Highlights & Basics
- Chronic keratotic lesions on adult skin that has been chronically exposed to ultraviolet rays.
- Has the potential to progress into an invasive squamous cell carcinoma (SCC).
- Although diagnosed clinically, a biopsy may help rule out SCC.
- Treatment consists of destructive methods (e.g., cryotherapy with liquid nitrogen, curettage with or without electrodesiccation, chemical peels, and photodynamic therapy) or topical medication (e.g., topical fluorouracil, imiquimod, diclofenac, or tirbanibulin).
Quick Reference
History & Exam
Key Factors
single or multiple scaly macules or plaques
scaly lesions with a hyperkeratotic surface
well-defined, scaly, brown lesions
lesions resembling seborrheic keratosis, melanocytic nevus, and early malignant melanoma
hypertrophic conical-shaped protuberances growing from the surface of the skin
scaly red roughness with induration, fissuring, and ulceration of the lower lip to the commissures
lesion on sun-exposed area of body
skin-colored, papillomatous, elevated wartlike papules
plaques with very mild scale over very thin shiny skin
violaceous well-defined papules with fine white lines on the surface
Other Factors
evidence of sun damage to skin
pruritus or bleeding
Diagnostics Tests
Other Tests to consider
dermoscopy
skin biopsy
Treatment Options
ongoing
confluent scalp lesions
thin lesions, few in number
thin lesions, numerous
thick lesions (any number)
head and face lesions, excluding periorbital, actinic cheilitis, and confluent scalp lesions
thin lesions, few in number
thin lesions, numerous
thick lesions, few in number
thick lesions, numerous
Definition
Classifications
Clinical classification
Vignette
Common Vignette
Other Presentations
Epidemiology
Etiology
Pathophysiology
Diagnostic Approach
History
Physical exam
- Scaly lesions with a hyperkeratotic surface (hyperkeratotic AKs)
- Well-defined, scaly, brown lesions resembling solar lentigo (pigmented AKs)[1]
- Lesions resembling seborrheic keratosis, melanocytic nevus, and early malignant melanoma (spreading pigmented AKs)[5]
- Skin-colored, papillomatous, elevated wartlike papules (verrucous AKs)
- Plaques with very mild scale over very thin shiny skin (atrophic AKs)
- Violaceous well-defined papules with fine white lines on the surface (lichen planus-like or lichenoid AKs)
- Hypertrophic conical-shaped protuberances growing from the surface of the skin (cutaneous horn)
Investigations
Risk Factors
History & Exam
Tests
Differential Diagnosis
Squamous cell carcinoma (SCC) in situ (Bowen disease)
Differentiating Signs/Symptoms
- Lesions similar to AKs, with similar distribution, but usually solitary. Can become larger, indurated, inflamed, redder, ulcerated, and bleeding.
- Can occur on covered areas including mucous membranes and genital areas.
Differentiating Tests
Invasive SCC
Differentiating Signs/Symptoms
- Lesions begin similarly to AKs or Bowen disease.
- Generally a larger red ulcer with a thick border and a granular base.
- Has the potential to metastasize.
Differentiating Tests
- Skin biopsy shows atypical (anaplastic) keratinocytes throughout entire epidermis, invading dermis.
- Differentiated tumors have less atypical cells and more keratinization (e.g., horn pearls) than undifferentiated.
Differentiating Signs/Symptoms
Differentiating Tests
- Early lesion skin biopsy shows ill-defined epidermal invaginations into dermis, containing keratinocytes with little nuclear atypia and mitotic figures, and some dyskeratotic cells.
Basal cell carcinoma
Differentiating Signs/Symptoms
- A small, smooth nodule with a translucent pearly border, and telangiectasia seen through the surface.
- Most are localized on the face; less likely to be found on the trunk.
- Hyperpigmented lesions sometimes occur, resembling malignant melanoma and other melanocytic lesions.[53]
Differentiating Tests
- Skin biopsy shows nodular masses of large basaloid cells with large nucleus and little cytoplasm, peripheral palisading that extends into dermis.
- Cystic spaces present between tumor cells and stroma.[53]
Seborrheic keratosis
Differentiating Signs/Symptoms
- Elevated, well-defined velvety plaques, localized on either sun-exposed or covered areas.
- Most have a verrucous surface, and may have keratotic plugs and irregular crypts.
- Lesions can grow and become thicker and more pigmented.
Localized discoid lupus erythematosus (DLE)
Differentiating Signs/Symptoms
- In general, lesions localized anywhere above the neck, in the same distribution as AKs.
Hypertrophic lupus erythematosus
Differentiating Signs/Symptoms
- A variant of DLE with verrucous hyperkeratotic and crusting lesions.
Subacute cutaneous lupus erythematosus
Differentiating Signs/Symptoms
- Localized on the trunk and extensor aspects of the upper extremities rather than face and neck.
- Unlike AKs, more likely to occur in women.
Differentiating Tests
- Skin biopsy shows interface lichenoid dermatitis, basal keratinocytic vacuolization, suprabasilar clefts and vesicles, lymphocytic exocytosis, colloid bodies in lower epidermis and papillary dermis, marked edema, and focal erythrocyte extravasation.
Psoriasis
Differentiating Signs/Symptoms
- Well-defined pink to erythematous confluent papules and plaques covered with silvery scales, revealing small bleeding points on scraping (Auspitz sign).
- An eruptive form with small plaques (guttate psoriasis) may occur after acute group A beta-hemolytic streptococcal throat infections.
Differentiating Tests
- Skin biopsy shows acanthosis, focal vacuolization, and disappearance of granular cells with overlying parakeratosis, edema, and capillary dilation in elongated papillary dermis.
Differentiating Signs/Symptoms
- Lesions are localized mostly in the extensor surfaces of the extremities and can occur in the face.
- Small, superficial, skin-colored, erythematous, or pigmented plaques surrounded by a narrow, elevated hyperkeratotic ridge.[53]
Differentiating Tests
- Clinical findings should suffice to distinguish from AKs. Skin biopsy shows characteristic deep invaginations of keratin into the epidermis with central parakeratosis (cornoid lamella).[53]
Differentiating Signs/Symptoms
- A small hyperkeratotic, well-defined plaque that develops in sun-exposed areas.
- Resembles AKs in the type of lesion, the pattern of distribution (e.g., head and extremities), and size of the lesions (<1 cm).
Differentiating Tests
- Skin biopsy shows large keratinocytes with large nuclei arranged in a disorganized pattern.[53]
- Nuclear dysplasia may be present, and mitoses are infrequent. Acanthosis, hypergranulosis, and orthohyperkeratosis may also be present.
Differentiating Signs/Symptoms
- Well-defined, irregular, very small hyperpigmented macules localized over sun-exposed areas.
Differentiating Tests
- Skin biopsy shows elongated, fused rete ridges, with small budlike extensions. Thin epidermis over the rete ridges. Low epidermis with hyperpigmented basaloid cells and strong DOPA-positive dendritic melanocytes.
- Dermoscopy: discrete regular network, uniform pigmented background, absent brown globules.[55]
Warts
Differentiating Signs/Symptoms
- Well-defined, usually round, firm, papillomatous papules associated with human papilloma virus (HPV) infection.
- Located on dorsal aspects of the fingers and hands, where they can resemble hyperkeratotic AKs.
- The filiform variant is mostly seen on the face and scalp of older children rather than in older people.[53]
Differentiating Tests
- Skin biopsy shows a thick epidermis with papillomatosis, and hyperkeratosis. Elongated rete ridges, focal cell vacuolization (koilocytotic cells), and parakeratotic cells.
- PCR HPV-DNA amplification may detect viral antigens including HPV common antigen.
- In-situ hybridization may identify viral genomic material.[53]
Lichen planus
Differentiating Signs/Symptoms
- Few or multiple violaceous well-defined papules with fine white lines on the surface.
- Lichen planus-like (lichenoid) AK lesions morphologically resemble lichen planus, and tend to be localized on sun-exposed areas.
- In addition, lichen planus can be frequently found in mucous membranes, genitals, and nails.
Differentiating Tests
- Skin biopsy reveals characteristic hyperkeratotic epidermis, irregular acanthosis, focal thickening of the granular layer, liquefaction of basement membrane, and bandlike lymphocytic infiltrate in the upper dermis.[53]
Lentigo maligna and melanoma in situ
Differentiating Signs/Symptoms
- Clinically resemble pigmented and spreading pigmented AK (SPAK).[73]
Differentiating Tests
- Dermoscopy: asymmetrically pigmented follicular ostia, irregular size and slate-gray dots and globules that are more irregularly and asymmetrically distributed. Hypopigmented follicular openings surrounded by a hyperpigmented rim.[73]
- Skin biopsy shows atypical melanocytes at the basal layer of atrophic sun-damaged skin; melanocyte nesting, vertical stacking, and pagetoid spread.[73]
- Immunostaining shows positivity to melanocyte antigen related to T cells (MART)-1, Melan-A, S-100, and HMB-45.[73]
Criteria
- Clinical: undetectable or flat, pink macule or patch on solar-damaged skin; background mottling; no roughness or hyperkeratosis
- Histologic: focal atypia of basal keratinocytes of lower one third of the epidermis.
- Clinical: pink to red papule or plaque with rough, hyperkeratotic surface; minimal induration.
- Histologic: focal atypia of keratinocytes of the lower two-thirds of the epidermis; alternating ortho- and parakeratosis with sparing of acrotrichia.
- Clinical: similar to IIa but more induration, more hyperkeratosis, and/or more erythema; all KIN lesions (other than KIN III) on lip and conjunctiva.
- Histologic: focal atypia of keratinocytes of at least the lower two-thirds of the epidermis; focal hyperkeratosis, often greater than IIa; 1 or more additional features such as acantholysis, involvement of adnexal structures, prominent acanthosis, and buds of keratinocytes into the upper papillary dermis present.
- Clinical: red, scaly, indurated plaques on sun-damaged skin; may be pigmented; seen on other sites such as mucosa in bowenoid papulosis and erythroplasia of Queyrat.
