Melanoma

WAIKOLOA, HAWAII – Using EMLA or lidocaine cream in conjunction with topical 5-aminolevulinic acid photodynamic therapy may boost uptake of the photosensitizer, but the clinical outcomes can be unpredictable, according to Dr. E. Victor Ross.

"Our worst scenarios have been when we’ve used EMLA on the skin. We’ve stopped using EMLA or lidocaine cream on the skin in ALA-PDT because of the very pronounced, enhanced photodynamic effects. You get great long-term results, but such a bad short-term result that lots of people didn’t want to go through it," said Dr. Ross of Scripps Clinic Laser and Cosmetic Dermatology Center in Carmel Valley, Calif.

Bruce Jancin/Elsevier Global Medical News

Using a topical numbing agent seemed to be an attractive option because patients often complain that photodynamic therapy (PDT) is painful. Plus, there seemed to be an added benefit: The anesthetic cream increased aminolevulanic acid (ALA) uptake by the skin, such that ALA incubation times before application of the light source could be greatly compressed. But clinical outcomes were too unpredictable, he said at the seminar sponsored by Skin Disease Education Foundation (SDEF). After several patients had unintended florid full photopeels involving 1½ weeks of downtime, it was time to abandon the practice.

When ALA-PDT first appeared about 10 years ago, the indication was for the treatment of actinic keratoses (AKs). Today this approved indication remains the No. 1 reason Dr. Ross utilizes the therapy, he said. But PDT’s role has expanded off label to include cosmetic procedures and the treatment of warts, nonmelanoma skin cancer, nevus sebaceous, as well as acne, which he considers "one of the great opportunities for PDT." In addition, in Asia, dermatologists are now refining the use of PDT with hematoporphyrin derivatives for the treatment of port wine stains and other vascular lesions.

Many U.S. dermatologists have incorporated PDT into their practices, with ALA being more widely used as a photosensitizer than methyl aminolevulinate (MAL). Yet PDT is a therapy that hasn’t been fully optimized; it is still fraught with side effects and suboptimal results, he said. Moreover, some fundamental issues regarding PDT remain unanswered: For example, the optimal duration of photosensitizer incubation time for various indications is still controversial.

Dr. Ross said he opts for what he considers a middle-of-the-road approach, with ALA application times of about 90-120 minutes, which he views as having an optimal balance between side effects and effectiveness. Even so, he noted that among the 8-10 patients per week he treats with ALA-PDT on average, 1 or 2 experience mild side effects.

"I don’t think we’re quite ‘there’ yet with PDT, although we’re getting closer. There are still so many tricks involved in making it work without side effects. We’ve still got some work to do," he said.

In addition to advising his colleagues to stay away from topical anesthetic creams, he offered additional tips for the use of ALA-PDT. Among them:

• Sending acne into long-term remission via PDT remains the Holy Grail, he said. The objective is to enhance the fluorescence of protoporphyrin 9 at the sebaceous gland while sparing the epidermis.

Some investigators are using low-intensity blue light at the skin surface while the photosensitizer is incubating in order to bleach it out of the epidermis, or, alternatively, warming and cooling the skin.

The best results Dr. Ross said he has seen have come through an arduous regimen involving three 3-hour-long ALA applications scheduled a month apart. There’s a delayed effect, with significant improvement coming at 3-6 months.

"It’s a tough, tough therapy to get through. There are lots of pustules and papules, and the acne invariably gets worse before it gets better. This doesn’t play into the hands of the typical teenager, who wants to get better right away," Dr. Ross said.

• A creamy solution of ALA will create more protoporphyrin 9 than an aqueous solution will.

• A red light source should be considered for deeper structures, such as basal cell carcinomas or sebaceous glands, and blue light for treating more superficial skin lesions. Although continuous blue light is 40 times more potent per photon than red light in exciting protoporphyrin 9, it doesn’t penetrate as deeply.

• Performing low-density fractional CO₂ ablative laser therapy prior to application of the photosensitizing agent is "an exciting advance" in PDT, he said.

The innovation was developed by an international team led by investigators at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, who published a split-face randomized study involving 15 patients with a total of 212 facial AKs. At the 3-month follow-up, the complete response rate of grade II-III lesions treated with MAL-PDT preceded by fractional ablative laser therapy was 87.5%, vs. 58.8% with conventional MAL-PDT. The complete response rate of grade I AKs was 100% with fractional laser/MAL-PDT, vs. 79% for MAL-PDT alone.

The fractional laser–pretreated areas also displayed significantly greater improvement in photoaging and fewer new AKs at follow-up: 3, compared with 11. But these superior outcomes came at a price: higher pain scores during illumination and significantly worse erythema and crusting post treatment (Br. J. Dermatol. 2012 Feb. 20 [doi:10.1111/j.1365-2133.2012.10893.x]).

Fractional CO₂ laser pretreatment enhances conversion of the photosensitizing agent to protoporphyrin 9, Dr. Ross explained. He compared the tiny holes in the skin created by the fractional laser to the process of aerating a lawn. The holes create conduits for the photosensitizer to bypass the stratum corneum, which is the major obstacle to uptake of ALA or MAL. Once the photosensitizer skips past the stratum corneum, it quickly spreads laterally throughout the epidermis.

However, Dr. Ross offered a note of caution regarding this novel approach. He said that he performed the therapy recently and found that 30 minutes of ALA incubation was too much.

