Dermatologic adverse events associated with chemotherapy and targeted anticancer therapy

Chemotherapeutic agents and drugs used for targeted tumor therapy often cause undesirable side effects of the skin which typically are toxic cutaneous reactions (toxicity grade 1 to 4). The first group of drugs that cause toxicities affecting the skin are inhibitors of epidermal growth factor receptor (EGFR). They cause a variety of skin changes (PRIDE syndrome), which are mainly manifested by papulopustular rash, also referred to as acneiform rash, occurring in 44–74% of patients. Another drug which causes cutaneous toxicities is inhibitor of CTLA4 (cytotoxic T lymphocyte-associated protein 4), which is represented by ipilimumab, used in the treatment of metastatic melanoma. The most common dermatological adverse event, observed in 40–64% of patients receiving ipilimumab, is generalized maculopapular rash with pruritus and dry skin, and in some cases vitiligo is also observed. BRAF and MEK inhibitors introduced for the treatment of advanced melanoma also cause skin rashes. BRAF inhibitors also affecting the proliferation of keratinocytes stimulate hypertrophic changes and cause the whole spectrum of lesions from benign and keratoacanthoma to squamous cell carcinoma. A hedgehog pathway inhibitor (vismodegib) is used for the treatment of metastatic basal cell carcinoma. The most common adverse events it causes are reversible alopecia and dysgeusia, but it can also cause the development of keratoacanthoma and squamous cell carcinoma. Among the most common side effects of chemotherapy and targeted therapy are toxic changes within the hands and feet (hand-foot skin reaction – HFSR) that early manifest as a neurological symptoms (numbness, paresthesia), and skin symptoms (erythematous swelling changes, blisters, hyperkeratosis) occur later. Anti-cancer drugs can also cause serious skin diseases such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and DRESS (drug rash with eosinophilia and systemic symptoms), whose course and prognosis may be unfavorable. Side effects that are observed after treatment with anti-cancer drugs can also affect the skin appendages, i.e. nails and hair. Nail changes manifest as a delay in their growth, thinning or onycholysis, whereas hair changes appear as decreased growth and structure abnormalities. The treatment of these various drug-induced complications depends on the severity of symptoms. In some cases ordinary care is sufficient, while others need to start systemic treatment, with eventual modification of therapy of the primary disease. In some patients it is necessary to interrupt the treatment of cancer. Note that in the case of very severe complications (SJS, TEN, DRESS), drugs that caused them can not be re-administered.