Dr Stephen Kownacki considers some newer treatments for actinic keratosis as reflected in the latest PCDS guideline and shows how therapies can be individualised
- Keep a high index of suspicion in patients with UV damage
- Have a low threshold for referral for high-risk patients
- Diagnostic skills need to be learned and refreshed
- The more AKs that are visible, the greater the risk of SCC
- Beware the keratosis with a fleshy base
- Pain or tenderness developing in a lesion can be a sinister sign
- Lesion and field treatments may need to be used sequentially
- If a benign diagnosis cannot confidently be made, then referral to secondary care is mandatory
- Diagnosis, sun protection advice, and treatment of AKs are all part of a GP’s role
- The patient should always be involved in the choice of treatment.
UV=ultraviolet; AK=actinic keratosis; SCC=squamous cell carcinoma
The incidence of actinic keratosis (AK) is increasing because the condition correlates strongly with cumulative sun exposure, and therefore also with age. In the UK and Ireland, 19%, 23%, and 24% of individuals aged over 60 years were found to have at least one AK in studies from Merseyside, South Wales, and Galway, respectively.1
Despite the relatively short time since the last Primary Care Dermatology Society (PCDS) actinic keratosis (AK) guideline was published in 2013, the PCDS guideline committee reconvened in January 2014 to consider whether two new agents were likely to change advice given for primary care prescribers. The outcome was that the group did consider the agents would add to treatment options for AK, and confer extra benefits for some patients, so an updated version of the PCDS AK guideline was issued in April 2014.2
It is important to start by explaining that the PCDS AK guideline is not a list of instructions, since it is not possible to provide an exact sequence to follow for all possible lesions or patients.2 Similarly, the cost of treatments was impossible to compare; for example, cost depends on the extent of the problem; the amount of keratin; patient attributes (physical and psychological); patient previous experience (‘I’m not having that again!’); and—perhaps most of all—local rules on treatment use! The guidance group felt that a range of treatments options, as well as the option not to treat, was necessary to cope with the range of presentations, but the choice requires diagnostic skills as well as discussion with the patient.
Diagnosis and treatment
We emphasise that diagnosis is key and the decision whether to treat at all will vary from one patient to another. On examination, it is vital to take the opportunity to check not just the presenting lesion but also to examine all the skin, or at least the sun-exposed areas. Look for AK and other skin malignancies, since the ultra violet (UV) radiation that causes AKs is implicated in the development of squamous cell carcinoma (SCC), many basal cell carcinomas (BCC), and some melanomas. This is especially important for those with history and evidence of significant sun exposure and is most relevant for patients with fair skin types (i.e. Fitzpatrick 1, 2; see Table 1).3
Initial information and advice
Sun avoidance and sun protection advice should be offered whether treatment is initiated or not. When a patient presents, or you notice a lesion that may be suspicious, use this as a teaching opportunity to influence not just the patient in front of you but also their whole family, regardless of whether or not the lesion is significant.2
History, examination, and when to refer
The big fear for healthcare practitioners is missing an SCC and this makes some GPs feel that it is easier or better to refer all lesions to a dermatologist; this, however, is impossible and bad practice. If a patient is referred as a 2-week wait, which is appropriate for a suspected SCC, then not only will the system completely collapse but the poor patient and their family are likely to spend 2 weeks in terror, looking at horrific pictures of the worst possible examples on the internet, only to be dismissed after a few seconds of assessment by secondary care! This then engenders or reinforces patient distrust of their primary care service.
The majority UK view is that the risk of conversion of AK to SCC is low and the risk of secondary spread is also low, although this is difficult to quantify from the published reviews.1,4 There is histological evidence to support the European and USA views, which lean towards treating all lesions on the basis that AKs (some of which are subclinical and so invisible until treated) are just SCCs at an early stage.5 It is difficult to know whether differences in remuneration between healthcare practitioners in different countries play a part in how they view the evidence guiding decisions whether to treat or not! This is an area where cost and benefit become difficult and open to opinion; personal communication from dermatologists in the south west of England, however, suggests that they are witnessing not only a tidal wave of BCCs but also a significant increase in SCCs, including those with metastatic spread, which adds weight to the ‘treat all AKs as potential cancers’ point of view.