"If you do these procedures, I would say go very light and just leave the ALA for less than 30 minutes to start, because the response you’re going to get when using a fractional laser beforehand is profound. It’s a huge difference," he said.

Dr. Ross reported that he serves as a consultant to and receives research support from Palomar. He also disclosed receiving research support from Candela, Cutera, Lumenis, Sciton, and Ulthera.

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Using EMLA or lidocaine cream in conjunction with topical 5-aminolevulinic acid photodynamic therapy may boost uptake of the photosensitizer, but the clinical outcomes can be unpredictable, according to Dr. E. Victor Ross.

"Our worst scenarios have been when we’ve used EMLA on the skin. We’ve stopped using EMLA or lidocaine cream on the skin in ALA-PDT because of the very pronounced, enhanced photodynamic effects. You get great long-term results, but such a bad short-term result that lots of people didn’t want to go through it," said Dr. Ross of Scripps Clinic Laser and Cosmetic Dermatology Center in Carmel Valley, Calif.

Bruce Jancin/Elsevier Global Medical News

Using a topical numbing agent seemed to be an attractive option because patients often complain that photodynamic therapy (PDT) is painful. Plus, there seemed to be an added benefit: The anesthetic cream increased aminolevulanic acid (ALA) uptake by the skin, such that ALA incubation times before application of the light source could be greatly compressed. But clinical outcomes were too unpredictable, he said at the seminar sponsored by Skin Disease Education Foundation (SDEF). After several patients had unintended florid full photopeels involving 1½ weeks of downtime, it was time to abandon the practice.

When ALA-PDT first appeared about 10 years ago, the indication was for the treatment of actinic keratoses (AKs). Today this approved indication remains the No. 1 reason Dr. Ross utilizes the therapy, he said. But PDT’s role has expanded off label to include cosmetic procedures and the treatment of warts, nonmelanoma skin cancer, nevus sebaceous, as well as acne, which he considers "one of the great opportunities for PDT." In addition, in Asia, dermatologists are now refining the use of PDT with hematoporphyrin derivatives for the treatment of port wine stains and other vascular lesions.

Many U.S. dermatologists have incorporated PDT into their practices, with ALA being more widely used as a photosensitizer than methyl aminolevulinate (MAL). Yet PDT is a therapy that hasn’t been fully optimized; it is still fraught with side effects and suboptimal results, he said. Moreover, some fundamental issues regarding PDT remain unanswered: For example, the optimal duration of photosensitizer incubation time for various indications is still controversial.

Dr. Ross said he opts for what he considers a middle-of-the-road approach, with ALA application times of about 90-120 minutes, which he views as having an optimal balance between side effects and effectiveness. Even so, he noted that among the 8-10 patients per week he treats with ALA-PDT on average, 1 or 2 experience mild side effects.

"I don’t think we’re quite ‘there’ yet with PDT, although we’re getting closer. There are still so many tricks involved in making it work without side effects. We’ve still got some work to do," he said.

In addition to advising his colleagues to stay away from topical anesthetic creams, he offered additional tips for the use of ALA-PDT. Among them:

• Sending acne into long-term remission via PDT remains the Holy Grail, he said. The objective is to enhance the fluorescence of protoporphyrin 9 at the sebaceous gland while sparing the epidermis.

Some investigators are using low-intensity blue light at the skin surface while the photosensitizer is incubating in order to bleach it out of the epidermis, or, alternatively, warming and cooling the skin.

The best results Dr. Ross said he has seen have come through an arduous regimen involving three 3-hour-long ALA applications scheduled a month apart. There’s a delayed effect, with significant improvement coming at 3-6 months.

"It’s a tough, tough therapy to get through. There are lots of pustules and papules, and the acne invariably gets worse before it gets better. This doesn’t play into the hands of the typical teenager, who wants to get better right away," Dr. Ross said.

• A creamy solution of ALA will create more protoporphyrin 9 than an aqueous solution will.

• A red light source should be considered for deeper structures, such as basal cell carcinomas or sebaceous glands, and blue light for treating more superficial skin lesions. Although continuous blue light is 40 times more potent per photon than red light in exciting protoporphyrin 9, it doesn’t penetrate as deeply.

• Performing low-density fractional CO₂ ablative laser therapy prior to application of the photosensitizing agent is "an exciting advance" in PDT, he said.

The innovation was developed by an international team led by investigators at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, who published a split-face randomized study involving 15 patients with a total of 212 facial AKs. At the 3-month follow-up, the complete response rate of grade II-III lesions treated with MAL-PDT preceded by fractional ablative laser therapy was 87.5%, vs. 58.8% with conventional MAL-PDT. The complete response rate of grade I AKs was 100% with fractional laser/MAL-PDT, vs. 79% for MAL-PDT alone.

The fractional laser–pretreated areas also displayed significantly greater improvement in photoaging and fewer new AKs at follow-up: 3, compared with 11. But these superior outcomes came at a price: higher pain scores during illumination and significantly worse erythema and crusting post treatment (Br. J. Dermatol. 2012 Feb. 20 [doi:10.1111/j.1365-2133.2012.10893.x]).

Fractional CO₂ laser pretreatment enhances conversion of the photosensitizing agent to protoporphyrin 9, Dr. Ross explained. He compared the tiny holes in the skin created by the fractional laser to the process of aerating a lawn. The holes create conduits for the photosensitizer to bypass the stratum corneum, which is the major obstacle to uptake of ALA or MAL. Once the photosensitizer skips past the stratum corneum, it quickly spreads laterally throughout the epidermis.

