Sharon Worcester

SAN ANTONIO – More of the children who present to the pediatric emergency department with asthma exacerbation received recommended care when the staff had instituted a nurse-initiated, evidence-based, standardized order set, according to Dr. Moira E. Breslin.

Specifically, the percentage of patients receiving at least one dose of ipratropium bromide improved from 55.4% before implementation of the order set to 90.9% after implementation. Compliance with the recommendation of the National Asthma Guidelines that patients receive three consecutive nebulized treatments of ipratropium bromide increased from 13.5% to 40.9%, Dr. Breslin of Duke University Medical Center, Durham, N.C., reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The median time to delivery of rescue medication also improved from 21 minutes to 14 minutes for first inhaled bronchodilator administration, and from 41 minutes to 19 minutes for delivery of systemic corticosteroids.

All differences were statistically significant.

The findings are based on a review of charts for 193 patients treated in the pediatric emergency department for status asthmaticus before implementation of the evidence-based standardized order set, or EBSOS, (between Feb. 23, 2009, and Feb. 22, 2012), and for 22 patients treated after implementation (between Feb. 23, 2012, and July 31, 2012).

The EBSOS for the treatment of pediatric asthma used in this study was developed and incorporated into the emergency department electronic ordering system because personnel were not consistently following national asthma treatment guidelines, according to a separate 2010 emergency department records review.

That review showed that 24% of patients admitted for status asthmaticus had not received the recommended ipratropium bromide treatment, and that only 14% of those who did receive ipratropium bromide received the recommended three consecutive doses.

Implementation of the EBSOS involved the use of an algorithm based on a validated Modified Pulmonary Index Score that allowed for triage nurse initiation of the EBSOS. The EBSOS called for continuous pulse oximetry, supplemental oxygen as needed, evaluation by a respiratory therapist, nebulized albuterol administration at 5 mg every 20 minutes for three treatments, administration of nebulized ipratropium bromide at 0.5 mg every 20 minutes for three treatments, and administration of one dose of oral prednisolone at 2 mg/kg up to a maximum of 60 mg.

"Implementation of an EBSOS improved compliance to national asthma guidelines, as evidenced by a higher proportion of pediatric emergency department patients in status asthmaticus receiving ipratropium bromide, as well as shortened time to delivery of inhaled bronchodilators and systemic steroids," Dr. Breslin concluded, noting that future analysis of this review will focus on patient-centered outcomes.

Dr. Breslin reported having no relevant financial disclosures

SAN ANTONIO – More of the children who present to the pediatric emergency department with asthma exacerbation received recommended care when the staff had instituted a nurse-initiated, evidence-based, standardized order set, according to Dr. Moira E. Breslin.

Specifically, the percentage of patients receiving at least one dose of ipratropium bromide improved from 55.4% before implementation of the order set to 90.9% after implementation. Compliance with the recommendation of the National Asthma Guidelines that patients receive three consecutive nebulized treatments of ipratropium bromide increased from 13.5% to 40.9%, Dr. Breslin of Duke University Medical Center, Durham, N.C., reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The median time to delivery of rescue medication also improved from 21 minutes to 14 minutes for first inhaled bronchodilator administration, and from 41 minutes to 19 minutes for delivery of systemic corticosteroids.

All differences were statistically significant.

The findings are based on a review of charts for 193 patients treated in the pediatric emergency department for status asthmaticus before implementation of the evidence-based standardized order set, or EBSOS, (between Feb. 23, 2009, and Feb. 22, 2012), and for 22 patients treated after implementation (between Feb. 23, 2012, and July 31, 2012).

The EBSOS for the treatment of pediatric asthma used in this study was developed and incorporated into the emergency department electronic ordering system because personnel were not consistently following national asthma treatment guidelines, according to a separate 2010 emergency department records review.

That review showed that 24% of patients admitted for status asthmaticus had not received the recommended ipratropium bromide treatment, and that only 14% of those who did receive ipratropium bromide received the recommended three consecutive doses.

Implementation of the EBSOS involved the use of an algorithm based on a validated Modified Pulmonary Index Score that allowed for triage nurse initiation of the EBSOS. The EBSOS called for continuous pulse oximetry, supplemental oxygen as needed, evaluation by a respiratory therapist, nebulized albuterol administration at 5 mg every 20 minutes for three treatments, administration of nebulized ipratropium bromide at 0.5 mg every 20 minutes for three treatments, and administration of one dose of oral prednisolone at 2 mg/kg up to a maximum of 60 mg.

"Implementation of an EBSOS improved compliance to national asthma guidelines, as evidenced by a higher proportion of pediatric emergency department patients in status asthmaticus receiving ipratropium bromide, as well as shortened time to delivery of inhaled bronchodilators and systemic steroids," Dr. Breslin concluded, noting that future analysis of this review will focus on patient-centered outcomes.

Dr. Breslin reported having no relevant financial disclosures

SAN ANTONIO – More of the children who present to the pediatric emergency department with asthma exacerbation received recommended care when the staff had instituted a nurse-initiated, evidence-based, standardized order set, according to Dr. Moira E. Breslin.

Specifically, the percentage of patients receiving at least one dose of ipratropium bromide improved from 55.4% before implementation of the order set to 90.9% after implementation. Compliance with the recommendation of the National Asthma Guidelines that patients receive three consecutive nebulized treatments of ipratropium bromide increased from 13.5% to 40.9%, Dr. Breslin of Duke University Medical Center, Durham, N.C., reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The median time to delivery of rescue medication also improved from 21 minutes to 14 minutes for first inhaled bronchodilator administration, and from 41 minutes to 19 minutes for delivery of systemic corticosteroids.

All differences were statistically significant.

The findings are based on a review of charts for 193 patients treated in the pediatric emergency department for status asthmaticus before implementation of the evidence-based standardized order set, or EBSOS, (between Feb. 23, 2009, and Feb. 22, 2012), and for 22 patients treated after implementation (between Feb. 23, 2012, and July 31, 2012).

The EBSOS for the treatment of pediatric asthma used in this study was developed and incorporated into the emergency department electronic ordering system because personnel were not consistently following national asthma treatment guidelines, according to a separate 2010 emergency department records review.

That review showed that 24% of patients admitted for status asthmaticus had not received the recommended ipratropium bromide treatment, and that only 14% of those who did receive ipratropium bromide received the recommended three consecutive doses.

Implementation of the EBSOS involved the use of an algorithm based on a validated Modified Pulmonary Index Score that allowed for triage nurse initiation of the EBSOS. The EBSOS called for continuous pulse oximetry, supplemental oxygen as needed, evaluation by a respiratory therapist, nebulized albuterol administration at 5 mg every 20 minutes for three treatments, administration of nebulized ipratropium bromide at 0.5 mg every 20 minutes for three treatments, and administration of one dose of oral prednisolone at 2 mg/kg up to a maximum of 60 mg.

"Implementation of an EBSOS improved compliance to national asthma guidelines, as evidenced by a higher proportion of pediatric emergency department patients in status asthmaticus receiving ipratropium bromide, as well as shortened time to delivery of inhaled bronchodilators and systemic steroids," Dr. Breslin concluded, noting that future analysis of this review will focus on patient-centered outcomes.

Dr. Breslin reported having no relevant financial disclosures

MIAMI BEACH – In practice, acne patients are treated three times longer than clinical trials suggest, based on data from more than 2,000 patients at an academic medical center.

The findings have implications both for setting patients’ treatment expectations and for designing future clinical trials, said Karen Huang of Wake Forest University, Winston-Salem, N.C., said at the annual meeting of the American Academy of Dermatology.

Ms. Huang and her colleagues reviewed electronic records for patients who were treated at an academic medical practice between Jan. 1, 2009, and Nov. 15, 2012. Overall, 2,250 patients had at least one acne-related visit with a dermatologist. Of these, 57% had only one visit and 43% had multiple visits.

For patients who had multiple visits, the mean duration of treatment from the first to the last visit was approximately 9 months (0.79 years). Approximately 25% continued seeing their dermatologists for about a year, and half continued treatment for nearly 5 months (0.4 years).

Not unexpectedly, patients treated with oral medication, including isotretinoin and other oral treatments, were more likely than those treated with topical medications to have multiple visits. In addition, the number of visits by patients who received isotretinoin slowed gradually at first, then declined more rapidly over time compared with patients who received topical treatments.

Approximately 90% of individuals experience acne during their lifetimes, but the actual duration of acne episodes has not been well characterized in the literature, said Ms. Huang. The duration of treatment seen in 40 recent studies of acne treatment identified at clinicaltrials.gov was about 12 weeks, she added.

The current findings represent a lower limit on the duration of acne treatment because of a lack of data on which patients may have discontinued treatment prematurely or continued treatment elsewhere, such as with a primary care physician, she said.

The study findings may be of interest not only for clinical trial design (in that researchers might want to simulate average treatment duration), but also for physicians who want to set realistic expectations about treatment for their patients.

"It has been shown that if you help set patients’ expectations of what their treatment will be like, it may help improve adherence," she said.

Ms. Huang had no financial conflicts to disclose.

MIAMI BEACH – In practice, acne patients are treated three times longer than clinical trials suggest, based on data from more than 2,000 patients at an academic medical center.

The findings have implications both for setting patients’ treatment expectations and for designing future clinical trials, said Karen Huang of Wake Forest University, Winston-Salem, N.C., said at the annual meeting of the American Academy of Dermatology.

Ms. Huang and her colleagues reviewed electronic records for patients who were treated at an academic medical practice between Jan. 1, 2009, and Nov. 15, 2012. Overall, 2,250 patients had at least one acne-related visit with a dermatologist. Of these, 57% had only one visit and 43% had multiple visits.

For patients who had multiple visits, the mean duration of treatment from the first to the last visit was approximately 9 months (0.79 years). Approximately 25% continued seeing their dermatologists for about a year, and half continued treatment for nearly 5 months (0.4 years).

Not unexpectedly, patients treated with oral medication, including isotretinoin and other oral treatments, were more likely than those treated with topical medications to have multiple visits. In addition, the number of visits by patients who received isotretinoin slowed gradually at first, then declined more rapidly over time compared with patients who received topical treatments.

Approximately 90% of individuals experience acne during their lifetimes, but the actual duration of acne episodes has not been well characterized in the literature, said Ms. Huang. The duration of treatment seen in 40 recent studies of acne treatment identified at clinicaltrials.gov was about 12 weeks, she added.

The current findings represent a lower limit on the duration of acne treatment because of a lack of data on which patients may have discontinued treatment prematurely or continued treatment elsewhere, such as with a primary care physician, she said.

The study findings may be of interest not only for clinical trial design (in that researchers might want to simulate average treatment duration), but also for physicians who want to set realistic expectations about treatment for their patients.

"It has been shown that if you help set patients’ expectations of what their treatment will be like, it may help improve adherence," she said.

Ms. Huang had no financial conflicts to disclose.

MIAMI BEACH – In practice, acne patients are treated three times longer than clinical trials suggest, based on data from more than 2,000 patients at an academic medical center.

The findings have implications both for setting patients’ treatment expectations and for designing future clinical trials, said Karen Huang of Wake Forest University, Winston-Salem, N.C., said at the annual meeting of the American Academy of Dermatology.

Ms. Huang and her colleagues reviewed electronic records for patients who were treated at an academic medical practice between Jan. 1, 2009, and Nov. 15, 2012. Overall, 2,250 patients had at least one acne-related visit with a dermatologist. Of these, 57% had only one visit and 43% had multiple visits.

For patients who had multiple visits, the mean duration of treatment from the first to the last visit was approximately 9 months (0.79 years). Approximately 25% continued seeing their dermatologists for about a year, and half continued treatment for nearly 5 months (0.4 years).

Not unexpectedly, patients treated with oral medication, including isotretinoin and other oral treatments, were more likely than those treated with topical medications to have multiple visits. In addition, the number of visits by patients who received isotretinoin slowed gradually at first, then declined more rapidly over time compared with patients who received topical treatments.

Approximately 90% of individuals experience acne during their lifetimes, but the actual duration of acne episodes has not been well characterized in the literature, said Ms. Huang. The duration of treatment seen in 40 recent studies of acne treatment identified at clinicaltrials.gov was about 12 weeks, she added.

The current findings represent a lower limit on the duration of acne treatment because of a lack of data on which patients may have discontinued treatment prematurely or continued treatment elsewhere, such as with a primary care physician, she said.

