Recently approved SK treatment spares melanocytes in preclinical study

A study using an ex vivo model to evaluate a seborrheic keratosis (SK) treatment shows that a topical application of 40% hydrogen peroxide is gentler on skin than a 5- or 10-second treatment with liquid nitrogen, particularly with respect to melanocytes, suggesting that the former may be less likely to produce disfiguring damage.

The 40% hydrogen peroxide solution (Eskata), also known as A-101, received Food and Drug Administration approval for the treatment of “seborrheic keratoses that are raised” in December, 2017. The study was published online in the Journal of the American Academy of Dermatology.

Melanocyte damage can lead to significant dyschromia, a poor cosmetic outcome that can have a tremendous impact on quality of life for dark-skinned patients, in whom it produces white spots. “A lot of these destructive approaches, especially liquid nitrogen, can leave more disfigurement upon treatment than the lesion itself,” the study’s lead author Adam Friedman, MD, said in an interview.

Melanocytes are particularly vulnerable to the effects of cold, so the destructive potential of liquid nitrogen is no surprise. But Dr. Friedman of the department of dermatology, George Washington University, Washington, wanted to get a better understanding of the impact of the new treatment on different skin cell types and the toxicity profile, so he approached the manufacturer, Aclaris Therapeutics, to do a study.

His team tested 40% hydrogen peroxide treatment and liquid nitrogen cryosurgery on a validated ex vivo human reconstituted full-thickness model derived from Fitzpatrick V skin, with 5 or 10 seconds of cryosurgery or 1 or 2 mcL of 40% hydrogen peroxide.

Using standard a hematoxylin and eosin stain as well as immunohistochemical staining to examine the architecture and cells types of the skin model following both treatments, the researchers found that 5- and 10-second cryosurgery resulted in significant thinning of the epidermis and increased cell death. There was also separation at the dermal-epidermal junction, which was more prominent in the 10-second cryosurgery group, although present even with a 5-second freeze cycle.

The hydrogen peroxide–treated groups showed acanthosis of the epidermis and mild pallor, but this was less noticeable than in the cryosurgery specimens. There was no epidermal clefting in the hydrogen peroxide–treated samples.

Tunel staining revealed 16.4 (plus or minus 0.6424) apoptotic cells per high-powered field in the 5-second cryosurgery experiment and 20.6 (plus or minus 0.6424) in the 10-second procedure. For the hydrogen peroxide treatment, those numbers were 8.65 (plus or minus 0.4122) in the 1 mcL experiment and 12.4 (plus or minus 0.3728) in the 2 mcL experiment.

As expected, melanocytes fared better with the hydrogen peroxide treatment. In the untreated samples, there were 2.5 melanocytes (plus or minus 0.1987) in the untreated sample and 2.0 (plus or minus 0.5000) melanocytes in the vehicle-treated sample. In the 5-second cryosurgery sample, there were 0.45 melanocytes (plus or minus 0.1535), and in the 10 second cryosurgery sample there were 0.2 (plus or minus 0.0918) melanocytes. In contrast, with the 1-mcL hydrogen peroxide-treated sample, there were 1.95 melanocytes in both the 1-mcL and 2-mcL samples (plus or minus 0.1535 for both groups).

“From a cytotoxicity perspective, [40% hydrogen peroxide] was much less toxic to the epidermis than the liquid nitrogen,” Dr. Friedman said. These results, he added, “offer us a lot of insight in terms of how damaging liquid nitrogen is, and it’s good to be reminded of that so that we don’t cause too much harm.”

The authors noted that a clinical trial evaluating the risk of hypopigmentation and hyperpigmentation with 40% hydrogen peroxide in people with darker skin types is underway. In the study, hydrogen peroxide is used to treat dermatosis papulosa nigra.

The study was funded by Aclaris Therapeutics. Senior author Adam Friedman, MD, is a consultant for Aclaris. Dr. Friedman is on the editorial board of Dermatology News.

SOURCE: Kao S et al. J Am Acad Dermatol. 2018 Mar 27. doi: 10.1016/j.jaad.2018.03.034.

