Dermatologic Manifestations of Systemic Oncologic Therapy of Cutaneous Malignancies

Alopecia

Chemotherapy-induced alopecia (CIA), one of the most common and distressing side effects, occurs in 65% of patients, with 47% considering it the most traumatic side effect of chemotherapy. Fear of hair loss would cause 8% of patients to decline chemotherapy. Although clinical patterns can vary, hair loss is usually acute, diffuse and of dystrophic anagen effluvium type. The onset is usually 1–3 weeks after beginning chemotherapy and is complete at 1–2 months. Doxorubicin causes alopecia in 60–100% of patients and paclitaxel in more than 80%. Other agents that usually cause alopecia include daunorubicin and docetaxel.

Although CIA is usually reversible, there is a 3–6-month delay of regrowth, which may be incomplete. In 65% of patients, there is a change in the color and/or texture of the new hair. Persistent alopecia after use of taxanes has been reported. Topical minoxidil and growth factor AS101 can shorten the duration of CIA but do not prevent it. Scalp cooling has shown a significant benefit in preventing alopecia, especially in cases of anthracyclines and taxanes. Using a cooling cap, cold air, or liquid during chemotherapy infusion may work by inducing vasoconstriction, thereby decreasing biochemical activity and cellular drug uptake. The putative risk of scalp metastases when scalp cooling is used has not been established.

Hand–foot syndrome (palmoplantar erythrodysesthesia)

Hand–foot syndrome can be caused by pegylated liposomal doxorubicin, continuous-infusion doxorubicin, cytarabine, floxuridine, high-dose interleukin-2, docetaxel, 5-fluorouracil (5-FU) and its prodrug capecitabine, vinorelbine, and gemcitabine. Symptoms begin 2–12 days after administration of the drug. The skin becomes erythematous and edematous, followed by dryness, scaling, and associated burning pain ( Fig. 35.1 ). Blisters and ulcerations can develop in advanced cases.

Like for many chemotherapeutic side effects, the mechanism is unknown, but several theories have been proposed. Increased toxicity in the palms and soles may be related to the high turnover rate of this skin, high density of sweat glands, absence of folliculo-sebaceous units, thickened stratum corneum, wide dermal papillae, and increased trauma and friction. Some studies have supported the theory that the chemotherapeutic is excreted in the sweat and the increased number of eccrine glands on the palms and soles may increase the toxicity in these areas.

Therapies such as cooling, topical dimethylsulfoxide, oral and topical steroids, topical urea and vitamin E, and oral pyridoxine may be effective, although data are limited. Small trials have described benefit of urea-containing moisturizers, oral vitamin E supplements, and celecoxib in patients receiving capecitabine.

Mucositis

Most patients rate mucositis as their worst side effect from chemotherapy. Part of the profound impact on quality of life of mucositis is impaired adequate nutrition, and increased risk of infection and sepsis. The rapidly dividing tissue of the mucosa of the aerodigestive tract is a frequent target of chemotherapy. Palifermin, a recombinant keratinocyte growth factor, decreases the incidence, duration, and severity of oral mucosal lesions in patients but has an unclear role in improved nutrition and survival. Cryotherapy using crushed ice during infusion of bolus 5-FU and low-level laser resurfacing may be effective.