The study findings may be of interest not only for clinical trial design (in that researchers might want to simulate average treatment duration), but also for physicians who want to set realistic expectations about treatment for their patients.

"It has been shown that if you help set patients’ expectations of what their treatment will be like, it may help improve adherence," she said.

Ms. Huang had no financial conflicts to disclose.

The oral phosphodiesterase-4 inhibitor apremilast significantly improves moderate to severe psoriasis with minimal side effects, according to data from a phase III, randomized controlled trial of 844 patients.

The drug had an excellent safety profile and resulted in significantly greater improvement in moderate to severe psoriasis than placebo after 16 weeks of treatment in the ESTEEM 1 trial.

The results were reported in a late-breaker session at the annual meeting of the American Academy of Dermatology.

Apremilast is "one of the new small molecules being developed for treatment of psoriasis," said Dr. Kristian Reich of SCIderm Research Institute and Dermatologikum, Hamburg, Germany.

"We believe it has anti-inflammatory properties, because by increasing the intracellular level of cyclic AMP (adenosine monophosphate), it actually activates protein kinase A to modulate the balance between proinflammatory and anti-inflammatory mediators released by a cell in a way that pro-inflammatory mediators are down-regulated and anti-inflammatory mediators are upregulated," he said.

Of 562 patients randomized to receive 30 mg of apremilast twice daily for 16 weeks, 33.1% achieved 75% improvement on the Psoriasis Area Severity Index (PASI-75) scale score, compared with only 5.3% of 282 patients who received placebo. Patients in the treatment group also showed significant improvement compared with the placebo group for secondary endpoints including physician global assessment (PGA) score, change in body surface area affected, and pruritus.

Improvements also were noted in difficult to treat areas such as the scalp and nails. For example, about 50% of affected patients achieved a 50% reduction in nail psoriasis severity, Dr. Reich said.

The study participants were adults with moderate to severe chronic plaque psoriasis, surface area involvement greater than 10%, and a PGA score of 3 or higher. All were candidates for phototherapy or systemic therapy, half had been treated previously with other systemic therapies, including biologics, and nearly 1 in 5 patients had been treated with tumor necrosis factor (TNF) blockers.

Patients initially receiving placebo switched over to active treatment after the first 16 weeks, and treatment in all patients continued at the 30-mg twice-daily dose for an additional 16 weeks, followed by a randomized withdrawal phase through week 52.

The treatment effects seen with apremilast at 16 weeks were slightly greater in patients who had not previously received conventional systemic or biologic therapy compared with the total patient population, but even those with prior failed TNF treatment achieved a PASI-75 response.

Onset of action occurred within 2-4 weeks, and clinically relevant improvement continued beyond 16 weeks. The mean percent change from baseline in PASI score was 54.9% at 16 weeks, and 61.9% at 32 weeks, Dr. Reich said. "It will be interesting to see, long-term, what happens beyond the 16-week endpoint," he added.

The 16-week outcomes in the apremilast group represent "significant moderate efficacy," but the safety profile of the drug is the real story of the data, Dr. Reich said.

"Safety is a major issue when it comes to systemic therapies for psoriasis," he emphasized.

A slightly higher rate of withdrawals in the apremilast group may have been due to gastrointestinal effects, a well-known side effect of TNF inhibitors.

Gastrointestinal side effects included diarrhea and nausea, but most cases were transient, and mild to moderate. Most side effects occurred and resolved within the first 15 days of treatment. In fact, more than 96% of patients reported experiencing either no adverse events or only mild to moderate adverse events. Reports of serious adverse events were similar in the treatment and placebo groups (2.1% v. 2.8%, respectively), as were reports of severe adverse events (3.6% vs. 3.2%, respectively).

No problems were noted with respect to lipid levels, liver enzymes, opportunistic infections, or cardiac abnormalities, and no cases of tuberculosis or lymphoma occurred during the study period.

"What stands out so far is an extremely good safety profile," Dr. Reich said.

ESTEEM 1 is the first of two phase III studies of apremilast for chronic plaque psoriasis. Statistical significance for the primary and major secondary endpoints of both ESTEEM 1 and ESTEEM 2 was announced previously by Celgene, the maker of apremilast.

"A NDA (New Drug Application) submission to the U.S. Food and Drug Administration, based on the combined ESTEEM 1 and 2 studies for psoriasis, is expected in the second half of 2013," according to a Celgene press release.

Celgene previously announced it would file a separate NDA for psoriatic arthritis in the first quarter of 2013, based on data from three other trials (PALACE-1, 2, and 3), which were released in 2012. Another phase III trial (POSTURE) began enrolling patients in April 2012 to evaluate apremilast in patients with ankylosing spondylitis.

Participants in the ESTEEM 1 trial will be enrolled in a 5-year extension study so researchers can collect long-term safety and efficacy data. However, based on the current findings, including data from psoriatic arthritis patients, the drug looks quite promising for the treatment of psoriasis, Dr. Reich said.

"I see this as a prime candidate for future management of psoriasis that allows us to treat a range of patients, including more moderate cases earlier on," he said. Such a treatment is needed, particularly in light of new disease concepts that characterize psoriasis as involving systemic inflammation that requires early control, he explained.

The study was sponsored by Celgene.

The oral phosphodiesterase-4 inhibitor apremilast significantly improves moderate to severe psoriasis with minimal side effects, according to data from a phase III, randomized controlled trial of 844 patients.

The drug had an excellent safety profile and resulted in significantly greater improvement in moderate to severe psoriasis than placebo after 16 weeks of treatment in the ESTEEM 1 trial.

The results were reported in a late-breaker session at the annual meeting of the American Academy of Dermatology.

Apremilast is "one of the new small molecules being developed for treatment of psoriasis," said Dr. Kristian Reich of SCIderm Research Institute and Dermatologikum, Hamburg, Germany.

"We believe it has anti-inflammatory properties, because by increasing the intracellular level of cyclic AMP (adenosine monophosphate), it actually activates protein kinase A to modulate the balance between proinflammatory and anti-inflammatory mediators released by a cell in a way that pro-inflammatory mediators are down-regulated and anti-inflammatory mediators are upregulated," he said.

Of 562 patients randomized to receive 30 mg of apremilast twice daily for 16 weeks, 33.1% achieved 75% improvement on the Psoriasis Area Severity Index (PASI-75) scale score, compared with only 5.3% of 282 patients who received placebo. Patients in the treatment group also showed significant improvement compared with the placebo group for secondary endpoints including physician global assessment (PGA) score, change in body surface area affected, and pruritus.

Improvements also were noted in difficult to treat areas such as the scalp and nails. For example, about 50% of affected patients achieved a 50% reduction in nail psoriasis severity, Dr. Reich said.

The study participants were adults with moderate to severe chronic plaque psoriasis, surface area involvement greater than 10%, and a PGA score of 3 or higher. All were candidates for phototherapy or systemic therapy, half had been treated previously with other systemic therapies, including biologics, and nearly 1 in 5 patients had been treated with tumor necrosis factor (TNF) blockers.

Patients initially receiving placebo switched over to active treatment after the first 16 weeks, and treatment in all patients continued at the 30-mg twice-daily dose for an additional 16 weeks, followed by a randomized withdrawal phase through week 52.

The treatment effects seen with apremilast at 16 weeks were slightly greater in patients who had not previously received conventional systemic or biologic therapy compared with the total patient population, but even those with prior failed TNF treatment achieved a PASI-75 response.

Onset of action occurred within 2-4 weeks, and clinically relevant improvement continued beyond 16 weeks. The mean percent change from baseline in PASI score was 54.9% at 16 weeks, and 61.9% at 32 weeks, Dr. Reich said. "It will be interesting to see, long-term, what happens beyond the 16-week endpoint," he added.

The 16-week outcomes in the apremilast group represent "significant moderate efficacy," but the safety profile of the drug is the real story of the data, Dr. Reich said.

"Safety is a major issue when it comes to systemic therapies for psoriasis," he emphasized.

A slightly higher rate of withdrawals in the apremilast group may have been due to gastrointestinal effects, a well-known side effect of TNF inhibitors.

Gastrointestinal side effects included diarrhea and nausea, but most cases were transient, and mild to moderate. Most side effects occurred and resolved within the first 15 days of treatment. In fact, more than 96% of patients reported experiencing either no adverse events or only mild to moderate adverse events. Reports of serious adverse events were similar in the treatment and placebo groups (2.1% v. 2.8%, respectively), as were reports of severe adverse events (3.6% vs. 3.2%, respectively).

No problems were noted with respect to lipid levels, liver enzymes, opportunistic infections, or cardiac abnormalities, and no cases of tuberculosis or lymphoma occurred during the study period.

"What stands out so far is an extremely good safety profile," Dr. Reich said.

ESTEEM 1 is the first of two phase III studies of apremilast for chronic plaque psoriasis. Statistical significance for the primary and major secondary endpoints of both ESTEEM 1 and ESTEEM 2 was announced previously by Celgene, the maker of apremilast.

"A NDA (New Drug Application) submission to the U.S. Food and Drug Administration, based on the combined ESTEEM 1 and 2 studies for psoriasis, is expected in the second half of 2013," according to a Celgene press release.

Celgene previously announced it would file a separate NDA for psoriatic arthritis in the first quarter of 2013, based on data from three other trials (PALACE-1, 2, and 3), which were released in 2012. Another phase III trial (POSTURE) began enrolling patients in April 2012 to evaluate apremilast in patients with ankylosing spondylitis.

Participants in the ESTEEM 1 trial will be enrolled in a 5-year extension study so researchers can collect long-term safety and efficacy data. However, based on the current findings, including data from psoriatic arthritis patients, the drug looks quite promising for the treatment of psoriasis, Dr. Reich said.

"I see this as a prime candidate for future management of psoriasis that allows us to treat a range of patients, including more moderate cases earlier on," he said. Such a treatment is needed, particularly in light of new disease concepts that characterize psoriasis as involving systemic inflammation that requires early control, he explained.

The study was sponsored by Celgene.

The oral phosphodiesterase-4 inhibitor apremilast significantly improves moderate to severe psoriasis with minimal side effects, according to data from a phase III, randomized controlled trial of 844 patients.

The drug had an excellent safety profile and resulted in significantly greater improvement in moderate to severe psoriasis than placebo after 16 weeks of treatment in the ESTEEM 1 trial.

The results were reported in a late-breaker session at the annual meeting of the American Academy of Dermatology.

Apremilast is "one of the new small molecules being developed for treatment of psoriasis," said Dr. Kristian Reich of SCIderm Research Institute and Dermatologikum, Hamburg, Germany.

"We believe it has anti-inflammatory properties, because by increasing the intracellular level of cyclic AMP (adenosine monophosphate), it actually activates protein kinase A to modulate the balance between proinflammatory and anti-inflammatory mediators released by a cell in a way that pro-inflammatory mediators are down-regulated and anti-inflammatory mediators are upregulated," he said.

Of 562 patients randomized to receive 30 mg of apremilast twice daily for 16 weeks, 33.1% achieved 75% improvement on the Psoriasis Area Severity Index (PASI-75) scale score, compared with only 5.3% of 282 patients who received placebo. Patients in the treatment group also showed significant improvement compared with the placebo group for secondary endpoints including physician global assessment (PGA) score, change in body surface area affected, and pruritus.

Improvements also were noted in difficult to treat areas such as the scalp and nails. For example, about 50% of affected patients achieved a 50% reduction in nail psoriasis severity, Dr. Reich said.

The study participants were adults with moderate to severe chronic plaque psoriasis, surface area involvement greater than 10%, and a PGA score of 3 or higher. All were candidates for phototherapy or systemic therapy, half had been treated previously with other systemic therapies, including biologics, and nearly 1 in 5 patients had been treated with tumor necrosis factor (TNF) blockers.

Patients initially receiving placebo switched over to active treatment after the first 16 weeks, and treatment in all patients continued at the 30-mg twice-daily dose for an additional 16 weeks, followed by a randomized withdrawal phase through week 52.

The treatment effects seen with apremilast at 16 weeks were slightly greater in patients who had not previously received conventional systemic or biologic therapy compared with the total patient population, but even those with prior failed TNF treatment achieved a PASI-75 response.

