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Guidelines for the treatment of actinic keratosis

Presentation

  • Clinically, actinic keratoses (AKs) typically present as scaly or keratotic patches, papules, or plaques on an erythematous base
  • Palpation reveals a sand paper-like texture. The diameter usually does not exceed 1 cm, although in some patients lesions can be numerous and confluent
  • Lesions usually have the same colour as the surrounding skin, but may also present as pink, red or brownish patches, papules or plaques
  • Surrounding skin may show signs of chronic sun damage, including telangiectasias, dyschromia, elastosis, and wrinkles
  • AKs may occur as single lesions, as multiple lesions, or in the context of field cancerisation
  • Risk factors for the development of AK include:
    • advanced age
    • male gender
    • cumulative sun exposure
    • fair skin type
    • concomitant immunosuppression
    • genetic syndromes (e.g. xeroderma pigmentosum, albinism, Rothmund-Thompson syndrome)
  • There might be significant variability from country to country, not only in regulatory approval and the availability of interventions, but also in terms of health care providers and insurance systems. Thus, these international guidelines are intended to be adapted to the national or regional conditions

Diagnosis

  • Clinical diagnosis of AK is recommended for most of the lesions. The following clinical classification is recommended for assessing single AK lesions:
    • grade 1: mild (slight palpability, with actinic keratoses felt better than seen)
    • grade 2: moderate (moderately thick actinic keratoses that are easily seen and felt)
    • grade 3: severe (very thick and/or obvious actinic keratoses)
  • Besides the differentiation of AK and (invasive) squamous cell carcinoma, possible differential diagnoses of AK include:
    • basal cell carcinoma
    • Bowen’s disease
    • porokeratosis
    • nevus
    • verruca vulgaris
    • discoid lupus erythematosis
    • large cell acanthoma
    • psoriasis
    • solar lentigo
    • lentigo maligna may be a differential diagnosis for pigmented AK lesions
  • A biopsy and histological assessment is recommended in the following cases:
    • clinical diagnosis unclear with respect to the underlying disease
    • clinical diagnosis unclear with respect to the biologic behaviour of the lesion. Clinical parameters that may indicate the progression of AK to invasive squamous cell carcinoma:
      • major criteria: ulceration, induration, bleeding, diameter >1 cm, rapid enlargement, erythema
      • minor criteria: pain, palpability, hyperkeratoses, pruritus, pigmentation
    • unresponsive AK lesions (no regression or early recurrence despite adequate therapy)
  • The following subgroups should be considered separately—patients with:
    1. single AK lesions—at least one and not more than five palpable or visible AK lesions per field or affected body region
    2. multiple AK lesions—at least six distinguishable AK lesions in one body region or field
    3. field cancerisation—at least six AK lesions in one body region or field, and contiguous areas of chronic actinic sun damage and hyperkeratosis
    4. concomitant immunosuppression—AK at any of the above-mentioned severity degrees and concomitant immunosuppression (e.g. due to chronic immunosuppressive medication or specific diseases affecting the function of the immune system, such as malignant hematologic disorders)
Overview of the recommendations for the treatment of AK
Single AK lesionsMultiple AK lesionsField cancerisationImmunocompromised patients with AK
≥1 and ≤5 palpable or visible AK lesions per field or affected body region ≥6 distinguishable AK lesions in one body region or field ≥ 6 AK lesions in one body region or field, and contiguous areas of chronic actinic sun damage and hyperkeratosis AK at any of the mentioned severity degrees and a concomitant condition of immunosuppression
Sun protection in all patient subgroups
STRONG RECOMMENDATION FOR THE USE OF AN INTERVENTION
  • Cryotherapy
  • 0.5% 5-FU
  • 3.75% imiquimod
  • Ingenol mebutate 0.015%/0.05%
  • MAL-PDT, ALA-PDT
WEAK RECOMMENDATION FOR THE USE OF AN INTERVENTION
  • Curettage*
  • 0.5% 5-FU, 5% 5-FU
  • 0.5% 5-FU + 10% SA*
  • 3.75% imiquimod
  • 5% imiquimod
  • Ingenol mebutate 0.015/0.05%
  • ALA-PDT, MAL-PDT
  • Cryotherapy
  • 3% diclofenac in 2.5% HA
  • 5% 5-FU
  • 0.5% 5-FU + 10% SA*
  • 5% imiquimod, 2.5% imiquimod
  • CO2-laser, Er:YAG-laser
  • Cryotherapy
  • Curettage*
  • 5% 5-FU
  • 5% imiquimod
  • ALA-PDT, MAL-PDT
NO RECOMMENDATION MADE WITH RESPECT TO AN INTERVENTION
  • 3% diclofenac in 2.5% HA
  • 2.5% imiquimod
  • CO2-laser, Er:YAG-laser
  • Curettage*
  • 3% diclofenac in 2.5% HA
  • 0.5% 5-FU
  • 0.5% 5-FU + 10% SA
  • 2.5% imiquimod, 3.75% imiquimod
  • Ingenol mebutate 0.015%/0.05%
WEAK RECOMMENDATION AGAINST THE USE OF AN INTERVENTION
  • CO2-laser, Er:YAG-laser
* discrete, hyperkeratotic AK lesions.
single or multiple discrete AK lesions, not for treatment of field cancerisation.
For immunosuppression, different clinical situations may exist, e.g. iatrogenic medical immunosuppression after organ transplantation, iatrogenic medical immunosuppression because of autoimmune disorders, immunosuppression due to other reasons (haematologic disorders, AIDS etc). Depending on the underlying disease, special care has to be given to the selection of the treatment to avoid (auto-) immunstimulation that may lead to a worsening of the underlying condition.
AK=actinic keratosis; 5-FU=fluorouracil; SA=salicylic acid; MAL-PDT=methyl aminolevulinate photodynamic therapy;
ALA-PDT=aminolevulinic acid photodynamic therapy; Er:YAG=erbium-doped yttrium aluminium garnet; HA=hyaluronic acid.

Photoprotection

  • Protection from sunlight is an integral part of management of patients with AK
  • Photoprotection strategies include:
    • avoiding sunlight during peak UVB hours of 10 am to 2 pm
    • wearing photoprotective outfit (including clothing, widebrimmed hat, and sunglasses)
    • applying broad spectrum sunscreens with SPF 30 or above
  • When available, UV index (low: 1–2, to extreme: 11+) can be used as a guide of photoprotection

full guidelines available from…
www.euroderm.org/edf/index.php/edf-guidelines/category/5-guidelines-miscellaneous

International League of Dermatological Societies (ILDS) in cooperation with the European Dermatology Forum (EDF). Evidence and consensus based (S3) guidelines for the treatment of actinic keratosis. Long Version (online supplement) 2015
Werner RN, Stockfleth E, Connolly SM et al. Evidence-and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis—International League of Dermatological Societies in cooperation with the European Dermatology Forum—Short version. J Eur Acad Dermatol Venereol 2015 Sep 14. doi: 10.1111/jdv.13180. (Epub ahead of print)
First included: October 2015.