Actinic keratosis: A clinician’s guide to diagnosis and treatment

  • Cleveland Clinic Journal of Medicine
  • September 2026,
  • 93
  • (9)
  • 541-549;
  • DOI: https://doi.org/10.3949/ccjm.93a.26005

CME/MOC

  • Release date: September 1, 2026
  • Expiration date: August 31, 2027
CME/MOC Accreditation Information.

ABSTRACT

Actinic keratoses are common premalignant skin lesions caused by chronic exposure to ultraviolet light. Early recognition and effective treatment are key to preventing them from progressing to invasive squamous cell carcinoma. The authors of the article outline an individualized approach for clinicians based on the number of lesions (lesion burden), their surface area (field cancerization), and patient preference.

KEY POINTS

  • The diagnosis is typically clinical, but dermoscopy or biopsy can help in uncertain cases or if lesions do not respond to treatment.

  • Lesion-directed therapies include cryotherapy and surgical excision, while field-directed treatments include 5-fluorouracil, imiquimod, diclofenac, tirbanibulin, and photodynamic therapy—the latter offering excellent cosmetic outcomes and new painless protocols.

  • Preventive strategies, including sun protection and the use of oral nicotinamide, can reduce rates of lesion formation and recurrence.

Actinic keratosis, also known as solar keratosis, is an intraepidermal neoplasm resulting from damage due to chronic exposure to ultraviolet light. Being a precursor to cutaneous squamous cell carcinoma, it warrants active management.1 It is commonly encountered in clinical practice, particularly among older adults with significant cumulative sun exposure.2

Here, we outline a practical, evidence-based approach to diagnosing and managing actinic keratosis with both established treatments and newer emerging therapies.

EPIDEMIOLOGY AND RISK FACTORS

Actinic keratosis is among the most common skin conditions in the United States. Reported prevalence rates vary, but as a round number we can say that about one-fifth of adults over age 30 have these lesions, with rates increasing with age.2 Risk factors for it, in addition to advanced age, include the following:

Chronic sun exposure, the most significant risk factor, damages DNA in keratinocytes, leading to mutations and abnormal cellular proliferation. The risk is cumulative over one’s lifetime.

Lighter skin. People with Fitzpatrick skin phototypes I and II, characterized by lighter pigmentation and less melanin-mediated photoprotection, are at particularly high risk.3

Male sex. Men are disproportionately affected, likely because they accumulate greater lifetime ultraviolet exposure through occupational and recreational activities, are less likely to consistently practice sun protection, and more commonly have androgenetic alopecia, resulting in increased sun exposure of the scalp.3

Immunosuppression, whether from medical conditions or immunosuppressive medications, significantly increases susceptibility to actinic keratosis by impairing the immune system’s ability to detect and eliminate atypical cells. Organ transplant recipients and other chronically immunosuppressed patients often develop more numerous, aggressive, and treatment-resistant lesions, with a substantially higher risk of progression to invasive squamous cell carcinoma. Many of these patients require closer surveillance and earlier field-directed therapy.4

Environmental factors such as living in regions with high ambient ultraviolet radiation levels (eg, near the equator or at higher altitudes) further compound risk.2,4

CLINICAL PRESENTATION AND DIAGNOSIS

Actinic keratoses present as rough, scaly, erythematous papules or plaques, most commonly on sun-exposed areas such as the face, scalp, ears, neck, forearms, and hands (Figure 1). They may be easier to detect by palpation than by visual inspection. Variants include hypertrophic, atrophic, pigmented, and lichenoid forms.5

Actinic keratosis. Scaly macule on the left helix of the ear (arrow); dermoscopy reveals targetoid follicles (follicular plugs with halos), rosettes, white-yellow scale, and a red pseudonetwork with out-of-focus vessels (strawberry pattern).
Figure 1

Actinic keratosis. Scaly macule on the left helix of the ear (arrow); dermoscopy reveals targetoid follicles (follicular plugs with halos), rosettes, white-yellow scale, and a red pseudonetwork with out-of-focus vessels (strawberry pattern).

