By Gary M. White, MD
Grouped hypertrophic actinic keratoses on the ear, facing the sun.
The actinic keratosis (AK) is a sun-damaged spot on the skin. Its transformation rate to squamous cell carcinoma (SCC) is low. In fact, 99.5% of AKs will not turn into skin cancer and 25% will go away without treatment.
The actinic keratosis is a fixed, rough, scaly spot on the sun-exposed area of an adult. The nose, forehead, temples and backs of the hands are particularly common sites. Those fair-skinned and particularly those of Scottish/Irish descent are prone to these lesions. Patients often present with multiple lesions.
Various morphologies include:
A review of all available studies looking at the rate of conversion of AK to SCC concluded that "currently, no reliable estimates concerning the frequency of AK developing into invasive carcinoma can be given, and further studies are needed." [Br J Dermatol. 2013 Sep;169(3):502-18]. Detailed study results vary widely, but is it is often quoted that individual AKs progress to SCC at a rate of approximately 1/250 to 1/1000 per year. Part of the problems is that there is a very high turnover of AKs with large numbers developing, regressing, and recurring. For example in one detailed study of the natural history of AKs over a 1 year period (no treatment, merely observation), 74% of AKs noted at the beginning of the study spontaneously regressed at some point over the ensuing year [J of Invest Dermatol 2000;115;273]. Another problems is that most studies don't biopsy the presumed AKs so indeed many may be SCCs or SCC in situ to begin with (see second paragraph below. Maybe the AK didn't convert to SCC, but instead was an SCC in the first place). Furthermore, some use conversion to SCC in situ as a positive event while others do not.
In one study that used accurate mapping of both SCCs and pre-existing AKS, it was found that 10/17 (60%) SCCs arose from a lesion diagnosed clinically as a solar keratosis in the previous year and the other 7 (40%) SCCs on what had been clinically normal skin 12 months previously. (The risk of malignant transformation of an AK to SCC within 1 year in that study was less than 1/1000 [Lancet 1988 Apr 9;1(8589):795].)
It is extremely common to be faced with a lesion that is most likely an AK, but could conceivably be Bowen's disease or a small SCC. In one study of 411 clinically typical AKs biopsied, 39% were AKs histologically, 30% were SCC, and 5% or less were BCC, seborrheic keratoses or other lesions [Cancer 2009;115;2523]. It is appropriate for lesions clinically typical as AK, to freeze once with instructions to the patient to return if the lesion is not completely gone or the skin is not smooth or "normal skin," etc. In general, any lesion frozen as a presumed AK that does not resolve should be biopsied.
In one study, a history of tenderness, bleeding or changing size predicted SCC over AK (but not itching or burning) [JAAD 2011;65:211]. In addition, if a lesion is painful on palpation, it is much more likely to be an SCC than AK.
A patient handout is available.
Every patient should be encouraged to apply sunscreen each morning and reapply if they are outside for 2 hours or more, especially if in water or sweating. Dramatic improvements can be made with just daily morning sunscreen use [Br J Dermatol. 2009 Nov;161 Suppl 3:78-84]. One review found that proper sunscreen use can reduce the number of AKs up to 53% [BJD 2013;169;502]. AKs are a marker of previous sun exposure, with more recent exposure, e.g., the last 2 years, having the greatest impact [Br J Cancer. 1996 Oct;74(8):1308-12].
Active surveillance is a new approach advocated by some that involves patient education, daily sunscreen use and monitoring for the development of skin cancer without the specific treatment of individual, minor and/or asymptomatic AKs [JAMADerm 2017;153;251]. It is based upon the concern of over treatment, the low conversion rate to SCC and that many AKs spontaneously remit.
However, 2-4 weeks of 5% 5-FU BID to the face and ears (along with daily SPF 30 sunscreen) reduced by 75% the incidence of SCC over the following year in a large VA study [JAMA Dermatol online 2018 Jan 3.]. Additionally, that same regimen reduced AKs counts and the need for spot treatment of AKs for longer than 2 years [JAMA Derm 2015;151;952].
It therefore seems prudent to recommend annual 5% 5-FU treatment along with daily morning sunscreen to all patients with a history of non-melanoma skin cancer.
Niacinamide 500 mg twice a day has been shown to reduce actinic keratoses on the order of 30% [Journal of Investigative Dermatology (2012) 132, 1497–1500]. It has also been shown reduce the development of new AKs [Australian Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) study].
