Dr David de Berker highlights the key recommendations from the guideline on management and treatment of AK, published by the British Association of Dermatologists
  • AKs are common: 15–25% of patients aged over 60 years will have one or more
  • They rarely progress to become skin cancer
  • Patients with AK have sun damage and so are at increased risk of skin cancer
  • Treatment should be guided by patient preference and clinical need, but may not be required in all cases

The guideline published by the British Association of Dermatologists in February 2007 defines actinic keratoses (AK) (also known as solar keratoses) in the following way:

'Actinic (syn. solar) keratoses are keratotic lesions occurring on chronically light-exposed adult skin. They represent focal areas of abnormal keratinocyte proliferation and differentiation that carry a low risk of progression to invasive squamous cell carcinoma (SCC). A spectrum of histology is seen but the cardinal feature of AK is epithelial dysplasia. This may be restricted to the basal layer or may extend to full-thickness atypia at which point differentiation from Bowen's disease can be difficult.'1

Incidence and natural history of actinic keratoses

Studies in the UK and Ireland indicate that 19–24% of people over 60 years of age have AK2–4 However, 15–25% of these lesions will spontaneously regress within 12 months,3,5 and less than 1 in 1000 progress to become invasive squamous cell carcinoma (SCC).6 Where there is concern over the possibility of this, the patient should be referred using the 2-week wait mechanism.7

Presentation and diagnosis

Symptoms and appearance of AK are as follows:

  • discrete, sometimes confluent, patches of redness and scaling on predominantly sun-exposed skin, usually in middle-aged and elderly individuals
  • often asymptomatic, but may occasionally be sore or itchy, with single or multiple lesions
  • scaling, which may be hard and gritty, with associated atrophy of the epidermis. Some lesions are thicker with prominent horny material, making distinction from early invasive SCC difficult.

Diagnosis can be confirmed by histopathology of excision biopsy, incisional biopsy, shave biopsy, or curettage.

Management

Studies in the UK and Australia of the natural history of individual AK lesions have shown that only about 1 in 10,000 cases progress to become SCC.8 On this basis, it is unreasonable to offer treatment, of any kind, for all incidences of AK when it is easy to treat the one case of SCC when it changes.

Where treatment is considered necessary, many modalities of therapy are available (Figure 1). The strength of recommendations and quality of evidence as assessed by the guideline are listed for each of the therapies below, as defined in Box 1 (please refer to hard copy of article or to the original guideline, link can be found below).

Emollient (strength of recommendation A, quality of evidence, I)

Where emollient has been used in the placebo limb of randomised control trials, it has resulted in improvement in over 40% of subjects;9 sun-damaged skin is often dry and emollient will address this aspect of the problem.

UVA (ultraviolet A) sun block cream (A,I)

A study of patients in a very sunny climate with AK showed that sun block with a sun protection factor >17, applied twice daily for 7 months, was superior to emollient in prevention of further AK lesions.10

Salicylic acid ointment (2%) BP (A, III)

This can be used to reduce the hyperkeratotic element of AK.1

5% 5-fluorouracil cream (A, I)

Application twice daily for 3 weeks reduces lesions to about 25% of their number or surface involvement.1 Benefits last 6–12 months, when they tend to recur.1 There is a vigorous inflammatory reaction to the 5% 5-fluorouracil cream during the course of treatment, which subsides after. It is important that patients are aware of this before commencing use or else they may stop treatment before an effective dose is given.

To minimise morbidity, less intense regimens of treatment have been tried, with applications of 5% 5-fluorouracil cream twice per week for 10 weeks. While this provokes less intense side-effects, it is difficult to judge efficacy from the small and inconsistent studies available.

Imiquimod 5% cream (B, I)

Complete clearance of all their AKs was achieved in 47% of people when treated three times a week for 16 weeks, in comparison to 7.2% who received the placebo.11 Imiquimod 5% cream provokes a reaction similar to that seen with 5% 5-fluorouracil cream treatment. Benefit is sustained for up to 8 weeks; data are lacking for improvements beyond this time. It is not, however, licensed for the treatment of AK and comes in a single application sachet, which makes it a very expensive treatment.