Dermoscopy can aid in diagnosis, revealing a “strawberry pattern” on facial lesions (red pseudonetwork with prominent follicles). If lesions are rapidly growing, painful, bleeding, ulcerated, or refractory to treatment, biopsy should be considered to rule out invasive squamous cell carcinoma.2

Squamous cell carcinoma in situ (Bowen disease) may clinically overlap with hypertrophic actinic keratosis but often presents as a larger, more sharply demarcated erythematous, scaly plaque with greater induration, persistent scaling, and progressive enlargement. Lesions that are unusually thick, tender, treatment-resistant, or clinically evolving should prompt biopsy to exclude squamous cell carcinoma in situ or invasive squamous cell carcinoma.6

DIFFERENTIAL DIAGNOSIS

Several dermatologic conditions can mimic the clinical appearance of actinic keratosis, but each has distinguishing features that aid in accurate diagnosis.

Seborrheic keratoses are typically well-demarcated, waxy or verrucous lesions with a “stuck-on” appearance, often varying in color from tan to dark brown or black, and lack the erythema, scaliness, and rough texture characteristic of actinic keratoses (Figure 2).7

Seborrheic keratosis. Brown, stuck-on plaque on the left forearm; dermoscopy reveals milia-like cysts (white and yellow dots), comedo-like openings (black and brown dots or craters), and fissures and ridges forming a network-like pattern.
Figure 2

Seborrheic keratosis. Brown, stuck-on plaque on the left forearm; dermoscopy reveals milia-like cysts (white and yellow dots), comedo-like openings (black and brown dots or craters), and fissures and ridges forming a network-like pattern.

Verruca vulgaris (common warts) tends to present as firm, hyperkeratotic papules with a verrucous surface, frequently on acral sites, and may exhibit pinpoint black dots (thrombosed capillaries) on dermoscopy (Figure 3), features not observed in actinic keratosis.7

Verruca vulgaris. Filiform verrucous plaque on the left arm; dermoscopy reveals filiform projections with thrombosed capillaries.
Figure 3

Verruca vulgaris. Filiform verrucous plaque on the left arm; dermoscopy reveals filiform projections with thrombosed capillaries.

Lichen planus, a pruritic inflammatory condition, often manifests as flat-topped, violaceous papules with Wickham striae and typically involves the wrists, ankles, or mucous membranes rather than sunexposed areas.2

Discoid lupus erythematosus may resemble hypertrophic actinic keratosis but usually presents as erythematous, scaly plaques with follicular plugging and postinflammatory dyspigmentation, often in a photo-distributed pattern; biopsy may demonstrate interface dermatitis and basement membrane thickening.8

Early squamous cell carcinoma can be difficult to distinguish from actinic keratosis clinically, but may show increased induration, tenderness, hyperkeratosis, or rapid growth—features suggestive of progression beyond intraepidermal atypia (Figure 4). If the diagnosis is uncertain, biopsy is warranted to exclude invasive malignancy or other mimickers.7

Squamous cell carcinoma in situ. Erythematous, thin plaque on the left lower leg; dermoscopy reveals diffuse glomerular (coiled) vessels arranged in a linear fashion.
Figure 4

Squamous cell carcinoma in situ. Erythematous, thin plaque on the left lower leg; dermoscopy reveals diffuse glomerular (coiled) vessels arranged in a linear fashion.

LESION-DIRECTED THERAPIES

Treatment should be tailored based on lesion burden, location, patient comorbidities, cosmetic concerns, and likelihood of patient adherence to the regimen. In general, lesion-directed therapies are preferred for patients with a single or a few discrete actinic keratoses, whereas field-directed therapies are favored for patients with multiple lesions or evidence of field cancerization because they treat both clinically apparent and subclinical disease. Combination therapy is often appropriate for patients with a high lesion burden, using lesion-directed treatment for thicker or symptomatic lesions together with field-directed therapy for the surrounding actinically damaged skin.

Cryotherapy

Cryotherapy is commonly used for isolated lesions. Performed in the office setting without anesthesia, it is done by applying liquid nitrogen with a spray applicator or other device at −196 °C, typically in 1 to 3 freeze-thaw cycles. Ice crystals form inside and outside of cells, leading to destruction of keratinocytes through cryolysis, vascular stasis, and apoptosis.

Reported complete clearance rates vary from 39% to 76%, with higher efficacy observed when combined with topical field therapies such as 5-fluorouracil or photodynamic therapy, achieving lesion-specific reductions of 73% to 89%.9 The efficacy is influenced by technical factors, including the number of freeze-thaw cycles, distance from the applicator to the lesion, and lesion thickness.

