Top tips: actinic keratosis

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Dr Neil Shroff shares some key points for managing actinic keratoses in primary care

1 Get the diagnosis right

Actinic keratosis (AK) is a chronic skin condition characterised by a scaly or hyperkeratotic lesion that has the potential to be malignant. Actinic keratoses tend to occur on sun-exposed areas such as the head and neck, and the back of forearms and hands. They are usually less than 1 cm in diameter and often felt as rough gritty areas even before they become visible. Rough, white surface scale is usually present.

2 Not all AKs need treatment

Opinions differ about whether all AKs should be treated. The European Dermatology Forum 2010 guideline recommends that all lesions should be treated, as it is impossible to predict which will progress to squamous cell carcinomas (SCCs). ¹ However, the British Association of Dermatologists 2007 guideline advocates no treatment where there is little clinical concern and the patient is not troubled by the lesions.² Around 15–25% of AKs spontaneously regress within 12 months, with less than 1 in 1000 per annum progressing into SCC of the skin.² Mathematical models predict that for an individual with an average of 7.7 AKs the probability of at least one transforming into SCC within a 10 year period is 10%.³

3 Classify AKs according to grade

Grading AKs will help with formulating a management plan. In 2007 a clinical classification for this purpose was developed. ⁴ The grading system has formed the basis of the Primary Care Dermatology Society Actinic (solar) keratosis primary care treatment pathway.⁵ They are classified as followed (see Figure 1, below):

Grade 1—slightly palpable, better felt than seen
Grade 2—moderately thick, easily felt and seen
Grade 3—very thick, hyperkeratotic, and/or obvious.

Figure 1: Examples of grades 1–3 actinic keratoses
Grade 1—actinic keratosis with evidence of surrounding chronic photo damage
Grade 2—actinic keratosis on the nasal side wall
Grade 3—close up of a solitary actinic keratosis, a keratotic papule on an erythematous base
Images from PCDS (www.pcds.org.uk); reproduced with permission.

4 When to refer—the red flags

Refer if transformation from AK into SCC is suspected. The risk of this is very low, but increases over time and with large numbers of lesions. The following features are suggestive of SCC:

recent growth
induration (i.e. swelling or thickness of the skin lesion)
pain and tenderness
inflammation
a nodular lesion
bleeding/ulceration/non-healing
lesions on the lips.

Such patients should be referred and seen in secondary care within the current 2-week rule for urgent referrals. Other reasons for referral are:

where there is diagnostic uncertainty
where the patient:
- has more widespread/severe actinic damage
- is immunosuppressed, e.g. following solid organ transplantation
- is very young (consider xeroderma pigmentosum).

5 Use the opportunity for patient education

Most patients will only need a diagnosis, an explanation of why it happens, and advice regarding:

reducing sun exposure
use of sunscreens
emollient use for symptomatic relief (may actually improve cosmesis)
potential changes in lesions and what to look for.

6 Perform a full skin examination in patients with multiple AKs on the head and neck

Patients with multiple AKs in this region are at increased risk of skin cancer, mainly basal cell carcinomas. Common areas to check are the periorbital areas, cheeks, ears, and the neglected back on men and the lower legs of females.

7 How to treat AKs in primary care

Consider treating both individual AKs as well as sun-damaged skin (referred to as field damage). This will manifest as erythema, chronic photo damage, and several actinic keratoses in close proximity. Field damage is more prone to developing into SCC and therefore treatment can reduce the risk of malignant transformation. The risk of transformation to SCC increases with greater numbers of AKs.

Treatment options can be divided into:

ablative—these are physical treatments that destroy the actinic keratoses. They include grade 2 or 3 AKs, especially where patients do not wish to apply creams or are not able to do so
topical—useful for widespread thinner lesions, such as grade 1 or 2 AKs, or where there is field damage.

8 What ablative treatments are available in primary care?

Cryotherapy using liquid nitrogen is a simple, effective technique for treating a solitary uncomplicated AK. A 5-second freeze in a single or double dose will usually suffice. It is quick, convenient, and easy to administer. Patients should be counselled about pain during the procedure and the sequelae of side effects including blistering, ulceration, and scarring that can occur afterwards. Other alternative ablative treatments include surgical excision, especially if SCC is suspected. Curettage and cautery as well as shave excision are effective treatments for larger AKs. Shave excision makes interpretation of the pathology easier as the architecture of the specimen is maintained.

9 What topical treatments are available in primary care?

A variety of topical treatments are available for the management of AKs (see Table 1, below). Uses will depend on the grade of AK and the presence or absence of field damage. With all the topical agents listed in Table 1, if the reaction is very florid, stop the topical treatment and give the patient an emollient to use. In the author's experience, this will usually encourage swift resolution of the reaction.

