Actinic Keratosis

ALBUQUERQUE – A long-wave infrared system distinguished malignant and benign skin lesions with a sensitivity of 96.97% and a specificity of 78.05%, with skin biopsies used as a benchmark, in a pilot study of 74 patients.

The results "suggest the technique is promising as a noninvasive screening tool" and merits continued research and development to improve sensitivity, specificity, and statistical confidence, reported Stephen Myers, Ph.D., of Skinfrared, and his associates.

Recent advances in infrared technology have led to the development of imaging devices that noninvasively detect tumors, based on differential thermal properties of malignant versus healthy tissue. The long-wave infrared detection device used in the pilot study was designed to identify thermal signatures of suspicious lesions and surrounding skin after the application of a temperature stimulus, Dr. Myers said at the annual conference of the Society for Investigative Dermatology.

In the United States skin cancers are diagnosed more often than all other cancers combined, noted Dr. Myers, but screening for them "requires the skill of a highly trained dermatologist," who must assess a range of morphologic characteristics. "This is a rather subjective approach that causes many biopsies to be performed on benign lesions," Dr. Myers added.

To test the device, investigators at the University of New Mexico, Albuquerque, Dermatology Clinic offered patients with suspicious skin lesions the option of being evaluated with the infrared device before undergoing biopsy.

The device has infrared and visible cameras, as well as a registration marker, a cold air source, and a computer and software to guide image acquisition and analysis, Dr. Myers said. Investigators placed the registration marker near the skin lesion of interest, captured a visible image of the lesion, and then took a 15-second baseline thermal image sequence. After cooling the lesions and surrounding skin to 10° C, they measured and compared 3-minute thermal recovery rates for the lesion and surrounding skin.

Participants averaged 55 years of age, and 53% were male. A total of 102 suspicious lesions were tested. Based on biopsy results, 55% were benign, 34% were basal cell carcinomas, 7% were squamous cell carcinomas, and 4% were melanomas, Dr. Myers reported. The receiver operating curve – calculated to assess the test’s ability to classify skin lesions – had an area under the curve of 95.3% (95% confidence interval, 90.0-99.0). Using biopsy results as a benchmark, the infrared device had a sensitivity of 96.97% and a specificity of 78.05%, Dr. Myers said.

The study was supported by the National Science Foundation and Skinfrared, which makes the device. Dr. Myers is an employee of Skinfrared.

ALBUQUERQUE – A long-wave infrared system distinguished malignant and benign skin lesions with a sensitivity of 96.97% and a specificity of 78.05%, with skin biopsies used as a benchmark, in a pilot study of 74 patients.

The results "suggest the technique is promising as a noninvasive screening tool" and merits continued research and development to improve sensitivity, specificity, and statistical confidence, reported Stephen Myers, Ph.D., of Skinfrared, and his associates.

Recent advances in infrared technology have led to the development of imaging devices that noninvasively detect tumors, based on differential thermal properties of malignant versus healthy tissue. The long-wave infrared detection device used in the pilot study was designed to identify thermal signatures of suspicious lesions and surrounding skin after the application of a temperature stimulus, Dr. Myers said at the annual conference of the Society for Investigative Dermatology.

In the United States skin cancers are diagnosed more often than all other cancers combined, noted Dr. Myers, but screening for them "requires the skill of a highly trained dermatologist," who must assess a range of morphologic characteristics. "This is a rather subjective approach that causes many biopsies to be performed on benign lesions," Dr. Myers added.

To test the device, investigators at the University of New Mexico, Albuquerque, Dermatology Clinic offered patients with suspicious skin lesions the option of being evaluated with the infrared device before undergoing biopsy.

The device has infrared and visible cameras, as well as a registration marker, a cold air source, and a computer and software to guide image acquisition and analysis, Dr. Myers said. Investigators placed the registration marker near the skin lesion of interest, captured a visible image of the lesion, and then took a 15-second baseline thermal image sequence. After cooling the lesions and surrounding skin to 10° C, they measured and compared 3-minute thermal recovery rates for the lesion and surrounding skin.

Participants averaged 55 years of age, and 53% were male. A total of 102 suspicious lesions were tested. Based on biopsy results, 55% were benign, 34% were basal cell carcinomas, 7% were squamous cell carcinomas, and 4% were melanomas, Dr. Myers reported. The receiver operating curve – calculated to assess the test’s ability to classify skin lesions – had an area under the curve of 95.3% (95% confidence interval, 90.0-99.0). Using biopsy results as a benchmark, the infrared device had a sensitivity of 96.97% and a specificity of 78.05%, Dr. Myers said.

The study was supported by the National Science Foundation and Skinfrared, which makes the device. Dr. Myers is an employee of Skinfrared.

ALBUQUERQUE – A long-wave infrared system distinguished malignant and benign skin lesions with a sensitivity of 96.97% and a specificity of 78.05%, with skin biopsies used as a benchmark, in a pilot study of 74 patients.

The results "suggest the technique is promising as a noninvasive screening tool" and merits continued research and development to improve sensitivity, specificity, and statistical confidence, reported Stephen Myers, Ph.D., of Skinfrared, and his associates.

Recent advances in infrared technology have led to the development of imaging devices that noninvasively detect tumors, based on differential thermal properties of malignant versus healthy tissue. The long-wave infrared detection device used in the pilot study was designed to identify thermal signatures of suspicious lesions and surrounding skin after the application of a temperature stimulus, Dr. Myers said at the annual conference of the Society for Investigative Dermatology.

In the United States skin cancers are diagnosed more often than all other cancers combined, noted Dr. Myers, but screening for them "requires the skill of a highly trained dermatologist," who must assess a range of morphologic characteristics. "This is a rather subjective approach that causes many biopsies to be performed on benign lesions," Dr. Myers added.

To test the device, investigators at the University of New Mexico, Albuquerque, Dermatology Clinic offered patients with suspicious skin lesions the option of being evaluated with the infrared device before undergoing biopsy.

The device has infrared and visible cameras, as well as a registration marker, a cold air source, and a computer and software to guide image acquisition and analysis, Dr. Myers said. Investigators placed the registration marker near the skin lesion of interest, captured a visible image of the lesion, and then took a 15-second baseline thermal image sequence. After cooling the lesions and surrounding skin to 10° C, they measured and compared 3-minute thermal recovery rates for the lesion and surrounding skin.

Participants averaged 55 years of age, and 53% were male. A total of 102 suspicious lesions were tested. Based on biopsy results, 55% were benign, 34% were basal cell carcinomas, 7% were squamous cell carcinomas, and 4% were melanomas, Dr. Myers reported. The receiver operating curve – calculated to assess the test’s ability to classify skin lesions – had an area under the curve of 95.3% (95% confidence interval, 90.0-99.0). Using biopsy results as a benchmark, the infrared device had a sensitivity of 96.97% and a specificity of 78.05%, Dr. Myers said.

The study was supported by the National Science Foundation and Skinfrared, which makes the device. Dr. Myers is an employee of Skinfrared.

ARUBA – Patients with actinic keratoses are a fixture in most dermatology practices, but is your practice up to date on the full range of treatments available?

At the Caribbean Dermatology Symposium, Dr. David Pariser presented a quick run-down of current, new, and up-and-coming treatments for AKs, including, but not limited to, cryosurgery and imiquimod.

Also, he discusses his experience with field therapy to treat AKs.

"The damage that occurred that caused the actinic keratosis in one specific spot has also occurred in adjacent areas," that can’t be detected visually, he said.