- Histologic: diffuse atypical keratinocytic proliferation involving the full thickness of the epidermis; parakeratosis, acanthosis, papillomatosis, involvement of adnexal structures.
Screening
Treatment Approach
- Number and size of AKs
- Anatomic location
- Change in growth pattern
- Suspected subclinical lesions
- Patient tolerability/adherence
- Prior treatment of the lesions
- Physician expertise
- Availability of treatment options.
Surgical therapies
Photodynamic therapy
Chemical peels
Topical therapies
Dermabrasion
Treatment for persistent or severe actinic cheilitis
Sunscreen
Treatment Options
confluent scalp lesions
thin lesions, few in number
cryosurgery
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AKs.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
topical therapy
Primary Options
- fluorouracil topical
(0.5%) apply to the affected area(s) once daily for 1-4 weeks; (5%) apply to the affected area(s) twice daily for 2-4 weeks
- fluorouracil topical
- imiquimod topical
(3.75%) apply to the affected area(s) once daily for 2 weeks initially, followed by 2 weeks of no treatment, followed by a further 2 weeks of treatment; (5%) apply to the affected area(s) twice weekly for 16 weeks; apply at bedtime and rinse off the next morning
- imiquimod topical
- diclofenac topical
(3%) apply to the affected area(s) twice daily for up to 12 weeks
- diclofenac topical
- tirbanibulin topical
(1%) apply to the affected area(s) once daily for 5 days
- tirbanibulin topical
Comments
- Can be used focally or in broad areas. Commonly used in the management of AKs that occur in areas of high density or areas with indistinct clinical borders.[48]
- Fluorouracil is recommended for field treatment of AK.[48] Among patients with multiple AK lesions (who underwent initial curettage), the probability of remaining free from treatment failure 12 months after the end of treatment was significantly greater among patients who received 5% fluorouracil (74.7%) than among those who received imiquimod or methyl aminolevulinate photodynamic therapy (53.9%, 37.7%, respectively).[91]
- High treatment failure rates, that may in part be attributable to reduced adherence subsequent to adverse effects (e.g., severe erythema, pain, stinging), have been reported among patients treated with 5% fluorouracil.[28] [92] [93] There is some evidence to suggest that 0.5% fluorouracil has similar efficacy to the 5% formulation, with reduced risk of adverse effects.[94] [95]
- Field treatment with imiquimod, a topical immune response modifier, is recommended.[48] Imiquimod is available in 5% and 3.75% formulations for the treatment of AK.
- Dosing regimens vary in clinical trials; a mean complete clearance rate of 41% has been reported in studies where 32 to 56 doses of 5% imiquimod were administered.[48] Randomized controlled trials evaluating 3.75% imiquimod suggest a post-treatment (14-17 weeks) complete clearance rate of approximately 35%.[96] [97]
- Long-term recurrence rates (18-24 months) of <30% have been reported among patients treated with 5% imiquimod.[98] [99] In clinical trials, treatment with 5% imiquimod resulted in a larger number of participant withdrawals due to adverse events (e.g., local skin reaction, influenza-like symptoms) than treatment with 3.75% imiquimod.[81]
- Diclofenac, a topical nonsteroidal anti-inflammatory drug (NSAID), is conditionally recommended to treat AK (low-quality evidence).[48] As with other oral and topical NSAIDs, topical diclofenac carries a warning for cardiovascular and gastrointestinal adverse effects (which may impact treatment choice).
- Diclofenac 3% (formulated in a hyaluronic acid vehicle) decreases the diffusion of diclofenac through the skin, increasing the time of exposure of the epidermis to diclofenac and enhancing its delivery to the atypical cells.[103] Patients receiving topical diclofenac may experience fewer adverse effects (e.g., severe erythema, pain, and stinging) than with other topical therapies; topical fluorouracil has, however, been shown to be more effective than topical diclofenac.[93] [104] [105]
- Tirbanibulin, a topical microtubule inhibitor, has been approved for the topical treatment of AK of the face or scalp by the Food and Drug Administration. The approval was based on two phase 3, double-blind, vehicle-controlled, randomized clinical trials that evaluated the efficacy and safety of tirbanibulin in adults with AKs on the face and scalp. Both trials reported that tirbanibulin significantly increased the rate of complete AK clearance at day 57 compared with the vehicle.[106] [107] Following a systematic review triggered by the Food and Drug Administration approval, the American Academy of Dermatology (AAD) has published a focused update of their guidelines on the management of AK, recommending that field treatment with tirbanibulin be included on the list of currently recommended topical therapies (strong recommendation, high certainty evidence).[108] The European Medicines Agency has approved tirbanulin for the field treatment of nonhyperkeratotic, nonhypertrophic AK of the face or scalp in adults.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
thin lesions, numerous
chemical peels
Primary Options
- trichloroacetic acid topical
(35-45%) apply to affected area(s) after oil debridement with acetone
- trichloroacetic acid topical
- salicylic acid topical
(20-30%) apply to affected area(s) after degreasing with acetone or alcohol
- salicylic acid topical
Comments
- Chemical peels are a treatment option for thin, numerous lesions (field treatment).[89]
- An application of caustic agent to the skin surface induces necrosis of a specific skin layer. The depth of the peel depends not only on the agent used but also on its concentration, time of application, and thickness of the skin area to be treated.
- Trichloroacetic acid, alpha hydroxy acids (including glycolic acid), and beta hydroxy acids (including salicylic acid) are medium-depth chemical peels. Trichloroacetic acid was not as effective as aminolevulinic acid photodynamic therapy for the treatment of multiple AKs in a small randomized observer-blinded comparative study.[90]
- Jessner peel (salicylic acid, lactic acid, and resorcinol) is a superficial-depth peel facilitating intraepidermic necrosis. Every application coat increases level of penetration, although usually there is no risk to deeper penetration or additional damage to the skin (overpeel).
- These products may need to be specially compounded by a pharmacist as they may not be available commercially.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
topical therapy
Primary Options
- fluorouracil topical
(0.5%) apply to the affected area(s) once daily for 1-4 weeks; (5%) apply to the affected area(s) twice daily for 2-4 weeks
- fluorouracil topical
- imiquimod topical
(3.75%) apply to the affected area(s) once daily for 2 weeks initially, followed by 2 weeks of no treatment, followed by a further 2 weeks of treatment; (5%) apply to the affected area(s) twice weekly for 16 weeks; apply at bedtime and rinse off the next morning
- imiquimod topical
- tirbanibulin topical
(1%) apply to the affected area(s) once daily for 5 days
- tirbanibulin topical
Comments
- Can be used focally or in broad areas. Commonly used in the management of AKs that occur in areas of high density or areas with indistinct clinical borders.[48]
- Fluorouracil is recommended for field treatment of AK.[48] Among patients with multiple AK lesions (who underwent initial curettage), the probability of remaining free from treatment failure 12 months after the end of treatment was significantly greater among patients who received 5% fluorouracil (74.7%) than among those who received imiquimod or methyl aminolevulinate photodynamic therapy (53.9%, 37.7%, respectively).[91]
- High treatment failure rates, that may in part be attributable to reduced adherence subsequent to adverse effects (e.g., severe erythema, pain, stinging), have been reported among patients treated with 5% fluorouracil.[28] [92] [93] There is some evidence to suggest that 0.5% fluorouracil has similar efficacy to the 5% formulation, with reduced risk of adverse effects.[94] [95]
- Field treatment with imiquimod, a topical immune response modifier, is recommended.[48] Imiquimod is available in 5% and 3.75% formulations for the treatment of AK.
- Dosing regimens vary in clinical trials; a mean complete clearance rate of 41% has been reported in studies where 32 to 56 doses of 5% imiquimod were administered.[48] Randomized controlled trials evaluating 3.75% imiquimod suggest a post-treatment (14-17 weeks) complete clearance rate of approximately 35%.[96] [97]
- Long-term recurrence rates (18-24 months) of <30% have been reported among patients treated with 5% imiquimod.[98] [99] In clinical trials, treatment with 5% imiquimod resulted in a larger number of participant withdrawals due to adverse events (e.g., local skin reaction, influenza-like symptoms) than treatment with 3.75% imiquimod.[81]
- Tirbanibulin, a topical microtubule inhibitor, has been approved for the topical treatment of AK of the face or scalp by the Food and Drug Administration. The approval was based on two phase 3, double-blind, vehicle-controlled, randomized clinical trials that evaluated the efficacy and safety of tirbanibulin in adults with AKs on the face and scalp. Both trials reported that tirbanibulin significantly increased the rate of complete AK clearance at day 57 compared with the vehicle.[106] [107] Following a systematic review triggered by the Food and Drug Administration approval, the American Academy of Dermatology (AAD) has published a focused update of their guidelines on the management of AK, recommending that field treatment with tirbanibulin be included on the list of currently recommended topical therapies (strong recommendation, high certainty evidence).[108] The European Medicines Agency has approved tirbanulin for the field treatment of nonhyperkeratotic, nonhypertrophic AK of the face or scalp in adults.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
cryosurgery
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AK.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
photodynamic therapy
Comments
- Photodynamic therapy (PDT) uses a specific wavelength of light to induce the production of cytotoxic substances when applied to skin previously treated with a photosensitizing agent (e.g., aminolevulinic acid).
- Evidence suggests that PDT with aminolevulinic acid is highly effective for treating AKs.[81] [82] [83] [84] [85] [86] [87] Conventional PDT with aminolevulinic acid has been substantially evaluated for the management of thin and moderate-thickness nonhyperkeratotic AKs of the face and scalp.[88] US guidelines conditionally recommend aminolevulinic acid blue-light PDT (moderate-quality evidence) and aminolevulinic acid red-light PDT (low-quality evidence); aminolevulinic acid daylight PDT is less painful than aminolevulinic acid red-light PDT, but equally effective (moderate-quality evidence).[48]
- PDT protocols and duration vary because photosensitizing compound incubation time and need for occlusion can vary depending on the aminolevulinic acid formulation used. The primary photosensitizing agent used in the US is aminolevulinic acid; methyl aminolevulinate is not available in the US.[48] A range of light sources can be used.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
topical diclofenac
Primary Options
- diclofenac topical
(3%) apply to the affected area(s) twice daily for up to 12 weeks
- diclofenac topical
Comments
- Diclofenac, a topical nonsteroidal anti-inflammatory drug (NSAID), is conditionally recommended to treat AK (low-quality evidence).[48] As with other oral and topical NSAIDs, topical diclofenac carries a warning for cardiovascular and gastrointestinal adverse effects (which may impact treatment choice).