Cryotherapy is a standard and effective lesion-directed therapy. It is simple and quick to perform. Patients do not need to go to the pharmacy, etc. It is very appropriate for one or a limited number of lesions. Its main drawback is that it fails to address the entire field of sun damage. Individual lesions along with a 1 mm margin are turned white for just a few seconds. Thin lesions need only that. Thicker lesions are more likely to clear if a longer, e.g., 10-20 seconds, freeze is used [Int J Dermatol 2004;43;687]. But pain, inflammation and risk of hypopigmentation is higher the longer the freeze. The patient's consent should be obtained before treating (pain while treating, blister, then crust and scab for 10 days). A study of liquid nitrogen cryotherapy found that longer freeze times improved 3-month AK clearance rates, with 39% success after freezing for ≤ 5 seconds, 69% success after freezing for ≥ 5 seconds and 83% success after freezing for at least 20 seconds.[Int J Dermatol 2004; 43:687–92]
Thicker, indurated, ulcerated or painful lesions are suggestive of SCC and should be considered for biopsy. Any lesion that does not clear after one (or at most two) freezings (or resistant to other topical therapy) should be biopsied.
Curettage, with or without electrodesiccation, is another lesion-directed therapy. It requires local anesthesia and is more likely to cause scarring. It is beneficial for hyperkeratotic lesions and/or when cryotherapy has failed. Just as with cryotherapy, any one lesion that recurs after one or two treatments should be biopsied.
Photodynamic therapy (PDT) can be effective in treating AKs, and there are many variations in the method. For example, the Levulan Kerastick contains 20% aminolevulinic acid and is activated by blue light illumination (peak wavelength 417 nm) to treat actinic keratoses of the face or scalp. Hypertrophic AKs tend not to respond. The highest clearance is with two treatments e.g., 8 weeks apart.
Other treatments employed include chemical peels and laser.
Field-directed therapy is a more comprehensive treatment approach. However, it is less commonly used than freezing for a variety of reasons including more time needed, longer downtime for the patient, higher cost for the patient, etc.
In a study of 131 patients, the four-day application of 5% 5-fluorouracil mixed with 0.0005% calcipotriene BID removed 88% of facial AKs compared with a 26% reduction in those who used 5-FU alone [Dermatology News July p. 4]. Redness and burning were the most common side effects but overall, the treatment was well tolerated. The majority of patients who had used the classic 5-fluorouracil treatment in the past preferred the new approach. Calcipotriol cream alone daily can reduce AKs [J Drugs Dermatol. 2009:451].
If lesions are widespread, 5-fluorouracil (5-FU) BID for 7-14 days on the face and 10-14 days on the body is effective although the patient should be fully informed of the tenderness, erosion, crusting and pain that is involved. Older regimens are BID for 2-3 weeks but BID for one week has 80% of the effect with much less inflammation, etc. Concentrations range from 0.5% (e.g., Carac) to 5%. But in general, the longer the treatment duration, the higher the clearance rate.
In one study of VA patients [JAMA Derm 2015;151;952], A single course of 5% topical fluorouracil cream BID for 4 weeks along with daily spf 30 sunscreen reduced AKs counts and the need for spot treatment for longer than 2 years. In addition, 2-4 weeks of 5% 5-FU BID reduces by 75% the incidence of SCC over the following year [JAMA Dermatol online 2018 Jan 3.].
Imiquimod is a topical agent that is used to treat the entire field of sun damage including actinic keratoses. Strengths include 5%, 3.75% and 2.5%. Many treatment regimens are used. The higher the concentration used and the more applications performed, the higher the clearance [JAAD 2010;62;582]. The manufacturer's prescribing information for imiquimod 5% cream states that patients should be treated twice weekly for 16 weeks and that treatment should be applied to a single contiguous treatment area of approximately 25 cm2 (forehead, scalp, or one cheek). Nowadays however, few clinicians use it in this manner as the duration of therapy rather long. A typical approach (but off label) is to use daily imiquimod for 2 weeks, then 2 weeks off therapy, then 2 weeks daily imiquimod. In one study, actinic keratoses cleared in the majority (82%) with imiquimod 3 times a week for 4 weeks and repeated after a month if necessary [JAAD 2002;47;571]. Others use the imiquimod 3/week until a good reaction is achieved. Finally, some use imiquimod once a week indefinitely.
Ingenol mebutate gel (Picato) is FDA approved to treat actinic keratoses. It is used as follows: Ingenol mebutate 0.015% daily for 3 days for the face and scalp. Ingenol mebutate 0.05% daily for 2 days on the trunk or extremities. The benefit with ingenol is the short treatment length compared with 5-FU and imiquimod. In one study for example [JEADV 2015;29;1822], local skin reaction peaked at day 4 and was almost entirely gone in 2 weeks.
Diclofenac (Solaraze) BID for 2-3 months can clear 1/3 to 1/2 of AKs. It is a "kindler-gentler treatment," but takes much longer.
An atrophic AK.
Multiple SPAKs in a common location.
Much sun damage and AKs on the back of the hands.
A hypertrophic AK. These often resist freezing. They may need biopsy to rule out SCC and gentle C&D x 1.
An AK on the eyebrow. A common place.
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