Synonyms: actinic (solar) keratosis

The term actinic keratosis (AK) was coined in 1958 and means literally thickened scaly growth (keratosis) caused by sunlight (actinic). Solar keratoses, or AKs, are ultraviolet (UV) light-induced lesions of the skin, which are by far the most common lesions with malignant potential to arise on the skin (they can progress to invasive squamous cell carcinoma (SCC)).

AK is seen in fair-skinned persons in areas of long-term sun exposure, like Australia, where about half of the population over the age of 40 years are affected. Although the condition is very similar to Bowen's disease or carcinoma in situ, most lesions do not progress to malignant change. However, recognition and simple treatment help to prevent progression.

Pathophysiology

• Cells within actinic keratoses (AKs) show characteristic UV-induced gene mutations.
• Histologically AKs share features with squamous cell carcinoma (SCC). AK is an epidermal lesion characterised by:
  • Collections of atypical, pleomorphic keratinocytes in the basal layer which can extend to the upper granular and cornified layers.
  • The epidermis is abnormal in architecture, with acanthosis, parakeratosis, and dyskeratoses. Cellular atypia is present with keratinocytes varying in size and shape.
  • Mitotic figures are present.
• It has features of Bowen's disease or carcinoma in situ:
  • They can be distinguished more by the degree of cellular change and the extent of the lesions rather than differences in the features of individual cells.
  • Often, marked hyperkeratosis and areas of parakeratosis with loss of the granular layer are present.
  • A dense inflammatory infiltrate is usually present.
  • AK is considered by some to be the the earliest manifestation of SCC and should be regarded as such rather than as a precancerous lesion.

Epidemiology

• Actinic keratosis (AK) occurs most often in whites at a rate according to cumulative UV exposure.
• Frequency increases according to a number of risk factors:
  • Increasing age, as the dose of UV is cumulative.
  • Proximity to the equator as this affects UV dosage and cumulative exposure.
  • Lifestyle and time spent outdoors. Outdoor lifestyles, whether with work or recreation and sport, will increase risk.
  • Other specific practices such as use of tanning booths. Artificial sunlight is a risk factor and may produce lesions in unusual places.
  • How fair the individual's skin is. Skin is graded from Fitzpatrick type I to VI according to sensitivity to sunlight, as displayed by a tendency to burn or to tan. These lesions are almost entirely confined to fair skin types I and II.
  • Patients who are immunosuppressed following organ transplantation have a markedly increased risk of developing AKs and of developing malignant change in the AKs.
• AKs are more common in men than in women. Traditionally men are more likely with work and recreational activities to spend time outdoors.
• AK has also been associated with a high-fat diet.
• Overall, the rate in Australia is highest with a prevalence around 50%.
• In the USA the rate is estimated to be between 11% and 26%.
• Elsewhere they are very common in fair-skinned people in countries like South Africa and New Zealand.
• They tend to present between the ages of 30 and 60 years but can present earlier or later.

Presentation

• Lesions occur in fair-skinned people in parts of the body exposed to long-term sun exposure, such as the head area (face, ears, scalp), forearms, and backs of the hands. Other areas repeatedly exposed to the sun include the back, the chest, and the legs.
• There may be other features of solar damage, such as telangiectasiae, elastosis, and pigmented lentigines.
• The first lesion is usually a single plaque on the face in the 20s or 30s but, with time and further exposure to strong sunlight, they tend to progress on the nose, forehead and cheeks.
• Actinic keratoses (AKs) begin as small rough spots that are more easily felt than seen (like rubbing sandpaper). Over several years, lesions enlarge, often becoming red and scaly. From small 3-10 mm lesions they can enlarge to several centimetres.
• Patients may develop a multiplicity of such lesions within a sun exposed area. Lesions collide and produce confluent AK over a relatively large area.
• Variations on this theme include brown (pigmented AK), lichen planus-like areas, and exaggerated hyperkeratosis (the hornlike projection known as a cutaneous horn for example).
• They flare and become more erythematous when immunity is suppressed. This may be with systemic disease or its treatment, such as chemotherapy for malignancy, but it can also be the result of much UV light.
• As the years progress, and especially with continued exposure to strong sunlight, about 10% will undergo malignant change.¹ This is more likely in those that are erythematous, elevated and indurated. It may be necessary to remove the layer of keratin to see this.

Diagnosis

This is according to clinical features. Skin biopsy is used where there are features which are high risk for malignant change.

• The roughness is more easily felt than seen, and occurs on sites which have had considerable exposure to the sun, such as a bald scalp, face, dorsum of the hands, and the lower legs.
• There must be signs of solar damage such as solar elastosis shown by yellow thickening of the skin with increased wrinkles.
• Seborrhoeic warts are not so rough and the keratin is more easily picked off.
• Squamous cell carcinomas (SCCs) may arise from solar keratoses but, under the surface keratin, there is a feel that the dermis has been infiltrated.