Good general practice involves informed patient choice and a full consideration of the patient’s circumstances. Our advice is first to take a history of both the patient and the lesion and then to perform a careful examination. Even when it is decided a lesion has no fleshy base and is not significantly changing in a patient with no previous history or increased risk of malignant lesions (see Box 1), it is nevertheless important to give advice regarding changes that should bring the patient back for review.
The bottom line is that if a benign diagnosis cannot be made, then the patient must be referred to secondary care. That means a 2-week-wait cancer referral for possible SCCs.6
Making a benign diagnosis requires skill and some experience and we hope that the PCDS guidance,2 the website at
www.pcds.org.uk, 7 and our nationwide series of teaching conferences, will offer training to all.
A factor often neglected in these cash-strapped times is the morbidity associated with red and scaly, sometimes itchy and/or sore lesions, on parts of the body that the world sees. We rightly emphasise the psychological distress young people have with acne, but sometimes forget that older people also care about their appearance; facial or scalp disfigurement can make them embarrassed and withdrawn. In addition, keratotic lesions catch and can bleed if traumatised (e.g. by lesions on the backs of hands pushed into pockets, or from combs and headwear on crusty scalps). Should we not consider these factors also?
Box 1: Identifying the high risk patient and red-flag indicators2
- Identifying the high risk patient:
- past history of skin cancer
- those with extensive UV damage
- immunosuppressed patients or the very young
- consider referral to secondary care or accredited GPwSI. If not high risk then consider treatment as outlined in the guidance.
- Red-flag indicators:
- lesions that:
- are rapidly growing
- have a firm and fleshy base and/or are painful
- are not responding to treatment
- refer urgently as Priority Cancer Referral to secondary care.
- lesions that:
- Adapted from: Primary Care Dermatology Society website. Actinic (solar) keratosis—primary care treatment pathway. www.pcds.org.uk/ee/images/uploads/general/AK_guidelines_2014_final_aw2.pdf (accessed 29 May 2014). By kind permission.
|Skin type||Skin colour||Characteristics|
|I||White; very fair; red or blond hair; blue eyes; freckles||Always burns, never tans|
|II||White; fair; red or blond hair; blue, hazel or green eyes||Usually burns, tans with difficulty|
|III||Cream white; fair with any eye or hair colour; very common||Sometimes mild burn, gradually tans|
|IV||Brown; typical Mediterranean Caucasian skin||Rarely burns, tans with ease|
|V||Dark brown: Middle Eastern skin types||Very rarely burns, tans very easily|
|VI||Black||Never burns, tans very easily|
NICE says the management of AKs is a role for primary care,8 so when a decision has been made to treat, what agents should you use? All have their place in therapy but, as with many dry skin conditions, the addition of an emollient is a first step and is likely to be helpful. There is also good evidence to support the use of sunscreens as part of reduced sun exposure.9
Small and large field areas
In the latest guidance, we have added a new column to differentiate between small and large areas of field change. This reflects the product characteristics of the most recent, useful additions to the treatment options (ingenol mebutate, and 3.75% imiquimod) and encompasses the existing treatments (3% diclofenac with hyaluronic acid [HA]; 5% fluorouracil [5-FU]; 5% imiquimod; and photodynamic therapy), all of which can be be used for the field changes as well as isolated lesion therapy.2
Some treatments are licensed for (or because of experience limited to) smaller areas, but can be used sequentially on large areas of affected skin.2 The degree of inflammation and morbidity is variable and may inhibit patients from returning for the next treatment session, but all treatments work in some way to produce inflammation. It is important to continue to explain this to the patient and/or carer, preferably with the help of nursing colleagues, to prevent premature cessation of treatment or overuse, since, unlike most medical therapies, these do not provide symptomatic relief—quite the opposite! Pictures of what to expect are also very useful.
Despite all this advice (in which we have not considered costs) we are still asked, ‘which is the best?’
A rural farmer with a high pain threshold and little concern for scarring (there’s a stereotype!) might prefer a yearly check and the freezing of nuisance lesions. Cryotherapy can be used in situations where there are a few (isolated) hyperkeratotic lesions within an area of field change before or after wider field treatment.