However, Dr. Ross offered a note of caution regarding this novel approach. He said that he performed the therapy recently and found that 30 minutes of ALA incubation was too much.

"If you do these procedures, I would say go very light and just leave the ALA for less than 30 minutes to start, because the response you’re going to get when using a fractional laser beforehand is profound. It’s a huge difference," he said.

Dr. Ross reported that he serves as a consultant to and receives research support from Palomar. He also disclosed receiving research support from Candela, Cutera, Lumenis, Sciton, and Ulthera.

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Using EMLA or lidocaine cream in conjunction with topical 5-aminolevulinic acid photodynamic therapy may boost uptake of the photosensitizer, but the clinical outcomes can be unpredictable, according to Dr. E. Victor Ross.

"Our worst scenarios have been when we’ve used EMLA on the skin. We’ve stopped using EMLA or lidocaine cream on the skin in ALA-PDT because of the very pronounced, enhanced photodynamic effects. You get great long-term results, but such a bad short-term result that lots of people didn’t want to go through it," said Dr. Ross of Scripps Clinic Laser and Cosmetic Dermatology Center in Carmel Valley, Calif.

Bruce Jancin/Elsevier Global Medical News

Using a topical numbing agent seemed to be an attractive option because patients often complain that photodynamic therapy (PDT) is painful. Plus, there seemed to be an added benefit: The anesthetic cream increased aminolevulanic acid (ALA) uptake by the skin, such that ALA incubation times before application of the light source could be greatly compressed. But clinical outcomes were too unpredictable, he said at the seminar sponsored by Skin Disease Education Foundation (SDEF). After several patients had unintended florid full photopeels involving 1½ weeks of downtime, it was time to abandon the practice.

When ALA-PDT first appeared about 10 years ago, the indication was for the treatment of actinic keratoses (AKs). Today this approved indication remains the No. 1 reason Dr. Ross utilizes the therapy, he said. But PDT’s role has expanded off label to include cosmetic procedures and the treatment of warts, nonmelanoma skin cancer, nevus sebaceous, as well as acne, which he considers "one of the great opportunities for PDT." In addition, in Asia, dermatologists are now refining the use of PDT with hematoporphyrin derivatives for the treatment of port wine stains and other vascular lesions.

Many U.S. dermatologists have incorporated PDT into their practices, with ALA being more widely used as a photosensitizer than methyl aminolevulinate (MAL). Yet PDT is a therapy that hasn’t been fully optimized; it is still fraught with side effects and suboptimal results, he said. Moreover, some fundamental issues regarding PDT remain unanswered: For example, the optimal duration of photosensitizer incubation time for various indications is still controversial.

Dr. Ross said he opts for what he considers a middle-of-the-road approach, with ALA application times of about 90-120 minutes, which he views as having an optimal balance between side effects and effectiveness. Even so, he noted that among the 8-10 patients per week he treats with ALA-PDT on average, 1 or 2 experience mild side effects.

"I don’t think we’re quite ‘there’ yet with PDT, although we’re getting closer. There are still so many tricks involved in making it work without side effects. We’ve still got some work to do," he said.

In addition to advising his colleagues to stay away from topical anesthetic creams, he offered additional tips for the use of ALA-PDT. Among them:

• Sending acne into long-term remission via PDT remains the Holy Grail, he said. The objective is to enhance the fluorescence of protoporphyrin 9 at the sebaceous gland while sparing the epidermis.

Some investigators are using low-intensity blue light at the skin surface while the photosensitizer is incubating in order to bleach it out of the epidermis, or, alternatively, warming and cooling the skin.

The best results Dr. Ross said he has seen have come through an arduous regimen involving three 3-hour-long ALA applications scheduled a month apart. There’s a delayed effect, with significant improvement coming at 3-6 months.

"It’s a tough, tough therapy to get through. There are lots of pustules and papules, and the acne invariably gets worse before it gets better. This doesn’t play into the hands of the typical teenager, who wants to get better right away," Dr. Ross said.

• A creamy solution of ALA will create more protoporphyrin 9 than an aqueous solution will.

• A red light source should be considered for deeper structures, such as basal cell carcinomas or sebaceous glands, and blue light for treating more superficial skin lesions. Although continuous blue light is 40 times more potent per photon than red light in exciting protoporphyrin 9, it doesn’t penetrate as deeply.

• Performing low-density fractional CO₂ ablative laser therapy prior to application of the photosensitizing agent is "an exciting advance" in PDT, he said.

The innovation was developed by an international team led by investigators at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, who published a split-face randomized study involving 15 patients with a total of 212 facial AKs. At the 3-month follow-up, the complete response rate of grade II-III lesions treated with MAL-PDT preceded by fractional ablative laser therapy was 87.5%, vs. 58.8% with conventional MAL-PDT. The complete response rate of grade I AKs was 100% with fractional laser/MAL-PDT, vs. 79% for MAL-PDT alone.

The fractional laser–pretreated areas also displayed significantly greater improvement in photoaging and fewer new AKs at follow-up: 3, compared with 11. But these superior outcomes came at a price: higher pain scores during illumination and significantly worse erythema and crusting post treatment (Br. J. Dermatol. 2012 Feb. 20 [doi:10.1111/j.1365-2133.2012.10893.x]).

