The Clinical and Histopathological Features of Cutaneous Immune-Related Adverse Events and Their Outcomes

Abstract

Immune checkpoint inhibitors (ICIs) cause a variety of inflammatory eruptions. The understanding of ICI-induced inflammatory eruptions with detailed histopathological findings is not adequate, particularly in Asian populations. In this study, we retrospectively reviewed 51 patients who were histopathologically diagnosed with cutaneous immune-related adverse events (irAEs) following ICI therapy between 2014 and 2020 at the Department of Dermatology of Kyushu University Hospital. Of the 51 patients (30 men, 21 women), maculopapular rash (38/51, 74.5%), erythema multiforme (2/51, 3.9%), lichenoid reaction (3/51, 5.9%), psoriasiform reaction (3/51, 5.9%), bullous pemphigoid (3/51, 5.9%), scleroderma-like reaction (1/51, 2.0%), and Stevens–Johnson syndrome (1/51, 2.0%) were observed. The clinical and histopathological findings of these eruptions were equivalent to typical cases of common drug eruptions. The onset of maculopapular rash was relatively early (more than half of events occurred within 1 month), whereas lichenoid reactions and autoimmune diseases occurred relatively late (4–8 months). With appropriate treatment and/or interruption of ICIs, most rashes improved (50/51, 98.0%). The ICI-induced inflammatory eruptions shared similar clinical and histopathological features with classical inflammatory eruptions, but a variety of inflammatory eruptions may occur with different degrees of severity. Dermatologists play an important role in providing specialized care for cutaneous irAEs.

Association of Bullous Pemphigoid With Immune Checkpoint Inhibitor Therapy in Patients With Cancer

“…Among these, 70 articles reporting clinical data from 127 individual patients were reviewed to include in the analytic component of the systematic review. The 7 other articles provided predominantly summarized data, with limited and inconsistent data from individual patients. Available data from these 7 articles were extracted and summarized but not included in the analysis (eTable 4 in the Supplement).…”

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

“…Cutaneous lichenoid reactions are one of the most common dermatologic toxicities associated with immunotherapy, affecting between 0.5% and 17% of patients treated, though the incidence is sporadically reported and is likely to be underestimated (Geisler et al, 2020;Hwang et al, 2016;Sibaud et al, 2017;Wongvibulsin et al, 2021). These events often spare the oral mucosa, or may be underdiagnosed, but there have been numerous reports of oral lichen planus (OLP)-like reactions with or without cutaneous or other mucosal involvement in patients on nivolumab, pembrolizumab, and atezolizumab (Bhattacharyya et al, 2020;Coleman et al, 2019;Enomoto et al, 2019;Hashimoto et al, 2021;Lacouture & Sibaud, 2018;Nguyen et al, 2019;Obara et al, 2018;Owosho et al, 2016;Schaberg et al, 2016;Shazib et al, 2020;Shi et al, 2016;Sibaud et al, 2017;Vigarios et al, 2017). Clinical features of OLP-like reactions include white reticulations (Wickham striae) with associated erythema and/or ulcers affecting the tongue, buccal mucosa, hard and soft palatal mucosa, lip mucosa, and gingiva, though the buccal mucosa and ventral tongue appear to be most commonly affected (Figure 1) (Bhattacharyya et al, 2020;Enomoto et al, 2019;Lacouture & Sibaud, 2018;Nguyen et al, 2019;Obara et al, 2018;Owosho et al, 2016;Schaberg et al, 2016;Shazib et al, 2020;Shi et al, 2016;Sibaud et al, 2017;Vigarios et al, 2017).…”

“…While there is an attempt to categorize the variable clinical and pathological characteristics, it must be recognized that patients may present with overlapping and/or unexpected features. Furthermore, oral irAEs can occur either in isolation or simultaneously with irAEs affecting other body systems (Hashimoto et al, 2021;Hwang et al, 2016;Ramos-Casals et al, 2019).…”

Meditating on Cancer Management at the Time of Immunotherapy

“…These results should not be surprising, as it is largely renowned that gut microbiota directly influences the therapeutic efficacy of ICI [ 13 ], while antibiotics negatively impact on the quality of the microbiota. This argument has also been discussed in the review article prepared by Tran and colleagues [ 14 ], who focused particularly on the effect of ICI and microbiota in the occurrence of gastrointestinal immune-related adverse events (irAEs), whereas a dedicated review on cutaneous irAES, illustrating their clinical and histopathological features as well as outcome, has been presented by Hashimoto and colleagues [ 15 ].…”

“…Thanks to the contributions provided by Franzi and colleagues [ 16 ] and Knetki-Wróblewska and colleagues [ 15 ], the Special Issue has been enriched with two review articles facing the potentials of chemo-immunotherapy in locally advanced NSCLC patients [ 16 ] and the therapeutic opportunities in those cases with coexistence of high PD-L1 expression and RET fusion [ 17 ], respectively. Clearly, the debate on the best treatment options in the era checkpoint inhibitors is far from being over; nevertheless, the literature reviews and insights provided by the abovementioned authors can help an attentive reader to shed some light on the arguments.…”