Table 4.

Pathophysiology

Phase	Cellular Level Changes	Body Response	Goal of Treatment	Patient Information
Phase I: weeks 0–1, erythema and edema like a sunburn. The patient feels a sunburn-like reaction (erythema, tenderness, slight swelling) on the face and areas that have previously been exposed to the sun.	EGFR inhibition in skin stops underlying keratinocytes from differentiating and migrating to skin surface to replace them, and they are arrested.	The body senses that these arrested replacement cells should not be there and thus causes them to undergo apoptosis or programmed cell death. The dead keratinocytes cause the release of chemokines, which recruit neutrophils to the area as part of the sterile, inflammatory response.	The goal is to preserve skin integrity, minimize discomfort, and prevent infection.	Key patient teaching includes (1) use skin cream with emollients to keep the skin from drying out; (2) avoid sun exposure, using a sunblock of SPF 30 or higher and protect skin with hat and clothes when out in the sun; (3) use a mild soap with active ingredients that reduce skin drying, such as pyrithione zinc (Head & Shoulders); (4) apply prescribed prophylactic skin creams; (5) report distressing tenderness, as pramoxine (lidocaine topical anesthetic) may help; (6) keep fingernails clean and trimmed.
Phase II: weeks 1–3, papulopustules appear The rash begins within 7–10 days of starting therapy and peaks in intensity in 2–3 weeks and then gradually gets better.	This sterile inflammatory process results in death of the keratinocytes (apoptosis) and the formation of debris, which causes a popular rash on the skin.	At the same time, the skin is no longer fortified by healthy keratinocytes, and thus, it thins and is unable to preserve water in the body, leading to skin dryness (xerosis) and itching.	The goal is to prevent infection, promote healing, and maximize comfort and coping during this time. See drug package inserts for specific information on holding or discontinuing drug for severe dermatologic adverse effects.
Phase III: weeks 3–5, lesions crust		The skin becomes drier (xerosis) with pruritus and the formation of telangiectasias (dilated capillaries in the skin).	The skin flakes and itches.	For flaking skin, keratolytics such as lactic acid, salicylic acid, or urea-containing topicals such as 12% Lac-Hydrin or other exfoliating lotions can be helpful
Phase IV: weeks 5–8, persistent dry skin, erythema, other skin/hair changes.		EGFR blockade of the hair follicles and nail beds results in hair changes (hair thinning or alopecia on scalp but increased hair growth on the eyelids (trichomegaly) or face (hypertrichosis).	The hair texture can change (changes in texture and strength). Paronychia (periungual inflammation) can develop with crusted lesions on nail folds and tenderness. Painful skin fissures on the fingers can develop.	It is important to assess eyelashes, and if they are long, they can fold back and irritate the conjunctiva; refer to an ophthalmologist for redirection as needed (Borkar et al., 2013).

Source: Lacouture, et al