Fractional CO₂ laser pretreatment enhances conversion of the photosensitizing agent to protoporphyrin 9, Dr. Ross explained. He compared the tiny holes in the skin created by the fractional laser to the process of aerating a lawn. The holes create conduits for the photosensitizer to bypass the stratum corneum, which is the major obstacle to uptake of ALA or MAL. Once the photosensitizer skips past the stratum corneum, it quickly spreads laterally throughout the epidermis.

However, Dr. Ross offered a note of caution regarding this novel approach. He said that he performed the therapy recently and found that 30 minutes of ALA incubation was too much.

"If you do these procedures, I would say go very light and just leave the ALA for less than 30 minutes to start, because the response you’re going to get when using a fractional laser beforehand is profound. It’s a huge difference," he said.

Dr. Ross reported that he serves as a consultant to and receives research support from Palomar. He also disclosed receiving research support from Candela, Cutera, Lumenis, Sciton, and Ulthera.

SDEF and this news organization are owned by Elsevier.

In this month's program, Dr. Alexa B. Kimball discusses why psoriasis treatment shouldn't be delayed.

Dr. James M. Spencer offers his insights on the pros and cons of bringing radiation treatment back to the dermatologist's office.

Then, a marketing guru offers tips on how to keep cosmetic patients coming back.

Cosmetic counter host Dr. Lily Talakoub explains what it really means when a product claims to be all "natural."

And finally, Dr. Alan Rockoff shares one of the more humorous places people have gone to read his new book.

In this month's program, Dr. Alexa B. Kimball discusses why psoriasis treatment shouldn't be delayed.

Dr. James M. Spencer offers his insights on the pros and cons of bringing radiation treatment back to the dermatologist's office.

Then, a marketing guru offers tips on how to keep cosmetic patients coming back.

Cosmetic counter host Dr. Lily Talakoub explains what it really means when a product claims to be all "natural."

And finally, Dr. Alan Rockoff shares one of the more humorous places people have gone to read his new book.

In this month's program, Dr. Alexa B. Kimball discusses why psoriasis treatment shouldn't be delayed.

Dr. James M. Spencer offers his insights on the pros and cons of bringing radiation treatment back to the dermatologist's office.

Then, a marketing guru offers tips on how to keep cosmetic patients coming back.

Cosmetic counter host Dr. Lily Talakoub explains what it really means when a product claims to be all "natural."

And finally, Dr. Alan Rockoff shares one of the more humorous places people have gone to read his new book.

WAIKOLOA, HAWAII – Oral aprepitant has shown considerable promise as a novel therapy in patients with refractory pruritus, including those with severe itching induced by biologic therapies for cancer.

"I think it’s a tool we should consider using in our patients with pruritus who do not respond to the usual measures," Dr. Mario E. Lacouture said at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

BRUCE JANCIN/Elsevier Global Medical News

Aprepitant (Emend) is approved as an antiemetic agent for cancer patients undergoing chemotherapy. But a growing body of data, including two single-arm proof-of-concept studies, has shown a high response rate in patients with itching resistant to standard treatment, including corticosteroids, UV therapy, and antihistamines, noted Dr. Lacouture, a dermatologist at Memorial Sloan-Kettering Cancer Center, New York.

Severe itching is increasingly recognized as an important side effect of targeted biologic agents for cancer, including erlotinib (Tarceva) and cetuximab (Erbitux). At last year’s meeting of the American Society of Clinical Oncology, Dr. Daniele Santini and coworkers at the Università "Campus Bio-Medico" di Roma presented a study involving 22 patients with severe pruritus treated with aprepitant using a regimen of 125 mg on day 1 and 80 mg on days 3 and 5.

After the single 3-dose cycle of aprepitant, the patients’ median pruritus intensity plummeted from a baseline of 8 down to 1 on a 0-10 visual analog scale (VAS). Twenty of 22 patients experienced a greater than 50% reduction in pruritus. The median duration of benefit following a 3-dose cycle given over 5 days was 25 days.

In the second proof-of-concept study, dermatologists at the Westfälische Wilhelms-Universität Münster (Germany) reported on 20 patients with refractory chronic pruritus from nonmalignant underlying disorders placed on aprepitant at 80 mg/day for 1 week. Sixteen of the 20 patients experienced a marked reduction in itch intensity. From a baseline mean of 8.4 points on the VAS, the group as a whole averaged a 42% improvement to a post-treatment score of 4.3.

A significant reduction in itching was observed as early as 2 days after initiating aprepitant in the study population (PLoS One. 2010;5:e10968).

Patients with itching related to prurigo nodularis or atopic disease responded better than those without the conditions, and patients under age 60 obtained greater improvement than older patients. However, patients with chronic kidney disease as the underlying cause of their itching achieved only minimal benefit.

Side effects were confined to mild, non-treatment-limiting nausea, dizziness, and drowsiness in three patients.

Between the two proof-of-concept studies and smaller published case series, Dr. Lacouture said that he is aware of 63 reported patients with severe refractory pruritus, including 6 with Sézary syndrome and 2 with mycosis fungoides, who were treated with aprepitant on various dosing regimens. The result was an improvement from a mean baseline VAS of 8.4 to 2.3.

Aprepitant’s mechanism of benefit in cases of severe pruritus is believed to lie in the drug’s high affinity as an antagonist of neurokinin receptor 1, which is expressed in the skin and CNS, he explained. Substance P, an important mediator in the initiation and maintenance of pruritus, binds to this receptor.

