Actinic (solar) keratoses are extremely common (pre)malignant lesions occurring
on chronically sun-exposed skin. They appear as rough, scaly erythematous
patches with poorly defined borders. The prevalence increases with advancing
age.
Actinic keratoses (AK) usually occur in fair skinned individuals over 45 years
of age (skin type I or II). They rarely occur in type IV skin. The prevalence
increases with advancing age. In Australia and in the southwestern US, younger
people are affected more frequently, though.
Accurate figures on the prevalence and incidence are hard to obtain. AK is the
most common precursor lesion for SCC in whites. Approximately 5-20% of AKs will
transform into SCC within 10-25 years. The 1-year risk that AK lesion transform
into SCC was estimated to 1.1% compared with the 10-year risk of 10.2%. By
treating AKs the development of SCC can be prevented.
In the early decades, actinic keratoses are more prevalent in males, probably
because of occupational and recreational sun exposure. In the age group from 50
to 86 years, the rates are more equal between the sexes.
Persons with occupational or recreational outdoors exposure, as well as those
living at latitudes closer to the equator have higher incidence rates.
Additionally, a 20th century change in fashion which dictates that a deep
suntan in a fair-skinned person is associated with increased socio-economic
status, has led to skin cancer and its precursors are now endemic in many
places of the world.
The most important risk factors for the development of actinic keratoses are a
combination of genetic factors ("fair skin phenotype") and cumulative
sun exposure, although they can also be caused by ultraviolet (UV) radiation
from artificial sources or exposure to polycyclic aromatic hydrocarbons. It is
assumed that ultraviolet radiation in sunlight produces changes in the genetic
material of the epidermal cells, leading to proliferations of transformed,
neoplastic keratinocytes.
Careful inspection of the clinical findings may lead to the correct diagnosis.
However, when the keratosis is pigmented it must be discerned from a seborrheic
wart, which appears greasy on palpation and displays a regular granular
texture. Flat or lichenoid actinic keratoses may resemble discoid lupus
erythematodes, which is usually bright red in colour and has an easily
detachable scale. Bowen's disease may also show a similar clinical picture, but
it usually has a more erythematous base and a more irregular contour. Arsenic
keratoses mainly occur in a different location, they prefer the palms and
soles. If there is any doubt concerning the diagnosis, a histological
examination should be performed.
The most common clinical presentation of an actinic keratosis is a red, scaling
papule or plaque on a sun-exposed area (erythematous type). At first, it is
only a few millimeters in size, but then it may grow several centimeters in
diameter. The surrounding areas may show evidence of sun damage with blotchy
pigmentation, telangiectases, and a yellowish discoloration.
The keratosis can progress into thickened or hypertrophic lesions (keratotic
type). The reddened patches are no longer visible, but instead one sees a
yellowish or dirty-brown hard, horny surface. The thickened lesions can
progress into invasive squamous cell carcinoma
Other clinical variants of actinic keratoses present with the following
characteristics:
Subjective symptoms are usually absent, though tenderness, itchiness and burning
are sometimes reported.
Clinically, actinic keratoses observed over a period of time display 3
evolutionary possibilities:
Actinic keratoses carry the risk of progression to invasive squamous cell
carcinoma.
Prevention of actinic keratosis is achieved through the use of effective
UVA/UVB sunscreens, on the face, ears, neck, and other sun exposed areas of the
skin. Broad-brimmed hats and sun protective clothing are also recommended.
Prolonged sun exposure should be avoided, especially in children.
Actinic keratoses carry the risk of progression to invasive squamous cell
carcinoma. Once this has occurred, the tumour may bleed, ulcerate, become
infected, destroy anatomic structures or even spread to internal organs.
CryosurgeryCost
$500-1000 pesos
Liquid nitrogen (-195.8°C), the most common cryogen, is applied using a spray
device or a cotton tip applicator. The atypical cells are destroyed when the
skin temperature is lowered to -50°C.
Advantages
Disadvantages
Curettage
Actinic keratoses can be scraped away with a curette. Afterwards,
electrosurgery may be used to stop bleeding or to apply more damage to the area
of the atypical cells. Aluminum chloride and ferric chloride are also used as
hemostatics.
Advantages
Disadvantages
5-fluorouracil is a cytostatic agent which inhibits several enzymes in tumor
cells, through interaction with RNA. It is applied locally in a thin layer and
the lesion is subsequently covered with a plastic film. The treatment is
repeated daily until the lesion erodes (usually a treatment length of 2 to 4
weeks is necessary).
Advantages
Disadvantages
Dermatological indications for PDT
The technique
PDT is based on the coaction of a photosensitizer, often a
porphyrin-derivative, with visible light and oxygen. The photosensitizer
specifically accumulates in rapid growing cells (e.g. tumor cells) and is
activated by irradiation with visible light. The tumor destruction is caused by
the formation of cytotoxic efficient reactive oxygen species, in particular
singlet oxygen.
There are several photosenitizer presently in use (porphyrins, porphines, phthalocyanines,
etc.) but most of them are not ideal for dermatological indications since they
have to be administered systemically and cause general photosensitivity in
patients. The most frequent used substance for PDT in dermatology is 5-ALA
(d-aminolevulinic acid) and its derivatives. 5-Ala works as a prodrug that is
metabolized intracellularly into protoporphyrin IX (PpIX) - the actual
photosensitizer. PpIX will, when activated by light, generate singlet oxygen
which will cause death of the tumor cells. Besides PDT the photosensitizer can
also be activated by Wood light leading to fluorescence of the targeted lesion.
In this way tumor lesions can be detected by photo diagnosis (PD).
The use
The standardized procedure for the treatment of AK involves the application of
20% ALA or its ester in a solution or cream. emulsion. 5-ALA then penetrates
the skin and is metabolized into PpIX. ALA-uptake is higher by dysplastic cells
and PpIX is synthesized more specifically in abnormal cells leading to a higher
concentration of PpIX in abnormal than in healthy cells. After an application
time of several hours the lesion will be exposed to light of a certain
wavelength and intensity. In clinical trials the complete response rate of
lesions was more than 90 % after one to two treatments. Furthermore, the
cosmetic outcome was rated excellent or good in more than 90 % of patients.
Consequentially 5-ALA PDT is at least as effective as standard treatments but
with superior cosmesis.
For Irradiation of the leasion there are now several non-coherent light sources
in use which differ mainly by their emission spectrum (red light, blue light,
green light) and the irradiation area.
Advantages
Disadvantages
Actinic keratoses may either disappear spontaneously, persist, or progress into
invasive skin cancer with the capacity of metastasizing. Clinically, there is
no possibility to distinguish between those lesions that will clear, persist or
progress. Studies performed between 1991 and 1998 on the basis of thousands of
keratoses distributed in a large population give us a risk for the progression
of actinic keratoses to squamous cell carcinoma of between 6% and 12% per year.