Dermatology & Skin Oncology & Family Medicine
Kératose actinique | Clinique Omicron Québec
Actinic keratosis (AK) - also known as senile or solar keratosis - is a precancerous (or intraepithelial) skin lesion resulting from the proliferation of atypical keratinocytes in the epidermis, induced by chronic exposure to ultraviolet radiation (UV-A and especially UV-B). It is the most common precancerous skin lesion in countries with a predominantly Northern European population, with an estimated prevalence of 11-26 % in adults over 40 in North America and Australia. In Canada, actinic keratosis mainly affects people with phototypes I to III (fair skin), people who have worked or lived outdoors for a long time, and immunocompromised individuals (organ transplants + HIV + immunosuppressive treatments). Actinic keratosis is considered to be a squamous cell carcinoma in situ (or at least a direct precursor) - its clinical importance lies in the risk of progression to invasive squamous cell carcinoma (SCC), estimated at 0.025-0.1 % per lesion per year for an isolated lesion, but reaching 6-10 % in patients with numerous lesions on photodamaged skin. Diagnosis is primarily clinical (appearance + location + context), confirmed by biopsy in case of doubt. Treatment is aimed at eliminating individual lesions (liquid nitrogen cryotherapy + photodynamic therapy) and treating the skin cancerization field (use of topical therapies: 5-FU + imiquimod + ingenol mebutate + tirbanibulin) to reduce the risk of progression to ECC.
Pathophysiology, risk factors and clinical presentation
- Pathophysiological mechanisms and risk factors for actinic keratosis : UV-induced photodamage and mutations: UV-B radiation (280-315 nm) → direct DNA damage to basal keratinocytes → cyclobutane pyrimidine dimers (CPD) → repair errors → characteristic UV mutations (C→T or CC→TT transitions) in tumor suppressor genes → TP53: mutated in over 90 % of KAs → loss of tumor suppression → proliferation of atypical keratinocytes → UV-A (315-400 nm): indirect damage via free radicals (reactive oxygen species - ROS) → DNA damage to melanocytes + keratinocytes → field cancerization phenomenon (Braakhuis 2003 - Cancer Research): chronic sun exposure creates a diffuse mutagenic field in photo-damaged skin → skin surrounding visible KA is already genetically altered (clonal TP53 mutations) even if visually normal → KA lesions emerge in this field → hence the importance of field treatment (topicals over the entire area) rather than lesion-by-lesion treatment alone → risk factors for actinic keratosis: high cumulative sun exposure (outdoor work + agriculture + outdoor sports + geography - equatorial zone + altitude) + phototype I-III: fair skin + red or blond hair + ephelides + light eyes + freckles → Fitzpatrick I: always burns + never tans → chronic inadequate photoprotection → age (accumulation of UV damage) + male sex (higher occupational exposure + lower use of sun protection) + immunodepression : solid organ transplantation (risk × 100 for CEC) → HIV → haemopathies + chronic immunosuppressive treatment (azathioprine + ciclosporin) → multiplied actinic keratoses + accelerated progression to CEC + history of severe sunburn (especially in childhood) + exposure to artificial UV (tanning booths) → IARC : class 1 carcinogen → genodermatoses: xeroderma pigmentosum (UV dimer repair deficiency) → early KA + CEC from childhood onwards
- Clinical presentation, classification and differential diagnosis : clinical appearance of actinic keratoses: erythematous + rough (scaly + keratotic) lesions → located on photoexposed areas → sandpaper sensation to the touch (pathognomonic sign - more reliable than visual appearance) + elective localization: face (forehead + nose + cheeks + temples + lower lip = actinic cheilitis) + scalp (baldness) + nape + ears + forearms + dorsum of hands + décolleté → clinical classification of AKs: grade I (mild): slightly palpable lesion + better perceived by touch than by sight → discrete erythema + fine scales → grade II (moderate): easily palpable and visible lesion → erythema + thick scales + grade III (severe): very thick lesion + keratotic + hyperkeratotic + indurated → grade III → higher risk of progression to ECC + actinic cheilitis : lower lip involvement → whitish + scaly lip + loss of vermilion + higher risk of lip CEC (lip CEC = poor prognosis - higher metastatic potential) + Olsen sign (Olsen classification) + frequently used in Europe; warning signs of progression to squamous cell carcinoma: induration at