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Checkpoint Inhibitor Therapeutics and the Skin

- In: Clinical Practice

As the population ages, healthcare providers are caring for more and more patients living with advanced malignancies. The introduction of immune checkpoint inhibitors has transformed the therapeutic landscape for advanced solid-organ malignancies. Immune checkpoint inhibitors target negative regulators of T-cell activation and include cytotoxic T-lymphocyte-associated-protein-4 (CTLA-4) inhibitors and programmed cell death ligand-1 (PD-1) inhibitors.1 Atezolimumab, avelumab, durvalumab cemiplimab, ipilimumab, nivolumab, pembrolizumab are used to treat a variety of advanced solid tumor malignancies from non-small cell lung cancer, bladder cancer, lung cancer and melanoma, among others. In addition to their primary function of preventing tumor-mediated immune evasion, they also stimulate non-specific immune activation that can impact several different organ systems. One of the more commonly affected organ systems is the skin.


The incidence of cutaneous adverse events from immune checkpoint inhibitors ranges from 30-60% and is often the first adverse reaction that the patient will encounter.1 On average, cutaneous manifestations occur within 3-4 weeks of treatment initiation.2 These cutaneous eruptions range from a mild, localized eruptions to life-threatening drug reactions requiring hospitalization and immediate cessation of the anti-cancer therapy. The following list highlights the more commonly reported cutaneous reactions that have been seen in patients receiving immune checkpoint inhibitor therapy:

  • Eczematous
  • Psoriasiform
  • Morbilliform
  • Pruritis
  • Lichenoid
  • Vitiligo
  • Bullous Disorders
  • Stevens Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN)
  • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

In addition to those listed above, small series or single case reports demonstrate other cutaneous manifestations such as alopecia areata, scleroderma, sarcoidosis, and vasculitis.1 The proposed mechanisms behind these varied cutaneous reactions are complex and involve a number of immunologic pathways involving T-cell self-reactivity and autoimmunity; as well as cross reactivity between tumor antigens and normal host tissue.1 For example, in patients being treated for advanced melanoma with PD-1 inhibitor therapy, vitiligo can be seen as a result of these agents targeting melanoma antigens but also targeting normal, healthy melanocytes.


Given the prevalence, varied presentations, and complex nature of cutaneous adverse reactions of immune checkpoint inhibitors, it is critical for clinicians to be aware of and able to recognize these entities promptly. Since many of these cutaneous eruptions can present atypically in those treated with these pharmaceuticals, one should have a low threshold to biopsy and perform advanced diagnostics. Active collaboration and communication with the patient’s primary oncology team is paramount in initiating a treatment plan that will reduce morbidity and mortality and improve their quality of life.


References:

  1. Quach HT, Johnson DB, LeBoeuf NR, Zwerner JP, Dewan AK. Cutaneous adverse events caused by immune checkpoint inhibitors. J Am Acad Dermatol. 2021 Oct;85(4):956-966.
  2. Geisler AN, Phillips GS, Barrios DM, Wu J, Leung DYM, Moy AP, Kern JA, Lacouture ME. Immune checkpoint inhibitor-related dermatologic adverse events. J Am Acad Dermatol. 2020 Nov;83(5):1255-1268. doi: 10.1016/j.jaad.2020.03.132.

Veronica Richardson MSN,ANP-BC, DCNP is a medical dermatology nurse practitioner with a passion for clinical education in Philadelphia, PA. On the weekends you can find her and her husband snowboarding, paddle boarding, hiking and cooking in their mountain getaway in the Poconos with their two dogs.