This is the current release of the guideline.

Actinic keratoses

Management
Treatment

Dermatology
Family Practice
Internal Medicine

Physicians

To provide recommendations for the management of actinic keratoses

Patients with actinic keratoses

1. No therapy
2. Topical therapies
   • Emollient
   • Sun block
   • Salicylic acid
   • 5-Fluorouracil
   • Imiquimod 5% cream
   • Diclofenac gel
   • Tretinoin cream
   • Masoprocol cream
3. Other treatments
   • Cryosurgery
   • Photodynamic therapy
   • Laser, chemical peels and dermabrasion
   • Systemic retinoids

• Efficacy of treatment modalities
• Ease of use of treatment modalities
• Morbidity
• Cost-benefit of treatment

Hand-searches of Published Literature (Primary Sources)
Searches of Electronic Databases

Medline (1966–2004) was the main source of references for this review. Relevant evidence was sought using the search terms "solar keratosis" and "actinic keratosis." Additional and earlier literature was reviewed on the basis of references within post-1966 publications. All articles of apparent relevance were reviewed independently of the nature of the publication. The National Ambulatory Medical Care Survey (U.S.A.) was used for further data on topical chemotherapy. Papers were reviewed and discussed by the contributors to the British Photobiology Group (BPG) Workshop (see Acknowledgments in the original guideline document).

Not stated

Weighting According to a Rating Scheme (Scheme Given)

Quality of Evidence

I: Evidence obtained from at least one properly designed, randomized controlled trial

II-i: Evidence obtained from well-designed controlled trials without randomization

II-ii: Evidence obtained from well-designed cohort or case–control analytical studies, preferably from more than one centre or research group

II-iii: Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence

III: Opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees

IV: Evidence inadequate owing to problems of methodology (e.g., sample size, or length of comprehensiveness of follow up, or conflicts in evidence)

Systematic Review

Not stated

Expert Consensus

These guidelines stemmed from a consensus meeting held by the British Photobiology Group (BPG) in 1999. Following one of these meetings one of the authors was invited to draw up guidelines for the management of actinic keratoses (AKs) by the British Association of Dermatologists (BAD) Therapy Guidelines and Audit Subcommittee.

Strength of Recommendations

1. There is good evidence to support the use of the procedure
2. There is fair evidence to support the use of the procedure
3. There is poor evidence to support the use of the procedure
4. There is fair evidence to support the rejection of the use of the procedure
5. There is good evidence to support the rejection of the use of the procedure

A formal cost analysis was not performed and published cost analyses were not reviewed.

Peer Review

Not stated

Strength of recommendations (A-D) and quality of evidence (I-IV) are defined at the end of the Major Recommendations field.

Management

Many options are open to patients with actinic keratoses (AKs). The natural history of individual lesions studied in the United Kingdom suggests that treatment is not universally required on the basis of preventing progression into squamous cell carcinoma (SCC). However, others feel that prevention of SCC is the main reason for therapy.

Some AKs have histological features within the spectrum of in-situ skin cancer. They can also represent a cause of symptoms and disfigurement which may be the main determinant of treatment choices. Clinical judgement should discern which lesions are more likely to represent a risk to the patient's health, but where the likelihood is low, options include no therapy or palliation with emollient or keratolytic agent such as low-strength salicylic acid ointment.

Where active treatment is sought, many modalities of therapy are available (see Table below). Good-quality data on the outcome of these different therapies are available in only a few instances. Treatment of an individual lesion may have a therapeutic effect on surrounding skin, with an effect on overall progression of actinic damage, but this potential benefit has not been quantified. Given the low morbidity and risk of the majority of AKs, the Strength of Recommendation made for treatments by the authors has an element of cost-benefit and risk-benefit included. This is derived from clinical experience in addition to the published evidence.

Topical Therapies

Additional Topical Therapies

• Salicylic acid ointment (A, III)
• Tretinoin cream (B, I)
• Masoprocol cream (C, I)

In conclusion, there is good evidence that 5% 5-FU cream used twice daily for 3 weeks is effective at reducing AKs on the face and back of hands by about 70% for up to 12 months. There is insufficient randomized controlled trial (RCT) evidence to support or refute the efficacy of alternative regimens and formulations, although one RCT suggests that a single night-time application for 3 months for AKs on the back of the hands is effective. Imiquimod has been more rigorously assessed with modern RCT design and may produce a similar pattern of side-effects and response to 5-FU. Diclofenac gel is a relatively mild agent that reduces the AK count but there are no follow-up data beyond 1 month. Topical tretinoin has some efficacy on the face, with partial clearance of AKs, but may need to be used for up to a year at a time to optimize benefit. Sun block, emollient and 2% salicylic acid ointment BP may reduce the AK count by a similar amount.

Other Treatments

Additional Other Therapies

• Laser, chemical peels and dermabrasion (C, III)
• Systemic retinoids (B, I)

Other Considerations

Should actinic keratoses be treated?

There is inadequate evidence to justify treatment of all AKs to try to prevent malignant change. Treatment should be considered on an individual basis according to signs, symptoms, and history. There will be instances where excision is undertaken for diagnostic purposes.

Overall, the data comparing individual treatments are not good enough to justify making a single recommendation. Decisions for an individual patient will be based on the clinical presentation, the efficacy, morbidity, availability and cost of relevant treatments and patient preference.

However, treatment of small numbers of AKs with cryotherapy is currently widely practised by dermatologists, while more extensive AKs are commonly treated with 5-fluorouracil. Due to expense and inconvenience photodynamic therapy (PDT) is probably best reserved for patients with extensive AKs that cannot be controlled with other therapies.