3% diclofenac in a 2.5% hyaluronic gel (B, I)

Use of this therapy for 60–90 days gives clearance of 50–70% of mild cases of AK, with follow-up limited to 30 days.12,13 It does not provoke the reactions seen with imiquimod 5% cream and 5% 5-fluorouracil cream.

Other treatments

Surgery is a way of ensuring that the clinical diagnosis is correct, while also delivering effective treatment.1 However, it is not proportionate with the pathology for most cases of AK where the diagnosis is easy. All samples should be sent for histopathological assessment. Surgical options include formal excision where there is concern that the diagnosis is SCC. This would only be undertaken by those experienced in the management of skin cancer and who participate regularly in the local skin cancer multidisciplinary team.

Curettage or shave biopsy are good treatments for larger AK lesions where the diagnosis is clear, but where topical therapy is contraindicated. A shave biopsy retains the architecture of the specimen, which can be helpful for the pathologist when offering his or her interpretation.

Cryosurgery with liquid nitrogen (A, I)

According to randomised controlled trials, cryotherapy is effective in 68–75% of lesions.1 It is usually administered as a 5-second freeze, in a single or double dose.14,15 It is more effective than photodynamic therapy (PDT) for thicker lesions. Redness, oedema, and blistering are common side-effects, especially on the face—a common site for AK. Hypopigmented scarring can be a sequel of treatment.

Photodynamic therapy (B, I)

This involves the use of a photosensitising cream in combination with an activating wavelength of light, which elicits a phototoxic reaction at the skin surface. It is similar in efficacy to cryotherapy and to 5% 5-fluorouracil cream, but requires the use of equipment and expensive cream.1 The benefits are on areas of confluent extensive AK, such as are found on the bald scalp and areas prone to poor healing, such as the lower leg.16

Laser treatment, chemical peels and dermabrasion (C, III)

These treatments all have some evidence of efficacy, but are rarely used in the UK for treatment of AK. They are more commonly used for cosmetic work, although they can be turned to general use. Compared with cryotherapy, which is cheap and also available for treatment of other dermatological diseases, laser treatment is expensive and usually on offer only in a minority of UK dermatology practices. While chemical peels are possible, there is much safety legislation linked to their use, which makes this difficult.

Treatment of AKs with PDT, laser treatment, chemical peels, and dermabrasion is available, but rarely used, in secondary care.

Systemic retinoids (B, I)

Systemic synthetic forms of vitamin A, such as Acitretin, are sometimes used for patients with extensive AK where other treatments are not containing the disease. This is particularly the case where lesions demonstrate a high rate of transformation into SCC, such as in some organ transplant patients.17 This treatment is not available in primary care.

Figure 1: Factors determining choice of active therapy from six main alternatives*

               

 

Cryosurgery 5-fluorouracil Diclofenac Imiquimod† Curettage PDT  
Main characteristic of actinic keratoses             Comments
               
Low number of AKs
••••
••••
••
••
 
High number of AKs
•••
••••
•••
•••
•••
 
Thin AKs
•••
••••
•••
•••
••
Thin lesions may not always require treatment.
Hypertrophic AKs
••
••••
Histology may be required. Formal excision may be preferred.
Isolated lesions failing to respond to other therapies
••
••••
Histology may be required. Formal excision may be preferred.
Confluent recalcitrant AKs, failing other treatments
•••
•••
•••
•••
Certain lesions within a resistant field may require histological assessment .
Location
 
 
 
 
 
 
 