- Diclofenac 3% (formulated in a hyaluronic acid vehicle) decreases the diffusion of diclofenac through the skin, increasing the time of exposure of the epidermis to diclofenac and enhancing its delivery to the atypical cells.[103] Patients receiving topical diclofenac may experience fewer adverse effects (e.g., severe erythema, pain, and stinging) than with other topical therapies; topical fluorouracil has, however, been shown to be more effective than topical diclofenac.[93] [104] [105]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
thick lesions (any number)
cryosurgery
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AK.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
dermabrasion
Comments
- Dermabrasion may be used as a second-line treatment for thick, numerous AK lesions. One small retrospective study suggests that dermabrasion provides long-term effective prophylaxis against AK.[109]
- Preoperative sedation, anxiolytic therapy, regional nerve blocking, and cryoanesthetics should be provided. Dermabrasion results in generation of bloodborne particles in the environment, including hepatitis B and HIV; measures to reduce infection risk should be implemented. Postoperative herpetic infection has been reported; prophylaxis is recommended for all patients, including those with no history of herpes infection.[110]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
head and face lesions, excluding periorbital, actinic cheilitis, and confluent scalp lesions
thin lesions, few in number
cryosurgery
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AK.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
topical therapy
Primary Options
- fluorouracil topical
(0.5%) apply to the affected area(s) once daily for 1-4 weeks; (5%) apply to the affected area(s) twice daily for 2-4 weeks
- fluorouracil topical
- imiquimod topical
(3.75%) apply to the affected area(s) once daily for 2 weeks initially, followed by 2 weeks of no treatment, followed by a further 2 weeks of treatment; (5%) apply to the affected area(s) twice weekly for 16 weeks; apply at bedtime and rinse off the next morning
- imiquimod topical
- diclofenac topical
(3%) apply to the affected area(s) twice daily for up to 12 weeks
- diclofenac topical
- tirbanibulin topical
(1%) apply to the affected area(s) once daily for 5 days
- tirbanibulin topical
Comments
- Can be used focally or in broad areas. Commonly used in the management of AKs that occur in areas of high density or areas with indistinct clinical borders.[48]
- Fluorouracil is recommended for field treatment of AK.[48] Among patients with multiple AK lesions (who underwent initial curettage), the probability of remaining free from treatment failure 12 months after the end of treatment was significantly greater among patients who received 5% fluorouracil (74.7%) than among those who received imiquimod or methyl aminolevulinate photodynamic therapy (53.9%, 37.7%, respectively).[91]
- High treatment failure rates, that may in part be attributable to reduced adherence subsequent to adverse effects (e.g., severe erythema, pain, stinging), have been reported among patients treated with 5% fluorouracil.[28] [92] [93] There is some evidence to suggest that 0.5% fluorouracil has similar efficacy to the 5% formulation, with reduced risk of adverse effects.[94] [95]
- Field treatment with imiquimod, a topical immune response modifier, is recommended.[48] Imiquimod is available in 5% and 3.75% formulations for the treatment of AK.
- Dosing regimens vary in clinical trials; a mean complete clearance rate of 41% has been reported in studies where 32 to 56 doses of 5% imiquimod were administered.[48] Randomized controlled trials evaluating 3.75% imiquimod suggest a post-treatment (14-17 weeks) complete clearance rate of approximately 35%.[96] [97]
- Long-term recurrence rates (18-24 months) of <30% have been reported among patients treated with 5% imiquimod.[98] [99] In clinical trials, treatment with 5% imiquimod resulted in a larger number of participant withdrawals due to adverse events (e.g., local skin reaction, influenza-like symptoms) than treatment with 3.75% imiquimod.[81]
- Diclofenac, a topical nonsteroidal anti-inflammatory drug (NSAID), is conditionally recommended to treat AK (low-quality evidence).[48] As with other oral and topical NSAIDs, topical diclofenac carries a warning for cardiovascular and gastrointestinal adverse effects (which may impact treatment choice).
- Diclofenac 3% (formulated in a hyaluronic acid vehicle) decreases the diffusion of diclofenac through the skin, increasing the time of exposure of the epidermis to diclofenac and enhancing its delivery to the atypical cells.[103] Patients receiving topical diclofenac may experience fewer adverse effects (e.g., severe erythema, pain, and stinging) than with other topical therapies; topical fluorouracil has, however, been shown to be more effective than topical diclofenac.[93] [104] [105]
- Tirbanibulin, a topical microtubule inhibitor, has been approved for the topical treatment of AK of the face or scalp by the Food and Drug Administration. The approval was based on two phase 3, double-blind, vehicle-controlled, randomized clinical trials that evaluated the efficacy and safety of tirbanibulin in adults with AKs on the face and scalp. Both trials reported that tirbanibulin significantly increased the rate of complete AK clearance at day 57 compared with the vehicle.[106] [107] Following a systematic review triggered by the Food and Drug Administration approval, the American Academy of Dermatology (AAD) has published a focused update of their guidelines on the management of AK, recommending that field treatment with tirbanibulin be included on the list of currently recommended topical therapies (strong recommendation, high certainty evidence).[108] The European Medicines Agency has approved tirbanulin for the field treatment of nonhyperkeratotic, nonhypertrophic AK of the face or scalp in adults.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
thin lesions, numerous
chemical peels
Primary Options
- trichloroacetic acid topical
(35-45%) apply to affected area(s) after oil debridement with acetone
- trichloroacetic acid topical
- salicylic acid topical
(20-30%) apply to affected area(s) after degreasing with acetone or alcohol
- salicylic acid topical
Comments
- Chemical peels are a treatment option for thin, numerous lesions (field treatment).[89]
- An application of caustic agent to the skin surface induces necrosis of a specific skin layer. The depth of the peel depends not only on the agent but also on its concentration, time of application, and thickness of the skin area to be treated.
- Trichloroacetic acid, alpha hydroxy acids (including glycolic acid), and beta hydroxy acids (including salicylic acid) are medium-depth chemical peels. Trichloroacetic acid was not as effective as aminolevulinic acid photodynamic therapy for the treatment of multiple AKs in a small randomized observer-blinded comparative study.[90]
- Jessner peel (salicylic acid, lactic acid, and resorcinol) is a superficial-depth peel facilitating intraepidermic necrosis. Every application coat increases level of penetration, although usually there is no risk to deeper penetration or additional damage to the skin (overpeel).
- These products may need to be specially compounded by a pharmacist as they may not be available commercially.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
cryosurgery
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AK.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
topical therapy
Primary Options
- fluorouracil topical
(0.5%) apply to the affected area(s) once daily for 1-4 weeks; (5%) apply to the affected area(s) twice daily for 2-4 weeks
- fluorouracil topical
- imiquimod topical
(3.75%) apply to the affected area(s) once daily for 2 weeks initially, followed by 2 weeks of no treatment, followed by a further 2 weeks of treatment; (5%) apply to the affected area(s) twice weekly for 16 weeks; apply at bedtime and rinse off the next morning
- imiquimod topical
- tirbanibulin topical
(1%) apply to the affected area(s) once daily for 5 days
- tirbanibulin topical
Comments
- Can be used focally or in broad areas. Commonly used in the management of AKs that occur in areas of high density or areas with indistinct clinical borders.[48]
- Fluorouracil is recommended for field treatment of AK.[48] Among patients with multiple AK lesions (who underwent initial curettage), the probability of remaining free from treatment failure 12 months after the end of treatment was significantly greater among patients who received 5% fluorouracil (74.7%) than among those who received imiquimod or methyl aminolevulinate photodynamic therapy (53.9%, 37.7%, respectively).[91]
- High treatment failure rates, that may in part be attributable to reduced adherence subsequent to adverse effects (e.g., severe erythema, pain, stinging), have been reported among patients treated with 5% fluorouracil.[28] [92] [93] There is some evidence to suggest that 0.5% fluorouracil has similar efficacy to the 5% formulation, with reduced risk of adverse effects.[94] [95]
- Field treatment with imiquimod, a topical immune response modifier, is recommended.[48] Imiquimod is available in 5% and 3.75% formulations for the treatment of AK.
- Dosing regimens vary in clinical trials; a mean complete clearance rate of 41% has been reported in studies where 32 to 56 doses of 5% imiquimod were administered.[48] Randomized controlled trials evaluating 3.75% imiquimod suggest a post-treatment (14-17 weeks) complete clearance rate of approximately 35%.[96] [97]
- Long-term recurrence rates (18-24 months) of <30% have been reported among patients treated with 5% imiquimod.[98] [99] In clinical trials, treatment with 5% imiquimod resulted in a larger number of participant withdrawals due to adverse events (e.g., local skin reaction, influenza-like symptoms) than treatment with 3.75% imiquimod.[81]
- Tirbanibulin, a topical microtubule inhibitor, has been approved for the topical treatment of AK of the face or scalp by the Food and Drug Administration. The approval was based on two phase 3, double-blind, vehicle-controlled, randomized clinical trials that evaluated the efficacy and safety of tirbanibulin in adults with AKs on the face and scalp. Both trials reported that tirbanibulin significantly increased the rate of complete AK clearance at day 57 compared with the vehicle.[106] [107] Following a systematic review triggered by the Food and Drug Administration approval, the American Academy of Dermatology (AAD) has published a focused update of their guidelines on the management of AK, recommending that field treatment with tirbanibulin be included on the list of currently recommended topical therapies (strong recommendation, high certainty evidence).[108] The European Medicines Agency has approved tirbanulin for the field treatment of nonhyperkeratotic, nonhypertrophic AK of the face or scalp in adults.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
photodynamic therapy
Comments
- Photodynamic therapy (PDT) uses a specific wavelength of light to induce the production of cytotoxic substances when applied to skin previously treated with a photosensitizing agent (e.g., aminolevulinic acid).