Common side effects are mild pain, stinging, erythema, blistering, and, occasionally, postinflammatory hypopigmentation, particularly in people with darker skin.1

Surgery

Surgical excision is not the first-line therapy for actinic keratosis but should be considered for lesions that are atypical, suspicious, or unresponsive to standard treatments. Histopathologic evaluation is crucial in these cases to confirm the diagnosis and rule out invasive squamous cell carcinoma or other malignancies.6 Surgery provides definitive management when there is diagnostic uncertainty or when rapid clearance of lesions is desired.2

FIELD-DIRECTED THERAPIES

These approaches are appropriate for patients with multiple lesions in areas of actinic damage (field cancerization).

The decision as to which field-directed therapy to use should be individualized based on lesion burden, treatment duration, expected local reactions, cosmetic outcomes, patient adherence, insurance coverage, and cost considerations. Shorter-duration therapies such as tirbanibulin or photodynamic therapy may improve adherence, while cryotherapy and topical agents such as 5-fluorouracil remain highly effective and relatively cost-efficient.

5-Fluorouracil

Topical 5-fluorouracil is a pyrimidine antimetabolite that blocks thymidylate synthase, disrupting DNA synthesis and RNA function in atypical keratinocytes. It is available as 0.5% to 5% creams or solutions, typically applied once or twice daily for 2 to 4 weeks, with some protocols extending to 12 weeks depending on lesion burden and tolerance. Clearance rates after 4 weeks of treatment were 48% and 58% with 0.5% cream in 2 studies,10,11 with minimal systemic absorption.

Expected adverse effects—erythema, pain, burning, crusting, and erosions—usually do not limit adherence but can present difficulties for patients who have lesions in sensitive areas such as the face. No dose adjustment is required in elderly patients, but careful monitoring is recommended in those with diabetes and sensory neuropathy. Clinicians should review potential drug interactions because antivirals (eg, brivudine), phenytoin, and methotrexate can increase systemic toxicity.1

Combination of 5-fluorouracil and calcipotriene

Combination therapy with topical 5-fluorouracil and calcipotriene has emerged as an effective short-course field therapy for actinic keratosis. Calcipotriene is thought to augment a T-cell–mediated immune response against dysplastic keratinocytes, enhancing the efficacy of 5-fluorouracil. Short treatment courses, often 4 to 7 days, can substantially reduce lesions while shortening overall treatment duration compared with traditional 5-fluorouracil monotherapy. Common adverse effects include erythema, crusting, and localized irritation at treatment sites.12

Imiquimod

Imiquimod is a topical immune-response modifier that targets toll-like receptors on dendritic cells, macrophages, monocytes, and Langerhans cells, stimulating both innate and adaptive immunity, driving the release of inflammatory cytokines and chemokines, and ultimately promoting clearance of atypical keratinocytes. It also exerts a direct apoptotic effect on tumor cells.

Imiquimod is available in 5%, 3.75%, and 2.5% cream formulations to treat actinic keratosis on the face or scalp in immunocompetent adults. The 5% cream is typically applied 3 times weekly to areas up to 25 cm2 for 4 weeks, with a second 4-week cycle if needed.1 The 3.75% and 2.5% formulations are used once daily in 2 treatment cycles—either 2 weeks on/2 weeks off/2 weeks on, or two 3-week cycles separated by 3 weeks off. These lower-strength preparations allow treatment of larger fields, such as the entire face or balding scalp, and provide similar efficacy with shorter overall treatment duration and a lower rate of local reactions.13

Diclofenac 3% gel

Diclofenac 3% gel in 2.5% hyaluronic acid is approved for treating actinic keratosis of the face and scalp, particularly for field-directed treatment of clustered lesions. As a cyclooxygenase-2 inhibitor, diclofenac down-regulates prostaglandin-mediated pathways that support keratinocyte proliferation, angiogenesis, and resistance to apoptosis.

Applied twice daily for 60 to 90 days in a clinical trial, diclofenac yielded a complete clearance rate of 41% at the end of the treatment and up to 58% at 1-month follow-up.14 A Cochrane review found its efficacy comparable to that of other topical field therapies (5-fluorouracil, imiquimod, ingenol mebutate) with excellent tolerability and favorable cost-effectiveness.15

Adverse effects—mild pruritus, erythema, edema, and xerosis—are usually self-limited. Diclofenac should be avoided in patients with asthma that is exacerbated by nonsteroidal anti-inflammatory drugs. In practice, its gentle side-effect profile makes it attractive for elderly patients or those in public-facing professions, although the long treatment course can challenge adherence.1

Piroxicam

Piroxicam is a nonsteroidal anti-inflammatory drug similar to diclofenac that has also been shown to be effective in treating actinic keratosis. It is a potent cyclooxygenase-1 inhibitor that also suppresses key proteinases implicated in tumor progression.