Dr. Pariser is a professor of clinical dermatology at Eastern Virginia Medical School in Norfolk, and a physician in a private group practice in Virginia.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

ARUBA – Patients with actinic keratoses are a fixture in most dermatology practices, but is your practice up to date on the full range of treatments available?

At the Caribbean Dermatology Symposium, Dr. David Pariser presented a quick run-down of current, new, and up-and-coming treatments for AKs, including, but not limited to, cryosurgery and imiquimod.

Also, he discusses his experience with field therapy to treat AKs.

"The damage that occurred that caused the actinic keratosis in one specific spot has also occurred in adjacent areas," that can’t be detected visually, he said.

Dr. Pariser is a professor of clinical dermatology at Eastern Virginia Medical School in Norfolk, and a physician in a private group practice in Virginia.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

ARUBA – Patients with actinic keratoses are a fixture in most dermatology practices, but is your practice up to date on the full range of treatments available?

At the Caribbean Dermatology Symposium, Dr. David Pariser presented a quick run-down of current, new, and up-and-coming treatments for AKs, including, but not limited to, cryosurgery and imiquimod.

Also, he discusses his experience with field therapy to treat AKs.

"The damage that occurred that caused the actinic keratosis in one specific spot has also occurred in adjacent areas," that can’t be detected visually, he said.

Dr. Pariser is a professor of clinical dermatology at Eastern Virginia Medical School in Norfolk, and a physician in a private group practice in Virginia.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Ingenol mebutate gel for the treatment of actinic keratosis is an effective adjunct therapy to cryosurgery, and the absence of attendant serious local reactions can increase compliance, based on data from more than 100 patients.

"By the time you do see a reaction, because the treatment time is only 2 or 3 days, the patient is done applying it, so the compliance is increased," Dr. Miriam S. Bettencourt, a community-based dermatologist in Las Vegas.

Dr. Bettencourt conducted her chart review of 135 patients "out of curiosity," she said in an interview. She found that at follow-ups of 1-4 months, nearly 100% of patients who received ingenol mebutate gel as an adjunctive therapy with cryosurgery for AK on the face had clearance rates of at least 75%. In addition, clearance of at least 75% was seen in 89% of patients treated on the scalp and 84% of patients treated on the forearms and/or hands. Most of the patients were male (88%), ranging in age from 39 to 85 years, with a median age of 70 years.

"One of the questions I had was, in a clinical practice, whether [the gel] mimics the clinical trial results that showed only a mild to moderate reaction," said Dr. Bettencourt. Common side affects of topical AK treatments include erythema, flaking, scaling, and crusting. In more extreme cases, vesicular pustulation is possible.

"I found that patients really didn’t complain of pain," said Dr. Bettencourt. "Most local skin reactions were resolved within a week." She prescribed moisturizers for patients whose reactions were moderate.

The findings were published in the March issue of the Journal of Drugs in Dermatology (J. Drugs Dermatol. 2014:13:269-73).

The results negate the common tenet that the more severe the reaction to the topical, the deeper the healing of the AK, said Dr. Bettencourt. "The degree of reaction does not correlate with the level of improvement. We used to think so, but that’s not true." The results show that the reaction can be "tolerable" and short lived despite dramatic results, she said.

The gel was approved by the Food and Drug Administration for use in the United States in early 2012 under the name Picato (LEO Pharmaceuticals). Unlike other topicals that must be applied over the course of weeks, the gel is applied for 2 or 3 days, with side effects lasting much of that time.

In addition to increased compliance, Dr. Bettencourt said she also measured whether her off-label "creativity" such as prescribing higher concentrations for the scalp and instructing patients to spread the gel over larger areas, yielded worthwhile results.

"I found that, especially for the face, you can spread the medication without jeopardizing the efficacy," said Dr. Bettencourt. However, when the gel is applied to the scalp, "You lose a little bit of the efficacy, because that’s a lot to cover using the prescribed three tubes, but you still get good results."

In addition, Dr. Bettencourt said that the gel offers cosmetic advantages over other treatments such as the topical imiquimod or photodynamic therapy because there is no hypo- or hyperpigmentation. And, because there is no photosensitivity associated with the gel, Dr. Bettencourt said she can offer it year-round.

She still prescribes other topicals, however, because not all patients’ insurance plans cover the gel. Medicare, does cover the gel, she noted, but only if the patient has a supplemental insurance policy.

While the study was unsponsored, and Dr. Bettencourt had no financial conflicts to disclose, she noted that she has shared her data with LEO Pharmaceuticals, the gel’s manufacturer. "They were thrilled, and helped me to put the results together," she said.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Ingenol mebutate gel for the treatment of actinic keratosis is an effective adjunct therapy to cryosurgery, and the absence of attendant serious local reactions can increase compliance, based on data from more than 100 patients.

"By the time you do see a reaction, because the treatment time is only 2 or 3 days, the patient is done applying it, so the compliance is increased," Dr. Miriam S. Bettencourt, a community-based dermatologist in Las Vegas.

Dr. Bettencourt conducted her chart review of 135 patients "out of curiosity," she said in an interview. She found that at follow-ups of 1-4 months, nearly 100% of patients who received ingenol mebutate gel as an adjunctive therapy with cryosurgery for AK on the face had clearance rates of at least 75%. In addition, clearance of at least 75% was seen in 89% of patients treated on the scalp and 84% of patients treated on the forearms and/or hands. Most of the patients were male (88%), ranging in age from 39 to 85 years, with a median age of 70 years.

"One of the questions I had was, in a clinical practice, whether [the gel] mimics the clinical trial results that showed only a mild to moderate reaction," said Dr. Bettencourt. Common side affects of topical AK treatments include erythema, flaking, scaling, and crusting. In more extreme cases, vesicular pustulation is possible.

"I found that patients really didn’t complain of pain," said Dr. Bettencourt. "Most local skin reactions were resolved within a week." She prescribed moisturizers for patients whose reactions were moderate.

The findings were published in the March issue of the Journal of Drugs in Dermatology (J. Drugs Dermatol. 2014:13:269-73).

The results negate the common tenet that the more severe the reaction to the topical, the deeper the healing of the AK, said Dr. Bettencourt. "The degree of reaction does not correlate with the level of improvement. We used to think so, but that’s not true." The results show that the reaction can be "tolerable" and short lived despite dramatic results, she said.

The gel was approved by the Food and Drug Administration for use in the United States in early 2012 under the name Picato (LEO Pharmaceuticals). Unlike other topicals that must be applied over the course of weeks, the gel is applied for 2 or 3 days, with side effects lasting much of that time.

In addition to increased compliance, Dr. Bettencourt said she also measured whether her off-label "creativity" such as prescribing higher concentrations for the scalp and instructing patients to spread the gel over larger areas, yielded worthwhile results.

"I found that, especially for the face, you can spread the medication without jeopardizing the efficacy," said Dr. Bettencourt. However, when the gel is applied to the scalp, "You lose a little bit of the efficacy, because that’s a lot to cover using the prescribed three tubes, but you still get good results."

In addition, Dr. Bettencourt said that the gel offers cosmetic advantages over other treatments such as the topical imiquimod or photodynamic therapy because there is no hypo- or hyperpigmentation. And, because there is no photosensitivity associated with the gel, Dr. Bettencourt said she can offer it year-round.

She still prescribes other topicals, however, because not all patients’ insurance plans cover the gel. Medicare, does cover the gel, she noted, but only if the patient has a supplemental insurance policy.

While the study was unsponsored, and Dr. Bettencourt had no financial conflicts to disclose, she noted that she has shared her data with LEO Pharmaceuticals, the gel’s manufacturer. "They were thrilled, and helped me to put the results together," she said.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Ingenol mebutate gel for the treatment of actinic keratosis is an effective adjunct therapy to cryosurgery, and the absence of attendant serious local reactions can increase compliance, based on data from more than 100 patients.