Onset of action occurred within 2-4 weeks, and clinically relevant improvement continued beyond 16 weeks. The mean percent change from baseline in PASI score was 54.9% at 16 weeks, and 61.9% at 32 weeks, Dr. Reich said. "It will be interesting to see, long-term, what happens beyond the 16-week endpoint," he added.

The 16-week outcomes in the apremilast group represent "significant moderate efficacy," but the safety profile of the drug is the real story of the data, Dr. Reich said.

"Safety is a major issue when it comes to systemic therapies for psoriasis," he emphasized.

A slightly higher rate of withdrawals in the apremilast group may have been due to gastrointestinal effects, a well-known side effect of TNF inhibitors.

Gastrointestinal side effects included diarrhea and nausea, but most cases were transient, and mild to moderate. Most side effects occurred and resolved within the first 15 days of treatment. In fact, more than 96% of patients reported experiencing either no adverse events or only mild to moderate adverse events. Reports of serious adverse events were similar in the treatment and placebo groups (2.1% v. 2.8%, respectively), as were reports of severe adverse events (3.6% vs. 3.2%, respectively).

No problems were noted with respect to lipid levels, liver enzymes, opportunistic infections, or cardiac abnormalities, and no cases of tuberculosis or lymphoma occurred during the study period.

"What stands out so far is an extremely good safety profile," Dr. Reich said.

ESTEEM 1 is the first of two phase III studies of apremilast for chronic plaque psoriasis. Statistical significance for the primary and major secondary endpoints of both ESTEEM 1 and ESTEEM 2 was announced previously by Celgene, the maker of apremilast.

"A NDA (New Drug Application) submission to the U.S. Food and Drug Administration, based on the combined ESTEEM 1 and 2 studies for psoriasis, is expected in the second half of 2013," according to a Celgene press release.

Celgene previously announced it would file a separate NDA for psoriatic arthritis in the first quarter of 2013, based on data from three other trials (PALACE-1, 2, and 3), which were released in 2012. Another phase III trial (POSTURE) began enrolling patients in April 2012 to evaluate apremilast in patients with ankylosing spondylitis.

Participants in the ESTEEM 1 trial will be enrolled in a 5-year extension study so researchers can collect long-term safety and efficacy data. However, based on the current findings, including data from psoriatic arthritis patients, the drug looks quite promising for the treatment of psoriasis, Dr. Reich said.

"I see this as a prime candidate for future management of psoriasis that allows us to treat a range of patients, including more moderate cases earlier on," he said. Such a treatment is needed, particularly in light of new disease concepts that characterize psoriasis as involving systemic inflammation that requires early control, he explained.

The study was sponsored by Celgene.

Antibiotic exposure during the first year of life is associated with an increased risk of food allergy in young children, according to findings from a large case-control study.

The risk is greatest among those exposed to multiple antibiotic courses, Bryan L. Love, Pharm.D., reported during a late-breaking abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The mean number of antibiotic courses received by 1,105 case patients with food allergy was 2.65, compared with 1.84 for 6,433 food allergy–free control patients. The mean time to first antibiotic course was 181.5 days for those with food allergies, compared with 190.1 days for controls. These differences were statistically significant, said Dr. Love of the South Carolina College of Pharmacy, Columbia.

Additionally, only 24% of case patients, compared with a third of controls, had never received an antibiotic.

Later vs. earlier antibiotic exposure (during months 7-12 vs. months 0-6) also was associated with greater likelihood of developing food allergy (odds ratio, 1.98).

"This makes sense, because [months 7-12] is typically when new foods are being introduced to children," Dr. Love said.

Furthermore, the risk increased in tandem with the number of antibiotic exposures. No significant increase in food allergy risk was seen with one or two antibiotic courses, but the odds ratio became significant with three or four courses, and was highest with five or more courses (odds ratio, 2.15), he noted.

Case patients in this study were children born between 2007 and 2009 with a diagnosis of food allergy made before Dec. 31, 2010 (and after first antibiotic exposure), based on South Carolina Medicaid billing data. Certain patients, such as those with asthma, atopic dermatitis, or eczema, were excluded, because they have an increased risk of food allergy and antibiotic exposure. Controls were matched to the case patients by birth year, sex, and race.

Penicillins were the most frequently prescribed type of antibiotic, followed by cephalosporins, Dr. Love said.

The findings support the hypothesis of this study, which is that alteration of normal gut flora that occurs after antibiotic exposure might contribute to the increasing prevalence of childhood food allergy. Normal gut immune response, including the interaction with a diverse microbiome, promotes the development of food tolerance, he explained.

Though limited by the study’s retrospective design and the reliance on ICD-9 coding for diagnoses, the findings do, indeed, suggest that early antibiotic exposures are problematic. The possibility that antibiotic exposures have a causative effect with respect to food allergy development in children deserves further study, particularly given the significant use of antibiotics in young children, who receive an average of 2.2 antibiotic prescriptions in the first year of life, and the increasing incidence of food allergy, he said.

Further analysis of the data will assess whether certain antibiotic drug classes confer greater risk of food allergy, he noted.

This study was funded by the Health Resources and Services Administration. Dr. Love reported having no other disclosures.

fpnews@frontlinemedcom.com

Antibiotic exposure during the first year of life is associated with an increased risk of food allergy in young children, according to findings from a large case-control study.

The risk is greatest among those exposed to multiple antibiotic courses, Bryan L. Love, Pharm.D., reported during a late-breaking abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The mean number of antibiotic courses received by 1,105 case patients with food allergy was 2.65, compared with 1.84 for 6,433 food allergy–free control patients. The mean time to first antibiotic course was 181.5 days for those with food allergies, compared with 190.1 days for controls. These differences were statistically significant, said Dr. Love of the South Carolina College of Pharmacy, Columbia.

Additionally, only 24% of case patients, compared with a third of controls, had never received an antibiotic.

Later vs. earlier antibiotic exposure (during months 7-12 vs. months 0-6) also was associated with greater likelihood of developing food allergy (odds ratio, 1.98).

"This makes sense, because [months 7-12] is typically when new foods are being introduced to children," Dr. Love said.

Furthermore, the risk increased in tandem with the number of antibiotic exposures. No significant increase in food allergy risk was seen with one or two antibiotic courses, but the odds ratio became significant with three or four courses, and was highest with five or more courses (odds ratio, 2.15), he noted.

Case patients in this study were children born between 2007 and 2009 with a diagnosis of food allergy made before Dec. 31, 2010 (and after first antibiotic exposure), based on South Carolina Medicaid billing data. Certain patients, such as those with asthma, atopic dermatitis, or eczema, were excluded, because they have an increased risk of food allergy and antibiotic exposure. Controls were matched to the case patients by birth year, sex, and race.

Penicillins were the most frequently prescribed type of antibiotic, followed by cephalosporins, Dr. Love said.

The findings support the hypothesis of this study, which is that alteration of normal gut flora that occurs after antibiotic exposure might contribute to the increasing prevalence of childhood food allergy. Normal gut immune response, including the interaction with a diverse microbiome, promotes the development of food tolerance, he explained.

Though limited by the study’s retrospective design and the reliance on ICD-9 coding for diagnoses, the findings do, indeed, suggest that early antibiotic exposures are problematic. The possibility that antibiotic exposures have a causative effect with respect to food allergy development in children deserves further study, particularly given the significant use of antibiotics in young children, who receive an average of 2.2 antibiotic prescriptions in the first year of life, and the increasing incidence of food allergy, he said.

Further analysis of the data will assess whether certain antibiotic drug classes confer greater risk of food allergy, he noted.

This study was funded by the Health Resources and Services Administration. Dr. Love reported having no other disclosures.

fpnews@frontlinemedcom.com

Antibiotic exposure during the first year of life is associated with an increased risk of food allergy in young children, according to findings from a large case-control study.

The risk is greatest among those exposed to multiple antibiotic courses, Bryan L. Love, Pharm.D., reported during a late-breaking abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The mean number of antibiotic courses received by 1,105 case patients with food allergy was 2.65, compared with 1.84 for 6,433 food allergy–free control patients. The mean time to first antibiotic course was 181.5 days for those with food allergies, compared with 190.1 days for controls. These differences were statistically significant, said Dr. Love of the South Carolina College of Pharmacy, Columbia.

Additionally, only 24% of case patients, compared with a third of controls, had never received an antibiotic.

Later vs. earlier antibiotic exposure (during months 7-12 vs. months 0-6) also was associated with greater likelihood of developing food allergy (odds ratio, 1.98).

"This makes sense, because [months 7-12] is typically when new foods are being introduced to children," Dr. Love said.

Furthermore, the risk increased in tandem with the number of antibiotic exposures. No significant increase in food allergy risk was seen with one or two antibiotic courses, but the odds ratio became significant with three or four courses, and was highest with five or more courses (odds ratio, 2.15), he noted.

Case patients in this study were children born between 2007 and 2009 with a diagnosis of food allergy made before Dec. 31, 2010 (and after first antibiotic exposure), based on South Carolina Medicaid billing data. Certain patients, such as those with asthma, atopic dermatitis, or eczema, were excluded, because they have an increased risk of food allergy and antibiotic exposure. Controls were matched to the case patients by birth year, sex, and race.

Penicillins were the most frequently prescribed type of antibiotic, followed by cephalosporins, Dr. Love said.

The findings support the hypothesis of this study, which is that alteration of normal gut flora that occurs after antibiotic exposure might contribute to the increasing prevalence of childhood food allergy. Normal gut immune response, including the interaction with a diverse microbiome, promotes the development of food tolerance, he explained.

Though limited by the study’s retrospective design and the reliance on ICD-9 coding for diagnoses, the findings do, indeed, suggest that early antibiotic exposures are problematic. The possibility that antibiotic exposures have a causative effect with respect to food allergy development in children deserves further study, particularly given the significant use of antibiotics in young children, who receive an average of 2.2 antibiotic prescriptions in the first year of life, and the increasing incidence of food allergy, he said.

Further analysis of the data will assess whether certain antibiotic drug classes confer greater risk of food allergy, he noted.

This study was funded by the Health Resources and Services Administration. Dr. Love reported having no other disclosures.

fpnews@frontlinemedcom.com

A short course of treatment with an investigational synthetic cat-peptide antigen desensitizing vaccine, or Cat-PAD, results in a substantial and persistent reduction in cat allergy symptom scores, according to two-year findings from a randomized, placebo-controlled phase II clinical study involving 202 adult patients.

Study participants were initially randomized to receive either eight 3-nmol intradermal doses at 2-week intervals, four 6 nmol-doses at 4-week intervals, or placebo. At 1-year follow-up, the improvement in Total Rhinoconjunctivitis Symptom Score (TRSS) was significantly greater in the patients who received four doses of Cat-PAD (ToleroMune Cat, Circassia Limited, Oxford, England), compared with those who received placebo (–7.1 points vs. –2.99 points), according to findings published online in the Journal of Allergy and Clinical Immunology (doi:10.1016/j.jaci.2012.12.1185).

Courtesy Kate Fulton

Data from a 2-year follow-up study were reported by Rod P. Hafner, Ph.D., and his colleagues in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Of 89 patients enrolled into the follow-up study, 50 returned at 2-years after the start of treatment, having received no additional treatment, for an environmental exposure chamber challenge. The magnitude of difference from baseline in TRSS seen at 1 year in those who received 4 doses and those who received placebo was maintained at 2 years (–5.87 vs. –2.02) among those who initially received the 4-dose regimen.

"Cat-PAD is the first in a new class of synthetic peptide immune-regulatory epitopes. The results from this study provide the first evidence that four doses of 6 nmol Cat-PAD over a 12-week period has a disease-modifying effect with subjects showing sustained improvement at 2 years," the investigators wrote.

Study participants were adults aged 18-65 years with cat allergy who underwent a baseline environmental exposure chamber (EEC) challenge, as well as follow-up EEC challenges at 18-22 weeks and at 100-104 weeks.

"Cat allergen was dispersed into the EEC to achieve a consistent mean level of approx. 50 ng Fel d1/m3, using a validated method," they explained, noting that TRSS was calculated at each EEC challenge based on self-scoring of four nasal symptoms (running nose, sneezing, blocked nose, itchy nose), and four ocular symptoms (itchy eyes, watery eyes, red eyes, sore eyes) on a scale of 0-3, every 30 minutes during the challenge.

Cat-PAD is a "potentially exciting new approach to cat allergy immunotherapy," the investigators said, noting that improvements in the TRSS seen in the initial phase II study and follow-up study represent a substantial improvement over numerous therapies investigated in the past, in some cases reaching a threefold improvement in symptom reduction.

