In short Article

Treatment of actinic keratosis with 5-FU cream

Actinic keratosis is a skin disorder which occurs in about 30% of persons aged over 50 years (more commonly among men). The main causative factor is exposure to sunlight. If not treated, there is a risk of malignant degeneration. The risk of squamous cell carcinoma is up to 20%, depending on the extent of the lesions. Based on its effectiveness and cost considerations, the use of 5-fluorouracil cream (5-FU cream) twice daily for 4 weeks remains a suitable treatment of first choice, especially if liquid nitrogen (cryotherapy) or watchful waiting is not (or no longer) an option. When using 5-FU cream, it is important to be aware of common local adverse effects such as erythema, local pain, itch, skin irritation and desquamation. The Guideline on suspicious skin disorders, issued by the Dutch College of General Practitioners, mentions 5-FU cream as a treatment option for actinic keratosis.

  • Dutch research has shown that 4 weeks of treatment with 5-fluorouracil cream (5-FU cream) is the most effective field-directed therapy for actinic keratosis in the head-neck region, compared to ingenol mebutate gel, imiquimod cream or methyl-5-aminolevulinate cream plus photodynamic therapy.
  • No known studies have shown that 4 weeks of 5-FU cream is effective in preventing malignant degeneration of actinic keratosis (squamous cell carcinoma).
  • From a cost perspective, the option of treating actinic keratosis with 5-FU cream is to be preferred over ingenol mebutate gel, imiquimod cream or methyl-5-aminolevulinate cream plus photodynamic therapy.
  • For variants of actinic keratosis with few lesions, local cryotherapy remains a cheap therapeutic option, for which there is sufficient evidence of effectiveness.
  • Watchful waiting is a justifiable option for small lesions that can be easily monitored by the patient.

  1. Siegel JA, Korgavkar K, Weinstock MA. Current perspective on actinic keratosis: a review. Br J Dermatol. 2017;177(2):350-8.
  2. Nederlands Huisartsen Genootschap. NHG-Standaard Verdachte huidafwijkingen 2017 [Available from:
  3. Nederlandse Vereniging voor Dermatologie en Venerologie. Richtlijn NVDV Actinische keratose 2018 [Available from:
  4. Werner RN, Stockfleth E, Connolly SM, Correia O, Erdmann R, Foley P, 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;29(11):2069-79.
  5. Jansen MHE, Kessels J, Nelemans PJ, Kouloubis N, Arits A, van Pelt HPA, et al. Randomized Trial of Four Treatment Approaches for Actinic Keratosis. N Engl J Med. 2019;380(10):935-46.
  6. Flohil SC, van der Leest RJ, Dowlatshahi EA, Hofman A, de Vries E, Nijsten T. Prevalence of actinic keratosis and its risk factors in the general population: the Rotterdam Study. J Invest Dermatol. 2013;133(8):1971-8.
  7. Werner RN, Sammain A, Erdmann R, Hartmann V, Stockfleth E, Nast A. The natural history of actinic keratosis: a systematic review. Br J Dermatol. 2013;169(3):502-18.
  8. Navarrete-Dechent C, Marchetti MA, Nehal KS. Treatment Approaches for Actinic Keratosis. N Engl J Med. 2019;380(23):2275.
  9. College ter Beoordeling van Geneesmiddelen. Geneesmiddeleninformatiebank 2019 [Available from:
  10. Zorginstituut Nederland. Farmacotherapeutisch Kompas 2019 [Available from:

*The literature refers to the Dutch text


  • Anton J.F.A. Kerst, Hein J.E.M. Janssens