Download inside - Australian Doctor

How toTreat
www.australiandoctor.com.au
PULL-OUT SECTION
inside
Complete How to Treat quizzes online (www.australiandoctor.com.au/cpd) to earn CPD or PDP points.
Aetiology
UV exposure
prevention
Treatment options
The authors
DR MICHAEL FREEMAN
director of dermatology, Gold
Coast Hospital, Southport; visiting
dermatologist, Princess Alexandra
Hospital, Brisbane; Associate
Professor of Dermatology, Bond
University, Gold Coast; and
dermatologist, the Skin Centre,
Benowa, Queensland.
Solar keratoses
DR ANDREW FREEMAN
medical officer, Princess Alexandra
Hospital, Woolloongabba,
Queensland.
Background
SOLAR keratoses, also known as
actinic keratoses, are skin lesions
that result from a localised abnormal proliferation of atypical epidermal keratinocytes that have been
damaged by UV radiation.
They share many of the same
mutations found in squamous cell
carcinoma, particularly in the p53
gene. Thus they are precursors of
SCC.
The lifetime risk of a Cauca-
sian Australian developing nonmelanoma skin cancer is more than
50%.1
Clinical features
The clinical features of typical solar
keratosis include a discrete lesion,
often subtle, with erythema that varies over time, an irregular shape and
a rough scaly surface.
They may be flat or form a keratin
horn and are often easier to feel than
see with the naked eye. Solar keratoses vary in size from 2mm to 6mm
in diameter. They rarely exceed
10mm, but may become confluent
and form sheets or plaques. They
are often asymptomatic but may,
on occasion, be pruritic or painful
and can bleed if traumatised. It is
not uncommon for patients to have
cosmetic concerns about them. Sunexposed areas such as the face, bald
scalp and the dorsum of the hands
< Australian Doctor Education logo>
SEMINAR FOR GPs
are the most common sites, and are
highly visible.
The main differential diagnoses are localised telangiectasia,
lichenoid keratosis, intra-epidermal
SCC, superficial basal cell carcinoma, discoid lupus erythematous,
superficial actinic porokeratosis
and psoriasis. Occasionally solar
keratoses can be hyperpigmented,
thereby mimicking solar lentigines.
cont’d next page
Earn CPD points
RURAL DOCTOR 2 DAY SEMINAR
RURAL DOCTOR 2 DAY SEMINAR
Authoritative, independent and relevant education for GPsPractical. Relevant. Comprehensive. Don’t miss Australian Doctor’s inaugural
EARN CPD POINTS
SYDNEY
3-4 November 2012
Novotel Sydney Manly Pacific
Rural Doctor seminar complete with the opportunity to do your ALS refresher.
For more information
visit www.australiandoctor.com.au/seminars
www.australiandoctor.com.au
19 October 2012 | Australian Doctor |
25
How To TREAT Solar keratoses
Aetiology
UV radiation, in particular UVB,
is the most important aetiological
factor in the development of solar
keratoses, as it is in non-melanoma
skin cancer.1
UV radiation causes a very specific mutation in DNA. Most solar
keratoses demonstrate a mutation in the p53 tumour suppressor gene. This gene is responsible
for apoptosis of damaged cells.1
Mutated keratinocytes become
resistant to apoptotic death and
are allowed to accumulate more
radiation-induced genetic damage. SCCs have the same types of
genetic mutations, thus suggesting
the potential for malignant transformation of solar keratoses.
Other factors have been implicated in the aetiology of solar
keratoses.
Patients
receiving
immunosuppressive therapy —
most commonly organ-transplant
recipients — are at an increased
risk of developing solar keratosis.
The incidence of non-melanoma
skin cancer (excluding basal cell
carcinoma) is proportional to the
level and duration of immunosuppression.
UV radiation also suppresses
cell-mediated
immunity
and
affects the function of antigenpresenting cells. The resultant
immunosuppression prevents the
normal immunological rejection of
UV-induced dysplastic cells. The
risk of solar keratoses increases
with advancing age as a result of
cumulative sun damage. Ageing is
The risk of solar
keratoses increases
with advancing age
as a result of
cumulative sun
damage.
also associated with immunosuppression.
HPV has also been implicated in
the aetiology of both solar kera-
toses and SCC. Although HPV is
not incorporated into the genome
of solar keratoses or SCC, an effect
has been suggested by the results
of a study of renal transplant
recipients.2 Immunosuppression
caused a much higher incidence of
non-genital HPV infection in the
patients in this study, who also
had a five-times higher incidence
of solar keratoses and SCC compared with BCC. This suggests the
involvement of a factor unrelated
to direct immune rejection of the
tumours. An infectious agent is
likely.
