Diverse types of dermatologic toxicities from immune checkpoint blockade therapy

Abstract

Immunomodulatory drugs that leverages host immune mechanisms to destroy tumor cells have been met with great promise in the treatment of cancer. Immunotherapy, targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have shown tremendous improvements in the survival of patients with advanced solid tumors. However, the development of dermatologic toxicity (DT) is a consequence to immunotherapy. Review of published reports of the DT to immunotherapy revealed patients receiving anti-CTCLA-4 antibody or anti-PD-1/PD-L1 antibody often develop a DT of any type and grade. In this article, of the 3825 patients who were treated with anti-PD-1 and of 556 patients receiving anti-PD-L1, DT of any type and grade were reported in 1474 (∼39%) and 95 (∼17%) of patients, respectively. The emergence of specific types of DT to immunotherapy is beginning to be recognized can be categorized into four groups: (a) inflammatory, (b) immunobullous, (c) alteration of keratinocytes and (d) alteration of melanocytes. Lichenoid dermatitis and bullous pemphigoid appear to be DT more associated with anti-PD-1/PD-L1 antibody. The DT profile in patients receiving immunotherapy is diverse, and early recognition of specific types of DT that clinicians may encounter is critical for optimal patient careKeywords: anti-CTLA-4, anti-PD-1, anti-PD-L1, dermatologic toxicities, immune checkpoint antibody Curry JL, Tetzlaff MT, Nagarajan P, Drucker C, Diab A, Hymes SR, Duvic M, Hwu W-J, Wargo JA, Torres-Cabala CA, Rapini RP, Prieto VG. Diverse types of dermatologic toxicities from immune checkpoint blockade therapy. J Cutan Pathol 2017; 44: 158-176.

Cutaneous Eruptions in Patients Receiving Immune Checkpoint Blockade

“…Immune checkpoint blockade agents are frequently associated with dermatologic irAEs 31 demonstrating variable clinical and histologic morphologies (see Table 2 for biopsy confirmed non-lichenoid patterns, and Curry, et al 21 for a comprehensive literature review of studies reporting cutaneous irAE). Previous reports of cutaneous toxicities associated with checkpoint blockers have reported lichenoid patterns in 54–94% of biopsied cases (Supplemental Table 2).…”

“…20 For a detailed, comprehensive review of the broad array of presentations published to date, see Curry, et al 2016. 21 Histologic presentations may also vary, with the lichenoid (or interface) pattern being the most commonly recognized. 22–29 Immunohistochemical analysis of anti-PD-1-induced lichenoid dermatitis shows similarity to idiopathic lichen planus 24 and suggests a T-cell-mediated process, 23 which is consistent with the recognized mechanism of action for these agents.…”

Cases from the irAE Tumor Board: A Multidisciplinary Approach to a Patient Treated with Immune Checkpoint Blockade Who Presented with a New Rash

“…Time to onset of cutaneous toxicities of ICIs can vary between 2 weeks to several months into treatment . The most common clinical presentation is a maculopapular rash and/or pruritus , often starting on the trunk and spreading peripherally, usually sparing the face.…”

Regulatory T cells in autoimmune skin diseases

“…Monoclonal antibodies to PD‐1 or CTLA‐4 have recently been applied for the treatment of melanoma and other neoplasms as immune checkpoint inhibitors, and they are known to suppress Tregs . Interestingly, several cases of BP after the administration of those antibodies have been reported . In addition, a case of pemphigoid nodularis, a BP subtype, was reported in an IPEX patient .…”