base (firm or hard palpation) + ulceration or spontaneous bleeding + rapid growth (>1 cm in a few weeks) + attachment to deep planes + intense pruritus + marked peripheral erythema + pain → biopsy mandatory; differential diagnosis: squamous cell carcinoma in situ (Bowen's disease): thick + well-demarcated + salmon-pink keratosis + often larger than KA + biopsy required to differentiate → superficial basal cell carcinoma: erythematous + scaly plaque + discrete pearly border → seborrheic keratosis: golden-brown lesion + «set on the skin» + velvety surface + non-pruritic → often confused with KA → no risk of progression to ECC → common warts + hypertrophic lichen planus + localized psoriasis + pigmented melanocytic nevus
Treatments for actinic keratoses
| Treatment / approach | Data, methods and results | Key studies and recommendations |
|---|---|---|
| Lesion treatment - cryotherapy and curettage Liquid nitrogen - cryotherapy - freezing time - double cycle - curettage - electrodessiccation - shave - biopsy - isolated lesions - recurrence - scars |
Liquid nitrogen cryotherapy - reference lesion treatment for isolated KAs: mechanism: direct application of liquid nitrogen (-196°C) → rapid freezing → formation of intracellular ice crystals → cell lysis → atypical cells (dysplastic keratinocytes) are more sensitive than normal keratinocytes → cell death → healing → new normal cells → technique: direct application with cotton swab or cryogun (cryogen spray) → freezing time: 5-20 seconds depending on thickness and location → allow to thaw then refreeze (double cycle - more effective) → appearance of a white halo of gel around the lesion (mark of the treated area) → inflammatory reaction in the following hours → phlyctene (blister) → crust → healing in 10-21 days → healing rate: 67-88 % per single cycle → improvement with double cycles → advantages: fast + inexpensive + no medication → disadvantages: moderate pain during procedure + risk of hypopigmented scar + no treatment of carcinogenesis field + recurrence if insufficient treatment + local recurrence possible in the medium term → curettage + electrodessiccation: curettage of the lesion with a curette (layer by layer) + electrodessiccation at the base → especially for thick hyperkeratotic lesions + result: scar often visible → less aesthetic on the face → biopsy-exeresis: if doubt about progression to ECC (induration + ulceration + rapid growth) → complete exeresis with margins + anatomopathology → confirmatory treatment + simultaneous diagnosis → photodynamic therapy (PTD): application of a topical photosensitizer (methylaminolevulinic acid - MAL - Metvix + or aminolevulinic acid - ALA) → absorption by atypical cells → irradiation with red light → production of free radicals → cell death of dysplastic keratinocytes → advantage: treatment of the field of carcinogenesis + excellent cosmetic result + disadvantage: intense pain during irradiation + limited outpatient availability + cost → cure rate: 70-90 % → Braathen 2007 - Journal of the European Academy of Dermatology and Venereology: PTD + KA → European reference | Thai 2004 - Archives of Dermatology: cryotherapy + KA → cure rate 67-88 % + Kaufman 2020 - Journal of the American Academy of Dermatology (JAAD): review of KA treatments → cryotherapy + topicals + PTD → recommendations + Braathen 2007 - Journal of the European Academy of Dermatology and Venereology: PTD + KA → efficacy + cosmetic result + EADV (European Academy of Dermatology and Venereology) 2022: guidelines KA → lesional treatment + field → Skin Cancer Foundation + Canadian Society of Dermatology (CSD): recommendations cryotherapy + assessment + INESSS Québec + RAMQ: cryotherapy reimbursed if KA diagnosed by physician |
| Topical therapies - treatment of the cancer field 5-FU fluorouracil - Efudex - imiquimod Zyclara - tirbanibulin Klisyri - ingenol mebutate - diclofenac - inflammatory reaction - treatment duration - cancer field - immunocompetence - results - recurrence |