Dry skin due to radiation therapy, chemotherapy, or cachexia is the most common cause of pruritus in oncology. But he added that pruritus is intrinsically often a prominent feature of a variety of paraneoplastic diseases and malignancies, and aprepitant is worthy of study in refractory cases.

Pruritic paraneoplastic dermatoses in which the skin findings are an indication of potential concurrent underlying malignancy include dermatomyositis, erythroderma, generalized granuloma annulare, and acrokeratosis paraneoplastica.

Hematologic malignancies where itch often figures prominently include Hodgkin’s disease, polycythemia vera, and Waldenström macroglobulinemia. The solid cancers most frequently accompanied by severe itching include malignancies of the brain, prostate, rectum, and vulva.

Dr. Lacouture reported serving as a consultant to more than a dozen pharmaceutical companies, although Merck, which markets aprepitant, is not among them.

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Oral aprepitant has shown considerable promise as a novel therapy in patients with refractory pruritus, including those with severe itching induced by biologic therapies for cancer.

"I think it’s a tool we should consider using in our patients with pruritus who do not respond to the usual measures," Dr. Mario E. Lacouture said at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

BRUCE JANCIN/Elsevier Global Medical News

Aprepitant (Emend) is approved as an antiemetic agent for cancer patients undergoing chemotherapy. But a growing body of data, including two single-arm proof-of-concept studies, has shown a high response rate in patients with itching resistant to standard treatment, including corticosteroids, UV therapy, and antihistamines, noted Dr. Lacouture, a dermatologist at Memorial Sloan-Kettering Cancer Center, New York.

Severe itching is increasingly recognized as an important side effect of targeted biologic agents for cancer, including erlotinib (Tarceva) and cetuximab (Erbitux). At last year’s meeting of the American Society of Clinical Oncology, Dr. Daniele Santini and coworkers at the Università "Campus Bio-Medico" di Roma presented a study involving 22 patients with severe pruritus treated with aprepitant using a regimen of 125 mg on day 1 and 80 mg on days 3 and 5.

After the single 3-dose cycle of aprepitant, the patients’ median pruritus intensity plummeted from a baseline of 8 down to 1 on a 0-10 visual analog scale (VAS). Twenty of 22 patients experienced a greater than 50% reduction in pruritus. The median duration of benefit following a 3-dose cycle given over 5 days was 25 days.

In the second proof-of-concept study, dermatologists at the Westfälische Wilhelms-Universität Münster (Germany) reported on 20 patients with refractory chronic pruritus from nonmalignant underlying disorders placed on aprepitant at 80 mg/day for 1 week. Sixteen of the 20 patients experienced a marked reduction in itch intensity. From a baseline mean of 8.4 points on the VAS, the group as a whole averaged a 42% improvement to a post-treatment score of 4.3.

A significant reduction in itching was observed as early as 2 days after initiating aprepitant in the study population (PLoS One. 2010;5:e10968).

Patients with itching related to prurigo nodularis or atopic disease responded better than those without the conditions, and patients under age 60 obtained greater improvement than older patients. However, patients with chronic kidney disease as the underlying cause of their itching achieved only minimal benefit.

Side effects were confined to mild, non-treatment-limiting nausea, dizziness, and drowsiness in three patients.

Between the two proof-of-concept studies and smaller published case series, Dr. Lacouture said that he is aware of 63 reported patients with severe refractory pruritus, including 6 with Sézary syndrome and 2 with mycosis fungoides, who were treated with aprepitant on various dosing regimens. The result was an improvement from a mean baseline VAS of 8.4 to 2.3.

Aprepitant’s mechanism of benefit in cases of severe pruritus is believed to lie in the drug’s high affinity as an antagonist of neurokinin receptor 1, which is expressed in the skin and CNS, he explained. Substance P, an important mediator in the initiation and maintenance of pruritus, binds to this receptor.

Dry skin due to radiation therapy, chemotherapy, or cachexia is the most common cause of pruritus in oncology. But he added that pruritus is intrinsically often a prominent feature of a variety of paraneoplastic diseases and malignancies, and aprepitant is worthy of study in refractory cases.

Pruritic paraneoplastic dermatoses in which the skin findings are an indication of potential concurrent underlying malignancy include dermatomyositis, erythroderma, generalized granuloma annulare, and acrokeratosis paraneoplastica.

Hematologic malignancies where itch often figures prominently include Hodgkin’s disease, polycythemia vera, and Waldenström macroglobulinemia. The solid cancers most frequently accompanied by severe itching include malignancies of the brain, prostate, rectum, and vulva.

Dr. Lacouture reported serving as a consultant to more than a dozen pharmaceutical companies, although Merck, which markets aprepitant, is not among them.

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Oral aprepitant has shown considerable promise as a novel therapy in patients with refractory pruritus, including those with severe itching induced by biologic therapies for cancer.

"I think it’s a tool we should consider using in our patients with pruritus who do not respond to the usual measures," Dr. Mario E. Lacouture said at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

BRUCE JANCIN/Elsevier Global Medical News

Aprepitant (Emend) is approved as an antiemetic agent for cancer patients undergoing chemotherapy. But a growing body of data, including two single-arm proof-of-concept studies, has shown a high response rate in patients with itching resistant to standard treatment, including corticosteroids, UV therapy, and antihistamines, noted Dr. Lacouture, a dermatologist at Memorial Sloan-Kettering Cancer Center, New York.

