Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

confluent scalp lesions

1st line – cryosurgery

Back
ONGOING
|
confluent scalp lesions
|
thin lesions, few in number
1st line – 

cryosurgery

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.[79]

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]

1st line – topical therapy

Back
ONGOING
|
confluent scalp lesions
|
thin lesions, few in number
1st line – 

topical therapy

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.[80]

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).

Pooled data from two randomized controlled trials indicate that 42% of patients treated with 3% diclofenac for 90 days achieved complete clearance compared with 14% for patients receiving vehicle control.[48][100][101] Longer-term efficacy has been demonstrated at 1 year.[102]

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 tirbanibulin 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]

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

OR

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

OR

diclofenac topical: (3%) apply to the affected area(s) twice daily for up to 12 weeks

OR

tirbanibulin topical: (1%) apply to the affected area(s) once daily for 5 days

1st line – chemical peels

Back
ONGOING
|
confluent scalp lesions
|
thin lesions, numerous
1st line – 

chemical peels

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 the level of penetration, although usually there is no risk of 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]

Primary options

trichloroacetic acid topical: (35-45%) apply to affected area(s) after oil debridement with acetone

More

OR

glycolic acid topical: (50-70%) apply to affected area(s) after degreasing with acetone or alcohol

More

OR

salicylic acid topical: (20-30%) apply to affected area(s) after degreasing with acetone or alcohol

More

OR

Jessner peel: apply to affected area(s) on face after degreasing with acetone or alcohol

More

1st line – topical therapy

Back
ONGOING
|
confluent scalp lesions
|
thin lesions, numerous
1st line – 

topical therapy

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.[80]

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 tirbanibulin 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]

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

OR

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

OR

tirbanibulin topical: (1%) apply to the affected area(s) once daily for 5 days

2nd line – cryosurgery

Back
ONGOING
|
confluent scalp lesions
|
thin lesions, numerous
2nd line – 

cryosurgery

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.[79]

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]

2nd line – photodynamic therapy

Back
ONGOING
|
confluent scalp lesions
|
thin lesions, numerous
2nd line – 

photodynamic therapy

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.[80][81][82][83][84][85][86]​ Conventional PDT with aminolevulinic acid has been substantially evaluated for the management of thin and moderate-thickness nonhyperkeratotic AKs of the face and scalp.[87] 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]​ The UK guidelines recommend PDT for all AKs but particularly for cosmetically sensitive areas, multiple lesions, or large lesions. For patients with residual lesions that have responded well to initial PDT, an additional treatment cycle is recommended.[88]

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]

3rd line – topical diclofenac

Back
ONGOING
|
confluent scalp lesions
|
thin lesions, numerous
3rd line – 

topical diclofenac

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).

Pooled data from two randomized controlled trials indicate that 42% of patients treated with 3% diclofenac for 90 days achieved complete clearance compared with 14% for patients receiving vehicle control.[48][100][101] Longer-term efficacy has been demonstrated at 1 year.[102]

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]

Primary options

diclofenac topical: (3%) apply to the affected area(s) twice daily for up to 12 weeks

1st line – cryosurgery

Back
ONGOING
|
confluent scalp lesions
|
thick lesions (any number)
1st line – 

cryosurgery

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.[79]

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]

2nd line – dermabrasion

Back
ONGOING
|
confluent scalp lesions
|
thick lesions (any number)
2nd line – 

dermabrasion

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]

Postoperative re-epithelialization is expected in 7 to 10 days, and redness can persist from 1 to 2 weeks up to 2 to 3 months. Complications include hypopigmentation (permanent in 10% to 20% of patients, particularly in dark-skinned males), reversible hyperpigmentation, and scarring.[111][112]

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

1st line – cryosurgery

Back
ONGOING
|
head and face lesions, excluding periorbital, actinic cheilitis, and confluent scalp lesions
|
thin lesions, few in number
1st line – 

cryosurgery

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.[79]

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]

1st line – topical therapy

Back
ONGOING
|
head and face lesions, excluding periorbital, actinic cheilitis, and confluent scalp lesions
|
thin lesions, few in number
1st line – 

topical therapy

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.[80]

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).

