Actinic keratosis (AK) is a premalignant skin condition
typically seen almost exclusively in Caucasians, due to
their fair skin. AKs develop on chronically sun-exposed
areas such as the face, the dorsum of the hands and forearms,
upper chest, and the scalp of bald men. While AKs have been
described as “precancers,” histologic and molecular features
suggest that they exist in a continuum with invasive squamous
cell carcinoma. A small percentage of AKs eventually evolve
into invasive squamous cell carcinoma; it is for this reason that
eradication of lesions is warranted. The estimated frequency of
conversion is from 0.1% to as high as 16%,1 but the likelihood
of a particular AK progressing to invasive squamous cell carcinoma
with metastatic potential is impossible to predict.
There are many treatment options that have similar efficacy.
Destructive therapies such as cryosurgery or electrodessication
and curettage are directed at specific clinical lesions. Medical
therapies, also known as field-directed therapies, use a pharmacologic
approach to destroy both the clinical AKs and the
subclinical lesions in the surrounding skin.
When selecting a treatment, the dermatologist must keep in mind
that the expectations of “baby boomers” may be different from
patients of prior generations. Patients today desire eradication of
lesions with rapid wound healing and minimal cosmetic alteration.2
Local destructive therapies are most commonly used when treating
a small number of lesions. Field-directed medical therapy is
warranted when there are many AKs and extensive photodamage.
It has been shown that the combination of targeted destructive
therapy with field-directed therapy has a synergistic effect.
I. Local Destructive Therapies
Cryosurgery is the most popular first-line treatment for AK.
Liquid nitrogen, at a temperature of -196°, freezes the lesions
and the atypical cells are destroyed. Since melanocytes in the
skin are also sensitive to cold, cryosurgery can leave macules
2. Curettage and Electrodessication
The use of curettage and electrodessication is a surgical
technique involving the use of a curette to physically scrape
atypical cells and electrocautery to obtain hemostasis and
thermally destroy additional atypical cells. The technique is
most useful for spot treating lesions, especially those that
II. Field-Directed Medical Therapies
There are currently 5 topical medications commonly used for
the treatment of AKs:
1. 5-fluorouracil (5FU) – (Efudex®, Flouroplex,® and Carac®)
5FU is an antimetabolite drug used in chemotherapy for treatment
of colorectal cancer.3 It is taken up by cells as if it were
uracil. Its active metabolites are subsequently incorporated
into DNA and RNA, disrupting replication, and causing cell destruction.
Common side effects include erythema, crusting and
burning. Formulations include a 5% cream or solution, a 2%
solution, a 1% cream or solution, and a micronized 0.5% cream.
2. Imiquimod – (Aldara®, Zyclara™)
Imiquimod is an immunomodulator that has been shown to
stimulate immune function by inducing cytokine expression,
interferon-α (IFN-α),4 interleukin-6 (IL-6), and tumor necrosis
factor-α (TNF-α). Formulations include 5% cream (Aldara®),
3.75% cream (Zyclara®), and 3.75% solution.
3. Diclofenac gel – (Solaraze™)
Diclofenac sodium 3% gel is a nonsteroidal anti-inflammatory
drug (NSAID). It is a non-selective cyclooxygenase (COX) inhibitor
which also exhibits anti-tumor effects, given that COX-2
has been implicated in keratinocyte proliferation.5,6 Diclofenac
has also been shown to induce apoptosis via death receptor
signaling.7 A lengthy, 3-month treatment course is typically required
to eradicate AKs.
4. Ingenol mebutate gel – (Picato®)
Ingenol mebutate is a naturally occurring active substance
found in the sap of the plant, Euphorbia peplus.8 The quick
action is thought to arise from both direct cytotoxicity leading
to cell death and activation of a neutrophil-mediated
inflammatory response.9 The short duration of therapy is
a plus, but the brisk inflammatory reaction can be a drawback.
This agent is typically used for only 3 consecutive days
(0.015%) for face and scalp, and 2 consecutive days (0.05%)
for the trunk and extremities.