"For example, studies of similar design in an EEC reported TRSS changes of approximately –1.5 units after 16 weeks treatment with a sublingual cat allergy tablet, while a single 180-mg dose of the antihistamine fexofenadine achieved a mean difference in TRSS of –1.3 in a cat allergen study. Moreover, the change in TRSS of –3.8 units reported here was observed after four administrations of Cat-PAD over a 12-week period and persisted 21 months after the end of treatment," they concluded.

In late 2012 the investigators began enrolling a phase III study, which will include individuals aged 12-65 years.

This study was funded by Circassia Limited. Dr. Hafner is employed by Circassia.

fpnews@frontlinemedcom.com

A short course of treatment with an investigational synthetic cat-peptide antigen desensitizing vaccine, or Cat-PAD, results in a substantial and persistent reduction in cat allergy symptom scores, according to two-year findings from a randomized, placebo-controlled phase II clinical study involving 202 adult patients.

Study participants were initially randomized to receive either eight 3-nmol intradermal doses at 2-week intervals, four 6 nmol-doses at 4-week intervals, or placebo. At 1-year follow-up, the improvement in Total Rhinoconjunctivitis Symptom Score (TRSS) was significantly greater in the patients who received four doses of Cat-PAD (ToleroMune Cat, Circassia Limited, Oxford, England), compared with those who received placebo (–7.1 points vs. –2.99 points), according to findings published online in the Journal of Allergy and Clinical Immunology (doi:10.1016/j.jaci.2012.12.1185).

Courtesy Kate Fulton

Data from a 2-year follow-up study were reported by Rod P. Hafner, Ph.D., and his colleagues in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Of 89 patients enrolled into the follow-up study, 50 returned at 2-years after the start of treatment, having received no additional treatment, for an environmental exposure chamber challenge. The magnitude of difference from baseline in TRSS seen at 1 year in those who received 4 doses and those who received placebo was maintained at 2 years (–5.87 vs. –2.02) among those who initially received the 4-dose regimen.

"Cat-PAD is the first in a new class of synthetic peptide immune-regulatory epitopes. The results from this study provide the first evidence that four doses of 6 nmol Cat-PAD over a 12-week period has a disease-modifying effect with subjects showing sustained improvement at 2 years," the investigators wrote.

Study participants were adults aged 18-65 years with cat allergy who underwent a baseline environmental exposure chamber (EEC) challenge, as well as follow-up EEC challenges at 18-22 weeks and at 100-104 weeks.

"Cat allergen was dispersed into the EEC to achieve a consistent mean level of approx. 50 ng Fel d1/m3, using a validated method," they explained, noting that TRSS was calculated at each EEC challenge based on self-scoring of four nasal symptoms (running nose, sneezing, blocked nose, itchy nose), and four ocular symptoms (itchy eyes, watery eyes, red eyes, sore eyes) on a scale of 0-3, every 30 minutes during the challenge.

Cat-PAD is a "potentially exciting new approach to cat allergy immunotherapy," the investigators said, noting that improvements in the TRSS seen in the initial phase II study and follow-up study represent a substantial improvement over numerous therapies investigated in the past, in some cases reaching a threefold improvement in symptom reduction.

"For example, studies of similar design in an EEC reported TRSS changes of approximately –1.5 units after 16 weeks treatment with a sublingual cat allergy tablet, while a single 180-mg dose of the antihistamine fexofenadine achieved a mean difference in TRSS of –1.3 in a cat allergen study. Moreover, the change in TRSS of –3.8 units reported here was observed after four administrations of Cat-PAD over a 12-week period and persisted 21 months after the end of treatment," they concluded.

In late 2012 the investigators began enrolling a phase III study, which will include individuals aged 12-65 years.

This study was funded by Circassia Limited. Dr. Hafner is employed by Circassia.

fpnews@frontlinemedcom.com

A short course of treatment with an investigational synthetic cat-peptide antigen desensitizing vaccine, or Cat-PAD, results in a substantial and persistent reduction in cat allergy symptom scores, according to two-year findings from a randomized, placebo-controlled phase II clinical study involving 202 adult patients.

Study participants were initially randomized to receive either eight 3-nmol intradermal doses at 2-week intervals, four 6 nmol-doses at 4-week intervals, or placebo. At 1-year follow-up, the improvement in Total Rhinoconjunctivitis Symptom Score (TRSS) was significantly greater in the patients who received four doses of Cat-PAD (ToleroMune Cat, Circassia Limited, Oxford, England), compared with those who received placebo (–7.1 points vs. –2.99 points), according to findings published online in the Journal of Allergy and Clinical Immunology (doi:10.1016/j.jaci.2012.12.1185).

Courtesy Kate Fulton

Data from a 2-year follow-up study were reported by Rod P. Hafner, Ph.D., and his colleagues in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Of 89 patients enrolled into the follow-up study, 50 returned at 2-years after the start of treatment, having received no additional treatment, for an environmental exposure chamber challenge. The magnitude of difference from baseline in TRSS seen at 1 year in those who received 4 doses and those who received placebo was maintained at 2 years (–5.87 vs. –2.02) among those who initially received the 4-dose regimen.

"Cat-PAD is the first in a new class of synthetic peptide immune-regulatory epitopes. The results from this study provide the first evidence that four doses of 6 nmol Cat-PAD over a 12-week period has a disease-modifying effect with subjects showing sustained improvement at 2 years," the investigators wrote.

Study participants were adults aged 18-65 years with cat allergy who underwent a baseline environmental exposure chamber (EEC) challenge, as well as follow-up EEC challenges at 18-22 weeks and at 100-104 weeks.

"Cat allergen was dispersed into the EEC to achieve a consistent mean level of approx. 50 ng Fel d1/m3, using a validated method," they explained, noting that TRSS was calculated at each EEC challenge based on self-scoring of four nasal symptoms (running nose, sneezing, blocked nose, itchy nose), and four ocular symptoms (itchy eyes, watery eyes, red eyes, sore eyes) on a scale of 0-3, every 30 minutes during the challenge.

Cat-PAD is a "potentially exciting new approach to cat allergy immunotherapy," the investigators said, noting that improvements in the TRSS seen in the initial phase II study and follow-up study represent a substantial improvement over numerous therapies investigated in the past, in some cases reaching a threefold improvement in symptom reduction.

"For example, studies of similar design in an EEC reported TRSS changes of approximately –1.5 units after 16 weeks treatment with a sublingual cat allergy tablet, while a single 180-mg dose of the antihistamine fexofenadine achieved a mean difference in TRSS of –1.3 in a cat allergen study. Moreover, the change in TRSS of –3.8 units reported here was observed after four administrations of Cat-PAD over a 12-week period and persisted 21 months after the end of treatment," they concluded.

In late 2012 the investigators began enrolling a phase III study, which will include individuals aged 12-65 years.

This study was funded by Circassia Limited. Dr. Hafner is employed by Circassia.

fpnews@frontlinemedcom.com

MIAMI BEACH – ATX-101, an investigational injectable deoxycholic acid, is safe and effective for the non-surgical reduction of submental fat, according to interim findings from a 12-month phase IIIb open-label study.

At 3-month follow-up after their last treatment, 87% and 83% of 165 study participants achieved at least a 1-point improvement on the clinician and patient submental fat rating scales, respectively, Dr. Susan Weinkle reported during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

"That is major," Dr. Weinkle, a dermatologist in private practice in Bradenton, Fla., said of the patients’ rating scale scores.

Patients reported feeling less bothered by, and self-conscious about, their submental fat, and they also reported feeling younger. Most – about 96% – experienced unchanged or improved skin laxity in the treated area.

"Many, despite the fact that their body mass index stayed the same, actually felt like they looked like they had lost weight ... let me tell you, they were very, very happy," she said.

In fact, 94% reported being happy they had the procedure.

The study participants were men and women of varying ages, races, and Fitzpatrick skin types, who were dissatisfied with their appearance associated with the chin region. All had submental fat scale scores of 2 to 4 on both clinician and patient rating scales, had stable weight, and had received no prior treatments to the submental fat region. They received up to 6 treatments, at 4-week intervals, with ATX-101 at a dosage of 2 mg/cm². Injections were administered with a 30-gauge needle, and "little microinjections at 2 mm areas across the submental region," Dr. Weinkle said, noting that the number of injections was tailored as the fat decreased over time.

Treatments were provided at 21 sites across the United States.

Treatment-related adverse events occurred in more than 91% of patients, but these were mainly mild-to-moderate injection site hematomas, numbness, pain, edema, and erythema – and all were transient, she said

No changes in blood lipids occurred.

This "really exciting research" suggests that ATX-101, a synthetically derived product that has been shown to destroy and eliminate fat through adipocytolysis, "may very well provide, in the future, an approach to submental fat for our patients who are so unhappy with this part of their body," she said.

"This is an important thing to people, and it makes a huge difference ... if [ATX-101] has the opportunity to come to market, it will make a big impact for our patients," she added.

To date, between 2,000 and 3,000 patients have been studied, including 1,500 who have received active treatment, and 1,500 who received placebo. Patients in the current study will be followed out to 12 months, she said.

This study was funded by Kythera. Dr. Weinkle disclosed that she worked with Kythera as an investigator for the study.

MIAMI BEACH – ATX-101, an investigational injectable deoxycholic acid, is safe and effective for the non-surgical reduction of submental fat, according to interim findings from a 12-month phase IIIb open-label study.

At 3-month follow-up after their last treatment, 87% and 83% of 165 study participants achieved at least a 1-point improvement on the clinician and patient submental fat rating scales, respectively, Dr. Susan Weinkle reported during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

"That is major," Dr. Weinkle, a dermatologist in private practice in Bradenton, Fla., said of the patients’ rating scale scores.

Patients reported feeling less bothered by, and self-conscious about, their submental fat, and they also reported feeling younger. Most – about 96% – experienced unchanged or improved skin laxity in the treated area.

"Many, despite the fact that their body mass index stayed the same, actually felt like they looked like they had lost weight ... let me tell you, they were very, very happy," she said.

In fact, 94% reported being happy they had the procedure.

The study participants were men and women of varying ages, races, and Fitzpatrick skin types, who were dissatisfied with their appearance associated with the chin region. All had submental fat scale scores of 2 to 4 on both clinician and patient rating scales, had stable weight, and had received no prior treatments to the submental fat region. They received up to 6 treatments, at 4-week intervals, with ATX-101 at a dosage of 2 mg/cm². Injections were administered with a 30-gauge needle, and "little microinjections at 2 mm areas across the submental region," Dr. Weinkle said, noting that the number of injections was tailored as the fat decreased over time.

Treatments were provided at 21 sites across the United States.

Treatment-related adverse events occurred in more than 91% of patients, but these were mainly mild-to-moderate injection site hematomas, numbness, pain, edema, and erythema – and all were transient, she said

No changes in blood lipids occurred.

This "really exciting research" suggests that ATX-101, a synthetically derived product that has been shown to destroy and eliminate fat through adipocytolysis, "may very well provide, in the future, an approach to submental fat for our patients who are so unhappy with this part of their body," she said.

"This is an important thing to people, and it makes a huge difference ... if [ATX-101] has the opportunity to come to market, it will make a big impact for our patients," she added.

To date, between 2,000 and 3,000 patients have been studied, including 1,500 who have received active treatment, and 1,500 who received placebo. Patients in the current study will be followed out to 12 months, she said.

This study was funded by Kythera. Dr. Weinkle disclosed that she worked with Kythera as an investigator for the study.

MIAMI BEACH – ATX-101, an investigational injectable deoxycholic acid, is safe and effective for the non-surgical reduction of submental fat, according to interim findings from a 12-month phase IIIb open-label study.

At 3-month follow-up after their last treatment, 87% and 83% of 165 study participants achieved at least a 1-point improvement on the clinician and patient submental fat rating scales, respectively, Dr. Susan Weinkle reported during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

"That is major," Dr. Weinkle, a dermatologist in private practice in Bradenton, Fla., said of the patients’ rating scale scores.

Patients reported feeling less bothered by, and self-conscious about, their submental fat, and they also reported feeling younger. Most – about 96% – experienced unchanged or improved skin laxity in the treated area.

"Many, despite the fact that their body mass index stayed the same, actually felt like they looked like they had lost weight ... let me tell you, they were very, very happy," she said.