A study using an ex vivo model to evaluate a seborrheic keratosis (SK) treatment shows that a topical application of 40% hydrogen peroxide is gentler on skin than a 5- or 10-second treatment with liquid nitrogen, particularly with respect to melanocytes, suggesting that the former may be less likely to produce disfiguring damage.

The 40% hydrogen peroxide solution (Eskata), also known as A-101, received Food and Drug Administration approval for the treatment of “seborrheic keratoses that are raised” in December, 2017. The study was published online in the Journal of the American Academy of Dermatology.

Melanocyte damage can lead to significant dyschromia, a poor cosmetic outcome that can have a tremendous impact on quality of life for dark-skinned patients, in whom it produces white spots. “A lot of these destructive approaches, especially liquid nitrogen, can leave more disfigurement upon treatment than the lesion itself,” the study’s lead author Adam Friedman, MD, said in an interview.

Melanocytes are particularly vulnerable to the effects of cold, so the destructive potential of liquid nitrogen is no surprise. But Dr. Friedman of the department of dermatology, George Washington University, Washington, wanted to get a better understanding of the impact of the new treatment on different skin cell types and the toxicity profile, so he approached the manufacturer, Aclaris Therapeutics, to do a study.

His team tested 40% hydrogen peroxide treatment and liquid nitrogen cryosurgery on a validated ex vivo human reconstituted full-thickness model derived from Fitzpatrick V skin, with 5 or 10 seconds of cryosurgery or 1 or 2 mcL of 40% hydrogen peroxide.

Using standard a hematoxylin and eosin stain as well as immunohistochemical staining to examine the architecture and cells types of the skin model following both treatments, the researchers found that 5- and 10-second cryosurgery resulted in significant thinning of the epidermis and increased cell death. There was also separation at the dermal-epidermal junction, which was more prominent in the 10-second cryosurgery group, although present even with a 5-second freeze cycle.

The hydrogen peroxide–treated groups showed acanthosis of the epidermis and mild pallor, but this was less noticeable than in the cryosurgery specimens. There was no epidermal clefting in the hydrogen peroxide–treated samples.

Tunel staining revealed 16.4 (plus or minus 0.6424) apoptotic cells per high-powered field in the 5-second cryosurgery experiment and 20.6 (plus or minus 0.6424) in the 10-second procedure. For the hydrogen peroxide treatment, those numbers were 8.65 (plus or minus 0.4122) in the 1 mcL experiment and 12.4 (plus or minus 0.3728) in the 2 mcL experiment.

As expected, melanocytes fared better with the hydrogen peroxide treatment. In the untreated samples, there were 2.5 melanocytes (plus or minus 0.1987) in the untreated sample and 2.0 (plus or minus 0.5000) melanocytes in the vehicle-treated sample. In the 5-second cryosurgery sample, there were 0.45 melanocytes (plus or minus 0.1535), and in the 10 second cryosurgery sample there were 0.2 (plus or minus 0.0918) melanocytes. In contrast, with the 1-mcL hydrogen peroxide-treated sample, there were 1.95 melanocytes in both the 1-mcL and 2-mcL samples (plus or minus 0.1535 for both groups).

“From a cytotoxicity perspective, [40% hydrogen peroxide] was much less toxic to the epidermis than the liquid nitrogen,” Dr. Friedman said. These results, he added, “offer us a lot of insight in terms of how damaging liquid nitrogen is, and it’s good to be reminded of that so that we don’t cause too much harm.”

The authors noted that a clinical trial evaluating the risk of hypopigmentation and hyperpigmentation with 40% hydrogen peroxide in people with darker skin types is underway. In the study, hydrogen peroxide is used to treat dermatosis papulosa nigra.

The study was funded by Aclaris Therapeutics. Senior author Adam Friedman, MD, is a consultant for Aclaris. Dr. Friedman is on the editorial board of Dermatology News.

SOURCE: Kao S et al. J Am Acad Dermatol. 2018 Mar 27. doi: 10.1016/j.jaad.2018.03.034.