Pooled data from two randomized controlled trials indicate that 42% of patients treated with 3% diclofenac for 90 days achieved complete clearance compared with 14% for patients receiving vehicle control.[48][100][101] Longer-term efficacy has been demonstrated at 1 year.[102]

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 tirbanibulin 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]

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

OR

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

OR

diclofenac topical: (3%) apply to the affected area(s) twice daily for up to 12 weeks

OR

tirbanibulin topical: (1%) apply to the affected area(s) once daily for 5 days

1st line – chemical peels

Back
ONGOING
|
head and face lesions, excluding periorbital, actinic cheilitis, and confluent scalp lesions
|
thin lesions, numerous
1st line – 

chemical peels

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 the level of penetration, although usually there is no risk of 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]

Primary options

trichloroacetic acid topical: (35-45%) apply to affected area(s) after oil debridement with acetone

More

OR

glycolic acid topical: (50-70%) apply to affected area(s) after degreasing with acetone or alcohol

More

OR

salicylic acid topical: (20-30%) apply to affected area(s) after degreasing with acetone or alcohol

More

OR

Jessner peel: apply to affected area(s) on face after degreasing with acetone or alcohol

More

1st line – cryosurgery

Back
ONGOING
|
head and face lesions, excluding periorbital, actinic cheilitis, and confluent scalp lesions
|
thin lesions, numerous
1st line – 

cryosurgery

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.[79]

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]

1st line – topical therapy

Back
ONGOING
|
head and face lesions, excluding periorbital, actinic cheilitis, and confluent scalp lesions
|
thin lesions, numerous
1st line – 

topical therapy

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.[80]

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 tirbanibulin 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]

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

OR

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

OR

tirbanibulin topical: (1%) apply to the affected area(s) once daily for 5 days

2nd line – photodynamic therapy

Back
ONGOING
|
head and face lesions, excluding periorbital, actinic cheilitis, and confluent scalp lesions
|
thin lesions, numerous
2nd line – 

photodynamic therapy

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.[80][81][82][83][84][85][86]​ Conventional PDT with aminolevulinic acid has been substantially evaluated for the management of thin and moderate-thickness nonhyperkeratotic AKs of the face and scalp.[87] 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]​ The UK guidelines recommend PDT for all AKs but particularly for cosmetically sensitive areas, multiple lesions, or large lesions. For patients with residual lesions that have responded well to initial PDT, an additional treatment cycle is recommended.[88]

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]

3rd line – topical diclofenac

Back
ONGOING
|
head and face lesions, excluding periorbital, actinic cheilitis, and confluent scalp lesions
|
thin lesions, numerous
3rd line – 

topical diclofenac

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).

Pooled data from two randomized controlled trials indicate that 42% of patients treated with 3% diclofenac for 90 days achieved complete clearance compared with 14% for patients receiving vehicle control.[48][100][101] Longer-term efficacy has been demonstrated at 1 year.[102]

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]

Primary options

diclofenac topical: (3%) apply to the affected area(s) twice daily for up to 12 weeks

1st line – cryosurgery

Back
ONGOING
|
head and face lesions, excluding periorbital, actinic cheilitis, and confluent scalp lesions
|
thick lesions, few in number
1st line – 

cryosurgery

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.[79]

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]

1st line – curettage ± electrodesiccation

Back
ONGOING
|
head and face lesions, excluding periorbital, actinic cheilitis, and confluent scalp lesions
|
thick lesions, few in number
1st line – 

curettage ± electrodesiccation

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]

1st line – cryosurgery

Back
ONGOING
|
head and face lesions, excluding periorbital, actinic cheilitis, and confluent scalp lesions
|
thick lesions, numerous
1st line – 

cryosurgery

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.[79]

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]

2nd line – dermabrasion

Back
ONGOING
|
head and face lesions, excluding periorbital, actinic cheilitis, and confluent scalp lesions
|
thick lesions, numerous
2nd line – 

dermabrasion

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]

Postoperative re-epithelialization is expected in 7 to 10 days, and redness can persist from 1 to 2 weeks up to 2 to 3 months. Complications include hypopigmentation (permanent in 10% to 20% of patients, particularly in dark-skinned males), reversible hyperpigmentation, and scarring.[111][112]

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

1st line – cryosurgery

Back
ONGOING
|
periorbital
|
thin lesions, few in number
1st line – 

cryosurgery

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.[79]

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]

1st line – curettage ± electrodesiccation

Back
ONGOING
|
periorbital
|
thin lesions, numerous
1st line – 

curettage ± electrodesiccation

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]

1st line – chemical peels

Back
ONGOING
|
periorbital
|
thin lesions, numerous
1st line – 

chemical peels

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 the level of penetration, although usually there is no risk of 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]