"By the time you do see a reaction, because the treatment time is only 2 or 3 days, the patient is done applying it, so the compliance is increased," Dr. Miriam S. Bettencourt, a community-based dermatologist in Las Vegas.

Dr. Bettencourt conducted her chart review of 135 patients "out of curiosity," she said in an interview. She found that at follow-ups of 1-4 months, nearly 100% of patients who received ingenol mebutate gel as an adjunctive therapy with cryosurgery for AK on the face had clearance rates of at least 75%. In addition, clearance of at least 75% was seen in 89% of patients treated on the scalp and 84% of patients treated on the forearms and/or hands. Most of the patients were male (88%), ranging in age from 39 to 85 years, with a median age of 70 years.

"One of the questions I had was, in a clinical practice, whether [the gel] mimics the clinical trial results that showed only a mild to moderate reaction," said Dr. Bettencourt. Common side affects of topical AK treatments include erythema, flaking, scaling, and crusting. In more extreme cases, vesicular pustulation is possible.

"I found that patients really didn’t complain of pain," said Dr. Bettencourt. "Most local skin reactions were resolved within a week." She prescribed moisturizers for patients whose reactions were moderate.

The findings were published in the March issue of the Journal of Drugs in Dermatology (J. Drugs Dermatol. 2014:13:269-73).

The results negate the common tenet that the more severe the reaction to the topical, the deeper the healing of the AK, said Dr. Bettencourt. "The degree of reaction does not correlate with the level of improvement. We used to think so, but that’s not true." The results show that the reaction can be "tolerable" and short lived despite dramatic results, she said.

The gel was approved by the Food and Drug Administration for use in the United States in early 2012 under the name Picato (LEO Pharmaceuticals). Unlike other topicals that must be applied over the course of weeks, the gel is applied for 2 or 3 days, with side effects lasting much of that time.

In addition to increased compliance, Dr. Bettencourt said she also measured whether her off-label "creativity" such as prescribing higher concentrations for the scalp and instructing patients to spread the gel over larger areas, yielded worthwhile results.

"I found that, especially for the face, you can spread the medication without jeopardizing the efficacy," said Dr. Bettencourt. However, when the gel is applied to the scalp, "You lose a little bit of the efficacy, because that’s a lot to cover using the prescribed three tubes, but you still get good results."

In addition, Dr. Bettencourt said that the gel offers cosmetic advantages over other treatments such as the topical imiquimod or photodynamic therapy because there is no hypo- or hyperpigmentation. And, because there is no photosensitivity associated with the gel, Dr. Bettencourt said she can offer it year-round.

She still prescribes other topicals, however, because not all patients’ insurance plans cover the gel. Medicare, does cover the gel, she noted, but only if the patient has a supplemental insurance policy.

While the study was unsponsored, and Dr. Bettencourt had no financial conflicts to disclose, she noted that she has shared her data with LEO Pharmaceuticals, the gel’s manufacturer. "They were thrilled, and helped me to put the results together," she said.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

DENVER – Changes in health insurance coverage are prompting a resurgence in the use of 5-fluorouracil to treat actinic keratoses, according to Dr. Linda Susan Marcus.

Not only is 5-fluorouracil (5-FU) effective, "but it has become increasingly difficult to get some of the newer topical agents covered by health insurance plans, especially Medicare. This is the reality now," Dr. Marcus said at the annual meeting of the American Academy of Dermatology.

Dr. Marcus, a dermatologist in Wyckoff, N.J., noted that 5-FU blocks methylation of deoxyuridylic acid to thymidylic acid in DNA, altering only fast-dividing cancerous cells. The agent is available in 1%, 2%, and 5% solutions, and in 1% and 5% creams. "We don’t really use the solutions much anymore; they’re very irritating," Dr. Marcus said. "The 1% cream is less irritating, but 5% cream is really the gold standard." Her approach is to have patients apply the 5% 5-FU cream to the affected area twice a day for 3 weeks. Another option is a 0.5% 5-FU cream with a microsphere delivery system "that traps the active ingredients in the skin surface to increase efficacy and decrease irritancy," she said. "Some people use this for maintenance or cycle therapy prior to cryosurgery."

As for side effects, 5-FU elicits erythema, scaliness, and crusting (which can be avoided with the milder preparations); but these conditions are self-limited, Dr. Marcus noted. Some dermatologists use topical steroids or hyaluronic acid gels "to make the erythema go away faster," she added. "There are studies that say if you use these topical steroids, it curtails efficacy and you might lose some efficacy. That might be true. However, you have to make it user-friendly for the patient. Use your clinical judgment."

Other topical preparations for actinic keratoses on the market include:

• Diclofenac sodium 3% in 2.5% hyaluronic acid gel. This colorless agent is designed to be applied twice a day for 2-3 months. "That can pose a compliance issue for some patients," Dr. Marcus said. "The mechanism is unknown, but it probably functions as an NSAID that may involve prostaglandin levels in UV exposed skin and upregulation of COX-2, which may promote proliferation. Cyclooxygenase is the rate-limiting enzyme step in prostaglandin synthesis."

Dr. Marcus said that that diclofenac sodium 3% in 2.5% hyaluronic acid gel may be best suited for patients with mild lesions and for pre- or post cryosurgery.

• Imiquimod. A 5% formulation of imiquimod "is becoming the new gold standard of topical therapies, but it can be irritating," Dr. Marcus said. A 3.75% formulation is available that is designed to be used for 2 weeks, followed by a 2-week break, and then the patient repeats the cycle, Dr. Marcus said, adding that she uses the 3.75% formulation most often for her patients with actinic keratoses.

Dr. Marcus described imiquimod as an immune response modifier that induces mRNA encoding cytokines like alpha-interferon, TNF, and interleukin-12 for a cytotoxic T-lymphocyte response.

"There’s a direct proapoptotic effect in changing cancerous cells as a result of bypassing transduction paths activating caspase-3 downstream of membrane-bound death receptor activation," she said. "You can get a severe reaction, but there shouldn’t be a lot of pain. You get excellent cosmetic results upon healing."

Dermatologists often tweak the frequency of application, she added, and results from some studies suggest that outcomes with imiquimod are similar to those obtained with 5-FU, while others hint that imiquimod may provide longer-lasting results. "Field-directed therapy is the advantage since it brings out subclinical lesions, but you need a lot of hand holding to encourage patients with this phenomenon," Dr. Marcus said.

• Ingenol mebutate (PEP005). Approved as a gel in January of 2012, ingenol mebutate is a natural diterpene from the Euphorbia peplus flowering plant in Southeast Asia. The agent is believed to augment neutrophil-killing ability on abnormal cells via damaging mitochondria, and its antiangiogenic properties promote healing and skin regeneration. "It’s proven histologically in superficial basal cell epithelioma, which is interesting, because this drug is approved only in the United States and the indication is only for actinic keratosis and not for superficial basal cells," Dr. Marcus said.

In early studies, a 0.0025% preparation resulted in 38% clearance and was tolerable, while a 0.125% preparation gave 100% clearance but was too irritating. The approved form of ingenol mebutate gel is a 0.015% formulation applied daily for 3 days to head areas and ingenol mebutate gel 0.05% applied daily for 2 days to body areas. "You apply it for 3 days, but the reaction actually peaks on the 4th day, so when the patients are not applying it, they are still going to get a bit of redness before they’re into the healing phase," Dr. Marcus said. "The advantage is that you’re only applying it for 2-3 days, and then you’re done, so it increases compliance."