In fact, 94% reported being happy they had the procedure.

The study participants were men and women of varying ages, races, and Fitzpatrick skin types, who were dissatisfied with their appearance associated with the chin region. All had submental fat scale scores of 2 to 4 on both clinician and patient rating scales, had stable weight, and had received no prior treatments to the submental fat region. They received up to 6 treatments, at 4-week intervals, with ATX-101 at a dosage of 2 mg/cm². Injections were administered with a 30-gauge needle, and "little microinjections at 2 mm areas across the submental region," Dr. Weinkle said, noting that the number of injections was tailored as the fat decreased over time.

Treatments were provided at 21 sites across the United States.

Treatment-related adverse events occurred in more than 91% of patients, but these were mainly mild-to-moderate injection site hematomas, numbness, pain, edema, and erythema – and all were transient, she said

No changes in blood lipids occurred.

This "really exciting research" suggests that ATX-101, a synthetically derived product that has been shown to destroy and eliminate fat through adipocytolysis, "may very well provide, in the future, an approach to submental fat for our patients who are so unhappy with this part of their body," she said.

"This is an important thing to people, and it makes a huge difference ... if [ATX-101] has the opportunity to come to market, it will make a big impact for our patients," she added.

To date, between 2,000 and 3,000 patients have been studied, including 1,500 who have received active treatment, and 1,500 who received placebo. Patients in the current study will be followed out to 12 months, she said.

This study was funded by Kythera. Dr. Weinkle disclosed that she worked with Kythera as an investigator for the study.

MIAMI BEACH -- Patients with chronic plaque psoriasis showed significant improvement after 16 weeks of treatment with the humanized monoclonal antibody MK-3222, based on early data from an ongoing randomized, controlled, dose-ranging study of 355 adults. The findings were presented in a late-breaker session at the annual meeting of the American Academy of Dermatology.

The patients were randomized to receive MK-3222 doses of 5 mg, 25 mg, 100 mg, 200 mg, or a placebo, injected subcutaneously at weeks 0 and 4, then every 12 weeks thereafter until week 52. The mean baseline Psoriasis Area and Severity (PASI) index score of the patients was 12, and all patients had greater than 10% body surface area involvement and at least a moderate Physician Global Assessment (PGA) scale score.

Responses at 16 weeks were dose-dependent; PASI 75 responses occurred in 33%, 64%, 66%, 74%, and 4.4% in the 5-mg, 25-mg, 100-mg, 200-mg and placebo groups respectively, said Dr. Kim Papp of Probity Medical Research, Waterloo, Ontario, Canada. PGA responses were 33%, 58%, 62%, 74%, and 2%, respectively. The differences were statistically significant for each dose compared with placebo for both PASI 75 responses and PGA responses.

MK-3222 is a high-affinity humanized anti-IL-23p19 monoclonal antibody that doesn't bind human IL-12 (subunit p40), Dr. Papp said. "We know from results of previous studies that blockade of IL-23 is, in fact, an effective route to treating psoriasis," he said.

Dr. Papp noted that safety signals have been linked with IL-12 blockade, but not with IL-23 blockade, which provides support for further research of this agent.

In this study, MK-3222 was generally safe and well-tolerated, with a low drop-out rate. Adverse events were similar across all treatment groups. Four serious adverse events were reported within the first 16 weeks of treatment, including one case of bacterial arthritis possibly related to treatment, and one death that was unrelated to treatment.

"Those of us who see these patients know that there is an exquisite need for additional therapies," Dr. Papp said. The findings are encouraging, and MK-3222, which is currently in phase III development, "certainly deserves further exploration as a therapy for psoriasis," he said.

MIAMI BEACH -- Patients with chronic plaque psoriasis showed significant improvement after 16 weeks of treatment with the humanized monoclonal antibody MK-3222, based on early data from an ongoing randomized, controlled, dose-ranging study of 355 adults. The findings were presented in a late-breaker session at the annual meeting of the American Academy of Dermatology.

The patients were randomized to receive MK-3222 doses of 5 mg, 25 mg, 100 mg, 200 mg, or a placebo, injected subcutaneously at weeks 0 and 4, then every 12 weeks thereafter until week 52. The mean baseline Psoriasis Area and Severity (PASI) index score of the patients was 12, and all patients had greater than 10% body surface area involvement and at least a moderate Physician Global Assessment (PGA) scale score.

Responses at 16 weeks were dose-dependent; PASI 75 responses occurred in 33%, 64%, 66%, 74%, and 4.4% in the 5-mg, 25-mg, 100-mg, 200-mg and placebo groups respectively, said Dr. Kim Papp of Probity Medical Research, Waterloo, Ontario, Canada. PGA responses were 33%, 58%, 62%, 74%, and 2%, respectively. The differences were statistically significant for each dose compared with placebo for both PASI 75 responses and PGA responses.

MK-3222 is a high-affinity humanized anti-IL-23p19 monoclonal antibody that doesn't bind human IL-12 (subunit p40), Dr. Papp said. "We know from results of previous studies that blockade of IL-23 is, in fact, an effective route to treating psoriasis," he said.

Dr. Papp noted that safety signals have been linked with IL-12 blockade, but not with IL-23 blockade, which provides support for further research of this agent.

In this study, MK-3222 was generally safe and well-tolerated, with a low drop-out rate. Adverse events were similar across all treatment groups. Four serious adverse events were reported within the first 16 weeks of treatment, including one case of bacterial arthritis possibly related to treatment, and one death that was unrelated to treatment.

"Those of us who see these patients know that there is an exquisite need for additional therapies," Dr. Papp said. The findings are encouraging, and MK-3222, which is currently in phase III development, "certainly deserves further exploration as a therapy for psoriasis," he said.

MIAMI BEACH -- Patients with chronic plaque psoriasis showed significant improvement after 16 weeks of treatment with the humanized monoclonal antibody MK-3222, based on early data from an ongoing randomized, controlled, dose-ranging study of 355 adults. The findings were presented in a late-breaker session at the annual meeting of the American Academy of Dermatology.

The patients were randomized to receive MK-3222 doses of 5 mg, 25 mg, 100 mg, 200 mg, or a placebo, injected subcutaneously at weeks 0 and 4, then every 12 weeks thereafter until week 52. The mean baseline Psoriasis Area and Severity (PASI) index score of the patients was 12, and all patients had greater than 10% body surface area involvement and at least a moderate Physician Global Assessment (PGA) scale score.

Responses at 16 weeks were dose-dependent; PASI 75 responses occurred in 33%, 64%, 66%, 74%, and 4.4% in the 5-mg, 25-mg, 100-mg, 200-mg and placebo groups respectively, said Dr. Kim Papp of Probity Medical Research, Waterloo, Ontario, Canada. PGA responses were 33%, 58%, 62%, 74%, and 2%, respectively. The differences were statistically significant for each dose compared with placebo for both PASI 75 responses and PGA responses.

MK-3222 is a high-affinity humanized anti-IL-23p19 monoclonal antibody that doesn't bind human IL-12 (subunit p40), Dr. Papp said. "We know from results of previous studies that blockade of IL-23 is, in fact, an effective route to treating psoriasis," he said.

Dr. Papp noted that safety signals have been linked with IL-12 blockade, but not with IL-23 blockade, which provides support for further research of this agent.

In this study, MK-3222 was generally safe and well-tolerated, with a low drop-out rate. Adverse events were similar across all treatment groups. Four serious adverse events were reported within the first 16 weeks of treatment, including one case of bacterial arthritis possibly related to treatment, and one death that was unrelated to treatment.

"Those of us who see these patients know that there is an exquisite need for additional therapies," Dr. Papp said. The findings are encouraging, and MK-3222, which is currently in phase III development, "certainly deserves further exploration as a therapy for psoriasis," he said.

SAN ANTONIO – Once-daily use of an investigational sublingual allergy immunotherapy liquid extracted from ragweed pollen resulted in highly significant and clinically meaningful improvements in ragweed allergy symptoms in a pivotal phase III multicenter trial involving more than 400 patients.

Mitchel L. Zoler/IMNG Medical Media

Given that subcutaneous immunotherapy is the mainstay of therapy in North America for seasonal allergic rhinoconjunctivitis and mild asthma that is unresponsive to pharmacotherapy, this ragweed sublingual allergy immunotherapy liquid (RW-SAIL) extract could represent an important and more convenient option for the management of allergic respiratory disease. Sublingual immunotherapy (SLIT) is used off label in the United States, because it is not approved by the Food and Drug Administration. SLIT is more commonly used in Europe, where studies have demonstrated varying degrees of success.

The current randomized, double-blind, placebo-controlled trial involved 429 adults between the ages of 18-55 years who had ragweed-induced allergic rhinitis, which had necessitated the use of antiallergy medication for at least 2 years and who were positive for ragweed pollen extract on puncture skin test reactivity. They were randomized to self-administered RW-SAIL (Greer Laboratories Inc.) or placebo beginning 8-16 weeks prior to and continued through the 2011 ragweed season.

Of these, 218 adults who were randomized to receive RW-SAIL experienced a 43% reduction in the primary study endpoint of total combined symptom and medication score (TCS) for the entire ragweed pollen season that followed treatment initiation, compared with 211 patients randomized to receive placebo. Breaking that response down by time of ragweed season, the treatment group patients experienced a 42% reduction in TCS during the 3 peak weeks of the season, a 42% reduction in the daily-symptom score (DSS) for the entire season, and a 41% reduction in the DSS during the 3 peak weeks of the season, compared with the placebo group, Dr. Peter Creticos, an allergy and asthma specialist in Warrenton, Va., and his colleagues reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The RW-SAIL group also experienced a significantly greater increase from baseline in ragweed-specific IgG4 antibody, and in ragweed-specific IgE antibody, compared with the placebo group (0.99 vs. –0.1 mg/L, and 55.92 kU/L vs. 4.97 kU/L, respectively).

"Treatment with ragweed SAIL was well tolerated, with no deaths, systemic allergic reactions, or life-threatening events. No study subjects experienced anaphylaxis or required administration of epinephrine," the investigators wrote, noting that most adverse event were mild, and included headache, upper respiratory infection, and gastrointestinal effects. None of eight serious adverse events that occurred during the trial were attributable to the study drug.

The improvements achieved with RW-SAIL among the patients in the active-treatment group exceeded the criteria recently established by consensus panel reports, the investigators noted.

The findings have potentially important implications for the treatment of patients with ragweed allergy, the investigators said.

"Ragweed is the dominant seasonal aeroallergen for much of North America with observational studies showing sensitivity in about 25% of patients. It causes significant morbidity, is associated with disease sequelae and adversely impacts economic burden," they wrote.

The conventional subcutaneous approach to immunotherapy can also be burdensome, requiring a prolonged injection schedule that decreases compliance, discomfort associated with injections, and a recognized risk of anaphylaxis, they noted, concluding that RW-SAIL represents a safe and effective alternative treatment option for patients with ragweed allergy.

This study was funded by Greer Laboratories. Dr. Creticos disclosed relationships with Cercassia, Greer Laboratories, and Merck/Schering-Plough.

fpnews@elsevier.com

SAN ANTONIO – Once-daily use of an investigational sublingual allergy immunotherapy liquid extracted from ragweed pollen resulted in highly significant and clinically meaningful improvements in ragweed allergy symptoms in a pivotal phase III multicenter trial involving more than 400 patients.

Mitchel L. Zoler/IMNG Medical Media

Given that subcutaneous immunotherapy is the mainstay of therapy in North America for seasonal allergic rhinoconjunctivitis and mild asthma that is unresponsive to pharmacotherapy, this ragweed sublingual allergy immunotherapy liquid (RW-SAIL) extract could represent an important and more convenient option for the management of allergic respiratory disease. Sublingual immunotherapy (SLIT) is used off label in the United States, because it is not approved by the Food and Drug Administration. SLIT is more commonly used in Europe, where studies have demonstrated varying degrees of success.

The current randomized, double-blind, placebo-controlled trial involved 429 adults between the ages of 18-55 years who had ragweed-induced allergic rhinitis, which had necessitated the use of antiallergy medication for at least 2 years and who were positive for ragweed pollen extract on puncture skin test reactivity. They were randomized to self-administered RW-SAIL (Greer Laboratories Inc.) or placebo beginning 8-16 weeks prior to and continued through the 2011 ragweed season.