Some patients might be happy to continue using 3% diclofenac with HA twice daily for 3 months, possibly repeated after breaks for mild diffuse lesions. A single or a few mildly keratotic lesions in someone with dexterity and adequate eyesight (or a helper) might be effectively treated with 0.5% 5-FU + 10% salicylic acid using a small brush applicator. For 5-FU, the size of area treated has a bearing on the inflammatory response. While 5-FU has the benefit of many years of doctor experience, 5% imiquimod is often considered a ‘strong’ treatment for severe areas but carries the risk of an interferon-type of malaise and other systemic symptoms in a few patients. Treatment with 3.75% imiquimod seems to have fewer side-effects and so can be used over the whole face or scalp. For a patient with application or compliance difficulties, ingenol mebutate has only to be applied daily for 3 (face) or 2 (limbs, trunk) days, and so can be performed in surgery or by a nurse or carer; since the treatment period is very short, it will be completed before the onset of the inevitable therapeutic inflammation. Both these factors aid compliance. In addition, faster recovery is anticipated.
Photodynamic therapy (PDT) is not widely available in primary care, mainly because of the costs of set-up and nursing for limited numbers of patients. It is, nevertheless, a useful treatment for severe or large areas, including for immunosuppressed people (in secondary care).10
Curettage is an option for hyperkeratotic lesions but not for suspicious lesions. If you think there may be SCC change, refer the patient to secondary care as a 2-week-wait referral.
The PCDS hopes that the revised guideline and additional material in this article will help you to choose whether (and with what) to treat when faced with the increasingly common problem of AK. Although the risk of progression to cancer is low, it increases with the number of lesions; moreover, AKs indicate the degree of UV damage sustained by the patient and thus the risk of other skin cancers. There is no ‘best buy’ for all circumstances and the guideline indicates our view of the options. However, none of this is of any use without diagnosis, which remains the essential role of primary care.
- Commissioners should ensure that there are clear local guidelines for the management of AK and possible skin cancers. These should include:
- formulary choices for topical agents
- recommendations for their use
- price (some of the newer agents are simpler to use than the older ones, but are expensive)
- Commissioners could consider using local community GPwSI or specialist nurse services to help manage AK in primary care. These services could:
- support GPs with education
- offer an opinion on individual cases
- Teledermatology could also help to support GPs in seeking assurance that a lesion is benign before they treat it. This can help save tariff costs and ease pressure on busy dermatology departments
- Tariff costs for dermatology outpatients: £104 (new), £68 follow up.a
- De Berker D, McGregor J, Hughes B, on behalf of the British Association of Dermatologists Therapy Guidelines and Audit Subcommittee. Guidelines for the management of actinic keratoses. Br J Dermatol 2007; 156 (2): 222–230.
- Primary Care Dermatology Society website. Actinic (solar) keratosis—primary care treatment pathway. www.pcds.org.uk/ee/images/uploads/general/AK_guidelines_2014_final_aw2.pdf (accessed 29 May 2014)
- Fitzpatrick T. The validity and practicality of sun reactive skin types I through VI. Arch Dermatol 1988; 124 (6): 869–871.
- Feldman S, Fleischer A. Progression of actinic keratosis to squamous cell carcinoma revisited: clinical and treatment implications. Cutis 2011; 87 (4): 201–207.
- Ackerman A. Solar keratosis is squamous cell carcinoma. Br J Dermatol 2003; 139 (9): 1216–1217.
- NICE. Referral guidelines for suspected cancer. Clinical Guideline 27. NICE, 2005. Available at: www.nice.org.uk/guidance/CG27
- Primary Care Dermatology Society website. www.pcds.org.uk (accessed 29 May 2014).
- National Collaborating Centre for Cancer. NICE guidance on cancer services. Improving outcomes for people with skin tumours including melanoma (update): the management of low-risk basal cell carcinomas in the community. NICE, 2010. Available at: www.nice.org.uk/nicemedia/live/10901/48878/48878.pdf
- Thompson S, Jolley D, Marks R. Reduction of solar keratoses with regular sunscreen use. N Eng J Med 1993; 329 (16): 1147–1151.
- Braathen L, Szeimies R, Basset-Seguin N et al. Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005. J Am Acad Dermatol 2007; 56 (1): 125–143 G