Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 19/03/2015
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Sherrif F. Ibrahim and Marc D. Brown
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Actinic keratoses (AK) are ill-defined pink to skin-colored, scaly papules found on chronically sun-exposed areas in light-skinned individuals. They most frequently appear on the face, ears, balding scalp, extensor forearms, and dorsal hands. AKs are a strong predictor for the development of squamous cell carcinoma (SCC) and, to a lesser extent, basal cell carcinoma. Australians have the highest reported prevalence, which approaches 60%, and in the US AKs are the second most common reason for visits to the dermatologist.
Actinic keratoses are common dysplastic intra-epidermal lesions that are considered to be precursors to SCC. Reports have varied as to the rates of progression to invasive SCC, from 0.025% to over 25% per year, and AKs are commonly located adjacent to SCC histologically. For these reasons, most practitioners advocate the treatment of AKs, as considerable morbidity and potential mortality can be associated with invasive disease. However, there have been no randomized controlled studies demonstrating a reduction in the frequency of SCC with treatment of AKs.
The diagnosis of AK is primarily clinical, and because of their superficial nature, a variety of effective management approaches exist. Biopsy of suspected AKs is typically not warranted; however, in patients with a history of multiple skin cancers, immunosuppressed patients, and lesions in high-risk areas such as the lip or ear, clinicians should have a low threshold for biopsy to rule out invasive SCC. Indications for biopsy include tenderness, rapid growth or thickening of lesions, bleeding, hyperkeratosis, and failure to respond to treatment.
Prevention of AKs through sun avoidance and diligent use of broad-spectrum sunscreens and blocking agents is an important aspect of management. This has been shown to prevent the development of new AKs and reduce the incidence of non-melanoma skin cancers.
With cumulative sun exposure and advancing age, rates of AK development increase, necessitating either ablative or topical treatment. Cryotherapy with liquid nitrogen is by far the most commonly employed therapeutic modality because it can be performed quickly and effectively in the office setting. However, given the common appearance of AKs on a background of diffuse actinic damage, individual lesions may be poorly defined and involve large, contiguous areas requiring field treatment with topical agents such as 5-fluorouracil (5-FU) or imiquimod. The latter has recently been shown to have high rates of treatment success with durable results and has become an accepted first-line therapy with a newer 3.75% formulation recently introduced. A novel agent, ingenol mebutate, is derived from the Euphorbia peplus plant and has been approved as an additional topical agent for the field treatment of AKs. The advantages of topical approaches are that they are patient-administered, non-invasive, carry little risk of scarring or pigmentary change, and can be used for anatomically difficult or cosmetically sensitive areas. However, these agents require adequate patient compliance and are often accompanied by prolonged erythema lasting several weeks. Photodynamic therapy (PDT) with aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) has continued to become more widespread, given its proven therapeutic results and excellent cosmetic outcome. PDT offers a physician-administered approach to field treatment with shorter periods of inflammation and erythema than several topical agents, and thus many studies indicate higher patient satisfaction. Variations in the light dose, light source, sensitizing agent and its application time, and frequency of treatments may improve efficacy. Head-to-head trials of different treatment approaches are difficult to perform, as variations in treatment protocols make direct comparisons challenging. Recently, there has been a growing trend towards combination therapy, such as topical agents either before or after cryotherapy, or sequential use of multiple topical modalities with varying mechanisms of action. Other approaches such as laser resurfacing, chemical peels, and dermabrasion may be considered in certain situations when lesions have failed the above treatments, or if severe photodamage is present. Finally, for recalcitrant or hyperkeratotic lesions, curettage or excision may be appropriate.
In selected cases:
Biopsy
Ehrig T, Cockerell C, Piacquadio D, Dromgoole S. Dermatol Surg 2006; 32: 1261–5.
A total of 271 clinically diagnosed AKs were biopsied. Clinical diagnosis was in agreement with histology 91% of the time, with about one in 25 lesions revealing invasive SCC.
Venna SS, Lee D, Stadecker MJ, Rogers GS. Arch Dermatol 2005; 141: 507–9.
Seventeen of 23 lesions (74%) with classic features of AK in patients with a history of previous skin cancer were confirmed histologically. Five lesions (22%) were shown to be SCC.
Actinic keratoses are typically diagnosed clinically. However, there should be a low threshold to biopsy tender, hyperkeratotic, large, or recalcitrant lesions to exclude malignancy.
Darlington S, Williams G, Neale R, Frost C, Green A. Arch Dermatol 2003; 139: 451–5
In this Australian study, 1621 adults were randomized to either daily use of sunscreen or application at their usual discretionary rate. There was a 24% reduction in AKs in the daily use group.
Thompson SC, Jolley D, Marks R. N Engl J Med 1993; 14: 1147–51.
In a 6-month randomized, placebo-controlled trial of 588 patients in Australia, SPF 17 sunscreen applied daily was found to both reduce the development of new AKs and increase the remission of existing AKs compared to a vehicle cream.
Thai K, Fergin P, Freeman M, Vinciullo C, Francis D, Spelman L, et al. Int J Dermatol 2004; 43: 687–92.
In this prospective multicenter study, 90 patients with 421 AKs on the face and scalp were treated with cryotherapy with a single freeze–thaw cycle using different freeze times. The patients were reviewed 3 months later. Overall, the complete response (CR) rate was 67.2%, varying from 39% for freeze times less than 5 seconds to 83% for times longer than 20 seconds. The authors also found that hypopigmentation was present in 29% of CR lesions. Patients rated cosmetic outcomes as good to excellent for 94% of CR lesions.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
Sunscreens
Cryosurgery
Topical 5-FU
Imiquimod
Photodynamic therapy
