Neutrophilic dermatoses as adverse effects of checkpoint inhibitors: A review

Abstract

Checkpoint inhibitors are a new class of drugs that enhance the immune system's intrinsic ability to destroy tumor cells by blocking signaling through the programmed cell death (PD‐1) receptor, its ligand (PD‐L1), and the cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4). The resulting increase in immunologic activity is responsible for a variety of adverse cutaneous reactions, which sometimes include neutrophilic dermatoses. We queried the PubMed database for existing cases of checkpoint inhibitors causing neutrophilic dermatoses. The literature search identified four cases of Sweet syndrome, four cases of pustular eruptions, two cases of pyoderma gangrenosum, and one case of bullous lupus erythematosus secondary to checkpoint inhibitors. All neutrophilic dermatoses were treated with topical or systemic steroids and most (9 of 11) completely resolved. Dermatologists should be aware of these rare, adverse cutaneous reactions to checkpoint inhibitors and how to approach their treatment, especially as their use increases.

Nivolumab‐induced erosive pustular dermatosis of the scalp

“…A dominant Th1‐type response is thought to be causative for some of the observed irAEs, such as autoimmune colitis and pulmonary sarcoid‐like granulomatosis, and might be the key pathogenic factor for the onset of EPDS in our patient 1,6 . As far as we are aware, this is the first case of EPDS reported in a patient receiving nivolumab; interestingly, there have been a few cases of other neutrophilic dermatoses, such as pyoderma gangrenosum and Sweet syndrome, during ICi treatment 7 . We invite clinicians to consider the diagnosis of EPDS when faced with a scalp eruption occurring in a patient receiving this specific class of drugs.…”

Anti-PD-1-Induced Hidradenitis Suppurativa

“…De novo or worsening of other neutrophilic skin diseases as pre-existing psoriasis, and conditions primarily neutrophilic, i.e., acute generalized exanthematous pustulosis and Sweet syndrome have been reported in patients under ICIs [3,7]. Overall, the usually observed mean latency period between drug initiation and onset of irCAEs depends on the type of reaction and has been estimated to be 3-6 weeks for maculopapular rashes and as long as 6-12 weeks for lichenoid eruptions [1].…”

Pembrolizumab-associated pyoderma gangrenosum in a patient with metastatic squamous cell carcinoma

“…|| Case Presentation checkpoint inhibitor which blocks binding to cytotoxic T lymphocyte-associated protein four[4]. This case suggests that PG can also occur with pembrolizumab therapy.…”

“…As a result, they frequently trigger adverse cutaneous effects, including lichenoid, maculopapular, psoriasiform, and immunobullous reactions [2,3]. Neutrophilic dermatoses have been more rarely reported with checkpoint blockade [4]. Pyoderma gangrenosum (PG) is a non-infectious neutrophilic dermatosis which commonly presents with a painful, erythematous pustule or papule that rapidly expands to a necrotic ulcer with undermined, violaceous borders [5].…”