Histologic Assessment of Lichenoid Dermatitis Observed in Patients With Advanced Malignancies on Antiprogramed Cell Death–1 (anti–PD-1) Therapy With or Without Ipilimumab

Abstract

Lichenoid drug reaction is a common adverse reaction in patients taking immune-modulatory agents such as antiprogramed cell death (PD-1) and cytotoxic T lymphocyte antigen-4 agents. The authors describe the clinical and histologic features of lichenoid drug reaction in 20 biopsies from 15 patients on anti-PD-1 agents and 9 biopsies from 7 patients on anti-PD-1 plus ipilimumab therapy. Clinically, all except 2 patients presented with discrete, violaceous exanthematous papules to plaques. The lichenoid inflammation in the majority (18 of 29 biopsies) was florid although histology was quite heterogeneous. Nevertheless, there was frequent involvement of the superficial follicular epithelium and acrosyringium, and also a propensity to blister that occurred in approximately 20% of the biopsies. Occasional patients had disease closely resembling lichen planus, although all of these biopsies had some atypical features for lichen planus such as parakeratosis. Dermal eosinophils were common particularly in those with mild inflammation. The lichenoid reaction was responsive to topical steroid or oral systemic treatment in general, and the anti-PD-1 agent had to be ceased in only one patient.

Oral lichenoid reactions associated with anti‐PD‐1/PD‐L1 therapies: clinicopathological findings

“…Histopathology findings (n=4) showed patchy-to-florid lichenoid interface dermatitis in the upper lamina propria, with variable degrees of basal vacuolar changes and apoptosis. Of note, and as previously reported in patients developing cutaneous lichenoid reactions with anti-PD-1, 8 more atypical features such as hypergranulosis and marked parakeratosis were also observed. Ancillary immunostaining demonstrated that the band-like T-cell infiltrate was predominantly CD4/CD8-positive (1:1).…”

“…4–7 In contrast, sparing of oral mucous membranes is often reported and oral lichenoid reactions (OLR) have only been anecdotally described. 4–8 Herein, we describe the clinicopathological features of 10 new cases in Table 1. To our knowledge, this is the largest series of patients developing OLRs with immune checkpoint antibodies reported to date.…”

“…Although reporting of immune checkpoint inhibitor-induced OLR is sparse in literature, 4–8 in our clinical practice, these reactions are not uncommon. As OLRs are usually asymptomatic, they may remain undiagnosed.…”

Resolution of Pembrolizumab-Associated Steroid-Refractory Lichenoid Dermatitis with Cyclosporine

“…Skin rash is one of the most common immune‐related adverse events seen in patients treated with either anti‐CTLA4 or anti‐PD‐1 therapies and can limit therapeutic efficacy because the dose may need to be decreased or treatment halted because of the severity of the cutaneous eruption . Specifically, lichenoid drug rash is a common adverse reaction in patients on PD‐1 inhibitors . Mid‐ to high‐potency topical corticosteroids and systemic antihistamines are first‐line treatments of grade 1 and 2 skin toxicities associated with PD‐1 inhibitor therapy.…”

Apremilast and suicidality – a retrospective analysis of three large databases: the FAERS, EudraVigilance and a large single‐centre US patient population

“…Dermatologic toxicities are one of the most frequent immunerelated adverse events (irAEs) induced by these new monoclonal antibodies. [4][5][6][7][8] Herein, we describe the clinicopathological features of 10 new cases in Table 1. vitiligo, alopecia areata and bullous pemphigoid) are amongst the most commonly reported AEs.…”