A pivotal event in apoptosis is
the release of apoptogenic factors
from the mitochondria, although
the mechanisms by which the different proteins are released are not
fully understood.
The HPV E6 protein prevents
the release of apoptosis-inducing
factors from mitochondria of
UV-damaged primary epidermal
keratinocytes.3 E6 also degrades
the pro-apoptotic protein Bak.
This process not only promotes
survival of HPV-infected cells but
allows genetically damaged keratinocytes to accumulate more UV
damage, hastening conversion of
these keratinocytes into solar keratoses and SCC.
The risk of progression of a solar
keratosis to SCC is estimated to be
up to 16% in a 10-year period.4 In
patients with extensive keratoses,
it can be difficult to identify early
carcinoma. Clearing of the background solar keratoses enables
easier visualisation of invasive skin
malignancy as well as preventing
invasive malignancy.
UV exposure prevention
Therapy for solar keratoses
begins with prevention, which
means minimising exposure to UV
light, especially — but not only
— UVB radiation. It is common
for patients to underestimate the
importance of avoidance of exposure to UV radiation.5
Patients are often unaware of the
significance of indirect UV radiation, for example, standing in the
shade. Explaining that light shade is
only equivalent to SPF2 (a reduction
of only 50% in incident UV) is helpful. Regulating outdoor activity to
minimise exposure between 10am
and 3pm is the optimal approach.
Clothing and lycra surfshirts are
more effective than sunscreens.
The more opaque the clothing, the
better the protection.
There is a natural resolution rate
of solar keratoses that is enhanced
by removing the immunosuppressive effect of UV radiation. Immune
suppression has been observed to
correlate with sensitivity to sunburn, which relates to skin type
(see table 1). Experimentally, nicotinamide in doses of 500mg bd has
been shown to reduce the immunosuppression of UV light.6 This can
be taken on the days of exposure.
There is far more evidence that
sunscreens prevent skin cancer than
there is evidence that they cause
problems, provided that the individual has normal vitamin D levels.
There is some controversy regarding nanoparticles in sunscreens. The
TGA has determined that there is no
particular risk from nanoparticles
provided that they stay in the outer
26
| Australian Doctor | 19 October 2012
Table 1: Skin types and their
sensitivity to sunburn
Skin type Sunburn sensitivity
stratum corneum.
Sunscreens have been shown
to reduce UV-induced p53 mutations and decrease the immunosuppressive effects of sunlight.1
The prevention of immunosuppression by sunscreens does not
correlate with the SPF, a measure
of UVB, but there is a strong correlation between immune protection and the evolving area of UVA
protection in sunscreens.
At present there is a significant
variation in the ability of various
sunscreens to protect against UVA.
However, daily use of a high SPF,
for example, 30 broad spectrum
sunscreen to affected areas 30 minutes before exposure, is advisable.
The sunscreen is exhausted after
two hours of maximal exposure
and therefore should be reapplied.
Vitamin D
A short exposure of unprotected
skin to sunlight between 10am
www.australiandoctor.com.au
and 2pm is necessary to produce
vitamin D. Only UVB radiation
generates vitamin D, hence exposure needs to occur in the middle
of the day when the UVB radiation is present.
This part of the UV spectrum
cannot pass through glass, therefore being exposed to sun while
driving in a car or sitting inside
does not generate any vitamin D
if the windows are closed.
In general, the time required to
Type I
White; Always burns,
never tans
Type II
Fair; Usually burns, tans
with difficulty
Type III
Sometimes burns,
usually tans
Type IV
Never burns, always tans
Type V
Moderately pigmented;
Never burns
Type VI
Heavily pigmented;
Never burns
produce adequate vitamin D is
one-quarter to one-half the time
required to just turn pink (minimal erythema dose) on a minimal surface area the size of both
arms.7 The minimal erythema
dose is a measure of sunburn sensitivity and thus skin type.
The actual time varies depending on season, geographic location, skin type and the presence
of a tan or sunscreen. All that is
necessary to produce adequate
vitamin D is 3-5 minutes for
unprotected type 1 skin on a
Queensland summer’s day.