Of these, 218 adults who were randomized to receive RW-SAIL experienced a 43% reduction in the primary study endpoint of total combined symptom and medication score (TCS) for the entire ragweed pollen season that followed treatment initiation, compared with 211 patients randomized to receive placebo. Breaking that response down by time of ragweed season, the treatment group patients experienced a 42% reduction in TCS during the 3 peak weeks of the season, a 42% reduction in the daily-symptom score (DSS) for the entire season, and a 41% reduction in the DSS during the 3 peak weeks of the season, compared with the placebo group, Dr. Peter Creticos, an allergy and asthma specialist in Warrenton, Va., and his colleagues reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The RW-SAIL group also experienced a significantly greater increase from baseline in ragweed-specific IgG4 antibody, and in ragweed-specific IgE antibody, compared with the placebo group (0.99 vs. –0.1 mg/L, and 55.92 kU/L vs. 4.97 kU/L, respectively).

"Treatment with ragweed SAIL was well tolerated, with no deaths, systemic allergic reactions, or life-threatening events. No study subjects experienced anaphylaxis or required administration of epinephrine," the investigators wrote, noting that most adverse event were mild, and included headache, upper respiratory infection, and gastrointestinal effects. None of eight serious adverse events that occurred during the trial were attributable to the study drug.

The improvements achieved with RW-SAIL among the patients in the active-treatment group exceeded the criteria recently established by consensus panel reports, the investigators noted.

The findings have potentially important implications for the treatment of patients with ragweed allergy, the investigators said.

"Ragweed is the dominant seasonal aeroallergen for much of North America with observational studies showing sensitivity in about 25% of patients. It causes significant morbidity, is associated with disease sequelae and adversely impacts economic burden," they wrote.

The conventional subcutaneous approach to immunotherapy can also be burdensome, requiring a prolonged injection schedule that decreases compliance, discomfort associated with injections, and a recognized risk of anaphylaxis, they noted, concluding that RW-SAIL represents a safe and effective alternative treatment option for patients with ragweed allergy.

This study was funded by Greer Laboratories. Dr. Creticos disclosed relationships with Cercassia, Greer Laboratories, and Merck/Schering-Plough.

fpnews@elsevier.com

SAN ANTONIO – Once-daily use of an investigational sublingual allergy immunotherapy liquid extracted from ragweed pollen resulted in highly significant and clinically meaningful improvements in ragweed allergy symptoms in a pivotal phase III multicenter trial involving more than 400 patients.

Mitchel L. Zoler/IMNG Medical Media

Given that subcutaneous immunotherapy is the mainstay of therapy in North America for seasonal allergic rhinoconjunctivitis and mild asthma that is unresponsive to pharmacotherapy, this ragweed sublingual allergy immunotherapy liquid (RW-SAIL) extract could represent an important and more convenient option for the management of allergic respiratory disease. Sublingual immunotherapy (SLIT) is used off label in the United States, because it is not approved by the Food and Drug Administration. SLIT is more commonly used in Europe, where studies have demonstrated varying degrees of success.

The current randomized, double-blind, placebo-controlled trial involved 429 adults between the ages of 18-55 years who had ragweed-induced allergic rhinitis, which had necessitated the use of antiallergy medication for at least 2 years and who were positive for ragweed pollen extract on puncture skin test reactivity. They were randomized to self-administered RW-SAIL (Greer Laboratories Inc.) or placebo beginning 8-16 weeks prior to and continued through the 2011 ragweed season.

Of these, 218 adults who were randomized to receive RW-SAIL experienced a 43% reduction in the primary study endpoint of total combined symptom and medication score (TCS) for the entire ragweed pollen season that followed treatment initiation, compared with 211 patients randomized to receive placebo. Breaking that response down by time of ragweed season, the treatment group patients experienced a 42% reduction in TCS during the 3 peak weeks of the season, a 42% reduction in the daily-symptom score (DSS) for the entire season, and a 41% reduction in the DSS during the 3 peak weeks of the season, compared with the placebo group, Dr. Peter Creticos, an allergy and asthma specialist in Warrenton, Va., and his colleagues reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The RW-SAIL group also experienced a significantly greater increase from baseline in ragweed-specific IgG4 antibody, and in ragweed-specific IgE antibody, compared with the placebo group (0.99 vs. –0.1 mg/L, and 55.92 kU/L vs. 4.97 kU/L, respectively).

"Treatment with ragweed SAIL was well tolerated, with no deaths, systemic allergic reactions, or life-threatening events. No study subjects experienced anaphylaxis or required administration of epinephrine," the investigators wrote, noting that most adverse event were mild, and included headache, upper respiratory infection, and gastrointestinal effects. None of eight serious adverse events that occurred during the trial were attributable to the study drug.

The improvements achieved with RW-SAIL among the patients in the active-treatment group exceeded the criteria recently established by consensus panel reports, the investigators noted.

The findings have potentially important implications for the treatment of patients with ragweed allergy, the investigators said.

"Ragweed is the dominant seasonal aeroallergen for much of North America with observational studies showing sensitivity in about 25% of patients. It causes significant morbidity, is associated with disease sequelae and adversely impacts economic burden," they wrote.

The conventional subcutaneous approach to immunotherapy can also be burdensome, requiring a prolonged injection schedule that decreases compliance, discomfort associated with injections, and a recognized risk of anaphylaxis, they noted, concluding that RW-SAIL represents a safe and effective alternative treatment option for patients with ragweed allergy.

This study was funded by Greer Laboratories. Dr. Creticos disclosed relationships with Cercassia, Greer Laboratories, and Merck/Schering-Plough.

fpnews@elsevier.com

The increasing use of methylisothiazolinone by itself in cosmetic and toiletry products has earned the preservative the title of contact allergen of the year from the American Contact Dermatitis Society.

Methylisothiazolinone (MI), a moderate-strong sensitizer, is important to know about, because a few years ago it was introduced into the market as a stand-alone preservative at up to 100 parts per million, Dr. Donald V. Belsito, professor of clinical dermatology at Columbia University, N.Y., said at the society’s annual meeting.

Previously, MI was used only in combination with methylchloroisothiazolinone (MCI), and the concentration limit of MI in that combination was 3.75 ppm for rinse-off products, and 1.8 ppm for leave-on products. Even at those lower limits, the MCI/MI combination in 2009-2010 was considered the fifth most common cause of preservative allergy.

The new 100-ppm limit (instituted based on the belief that MI was a weaker sensitizer than MCI) represents a 25-fold increase in the permitted concentration in cosmetics, Dr. Belsito noted.

At least one study, however, has shown that the eliciting concentration for MI reactivity can be as low as 5 ppm, Dr. Mari Paz Castanedo-Tardana of the Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and Dr. Kathryn A. Zug of Geisel School of Medicine at Dartmouth, Hanover, N.H., noted in an article in the January/February issue of Dermatitis, which granted MI its dubious 2013 title.

Dr. Castanedo-Tardana and Dr. Zug noted that in 2010, data suggested that more than 2,400 U.S. cosmetic products contained MI, which represents a doubling since 2007. The preservative is also used in industrial products without limit, thus providing other opportunities for exposure, such as occupational exposure (Dermatitis 2013;24:1-6).

An important problem is that few data exist concerning the cross-reaction patterns of MCI and MI, the authors noted.

"Bruze et al. showed that a small proportion of patch test subjects sensitized to MCI/MI also reacted to MI. Isaksson et al. also suggested that patients with high patch test reactivity to MCI may also react to high concentrations of MI (1,000 ppm). The percentage of concomitant reactions between MCI/MI and MI in the patch test population is relevant with regard to the diagnosis of MI contact allergy," according to the authors. They also noted that in a Danish study, a Finnish study, and a German study, only 40%, 66%, and 67% of patients with a positive reaction to MI, respectively, also had a positive reaction to MCI/MI.

The limited experience with MI-only patch tests concentrations also helped the allergen gain its newly bestowed title.

Concentrations of 300 ppm (0.03% aq), 500 ppm (0.05% aq), 1,000 ppm (0.1% aq), and 2,000 ppm (0.2% aq) have been tested, and all have yielded relatively similar percentages of positive test reactions.

"As with any other allergen, the ideal patch test concentration should be able to detect as many cases of contact allergy as possible without causing irritant reactions or active sensitization," the authors said, noting that preliminary results from Denmark suggest that 2,000 ppm (0.2% aq) is an appropriate concentration.

For now, however, it is likely that since MI is not routinely tested in any standard screening series, allergy to this preservative is being widely overlooked.

In fact, reports from Europe show that the frequency of allergy to MI is already at the same level as other preservatives that have been available for many years.

"Methylisothiazolinone should be considered as a potential suspect allergen among patients with suspected cosmetic dermatitis, facial dermatitis, and sunscreen allergy," the authors said, concluding that the addition of MI to an allergen screening series "will likely uncover otherwise undiagnosed cases of preservative contact allergy."

The presenter and authors reported having no disclosures.

sknews@elsevier.com

The increasing use of methylisothiazolinone by itself in cosmetic and toiletry products has earned the preservative the title of contact allergen of the year from the American Contact Dermatitis Society.

Methylisothiazolinone (MI), a moderate-strong sensitizer, is important to know about, because a few years ago it was introduced into the market as a stand-alone preservative at up to 100 parts per million, Dr. Donald V. Belsito, professor of clinical dermatology at Columbia University, N.Y., said at the society’s annual meeting.

Previously, MI was used only in combination with methylchloroisothiazolinone (MCI), and the concentration limit of MI in that combination was 3.75 ppm for rinse-off products, and 1.8 ppm for leave-on products. Even at those lower limits, the MCI/MI combination in 2009-2010 was considered the fifth most common cause of preservative allergy.

The new 100-ppm limit (instituted based on the belief that MI was a weaker sensitizer than MCI) represents a 25-fold increase in the permitted concentration in cosmetics, Dr. Belsito noted.

At least one study, however, has shown that the eliciting concentration for MI reactivity can be as low as 5 ppm, Dr. Mari Paz Castanedo-Tardana of the Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and Dr. Kathryn A. Zug of Geisel School of Medicine at Dartmouth, Hanover, N.H., noted in an article in the January/February issue of Dermatitis, which granted MI its dubious 2013 title.

Dr. Castanedo-Tardana and Dr. Zug noted that in 2010, data suggested that more than 2,400 U.S. cosmetic products contained MI, which represents a doubling since 2007. The preservative is also used in industrial products without limit, thus providing other opportunities for exposure, such as occupational exposure (Dermatitis 2013;24:1-6).

An important problem is that few data exist concerning the cross-reaction patterns of MCI and MI, the authors noted.

"Bruze et al. showed that a small proportion of patch test subjects sensitized to MCI/MI also reacted to MI. Isaksson et al. also suggested that patients with high patch test reactivity to MCI may also react to high concentrations of MI (1,000 ppm). The percentage of concomitant reactions between MCI/MI and MI in the patch test population is relevant with regard to the diagnosis of MI contact allergy," according to the authors. They also noted that in a Danish study, a Finnish study, and a German study, only 40%, 66%, and 67% of patients with a positive reaction to MI, respectively, also had a positive reaction to MCI/MI.

The limited experience with MI-only patch tests concentrations also helped the allergen gain its newly bestowed title.

Concentrations of 300 ppm (0.03% aq), 500 ppm (0.05% aq), 1,000 ppm (0.1% aq), and 2,000 ppm (0.2% aq) have been tested, and all have yielded relatively similar percentages of positive test reactions.

"As with any other allergen, the ideal patch test concentration should be able to detect as many cases of contact allergy as possible without causing irritant reactions or active sensitization," the authors said, noting that preliminary results from Denmark suggest that 2,000 ppm (0.2% aq) is an appropriate concentration.

For now, however, it is likely that since MI is not routinely tested in any standard screening series, allergy to this preservative is being widely overlooked.

In fact, reports from Europe show that the frequency of allergy to MI is already at the same level as other preservatives that have been available for many years.

"Methylisothiazolinone should be considered as a potential suspect allergen among patients with suspected cosmetic dermatitis, facial dermatitis, and sunscreen allergy," the authors said, concluding that the addition of MI to an allergen screening series "will likely uncover otherwise undiagnosed cases of preservative contact allergy."

The presenter and authors reported having no disclosures.

sknews@elsevier.com

The increasing use of methylisothiazolinone by itself in cosmetic and toiletry products has earned the preservative the title of contact allergen of the year from the American Contact Dermatitis Society.