A study using an ex vivo model to evaluate a seborrheic keratosis (SK) treatment shows that a topical application of 40% hydrogen peroxide is gentler on skin than a 5- or 10-second treatment with liquid nitrogen, particularly with respect to melanocytes, suggesting that the former may be less likely to produce disfiguring damage.

The 40% hydrogen peroxide solution (Eskata), also known as A-101, received Food and Drug Administration approval for the treatment of “seborrheic keratoses that are raised” in December, 2017. The study was published online in the Journal of the American Academy of Dermatology.

Melanocyte damage can lead to significant dyschromia, a poor cosmetic outcome that can have a tremendous impact on quality of life for dark-skinned patients, in whom it produces white spots. “A lot of these destructive approaches, especially liquid nitrogen, can leave more disfigurement upon treatment than the lesion itself,” the study’s lead author Adam Friedman, MD, said in an interview.

Melanocytes are particularly vulnerable to the effects of cold, so the destructive potential of liquid nitrogen is no surprise. But Dr. Friedman of the department of dermatology, George Washington University, Washington, wanted to get a better understanding of the impact of the new treatment on different skin cell types and the toxicity profile, so he approached the manufacturer, Aclaris Therapeutics, to do a study.

His team tested 40% hydrogen peroxide treatment and liquid nitrogen cryosurgery on a validated ex vivo human reconstituted full-thickness model derived from Fitzpatrick V skin, with 5 or 10 seconds of cryosurgery or 1 or 2 mcL of 40% hydrogen peroxide.

Using standard a hematoxylin and eosin stain as well as immunohistochemical staining to examine the architecture and cells types of the skin model following both treatments, the researchers found that 5- and 10-second cryosurgery resulted in significant thinning of the epidermis and increased cell death. There was also separation at the dermal-epidermal junction, which was more prominent in the 10-second cryosurgery group, although present even with a 5-second freeze cycle.

The hydrogen peroxide–treated groups showed acanthosis of the epidermis and mild pallor, but this was less noticeable than in the cryosurgery specimens. There was no epidermal clefting in the hydrogen peroxide–treated samples.

Tunel staining revealed 16.4 (plus or minus 0.6424) apoptotic cells per high-powered field in the 5-second cryosurgery experiment and 20.6 (plus or minus 0.6424) in the 10-second procedure. For the hydrogen peroxide treatment, those numbers were 8.65 (plus or minus 0.4122) in the 1 mcL experiment and 12.4 (plus or minus 0.3728) in the 2 mcL experiment.

As expected, melanocytes fared better with the hydrogen peroxide treatment. In the untreated samples, there were 2.5 melanocytes (plus or minus 0.1987) in the untreated sample and 2.0 (plus or minus 0.5000) melanocytes in the vehicle-treated sample. In the 5-second cryosurgery sample, there were 0.45 melanocytes (plus or minus 0.1535), and in the 10 second cryosurgery sample there were 0.2 (plus or minus 0.0918) melanocytes. In contrast, with the 1-mcL hydrogen peroxide-treated sample, there were 1.95 melanocytes in both the 1-mcL and 2-mcL samples (plus or minus 0.1535 for both groups).

“From a cytotoxicity perspective, [40% hydrogen peroxide] was much less toxic to the epidermis than the liquid nitrogen,” Dr. Friedman said. These results, he added, “offer us a lot of insight in terms of how damaging liquid nitrogen is, and it’s good to be reminded of that so that we don’t cause too much harm.”

The authors noted that a clinical trial evaluating the risk of hypopigmentation and hyperpigmentation with 40% hydrogen peroxide in people with darker skin types is underway. In the study, hydrogen peroxide is used to treat dermatosis papulosa nigra.

The study was funded by Aclaris Therapeutics. Senior author Adam Friedman, MD, is a consultant for Aclaris. Dr. Friedman is on the editorial board of Dermatology News.

SOURCE: Kao S et al. J Am Acad Dermatol. 2018 Mar 27. doi: 10.1016/j.jaad.2018.03.034.