As vitamin D is stored, exposure twice a week with the previously mentioned exposure times
would be appropriate. In patients
with significant sun damage, a
vitamin D supplement is preferable to seeking UVB exposure.7
cont’d page 28
Treatment options
TREATMENT is aimed at achieving the highest cure rate without
complication. The choice of treatment may be influenced by the site
and size of the lesion and the cost
and convenience for the patient.
The time to consider referral to
a dermatologist is when the keratoses are not responding to treatment or if a treatment is indicated
that is unavailable in your practice.
Lesions that are already showing
clinical signs suggesting possible
SCC — for example those showing
rapid growth, induration, bleeding
or tenderness — should be biopsied
before treatment to exclude malignancy.
There are many different treatments available. Appropriate treatment will depend on the factors
listed in the box top right.
Treatment modalities can be
grouped according to the grade
of solar keratosis (see box, below
right). Many topical applications
such as topical imiquimod, 5-fluorouracil, photodynamic therapy,
diclofenac, ingenol mebutate and
laser therapy have the ability to
clear not only the visible solar
keratoses but also the non-visible
lesions.
Because solar keratoses continue
to erupt, depending on the ongoing level of UV exposure, interval
treatments will be necessary. Some
patients with severe disease require
lesional treatments such as cryotherapy as frequently as every six
weeks. Others can require treatment at a 12-monthly intervals
or sometimes longer. By treating
the preclinical lesions particularly
with field therapy, the interval
between treatment schedules can be
increased significantly. Field therapy also reduces the risk of tumour
conversion from pre-existent solar
keratoses and allows for easier
identification of skin malignancies.
Figure 1: Photodynamic therapy. A: The affected area before treatment.
B: One day after treatment. C: Six weeks after treatment.
Factors determining
treatment selection
A
Keratosis thickness
Site of the keratoses
Extent of keratoses
Density of keratoses
Patient immunosuppression
Age of the patient
Patient pain tolerance
Cosmetic considerations
Presence of carcinoma
Treatment options according
to grade of solar keratosis
Mild disease treatments
Topical retinoids
Alpha hydroxy acids
B
Salicylic acid and other keratolytics
Gentle cryosurgery
Topical 5-fluorouracil
Topical imiquimod
Topical ingenol mebutate
Topical diclofenac
1927nm laser treatment
Moderate disease treatments
Moderate cryosurgery
Photodynamic therapy
Chemical peels
Topical 5-fluorouracil
Topical imiquimod
Topical ingenol mebutate
Topical diclofenac
1927nm laser treatments
C
Fractionated CO2 or erbium laser
treatments
Severe disease treatments
Aggressive cryosurgery
Curettage with or without
electrosurgery
Dermabrasion
Ablative Laser resurfacing with
erbium or CO2 (non-fractionated)
Keratolytics and retinoids
Several available keratolytics have
been used for solar keratoses for
many years. These include 3-6%
salicylic acid, 10% urea cream,
50% propylene glycol preparations and various alpha hydroxy
acid preparations. They often clear
minor keratosis, enabling visualisation of underlying neoplasia.
Twice-daily application is more
efficacious than once daily. These
agents have the advantage of high
patient acceptance. However, there
is often incomplete clearance and
recurrence is routine on cessation.
This type of treatment suits a patient
with very mild disease or an older
patient who is not tolerant of more
aggressive therapies.
Topical retinoids can treat solar
keratoses but are probably not optimal as monotherapy. Agents such as
tretinoin, adapalene and tazarotene
can significantly reduce the number
and size of solar keratoses. Local
side effects include photosensitivity and mild erythema, peeling and
dryness of the skin. Unfortunately,
there is often not a lasting improvement on cessation. Care must be
taken to advise on appropriate sun
protection, particularly when treatment is prolonged.
Apply the retinoid at night and
reduce the number of nights of
application each week if scaling is
28
| Australian Doctor | 19 October 2012
Adjunctive oral retinoids
Excisional surgery
Photodynamic therapy (Metvix)
reported. The more hyperkeratotic
lesions tend to be, the less responsive they will be to the retinoid.
Oral retinoids (acitretin) can slow
the progression of solar keratoses to
SCC particularly in the immunosuppressed patient. The effect is greatest
at four weeks. Unfortunately longterm oral retinoid use has a significant risk of side effects, particularly
mucocutaneous ones, which are best
avoided if possible.