Methylisothiazolinone (MI), a moderate-strong sensitizer, is important to know about, because a few years ago it was introduced into the market as a stand-alone preservative at up to 100 parts per million, Dr. Donald V. Belsito, professor of clinical dermatology at Columbia University, N.Y., said at the society’s annual meeting.

Previously, MI was used only in combination with methylchloroisothiazolinone (MCI), and the concentration limit of MI in that combination was 3.75 ppm for rinse-off products, and 1.8 ppm for leave-on products. Even at those lower limits, the MCI/MI combination in 2009-2010 was considered the fifth most common cause of preservative allergy.

The new 100-ppm limit (instituted based on the belief that MI was a weaker sensitizer than MCI) represents a 25-fold increase in the permitted concentration in cosmetics, Dr. Belsito noted.

At least one study, however, has shown that the eliciting concentration for MI reactivity can be as low as 5 ppm, Dr. Mari Paz Castanedo-Tardana of the Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and Dr. Kathryn A. Zug of Geisel School of Medicine at Dartmouth, Hanover, N.H., noted in an article in the January/February issue of Dermatitis, which granted MI its dubious 2013 title.

Dr. Castanedo-Tardana and Dr. Zug noted that in 2010, data suggested that more than 2,400 U.S. cosmetic products contained MI, which represents a doubling since 2007. The preservative is also used in industrial products without limit, thus providing other opportunities for exposure, such as occupational exposure (Dermatitis 2013;24:1-6).

An important problem is that few data exist concerning the cross-reaction patterns of MCI and MI, the authors noted.

"Bruze et al. showed that a small proportion of patch test subjects sensitized to MCI/MI also reacted to MI. Isaksson et al. also suggested that patients with high patch test reactivity to MCI may also react to high concentrations of MI (1,000 ppm). The percentage of concomitant reactions between MCI/MI and MI in the patch test population is relevant with regard to the diagnosis of MI contact allergy," according to the authors. They also noted that in a Danish study, a Finnish study, and a German study, only 40%, 66%, and 67% of patients with a positive reaction to MI, respectively, also had a positive reaction to MCI/MI.

The limited experience with MI-only patch tests concentrations also helped the allergen gain its newly bestowed title.

Concentrations of 300 ppm (0.03% aq), 500 ppm (0.05% aq), 1,000 ppm (0.1% aq), and 2,000 ppm (0.2% aq) have been tested, and all have yielded relatively similar percentages of positive test reactions.

"As with any other allergen, the ideal patch test concentration should be able to detect as many cases of contact allergy as possible without causing irritant reactions or active sensitization," the authors said, noting that preliminary results from Denmark suggest that 2,000 ppm (0.2% aq) is an appropriate concentration.

For now, however, it is likely that since MI is not routinely tested in any standard screening series, allergy to this preservative is being widely overlooked.

In fact, reports from Europe show that the frequency of allergy to MI is already at the same level as other preservatives that have been available for many years.

"Methylisothiazolinone should be considered as a potential suspect allergen among patients with suspected cosmetic dermatitis, facial dermatitis, and sunscreen allergy," the authors said, concluding that the addition of MI to an allergen screening series "will likely uncover otherwise undiagnosed cases of preservative contact allergy."

The presenter and authors reported having no disclosures.

sknews@elsevier.com

Noninvasive procedural dermatology has evolved at a dizzying pace, and continues to do so.

In addition to an array of procedures for skin tightening, skin resurfacing, and fat reduction, emerging technologies such as complex feedback devices, nanotechnology, and stem cell–based therapies promise to keep dermatology at the forefront of the cosmetic and esthetic realm, according to Dr. Murad Alam.

In an article featured in the March issue of Seminars in Cutaneous Medicine and Surgery, Dr. Alam of Northwestern University, Chicago, makes several predictions about the future of these technologies (Semin. Cutan. Med. Surg. 2013;32:61-63).

For example, like modern vehicles equipped with computer chips that can change steering and braking in response to environmental conditions, dermatologic devices will soon include technology that uses precise feedback to make automated setting changes, he said.

"Over time, the reduced cost of microelectronics, feedback controls, and computing power is simplifying the capacity of devices to analyze intraoperative information and adjust the procedure to compensate. For instance, certain laser and energy devices already have tips that are able to sense the temperature in the microenvironment and adjust power output to maintain site-specific temperature within a narrow band," he explained.

This technology could increase effectiveness and improve the safety of devices by reducing the level of operator time and expertise needed, and by making setting changes faster than humanly possible.

Autonomous nanotechnology devices are another advance described by Dr. Alam.

Miniaturization will become more feasible and affordable, and eventually devices will become "so exceedingly small that they will be mostly disposable and deployed in large numbers to the treatment site," he said.

The concept of hundreds of minuscule machines deployed to resurface skin or repair a wound may sound like science fiction, but the rapid advances in nanotechnology could make it a reality that could lead to the creation of new procedures such as ways to treat scars that can’t be corrected using currently available technologies, he added.

Dr. Alam’s other predictions for the future of noninvasive procedural dermatology included:

• Optimization of minimally invasive procedures for fat reduction and skin tightening, which currently provide only mild to modest results and longevity.

• The use of stem cells for augmentation of tissue layers, which could provide genuine rejuvenation rather than simply repair and concealment.

• The improvement of artificial dermal substitutes that can develop many of the functions of live skin, and can be grafted without inducing contractures.

• The development of rapid treatments for pigmentation using nanotechnology and cellular therapies, which will allow for precise melanocyte and melanosome transfer and automatic recoloration of discolored skin.

While these technologies continue to emerge, plenty of others have already established their places in the dermatology arena. The many and varied applications of one of these – low-level laser therapy, or LLLT – are described in another article in the March issue of Seminars in Cutaneous Medicine and Surgery (Semin. Cutan. Med. Surg. 2013;32:42-54).

"LLLT involves exposing cells or tissue to low levels of red and near-infrared light. ... Recently, medical treatment with LLLT at various intensities has been found to stimulate or inhibit an assortment of cellular processes," wrote Dr. Pinar Avci of Massachusetts General Hospital, Boston, and his colleagues, noting that the mechanism associated with the cellular photobiostimulation by LLLT is not yet fully understood, but appears to have a wide range of effects at the molecular, cellular, and tissue levels.

Describing LLLT as "possibly the ultimate noninvasive approach to treating the skin," the researchers highlighted numerous existing or emerging applications for the technology, outlined below.

Skin rejuvenation

Many modalities developed to reverse the dermal and epidermal signs of photoaging and chronological aging depend on the removal of the epidermis and the induction of a controlled form of skin wounding to promote collagen biosynthesis and dermal matrix remodeling. Examples include retinoic acid, dermabrasion, chemical peels, and ablative laser resurfacing.

These modalities require intensive posttreatment care and prolonged down time, and are associated with a risk of numerous complications, the researchers said.

LLLT represents an alternative that is known to increase microcirculation and vascular perfusion in the skin. Data from previous studies have shown that LLLT increased collagen and improved wrinkles and skin laxity with less down time and risk than that of other treatments.

In one study, for example, 300 patients treated with only a light-emitting diode (LED) LLLT device set at 590 nm, 0.10 J/cm², were compared with 600 patients who received the LED therapy in combination with a thermal-based photorejuvenation procedure. Of those who received LED therapy alone, 90% reported softer skin and less roughness and fine lines. The changes ranged from subtle to significant.

Those who received thermal photorejuvenation laser treatment reported a reduction in posttreatment erythema and an overall impression of increased efficacy with the additional LED treatment – an effect that could be attributed to anti-inflammatory effects of LLLT, they noted.

In another study, more than 90% of 90 patients receiving eight LED treatments over 4 weeks experienced favorable results, improving by at least one Fitzpatrick photoaging category. In addition, 65% of patients experienced global improvement in facial texture, fine lines, background erythema, and pigmentation, with results peaking 4-6 months after completion.

Acne treatment

LLLT in the red to near-infrared (NIR) spectral range (630-1000 nm) and with nonthermal power (less than 200 mW) has been shown in several studies to improve acne vulgaris. In one study, a significant reduction in active acne lesions occurred after 12 twice-weekly sessions using 630 nm red-spectrum LLLT with a fluence of 12 J/cm² in conjunction with 2% topical clindamycin. No significant effects were seen using an 890-nm laser. Other studies have demonstrated that the combination of blue and red light is synergistic for treating acne.

Photoprotection

Recent suggestions that infrared exposure might have protective effects against ultraviolet light–induced skin damage are based on the theory that the exposure might trigger protective or repair responses to UV irradiation. While controversial, this view is supported by data suggesting potential mechanisms of action. For example, some data suggest a role of p53, a sensor of gene integrity involved in cell apoptosis and repair mechanisms. In one study, the response to infrared (IR) irradiation was shown to be p53 dependent, suggesting the IR irradiation prepares cells to resist and/or repair further UV-induced DNA damage. Data from another study showed that IR irradiation induced the protective protein ferritin, which is involved in skin repair.

Data from yet another study suggested that nerve growth factor (NGF) production induced by LLLT using the helium neon semiconductor laser diode (HeNe, 633 nm) might explain the photoprotective effects of LLLT. In that study, NGF – a major paracrine maintenance factor for melanocyte survival in skin, was shown to protect melanocytes from UV-induced apoptosis by upregulating the level of Bcl-2 (an antiapoptotic protein) in the cells.

Herpesvirus lesion treatment

New therapies are needed to shorten recurrent herpesvirus episodes and reduce related pain and inflammation. LLLT has been suggested as an alternative to current medications. In one study of 50 patients with recurrent perioral HSV infection, LLLT at 690 nm, 80 mW/cm², 48 J/cm² daily for 2 weeks during recurrence-free periods decreased the frequency of herpes labialis episodes, the authors said.

In another study with similar parameters, patients achieved a significant prolongation of remission intervals from 30 to 73 days.

The mechanism of action remains unclear, but an indirect effect of LLLT on cellular and humoral components of the immune system may be involved in antiviral responses, as opposed to a direct virus-inactivating effect, the researchers noted.

Vitiligo treatment

Modest efficacy seen with the low-energy HeNe laser (632 nm, 25 mW/cm²) for the treatment of 18 vitiligo patients led to speculation that LLLT could serve as an alternative effective treatment for this typically treatment-resistant condition. (Repigmentation was observed in 64%, and some follicular repigmentation was observed in the remaining patients).

In a subsequent study of local administration of the HeNe laser light at 3 J/cm², 1.0 mW, 632.8 nm in patients with segmental type vitiligo, marked perilesional and perifollicular repigmentation of more than 50% was observed in 60% of patients.

"Both NGF and (basic fibroblast growth factor) stimulate melanocyte migration, and deficiencies of these mediators may participate in the development of vitiligo," the researchers wrote.

Depigmentation

During tests of red and blue light for acne, researchers unexpectedly found that patients treated with both red and blue light experienced an overall decrease in melanin.

Based on instrumental measurement results, blue light exposure (415 nm, 40 mW/cm², 48 J/cm²), increased the melanin level by 6.7, whereas red light exposure (633 nm, 80 mW/cm², 96 J/cm²) decreased the melanin level by 15.5.

"This finding may have some relationship with the laser’s brightening effect of the skin tone, which 14 of 24 patients spontaneously reported after the treatment period. However, as of today, no other studies investigated or reported a similar decrease in melanin levels after red light irradiations," the researchers said.

Hypertrophic scar and keloid eradication

LLLT has shown promise for preventing hypertrophic and keloid scars in patients who undergo scar revision by surgery or CO₂ laser. The use of daily near-infrared LED (NIR-LED) treatment on one of the two bilateral sites safely reduced the risk of scar development in that lesion, compared with the untreated lesion in three patients with bilateral scars. One underwent surgical revision/excision for preauricular linear keloids that developed after a face-lift procedure, one underwent CO₂ resurfacing for hypertrophic acne scars on the chest, and one underwent CO₂ resurfacing after excision of hypertrophic scars on the back. No significant treatment-related adverse effects were reported.

LLLT may work in these types of scars through an inhibitory effect on interleukin-6 mRNA levels and the modulating of platelet derived growth factor, transforming growth factor–beta, interleukins, and MMPs, which are associated with abnormal wound healing, the researchers noted.

Burn treatment

LED exposure was shown to provide benefit for the treatment of acute sunburn in a study of 10 patients.