Topical therapies - treatment of the field of carcinogenesis (field-directed therapy): principle: treat not only visible lesions but also peri-lesional skin containing subclinical UV-induced mutations (mutagenic field) → reduced risk of new KA and progression to CEC on the treated area → 5-fluorouracil (5-FU) cream 5 % (Efudex - Fluoroplex): mechanism: uracil analog → inhibition of thymidylate synthase → blockade of DNA synthesis in proliferating cells → actively proliferating atypical keratinocytes are more sensitive → standard protocol: 2 applications/d × 2-4 weeks → subclinical lesions become visible and inflamed before detaching → expected + normal inflammatory reaction → adverse effects: erythema + edema + erosions + ulcerations + intense desquamation → very uncomfortable but essential for efficacy → results: complete clearance 50-60 % + reduction in number of KA: 70-80 % → Gold 2010 - JAAD: 5-FU + KA → efficacy → imiquimod cream (Zyclara 3.75 % + Aldara 5 %): mechanism: Toll-Like 7 receptor (TLR7) + TLR8 agonist → activation of local innate immunity + production of pro-inflammatory cytokines (IFN-α + IFN-γ + TNF-α) → recruitment of NK cells + cytotoxic T lymphocytes → destruction of atypical keratinocytes → Zyclara 3.75 % protocol: 1 application/d × 2 2-week cycles (with one week off) → Aldara 5 % protocol: 3 applications/week × 4-8 weeks → inflammatory reaction similar to 5-FU → complete clearance 30-45 % + KA reduction: 55-80 % → Lebwohl 2004 - NEJM: imiquimod 5 % + KA → efficacy + Stockfleth 2012 - British Journal of Dermatology: imiquimod 3.75 % + KA → results + tirbanibulin 1 % cream (Klisyri): new dual mechanism → tubulin inhibitor (anti-mitotic) + Src kinase inhibitor → protocol: 1 application/d × 5 days on an area ≤25 cm² → targeted efficacy + less inflammatory reaction than 5-FU + Bourcier 2020 - NEJM Evidence (KX01-AK-003 + KX01-AK-004 RCT): tirbanibulin + KA → complete clearance 44 % vs 5 % placebo + FDA approved 2020 + Health Canada 2022 + ingenol mebutate gel (Picato): mechanism: direct cytotoxicity + PKC activation + immune response → very short protocol (3 days) → now withdrawn from the market (increased risk of skin carcinoma in studies) → NOT recommended → diclofenac gel 3 % (Solaraze): COX-2 inhibitor → reduction of cell proliferation → protocol: 2 applications/d × 60-90 days → minimal inflammatory reaction → modest clearance (30-40 %) → useful if light lesions + patient intolerant of other topicals | Gold 2010 - JAAD: 5-FU cream 5 % + KA → clearance 60 % + Lebwohl 2004 - NEJM: imiquimod 5 % + KA → efficacy demonstrated → reference imiquimod + Stockfleth 2012 - British Journal of Dermatology: imiquimod 3.75 % (Zyclara) + KA → results + Bourcier 2020 - NEJM Evidence (RCT): tirbanibulin + KA → clearance 44 % vs 5 % → FDA 2020 + Health Canada 2022 → Kaufman 2020 - JAAD: review of topical therapies + KA → 5-FU + imiquimod + tirbanibulin → EADV 2022 + NICE 2023: guidelines KA → field-directed therapy + Braakhuis 2003 - Cancer Research: field of carcinogenesis → founding concept → SCD (Canadian Society of Dermatology): recommendations KA → topical + PTD + RAMQ Quebec: 5-FU + imiquimod reimbursed in documented KA + tirbanibulin under evaluation INESSS |
| Prevention, monitoring and special cases - immunocompromised patients Photoprotection - SPF 50 sunscreen - clothing - UV avoidance - annual monitoring - biopsy - progression towards CEC - organ transplant recipients - HIV - acitrethine - nicotinamide - dermatological monitoring - self-examination |
Prevention of actinic keratosis and squamous cell carcinoma - essential measures: daily sun protection: broad-spectrum sun cream (UV-A + UV-B) + SPF (Sun Protection Factor) ≥50 → generous application (2 mg/cm² - amount often underestimated) + renewal every 2h if exposed + protective clothing: UPF (Ultraviolet Protection Factor) ≥50 → wide-brimmed hat (≥7.5 cm) + long-sleeved shirts + CE sunglasses + avoidance of peak UV exposure (10am-4pm) + no UV → IARC tanning booths: tanning booths = class 1 carcinogen + Green 2011 - Lancet: daily application of sunscreen + 50 % reduction in incidence of CEC and melanoma → over 10 years' follow-up → convincing Australian data → nicotinamide (vitamin B3) 500 mg × 2/d. : reduced incidence of new KA + non-melanoma skin carcinomas → Chen 2015 - NEJM (RCT n=386): nicotinamide 500 mg × 2/d + history of skin carcinomas → 23 % reduction in new non-melanoma skin carcinomas → mechanism: enhances UV-induced DNA repair → not expensive + well tolerated → recommended in high-risk patients (numerous KA + history of skin carcinomas); monitoring and follow-up: annual dermatological follow-up (at least) in any patient with KA → or every 6 months if numerous KA + history of CEC → monthly self-examination of the skin → alarm signs of progression → induration + ulceration + rapid growth → immediate biopsy → biopsy indicated if: KA grade III + resistant to treatment + ulcerated + indurated + rapidly growing + lesion in an immunocompromised + on the lip (actinic cheilitis) + ear + ; special cases - immunocompromised patients (organ transplant