Cryotherapy
Cryotherapy remains the current
standard technique to manage solar
keratoses. Liquid nitrogen achieves
skin temperatures of -50°C. Cure
rates of 98.8% have been reported.8
An Australian trial showed
freeze–thaw times of less than
five seconds resulted in cure rates
of only 39%.9 (The freeze–thaw
time is the time from the white ice
appearing until the ice has thawed
out). Treatment with more than 10
seconds of cryotherapy gave a cure
rate of at least 80%. Freezing times
of greater than 10 seconds, but
less than 15 seconds, produced the
optimal balance between maximisation of efficacy and minimisation
of undesirable effects.
The incidence of hypopigmentation increases with the freezing
time used. Hypopigmentation has
been found in 29% of completely
responding lesions. In addition,
hyperpigmentation has been found
in 6% of lesions treated.9 Cryotherapy is more efficacious with
a double freeze–thaw cycle; this
can be utilised in hyperkeratotic
keratoses. There are several conical silicone or plastic aids that can
be used to concentrate the nitrogen
in an area, thus leading to a colder
temperature at a greater depth
ensuring treatment of the base.
These are very useful for the hyperwww.australiandoctor.com.au
keratotic varieties.
Cryotherapy can cause significant pain, particularly on the scalp
and forehead region. Techniques
to reduce the discomfort of this
therapy include infiltration with
local anaesthesia before cryotherapy. Oral painkillers can also be
helpful taken half an hour before
a treatment cycle. Painkillers can
also be useful in managing postprocedural pain.
Various techniques of after-care
can help reduce the risk of infection, such as the application of
weak antiseptics twice a day for
two days, for example, condys
crystals solution or methyl alcohol.
Any significant blister formation
can be treated by deflating with a
sterile pin.
The ensuing dark eschar should
be allowed to fall off naturally.
The time for this is variable (on the
legs it can take weeks).
Photodynamic therapy is a successful therapy for solar keratoses,
particularly field change, but its use
may be limited by availability and
cost.
Photodynamic therapy involves
the use of a photosensitising agent,
oxygen and light of a specific wavelength, to produce controlled cell
death. The therapy involves topical application of aminolevulinic
acid or methyl-aminolevulinic acid,
which is converted to photoactive porphyrins through enzymes
in the haem biosynthetic pathway.
The porphyrins are then photoactivated by light of two main wavelengths 405nm (blue) and 635nm
(red). Dysplastic and neoplastic
cells take up greater quantities of
the photosensitising agent than normal keratinocytes, thus resulting
in faster destruction of these cells
upon application of light. Aminolevulinic acid preparations are mostly
applied to lesions for 4-6 hours
before irradiation with red light.
A shorter incubation time of three
hours is required for methyl-aminolevulinic acid, because of preferential uptake and higher selectivity.
cont’d page 30
How To TREAT Solar keratoses
from page 28
This in turn reduces the potential
for unwanted phototoxicity.
Methyl-aminolevulinic
acid
has been found to be effective in
removing 91% of keratoses if two
treatment sessions are used.10 The
advantages of photodynamic therapy are that it can be used as a field
treatment, the cosmetic outcome is
superior to cryotherapy and it can
be repeated (figure 1). Photodynamic therapy may be particularly
advantageous for large and/or multiple lesions and for those in sites
where disfigurement or poor healing from conventional therapies is a
particular risk. This treatment does
not give any longer clearance times
than other field treatments (as it
often only lasts two years).
The disadvantage of photodynamic therapy is that in about
10-15% of patients there is
significant
discomfort
associated with the light activation of
protoporphyrin. Affected patients
may require anaesthesia such as
regional local anaesthesia and/or
skin cooling. There is unpredictable
variation between individuals in the
degree of pain experienced. Pain
is less common with methylatedaminolevulinic acid compared with
aminolevulinic acid, because of the
reduced uptake by the cutaneous
nerves. Methyl-aminolevulinic acid
photodynamic therapy is approved
by the Therapeutic Goods Administration for the treatment of thin
solar keratoses on the face and scalp
when other therapies are unacceptable.
Figure 2: Strong reaction to 5-fluorouracil during treatment at week 4 (A) and
the area after treatment (B).
Figure 3: Imiquimod treatment. A: At week 3, during treatment. B: After
treatment, at week 10.
A
A
B
B
5-fluorouracil (Efudix)
For many years 5-fluorouracil has
been used and has been found to
be very efficacious. The cream is
applied twice a day for 2-3 weeks
on the face. Off-the-face treatment
times need to be extended for 4-6
weeks (figure 2).