Severe itching is increasingly recognized as an important side effect of targeted biologic agents for cancer, including erlotinib (Tarceva) and cetuximab (Erbitux). At last year’s meeting of the American Society of Clinical Oncology, Dr. Daniele Santini and coworkers at the Università "Campus Bio-Medico" di Roma presented a study involving 22 patients with severe pruritus treated with aprepitant using a regimen of 125 mg on day 1 and 80 mg on days 3 and 5.

After the single 3-dose cycle of aprepitant, the patients’ median pruritus intensity plummeted from a baseline of 8 down to 1 on a 0-10 visual analog scale (VAS). Twenty of 22 patients experienced a greater than 50% reduction in pruritus. The median duration of benefit following a 3-dose cycle given over 5 days was 25 days.

In the second proof-of-concept study, dermatologists at the Westfälische Wilhelms-Universität Münster (Germany) reported on 20 patients with refractory chronic pruritus from nonmalignant underlying disorders placed on aprepitant at 80 mg/day for 1 week. Sixteen of the 20 patients experienced a marked reduction in itch intensity. From a baseline mean of 8.4 points on the VAS, the group as a whole averaged a 42% improvement to a post-treatment score of 4.3.

A significant reduction in itching was observed as early as 2 days after initiating aprepitant in the study population (PLoS One. 2010;5:e10968).

Patients with itching related to prurigo nodularis or atopic disease responded better than those without the conditions, and patients under age 60 obtained greater improvement than older patients. However, patients with chronic kidney disease as the underlying cause of their itching achieved only minimal benefit.

Side effects were confined to mild, non-treatment-limiting nausea, dizziness, and drowsiness in three patients.

Between the two proof-of-concept studies and smaller published case series, Dr. Lacouture said that he is aware of 63 reported patients with severe refractory pruritus, including 6 with Sézary syndrome and 2 with mycosis fungoides, who were treated with aprepitant on various dosing regimens. The result was an improvement from a mean baseline VAS of 8.4 to 2.3.

Aprepitant’s mechanism of benefit in cases of severe pruritus is believed to lie in the drug’s high affinity as an antagonist of neurokinin receptor 1, which is expressed in the skin and CNS, he explained. Substance P, an important mediator in the initiation and maintenance of pruritus, binds to this receptor.

Dry skin due to radiation therapy, chemotherapy, or cachexia is the most common cause of pruritus in oncology. But he added that pruritus is intrinsically often a prominent feature of a variety of paraneoplastic diseases and malignancies, and aprepitant is worthy of study in refractory cases.

Pruritic paraneoplastic dermatoses in which the skin findings are an indication of potential concurrent underlying malignancy include dermatomyositis, erythroderma, generalized granuloma annulare, and acrokeratosis paraneoplastica.

Hematologic malignancies where itch often figures prominently include Hodgkin’s disease, polycythemia vera, and Waldenström macroglobulinemia. The solid cancers most frequently accompanied by severe itching include malignancies of the brain, prostate, rectum, and vulva.

Dr. Lacouture reported serving as a consultant to more than a dozen pharmaceutical companies, although Merck, which markets aprepitant, is not among them.

SDEF and this news organization are owned by Elsevier.

Jennifer G. Powers, MD, and Barbara A. Gilchrest, MD

“Vitamin D” is the term commonly used to denote the lipid-soluble hormone critical for calcium homeostasis and skeletal maintenance. A precursor to the active compound is found in many plants and animal tissues and can be absorbed from the gut; it can also be derived from cell membranes in the epidermis during ultraviolet B irradiation. This compound is then hydroxylated sequentially in the liver and kidney to produce the active hormone 1,25(OH)2D that binds its nuclear receptor to modulate gene expression. Recently, vitamin D hydroxylases and the nuclear receptor have been identified in many tissues, suggesting previously unrecognized roles for vitamin D. Some epidemiologic studies have also correlated low levels of the inactive storage form 25(OH)D with an increased incidence or prevalence of a variety of diseases, suggesting that large oral supplements and/or increased ultraviolet (UV) exposure might therefore improve individual health. However, randomized, prospective controlled trials comparing vitamin D supplements with placebo have not supported this belief. Moreover, current evidence supports the conclusion that protection from UV radiation does not compromise vitamin D status or lead to iatrogenic disease. In contrast, high vitamin D levels appear to incur a risk of kidney stones and other adverse effects. In the case of true vitamin D deficiency, supplements are a more reliable and quantifiable source of the vitamin than UV exposure.

*For a PDF of the full article, click on the link to the left of this introduction.

Jennifer G. Powers, MD, and Barbara A. Gilchrest, MD

“Vitamin D” is the term commonly used to denote the lipid-soluble hormone critical for calcium homeostasis and skeletal maintenance. A precursor to the active compound is found in many plants and animal tissues and can be absorbed from the gut; it can also be derived from cell membranes in the epidermis during ultraviolet B irradiation. This compound is then hydroxylated sequentially in the liver and kidney to produce the active hormone 1,25(OH)2D that binds its nuclear receptor to modulate gene expression. Recently, vitamin D hydroxylases and the nuclear receptor have been identified in many tissues, suggesting previously unrecognized roles for vitamin D. Some epidemiologic studies have also correlated low levels of the inactive storage form 25(OH)D with an increased incidence or prevalence of a variety of diseases, suggesting that large oral supplements and/or increased ultraviolet (UV) exposure might therefore improve individual health. However, randomized, prospective controlled trials comparing vitamin D supplements with placebo have not supported this belief. Moreover, current evidence supports the conclusion that protection from UV radiation does not compromise vitamin D status or lead to iatrogenic disease. In contrast, high vitamin D levels appear to incur a risk of kidney stones and other adverse effects. In the case of true vitamin D deficiency, supplements are a more reliable and quantifiable source of the vitamin than UV exposure.