- Evidence suggests that PDT with aminolevulinic acid is highly effective for treating AKs.[81] [82] [83] [84] [85] [86] [87] Conventional PDT with aminolevulinic acid has been substantially evaluated for the management of thin and moderate-thickness nonhyperkeratotic AKs of the face and scalp.[88] US guidelines conditionally recommend aminolevulinic acid blue-light PDT (moderate-quality evidence) and aminolevulinic acid red-light PDT (low-quality evidence); aminolevulinic acid daylight PDT is less painful than aminolevulinic acid red-light PDT, but equally effective (moderate-quality evidence).[48]
- PDT protocols and duration vary because photosensitizing compound incubation time and need for occlusion can vary depending on the aminolevulinic acid formulation used. The primary photosensitizing agent used in the US is aminolevulinic acid; methyl aminolevulinate is not available in the US.[48] A range of light sources can be used.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
topical diclofenac
Primary Options
- diclofenac topical
(3%) apply to the affected area(s) twice daily for up to 12 weeks
- diclofenac topical
Comments
- Diclofenac, a topical nonsteroidal anti-inflammatory drug (NSAID), is conditionally recommended to treat AK (low-quality evidence).[48] As with other oral and topical NSAIDs, topical diclofenac carries a warning for cardiovascular and gastrointestinal adverse effects (which may impact treatment choice).
- Diclofenac 3% (formulated in a hyaluronic acid vehicle) decreases the diffusion of diclofenac through the skin, increasing the time of exposure of the epidermis to diclofenac and enhancing its delivery to the atypical cells.[103] Patients receiving topical diclofenac may experience fewer adverse effects (e.g., severe erythema, pain, and stinging) than with other topical therapies; topical fluorouracil has, however, been shown to be more effective than topical diclofenac.[93] [104] [105]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
thick lesions, few in number
cryosurgery
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AK.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
curettage ± electrodesiccation
Comments
- Curettage is an alternative surgical choice for thick isolated lesions of the scalp, ears, nose, cheeks, forehead, and perioral region that fail to respond to topical therapy, and where there is suspicion of squamous cell carcinoma.[12] It is performed by mechanically scraping away the atypical keratinocytes with a curette, thereby providing tissue samples for histologic evaluation.
- Unlike cryosurgery, which can be performed in the office setting, curettage requires intradermal local anesthetic, and scarring is seen more frequently.[28] Experience is required to perform curettage, to feel the difference between atypical cells and healthy dermal tissue, where the scraping should stop in all perimeters.[2]
- Electrodesiccation is used in addition to curettage when residual marginal lesions require destruction and if further hemostasis is necessary.
- Curettage may be used alone or in combination with electrodesiccation, cryotherapy, chemical applications, or photodynamic therapy.
- Electrodesiccation is used in addition to curettage when residual marginal lesions require destruction, and if further hemostasis is necessary.
- If collecting for histopathology, care should be taken to preserve the tissue, and collection should be done before electrodesiccation.
- ll patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
thick lesions, numerous
cryosurgery
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AK.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
dermabrasion
Comments
- Dermabrasion may be used as a second-line treatment for thick, numerous AK lesions. One small retrospective study suggests that dermabrasion provides long-term effective prophylaxis against AK.[109]
- Preoperative sedation, anxiolytic therapy, regional nerve blocking, and cryoanesthetics should be provided. Dermabrasion results in generation of bloodborne particles in the environment, including hepatitis B and HIV; measures to reduce infection risk should be implemented. Postoperative herpetic infection has been reported; prophylaxis is recommended for all patients, including those with no history of herpes infection.[110]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
periorbital
thin lesions, few in number
cryosurgery
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AK.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
thin lesions, numerous
curettage ± electrodesiccation
Comments
- Curettage is an alternative surgical choice for thick isolated lesions of the scalp, ears, nose, cheeks, forehead, and perioral region that fail to respond to topical therapy, and where there is suspicion of squamous cell carcinoma.[12] It is performed by mechanically scraping away the atypical keratinocytes with a curette, thereby providing tissue samples for histologic evaluation.
- Unlike cryosurgery, which can be performed in the office setting, curettage requires intradermal local anesthetic, and scarring is seen more frequently.[28] Experience is required to perform curettage, to feel the difference between atypical cells and healthy dermal tissue, where the scraping should stop in all perimeters.[2]
- Curettage may be used alone or in combination with electrodesiccation, cryotherapy, chemical applications, or photodynamic therapy.
- Electrodesiccation is used in addition to curettage when residual marginal lesions require destruction, and if further hemostasis is necessary.
- If collecting for histopathology, care should be taken to preserve the tissue, and collection should be done before electrodesiccation.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
chemical peels
Primary Options
- trichloroacetic acid topical
(35-45%) apply to affected area(s) after oil debridement with acetone
- trichloroacetic acid topical
- salicylic acid topical
(20-30%) apply to affected area(s) after degreasing with acetone or alcohol
- salicylic acid topical
Comments
- Chemical peels are a treatment option for thin, numerous lesions (field treatment).[89]
- An application of caustic agent to the skin surface induces necrosis of a specific skin layer. The depth of the peel depends not only on the agent but also on its concentration, time of application, and thickness of the skin area to be treated.
- Trichloroacetic acid, alpha hydroxy acids (including glycolic acid), and beta hydroxy acids (including salicylic acid) are medium-depth chemical peels. Trichloroacetic acid was not as effective as aminolevulinic acid photodynamic therapy for the treatment of multiple AKs in a small randomized observer-blinded comparative study.[90]
- Jessner peel (salicylic acid, lactic acid, and resorcinol) is a superficial-depth peel facilitating intraepidermic necrosis. Every application coat increases level of penetration, although usually there is no risk to deeper penetration or additional damage to the skin (overpeel).
- These products may need to be specially compounded by a pharmacist as they may not be available commercially.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with aa sun protection factor of 15 or higher.[48]
photodynamic therapy
Comments
- Photodynamic therapy (PDT) uses a specific wavelength of light to induce the production of cytotoxic substances when applied to skin previously treated with a photosensitizing agent (e.g., aminolevulinic acid).
- Evidence suggests that PDT with aminolevulinic acid is highly effective for treating AKs.[81] [82] [83] [84] [85] [86] [87] Conventional PDT with aminolevulinic acid has been substantially evaluated for the management of thin and moderate-thickness nonhyperkeratotic AKs of the face and scalp.[88] US guidelines conditionally recommend aminolevulinic acid blue-light PDT (moderate-quality evidence) and aminolevulinic acid red-light PDT (low-quality evidence); aminolevulinic acid daylight PDT is less painful than aminolevulinic acid red-light PDT, but equally effective (moderate-quality evidence).[48]
- PDT protocols and duration vary because photosensitizing compound incubation time and need for occlusion can vary depending on the aminolevulinic acid formulation used. The primary photosensitizing agent used in the US is aminolevulinic acid; methyl aminolevulinate is not available in the US.[48] A range of light sources can be used.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
thick lesions (any number)
cryosurgery
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AK.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
persistent or severe actinic cheilitis
laser surgery
Comments
- Carbon dioxide laser vermilionectomy for actinic cheilitis has high efficacy, few recurrences, minimal scarring, and excellent cosmetic outcomes.
- The laser uses very low energy fluences to precisely destroy the epidermis and superficial papillary dermis. It produces coagulation of the epidermis, which is wiped off, and the wound on the lip is allowed to heal by second intention.
- The erbium:yttrium-aluminum-garnet (Er:YAG) laser is an alternative. It is associated with high cure rates with no recurrences, satisfactory cosmetic results, a short healing period, and no functional or anatomic alterations.[113]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
surgical vermilionectomy
Comments
- Consists of a partial or complete shave excision of the vermilion, followed by primary closure with an oral mucosal flap.
- Highly effective, with excellent cosmetic and functional outcomes.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
back of hands
thin lesions, few in number
cryosurgery
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AK.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
topical fluorouracil
Primary Options
- fluorouracil topical
(0.5%) apply to the affected area(s) once daily for 1-4 weeks; (5%) apply to the affected area(s) twice daily for 2-4 weeks
- fluorouracil topical
Comments
- Field treatment with topical fluorouracil, a topical antimetabolite, is recommended to treat patients with AKs.[48]
- Among patients with multiple AK lesions (who underwent initial curettage), the probability of remaining free from treatment failure 12 months after the end of treatment was significantly greater among patients who received 5% fluorouracil (74.7%) than among those who received imiquimod or methyl aminolevulinate photodynamic therapy (53.9%, 37.7%, respectively).[91]
- High treatment failure rates, that may in part be attributable to reduced adherence subsequent to adverse effects (e.g., severe erythema, pain, stinging), have been reported among patients treated with 5% fluorouracil.[28] [92] [93] There is some evidence to suggest that 0.5% fluorouracil has similar efficacy to the 5% formulation, with reduced risk of adverse effects.[94] [95]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
thin lesions, numerous
cryosurgery
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AK.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
chemical peels
Primary Options
- trichloroacetic acid topical
(35-45%) apply to affected area(s) after oil debridement with acetone
- trichloroacetic acid topical
- salicylic acid topical
(20-30%) apply to affected area(s) after degreasing with acetone or alcohol
- salicylic acid topical
Comments
- Chemical peels are a treatment option for thin, numerous lesions.[89]
- An application of caustic agent to the skin surface induces necrosis of a specific skin layer. The depth of the peel depends not only on the agent but also on its concentration, time of application, and thickness of the skin area to be treated.
- Trichloroacetic acid, alpha hydroxy acids (including glycolic acid), and beta hydroxy acids (including salicylic acid) are medium-depth chemical peels. Trichloroacetic acid was not as effective as aminolevulinic acid photodynamic therapy for the treatment of multiple AKs in a small randomized observer-blinded comparative study.[90]
- Jessner peel (salicylic acid, lactic acid, and resorcinol) is a superficial-depth peel facilitating intraepidermic necrosis. Every application coat increases level of penetration, although usually there is no risk to deeper penetration or additional damage to the skin (overpeel).
