Safety of topical interventions for the treatment of actinic keratosis

ABSTRACT

Introduction: Actinic keratosis (AK) are proliferations of atypical keratinocytes that may eventually progress to cutaneous squamous cell carcinoma. Therefore, AK requires consequent and early treatment. Areas covered: A variety of effective approaches is currently available for the clearance of AK. These interventions may be applied either in a lesion-directed or field-directed mode as AK can occur as single or multiple lesions. Field-directed approaches typically comprise topical drug-mediated interventions which aim at eliminating all visible lesions and also at clearing subclinical changes of the actinically damaged field. However, most treatment options are associated with local adverse events such as erythema, scaling, pain, and rarely with systemic symptoms. This expert review provides a comprehensive and up-to-date overview of the safety considerations of the commonly prescribed topical treatment agents cyclooxygenase inhibitors, 5-fluorouracil, imiquimod, ingenol mebutate, and photodynamic therapy. All these therapies have been proven efficient, yet they differ considerably regarding their safety profile. Expert opinion: In the future, safety concerns will relate to long-term and irreversible adverse drug events instead of application site reactions. In particular, the rate of treatment-associated non-melanoma skin cancers will increasingly come into focus and warrant investigation in postmarketing surveillance trials with a long-term follow-up.

KEYWORDS:

• 5-fluorouracil
• actinic keratosis
• diclofenac
• imiquimod
• ingenol mebutate
• photodynamic therapy

Article highlights

• Multiple interventions are available for the treatment of actinic keratosis that are common lesions of the skin that may progress to cutaneous squamous cell carcinoma

• This expert review provides a comprehensive and up-to-date overview of the safety considerations of the commonly prescribed topical treatment agents diclofenac and other topical cyclooxygenase inhibitors, 5-fluorouracil, imiquimod, ingenol mebutate, and photodynamic therapy

• We propose a classification scheme of treatment-induced adverse events (AE) into local versus systemic AE, mild versus severe AE, and transient versus irreversible AE

• Local application site reactions are observed for almost all interventions and are transient in most cases

• Systemic side effects are mainly observed with 5-fluorouracil and imiquimod and can lead to significant discomfort and premature treatment discontinuation

• Potentially irreversible local side effects such as persistent hyperpigmentation, scarring, or the occurrence of benign and malignant skin tumors should be considered in the treatment selection

This box summarizes key points contained in the article.

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Declaration of interest

C Berking has been member of advisory boards for Almirall Hermal, Biofrontera, Galderma, and Leo Pharma. C Berking has received speaker´s honoraria by Almirall Hermal, Galderma, and Leo Pharma. C Berking has received funding for clinical research by Leo Pharma. MV Heppt has received honoraria by Galderma, Almirall Hermal and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.