For
maximum
effectiveness
(>90%) the endpoint of treatment is
erosion of the keratoses. The limitation of treatment has always been
that patients become extremely
uncomfortable when the solar
keratoses erode. Patients with a
large number of lesions on the face
(>100) often experience significant
discomfort. Scarring is also possible
when erosions occur and particularly if they are prolonged.
Side effects may be minimised by
treating smaller regions at a time
and limiting the treatment to visible
lesions after the first week of treatment. Sunlight should be minimised
as it can cause intense pain in areas
being treated. Flexures near the
nose, mouth, or eyes are commonly
irritated and are best avoided.
Topical 5-fluorouracil can worsen
other cutaneous conditions such as
melasma or rosacea.
Allergy to the medication or its
vehicle can be quite severe. This
can be identified by the presence of
erythema in all regions where the
cream is applied to rather than only
the keratoses. In addition, the reaction continues to worsen for a week
or two, despite the withdrawal of
the agent.
If allergy occurs, 1% hydrocortisone cream twice daily for one week
is appropriate. Rarely, oral corticosteroids are necessary.
An effective 5-fluorouracil treatment can last up to five years before
needing to be repeated, providing
30
| Australian Doctor | 19 October 2012
strict UV protection is undertaken.
Imiquimod (Aldara)
Imiquimod is the first immuneresponse modifier that has been
found to be effective in treating
solar keratoses. Complete clearance rates of up to 50% and partial clearance rates of over 75%
have been achieved.
Imiquimod has been approved
by the TGA for treatment of solar
keratoses, superficial BCC, genital
and perianal warts. Imiquimod
stimulates the innate immune
response by stimulating Toll-like
receptor (a natural ligand for
influenza RNA).7 The consequent
induction, and release of proinflammatory cytokines, predominantly interferon (IFN)-alpha,
TNF-alpha and interleukin (IL)12, results in indirect antitumour
and antiviral effects.
The mechanism of action causes
application site reactions, including itching, burning and pain,
which are surprisingly generally
well tolerated. In the setting of
www.australiandoctor.com.au
marked involvement of a field with
solar keratoses more inflammation can be expected. Patients who
experience excessive inflammation
should have a dose reduction recommended — either a reduction in
the dosing regimen or the addition
of a rest week.
Uncommonly, excessive release
of interferon can lead to flu-like
symptoms: headache, lethargy or
painful lymphadenopathy. This
can be disabling and generally precludes further treatment.
A recent study has shown a simple check of the medical history can
halve the potential for side effect
in imiquimod-naive patients.11 A
history of restriction to bed for
more than five days with seasonal
influenza (suspected on history)
at any time in the past indicates a
high probability of significant side
effects with imiquimod therapy.
The identification of patients
who are likely to experience significant side effects enables the treating doctor to find a more suitable
treatment or to reduce the dosing
regimen and supervise closely. In
patients who have not been significantly affected by influenza (never
restricted to bed) the therapeutic
reaction to imiquimod is also negligible. In these patients, treatment
with Imiquimod may be ineffective
at normal dosing rates.11
Imiquimod is a very useful agent
in both field and individual lesion
treatment. In cosmetically sensitive areas, particularly on the face,
the outcome is excellent in most
patients (figure 3). Lesional inflammation is to be expected with current protocols and correlates with
resolution of the solar keratoses.
Of the various treatment regimes
proposed, the protocol of three
applications per week (eg, Monday,
Wednesday and Friday) for four
weeks seems the best. Treatment is
then reviewed four weeks after the
cycle and repeated if necessary for
one further cycle. There is little to
gain from further cycles if the keratoses are resistant. When complete
clearance is achieved remissions of
2-3 years can be expected.
Figure 4: Ingenol mebutate treatment. A: The affected area before treatment. B:
During treatment, at day 4. C: After treatment, at day 57.
Figure 5: Half-face 1927nm laser, right side; Trichloracetic acid 35%, left side.
A: Immediately postoperative. B: At two months.
A
A
B
B
C
eye pain, eyelid oedema, eyelid ptosis and periorbital oedema.
Seventy per cent of patients can
expect a partial clearance, while
50% will achieve a complete clearance with 2-3 days of therapy.