Is there a role for prevention and what works?

AKs are a marker for sun damage and therefore are an indication to increase sun-avoidance measures. There is some evidence that regular use of sunscreen reduces the number of AKs and the risk of SCC.

Should patients with actinic keratoses have follow up?

There are no data concerning the benefit of follow up in patients with AKs. Patients and their carers should be educated regarding changes that suggest malignancy. Those at high risk of nonmelanoma skin cancer, e.g., organ transplant recipients, may warrant follow up; the presence of numerous AKs is an indicator of this risk.

Are there high-risk groups and is their management different?

Patients with multiple and confluent AKs are likely to be at higher risk of nonmelanoma skin cancer, particularly patients with organ transplants who are estimated to have 50 to 100 times the risk of an age- and sex-matched control population. Anecdotal and limited trial data suggest that treatments for AKs in transplant patients are less effective than in the general population, perhaps because AKs are more proliferative and hyperkeratotic in this group, or because new lesions rapidly appear in the treated site. One study in transplant recipients failed to demonstrate a reduction in the development of subsequent skin cancers in those areas of skin previously treated for AKs with PDT.

Cost-benefit of Treatment

Most AKs result in few or no symptoms and are not dangerous. Where there is a wide range of treatments it is necessary to balance the benefits of treatment against side-effects. In many health care systems this calculation will have some element of cost-benefit, where the cost is to the state and the indication must justify the expense. These guidelines are not able to give details on the complex matter of cost-benefit, but it is apparent that some treatments are considerably more expensive than others. Where outcomes are comparable and morbidity of treatment tolerable, we have tended to give a higher strength of recommendation to the cheaper treatment or one that is more easily used in primary care.

Summary of Recommendations

AKs represent a spectrum of clinical complaint and pathology. Most patients can be diagnosed and managed in primary care. In many instances, management may entail little or no medical treatment other than advice on sun avoidance and self-monitoring. Where there is clinical concern or the patient specifically wants treatment, cryosurgery or one of the many topical therapies can be employed taking into consideration the specifics of the situation. If there is diagnostic concern or failure to respond to first-line treatment, a histological specimen, such as obtained at curettage with cautery or formal excision, may be both diagnostic and curative. Where AKs are multiple or confluent, at sites of poor healing or with poor response to standard therapies, photodynamic therapy may be helpful. Such patients may also warrant long-term follow up for the associated increased risk of nonmelanoma skin cancer.

****, good treatment; ***, fair treatment, **, can be used depending on circumstances; *, rarely used in these circumstances.

^aImiquimod is not currently licensed for use in the treatment of AKs.

Definitions:

Strength of Recommendations

1. There is good evidence to support the use of the procedure
2. There is fair evidence to support the use of the procedure
3. There is poor evidence to support the use of the procedure
4. There is fair evidence to support the rejection of the use of the procedure
5. There is good evidence to support the rejection of the use of the procedure

Quality of Evidence

I: Evidence obtained from at least one properly designed, randomized controlled trial

II-i: Evidence obtained from well-designed controlled trials without randomization

II-ii: Evidence obtained from well-designed cohort or case–control analytical studies, preferably from more than one centre or research group

II-iii: Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence

III: Opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees

IV: Evidence inadequate owing to problems of methodology (e.g., sample size, or length of comprehensiveness of follow up, or conflicts in evidence)

None provided

The type of evidence supporting the recommendations is specifically stated for selected recommendations (see "Major Recommendations" field).

• Appropriate prevention and treatment of actinic keratoses
• Prevention of progression to squamous cell carcinoma

• The side-effects of imiquimod cream are similar to 5-fluorouracil (5-FU) with severe erythema (30.6%), scabbing and crusting (29.9%), and erosions or ulceration (10.2%).
• Side effects seen with diclofenac cream include pruritus and rash.
• Photodynamic therapy can be painful and cause local adverse reactions
• Anecdotal evidence over the last 20 years suggests that there can be some considerable morbidity employing systemic retinoids. In addition, there may be a rebound effect once the systemic therapy is stopped.
• Cryosurgery may cause scarring

These guidelines have been prepared for dermatologists on behalf of the British Association of Dermatologists (BAD) and reflect the best data available at the time the report was prepared. Caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations in this report. It may be necessary or even desirable to depart from the guidelines in the interests of specific patients and special circumstances. Just as adherence to the guidelines may not constitute defence against a claim of negligence, so deviation from them should not necessarily be deemed negligent.

An implementation strategy was not provided.

Getting Better
Living with Illness

Effectiveness

Not applicable: The guideline was not adapted from another source.

2007 Feb

British Association of Dermatologists - Medical Specialty Society

British Association of Dermatologists

British Association of Dermatologists Therapy Guidelines and Audit Subcommittee

Primary Authors: D. de Berker, Bristol Dermatology Centre, Bristol Royal Infirmary, Bristol, UK; J.M. McGregor; Department of Dermatology, St Bartholomew's and the London NHS Trust, London, UK; B.R. Hughes, Portsmouth Dermatology Centre, St Mary's Hospital, Milton Road, Portsmouth, UK

British Association of Dermatologists Therapy Guidelines and Audit Subcommittee Members: A.D. Ormerod (Chairman); D.J. Eedy; D. Mitchell; F. Humphreys; J. Peters; R. Bull; H. Bell; M. Kouimtzi; S. Jones

D. de B., none; J.M.M. has received an honorarium from 3M as an invited member of an advisory board for the treatment of actinic keratoses; B.R.H., none.

This is the current release of the guideline.

This NGC summary was completed by ECRI Institute on July 25, 2007. The information was verified by the guideline developer on August 19, 2007.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.