Photodynamic therapy is useful for field therapy, and it is done in one office visit, so compliance is not an issue, Dr. Marcus said. Photodynamic therapy also is covered by Medicare. "It may illicit some burning and require hand holding, but is effective," she said. "The key is combination therapy."

Dr. Marcus disclosed that she has received honoraria, grants, and research support from numerous pharmaceutical companies.

dbrunk@frontlinemedcom.com

DENVER – Changes in health insurance coverage are prompting a resurgence in the use of 5-fluorouracil to treat actinic keratoses, according to Dr. Linda Susan Marcus.

Not only is 5-fluorouracil (5-FU) effective, "but it has become increasingly difficult to get some of the newer topical agents covered by health insurance plans, especially Medicare. This is the reality now," Dr. Marcus said at the annual meeting of the American Academy of Dermatology.

Dr. Marcus, a dermatologist in Wyckoff, N.J., noted that 5-FU blocks methylation of deoxyuridylic acid to thymidylic acid in DNA, altering only fast-dividing cancerous cells. The agent is available in 1%, 2%, and 5% solutions, and in 1% and 5% creams. "We don’t really use the solutions much anymore; they’re very irritating," Dr. Marcus said. "The 1% cream is less irritating, but 5% cream is really the gold standard." Her approach is to have patients apply the 5% 5-FU cream to the affected area twice a day for 3 weeks. Another option is a 0.5% 5-FU cream with a microsphere delivery system "that traps the active ingredients in the skin surface to increase efficacy and decrease irritancy," she said. "Some people use this for maintenance or cycle therapy prior to cryosurgery."

As for side effects, 5-FU elicits erythema, scaliness, and crusting (which can be avoided with the milder preparations); but these conditions are self-limited, Dr. Marcus noted. Some dermatologists use topical steroids or hyaluronic acid gels "to make the erythema go away faster," she added. "There are studies that say if you use these topical steroids, it curtails efficacy and you might lose some efficacy. That might be true. However, you have to make it user-friendly for the patient. Use your clinical judgment."

Other topical preparations for actinic keratoses on the market include:

• Diclofenac sodium 3% in 2.5% hyaluronic acid gel. This colorless agent is designed to be applied twice a day for 2-3 months. "That can pose a compliance issue for some patients," Dr. Marcus said. "The mechanism is unknown, but it probably functions as an NSAID that may involve prostaglandin levels in UV exposed skin and upregulation of COX-2, which may promote proliferation. Cyclooxygenase is the rate-limiting enzyme step in prostaglandin synthesis."

Dr. Marcus said that that diclofenac sodium 3% in 2.5% hyaluronic acid gel may be best suited for patients with mild lesions and for pre- or post cryosurgery.

• Imiquimod. A 5% formulation of imiquimod "is becoming the new gold standard of topical therapies, but it can be irritating," Dr. Marcus said. A 3.75% formulation is available that is designed to be used for 2 weeks, followed by a 2-week break, and then the patient repeats the cycle, Dr. Marcus said, adding that she uses the 3.75% formulation most often for her patients with actinic keratoses.

Dr. Marcus described imiquimod as an immune response modifier that induces mRNA encoding cytokines like alpha-interferon, TNF, and interleukin-12 for a cytotoxic T-lymphocyte response.

"There’s a direct proapoptotic effect in changing cancerous cells as a result of bypassing transduction paths activating caspase-3 downstream of membrane-bound death receptor activation," she said. "You can get a severe reaction, but there shouldn’t be a lot of pain. You get excellent cosmetic results upon healing."

Dermatologists often tweak the frequency of application, she added, and results from some studies suggest that outcomes with imiquimod are similar to those obtained with 5-FU, while others hint that imiquimod may provide longer-lasting results. "Field-directed therapy is the advantage since it brings out subclinical lesions, but you need a lot of hand holding to encourage patients with this phenomenon," Dr. Marcus said.

• Ingenol mebutate (PEP005). Approved as a gel in January of 2012, ingenol mebutate is a natural diterpene from the Euphorbia peplus flowering plant in Southeast Asia. The agent is believed to augment neutrophil-killing ability on abnormal cells via damaging mitochondria, and its antiangiogenic properties promote healing and skin regeneration. "It’s proven histologically in superficial basal cell epithelioma, which is interesting, because this drug is approved only in the United States and the indication is only for actinic keratosis and not for superficial basal cells," Dr. Marcus said.

In early studies, a 0.0025% preparation resulted in 38% clearance and was tolerable, while a 0.125% preparation gave 100% clearance but was too irritating. The approved form of ingenol mebutate gel is a 0.015% formulation applied daily for 3 days to head areas and ingenol mebutate gel 0.05% applied daily for 2 days to body areas. "You apply it for 3 days, but the reaction actually peaks on the 4th day, so when the patients are not applying it, they are still going to get a bit of redness before they’re into the healing phase," Dr. Marcus said. "The advantage is that you’re only applying it for 2-3 days, and then you’re done, so it increases compliance."

Photodynamic therapy is useful for field therapy, and it is done in one office visit, so compliance is not an issue, Dr. Marcus said. Photodynamic therapy also is covered by Medicare. "It may illicit some burning and require hand holding, but is effective," she said. "The key is combination therapy."

Dr. Marcus disclosed that she has received honoraria, grants, and research support from numerous pharmaceutical companies.

dbrunk@frontlinemedcom.com

DENVER – Changes in health insurance coverage are prompting a resurgence in the use of 5-fluorouracil to treat actinic keratoses, according to Dr. Linda Susan Marcus.

Not only is 5-fluorouracil (5-FU) effective, "but it has become increasingly difficult to get some of the newer topical agents covered by health insurance plans, especially Medicare. This is the reality now," Dr. Marcus said at the annual meeting of the American Academy of Dermatology.

Dr. Marcus, a dermatologist in Wyckoff, N.J., noted that 5-FU blocks methylation of deoxyuridylic acid to thymidylic acid in DNA, altering only fast-dividing cancerous cells. The agent is available in 1%, 2%, and 5% solutions, and in 1% and 5% creams. "We don’t really use the solutions much anymore; they’re very irritating," Dr. Marcus said. "The 1% cream is less irritating, but 5% cream is really the gold standard." Her approach is to have patients apply the 5% 5-FU cream to the affected area twice a day for 3 weeks. Another option is a 0.5% 5-FU cream with a microsphere delivery system "that traps the active ingredients in the skin surface to increase efficacy and decrease irritancy," she said. "Some people use this for maintenance or cycle therapy prior to cryosurgery."

As for side effects, 5-FU elicits erythema, scaliness, and crusting (which can be avoided with the milder preparations); but these conditions are self-limited, Dr. Marcus noted. Some dermatologists use topical steroids or hyaluronic acid gels "to make the erythema go away faster," she added. "There are studies that say if you use these topical steroids, it curtails efficacy and you might lose some efficacy. That might be true. However, you have to make it user-friendly for the patient. Use your clinical judgment."

Other topical preparations for actinic keratoses on the market include:

• Diclofenac sodium 3% in 2.5% hyaluronic acid gel. This colorless agent is designed to be applied twice a day for 2-3 months. "That can pose a compliance issue for some patients," Dr. Marcus said. "The mechanism is unknown, but it probably functions as an NSAID that may involve prostaglandin levels in UV exposed skin and upregulation of COX-2, which may promote proliferation. Cyclooxygenase is the rate-limiting enzyme step in prostaglandin synthesis."