- These products may need to be specially compounded by a pharmacist as they may not be available commercially.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
topical fluorouracil
Primary Options
- fluorouracil topical
(0.5%) apply to the affected area(s) once daily for 1-4 weeks; (5%) apply to the affected area(s) twice daily for 2-4 weeks
- fluorouracil topical
Comments
- Field treatment with topical fluorouracil, a topical antimetabolite, is recommended to treat patients with AKs.[48]
- Among patients with multiple AK lesions (who underwent initial curettage), the probability of remaining free from treatment failure 12 months after the end of treatment was significantly greater among patients who received 5% fluorouracil (74.7%) than among those who received imiquimod or methyl aminolevulinate photodynamic therapy (53.9%, 37.7%, respectively).[91]
- High treatment failure rates, that may in part be attributable to reduced adherence subsequent to adverse effects (e.g., severe erythema, pain, stinging), have been reported among patients treated with 5% fluorouracil.[28] [92] [93] There is some evidence to suggest that 0.5% fluorouracil has similar efficacy to the 5% formulation, with reduced risk of adverse effects.[94] [95]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
curettage ± electrodesiccation
Comments
- Curettage is an alternative surgical choice for thick isolated lesions of the scalp, ears, nose, cheeks, forehead, and perioral region that fail to respond to topical therapy, and where there is suspicion of squamous cell carcinoma.[12] It is performed by mechanically scraping away the atypical keratinocytes with a curette, thereby providing tissue samples for histologic evaluation.
- Unlike cryosurgery, which can be performed in the office setting, curettage requires intradermal local anesthetic, and scarring is seen more frequently.[28] Experience is required to perform curettage, to feel the difference between atypical cells and healthy dermal tissue, where the scraping should stop in all perimeters.[2]
- Curettage may be used alone or in combination with electrodesiccation, cryotherapy, chemical applications, or photodynamic therapy.
- Electrodesiccation is used in addition to curettage when residual marginal lesions require destruction, and if further hemostasis is necessary.
- If collecting for histopathology, care should be taken to preserve the tissue and collection should be done before electrodesiccation.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
photodynamic therapy
Comments
- Photodynamic therapy (PDT) uses a specific wavelength of light to induce the production of cytotoxic substances when applied to skin previously treated with a photosensitizing agent (e.g., aminolevulinic acid).
- Evidence suggests that PDT with aminolevulinic acid is highly effective for treating AKs.[81] [82] [83] [84] [85] [86] [87] Conventional PDT with aminolevulinic acid has been substantially evaluated for the management of thin and moderate-thickness nonhyperkeratotic AKs of the face and scalp.[88] US guidelines conditionally recommend aminolevulinic acid blue-light PDT (moderate-quality evidence) and aminolevulinic acid red-light PDT (low-quality evidence); aminolevulinic acid daylight PDT is less painful than aminolevulinic acid red-light PDT, but equally effective (moderate-quality evidence).[48]
- PDT protocols and duration vary because photosensitizing compound incubation time and need for occlusion can vary depending on the aminolevulinic acid formulation used. The primary photosensitizing agent used in the US is aminolevulinic acid; methyl aminolevulinate is not available in the US.[48] A range of light sources can be used.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
thick lesions (any number)
cryosurgery
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AK.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
curettage ± electrodesiccation
Comments
- Curettage is an alternative surgical choice for thick isolated lesions of the scalp, ears, nose, cheeks, forehead, and perioral region that fail to respond to topical therapy, and where there is suspicion of squamous cell carcinoma.[12] It is performed by mechanically scraping away the atypical keratinocytes with a curette, thereby providing tissue samples for histologic evaluation.
- Unlike cryosurgery, which can be performed in the office setting, curettage requires intradermal local anesthetic, and scarring is seen more frequently.[28] Experience is required to perform curettage, to feel the difference between atypical cells and healthy dermal tissue, where the scraping should stop in all perimeters.[2]
- Curettage may be used alone or in combination with electrodesiccation, cryotherapy, chemical applications, or photodynamic therapy.
- Electrodesiccation is used in addition to curettage when residual marginal lesions require destruction, and if further hemostasis is necessary.
- If collecting for histopathology, care should be taken to preserve the tissue and collection should be done before electrodesiccation.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
below the knee
thick or thin lesions, few in number
cryosurgery + leg compression and elevation
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AK.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All treatment modalities can lead to poor healing and ulceration in this location (below the knee). Compression bandaging and elevation of the leg(s) should be combined with the treatment.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
curettage ± electrodesiccation + leg compression and elevation
Comments
- Curettage is an alternative surgical choice for thick isolated lesions of the scalp, ears, nose, cheeks, forehead, and perioral region that fail to respond to topical therapy, and where there is suspicion of squamous cell carcinoma.[12] It is performed by mechanically scraping away the atypical keratinocytes with a curette, thereby providing tissue samples for histologic evaluation.
- Unlike cryosurgery, which can be performed in the office setting, curettage requires intradermal local anesthetic, and scarring is seen more frequently.[28] Experience is required to perform curettage, to feel the difference between atypical cells and healthy dermal tissue, where the scraping should stop in all perimeters.[2]
- Curettage may be used alone or in combination with electrodesiccation, cryotherapy, chemical applications, or photodynamic therapy.
- Electrodesiccation is used in addition to curettage when residual marginal lesions require destruction, and if further hemostasis is necessary.
- If collecting for histopathology, care should be taken to preserve the tissue, and collection should be done before electrodesiccation.
- All treatment modalities can lead to poor healing and ulceration in this location (below the knee). Compression bandaging and elevation of the leg(s) should be combined with the treatment.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
thin lesions, numerous
chemical peels + leg compression and elevation
Primary Options
- trichloroacetic acid topical
(35-45%) apply to affected area(s) after oil debridement with acetone
- trichloroacetic acid topical
- salicylic acid topical
(20-30%) apply to affected area(s) after degreasing with acetone or alcohol
- salicylic acid topical
Comments
- Chemical peels are a treatment option for thin, numerous lesions (field treatment).[89]
- An application of caustic agent to the skin surface induces necrosis of a specific skin layer. The depth of the peel depends not only on the agent but also on its concentration, time of application, and thickness of the skin area to be treated.
- Trichloroacetic acid, alpha hydroxy acids (including glycolic acid), and beta hydroxy acids (including salicylic acid) are medium-depth chemical peels. Trichloroacetic acid was not as effective as aminolevulinic acid photodynamic therapy for the treatment of multiple AKs in a small randomized observer-blinded comparative study.[90]
- Jessner peel (salicylic acid, lactic acid, and resorcinol) is a superficial-depth peel facilitating intraepidermic necrosis. Every application coat increases level of penetration, although usually there is no risk to deeper penetration or additional damage to the skin (overpeel).
- These products may need to be specially compounded by a pharmacist as they may not be available commercially.
- All treatment modalities can lead to poor healing and ulceration in this location (below the knee). Compression bandaging and elevation of the leg(s) should be combined with the treatment.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
cryosurgery + leg compression and elevation
Comments
- Cryosurgery with liquid nitrogen is recommended to treat AK.[48] It is the preferred therapy for thick and thin lesions in many different anatomic locations.
- Patient discomfort and long-term adverse effects (hypopigmentation, scarring) may serve as practical limitations to the absolute number of AK lesions that can be treated using cryotherapy.[48] Extensive cryosurgery over large areas to treat fields of AKs and background damage has, however, been reported.[80]
- All treatment modalities can lead to poor healing and ulceration in this location (below the knee). Compression bandaging and elevation of the leg(s) should be combined with the treatment.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
photodynamic therapy + leg compression and elevation
Comments
- Photodynamic therapy (PDT) uses a specific wavelength of light to induce the production of cytotoxic substances when applied to skin previously treated with a photosensitizing agent (e.g., aminolevulinic acid).
- Evidence suggests that PDT with aminolevulinic acid is highly effective for treating AKs.[81] [82] [83] [84] [85] [86] [87] Conventional PDT with aminolevulinic acid has been substantially evaluated for the management of thin and moderate-thickness nonhyperkeratotic AKs of the face and scalp.[88] US guidelines conditionally recommend aminolevulinic acid blue-light PDT (moderate-quality evidence) and aminolevulinic acid red-light PDT (low-quality evidence); aminolevulinic acid daylight PDT is less painful than aminolevulinic acid red-light PDT, but equally effective (moderate-quality evidence).[48]
- Treatment protocols
- PDT protocols and duration vary because photosensitizing compound incubation time and need for occlusion can vary depending on the aminolevulinic acid formulation used. The primary photosensitizing agent used in the US is aminolevulinic acid; methyl aminolevulinate is not available in the US.[48] A range of light sources can be used.
- All treatment modalities can lead to poor healing and ulceration in this location (below the knee). Compression bandaging and elevation of the leg(s) should be combined with the treatment.