Table 1: Topical treatments that are available in primary care
Treatment	Applications
5-fluorouracil	used twice daily for 3–4 weeks treatment usually causes a vigorous skin reaction leading to pain, itching, ulceration and even scarring. It is mandatory that patients are counselled in advance. Consider using photographs (see Figure 2, below) to demonstrate what the patient can expect throughout the process and its end results, in order to manage expectations and enable treatment concordance can be used to treat grade 1 or 2 AKs, or field damage in a sequential way so as to avoid a vigorous reaction in a large area.
5-fluorouracil 0.5% and salicylic acid 10%	used once daily for 8–12 weeks usually forms a whitish membrane overlying the AK and this should be peeled off the following day after application can be used to treat an area of field damage (up to 5 × 5 cm) or 10 grade 1 or 2 AKs.
Imiquimod 3.75% and 5%	imiquimod 3.75% can be used to treat larger areas of field damage as well as grade 1 or 2 AKs used once daily for 2 weeks, then 2 weeks off followed by another 2 weeks on there appear to be fewer side effects compared with imiquimod 5% (in the author's experience) and the whole face and scalp can be treated simultaneously imiquimod 5% (see Figure 2, below) can be used to treat grade 1 or 2 AKs as well as small areas of field damage up to 5 × 5 cm used 3 times a week for 4 weeks, followed by a 1-month break and another 4-week course of treatment if needed can cause flu-like symptoms (e.g. fever, myalgia, arthralgia) because of increased levels of interferon being released.
Ingenol mebutate 150 μg/g and 500 μg/g	the advantage of using this product is the skin reactions, which are often significant and can resolve far quicker than with other topical agents useful where treatment concordance may be an issue ingenol mebutate 150 μg/g (see Figure 2, below) useful for treating grade 1 or 2 AKs on the face and scalp, as well as small areas of field damage (up to 5 × 5 cm) applied once daily for 3 days ingenol mebutate 500 μg/g useful for the trunk and extremities applied once daily for 2 days.
Topical 3% diclofenac in 2.5% hyaluronic acid gel	used twice daily for 60 days ideally used for areas of field damage, grade 1 AKs, and possibly grade 2 AKs has moderate efficacy and is well tolerated—usually there is less irritation and inflammation of the skin compared with other topical agents, i.e. 5-fluorouracil and ingenue mebutate (in the author's experience).

10 Get a feel for different treatment regimes

This will come with experience and tailoring the treatment to the patient, and the type of AK they have as well as the presence of field damage. A degree of pragmatism should be allowed, as not all AKs need treatment especially in the age of austerity. It is always important to consider the immunosuppressed patient. The practice of treating AKs and field damage prior to transplantation surgery may become more prevalent as individuals are at much higher risk of malignant change when taking immunosuppressive drugs.

Figure 2: photos showing examples of reactions with topical treatments for AK
5-fluorouracil reaction when used for field treatment
Day 14 of treatment: the patient was in discomfort and decided to stop treatment at this point. To avoid such a vigorous reaction, divide the scalp into quadrants and treat sequentially. Gentler regimes can be initiated, e.g. using 5-fluorouracil on a once-daily basis for 6 weeks	3 months after treatment: the patient's scalp is clear of clinically detectable AKs. Treatment stopped and use of emollient has aided recovery
Reaction with imiquimod 5% applied 3 times per week
Typical reaction at 3–4 weeks into treatment	3 months after treatment—a pristine scalp
Ingenol mebutate reaction 150 μg/g applied once daily for 3 days

References

Stockfleth E, Terhorst D, Braathen L et al.Guideline on actinic keratoses. European Dermatology Forum, 2010. Available at: www. euroderm.org/edf/index.php/edf-guidelines/category/5-guidelines-miscellaneous
De Berker D, McGregor J, Hughes B. Guidelines for the management of actinic keratoses. Br J Dermatol 2007; 156: 222–230.
Dodson J, DeSpain J, Hewett J, Clark D. Malignant potential of actinic keratoses and the controversy over treatment. A patient-oriented perspective. Arch Dermatol 1991; 127 (7): 10291–31.
Röwert-Huber J, Patel M, Forschner T et al. Actinic keratosis is an early in situ squamous cell carcinoma: a proposal for reclassification. Br J Dermatol 2007; 156 (suppl3): 8–12.
Keohane S, Kownacki S, Moncrieff G et al. Actinic (solar) keratosis primary care treatment pathway. Primary Care Dermatology Society, 2012. Available at: www.pcds.org.uk/ee/ images/uploads/general/Actinic_(Solar)_ Keratosis_Primary_Care_Treatment_Pathway.pdf