*For a PDF of the full article, click on the link to the left of this introduction.

Jennifer G. Powers, MD, and Barbara A. Gilchrest, MD

“Vitamin D” is the term commonly used to denote the lipid-soluble hormone critical for calcium homeostasis and skeletal maintenance. A precursor to the active compound is found in many plants and animal tissues and can be absorbed from the gut; it can also be derived from cell membranes in the epidermis during ultraviolet B irradiation. This compound is then hydroxylated sequentially in the liver and kidney to produce the active hormone 1,25(OH)2D that binds its nuclear receptor to modulate gene expression. Recently, vitamin D hydroxylases and the nuclear receptor have been identified in many tissues, suggesting previously unrecognized roles for vitamin D. Some epidemiologic studies have also correlated low levels of the inactive storage form 25(OH)D with an increased incidence or prevalence of a variety of diseases, suggesting that large oral supplements and/or increased ultraviolet (UV) exposure might therefore improve individual health. However, randomized, prospective controlled trials comparing vitamin D supplements with placebo have not supported this belief. Moreover, current evidence supports the conclusion that protection from UV radiation does not compromise vitamin D status or lead to iatrogenic disease. In contrast, high vitamin D levels appear to incur a risk of kidney stones and other adverse effects. In the case of true vitamin D deficiency, supplements are a more reliable and quantifiable source of the vitamin than UV exposure.

*For a PDF of the full article, click on the link to the left of this introduction.

M. Shane Chapman, MD

Vitamin A is required for the proper functioning of many important metabolic and physiologic activities, including vision, gene transcription, the immune system and skin cell differentiation. Both excessive and deficient levels of vitamin A lead to poor functioning of many human systems. The biologically active form, retinoic acid, binds to nuclear receptors that facilitate transcription that ultimately leads to it’s physiological effects. Retinoids are derivatives of vitamin A that are medications used to treat acne vulgaris, psoriasis, ichthyosis (and other disorders of keratinization), skin cancer prevention as well as several bone marrow derived neoplasias. Systemic retinoids are teratogenic and have to be prescribed with caution and close oversight. Other potential adverse events are controversial. These include the relationship of retinoid derivatives in sunscreens, their effects on bone mineral density, depression and suicidal ideation and inflammatory bowel disease. These controversies will be discussed in detail.

*For a PDF of the full article, click on the link to the left of this introduction.

M. Shane Chapman, MD

Vitamin A is required for the proper functioning of many important metabolic and physiologic activities, including vision, gene transcription, the immune system and skin cell differentiation. Both excessive and deficient levels of vitamin A lead to poor functioning of many human systems. The biologically active form, retinoic acid, binds to nuclear receptors that facilitate transcription that ultimately leads to it’s physiological effects. Retinoids are derivatives of vitamin A that are medications used to treat acne vulgaris, psoriasis, ichthyosis (and other disorders of keratinization), skin cancer prevention as well as several bone marrow derived neoplasias. Systemic retinoids are teratogenic and have to be prescribed with caution and close oversight. Other potential adverse events are controversial. These include the relationship of retinoid derivatives in sunscreens, their effects on bone mineral density, depression and suicidal ideation and inflammatory bowel disease. These controversies will be discussed in detail.

*For a PDF of the full article, click on the link to the left of this introduction.

M. Shane Chapman, MD

Vitamin A is required for the proper functioning of many important metabolic and physiologic activities, including vision, gene transcription, the immune system and skin cell differentiation. Both excessive and deficient levels of vitamin A lead to poor functioning of many human systems. The biologically active form, retinoic acid, binds to nuclear receptors that facilitate transcription that ultimately leads to it’s physiological effects. Retinoids are derivatives of vitamin A that are medications used to treat acne vulgaris, psoriasis, ichthyosis (and other disorders of keratinization), skin cancer prevention as well as several bone marrow derived neoplasias. Systemic retinoids are teratogenic and have to be prescribed with caution and close oversight. Other potential adverse events are controversial. These include the relationship of retinoid derivatives in sunscreens, their effects on bone mineral density, depression and suicidal ideation and inflammatory bowel disease. These controversies will be discussed in detail.

*For a PDF of the full article, click on the link to the left of this introduction.

Brian Poligone, MD, PhD, and Peter Heald, MD

In the management of patients with cutaneous T-cell lymphoma (CTCL), there are numerous distinct therapy options. Each of these therapies is discussed in terms of when to use it, what factors limit the success of the treatment, and what to expect. A menu is defined as a list of items from which to choose. The treatments for CTCL are presented in various menus where they are options for a particular goal in a particular setting of CTCL. The best recognized clinical scenarios of CTCL are those recognized by the staging system: limited patch plaque (T1), disseminated patch plaque (T2), erythroderma (T4), and tumor (T3). Each phase of the disease will have the menu of therapy options presented for a given goal of management.

*For a PDF of the full article, click on the link to the left of this introduction.