- All patients with AKs should wear broad-spectrum sunscreen (i.e., protection against UVA and UVB), with a sun protection factor of 15 or higher.[48]
Emerging Tx
Niacinamide
Low-dose fluorouracil in salicylic acid
Fluorouracil cream (4%) with peanut oil
Prevention
Primary Prevention
Secondary Prevention
Follow-Up Overview
Prognosis
Outcome in high-risk people (e.g., immunocompromised)
Treatment outcomes
Monitoring
Complications
Citations
de Berker D, McGregor JM, Mohd Mustapa MF, et al. British Association of Dermatologists' guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol. 2017 Jan;176(1):20-43.[Abstract]
Eisen DB, Asgari MM, Bennett DD, et al. Guidelines of care for the management of actinic keratosis. J Am Acad Dermatol. 2021 Oct;85(4):e209-33.[Abstract][Full Text]
Berman B, Bienstock L, Kuritzky L, et al. Primary Care Education Consortium; Texas Academy of Family Physicians. Actinic keratoses: sequelae and treatments. Recommendations from a consensus panel. J Fam Pract. 2006 May;55(5):suppl 1-8.[Abstract]
European Dermatology Forum. Evidence and consensus based (S3) guidelines for the treatment of actinic keratosis. 2015 [internet publication].[Full Text]
European Dermatology Forum. Evidence and consensus based (S3) guidelines for the treatment of actinic keratosis. 2015 [internet publication].[Full Text]
Eisen DB, Dellavalle RP, Frazer-Green L, et al. Focused update: guidelines of care for the management of actinic keratosis. J Am Acad Dermatol. 2022 Aug;87(2):373-4.e5.[Abstract][Full Text]
1. Moy R. Clinical presentation of actinic keratosis and squamous cell carcinoma. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):8-10.[Abstract]
2. Berman B, Bienstock L, Kuritzky L, et al. Primary Care Education Consortium; Texas Academy of Family Physicians. Actinic keratoses: sequelae and treatments. Recommendations from a consensus panel. J Fam Pract. 2006 May;55(5):suppl 1-8.[Abstract]
3. Hawrot A, Alam M, Ratner D. Squamous cell carcinoma. Curr Probl Dermatol. 2003 May 1;15(3):91-133.
4. Schwartz RA. The actinic keratosis: a perspective and update. Dermatol Surg. 1997 Nov;23(11):1009-19.[Abstract]
5. Kuflik AS, Schwartz RA. Actinic keratosis and squamous cell carcinoma. Am Fam Physician. 1994 Mar;49(4):817-20.[Abstract]
6. Chung HJ, McGuigan KL, Osley KL, et al. Pigmented solar (actinic) keratosis: an underrecognized collision lesion. J Am Acad Dermatol. 2013 Apr;68(4):647-53.[Abstract]
7. Yu RC, Pryce DW, Macfarlane AW, et al. A histopathological study of 643 cutaneous horns. Br J Dermatol. 1991 May;124(5):449-52.[Abstract]
8. Schosser RH, Hodge SJ, Gaba CR, et al. Cutaneous horns: a histopathologic study. South Med J. 1979 Sep;72(9):1129-31.[Abstract]
9. Hemminki K, Zhang H, Czene K. Time trends and familial risks in squamous cell carcinoma of the skin. Arch Dermatol. 2003 Jul;139(7):885-9.[Abstract][Full Text]
10. Diepgen TL, Mahler V. The epidemiology of skin cancer. Br J Dermatol. 2002 Apr;146 Suppl 61:1-6.[Abstract]
11. Christenson LJ, Borrowman TA, Vachon CM, et al. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA. 2005 Aug 10;294(6):681-90.[Abstract][Full Text]
12. de Berker D, McGregor JM, Mohd Mustapa MF, et al. British Association of Dermatologists' guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol. 2017 Jan;176(1):20-43.[Abstract]
13. Anwar J, Wrone DA, Kimyai-Asadi A, et al. The development of actinic keratosis into invasive squamous cell carcinoma: evidence and evolving classification schemes. Clin Dermatol. 2004 May-Jun;22(3):189-96.[Abstract]
14. Helfand M, Gorman AK, Mahon S, et al; US Department of Health and Human Services. Actinic keratoses: final report. May 2001 [internet publication].[Full Text]
15. Lookingbill DP, Lookingbill GL, Leppard B. Actinic damage and skin cancer in albinos in northern Tanzania: findings in 164 patients enrolled in an outreach skin care program. J Am Acad Dermatol. 1995 Apr;32(4):653-8.[Abstract]
16. Lehmann AR, Bridges BA. Sunlight-induced cancer: some new aspects and implications of the xeroderma pigmentosum model. Br J Dermatol. 1990 Apr;122 Suppl 35:115-9.[Abstract]
17. Lambert WC, Kuo HR, Lambert MW. Xeroderma pigmentosum. Dermatol Clin. 1995 Jan;13(1):169-209.[Abstract]
18. Luande J, Henschke CI, Mohammed N. The Tanzanian human albino skin. Natural history. Cancer. 1985 Apr 15;55(8):1823-8.[Abstract]
19. Memon AA, Tomenson JA, Bothwell J. Prevalence of solar damage and actinic keratosis in a Merseyside population. Br J Dermatol. 2000 Jun;142(6):1154-9.[Abstract]
20. Zagula-Mally ZW, Rosenberg EW, Kashgarian M. Frequency of skin cancer and solar keratoses in a rural southern county as determined by population sampling. Cancer. 1974 Aug;34(2):345-9.[Abstract]
21. Frost C, Williams G, Green A. High incidence and regression rates of solar keratoses in a Queensland community. J Invest Dermatol. 2000 Aug;115(2):273-7.[Abstract][Full Text]
22. Green A, Beardmore G, Hart V, et al. Skin cancer in a Queensland population. J Am Acad Dermatol. 1988 Dec;19(6):1045-52.[Abstract]
23. Cooper KD, Fox P, Neises G, et al. Effects of ultraviolet radiation on human epidermal cell alloantigen presentation: initial depression of Langerhans cell-dependent function is followed by the appearance of T6- Dr+ cells that enhance epidermal alloantigen presentation. J Immunol. 1985 Jan;134(1):129-37.[Abstract]
24. Granstein RD, Askari M, Whitaker D, et al. Epidermal cells in activation of suppressor lymphocytes: further characterization. J Immunol. 1987 Jun 15;138(12):4055-62.[Abstract]
25. Winkelmann, Baldes EJ, Zollman PE. Squamous cell tumors induced in hairless mice with ultraviolet light. J Invest Dermatol. 1960 Feb;34:131-8.[Abstract]
26. Nomura T, Nakajima H, Hongyo T, et al. Induction of cancer, actinic keratosis, and specific p53 mutations by UVB light in human skin maintained in severe combined immunodeficient mice. Cancer Res. 1997 Jun 1;57(11):2081-4.[Abstract][Full Text]
27. Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene. Nature. 1991 Jun 6;351(6326):453-6.[Abstract]
28. Fu W, Cockerell CJ. The actinic (solar) keratosis: a 21st-century perspective. Arch Dermatol. 2003 Jan;139(1):66-70.[Abstract]
29. Del Rosso JQ. Current regimens and guideline implications for the treatment of actinic keratosis: proceedings of a clinical roundtable at the 2011 Winter Clinical Dermatology Conference. Cutis. 2011 Jul;88(1):suppl 1-8.[Abstract]
30. Vogelstein B, Kinzler KW. p53 function and dysfunction. Cell. 1992 Aug 21;70(4):523-6.[Abstract]
31. Lane DP. Cancer. p53, guardian of the genome. Nature. 1992 Jul 2;358(6381):15-6.[Abstract]
32. Satchell AC, Barnetson RS, Halliday GM. Increased Fas ligand expression by T cells and tumour cells in the progression of actinic keratosis to squamous cell carcinoma. Br J Dermatol. 2004 Jul;151(1):42-9.[Abstract]
33. Clifford JL, Walch E, Yang X, et al. Suppression of type I interferon signaling proteins is an early event in squamous skin carcinogenesis. Clin Cancer Res. 2002 Jul;8(7):2067-72.[Abstract][Full Text]
34. Yaar M, Karassik RL, Schnipper LE, et al. Effects of alpha and beta interferons on cultured human keratinocytes. J Invest Dermatol. 1985 Jul;85(1):70-4.[Abstract]
35. Bromberg JF, Horvath CM, Wen Z, et al. Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7673-8.[Abstract][Full Text]
36. Smit NP, Vink AA, Kolb RM, et al. Melanin offers protection against induction of cyclobutane pyrimidine dimers and 6-4 photoproducts by UVB in cultured human melanocytes. Photochem Photobiol. 2001 Sep;74(3):424-30.[Abstract]
37. Ortonne JP. Photoprotective properties of skin melanin. Br J Dermatol. 2002 Apr;146 Suppl 61:7-10.[Abstract]
38. Frost CA, Green AC. Epidemiology of solar keratoses. Br J Dermatol. 1994 Oct;131(4):455-64.[Abstract]
39. Giles GG, Marks R, Foley P. Incidence of non-melanocytic skin cancer treated in Australia. Br Med J (Clin Res Ed). 1988 Jan 2;296(6614):13-7.[Abstract][Full Text]
40. Marks R, Jolley D, Lectsas S, Foley P. The role of childhood exposure to sunlight in the development of solar keratoses and non-melanocytic skin cancer. Med J Aust. 1990 Jan 15;152(2):62-6.[Abstract]
41. Salasche SJ. Epidemiology of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):4-7.[Abstract]
42. Stockfleth E, Ulrich C, Meyer T, et al. Epithelial malignancies in organ transplant patients: clinical presentation and new methods of treatment. Recent Results Cancer Res. 2002;160:251-8.[Abstract]
43. Ulrich C, Schmook T, Sachse MM, et al. Comparative epidemiology and pathogenic factors for nonmelanoma skin cancer in organ transplant patients. Dermatol Surg. 2004 Apr;30(4 Pt 2):622-7.[Abstract]
44. Thompson SC, Jolley D, Marks R. Reduction of solar keratoses by regular sunscreen use. N Engl J Med. 1993 Oct 14;329(16):1147-51.[Abstract]
45. Naylor MF, Boyd A, Smith DW, et al. High sun protection factor sunscreens in the suppression of actinic neoplasia. Arch Dermatol. 1995 Feb;131(2):170-5.[Abstract]
46. Rigel DS. Photoprotection: a 21st century perspective. Br J Dermatol. 2002 Apr;146 Suppl 61:34-7.[Abstract]
47. Darlington S, Williams G, Neale R, et al. A randomized controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses. Arch Dermatol. 2003 Apr;139(4):451-5.[Abstract][Full Text]
48. Eisen DB, Asgari MM, Bennett DD, et al. Guidelines of care for the management of actinic keratosis. J Am Acad Dermatol. 2021 Oct;85(4):e209-33.[Abstract][Full Text]
49. Black HS, Herd JA, Goldberg LH, et al. Effect of a low-fat diet on the incidence of actinic keratosis. N Engl J Med. 1994 May 5;330(18):1272-5.[Abstract]
50. Zalaudek I, Giacomel J, Argenziano G, et al. Dermoscopy of facial nonpigmented actinic keratosis. Br J Dermatol. 2006 Nov;155(5):951-6.[Abstract]
51. Zalaudek I, Giacomel J, Schmid K, et al. Dermatoscopy of facial actinic keratosis, intraepidermal carcinoma, and invasive squamous cell carcinoma: A progression model. J Am Acad Dermatol. 2012 Apr;66(4):589-97.[Abstract]
52. Quaedvlieg PJ, Tirsi E, Thissen MR, et al. Actinic keratosis: how to differentiate the good from the bad ones? Eur J Dermatol. 2006 Jul-Aug;16(4):335-9.[Abstract]
53. Elder DE, Elenitsas R, Johnson Jr. BL, et al. Lever's histopathology of the skin. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
54. Stolz W, Braun-Falco O, Bilek P, et al. Color atlas of dermatoscopy. 1st ed. London, UK: Blackwell Science Ltd; 1994.
