¹ regarding the important role of tissue biopsy in the management of immune checkpoint inhibitor (ICI) toxicity. The authors succinctly describe the benefit of biopsy when evaluating ICI adverse events affecting the colon, liver, lungs, heart, and kidneys. In addition to these organs, tissue biopsy is also essential in the assessment of cutaneous toxicity from ICI.²

ICI-associated adverse effects to the skin have been not only observed but also characterized morphologically and pathologically.^3,4 More commonly occurring cutaneous reactions to these agents include dermatitis, lichenoid reactions, maculopapular eruption, and psoriasis. In addition, less frequently observed ICI-associated cutaneous adverse events are alopecia areata, bullous pemphigoid, drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), skin hypopigmentation and hyperpigmentation, and Stevens-Johnson syndrome/toxic epiderma necrolysis (SJS/TEN). Rarely noted ICI-induced cutaneous adverse events include acute febrile neutrophilic dermatosis, dermatomyositis, pyoderma gangrenosum, sarcoidosis, sclerodermoid reaction, sicca syndrome, vasculitis, and vitiligo.^2–5

The diagnosis of some ICI-induced skin conditions can be suspected, diagnosed, or both based on the morphologic presentation, thereby enabling prompt dose reduction or discontinuation of the ICI and/or pharmacologic therapeutic intervention directed toward the dermatosis.^2,3,5 However, in other situations, a skin biopsy of the lesion (or perilesional skin for immunofluorescence studies when bullous pemphigoid is in the differential diagnosis) may be essential for evaluating and/or confirming the diagnosis of an ICI-associated cutaneous adverse event.^4,5 Indeed, skin biopsy has been recommended when other skin immune-related adverse events in addition to bullous pemphigoid are being considered, such as cutaneous sarcoidosis, DIHS/DRESS, lichenoid reactions, SJS/TEN, transient acantholytic dermatosis, and sometimes psoriasiform rash.⁵

In summary, ICIs are essential antineoplastic agents. Their use in oncology patients is associated with well-defined adverse events that can potentially affect various solid organs. The crucial role of tissue biopsy for the evaluation of ICI-associated toxicity is paramount for not only these visceral tissues but also the cutaneous integument.