Scalp, ears, nose, cheeks, forehead, perioral
••••
••••
•••
••••
•••
•••
 
Periorbital
•••
•••
•••
Topical therapies can be difficult to use near mouth and eyes.
Confluent scalp
•••
••••
•••
••••
••••
Pretreatment with 5% salicyclic acid ointment may improve outcome.
Below the knee
•••
••
••••
••••
Poor healing is a particular concern at this site. All modalities can lead to ulceration. Treatment may be combined with advice on elevation and compression bandaging where possible.
Back of hands
••••
••••
••
•••
•••
Courses of topical therapy may need to be extended and pre-treatment with 5% salicyclic acid ointment may improve outcome.
Characteristics of patient (rating may be considered in context of clinical need indicated by characteristic of AK and location
               
Medically dependent or senile
•••
••
•••
•••
Morbidity of treatment may dictate choice of modality.
Self-reliant
•••
••••
•••
••••
5-fluorouracil may be repeated at sites of relapse or new lesions in primary care.
One off treatment
••••
••••
••••
•••
•••
 
Lives far from hospital
•••
••••
•••
••••
May favour treatment that allows monitoring in primary care.
Part of continuous management plan
••••
••••
•••
•••
 

*The scoring is based on the authors' evaluation of efficacy, ease of use, morbidity, and cost-benefit.
Imiquimod is not currently licensed for use in the treatment of AKs.
AKs=actinic keratoses; PDT=photodynamic therapy; ••••=good treatment; •••=fair treatment, ••=can be used depending on circumstances; =rarely used in these circumstances.
Reproduced from Br J Dermatol with kind permission from Blackwell Publishing

Patient characteristics

The choice of whether and how to treat AK is based not only on the nature of the keratosis, but on the demeanour, health and capabilities of the patient. Any decision will be a clinical judgement that could run contrary to the apparent best choice. Many people with AKs will have multiple medical and social factors to consider. They may not manage the morbidity of 5% 5-fluorouracil, or they may need the immediacy of curettage to ensure the job is done in the most reliable manner. Figure 1 highlights the different factors that need to be considered in terms of the patient, the treatment option, and the keratosis.

Patient education is important

It is important that patients are fully informed about their condition, for the following reasons:

  • to ensure that they seek help for any lesion that changes to develop features of an SCC
  • so that they are aware of the importance of sun protection
  • to encourage them to educate younger relatives on sun protection.

Is follow-up necessary?

Continued follow-up of AK patients is important for the following reasons:

  • some treatments have high morbidity and patients may benefit from assessment early in treatment to provide guidance and reassurance. All the treatments with efficacy observed over a period of more than 3 months cause some morbidity. This is the result of inflammation arising through tissue destruction. Most people are well able to tolerate this if it occurs at a site that does not interfere excessively with normal function, and they are well counselled before treatment. Treatments with less morbidity, such as emollient and diclofenac gel, have no good longer-term data to confirm efficacy
  • over time, most patients will notice they acquire further lesions, and education should be provided to enable them to recognise new instances of AK and also those that are changing and may represent early SCCs
  • patients with high numbers of lesions are in a risk group for invasive SCC,18 independent of the possibility of transformation of individual examples of AK. Shared skin surveillance with the patient may help to ensure early treatment and thus avoid the necessity of complex surgery for larger SCCs
  • organ transplant patients have more occurrences of AK and SCC than their healthy counterparts and SCCs can develop rapidly in this group.1 Monitoring is advised, with a view to early treatment of all suspicious lesions.

Role of the GP

Actinic keratoses are numerous in an ageing population. They are not threatening, in that individual lesions rarely transform into SCC. However, they are an indicator of sun damage and mean that the patient is at increased risk of both basal cell carcinoma and SCC. There are many therapeutic options for GPs to offer the patient, and they need to supplement this with education so that patients can report changes early if new or existing lesions enlarge, bleed, or become keratotic, such that they might represent an SCC.