55. Menzies SW, Crotty KA, Ingvar C, et al. An atlas of surface microscopy of pigmented skin lesions. 1st ed. Sydney, Australia: McGraw-Hill Book Company Australia Pty Limited; 1996.
56. Donnelly AM, Halbert AR, Rohr JB. Discoid lupus erythematosus. Australas J Dermatol. 1995 Feb;36(1):3-10; quiz 11-2.[Abstract]
57. Weber F, Fritsch P. Clinical differential diagnosis of cutaneous lupus erythematosus. In: Kuhn A, Lehmann P, Ruzica T, eds. Cutaneous lupus erythematosus. Berlin: Springer-Verlag; 2005.
58. Kontos AP, Jirsari M, Jacobsen G, et al. Immunoglobulin M predominance in cutaneous lupus erythematosus. J Cutan Pathol. 2005 May;32(5):352-5.[Abstract]
59. Zedek DC, Smith ET Jr, Hitchcock MG, et al. Cutaneous lupus erythematosus simulating squamous neoplasia: the clinicopathologic conundrum and histopathologic pitfalls. J Am Acad Dermatol. 2007 Jun;56(6):1013-20.[Abstract]
60. Perniciaro C, Randle HW, Perry HO. Hypertrophic discoid lupus erythematosus resembling squamous cell carcinoma. Dermatol Surg. 1995 Mar;21(3):255-7.[Abstract]
61. Uitto J, Santa-Cruz DJ, Eisen AZ, et al. Verrucous lesion in patients with discoid lupus erythematosus. Clinical, histopathological and immunofluorescence studies. Br J Dermatol. 1978 May;98(5):507-20.[Abstract]
62. Patel P, Werth V. Cutaneous lupus erythematosus: a review. Dermatol Clin. 2002 Jul;20(3):373-85.[Abstract]
63. Reid C. Drug treatment of cutaneous lupus. Am J Clin Dermatol. 2000 Nov-Dec;1(6):375-9.[Abstract]
64. Tebbe B, Orfanos CE. Epidemiology and socioeconomic impact of skin disease in lupus erythematosus. Lupus. 1997 Feb 1;6(2):96-104.[Abstract]
65. Sontheimer RD. Subacute cutaneous lupus erythematosus: a decade's perspective. Med Clin North Am. 1989 Sep;73(5):1073-90.[Abstract]
66. Telfer NR, Chalmers RJ, Whale K, et al. The role of streptococcal infection in the initiation of guttate psoriasis. Arch Dermatol. 1992 Jan;128(1):39-42.[Abstract]
67. Christophers E, Kiene P. Guttate and plaque psoriasis. Dermatol Clin. 1995 Oct;13(4):751-6.[Abstract]
68. Mehregan DR, Hamzavi F, Brown K. Large cell acanthoma. Int J Dermatol. 2003 Jan;42(1):36-9.[Abstract]
69. Roewert HJ, Ackerman AB. Large-cell acanthoma is a solar lentigo. Am J Dermatopathol. 1992 Apr;14(2):122-32.[Abstract]
70. Sanchez Yus E, del Rio E, Requena L. Large-cell acanthoma is a distinctive condition. Am J Dermatopathol. 1992 Apr;14(2):140-7.[Abstract]
71. Rahbari H, Pinkus H. Large cell acanthoma. One of the actinic keratoses. Arch Dermatol. 1978 Jan;114(1):49-52.[Abstract]
72. Sanchez Yus E, de Diego V, Urrutia S. Large cell acanthoma. A cytologic variant of Bowen's disease? Am J Dermatopathol. 1988 Jun;10(3):197-208.[Abstract]
73. Uhlenhake EE, Sangueza OP, Lee AD, et al. Spreading pigmented actinic keratosis: a review. J Am Acad Dermatol. 2010 Sep;63(3):499-506.[Abstract]
74. Yantsos VA, Conrad N, Zabawski E, et al. Incipient intraepidermal cutaneous squamous cell carcinoma: a proposal for reclassifying and grading solar (actinic) keratoses. Semin Cutan Med Surg. 1999 Mar;18(1):3-14.[Abstract]
75. Carag HR, Prieto VG, Yballe LS, et al. Utility of step sections: demonstration of additional pathological findings in biopsy samples initially diagnosed as actinic keratosis. Arch Dermatol. 2000 Apr;136(4):471-5.[Abstract][Full Text]
76. Scurry J. Grading of actinic keratoses. J Am Acad Dermatol. 2001 Jun;44(6):1052-3.[Abstract]
77. Berman B, Bienstock L, Kuritzky L, et al. Primary Care Education Consortium; Texas Academy of Family Physicians. Actinic keratoses: sequelae and treatments. Recommendations from a consensus panel. J Fam Pract. 2006 May;55(5):suppl 1-8.[Abstract]
78. European Dermatology Forum. Evidence and consensus based (S3) guidelines for the treatment of actinic keratosis. 2015 [internet publication].[Full Text]
79. European Dermatology Forum. Evidence and consensus based (S3) guidelines for the treatment of actinic keratosis. 2015 [internet publication].[Full Text]
80. Chiarello SE. Cryopeeling (extensive cryosurgery) for treatment of actinic keratoses: an update and comparison. Dermatol Surg. 2000 Aug;26(8):728-32.[Abstract]
81. Gupta AK, Paquet M, Villanueva E, et al. Interventions for actinic keratoses. Cochrane Database Syst Rev. 2012 Dec 12;12(12):CD004415.[Abstract][Full Text]
82. Patel G, Armstrong AW, Eisen DB. Efficacy of photodynamic therapy vs other interventions in randomized clinical trials for the treatment of actinic keratoses: a systematic review and meta-analysis. JAMA Dermatol. 2014 Dec;150(12):1281-8.[Abstract][Full Text]
83. Brian Jiang SI, Kempers S, Rich P, et al. A randomized, vehicle-controlled phase 3 study of aminolevulinic acid photodynamic therapy for the treatment of actinic keratoses on the upper extremities. Dermatol Surg. 2019 Jul;45(7):890-7.[Abstract]
84. Touma D, Yaar M, Whitehead S, et al. A trial of short incubation, broad-area photodynamic therapy for facial actinic keratoses and diffuse photodamage. Arch Dermatol. 2004 Jan;140(1):33-40.[Abstract][Full Text]
85. Braathen LR, Szeimies RM, Basset-Seguin N, et al; International Society for Photodynamic Therapy in Dermatology. Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005. J Am Acad Dermatol. 2007 Jan;56(1):125-43.[Abstract]
86. Piacquadio DJ, Chen DM, Farber HF, et al. Photodynamic therapy with aminolevulinic acid topical solution and visible blue light in the treatment of multiple actinic keratoses of the face and scalp: investigator-blinded, phase 3, multicenter trials. Arch Dermatol. 2004 Jan;140(1):41-6.[Abstract][Full Text]
87. Fayter D, Corbett M, Heirs M, et al. A systematic review of photodynamic therapy in the treatment of pre-cancerous skin conditions, Barrett's oesophagus and cancers of the biliary tract, brain, head and neck, lung, oesophagus and skin. Health Technol Assess. 2010 Jul;14(37):1-288.[Abstract]
88. Morton CA, Szeimies RM, Basset-Seguin N, et al. European Dermatology Forum guidelines on topical photodynamic therapy 2019 part 1: treatment delivery and established indications - actinic keratoses, Bowen's disease and basal cell carcinomas. J Eur Acad Dermatol Venereol. 2019 Dec;33(12):2225-38.[Abstract][Full Text]
89. Jiang AJ, Soon SL, Rullan P, et al. Chemical peels as field therapy for actinic keratoses: a systematic review. Dermatol Surg. 2021 Oct 1;47(10):1343-6.[Abstract]
90. Holzer G, Pinkowicz A, Radakovic S, et al. Randomized controlled trial comparing 35% trichloroacetic acid peel and 5-aminolaevulinic acid photodynamic therapy for treating multiple actinic keratosis. Br J Dermatol. 2017 May;176(5):1155-61.[Abstract]
91. Jansen MHE, Kessels JPHM, Nelemans PJ, et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med. 2019 Mar 7;380(10):935-46.[Abstract][Full Text]
92. Krawtchenko N, Roewert-Huber J, Ulrich M, et al. A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up. Br J Dermatol. 2007 Dec;157 (Suppl 2):34-40.[Abstract]
93. Stockfleth E, Zwingers T, Willers C. Recurrence rates and patient assessed outcomes of 0.5% 5-fluorouracil in combination with salicylic acid treating actinic keratoses. Eur J Dermatol. 2012 May-Jun;22(3):370-4.[Abstract]
94. Kaur RR, Alikhan A, Maibach HI. Comparison of topical 5-fluorouracil formulations in actinic keratosis treatment. J Dermatolog Treat. 2010 Sep;21(5):267-71.[Abstract]
95. Loven K, Stein L, Furst K, et al. Evaluation of the efficacy and tolerability of 0.5% fluorouracil cream and 5% fluorouracil cream applied to each side of the face in patients with actinic keratosis. Clin Ther. 2002 Jun;24(6):990-1000.[Abstract]
96. Swanson N, Abramovits W, Berman B, et al. 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 2-week cycles. J Am Acad Dermatol. 2010 Apr;62(4):582-90.[Abstract]
97. Hanke CW, Beer KR, Stockfleth E, et al. 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 Apr;62(4):573-81.[Abstract]
98. Stockfleth E, Christophers E, Benninghoff B, et al. Low incidence of new actinic keratoses after topical 5% imiquimod cream treatment: a long-term follow-up study. Arch Dermatol. 2004 Dec;140(12):1542.[Abstract]
