INTRODUCTION
Actinic keratosis (AK), a highly prevalent dermatologic
condition resulting from long-term sun exposure,1,2
most commonly occurs in older individuals and those
with fair skin.1-3 AKs are typically present as red, scaling or
hyperkeratotic papules and plaques on the scalp, face, dorsal
hands and lower extremities.3,4 AK is the second most frequent
diagnosis made by dermatologists in the United States, accounting
for 14 percent of patients.1
AK is part of a biologic continuum beginning with photodamage
and may potentially develop into invasive squamous cell
carcinoma (SCC). The 10-year conversion of AK to SCC is estimated
to range from 6 percent to 20 percent.5 AKs should
be treated and removed, and a wide variety of treatments are
available for this purpose.6 Although cryotherapy is well suited
for removing well-defined individual lesions, field-directed
therapies, such as topical 5-fluorouracil (5-FU), diclofenac, imiquimod
and photodynamic therapy (PDT) are appropriate for
removing widespread lesions.6,7
Topical 5-FU is the standard of care for widespread AKs,8,9 and its
efficacy in this regard is well established.10 In addition to selectively
targeting actinically damaged skin,8,11 5-FU induces an inflammatory
response in occult lesions, revealing subclinical lesions.12 PDT
with 5-aminolevulinic acid (ALA) is effective for treating AK using
various incubation periods and light sources.13-17
Combination therapy is often used in clinical practice because
of the variability in AK and individual patient needs, as well as
the varied mechanisms of action of different treatments.7 Several studies have demonstrated the efficacy of sequential therapy
with 5-FU or topical imiquimod with short-incubation (0.5-1.0
hour) ALA-PDT in patients with widespread AKs.17,18 Although
data are limited, sequential therapy offers the potential for enhanced
efficacy and improved 5-FU tolerability associated with
a shorter duration of therapy (e.g., 7-10 days), patient convenience
and cosmetic outcomes (e.g., clinical improvement in
skin texture) than would be expected with standard, four-week
treatment with 5-FU.17 The following cases describe a prospective
analysis of three patients undergoing the sequential use of
5-FU cream 0.5% and short-contact (one hour) ALA-PDT, utilizing
a split-face/arm approach to assess combination 5-FU/ALA
treatment versus PDT alone (Figure 1).
Case Report
Three men with a consistent history of AK and photodamaged
skin presented to the Dermatology and Laser Center of Maui
(Kihei, HI). These men were selected for participation in this
prospective, case-based assessment because of their clinical