Diclofenac gel (Solaraze)
Ingenol mebutate (Picato)
This colourless gel (0.015% or
0.05%) contains the active substance ingenol mebutate, an inducer
of cell death. This new agent has
been developed and extensively
studied in Australia for treatment of
both solar keratoses and superficial
BCC over the past 10 years.12
Ingenol mebutate has already
been released in the US. When it
becomes available for use in Australia it will add to the available
treatments. Specifically the advantage is that treatment times are far
shorter (2-3 days). While field treatments are the ideal form of therapy,
a very acute and inflammatory reaction is to be expected.
Test-treating one or two individual lesions first will help to identify
patients who might experience such
a reaction. For these individuals, a
single application with close supervision is advisable. Care needs to
be exercised in skin preparation.
Over-cleansing or weakening of
the epidermal barrier will cause an
excessive reaction, which could lead
to unwanted side effects.
For the treatment of solar keratosis on the face and scalp, 0.015%
gel should be applied to the affected
area once daily for three consecutive
days.
For the treatment of solar keratosis on the trunk and extremities,
0.05% gel should be applied to the
affected area once daily for two
consecutive days. There is a limit of
25cm2 to the area that can be treated
at one time due to the limitations in
current clinical trial data.
A normal skin response includes
erythema, crusting, swelling, vesiculation or pustulation, erosion and —
less commonly — ulceration. Local
skin reactions typically occur within
one day of treatment initiation, peak
in intensity up to one week following completion of treatment, and
resolve within two weeks for areas
treated on the face and scalp, and
within four weeks for areas treated
on the trunk and extremities (figure
4). As the gel is an irritant, eye and
eyelid exposures are to be avoided.
Accidental exposure causes severe
Diclofenac 3% in 2.5% hyaluronan
gel is applied on a twice-daily basis
for 12 weeks. The mechanism of
action of diclofenac in treating solar
keratoses is unknown. Combining
hyaluronan gel with the diclofenac
enables the drug to be localised to
the skin. A 50% reduction in lesions
is typically seen during treatment.
Complete response rates of 29%
have been reported. Unfortunately,
most patients do not experience a
long-term remission. Commonly,
keratoses recur in 12 months. The
patients in whom there is a larger
inflammatory reaction will often
have a more prolonged remission.
Common side effects are localised
pain and irritation seen in up to
72% of patients.
Chemical peels
Almost every chemical peel has been
used to control solar keratoses. The
more aggressive the agent, the more
improvement one can expect. Usually a medium strength peel (eg,
35% trichloracetic acid) would
be necessary to have significant
improvement in solar keratoses.13
Not all patients can cope with the
inevitable postoperative swelling
www.australiandoctor.com.au
and discomfort required to achieve
the desired results.
A week of rest is necessary after
a medium-strength peel. For these
treatments, referral to a dermatologist will often be necessary. The
improvement should last for 2-3
years for a medium-strength peel.
There is a significant risk of hypopigmentation, which relegates this
treatment to a last resort.
Curettage and electrodessication
Hyperkeratotic keratoses (eg, cutaneous horn) are best treated with
this option, once SCC is excluded.
Any induration not caused by the
keratin may indicate an SCC. Histologic evaluation is often necessary for these hypertrophic lesions.
Rarely excision will be necessary for
a persisting hypertrophic keratosis.
Facial resurfacing
Recently the Fraxel 1927nm laser,
a non-ablative fractional laser, has
been shown to significantly improve
facial solar keratosis.13 Although
more than a single treatment is often
necessary, the cosmetic outcome is
excellent (figure 5). Hypopigmentation does not need to occur in order
to achieve improvement in the keratoses. This modality is best for the
mild keratoses.
Full-face resurfacing with either
an ablative laser or dermabrasion is
considered in severely sun-damaged
patients who have a significant
cont’d next page
References
1. H
olmes C, et al. Solar keratosis:
epidemiology, pathogenesis,
presentation and treatment.
Australasian Journal of
Dermatology 2007; 48:67-74.
2. A
rron St, et al. Viral oncogenesis
and its role in nonmelanoma
skin cancer. British Journal of
Dermatology 2011; 164:120113.
3. L
everrier S, et al. Role of HPV
E6 proteins in preventing UVBinduced release of pro-apoptotic
factors from the mitochondria.
Apoptosis 2007, 12:549 - 560.
4. B
abilas P, et al. [Actinic
keratoses]. Hautarzt 2003;
54:551-60.
5. M
arks R. Epidemiology of
non-melanoma skin cancer and
actinic keratoses in Australia: a
tale of self-immolation in Elysian
fields. Australasian Journal of
Dermatology 1997; 38 Suppl
1:S26-29.
