Treatment of Persistent Actinic Keratoses With 5-Fluorouracil and Calcipotriene Solutions

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Actinic keratosis (AK) is a common dermatologic diagnosis that requires treatment due to its malignant potential.1 Patients with diffuse AKs are commonly treated with topical medications. However, adherence to topical medications is low and applying topical treatment to hair-bearing areas can be difficult and time consuming, further hindering adherence.^2,3 In this article, we discuss a patient with diff use AKs of the scalp present for 5 years treated with 5-fl uorouracil (5-FU) solution in combination with calcipotriene solution.

Case Report
An 87-year-old woman with a past dermatologic history of basal cell carcinoma (post Mohs micrographic surgery), multiple AKs, and rosacea presented for evaluation of scaly patches on the face and scalp. She was diagnosed with AKs and prescribed 5-FU solution for 2 weeks in August 2017. Over the next 2 years, she continued to follow up in the clinic for persistent AKs and was prescribed 5-FU cream and treated with cryotherapy for the lesions. In September 2019, she still had extensive AKs and was started on blue light photodynamic therapy; however, she did not see any benefit after 1 treatment and decided not to pursue further light therapy.

In December 2019, the patient was started on trichloroacetic acid peels along the frontal hairline, scalp, and forehead. After 2 treatments, she reported that the peels were not efficacious, and she was started again on 5-FU cream for 5 weeks in June 2020.

In October 2020, she returned for follow up and was prescribed imiquimod cream for the face and scalp for 2 weeks. At the next follow-up visit, AKs on the forehead had developed into sores and subsequently healed. At this visit, imiquimod cream was progressed to daily treatment, but she continued to have minimal improvement and persistent actinic damage.

Over the next 2 years, the patient continued to return for follow up of persistent AKs. She was prescribed courses of 5-FU solution or cream or imiquimod cream for 2 weeks up to 1 month in addition to cryotherapy to visible lesions on the face and scalp. Despite these treatments, she continued to return to the clinic with actinic damage and had no improvement.

In early May 2023, she was started on 5-FU solution plus calcipotriene solution twice daily for 1 week. She returned for follow up 2 weeks later and reported improvement in the lesions, despitenusing once daily for 8 days (Figure). At that time, the treatment was continued for 2 more weeks, and she experience some improvement in her scalp. She continued to follow up at 1-week intervals where she presented with improvement in actinic damage but increased erythema. She was seen in July 2023 with increased irritation and reaction to the topical treatment. She was instructed to continue use of combination treatment for 1 week and follow up in 1 month after the skin healed.

Discussion
Adherence to topical treatments is low.^3,4 Poor adherence leads to decreased clinical effect of topical drugs. In the presented case, the patient reported not using the topical treatment as prescribed at her most recent visit. She used the combination of medications only once daily for 8 days instead of twice daily for 7 days as instructed. Close in-person follow up can improve adherence.⁵ The patient presented to the clinic roughly every 4 to 6 months but continued to have limited treatment benefit (Table).

Combination treatment for actinic damage using 5-FU and calcipotriene leads to increased erythema and scaling, but also decreased development of squamous cell carcinomas in the future.⁶ This combination also suppresses skin cancer formation and results in a greater reduction in AK formation compared with 5-FU alone, but treatment courses typically last for 10 to 11 days.⁷

Long treatment courses decrease adherence.^8,9 The patient in this case was on and off treatment for AKs for approximately 5 years. Breaks in treatment were due to reactions to 5-FU, including excessive erythema and crusting after using 5-FU for 1 month. The formulation of medications also plays a role in adherence. Some patients may prefer foams and solutions over creams or ointments.¹⁰ Although this patient was initially prescribed a solution, she was eventually switched to creams and ointments before being finally switched back to solution.

Conclusion
The length of her treatment, types of topical medication, and general difficulty with adherence to topical therapies may have contributed to this patient’s prolonged course. Adherence to topical regimens continues to be a barrier to successful noninvasive treatment of dermatologic disease.

References
1. Chetty P, Choi F, Mitchell T. Primary care review of actinic keratosis and its therapeutic options: a global perspective. Dermatol Ther (Heidelb). 2015;5(1): 19-35. doi:10.1007/s13555-015-0070-9

2. Rajabi-Estarabadi A, Hasanzadeh H, Taheri A, Feldman SR, Firooz A. The efficacy of short-term clobetasol lotion in the treatment of scalp psoriasis. J Dermatolog Treat. 2018;29(2):111-115. doi:10.1080/09546634.2017.1341616

3. Tier HL, Balogh EA, Bashyam AM, et al. Tolerability of and adherence to topical treatments in atopic dermatitis: a narrative review. Dermatol Ther (Heidelb). 2021;11(2):415-431. doi:10.1007/s13555-021-00500-4

4. Patel NU, D’Ambra V, Feldman SR. Increasing adherence with topical agents for atopic dermatitis. Am J Clin Dermatol. 2017;18(3):323-332. doi:10.1007/s40257-017-0261-5

5. Perino F, Fattori A, Piccerillo A, et al. Treatment adherence with diclofenac 3% gel among patients with multiple actinic keratoses: an integrated low intensity intervention program versus standard-of-care. Ital J Dermatol Venerol. 2022;157(2):164-172. doi:10.23736/s2784-8671.21.07111-5

6. Rosenberg AR, Tabacchi M, Ngo KH, et al. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight. 2019;4(6):e125476. doi:10.1172/jci.insight.125476

7. Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127(1):106-116. doi:10.1172/jci89820

8. Miller AC, Adjei S, Temiz LA, Tyring SK. Tirbanibulin for the treatment of actinic keratosis: a review. Skin Therapy Lett. 2022;27(4):4-7.

9. Grada A, Feldman SR, Bragazzi NL, Damiani G. Patient-reported outcomes of topical therapies in actinic keratosis: a systematic review. Dermatol Ther. 2021;34(2):e14833. doi:10.1111/dth.14833

10. Housman TS, Mellen BG, Rapp SR, Fleischer AB Jr, Feldman SR. Patients with psoriasis prefer solution and foam vehicles: a quantitative assessment of vehicle preference. Cutis. 2002;70(6):327-332.