Primary options

trichloroacetic acid topical: (35-45%) apply to affected area(s) after oil debridement with acetone

More

OR

glycolic acid topical: (50-70%) apply to affected area(s) after degreasing with acetone or alcohol

More

OR

salicylic acid topical: (20-30%) apply to affected area(s) after degreasing with acetone or alcohol

More

OR

Jessner peel: apply to affected area(s) on face after degreasing with acetone or alcohol

More

2nd line – photodynamic therapy

Back
ONGOING
|
periorbital
|
thin lesions, numerous
2nd line – 

photodynamic therapy

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.[80][81][82][83][84][85][86] Conventional PDT with aminolevulinic acid has been substantially evaluated for the management of thin and moderate-thickness nonhyperkeratotic AKs of the face and scalp.[87] 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]

1st line – cryosurgery

Back
ONGOING
|
periorbital
|
thick lesions (any number)
1st line – 

cryosurgery

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.[79]

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]

actinic cheilitis

1st line – cryosurgery

Back
ONGOING
|
actinic cheilitis
1st line – 

cryosurgery

Cryosurgery with liquid nitrogen is commonly used in clinical practice to treat actinic cheilitis, although there is very limited evidence for this indication.[115][116]

One 1983 study reported that out of 53 patients with actinic cheilitis treated with liquid nitrogen, two patients experienced recurrence.[117]

Potential adverse effects of cryosurgery include patient discomfort, local neuropathy, and cosmetic changes such as scarring and hyperpigmentation/hypopigmentation.[118]

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]

1st line – topical therapy

Back
ONGOING
|
actinic cheilitis
1st line – 

topical therapy

Topical therapies (fluorouracil, diclofenac, imiquimod, or trichloroacetic acid) are commonly used to treat actinic cheilitis. However, most of the supporting evidence for these treatments is based on their use for AK of the skin.[114][119]

One 2021 systematic review reported outcomes of fluorouracil treatment in 28 patients with actinic cheilitis across three studies.[116]​ Complete clinical response was achieved in 75% of patients, with 1% fluorouracil achieving a 100% complete response rate and 5% fluorouracil achieving 68.2%. However, the recurrence rate was relatively high at 31.8%. Histopathologic follow-up showed that 5 out of 6 patients evaluated achieved partial clearance, while one had a poor response. Ten percent of patients discontinued treatment due to adverse events, which can include erythema, edema, and ulceration for the entire course of therapy.[116][118]

The same review reported a 45.2% complete clinical response rate in 62 patients treated with 3% diclofenac (in hyaluronic acid gel).[116]​ Complete histopathologic response was achieved in 4 out of 6 assessed patients, while all six patients reported an excellent cosmetic outcome. Estimated recurrence rate was low (6.5%). Although patients generally experience fewer adverse effects with this treatment compared to other topical options for AK, 15.2% discontinued treatment due to adverse effects.[116][118]

One 2019 systematic review found that 73.3% of 30 patients with actinic cheilitis achieved a complete clinical response following treatment with 5% imiquimod.[115]​ However, only 2 out of 5 cases evaluated achieved a complete histopathologic response. Adverse effects included pain, erythema, edema, ulceration, and occasionally an atypical flu-like syndrome.[115][118]

Trichloroacetic acid is another topical option frequently used for actinic cheilitis, but there is limited evidence supporting its use. One study reported that only 3 out of 10 patients treated with trichloroacetic acid 50% had complete clinical clearance.[120]​ Adverse effects are minimal.

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]

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

OR

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

OR

diclofenac topical: (3%) apply to the affected area(s) twice daily for up to 12 weeks

OR

trichloroacetic acid topical: (35-45%) apply to affected area(s) after oil debridement with acetone

More

1st line – photodynamic therapy

Back
ONGOING
|
actinic cheilitis
1st line – 

photodynamic therapy

Evidence suggests that PDT is effective in treating actinic cheilitis.[121]

One 2022 systematic review evaluated the efficacy of different types of PDT, including aminolevulinic acid PDT, traditional PDT and daylight PDT, in 292 patients.[121] Complete clinical response was greatest for aminolevulinic acid PDT at 80.0%, with traditional PDT and daylight PDT achieving response rates of 65.1% and 76.7%, respectively. Daylight PDT was the most well-tolerated therapy.[121]

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]

1st line – laser surgery

Back
ONGOING
|
actinic cheilitis
1st line – 

laser surgery

Carbon dioxide laser therapy for actinic cheilitis has high efficacy, few recurrences, minimal scarring, and excellent cosmetic outcomes.[122][123]​ 