Images

Solar keratosis on the ear

Solar keratosis on the hand

Differential diagnosis

• Basal cell carcinoma (BCC) and squamous cell carcinomas (SCC) (these are indurated nodular lesions reflecting more rapid growth and tend to be eroded or ulcerated on the surface).
• Seborrhoeic keratosis (produces greasy, brown crusts with sharply demarcated borders and a non-erythematous base. They may occur in areas that are not exposed to sun).
• Bowen's disease (tends to be a large plaque with a sharp outline).
• Discoid lupus erythematosus (shows abnormal pigmentation, dilated follicles and atrophy).

Investigations

No specific investigations are required unless there is suspicion that the lesion may be malignant, when biopsy is needed. This includes:

• Lesions with pronounced hyperkeratosis, increased erythema, or induration.
• Lesions that recur.
• Lesions which are unresponsive to treatment.
• Large confluent lesions.
• Lesions in transplant recipients.
• Lesions in patients with a history of squamous cell carcinoma (SCC).

Management

Many options are open to patients with actinic keratoses (AKs). The natural history of individual lesions studied in the UK suggests that treatment is not universally required on the basis of preventing progression into squamous cell carcinoma (SCC).² However, others feel that prevention of SCC is the main reason for therapy.

• The first part of management is education of the patient about the nature of the lesion and the need to avoid excessive exposure to sunlight. Both sunscreens and protective clothing should be worn. The public's awareness of the dangers of the sun is poor.³
• Cryotherapy with liquid nitrogen is very effective, especially if lesions are few and this can be done in primary care.
• Dermabrasion and chemical peels can be used for facial and scalp lesions. Recurrence 6 months after chemical peels is quite high.²
• Topical 5-fluorouracil can be used. The 5% cream is applied twice daily for 3 to 4 weeks for facial lesions but lesions on other parts of the body need 6 to 8 weeks. The whole area should be treated rather than just the lesions. During treatment the lesions become more red and small subclinical lesions may appear. Red ulcers and crusts are a cosmetic embarrassment but the course should be completed and, within 2 weeks, a smooth complexion replaces the lesions. The course can be repeated and resistant lesions can be treated surgically but resistant lesions should probably be biopsied in case of malignant change.
• Systemic retinoids in very high-risk patients, such as transplant patients, may be justified.²
• PDT is another treatment option.⁴ Topical 5-aminolevulinic acid accumulates preferentially in the dysplastic cells. Exposure to irradiation with light of an appropriate wavelength generates oxygen free radicals that kill the cells. There is pain in the areas treated, similar to that from topical 5-FU. One treatment with PDT appears to be as effective as 5-FU and may be considered in patients with contact sensitivity to 5-FU. The cosmetic result can be better and patients prefer it.⁵

Complications

The most important complication is the progression to malignant change.

Prognosis

Progression to squamous cell carcinoma (SCC) occurs slowly and affects about 10%.¹ The problem is to decide who is in that 10%. It is more likely to occur in the over-70s, and look for the warning signs mentioned above. The cost-effectiveness of treating all solar keratoses to prevent malignant transformation is questionable.⁶ When it does undergo malignant change it tends to be of low aggression and distant metastases are rare.

Prevention

It is important to educate patients that actinic keratoses (AKs) can be reduced or delayed by use of sunscreens but, most importantly, by reducing sun exposure:

• Patients should limit all sun exposure, whether recreational or work-related.
• It is particularly important to avoid sun in tropical areas.
• It is best to seek shade, particularly when the sun is high between 11 am and 3 pm.
• For patients unable to avoid sun exposure, apply a sunscreen (sun protection factor (SPF) 30 or more), and wear protective clothing daily (hats, long sleeves for example).

When to refer

Widespread lesions and suspected malignant change require referral. Patients with multiple and confluent actinic keratoses (AKs) are likely to be at higher risk of nonmelanoma skin cancer, particularly patients with organ transplants.² GPs should be aware of those at high risk of malignant change. In such patients, lesions of an actinic nature or unclear diagnosis should be promptly referred.²

Document references

1. Glogau RG; The risk of progression to invasive disease. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):23-4. [abstract]
2. Guidelines for the management of actinic keratoses, British Association of Dermatologists (2007)
3. MacKie RM; Awareness, knowledge and attitudes to basal cell carcinoma and actinic keratoses among the general public within Europe. J Eur Acad Dermatol Venereol. 2004 Sep;18(5):552-5. [abstract]
4. Chamberlain AJ, Kurwa HA; Photodynamic therapy: is it a valuable treatment option for actinic keratoses? Am J Clin Dermatol. 2003;4(3):149-55. [abstract]
5. Morton C, Campbell S, Gupta G, et al; Intraindividual, right-left comparison of topical methyl aminolaevulinate-photodynamic therapy and cryotherapy in subjects with actinic keratoses: a multicentre, randomized controlled study. Br J Dermatol. 2006 Nov;155(5):1029-36. [abstract]
6. Marks R, Rennie G, Selwood TS; Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet. 1988 Apr 9;1(8589):795-7. [abstract]

Internet and further reading

• British Association of Dermatologists
• Solar keratoses, DermNet NZ (images)
• Spencer JM; Actinic Keratosis, eMedicine, Feb 2009

Acknowledgements