Dr. Marcus said that that diclofenac sodium 3% in 2.5% hyaluronic acid gel may be best suited for patients with mild lesions and for pre- or post cryosurgery.

• Imiquimod. A 5% formulation of imiquimod "is becoming the new gold standard of topical therapies, but it can be irritating," Dr. Marcus said. A 3.75% formulation is available that is designed to be used for 2 weeks, followed by a 2-week break, and then the patient repeats the cycle, Dr. Marcus said, adding that she uses the 3.75% formulation most often for her patients with actinic keratoses.

Dr. Marcus described imiquimod as an immune response modifier that induces mRNA encoding cytokines like alpha-interferon, TNF, and interleukin-12 for a cytotoxic T-lymphocyte response.

"There’s a direct proapoptotic effect in changing cancerous cells as a result of bypassing transduction paths activating caspase-3 downstream of membrane-bound death receptor activation," she said. "You can get a severe reaction, but there shouldn’t be a lot of pain. You get excellent cosmetic results upon healing."

Dermatologists often tweak the frequency of application, she added, and results from some studies suggest that outcomes with imiquimod are similar to those obtained with 5-FU, while others hint that imiquimod may provide longer-lasting results. "Field-directed therapy is the advantage since it brings out subclinical lesions, but you need a lot of hand holding to encourage patients with this phenomenon," Dr. Marcus said.

• Ingenol mebutate (PEP005). Approved as a gel in January of 2012, ingenol mebutate is a natural diterpene from the Euphorbia peplus flowering plant in Southeast Asia. The agent is believed to augment neutrophil-killing ability on abnormal cells via damaging mitochondria, and its antiangiogenic properties promote healing and skin regeneration. "It’s proven histologically in superficial basal cell epithelioma, which is interesting, because this drug is approved only in the United States and the indication is only for actinic keratosis and not for superficial basal cells," Dr. Marcus said.

In early studies, a 0.0025% preparation resulted in 38% clearance and was tolerable, while a 0.125% preparation gave 100% clearance but was too irritating. The approved form of ingenol mebutate gel is a 0.015% formulation applied daily for 3 days to head areas and ingenol mebutate gel 0.05% applied daily for 2 days to body areas. "You apply it for 3 days, but the reaction actually peaks on the 4th day, so when the patients are not applying it, they are still going to get a bit of redness before they’re into the healing phase," Dr. Marcus said. "The advantage is that you’re only applying it for 2-3 days, and then you’re done, so it increases compliance."

Photodynamic therapy is useful for field therapy, and it is done in one office visit, so compliance is not an issue, Dr. Marcus said. Photodynamic therapy also is covered by Medicare. "It may illicit some burning and require hand holding, but is effective," she said. "The key is combination therapy."

Dr. Marcus disclosed that she has received honoraria, grants, and research support from numerous pharmaceutical companies.

dbrunk@frontlinemedcom.com

WASHINGTON – Patients with acute heart failure who were discharged on an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker were significantly less likely to be readmitted to the hospital within 30 days of discharge than patients who were not prescribed these drugs, in a retrospective study of Medicare beneficiaries.

Using data from the Alabama Heart Failure Project, the study looked at hospital readmission rates in 1,348 patients with acute decompensated heart failure and an ejection fraction under 45%, discharged from 106 hospitals in the United States. Their mean age was 75 years, they had similar renal function, they were on various baseline cardiac medications, and they had no contraindications for angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) treatment. Of these patients, 734 were prescribed one of these drugs before discharge.

Nick Piegari/Frontline Medical News

The heart failure readmission and all-cause mortality rates were significantly higher among those who were not started on an ACE inhibitor or ARB before discharge: The 30-day heart failure readmission rate was 14% among those who did not receive an ACE inhibitor or ARB, compared with 7% of those who did – a 48% reduced risk, said Dr. Kumar Sanam, a heart failure fellow at the University of Alabama, Birmingham, at the annual meeting of the American College of Cardiology.

The all-cause readmission rate within 30 days among patients discharged without an ACE inhibitor or ARB was also significantly higher, at 24%, compared with 18% of those discharged with an ACE or an ARB, a relative risk reduction of 26%. The risk of all-cause mortality was reduced by 44% among those prescribed an ACE inhibitor or ARB, Dr. Sanam said.

Under the Affordable Care Act, hospitals will be penalized for above-average, all-cause 30-day readmission rates, he noted, and these findings highlight how the use of treatment recommended in evidence-based guidelines "could be used to reduce a costly health care problem," in the United States, Dr. Sanam said. An estimated one in four patients hospitalized with heart failure return to the hospital within 30 days, and heart failure is the most common cause of 30-day all-cause readmissions, he noted.

Dr. Sanam had no disclosures.

emechcatie@frontlinemedcom.com

WASHINGTON – Patients with acute heart failure who were discharged on an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker were significantly less likely to be readmitted to the hospital within 30 days of discharge than patients who were not prescribed these drugs, in a retrospective study of Medicare beneficiaries.

Using data from the Alabama Heart Failure Project, the study looked at hospital readmission rates in 1,348 patients with acute decompensated heart failure and an ejection fraction under 45%, discharged from 106 hospitals in the United States. Their mean age was 75 years, they had similar renal function, they were on various baseline cardiac medications, and they had no contraindications for angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) treatment. Of these patients, 734 were prescribed one of these drugs before discharge.

Nick Piegari/Frontline Medical News

The heart failure readmission and all-cause mortality rates were significantly higher among those who were not started on an ACE inhibitor or ARB before discharge: The 30-day heart failure readmission rate was 14% among those who did not receive an ACE inhibitor or ARB, compared with 7% of those who did – a 48% reduced risk, said Dr. Kumar Sanam, a heart failure fellow at the University of Alabama, Birmingham, at the annual meeting of the American College of Cardiology.

The all-cause readmission rate within 30 days among patients discharged without an ACE inhibitor or ARB was also significantly higher, at 24%, compared with 18% of those discharged with an ACE or an ARB, a relative risk reduction of 26%. The risk of all-cause mortality was reduced by 44% among those prescribed an ACE inhibitor or ARB, Dr. Sanam said.

Under the Affordable Care Act, hospitals will be penalized for above-average, all-cause 30-day readmission rates, he noted, and these findings highlight how the use of treatment recommended in evidence-based guidelines "could be used to reduce a costly health care problem," in the United States, Dr. Sanam said. An estimated one in four patients hospitalized with heart failure return to the hospital within 30 days, and heart failure is the most common cause of 30-day all-cause readmissions, he noted.

Dr. Sanam had no disclosures.

emechcatie@frontlinemedcom.com

WASHINGTON – Patients with acute heart failure who were discharged on an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker were significantly less likely to be readmitted to the hospital within 30 days of discharge than patients who were not prescribed these drugs, in a retrospective study of Medicare beneficiaries.

Using data from the Alabama Heart Failure Project, the study looked at hospital readmission rates in 1,348 patients with acute decompensated heart failure and an ejection fraction under 45%, discharged from 106 hospitals in the United States. Their mean age was 75 years, they had similar renal function, they were on various baseline cardiac medications, and they had no contraindications for angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) treatment. Of these patients, 734 were prescribed one of these drugs before discharge.

Nick Piegari/Frontline Medical News

The heart failure readmission and all-cause mortality rates were significantly higher among those who were not started on an ACE inhibitor or ARB before discharge: The 30-day heart failure readmission rate was 14% among those who did not receive an ACE inhibitor or ARB, compared with 7% of those who did – a 48% reduced risk, said Dr. Kumar Sanam, a heart failure fellow at the University of Alabama, Birmingham, at the annual meeting of the American College of Cardiology.