In a clinical study, twice-daily application of a topical formulation containing 0.8% piroxicam combined with a broad-spectrum sunscreen for 6 months produced significant improvement in actinic keratosis.16 Complete clearance was achieved in 55% of patients, and this response was sustained 1 year after treatment. Reported adverse effects were limited to mild local irritation.

Further controlled trials are warranted to confirm the efficacy and tolerability of topical piroxicam relative to standard therapies. Piroxicam is not approved by the US Food and Drug Administration (FDA) for treating actinic keratosis and is primarily used off-label, particularly in Europe.17

Tirbanibulin

Tirbanibulin is a non–ATP-competitive Src kinase inhibitor that also disrupts tubulin polymerization in actively dividing keratinocytes. The FDA-approved regimen consists of 1% tirbanibulin ointment applied once daily for 5 consecutive days to actinic keratosis lesions and field cancerization on the face or scalp. Phase 3 trials showed complete clearance in 44% to 54% of patients at 2 months, with most experiencing transient local reactions.1,18 However, about half of lesions recurred by 1 year.

Photodynamic therapy

Photodynamic therapy selectively targets dysplastic keratinocytes using a photosensitizing agent, most commonly 5-aminolevulinic acid, followed by activation with visible light. On illumination, 5-aminolevulinic acid is converted into protoporphyrin IX within neoplastic cells, generating reactive oxygen species.

Photodynamic therapy is FDA-approved for actinic keratosis of the face and scalp and is particularly useful for treating multiple lesions and large areas of field cancerization.19

Historically, conventional photodynamic therapy protocols involved long 5-aminolevulinic acid incubation times and were frequently associated with significant burning, stinging, and treatment-related pain during illumination, which has remained one of the primary barriers limiting broader adoption of photodynamic therapy in clinical practice. Newer “painless” regimens—including simultaneous 5-aminolevulinic acid application with immediate illumination and daylight photodynamic therapy—were specifically developed to reduce treatment-associated pain while maintaining high efficacy. These advances have made photodynamic therapy a much more favorable option in clinical practice, allowing clinicians to treat larger areas and improve patient adherence without compromising outcomes.19–21

Head-to-head clinical trials comparing photodynamic therapy with other first-line therapies for actinic keratosis consistently show comparable or superior efficacy along with markedly better tolerability. Compared with cryotherapy, photodynamic therapy achieved equivalent clearance of facial or scalp actinic keratosis in 1 trial22 and significantly higher clearance rates in 2 trials,23,24 while also avoiding the hypopigmented scarring frequently observed after cryotherapy.

Similarly, compared with topical 5-fluorouracil, photodynamic therapy produced similar lesion clearance rates in 2 trials,25,26 but was clearly superior in both a small split-region study in transplant recipients26 and a randomized trial with 225 participants.24 Across all 4 studies, photodynamic therapy was consistently favored by patients, with higher satisfaction and preference scores than 5-fluorouracil.24–27

Finally, compared with imiquimod, photodynamic therapy was as good or better in terms of complete clearance rates in 4 studies,28–31 and sequential use of the 2 treatments was better than either alone in another study.32 Notably, in every study, patients universally preferred photodynamic therapy over imiquimod because it was much more tolerable.

Taken together, the available comparative evidence strongly supports photodynamic therapy as at least equivalent—and often superior—to cryotherapy, 5-fluorouracil, and imiquimod for actinic keratosis lesion clearance, with the added advantage of markedly better patient satisfaction.

Chemical peels

Chemical peels have been used off-label for field-directed treatment of multiple or clustered actinic keratosis lesions.

A meta-analysis of 8 studies evaluated the efficacy of different peeling agents.33 Monotherapy with trichloroacetic acid or Jessner solution showed lower lesion clearance rates compared with 5% 5-fluorouracil cream. Combining 5% 5-fluorouracil with 70% glycolic acid significantly improved the clearance of actinic keratoses compared with glycolic acid alone. Similarly, medium-depth peels with 30% to 50% trichloroacetic acid were less effective than conventional photodynamic therapy for field-directed treatment.