6. D
amian DL. Photoprotective
effects of nicotinamide.
Photochemical and
Photobiological Sciences 2010;
9:578-85.
7. N
owson CA, et al. Vitamin D
and health in adults in Australia
and New Zealand: a position
statement. Medical Journal of
Australia 2012; 196:686-87.
8. L
ubritz RR, Smolewski SA.
Cryosurgery cure rate of
actinic keratoses. Journal of
the American Academy of
Dermatology 1982; 7:631-32.
9. T
hai KE, et al. A prospective
study of the use of cryosurgery
for the treatment of actinic
keratoses. International Journal
of Dermatology 2004; 43:68792.
10. Freeman M, et al. A
comparison of photodynamic
therapy using topical methyl
aminolevulinate (Metvix)
with single cycle cryotherapy
in patients with actinic
keratosis: a prospective,
randomized study. Journal
of Dermatological Treatment
2003; 14:99-106.
11. Freeman A, Freeman M.
Predicting success and side
effects with imiquimod therapy.
Journal of the American
Academy of Dermatology
2012; 66:AB157.
12. Siller G, et al. PEP005 (ingenol
mebutate) gel for the topical
treatment of superficial basal
cell carcinoma: Results of a
randomized phase IIa trial.
Australasian Journal of
Dermatology 2010; 51:99-105.
13. Freeman AM, Freeman MG.
Efficacy and safety of 35%
trichloroacetic acid vs Fraxel
1927 nm fractionated laser in
the treatment of facial actinic
keratosis. Australasian Journal
of Dermatology 2011; 52(Suppl
1):25.
19 October 2012 | Australian Doctor |
31
How To TREAT Solar keratoses
from previous page
number of keratoses and have required
multiple excisions for skin tumours.
Because there will be significant postoperative hypopigmentation, ongoing UV
exposure is contraindicated. Therefore
only older patients who are able to avoid
ongoing sun exposure should be considered for this more aggressive procedure.
With the significant healing times and
risks of scarring, the patients need to be
selected very carefully.
Counselling patients before this procedure is very important. In contrast to the
1927nm laser, full-face ablative resurfacing is a major procedure and has unacceptable complications unless performed
by an experienced operator, usually a dermatologist or plastic surgeon. Unlike fractional CO2 resurfacing, repeat procedures
with ablative technology are not advisable
as the risks particularly of scarring are
greatly increased.
Conclusion
AN increasing array of treatments
is available for solar keratoses. By
studying the various treatments and
being aware of their limitations, GPs
can reduce the burden of disease, and
help to prevent SCC in particular.
Referral to a dermatologist will
be necessary for therapy with CO2,
erbium, 1927nm laser, photodynamic therapy (when not otherwise available), oral retinoids and in
situations when treatment decisions
are difficult.
New advances in prevention could
ultimately help lead to a reduction in
this disease.
Radiotherapy
Radiotherapy, although very effective, is
not recommended as treatment precludes
future radiotherapy treatments in the
region should it be necessary if skin cancer develops.
How to Treat Quiz
Solar keratoses — 19 October 2012
1. Which TWO statements are correct?
a) Solar keratoses are also known as
seborrhoeic keratoses
b) Solar keratoses are lesions of the skin
that result from a localised abnormal
proliferation of atypical epidermal
keratinocytes that have incurred damage
by UV radiation
c) Solar keratoses are defined as skin
cancers
d) The lifetime risk of a Caucasian
Australian developing non-melanoma
skin cancer is more than 50%
2. Which THREE statements regarding
the aetiology of solar kertatoses are
correct?
a) Ultraviolet radiation, in particular UVB, is
the most important aetiological factor in
the development of solar keratoses
b) Patients receiving immunosuppressive
therapy — most commonly organtransplant recipients — are at an
increased risk of developing solar
keratoses
c) The risk of solar keratoses increases with
advancing age
d) Merkel cell polyomavirus has been
implicated primarily in the aetiology of
both solar keratoses and SCC
3. Which THREE statements regarding
the clinical features of solar keratoses
are correct?
a) Solar keratoses typically appear as small,
smooth, round lesions that are easily
visible
b) Solar keratoses vary in size from 2mm
to 6mm in diameter and rarely exceed
10mm, but may become confluent and
form sheets or plaques
c) Sun-exposed areas such as the face,
bald scalp and the dorsum of the hands
are the most common sites
d) The main differential diagnoses for
solar keratoses include localised
telangiectasia, lichenoid keratosis, intraepidermal SCC, superficial basal cell
carcinoma, discoid lupus erythematous,
superficial actinic porokeratosis and
psoriasis
4. Which THREE statements regarding
protection from solar radiation are
correct?