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.[124]

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]

2nd line – surgical vermilionectomy

Back
ONGOING
|
actinic cheilitis
2nd line – 

surgical vermilionectomy

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

1st line – cryosurgery

Back
ONGOING
|
back of hands
|
thin lesions, few in number
1st line – 

cryosurgery

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.[79]

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]

2nd line – topical fluorouracil

Back
ONGOING
|
back of hands
|
thin lesions, few in number
2nd line – 

topical fluorouracil

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]

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

1st line – cryosurgery

Back
ONGOING
|
back of hands
|
thin lesions, numerous
1st line – 

cryosurgery

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.[79]

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]

1st line – chemical peels

Back
ONGOING
|
back of hands
|
thin lesions, numerous
1st line – 

chemical peels

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]

Primary options

trichloroacetic acid topical: (35-45%) apply to affected area(s) after oil debridement with acetone

More

OR

glycolic acid topical: (50-70%) apply to affected area(s) after degreasing with acetone or alcohol

More

OR

salicylic acid topical: (20-30%) apply to affected area(s) after degreasing with acetone or alcohol

More

OR

Jessner peel: apply to affected area(s) on face after degreasing with acetone or alcohol

More

2nd line – topical fluorouracil

Back
ONGOING
|
back of hands
|
thin lesions, numerous
2nd line – 

topical fluorouracil

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]

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

2nd line – curettage ± electrodesiccation

Back
ONGOING
|
back of hands
|
thin lesions, numerous
2nd line – 

curettage ± electrodesiccation

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]

2nd line – photodynamic therapy

Back
ONGOING
|
back of hands
|
thin lesions, numerous
2nd line – 

photodynamic therapy

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.[80][81][82][83][84][85][86]​ Conventional PDT with aminolevulinic acid has been substantially evaluated for the management of thin and moderate-thickness nonhyperkeratotic AKs of the face and scalp.[87] 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]​ The UK guidelines recommend PDT for all AKs but particularly for cosmetically sensitive areas, multiple lesions, or large lesions. For patients with residual lesions that have responded well to initial PDT, an additional treatment cycle is recommended.[88]

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]

1st line – cryosurgery

Back
ONGOING
|
back of hands
|
thick lesions (any number)
1st line – 

cryosurgery

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.[79]

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]

2nd line – curettage ± electrodesiccation

Back
ONGOING
|
back of hands
|
thick lesions (any number)
2nd line – 

curettage ± electrodesiccation

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

1st line – cryosurgery + leg compression and elevation

Back
ONGOING
|
below the knee
|
thick or thin lesions, few in number
1st line – 

cryosurgery + leg compression and elevation

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.[79]

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]

2nd line – curettage ± electrodesiccation + leg compression and elevation

Back
ONGOING
|
below the knee
|
thick or thin lesions, few in number
2nd line – 

curettage ± electrodesiccation + leg compression and elevation

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]

1st line – chemical peels + leg compression and elevation

Back
ONGOING
|
below the knee
|
thin lesions, numerous
1st line – 

chemical peels + leg compression and elevation

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 the level of penetration, although usually there is no risk of 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]

Primary options

trichloroacetic acid topical: (35-45%) apply to affected area(s) after oil debridement with acetone

More

OR

glycolic acid topical: (50-70%) apply to affected area(s) after degreasing with acetone or alcohol

More

OR

salicylic acid topical: (20-30%) apply to affected area(s) after degreasing with acetone or alcohol

More

OR

Jessner peel: apply to affected area(s) on face after degreasing with acetone or alcohol

More

1st line – cryosurgery + leg compression and elevation

Back
ONGOING
|
below the knee
|
thin lesions, numerous
1st line – 

cryosurgery + leg compression and elevation

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.[79]

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]

2nd line – photodynamic therapy + leg compression and elevation

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ONGOING
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below the knee
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thin lesions, numerous
2nd line – 

photodynamic therapy + leg compression and elevation

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.[80][81][82][83][84][85][86]​ Conventional PDT with aminolevulinic acid has been substantially evaluated for the management of thin and moderate-thickness nonhyperkeratotic AKs of the face and scalp.[87] 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]​ The UK guidelines recommend PDT for all AKs but particularly for cosmetically sensitive areas, multiple lesions, or large lesions. For patients with residual lesions that have responded well to initial PDT, an additional treatment cycle is recommended.[88]

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]

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