These findings suggest that chemical peels can be used for actinic keratoses, particularly when combined with topical agents, but their efficacy as monotherapy is generally lower than that of other established field therapies.1,33

In clinical practice, chemical peels are used less commonly than established field therapies due to procedural discomfort, downtime, risk of dyspigmentation or scarring, and variable insurance coverage. As a result, they are generally considered adjunctive or off-label approaches rather than routine first-line therapies for actinic keratoses.

Laser therapy

Laser resurfacing removes epidermal and superficial dermal tissue containing actinic damage, allowing re-epithelialization with healthier skin. Fully ablative CO2 and Er:YAG (erbium-doped yttrium aluminum garnet) lasers have demonstrated efficacy for both localized lesions and areas of field cancerization, although long-term clearance rates may be lower than with cryotherapy.34

Treatment outcomes are operator-dependent, and potential adverse effects include infection, scarring, and dyschromia. Fully ablative laser procedures should be performed with caution in immunocompromised patients because of their increased risk of infection.

While laser resurfacing can improve photodamage and treat actinic keratoses, its role as a primary therapy for actinic keratoses remains limited. Additionally, laser resurfacing is often limited in routine clinical practice by equipment costs, procedural time, operator dependence, recovery time, and potential adverse effects including prolonged erythema, infection, scarring, and pigment alteration.2,34,35

PREVENTION AND FOLLOW-UP

Prevention of actinic keratosis focuses on minimizing ultraviolet exposure and monitoring at-risk patients.

Sun protection. Daily use of broad-spectrum sunscreen (sun protection factor [SPF] ≥ 30), wearing protective clothing, and avoiding sun exposure during peak ultraviolet hours are foundational strategies for reducing cumulative ultraviolet damage.

Oral nicotinamide (vitamin B3), an over-the-counter supplement typically dosed at 500 mg twice daily, has been shown to reduce the incidence of new actinic keratosis lesions and nonmelanoma skin cancers. In a study in patients at high risk, using nicotinamide for 3 months resulted in an 11% reduction in actinic keratoses and a 23% reduction in nonmelanoma skin cancers compared with placebo.36 In practice, nicotinamide is most commonly considered for patients with numerous actinic keratosis lesions or a history of nonmelanoma skin cancer rather than universally after a first diagnosis of actinic keratosis.

Topical and oral retinoids, synthetic derivatives of vitamin A, are also used for chemoprevention of actinic keratosis and nonmelanoma skin cancer. Early studies showed that topical tretinoin 0.1% to 0.3% could reduce actinic keratosis lesions by about 50%, though more recent data have been mixed.2,37 Oral retinoids, including acitretin, etretinate, and isotretinoin, can be used for patients at high risk.38

Patients with a history of actinic keratosis should undergo regular skin examinations, with follow-up intervals guided by lesion burden and personal or family history of skin cancer.1

WHEN TO REFER

Referral to a specialist should be considered for patients with actinic keratoses that do not respond to first-line treatments, lesions clinically suspected of being invasive squamous cell carcinoma, or extensive field cancerization that may require photodynamic therapy or other field-directed interventions. Immunocompromised patients with a high lesion burden also warrant early specialist evaluation due to their increased risk of progression.1

TAKE-HOME POINTS

  • Actinic keratoses are common sun-induced precancerous lesions that clinicians are well-positioned to diagnose and manage.

  • With numerous effective treatments available, individualized care plans based on lesion characteristics and patient preferences are essential.

  • Photodynamic therapy, increasingly favored due to newer painless regimens, offers an effective field-therapy alternative with excellent cosmetic outcomes.19,21

  • Preventive strategies, including sun protection and oral nicotinamide, are effective adjuncts to reduce recurrence and improve patient outcomes.36

DISCLOSURES

The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.

CME/MOC

Clicking the link below will connect you to begin the credit-claiming process for CME and MOC. After clicking on the link, scroll to the bottom of the page and click on “Complete the CME/MOC Process.” You will need your myCME login information to access this.

Click here to complete the CME/MOC process.