99. Lee PK, Harwell WB, Loven KH, et al. Long-term clinical outcomes following treatment of actinic keratosis with imiquimod 5% cream. Dermatol Surg. 2005 Jun;31(6):659-64.[Abstract]
100. Gebauer K, Brown P, Varigos G. Topical diclofenac in hyaluronan gel for the treatment of solar keratoses. Australas J Dermatol. 2003 Feb;44(1):40-3.[Abstract]
101. Wolf JE Jr, Taylor JR, Tschen E, et al. Topical 3.0% diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses. Int J Dermatol. 2001 Nov;40(11):709-13.[Abstract]
102. Nelson C, Rigel D. Long-term follow up of diclofenac sodium 3% in 2.5% hyaluronic acid gel for actinic keratosis: one-year evaluation. J Clin Aesth Dermatol. 2009 Jul;2(7):20-5.[Full Text]
103. Berman B, Villa AM, Ramirez CC. Mechanisms of action of new treatment modalities for actinic keratosis. J Drugs Dermatol. 2006 Feb;5(2):167-73.[Abstract]
104. Smith SR, Morhenn VB, Piacquadio DJ. Bilateral comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% 5-fluorouracil cream in the treatment of actinic keratoses of the face and scalp. J Drugs Dermatol. 2006 Feb;5(2):156-9.[Abstract]
105. Iraji F, Siadat AH, Asilian A, et al. The safety of diclofenac for the management and treatment of actinic keratoses. Expert Opin Drug Saf. 2008 Mar;7(2):167-72.[Abstract]
106. ClinicalTrials.gov. A multi-center study to evaluate the efficacy and safety of KX2-391 ointment 1% on AK on face or scalp (AK003). April 2021 [internet publication].[Full Text]
107. ClinicalTrials.gov. A multi-center study to evaluate the efficacy and safety of KX2-391 ointment 1% on actinic keratosis on face or scalp (AK004). March 2021 [internet publication].[Full Text]
108. Eisen DB, Dellavalle RP, Frazer-Green L, et al. Focused update: guidelines of care for the management of actinic keratosis. J Am Acad Dermatol. 2022 Aug;87(2):373-4.e5.[Abstract][Full Text]
109. Coleman WP 3rd, Yarborough JM, Mandy SH. Dermabrasion for prophylaxis and treatment of actinic keratoses. Dermatol Surg. 1996 Jan;22(1):17-21.[Abstract]
110. Perkins SW, Sklarew EC. Prevention of facial herpetic infections after chemical peel and dermabrasion: new treatment strategies in the prophylaxis of patients undergoing procedures of the perioral area. Plast Reconstr Surg. 1996 Sep;98(3):427-35.[Abstract]
111. Harmon CB. Dermabrasion. Dermatol Clin. 2001 Jul;19(3):439-42, viii.[Abstract]
112. Fewkes JL, Cheney ML, Pollack SV. Dermabrasion. In: Illustrated atlas of cutaneous surgery. 1st ed. Philadelphia, PA: J.B. Lippincott Company; 1992:26.1-26.11.
113. Orenstein A, Goldan O, Weissman O, et al. A new modality in the treatment of actinic cheilitis using the Er:YAG laser. J Cosmet Laser Ther. 2007 Mar;9(1):23-5.[Abstract]
114. Chen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med. 2015 Oct 22;373(17):1618-26.[Abstract][Full Text]
115. Dohil MA. Efficacy, Safety, and Tolerability of 4% 5-Fluorouracil Cream in a Novel Patented Aqueous Cream Containing Peanut Oil Once Daily Compared With 5% 5-Fluorouracil Cream Twice Daily: Meeting the Challenge in the Treatment of Actinic Keratosis. J Drugs Dermatol. 2016 Oct 1;15(10):1218-24.[Abstract]
116. Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet. 1988 Apr 9;1(8589):795-7.[Abstract]
117. Glogau RG. The risk of progression to invasive disease. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):23-4.[Abstract]
118. Marks R, Foley P, Goodman G, et al. Spontaneous remission of solar keratoses: the case for conservative management. Br J Dermatol. 1986 Dec;115(6):649-55.[Abstract]
119. Suchniak JM, Baer S, Goldberg LH. High rate of malignant transformation in hyperkeratotic actinic keratoses. J Am Acad Dermatol. 1997 Sep;37(3 Pt 1):392-4.[Abstract]
120. Ehrig T, Cockerell C, Piacquadio D, et al. Actinic keratoses and the incidence of occult squamous cell carcinoma: a clinical-histopathologic correlation. Dermatol Surg. 2006 Oct;32(10):1261-5.[Abstract]
121. Kinlen LJ, Sheil AG, Peto J, et al. Collaborative United Kingdom-Australasian study of cancer in patients treated with immunosuppressive drugs. Br Med J. 1979 Dec 8;2(6203):1461-6.[Abstract][Full Text]
122. Blohme I, Larko O. Skin lesions in renal transplant patients after 10-23 years of immunosuppressive therapy. Acta Derm Venereol. 1990;70(6):491-4.[Abstract]
123. Walder BK, Robertson MR, Jeremy D. Skin cancer and immunosuppression. Lancet. 1971 Dec 11;2(7737):1282-3.[Abstract]
124. Hardie IR, Strong RW, Hartley LC, et al. Skin cancer in Caucasian renal allograft recipients living in a subtropical climate. Surgery. 1980 Feb;87(2):177-83.[Abstract]
125. Bouwes Bavinck JN, Hardie DR, et al. The risk of skin cancer in renal transplant recipients in Queensland, Australia. A follow-up study. Transplantation. 1996 Mar 15;61(5):715-21.[Abstract]
126. Dinehart SM. The treatment of actinic keratoses. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):25-8.[Abstract]
127. Lubritz RR, Smolewski SA. Cryosurgery cure rate of actinic keratoses. J Am Acad Dermatol. 1982 Nov;7(5):631-2.[Abstract]
128. Thai KE, Fergin P, Freeman M, et al A prospective study of the use of cryosurgery for the treatment of actinic keratoses. Int J Dermatol. 2004 Sep;43(9):687-92.[Abstract]
129. Zouboulis CC, Rohrs H. Cryosurgical treatment of actinic keratoses and evidence-based review. Hautarzt. 2005 Apr;56(4):353-8.[Abstract]
130. Stockfleth E, Kerl H; Guideline Subcommittee of the European Dermatology Forum. Guidelines for the management of actinic keratoses. Eur J Dermatol. 2006 Nov-Dec;16(6):599-606.[Abstract]
131. Cox NH, Eedy DJ, Morton CA; Therapy Guidelines and Audit Subcommittee, British Association of Dermatologists. Guidelines for management of Bowen's disease: 2006 update. Br J Dermatol. 2007 Jan;156(1):11-21.[Abstract]
132. Montgomery H, Dorffel J. Verruca senilis und keratoma senile. Arch f Dermat u Syphil (Berlin). 1932;166:286-97.
133. Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol. 1992 Jun;26(6):976-90.[Abstract]
134. Czarnecki D, Staples M, Mar A, et al. Metastases from squamous cell carcinoma of the skin in southern Australia. Dermatology. 1994;189(1):52-4.[Abstract]
135. Lang K, Schulte KW, Ruzicka T, et al. Aminolevulinic acid (Levulan) in photodynamic therapy of actinic keratoses. Skin Therapy Lett. 2001 Sep;6(10):1-2, 5.[Abstract]
136. North P, Zembowicz A, Mihm M, et al. Sun induced skin diseases. Pathol Int. 2004;54:S559-69.
137. Monheit GD. Medium-depth chemical peels. Dermatol Clin. 2001 Jul;19(3):413-25, vii.[Abstract]
138. Grimes PE. The safety and efficacy of salicylic acid chemical peels in darker racial-ethnic groups. Dermatol Surg. 1999 Jan;25(1):18-22.[Abstract]
139. Kligman D, Kligman AM. Salicylic acid peels for the treatment of photoaging. Dermatol Surg. 1998 Mar;24(3):325-8.[Abstract]
140. Ghersetich I, Teofoll P, Gantcheva M, et al. Chemical peeling: how, when, why? J Eur Acad Dermatol Venereol. 1997 Jan;8(1):1-11.
141. Rubin MG. Salicylic acid peels (nonfacial). In: Rubin MG, ed. Manual of chemical peels. Superficial and medium depth. 1st ed. Philadelphia, PA: J.B. Lippincott Company; 1995:103-9.
142. Dolezal J. Jessner's peels. In: Rubin MG, ed. Manual of chemical peels. Superficial and medium depth. 1st ed. Philadelphia, PA: J.B. Lippincott Company; 1995:79-88.
Key Articles
Referenced Articles
Guidelines
Diagnostic
Summary
Includes diagnostic recommendations for AK.Published by
European Dermatology Forum
Published
2015
Treatment
Summary
Updated recommendations for the management of AK.Published by
American Academy of Dermatology
Published
2022
Summary
Recommendations for the management of AK.Published by
American Academy of Dermatology
Published
2021
Summary
The evidence-based recommendations in this guideline are designed for practical use in the clinic.Published by
British Association of Dermatologists
Published
2017
Summary
Provides treatment recommendations appropriate for different subgroups of patients presenting with AK.Published by
European Dermatology Forum
Published
2015
Credits
Patient Instructions
- For the initial 48 hours after photodynamic therapy
- Up to 2 weeks after any chemical peels
- During treatment with imiquimod, fluorouracil, or diclofenac
- After any of the destructive treatments.