Toxic Side Effects of Targeted Therapies and Immunotherapies Affecting the Skin, Oral Mucosa, Hair, and Nails

Abstract

Targeted therapies and immunotherapies are associated with a wide range of dermatologic adverse events (dAEs) resulting from common signaling pathways involved in malignant behavior and normal homeostatic functions of the epidermis and dermis. Dermatologic toxicities include damage to the skin, oral mucosa, hair, and nails. Acneiform rash is the most common dAE, observed in 25–85% of patients treated by epidermal growth factor receptor and mitogen-activated protein kinase kinase inhibitors. BRAF inhibitors mostly induce secondary skin tumors, squamous cell carcinoma and keratoacanthomas, changes in pre-existing pigmented lesions, as well as hand-foot skin reactions and maculopapular hypersensitivity-like rash. Immune checkpoint inhibitors (ICIs) most frequently induce nonspecific maculopapular rash, but also eczema-like or psoriatic lesions, lichenoid dermatitis, xerosis, and pruritus. Of the oral mucosal toxicities observed with targeted therapies, oral mucositis is the most frequent with mammalian target of rapamycin (mTOR) inhibitors, followed by stomatitis associated to multikinase angiogenesis and HER inhibitors, geographic tongue, oral hyperkeratotic lesions, lichenoid reactions, and hyperpigmentation. ICIs typically induce oral lichenoid reactions and xerostomia. Targeted therapies and endocrine therapy also commonly induce alopecia, although this is still underreported with the latter. Finally, targeted therapies may damage nail folds, with paronychia and periungual pyogenic granuloma distinct from chemotherapy-induced lesions. Mild onycholysis, brittle nails, and a slower nail growth rate may also be observed. Targeted therapies and immunotherapies often profoundly diminish patients’ quality of life, which impacts treatment outcomes. Close collaboration between dermatologists and oncologists is therefore essential.

Impact of cutaneous adverse events on the quality of life in patients receiving anticancer agents: Results from an observational, cross-sectional study

“…According to Lacouture et al, cutaneous toxicities are very common and varied in patients treated with targeted therapies. These toxicities diminish patients' QoL, which impacts their adherence to the treatment, jeopardizing its success and patients' survival [31]. High-grade CAEs may have a signi cantly impact on QoL and may lead to treatment interruption or dose modi cation.…”

Development of a Functional Assessment of Chronic Illness Therapy item library and primary symptom list for the assessment of patient-reported adverse events associated with immune checkpoint modulators

“…Our literature review yielded 25 articles documenting irAE incidence, management guidelines, toxicity profiles, and associated symptomatology [4,9,[11][12][13][14][15][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] . From these, we identified 75 possible inflammatory reactions/immune conditions across 11 organ systems, ranging from very common to rare.…”

Blockade of CCR5 in melanoma: An alternative immune checkpoint modulator

“…However, a significant downside of immunotherapy is toxicity. Immune side effects manifest in all organs and systems including skin rashes, pneumonitis, colitis, hepatitis, nephritis, encephalitis, endocrine and rheumatologic side effects and reactivation of immune diseases . Therefore, pursuing treatment alternatives with fewer side effects is warranted.…”