REFERENCES

  1. 1
    ↵
    Del Regno L, Catapano S, Di Stefani A, Cappilli S, Peris K. A review of existing therapies for actinic keratosis: current status and future directions. Am J Clin Dermatol 2022; 23(3):339–352. doi:10.1007/s40257-022-00674-3
    Google ScholarOpenURLCrossRefPubMed
  2. 2
    ↵
    Reinehr CPH, Bakos RM. Actinic keratoses: review of clinical, dermoscopic, and therapeutic aspects. An Bras Dermatol 2019; 94(6): 637–657. doi:10.1016/j.abd.2019.10.004
    Google ScholarOpenURLCrossRefPubMed
  3. 3
    ↵
    Hensen P, Müller ML, Haschemi R, et al. Predisposing factors of actinic keratosis in a North-West German population. Eur J Dermatol 2009; 19(4):345–354. doi:10.1684/ejd.2009.0706
    Google ScholarOpenURLCrossRefPubMed
  4. 4
    ↵
    Wenande E, Togsverd-Bo K, Hastrup A, Lei U, Philipsen PA, Haedersdal M. Skin cancer development is strongly associated with actinic keratosis in solid organ transplant recipients: a Danish cohort study. Dermatology 2023; 239(3):393–402. doi:10.1159/000529369
    Google ScholarOpenURLCrossRefPubMed
  5. 5
    ↵
    Rigel DS, Stein Gold LF. The importance of early diagnosis and treatment of actinic keratosis. J Am Acad Dermatol 2013; 68(1 suppl 1):S20–S27. doi:10.1016/j.jaad.2012.10.001
    Google ScholarOpenURLCrossRefPubMed
  6. 6
    ↵
    de Berker D, McGregor JM, Mohd Mustapa MF, Exton LS, Hughes BR. British Association of Dermatologists’ guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol 2017; 176(1):20–43. doi:10.1111/bjd.15107
    Google ScholarOpenURLCrossRefPubMed
  7. 7
    ↵
    Trost JG, Applebaum DS, Orengo I. Common adult skin and soft tissue lesions. Semin Plast Surg 2016; 30(3):98–107. doi:10.1055/s-0036-1584823
    Google ScholarOpenURLCrossRefPubMed
  8. 8
    ↵
    Lallas A, Apalla Z, Argenziano G, Moscarella E, Longo C, Zalaudek I. Clues for differentiating discoid lupus erythematosus from actinic keratosis. J Am Acad Dermatol 2013; 69(1):e5–e6. doi:10.1016/j.jaad.2013.01.041
    Google ScholarOpenURLCrossRefPubMed
  9. 9
    ↵
    Heppt MV, Steeb T, Ruzicka T, Berking C. Cryosurgery combined with topical interventions for actinic keratosis: a systematic review and meta-analysis. Br J Dermatol 2019; 180(4):740–748. doi:10.1111/bjd.17435
    Google ScholarOpenURLCrossRefPubMed
  10. 10
    ↵
    Jorizzo J, Stewart D, Bucko A, et al. Randomized trial evaluating a new 0.5% fluorouracil formulation demonstrates efficacy after 1-, 2-, or 4-week treatment in patients with actinic keratosis. Cutis 2002; 70(6):335–339. pmid:12502122
    Google ScholarOpenURLPubMedWeb of Science
  11. 11
    ↵
    Weiss J, Menter A, Hevia O, et al. Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks. Cutis 2002; 70(2 suppl):22–29. pmid:12353677
    Google ScholarOpenURLPubMedWeb of Science
  12. 12
    ↵
    Dlott AH, Spencer SA, Di Pasqua AJ. Calcipotriol and 5-fluorouracil combination therapy for the treatment of actinic keratosis in the clinic: a review article. Clin Drug Investig 2024; 44(10):733–737. doi:10.1007/s40261-024-01392-w
    Google ScholarOpenURLCrossRefPubMed
  13. 13
    ↵
    Hanke CW, Beer KR, Stockfleth E, Wu J, Rosen T, Levy S. Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two placebo-controlled studies of daily application to the face and balding scalp for two 3-week cycles. J Am Acad Dermatol 2010; 62(4):573–581. doi:10.1016/j.jaad.2009.06.020
    Google ScholarOpenURLCrossRefPubMed
  14. 14
    ↵
    Nelson C, Rigel D, Smith S, Swanson N, Wolf J. Phase IV, open-label assessment of the treatment of actinic keratosis with 3.0% diclofenac sodium topical gel (Solaraze). J Drugs Dermatol 2004; 3(4):401–407. pmid:15303784
    Google ScholarOpenURLPubMed
  15. 15
    ↵