a) Light shade is only equivalent to SPF 2
b) Sunscreen offers more effective
protection from solar radiation than
clothing
c) Sunscreen should be applied 30 minutes
before exposure and should be reapplied
every two hours
d) Vitamin D is generated by UVB radiation,
which is present in the middle of the day
5. Which THREE factors are important in
deciding treatment selection for solar
keratoses?
a) Whether the patient is immunosuppressed
b) The age of the patient
c) The site of the keratoses
d) The appearance of the borders of the
keratoses
6. Which THREE statements regarding
treatment with keratolytics and
retinoids are correct?
a) Keratolytics include 3-6% salicylic acid,
10% urea cream, 50% propylene glycol
preparations and various alpha hydroxy
Instructions
Complete this quiz online and fill in the GP evaluation form to earn 2 CPD or PDP points. We no longer accept quizzes
by post or fax.
The mark required to obtain points is 80%. Please note that some questions have more than one correct answer.
Online ONLY
www.australiandoctor.com.au/cpd/ for immediate feedback
acid preparations
b) Complete clearance is rarely achieved
with keratolytics and recurrence is routine
on cessation
c) Topical retinoids are an excellent
monotherapy for treating solar keratoses
d) Long-term oral retinoids are best avoided
if possible, as there is a significant risk of
side effects, particularly mucocutaneous
ones
7. Which TWO statements regarding
cryotherapy and photodynamic therapy
are correct?
a) Freeze–thaw times of less than five
seconds resulted in cure rates of 80% in
patients treated with cryotherapy
b) Hypopigmentation is present in 29% of
completely responding lesions treated
with cryotherapy
c) The advantages of photodynamic
therapy are that it can be used as a field
treatment, the cosmetic outcome is
superior to cryotherapy and treatment
can be repeated
d) Photodynamic treatment gives longer
clearance times than other field
treatments
8. Which TWO statements regarding
5-fluorouracil and imiquimod are
correct?
a) Topical 5-fluorouracil can worsen other
cutaneous conditions such as melasma or
rosacea
b) The effect of 5-fluorouracil treatment can
last up to three years before needing to
be repeated
c) Occasionally, imiquimod can result in
excessive release of interferon, which
can lead to symptoms of a flu-like
illness, headache, lethargy or painful
lymphadenopathy
d) A limiting factor in the use of imiquimod
is the poor outcome on cosmetically
sensitive areas such as the face
9. W
hich TWO statements regarding
ingenol mebutate and diclofenac gel
are correct?
a) Treatment times with ingenol mebutate
are far shorter, at 2-3 days, compared
with other topical treatments
b) Eighty-five per cent of patients will
achieve a complete clearance of solar
keratoses with 2-3 days of ingenol
mebutate therapy
c) Keratoses commonly recur in 12 months
after treatment with diclofenac gel
d) Side-effects of localised pain and irritation
are rare with diclofenac gel treatment,
occurring in fewer than 10% of patients
10. Which THREE statements regarding
chemical peels, curettage and
electrodessication, and facial abrasion
are correct?
a) There is a significant risk of
hypopigmentation following treatment
with chemical peels
b) Once SCC has been excluded,
curettage and electrodessication is
the best treatment for hyperkeratotic
keratoses
c) Cosmetic outcome is excellent after
treatment of solar keratoses with the
Fraxel 1927nm laser
d) Full-facial ablative resurfacing can
be performed safely by any laser
operator
CPD QUIZ UPDATE
The RACGP requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2011-13 triennium. You can
complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept the quiz by post or
fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online.
how to treat Editor: Dr Barbara Tink
Email: barbara.tink@reedbusiness.com.au
Next week Dental problems in early childhood are predictive of future dental problems and also influence general growth and cognitive development. Historically, the separation of medical and dental
teaching has led to generations of GPs who have felt inadequately prepared to manage oral healthcare. The next How to Treat sheds light on treating the main issues of paediatric dentistry. The author is
Associate Professor Richard Widmer, Associate Clinical Professor in Paediatric Dentistry, University of Sydney, and director, department of dentistry, Children’s Hospital at Westmead, Sydney, NSW.
32
| Australian Doctor | 19 October 2012
www.australiandoctor.com.au