Cutaneous Adverse Events of Immune Checkpoint Inhibitors: A Literature Review

Abstract

Immune checkpoints assist with self-tolerance and minimize collateral tissue damage when immune responses are activated. Although immune checkpoint inhibitors (CPIs) are characterized by a favorable risk/benefit ratio, immune checkpoint blockade has been associated with a new subset of autoimmune-like toxicities, named immune-related adverse events (irAEs). Dermatologic reactions are among the most prevalent irAEs triggered by CPIs. In a majority of cases they are self-limiting and readily manageable. However, it is not uncommon that they result in severe skin involvement and impairment of patients' quality of life. Awareness of the spectrum of cutaneous irAEs is mandatory for every clinician involved in the management of oncologic patients. The role of the dermatologists is essential because early recognition and appropriate management of skin toxicity may prevent dose modifications and discontinuation of CPIs. The latter is particularly relevant, considering that recent data suggest favorable oncologic response in patients developing irAEs.

Keywords: adverse effects; immune checkpoint inhibitors; ipilimumab; nivolumab; pembrolizumab; skin toxicity.

Figure 1

The most common skin toxicities during the course of immunotherapy include (A) maculopapular, (B) psoriasiform and (C) lichenoid eruptions.

Figure 2

(A) A lichenoid eruption in a patient with Merkel cell carcinoma treated with pembrolizumab. (B) Dermoscopy highlights the Wickham striae, facilitating the diagnosis.

Figure 3

(A) A patient with non-small cell lung carcinoma who was treated with a combination of nivolumab and ipilimumab developed palmoplantar pustulosis after the third cycle. (B) Significant improvement of the skin after 2 months of treatment. (C) However, the patient experienced severe psoriatic arthritis and was switched to apremilast.

Figure 4

Uncommon skin toxicities include bullous disorders like (A) bullous pemphigoid and (B) bullous lichen planus.

Figure 5

Concomitant development of more than one skin toxicity is not unusual. The patient illustrated in (A) experienced vitiligo and psoriasis (see Figure 1B) and the patient in (B) experienced vitiligo and bullous pemphigoid, both during treatment with nivolumab for advanced melanoma.