The all-cause readmission rate within 30 days among patients discharged without an ACE inhibitor or ARB was also significantly higher, at 24%, compared with 18% of those discharged with an ACE or an ARB, a relative risk reduction of 26%. The risk of all-cause mortality was reduced by 44% among those prescribed an ACE inhibitor or ARB, Dr. Sanam said.

Under the Affordable Care Act, hospitals will be penalized for above-average, all-cause 30-day readmission rates, he noted, and these findings highlight how the use of treatment recommended in evidence-based guidelines "could be used to reduce a costly health care problem," in the United States, Dr. Sanam said. An estimated one in four patients hospitalized with heart failure return to the hospital within 30 days, and heart failure is the most common cause of 30-day all-cause readmissions, he noted.

Dr. Sanam had no disclosures.

emechcatie@frontlinemedcom.com

CHAMPIONSGATE, FLA. – Do you use photodynamic therapy to treat actinic keratoses? Dr. Joel Cohen has some tips for you. At the Orlando Dermatology Aesthetic and Clinical Conference, Dr. Cohen spoke to us about current strategies for making the most of PDT, and which treatment plans work best for certain patients. What’s next for PDT? Dr. Cohen of the department of dermatology at the University of Colorado, Denver, highlights promising preliminary studies involving different types of combination therapies that can yield cosmetic and medical benefits.

hsplete@frontlinemedcom.com

CHAMPIONSGATE, FLA. – Do you use photodynamic therapy to treat actinic keratoses? Dr. Joel Cohen has some tips for you. At the Orlando Dermatology Aesthetic and Clinical Conference, Dr. Cohen spoke to us about current strategies for making the most of PDT, and which treatment plans work best for certain patients. What’s next for PDT? Dr. Cohen of the department of dermatology at the University of Colorado, Denver, highlights promising preliminary studies involving different types of combination therapies that can yield cosmetic and medical benefits.

hsplete@frontlinemedcom.com

CHAMPIONSGATE, FLA. – Do you use photodynamic therapy to treat actinic keratoses? Dr. Joel Cohen has some tips for you. At the Orlando Dermatology Aesthetic and Clinical Conference, Dr. Cohen spoke to us about current strategies for making the most of PDT, and which treatment plans work best for certain patients. What’s next for PDT? Dr. Cohen of the department of dermatology at the University of Colorado, Denver, highlights promising preliminary studies involving different types of combination therapies that can yield cosmetic and medical benefits.

hsplete@frontlinemedcom.com

Sequential topical field-directed therapy with ingenol mebutate gel for 3 days following cryosurgery significantly improves the outcomes in patients with actinic keratosis, a phase III randomized study showed.

Enrolled patients had four to eight clinically typical lesions on the face or scalp and received cryosurgery to all visible lesions followed by once-daily treatment of ingenol mebutate 0.015% gel or vehicle gel for 3 consecutive days at home, after 3 weeks of healing.

At 11 weeks, patients who received treatment with ingenol mebutate gel (n = 167) postsurgery, saw higher rates of complete clearance of lesions, compared with patients receiving the vehicle alone after surgery (n = 162) (60.5% vs. 49.4%; P=.04), reported Dr. Stephen K. Tyring and his associates this month (J. Drugs Dermatol. 2014;13:154-60).

In longer-term follow-up at 12 months, ingenol mebutate gel continued to show significantly improved complete clearance rates, compared with vehicle gel (30.5% vs. 18.5%; P = .01), Dr. Tyring reported at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

The mean percentage reduction of lesions at 12 months was significantly higher with ingenol mebutate for all lesions (59.5% vs 44.4%, P=0.004) and 38.9% of patients receiving ingenol mebutate saw emergence of new lesions on the treatment area between baseline lesions, compared with 51.9% of patients in the vehicle group (P=0.01), he said.

The complete clearance at 11 weeks (60.5% vs 49.4%; P=0.04) with a relative complete actinic keratosis clearance ratio of 1.22 (1.01-1.49) increased to 1.67 (1.12-2.50) at 12 months in the treatment group vs vehicle, following cryosurgery, noted Dr. Tyring of University of Texas Health Science Center at Houston.

The most frequently reported adverse events in the treatment group were application site discomfort and pruritus. Over the 12-month follow-up, 16 patients in the ingenol mebutate group reported one or more adverse events, as did 6 in the vehicle group. These events, however, were minor and well tolerated, said Dr. Tyring.

Ingenol mebutate gel was approved by the Food and Drug Administration in 2012 to treat actinic keratosis. Its advantage over other topical field agents such as 5-fluorouracil, imiquimod, and diclofenac is its short treatment period of 2-3 days, depending on the treatment area. This reduces the likelihood of patients discontinuing because of inflammation, burning, or other adverse events, Dr. Tyring noted.

Ingenol mebutate significantly enhanced the efficacy of cryosurgery, a difference that comes "both from enhancing the effect of cryosurgery with ingenol mebutate on the visible baseline lesions, and from a field treatment effect of ingenol mebutate on subclinical lesions not visible at baseline," Dr. Tyring said.

Dr. Tyring disclosed financial relationships with Astellas, Epiphany, Catalyst, GlaxoSmithKline, Novartis, 3M, VaxGen, Merck, BMS, Amgen, Biogen, Genentech, Corixa, Abbott, Graceway, Leo, and Warner Chilcott. SDEF and this news organization are owned by the same parent company.

sknews@frontlinemedcom.com

Sequential topical field-directed therapy with ingenol mebutate gel for 3 days following cryosurgery significantly improves the outcomes in patients with actinic keratosis, a phase III randomized study showed.

Enrolled patients had four to eight clinically typical lesions on the face or scalp and received cryosurgery to all visible lesions followed by once-daily treatment of ingenol mebutate 0.015% gel or vehicle gel for 3 consecutive days at home, after 3 weeks of healing.

At 11 weeks, patients who received treatment with ingenol mebutate gel (n = 167) postsurgery, saw higher rates of complete clearance of lesions, compared with patients receiving the vehicle alone after surgery (n = 162) (60.5% vs. 49.4%; P=.04), reported Dr. Stephen K. Tyring and his associates this month (J. Drugs Dermatol. 2014;13:154-60).

In longer-term follow-up at 12 months, ingenol mebutate gel continued to show significantly improved complete clearance rates, compared with vehicle gel (30.5% vs. 18.5%; P = .01), Dr. Tyring reported at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

The mean percentage reduction of lesions at 12 months was significantly higher with ingenol mebutate for all lesions (59.5% vs 44.4%, P=0.004) and 38.9% of patients receiving ingenol mebutate saw emergence of new lesions on the treatment area between baseline lesions, compared with 51.9% of patients in the vehicle group (P=0.01), he said.

The complete clearance at 11 weeks (60.5% vs 49.4%; P=0.04) with a relative complete actinic keratosis clearance ratio of 1.22 (1.01-1.49) increased to 1.67 (1.12-2.50) at 12 months in the treatment group vs vehicle, following cryosurgery, noted Dr. Tyring of University of Texas Health Science Center at Houston.

The most frequently reported adverse events in the treatment group were application site discomfort and pruritus. Over the 12-month follow-up, 16 patients in the ingenol mebutate group reported one or more adverse events, as did 6 in the vehicle group. These events, however, were minor and well tolerated, said Dr. Tyring.

Ingenol mebutate gel was approved by the Food and Drug Administration in 2012 to treat actinic keratosis. Its advantage over other topical field agents such as 5-fluorouracil, imiquimod, and diclofenac is its short treatment period of 2-3 days, depending on the treatment area. This reduces the likelihood of patients discontinuing because of inflammation, burning, or other adverse events, Dr. Tyring noted.