    Gupta AK, Paquet M, Villanueva E, Brintnell W. Interventions for actinic keratoses. Cochrane Database Syst Rev 2012; 12(12):CD004415. doi:10.1002/14651858.CD004415.pub2
    Google ScholarOpenURLCrossRefPubMed
  16. 16
    ↵
    Babino G, Diluvio L, Bianchi L, et al. Long-term use of a new topical formulation containing piroxicam 0.8% and sunscreen: efficacy and tolerability on actinic keratosis. A proof of concept study. Curr Med Res Opin 2016; 32(8):1345–1349. doi:10.1080/03007995.2016.1174678
    Google ScholarOpenURLCrossRefPubMed
  17. 17
    ↵
    de Oliveira ECV, da Motta VRV, Pantoja PC, et al. Actinic keratosis—review for clinical practice. Int J Dermatol 2019; 58(4):400–407. doi:10.1111/ijd.14147
    Google ScholarOpenURLCrossRefPubMed
  18. 18
    ↵
    Blauvelt A, Kempers S, Lain E, et al. Phase 3 trials of tirbanibulin ointment for actinic keratosis. N Engl J Med 2021; 384(6):512–520. doi:10.1056/NEJMoa2024040
    Google ScholarOpenURLCrossRefPubMed
  19. 19
    ↵
    Kaw U, Ilyas M, Bullock T, et al. A regimen to minimize pain during blue light photodynamic therapy of actinic keratoses: bilaterally controlled, randomized trial of simultaneous versus conventional illumination. J Am Acad Dermatol 2020; 82(4):862–868. doi:10.1016/j.jaad.2019.09.010
    Google ScholarOpenURLCrossRefPubMed
  20. 20
    Johnson JS, Hanna J, Nowacki AS, Anand S, Shen AS, Maytin EV. Painless PDT using 10% aminolevulinate gel and red light: a pilot clinical trial of short-contact protocols to reduce discomfort during illumination. Photodiagnosis Photodyn Ther 2025; 54:104698. doi:10.1016/j.pdpdt.2025.104698
    Google ScholarOpenURLCrossRefPubMed
  21. 21
    ↵
    Bullock TA, Negrey J, Hu B, Warren CB, Hasan T, Maytin EV. Significant improvement of facial actinic keratoses after blue light photodynamic therapy with oral vitamin D pretreatment: an interventional cohort-controlled trial. J Am Acad Dermatol 2022; 87(1):80–86. doi:10.1016/j.jaad.2022.02.067
    Google ScholarOpenURLCrossRefPubMed
  22. 22
    ↵
    Szeimies RM, Karrer S, Radakovic-Fijan S, et al. Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: a prospective, randomized study. J Am Acad Dermatol 2002; 47(2):258–262. pmid:12140473
    Google ScholarOpenURLCrossRefPubMedWeb of Science
  23. 23
    ↵
    Morton C, Campbell S, Gupta G, et al. Intraindividual, right-left comparison of topical methyl aminolaevulinate-photodynamic therapy and cryotherapy in subjects with actinic keratoses: a multicentre, randomized controlled study. Br J Dermatol 2006; 155(5):1029–1036. doi:10.1111/j.1365-2133.2006.07470.x
    Google ScholarOpenURLCrossRefPubMedWeb of Science
  24. 24
    ↵
    Morton C, Horn M, Leman J, et al. Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or fluorouracil for treatment of squamous cell carcinoma in situ: results of a multicenter randomized trial. Arch Dermatol 2006; 142(6):729–35. doi:10.1001/archderm.142.6.729
    Google ScholarOpenURLCrossRefPubMedWeb of Science
  25. 25
    ↵
    Kurwa HA, Yong-Gee SA, Seed PT, Markey AC, Barlow RJ. A randomized paired comparison of photodynamic therapy and topical 5-fluorouracil in the treatment of actinic keratoses. J Am Acad Dermatol 1999; 41(3 Pt 1):414–418. doi:10.1016/s0190-9622(99)70114-3
    Google ScholarOpenURLCrossRefPubMedWeb of Science
  26. 26
    ↵
    Smith S, Piacquadio D, Morhenn V, Atkin D, Fitzpatrick R. Short incubation PDT versus 5-FU in treating actinic keratoses. J Drugs Dermatol 2003; 2(6):629–635. pmid:14711141
    Google ScholarOpenURLPubMed
  27. 27
    ↵
    Perrett CM, McGregor JM, Warwick J, et al. Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy. Br J Dermatol 2007; 156(2):320–328. doi:10.1111/j.1365-2133.2006.07616.x
    Google ScholarOpenURLCrossRefPubMed
  28. 28
    ↵