recipients + HIV + IS treatments): risk × 50-100 times of CEC vs general population → multiplied KA + aggressive + faster progression to CEC → dermatological monitoring every 3-6 months → aggressive field treatment (repeated 5-FU + imiquimod) + acitrethine (oral retinoid - Soriatane) 10-25 mg/d. : reduces incidence of new KA and CEC in transplant recipients → adverse effects: skin dryness + labial + cheilitis + teratogen → strict contraception + Euvrard 1990 - NEJM: retinoids + KA + transplant recipients → reduction in CEC → Otley 2006 - Current Oncology: KA + immunosuppressed → treatment + monitoring + discussion with IS prescribing physician: if possible → reduction or substitution of immunosuppression (sirolimus instead of cyclosporine - less pro-carcinogenic for CEC) | Green 2011 - Lancet: daily sunscreen SPF ≥15 + 10-year follow-up → reduction 50 % CEC + melanoma → convincing Australian data + Chen 2015 - NEJM (RCT n=386): nicotinamide 500 mg × 2/d + history of skin carcinomas → -23 % new non-melanoma skin carcinomas → recommended high-risk patients + Euvrard 1990 - NEJM: retinoids + KA + organ transplant recipients → reduction CEC + Braakhuis 2003 - Cancer Research: field of carcinogenesis + founding concept + EADV 2022 guidelines KA + immunosuppressed: surveillance + treatment + SCD (Canadian Dermatology Society): recommendations annual surveillance + patients at risk + Otley 2006 - Current Oncology: KA + immunosuppressed → treatment + Kaufman 2020 - JAAD: complete review of KA + Skin Cancer Foundation: recommendations photoprotection + self-examination + INESSS Québec + RAMQ: acitrethine reimbursed in defined indications (transplant patients + multiple CEC) |
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Actinic keratosis is better perceived by touch than by sight - the sensation of sandpaper under the fingers on a photo-exposed area is more reliable than visual appearance alone: treatment is not limited to the destruction of isolated visible lesions by cryotherapy, but must also include treatment of the cancer field (topical therapies: 5-FU + imiquimod + tirbanibulin over the entire area) to reduce the emergence of new KAs and the risk of progression to squamous cell carcinoma. Any indurated, ulcerated or rapidly growing KA should be biopsied to exclude invasive squamous cell carcinoma.
Situations requiring urgent biopsy or dermatological consultation
Skin lesion on photoexposed area with induration at base (hard or firm to palpation) + spontaneous ulceration + bleeding on contact + rapid growth over several weeks + irregular OR ill-defined margins → invasive squamous cell carcinoma possible → urgent skin biopsy (punch or shave) before any topical treatment → referral to urgent dermatology → if CEC confirmed → surgical treatment (excision with margins) or Mohs depending on location.
Solid organ transplant patient with multiple actinic keratoses (≥10 lesions) on exposed areas + history of CEC or CBC → appearance of a new rapidly evolving indurated keratotic lesion → quarterly dermatological monitoring + biopsy of suspected lesion + discussion acitrethine (Soriatane) + modification of immunosuppression (ciclosporin → sirolimus substitution if possible) → specialized dermatological oncological referral.
Actinic cheilitis (whitish + scaly lower lip + loss of vermilion) persisting after 4 weeks of topical treatment (5-FU + imiquimod) → lip biopsy → exclude lip ECC (more severe prognosis than cutaneous ECC - high metastatic potential) → dermatological consultation or oral surgery → vermillonectomy if ECC in situ or severe uncontrolled cheilitis.
Consult at Clinique Omicron
Clinique Omicron doctors clinically diagnose actinic keratoses by inspection and palpation of photoexposed areas, perform liquid nitrogen cryotherapy on isolated lesions, prescribe topical field therapies (5-FU + imiquimod + tirbanibulin), refer to dermatologists for lesions suspected of progression, provide photoprotection counseling and screen high-risk patients (immunosuppressed + numerous KAs + history of skin carcinomas). Consultations are available at several points of service in Quebec and via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is provided for information purposes only and does not replace the advice of a physician or dermatologist. Any atypical or progressive skin lesion should be evaluated by a healthcare professional. Skin biopsy is the gold standard for distinguishing actinic keratosis from invasive squamous cell carcinoma.
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