Ingenol mebutate significantly enhanced the efficacy of cryosurgery, a difference that comes "both from enhancing the effect of cryosurgery with ingenol mebutate on the visible baseline lesions, and from a field treatment effect of ingenol mebutate on subclinical lesions not visible at baseline," Dr. Tyring said.

Dr. Tyring disclosed financial relationships with Astellas, Epiphany, Catalyst, GlaxoSmithKline, Novartis, 3M, VaxGen, Merck, BMS, Amgen, Biogen, Genentech, Corixa, Abbott, Graceway, Leo, and Warner Chilcott. SDEF and this news organization are owned by the same parent company.

sknews@frontlinemedcom.com

Sequential topical field-directed therapy with ingenol mebutate gel for 3 days following cryosurgery significantly improves the outcomes in patients with actinic keratosis, a phase III randomized study showed.

Enrolled patients had four to eight clinically typical lesions on the face or scalp and received cryosurgery to all visible lesions followed by once-daily treatment of ingenol mebutate 0.015% gel or vehicle gel for 3 consecutive days at home, after 3 weeks of healing.

At 11 weeks, patients who received treatment with ingenol mebutate gel (n = 167) postsurgery, saw higher rates of complete clearance of lesions, compared with patients receiving the vehicle alone after surgery (n = 162) (60.5% vs. 49.4%; P=.04), reported Dr. Stephen K. Tyring and his associates this month (J. Drugs Dermatol. 2014;13:154-60).

In longer-term follow-up at 12 months, ingenol mebutate gel continued to show significantly improved complete clearance rates, compared with vehicle gel (30.5% vs. 18.5%; P = .01), Dr. Tyring reported at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

The mean percentage reduction of lesions at 12 months was significantly higher with ingenol mebutate for all lesions (59.5% vs 44.4%, P=0.004) and 38.9% of patients receiving ingenol mebutate saw emergence of new lesions on the treatment area between baseline lesions, compared with 51.9% of patients in the vehicle group (P=0.01), he said.

The complete clearance at 11 weeks (60.5% vs 49.4%; P=0.04) with a relative complete actinic keratosis clearance ratio of 1.22 (1.01-1.49) increased to 1.67 (1.12-2.50) at 12 months in the treatment group vs vehicle, following cryosurgery, noted Dr. Tyring of University of Texas Health Science Center at Houston.

The most frequently reported adverse events in the treatment group were application site discomfort and pruritus. Over the 12-month follow-up, 16 patients in the ingenol mebutate group reported one or more adverse events, as did 6 in the vehicle group. These events, however, were minor and well tolerated, said Dr. Tyring.

Ingenol mebutate gel was approved by the Food and Drug Administration in 2012 to treat actinic keratosis. Its advantage over other topical field agents such as 5-fluorouracil, imiquimod, and diclofenac is its short treatment period of 2-3 days, depending on the treatment area. This reduces the likelihood of patients discontinuing because of inflammation, burning, or other adverse events, Dr. Tyring noted.

Ingenol mebutate significantly enhanced the efficacy of cryosurgery, a difference that comes "both from enhancing the effect of cryosurgery with ingenol mebutate on the visible baseline lesions, and from a field treatment effect of ingenol mebutate on subclinical lesions not visible at baseline," Dr. Tyring said.

Dr. Tyring disclosed financial relationships with Astellas, Epiphany, Catalyst, GlaxoSmithKline, Novartis, 3M, VaxGen, Merck, BMS, Amgen, Biogen, Genentech, Corixa, Abbott, Graceway, Leo, and Warner Chilcott. SDEF and this news organization are owned by the same parent company.

sknews@frontlinemedcom.com

ISTANBUL – A novel form of photodynamic therapy achieved a much higher cure rate than did conventional PDT, based on a randomized controlled trial of organ transplant recipients with numerous actinic keratoses.

The novel approach combines pretreatment with ablative fractional laser resurfacing followed immediately by application of a photosensitizing agent and natural light exposure. In addition to its efficacy, the novel PDT approach was painless. Conventional PDT can be particularly painful for organ transplant recipients as they tend to have particularly thick and widespread lesions located at pain-sensitive sites including the underarms, dorsal hands, and face, Dr. Merete Haedersdal reported at the annual congress of the European Academy of Dermatology and Venereology.

"From a clinical point of view, we are struggling with these patients. ... Now we can individualize PDT. We already have a wonderful conventional PDT, but now we’re better off with these combined techniques, especially when we are going to treat larger areas as in this high-risk group of patients," said Dr. Haedersdal, professor of dermatology at the University of Copenhagen.

As a result of their long-term immunosuppressive therapy, organ transplant recipients have a 100-fold higher risk than the general population for squamous cell carcinoma. Further, their skin tumors grow aggressively; 6%-8% of organ transplant recipients die due to nonmelanoma skin cancers.

The novel PDT approach begins with ablative fractional laser resurfacing to create tiny holes in the skin, allowing increased uptake of the photosensitizer. Dr. Haedersdal and her coworkers used methyl aminolevulinate 16% cream, applied immediately after laser treatment. It takes 30 minutes to start the biochemical process of protoporphyrin-9 production, and the patient then goes outside for a full 2 hours of natural light exposure. This photoactivation period averaged 62,583 lux in the study. The patient then covers the treated area or stays inside for the rest of the day.

Dr. Haedersdal reported on 16 patients with a total of 542 actinic keratoses (AKs) on the scalp, chest, and extremities. The patients had received a donor organ a median of 14 years earlier. In each patient, four symmetrical skin areas within the same anatomic region were mapped out and randomized to receive a single treatment with either the novel laser-assisted daylight PDT, conventional PDT with a red light–emitting diode light source, PDT with daylight rather than the LED light source, or ablative fractional laser therapy alone.

The primary endpoint was the cure rate, or complete lesion response of all AKs at 3 months post treatment. The cure rate was 74% in the laser-assisted daylight PDT group compared with 50% with daylight PDT, 48% with conventional PDT, and 0 with laser-only treatment. When the analysis was restricted to the thicker, grade II and III AKs, the cure rate was 67% with the novel therapy, 50% with conventional PDT, 40% with daylight PDT, and 0 with laser-only treatment.

Median pain scores on a 0-10 visual analog scale were 0 for the areas treated with laser-assisted daylight PDT, laser only, and daylight PDT compared with 4.5 for the portion of skin targeted with conventional PDT. The key to pain-free PDT, according to Dr. Haedersdal, is to do the laser resurfacing at a very low fluence, allowing for continuous daylight photobleaching. The fractional laser therapy is delivered at a total of 5.6 mJ using 4.6 mJ per pulse, 1.15 W, a 50-microsecond pulse duration, 500 Hz, and 2.4% density using a 2,940-nm erbium laser. The laser holes are drilled into the epidermal layer, but not below the basement membrane.

Crusting and erythema developed in all PDT-treated patients but were slightly more intense in the areas treated with laser-assisted PDT. One patient in the laser-assisted PDT group had transient hypopigmentation.

Based on blinded assessments at 3 months, the laser-assisted daylight PDT areas displayed significantly greater skin smoothening and rejuvenation with less dyschromia than the other treatment zones. Cosmesis was rated "excellent" in the laser-treated zones of 10 out of 16 patients, a much higher rate than seen in the other treatment areas.

Dr. Haedersdal reported having received research grants from roughly half a dozen medical device and pharmaceutical companies.

bjancin@frontlinemedcom.com

ISTANBUL – A novel form of photodynamic therapy achieved a much higher cure rate than did conventional PDT, based on a randomized controlled trial of organ transplant recipients with numerous actinic keratoses.