    Serra-Guillen C, Nagore E, Hueso L, et al. A randomized comparative study of tolerance and satisfaction in the treatment of actinic keratosis of the face and scalp between 5% imiquimod cream and photodynamic therapy with methyl aminolaevulinate. Br J Dermatol 2011; 164(2):429–433. doi:10.1111/j.1365-2133.2010.10098.x
    Google ScholarOpenURLCrossRefPubMed
  29. 29
    Hadley J, Tristani-Firouzi P, Hull C, Florell S, Cotter M, Hadley M. Results of an investigator-initiated single-blind split-face comparison of photodynamic therapy and 5% imiquimod cream for the treatment of actinic keratoses. Dermatol Surg 2012; 38(5):722–727. doi:10.1111/j.1524-4725.2012.02340.x
    Google ScholarOpenURLCrossRefPubMed
  30. 30
    Sotiriou E, Apalla Z, Vrani F, Lallas A, Chovarda E, Ioannides D. Photodynamic therapy vs. imiquimod 5% cream as skin cancer preventive strategies in patients with field changes: a randomized intraindividual comparison study. J Eur Acad Dermatol Venereol 2015; 29(2):325–329. doi:10.1111/jdv.12538
    Google ScholarOpenURLCrossRefPubMed
  31. 31
    ↵
    Togsverd-Bo K, Halldin C, Sandberg C, et al. Photodynamic therapy is more effective than imiquimod for actinic keratosis in organ transplant recipients: a randomized intraindividual controlled trial. Br J Dermatol 2018; 178(4):903–909. doi:10.1111/bjd.15884
    Google ScholarOpenURLCrossRefPubMed
  32. 32
    ↵
    Serra-Guillén C, Nagore E, Hueso L, et al. A randomized pilot comparative study of topical methyl aminolevulinate photodynamic therapy versus imiquimod 5% versus sequential application of both therapies in immunocompetent patients with actinic keratosis: clinical and histologic outcomes. J Am Acad Dermatol 2012; 66(4): e131–e137. doi:10.1016/j.jaad.2011.11.933
    Google ScholarOpenURLCrossRefPubMed
  33. 33
    ↵
    Steeb T, Koch EAT, Wessely A, et al. Chemical peelings for the treatment of actinic keratosis: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol 2021; 35(3):641–649. doi:10.1111/jdv.16844
    Google ScholarOpenURLCrossRefPubMed
  34. 34
    ↵
    Zane C, Facchinetti E, Rossi MT, Specchia C, Ortel B, Calzavara-Pinton P. Cryotherapy is preferable to ablative CO2 laser for the treatment of isolated actinic keratoses of the face and scalp: a randomized clinical trial. Br J Dermatol 2014; 170(5):1114–1121. doi:10.1111/bjd.12847
    Google ScholarOpenURLCrossRefPubMed
  35. 35
    ↵
    Soleymani T, Abrouk M, Kelly KM. An analysis of laser therapy for the treatment of nonmelanoma skin cancer. Dermatol Surg 2017; 43(5):615–624. doi:10.1097/DSS.0000000000001048
    Google ScholarOpenURLCrossRefPubMed
  36. 36
    ↵
    Chen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med 2015; 373(17):1618–1626. doi:10.1056/NEJMoa1506197
    Google ScholarOpenURLCrossRefPubMed
  37. 37
    ↵
    Bollag W, Ott F. Retinoic acid: topical treatment of senile or actinic keratoses and basal cell carcinomas. Agents Actions 1970; 1(4): 172–175. doi:10.1007/BF01965758
    Google ScholarOpenURLCrossRefPubMed
  38. 38
    ↵
    Bettoli V, Zauli S, Virgili A. Retinoids in the chemoprevention of non-melanoma skin cancers: why, when and how. J Dermatolog Treat 2013; 24(3):235–237. doi:10.3109/09546634.2012.746634
    Google ScholarOpenURLCrossRefPubMed
Loading
Loading
PDF
Back to top

In this issue

Cleveland Clinic Journal of Medicine

Cleveland Clinic Journal of Medicine

Vol. 93, Issue 9

1 Sep 2026

Table of Contents Table of Contents (PDF) Index by author Complete Issue (PDF)
  • Share

    Share This Article

    Actinic keratosis: A clinician’s guide to diagnosis and treatment
    • Cleveland Clinic Journal of Medicine
    • September 2026,
    • 93
    • (9)
    • 541-549;
    • DOI: 10.3949/ccjm.93a.26005

Jump to section