Further advice can be obtained from the website for the British Association of Dermatologists, where a pdf version of the full guideline can be found:
http://www.bad.org.uk/healthcare/guidelines/Actinic_Keratoses.pdf

  • This guideline could form the basis of a local treatment algorithm for PBC consortia
  • Treatment of actinic keratoses and non-melanoma skin cancers are ideal candidates for community practice-based commissioning provision
  • Specific referral criteria should be developed locally with the input of consultant dermatologists for lesions suspicious of cancer
  • Many non-suspicious lesions can be treated effectively without specialist referral and often by trained nurses
  • Remember it is often cheaper to employ a consultant than use GPwSIs
  • Tariff prices: dermatology outpatient = £118 (new), £58 (follow-up)19
  1. de Berker D, McGregor J, Hughes B. British Association of Dermatologists Therapy Guidelines and Audit Subcommittee. Guidelines for the management of actinic keratoses. Br J Dermatol 2007; 156 (2): 222–230.
  2. O'Beirn S, Judge P, Maccon C, Martin C. Skin cancer in County Galway, Ireland. In: Proceedings of the Sixth National Cancer Conference, sponsored by the American Cancer Society Inc. and the National Cancer Institute, September 1968. Philadelphia: Lippincott, 1970: pp. 489–550.
  3. Harvey I, Frankel S, Marks R et al. Non-melanoma skin cancer and solar keratoses. I. Methods and descriptive results of the South Wales skin cancer study. Br J Cancer 1996; 74 (8): 1302–1307.
  4. Memon A, Tomenson J, Bothwell J, Friedmann P. Prevalence of solar damage and actinic keratosis in a Merseyside population. Br J Dermatol 2000; 142 (6): 1154–1159.
  5. Marks R, Foley P, Goodman G et al. Spontaneous remission of solar keratoses: the case for conservative management. Br J Dermatol 1986; 155 (6): 649–655.
  6. Marks R, Rennie G, Selwood T. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet 1988; 1 (8589): 795–797.
  7. Department of Health. Manual for Cancer Services. London: Department of Health, 2004.
  8. Callen J, Bickers D, Moy R. Actinic keratoses. J Am Acad Dermatol 1997; 36 (4): 650–653.
  9. Olsen E, Abernathy M, Kulp-Shorten C et al. A double blind, vehicle-controlled study evaluating masoprocol cream in the treatment of actinic keratoses of the head and neck. J Am Acad Dermatol 1991; 24 (5 Pt 1): 738–743.
  10. Thompson S, Jolley D, Marks R. Reduction of solar keratoses by regular sunscreen use. N Engl J Med 1993; 329 (16): 1147–1151.
  11. Korman N, Moy R, Ling M et al. Dosing with 5% imiquimod cream 3 times per week for the treatment of actinic keratosis: results of two phase 3, randomized, double-blind, parallel-group, vehicle-controlled trials. Arch Dermatol 2005; 141 (4): 467–473.
  12. Rivers J, Arlette J, Shear N et al. Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel. Br J Dermatol 2002; 146 (1): 94–100.
  13. Wolf J, Taylor J, Tschen E, Kang S. Topical 3.0% diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses. Int J Dermatol 2001; 40 (11): 709–713.
  14. Szeimies R, Karrer S, Radakovic-Fijan S et al. Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study. J Am Acad Dermatol 2002; 47 (2): 258–262.
  15. Freeman M, Vinciullo C, Francis D 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. J Dermatolog Treat 2003; 14 (2): 99–106.
  16. Morton C, Brown S, Collins S et al. Guidelines for topical photodynamic therapy: report of a workshop of the British Photodermatology Group. Br J Dermatol 2002; 146 (4): 552–567.
  17. McNamara I, Muir J, Galbraith A. Acitretin for prophylaxis of cutaneous malignancies after cardiac transplantation. J Heart Lung Transplant 2002; 21 (11): 1201–1205.
  18. Foote J, Harris R, Giuliano A et al. Predictors for cutaneous basal- and squamous-cell carcinoma among actinically damaged adults. Int J Cancer 2001; 95 (1): 7–11.
  19. www.dh.gov.uk G