The novel approach combines pretreatment with ablative fractional laser resurfacing followed immediately by application of a photosensitizing agent and natural light exposure. In addition to its efficacy, the novel PDT approach was painless. Conventional PDT can be particularly painful for organ transplant recipients as they tend to have particularly thick and widespread lesions located at pain-sensitive sites including the underarms, dorsal hands, and face, Dr. Merete Haedersdal reported at the annual congress of the European Academy of Dermatology and Venereology.

"From a clinical point of view, we are struggling with these patients. ... Now we can individualize PDT. We already have a wonderful conventional PDT, but now we’re better off with these combined techniques, especially when we are going to treat larger areas as in this high-risk group of patients," said Dr. Haedersdal, professor of dermatology at the University of Copenhagen.

As a result of their long-term immunosuppressive therapy, organ transplant recipients have a 100-fold higher risk than the general population for squamous cell carcinoma. Further, their skin tumors grow aggressively; 6%-8% of organ transplant recipients die due to nonmelanoma skin cancers.

The novel PDT approach begins with ablative fractional laser resurfacing to create tiny holes in the skin, allowing increased uptake of the photosensitizer. Dr. Haedersdal and her coworkers used methyl aminolevulinate 16% cream, applied immediately after laser treatment. It takes 30 minutes to start the biochemical process of protoporphyrin-9 production, and the patient then goes outside for a full 2 hours of natural light exposure. This photoactivation period averaged 62,583 lux in the study. The patient then covers the treated area or stays inside for the rest of the day.

Dr. Haedersdal reported on 16 patients with a total of 542 actinic keratoses (AKs) on the scalp, chest, and extremities. The patients had received a donor organ a median of 14 years earlier. In each patient, four symmetrical skin areas within the same anatomic region were mapped out and randomized to receive a single treatment with either the novel laser-assisted daylight PDT, conventional PDT with a red light–emitting diode light source, PDT with daylight rather than the LED light source, or ablative fractional laser therapy alone.

The primary endpoint was the cure rate, or complete lesion response of all AKs at 3 months post treatment. The cure rate was 74% in the laser-assisted daylight PDT group compared with 50% with daylight PDT, 48% with conventional PDT, and 0 with laser-only treatment. When the analysis was restricted to the thicker, grade II and III AKs, the cure rate was 67% with the novel therapy, 50% with conventional PDT, 40% with daylight PDT, and 0 with laser-only treatment.

Median pain scores on a 0-10 visual analog scale were 0 for the areas treated with laser-assisted daylight PDT, laser only, and daylight PDT compared with 4.5 for the portion of skin targeted with conventional PDT. The key to pain-free PDT, according to Dr. Haedersdal, is to do the laser resurfacing at a very low fluence, allowing for continuous daylight photobleaching. The fractional laser therapy is delivered at a total of 5.6 mJ using 4.6 mJ per pulse, 1.15 W, a 50-microsecond pulse duration, 500 Hz, and 2.4% density using a 2,940-nm erbium laser. The laser holes are drilled into the epidermal layer, but not below the basement membrane.

Crusting and erythema developed in all PDT-treated patients but were slightly more intense in the areas treated with laser-assisted PDT. One patient in the laser-assisted PDT group had transient hypopigmentation.

Based on blinded assessments at 3 months, the laser-assisted daylight PDT areas displayed significantly greater skin smoothening and rejuvenation with less dyschromia than the other treatment zones. Cosmesis was rated "excellent" in the laser-treated zones of 10 out of 16 patients, a much higher rate than seen in the other treatment areas.

Dr. Haedersdal reported having received research grants from roughly half a dozen medical device and pharmaceutical companies.

bjancin@frontlinemedcom.com

ISTANBUL – A novel form of photodynamic therapy achieved a much higher cure rate than did conventional PDT, based on a randomized controlled trial of organ transplant recipients with numerous actinic keratoses.

The novel approach combines pretreatment with ablative fractional laser resurfacing followed immediately by application of a photosensitizing agent and natural light exposure. In addition to its efficacy, the novel PDT approach was painless. Conventional PDT can be particularly painful for organ transplant recipients as they tend to have particularly thick and widespread lesions located at pain-sensitive sites including the underarms, dorsal hands, and face, Dr. Merete Haedersdal reported at the annual congress of the European Academy of Dermatology and Venereology.

"From a clinical point of view, we are struggling with these patients. ... Now we can individualize PDT. We already have a wonderful conventional PDT, but now we’re better off with these combined techniques, especially when we are going to treat larger areas as in this high-risk group of patients," said Dr. Haedersdal, professor of dermatology at the University of Copenhagen.

As a result of their long-term immunosuppressive therapy, organ transplant recipients have a 100-fold higher risk than the general population for squamous cell carcinoma. Further, their skin tumors grow aggressively; 6%-8% of organ transplant recipients die due to nonmelanoma skin cancers.

The novel PDT approach begins with ablative fractional laser resurfacing to create tiny holes in the skin, allowing increased uptake of the photosensitizer. Dr. Haedersdal and her coworkers used methyl aminolevulinate 16% cream, applied immediately after laser treatment. It takes 30 minutes to start the biochemical process of protoporphyrin-9 production, and the patient then goes outside for a full 2 hours of natural light exposure. This photoactivation period averaged 62,583 lux in the study. The patient then covers the treated area or stays inside for the rest of the day.

Dr. Haedersdal reported on 16 patients with a total of 542 actinic keratoses (AKs) on the scalp, chest, and extremities. The patients had received a donor organ a median of 14 years earlier. In each patient, four symmetrical skin areas within the same anatomic region were mapped out and randomized to receive a single treatment with either the novel laser-assisted daylight PDT, conventional PDT with a red light–emitting diode light source, PDT with daylight rather than the LED light source, or ablative fractional laser therapy alone.

The primary endpoint was the cure rate, or complete lesion response of all AKs at 3 months post treatment. The cure rate was 74% in the laser-assisted daylight PDT group compared with 50% with daylight PDT, 48% with conventional PDT, and 0 with laser-only treatment. When the analysis was restricted to the thicker, grade II and III AKs, the cure rate was 67% with the novel therapy, 50% with conventional PDT, 40% with daylight PDT, and 0 with laser-only treatment.

Median pain scores on a 0-10 visual analog scale were 0 for the areas treated with laser-assisted daylight PDT, laser only, and daylight PDT compared with 4.5 for the portion of skin targeted with conventional PDT. The key to pain-free PDT, according to Dr. Haedersdal, is to do the laser resurfacing at a very low fluence, allowing for continuous daylight photobleaching. The fractional laser therapy is delivered at a total of 5.6 mJ using 4.6 mJ per pulse, 1.15 W, a 50-microsecond pulse duration, 500 Hz, and 2.4% density using a 2,940-nm erbium laser. The laser holes are drilled into the epidermal layer, but not below the basement membrane.

Crusting and erythema developed in all PDT-treated patients but were slightly more intense in the areas treated with laser-assisted PDT. One patient in the laser-assisted PDT group had transient hypopigmentation.

Based on blinded assessments at 3 months, the laser-assisted daylight PDT areas displayed significantly greater skin smoothening and rejuvenation with less dyschromia than the other treatment zones. Cosmesis was rated "excellent" in the laser-treated zones of 10 out of 16 patients, a much higher rate than seen in the other treatment areas.

Dr. Haedersdal reported having received research grants from roughly half a dozen medical device and pharmaceutical companies.

bjancin@frontlinemedcom.com