Brian Poligone, MD, PhD, and Peter Heald, MD

In the management of patients with cutaneous T-cell lymphoma (CTCL), there are numerous distinct therapy options. Each of these therapies is discussed in terms of when to use it, what factors limit the success of the treatment, and what to expect. A menu is defined as a list of items from which to choose. The treatments for CTCL are presented in various menus where they are options for a particular goal in a particular setting of CTCL. The best recognized clinical scenarios of CTCL are those recognized by the staging system: limited patch plaque (T1), disseminated patch plaque (T2), erythroderma (T4), and tumor (T3). Each phase of the disease will have the menu of therapy options presented for a given goal of management.

*For a PDF of the full article, click on the link to the left of this introduction.

Brian Poligone, MD, PhD, and Peter Heald, MD

In the management of patients with cutaneous T-cell lymphoma (CTCL), there are numerous distinct therapy options. Each of these therapies is discussed in terms of when to use it, what factors limit the success of the treatment, and what to expect. A menu is defined as a list of items from which to choose. The treatments for CTCL are presented in various menus where they are options for a particular goal in a particular setting of CTCL. The best recognized clinical scenarios of CTCL are those recognized by the staging system: limited patch plaque (T1), disseminated patch plaque (T2), erythroderma (T4), and tumor (T3). Each phase of the disease will have the menu of therapy options presented for a given goal of management.

*For a PDF of the full article, click on the link to the left of this introduction.

Allison T. O’Donnell, MPH, and Caroline C. Kim, MD

The incidence of melanoma is on the rise, and early detection of disease is imperative to reduce mortality. Dermatologists are key players in the early detection of melanoma; however, some clinicians rely on their clinical examination without any additional diagnostic tools to make this important diagnosis. Certain patients, such as atypical nevus patients, have more complicated mole examinations, making the diagnosis of melanoma difficult, whereas some melanomas, such as amelanotic melanomas, can be diagnostically challenging. The goal of the clinician is to detect melanoma with the highest accuracy, while avoiding unnecessary biopsies. Using diagnostic melanoma tools as an adjunct to the clinical examination, dermatologists have the opportunity to increase both their sensitivity and specificity for melanoma detection. This article will review current imaging technologies and those in development for pigmented lesions, updating the clinician on basic principals of such modalities and clinical use of such technologies in practice.

*For a PDF of the full article, click on the link to the left of this introduction.

Allison T. O’Donnell, MPH, and Caroline C. Kim, MD

The incidence of melanoma is on the rise, and early detection of disease is imperative to reduce mortality. Dermatologists are key players in the early detection of melanoma; however, some clinicians rely on their clinical examination without any additional diagnostic tools to make this important diagnosis. Certain patients, such as atypical nevus patients, have more complicated mole examinations, making the diagnosis of melanoma difficult, whereas some melanomas, such as amelanotic melanomas, can be diagnostically challenging. The goal of the clinician is to detect melanoma with the highest accuracy, while avoiding unnecessary biopsies. Using diagnostic melanoma tools as an adjunct to the clinical examination, dermatologists have the opportunity to increase both their sensitivity and specificity for melanoma detection. This article will review current imaging technologies and those in development for pigmented lesions, updating the clinician on basic principals of such modalities and clinical use of such technologies in practice.

*For a PDF of the full article, click on the link to the left of this introduction.

Allison T. O’Donnell, MPH, and Caroline C. Kim, MD

The incidence of melanoma is on the rise, and early detection of disease is imperative to reduce mortality. Dermatologists are key players in the early detection of melanoma; however, some clinicians rely on their clinical examination without any additional diagnostic tools to make this important diagnosis. Certain patients, such as atypical nevus patients, have more complicated mole examinations, making the diagnosis of melanoma difficult, whereas some melanomas, such as amelanotic melanomas, can be diagnostically challenging. The goal of the clinician is to detect melanoma with the highest accuracy, while avoiding unnecessary biopsies. Using diagnostic melanoma tools as an adjunct to the clinical examination, dermatologists have the opportunity to increase both their sensitivity and specificity for melanoma detection. This article will review current imaging technologies and those in development for pigmented lesions, updating the clinician on basic principals of such modalities and clinical use of such technologies in practice.

*For a PDF of the full article, click on the link to the left of this introduction.

Michael Krathen, MD

The detection of cutaneous melanoma still largely relies on clinical suspicion, skin biopsy, and histopathologic evaluation. New technologies are being evaluated to bypass the skin biopsy in the detection of melanoma. The quest for reliable biomarkers, with respect to subclinical detection, prognosis, and predicting treatment response, is longstanding and ongoing. New therapies have been developed for metastatic disease, including targeted small molecule inhibitors as well as immune modulators.

*For a PDF of the full article, click on the link to the left of this introduction.

Michael Krathen, MD

The detection of cutaneous melanoma still largely relies on clinical suspicion, skin biopsy, and histopathologic evaluation. New technologies are being evaluated to bypass the skin biopsy in the detection of melanoma. The quest for reliable biomarkers, with respect to subclinical detection, prognosis, and predicting treatment response, is longstanding and ongoing. New therapies have been developed for metastatic disease, including targeted small molecule inhibitors as well as immune modulators.

*For a PDF of the full article, click on the link to the left of this introduction.

Michael Krathen, MD

The detection of cutaneous melanoma still largely relies on clinical suspicion, skin biopsy, and histopathologic evaluation. New technologies are being evaluated to bypass the skin biopsy in the detection of melanoma. The quest for reliable biomarkers, with respect to subclinical detection, prognosis, and predicting treatment response, is longstanding and ongoing. New therapies have been developed for metastatic disease, including targeted small molecule inhibitors as well as immune modulators.

*For a PDF of the full article, click on the link to the left of this introduction.