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#204 Actinic Keratosis: Out Damned Spot!


CLINICAL QUESTION
QUESTION CLINIQUE
Which commonly used topical therapies (cryotherapy, 5-Fluorouracil, imiquimod, or ingenol) are preferred for actinic keratosis?


BOTTOM LINE
RÉSULTAT FINAL
Topical treatments have similar efficacy to each other and will result in complete clearance of lesions beyond placebo for every 3-4 patients treated. Clearance rates may reach ~90% depending on strength of cream (5% 5-fluorouracil [5FU] greater than 0.5%), longer duration of therapy, and complexity of lesion. The effects on cancer incidence have not been studied.



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EVIDENCE
DONNÉES PROBANTES
Five systematic reviews.1-5 Most complete: 83 Randomized Controlled Trials (RCTs), 10,036 participants, >350 comparisons of all interventions:1 
  • Versus placebo (complete clearance): 
    • 0.5% 5-FU (three RCTs, 522 patients):
      • 30% versus 1.5% after 1-4 weeks of treatment with four weeks follow-up. Number Needed to Treat (NNT)=4. 
    • 5% imiquimod (11 RCTs, 2,880 patients): 42% versus 5%, NNT=3. 
      • Decreased roughness, scaliness/dryness: 55% versus 18%, NNT~3. 
    • Ingenol mebutate (two RCTs, 456 patients): 38% versus 7%, NNT=4. 
      • Pigmentation changes: No difference. 
  • Versus cryotherapy (complete clearanceone RCT, 51 patients):
    • 5% 5-FU: 96% versus 68%, NNT=4. 
      • “Excellent” cosmetic outcomes: No difference. 
    • 5% imiquimod84% versus 68%, no statistical difference. 
      • “Excellent” cosmetic outcomes 81% versus 4%, NNT=2. 
  • Versus 5% 5-FU (complete clearance): 
    • 5% imiquimod (two RCTs, 89 patients): Larger study, 85% versus 88%, no statistical difference.  
      • “Excellent” cosmetic outcome (one RCT, 50 patients): 81% versus 4%, NNT=2. Results unreliable.  
Context: 
  • Large, extensive, or atypical lesions often excluded from RCTs. 
  • No RCTs have investigated effects of treatments on cancer incidence. 
  • Rate of progression to squamous cell carcinoma (individual lesions) varies0-0.53%/year depending on sun exposure, age, and number/size of lesions.6  
  • Hypertrophic, painful, atypically broad lesions may progress faster.5  
  • Guidelines suggest cryotherapy for smaller, isolated lesions, and topical creams (field-directed treatment) for 4 clustered lesions.7   
  • Whether creams after cryotherapy improve effectiveness over creams alone is unclear.7  
  • Adverse effects include (all): Localized pain, erythema, swelling, vesicles/bullae, pigmentation changes.   
    • Cryotherapy: Rarely scars/hair loss. 
    • Creams: Burning/itchingerosions. 
      • 5-FU: Ulcers, toxic agranulocytosis (very rare). 
      • Imiquimod: Photosensitivity, systemic effects if applied on larger areas (joint/muscle pain, fever, headache). 
      • Ingenol: Hypersensitivity. 


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Author(s)
Auteur(s)
  • Adrienne J Lindblad BSP ACPR PharmD
  • Qudsiyyah Bhayat MBChB CCFP FCFP

1. Gupta AK, Paquet M, Villanueva E, et al. Cochrane Database Syst Rev. 2012; 12:CD004415.

2. Stockfleth E, Sibbring GC, Alarcon I. Acta Derm Venereol. 2016; 96(1):17-22.

3. Vegter S, Tolley K. PLoS ONE. 2014; 9(6):e96829.

4. Gupta AK, Paquet M. Br J Dermatol. 2013; 169:250-9.

5. Nashan D, Meiss F, Müller M. Eur J Dermatol. 2013; 23(1):14-32.

6. Werner RN, Sammain A, Erdman R, et al. Br J Dermatol. 2013; 169:502-18.

7. Poulin Y, Lynde CW, Barber K, et al. J Cut Med Surg. 2015; 19(3):227-38.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.