Treatment once or twice daily for 3 days on half of the affected area decreased symptoms of burning, redness, swelling, and peeling compared with the untreated half. Decreased MMP-1 was noted on the treated side through immunofluorescence staining in one patient, and real-time polymerase chain reaction gene expression analysis showed a significant decrease in MMP-1 gene expression at both 4 and 24 hours after the UV injury on the treated side.

In another study, LED treatment was effective compared with control for speeding the healing process of laser treatment–related burns. In nine patients with second-degree burns from nonablative laser devices, LED therapy once daily for 1 week was associated with 50% faster healing based on both patient and physician accounts.

LED treatment also was shown in a pilot study to accelerate re-epithelialization of a forearm injury induced by a CO₂ laser; identical test sites were treated with daily dressing changes and polysporin ointment, but the site with faster re-epithelialization had also received the LED treatment (a computer pattern generator was used to deliver the identical CO₂ treatment to both sites).

Psoriasis

LLLT also shows promise for the treatment of plaque psoriasis. In a preliminary study, the combined use of sequential NIR (830 nm) and visible red light (630 nm) led to resolution of psoriasis in patients who were resistant to conventional therapy. The patients received treatment in two 20-minute sessions, 48 hours apart, for 4 or 5 weeks. No adverse side effects occurred.

Despite the variety of potential applications for the technology, LLLT remains somewhat controversial due to "uncertainties about the fundamental molecular and cellular mechanisms responsible for transducing signals from the photons incident on the cells to the biological effects that take place in the irradiated tissue" and because "there are significant variations in terms of dosimetry parameter: wavelength, irradiance or power density, pulse structure, coherence, polarization, energy, fluence, irradiation time, contact versus noncontact application, and repetition regimen," the researchers said.

They noted, however, that problems that have been experienced with LLLT – as well as negative study results – could be the result of inappropriate parameters, skin preparation, and/or device maintenance.

"LLLT appears to have a wide range of applications in dermatology, especially in indications where stimulation of healing, reduction of inflammation, reduction of cell death, and skin rejuvenation are required," they noted, but added that the lack of agreement on important parameters (particularly whether red, NIR, or a combination of both is optimal for a given application) has created a credibility gap that must be overcome before LLLT is routinely applied in every dermatologist’s office.

Once LLLT does become so widely accepted, however, it may be time for dermatologists to move on to the next big thing, Dr. Alam said in his article on the future of procedural dermatology.

"For several decades, dermatologists have worked closely with start-up companies to commercialize new devices and technologies ... when new toxins, fillers, and energy devices have been marketed, dermatologists have been early adopters," he said. "Over time, each device or procedure has diminished in cost and exclusivity as other physicians and nonphysicians have entered the market, and dermatologists have moved on to greener pastures. In all likelihood, this cycle will continue," he noted. "Dermatologists cannot prevent the dissemination of stable technologies, but they can continue to innovate and create new ones."

In fact, he added, continued success in this arena will rest largely on clinicians’ ability to nurture innovation to ensure a healthy pipeline of novel technologies.

The authors of the articles had no financial conflicts to disclose.

Noninvasive procedural dermatology has evolved at a dizzying pace, and continues to do so.

In addition to an array of procedures for skin tightening, skin resurfacing, and fat reduction, emerging technologies such as complex feedback devices, nanotechnology, and stem cell–based therapies promise to keep dermatology at the forefront of the cosmetic and esthetic realm, according to Dr. Murad Alam.

In an article featured in the March issue of Seminars in Cutaneous Medicine and Surgery, Dr. Alam of Northwestern University, Chicago, makes several predictions about the future of these technologies (Semin. Cutan. Med. Surg. 2013;32:61-63).

For example, like modern vehicles equipped with computer chips that can change steering and braking in response to environmental conditions, dermatologic devices will soon include technology that uses precise feedback to make automated setting changes, he said.

"Over time, the reduced cost of microelectronics, feedback controls, and computing power is simplifying the capacity of devices to analyze intraoperative information and adjust the procedure to compensate. For instance, certain laser and energy devices already have tips that are able to sense the temperature in the microenvironment and adjust power output to maintain site-specific temperature within a narrow band," he explained.

This technology could increase effectiveness and improve the safety of devices by reducing the level of operator time and expertise needed, and by making setting changes faster than humanly possible.

Autonomous nanotechnology devices are another advance described by Dr. Alam.

Miniaturization will become more feasible and affordable, and eventually devices will become "so exceedingly small that they will be mostly disposable and deployed in large numbers to the treatment site," he said.

The concept of hundreds of minuscule machines deployed to resurface skin or repair a wound may sound like science fiction, but the rapid advances in nanotechnology could make it a reality that could lead to the creation of new procedures such as ways to treat scars that can’t be corrected using currently available technologies, he added.

Dr. Alam’s other predictions for the future of noninvasive procedural dermatology included:

• Optimization of minimally invasive procedures for fat reduction and skin tightening, which currently provide only mild to modest results and longevity.

• The use of stem cells for augmentation of tissue layers, which could provide genuine rejuvenation rather than simply repair and concealment.

• The improvement of artificial dermal substitutes that can develop many of the functions of live skin, and can be grafted without inducing contractures.

• The development of rapid treatments for pigmentation using nanotechnology and cellular therapies, which will allow for precise melanocyte and melanosome transfer and automatic recoloration of discolored skin.

While these technologies continue to emerge, plenty of others have already established their places in the dermatology arena. The many and varied applications of one of these – low-level laser therapy, or LLLT – are described in another article in the March issue of Seminars in Cutaneous Medicine and Surgery (Semin. Cutan. Med. Surg. 2013;32:42-54).

"LLLT involves exposing cells or tissue to low levels of red and near-infrared light. ... Recently, medical treatment with LLLT at various intensities has been found to stimulate or inhibit an assortment of cellular processes," wrote Dr. Pinar Avci of Massachusetts General Hospital, Boston, and his colleagues, noting that the mechanism associated with the cellular photobiostimulation by LLLT is not yet fully understood, but appears to have a wide range of effects at the molecular, cellular, and tissue levels.

Describing LLLT as "possibly the ultimate noninvasive approach to treating the skin," the researchers highlighted numerous existing or emerging applications for the technology, outlined below.

Skin rejuvenation

Many modalities developed to reverse the dermal and epidermal signs of photoaging and chronological aging depend on the removal of the epidermis and the induction of a controlled form of skin wounding to promote collagen biosynthesis and dermal matrix remodeling. Examples include retinoic acid, dermabrasion, chemical peels, and ablative laser resurfacing.

These modalities require intensive posttreatment care and prolonged down time, and are associated with a risk of numerous complications, the researchers said.

LLLT represents an alternative that is known to increase microcirculation and vascular perfusion in the skin. Data from previous studies have shown that LLLT increased collagen and improved wrinkles and skin laxity with less down time and risk than that of other treatments.

In one study, for example, 300 patients treated with only a light-emitting diode (LED) LLLT device set at 590 nm, 0.10 J/cm², were compared with 600 patients who received the LED therapy in combination with a thermal-based photorejuvenation procedure. Of those who received LED therapy alone, 90% reported softer skin and less roughness and fine lines. The changes ranged from subtle to significant.

Those who received thermal photorejuvenation laser treatment reported a reduction in posttreatment erythema and an overall impression of increased efficacy with the additional LED treatment – an effect that could be attributed to anti-inflammatory effects of LLLT, they noted.

In another study, more than 90% of 90 patients receiving eight LED treatments over 4 weeks experienced favorable results, improving by at least one Fitzpatrick photoaging category. In addition, 65% of patients experienced global improvement in facial texture, fine lines, background erythema, and pigmentation, with results peaking 4-6 months after completion.

Acne treatment

LLLT in the red to near-infrared (NIR) spectral range (630-1000 nm) and with nonthermal power (less than 200 mW) has been shown in several studies to improve acne vulgaris. In one study, a significant reduction in active acne lesions occurred after 12 twice-weekly sessions using 630 nm red-spectrum LLLT with a fluence of 12 J/cm² in conjunction with 2% topical clindamycin. No significant effects were seen using an 890-nm laser. Other studies have demonstrated that the combination of blue and red light is synergistic for treating acne.

Photoprotection

Recent suggestions that infrared exposure might have protective effects against ultraviolet light–induced skin damage are based on the theory that the exposure might trigger protective or repair responses to UV irradiation. While controversial, this view is supported by data suggesting potential mechanisms of action. For example, some data suggest a role of p53, a sensor of gene integrity involved in cell apoptosis and repair mechanisms. In one study, the response to infrared (IR) irradiation was shown to be p53 dependent, suggesting the IR irradiation prepares cells to resist and/or repair further UV-induced DNA damage. Data from another study showed that IR irradiation induced the protective protein ferritin, which is involved in skin repair.

Data from yet another study suggested that nerve growth factor (NGF) production induced by LLLT using the helium neon semiconductor laser diode (HeNe, 633 nm) might explain the photoprotective effects of LLLT. In that study, NGF – a major paracrine maintenance factor for melanocyte survival in skin, was shown to protect melanocytes from UV-induced apoptosis by upregulating the level of Bcl-2 (an antiapoptotic protein) in the cells.

Herpesvirus lesion treatment

New therapies are needed to shorten recurrent herpesvirus episodes and reduce related pain and inflammation. LLLT has been suggested as an alternative to current medications. In one study of 50 patients with recurrent perioral HSV infection, LLLT at 690 nm, 80 mW/cm², 48 J/cm² daily for 2 weeks during recurrence-free periods decreased the frequency of herpes labialis episodes, the authors said.

In another study with similar parameters, patients achieved a significant prolongation of remission intervals from 30 to 73 days.

The mechanism of action remains unclear, but an indirect effect of LLLT on cellular and humoral components of the immune system may be involved in antiviral responses, as opposed to a direct virus-inactivating effect, the researchers noted.

Vitiligo treatment

Modest efficacy seen with the low-energy HeNe laser (632 nm, 25 mW/cm²) for the treatment of 18 vitiligo patients led to speculation that LLLT could serve as an alternative effective treatment for this typically treatment-resistant condition. (Repigmentation was observed in 64%, and some follicular repigmentation was observed in the remaining patients).

In a subsequent study of local administration of the HeNe laser light at 3 J/cm², 1.0 mW, 632.8 nm in patients with segmental type vitiligo, marked perilesional and perifollicular repigmentation of more than 50% was observed in 60% of patients.

"Both NGF and (basic fibroblast growth factor) stimulate melanocyte migration, and deficiencies of these mediators may participate in the development of vitiligo," the researchers wrote.

Depigmentation

During tests of red and blue light for acne, researchers unexpectedly found that patients treated with both red and blue light experienced an overall decrease in melanin.

Based on instrumental measurement results, blue light exposure (415 nm, 40 mW/cm², 48 J/cm²), increased the melanin level by 6.7, whereas red light exposure (633 nm, 80 mW/cm², 96 J/cm²) decreased the melanin level by 15.5.

"This finding may have some relationship with the laser’s brightening effect of the skin tone, which 14 of 24 patients spontaneously reported after the treatment period. However, as of today, no other studies investigated or reported a similar decrease in melanin levels after red light irradiations," the researchers said.

Hypertrophic scar and keloid eradication

LLLT has shown promise for preventing hypertrophic and keloid scars in patients who undergo scar revision by surgery or CO₂ laser. The use of daily near-infrared LED (NIR-LED) treatment on one of the two bilateral sites safely reduced the risk of scar development in that lesion, compared with the untreated lesion in three patients with bilateral scars. One underwent surgical revision/excision for preauricular linear keloids that developed after a face-lift procedure, one underwent CO₂ resurfacing for hypertrophic acne scars on the chest, and one underwent CO₂ resurfacing after excision of hypertrophic scars on the back. No significant treatment-related adverse effects were reported.

LLLT may work in these types of scars through an inhibitory effect on interleukin-6 mRNA levels and the modulating of platelet derived growth factor, transforming growth factor–beta, interleukins, and MMPs, which are associated with abnormal wound healing, the researchers noted.

Burn treatment

LED exposure was shown to provide benefit for the treatment of acute sunburn in a study of 10 patients.

Treatment once or twice daily for 3 days on half of the affected area decreased symptoms of burning, redness, swelling, and peeling compared with the untreated half. Decreased MMP-1 was noted on the treated side through immunofluorescence staining in one patient, and real-time polymerase chain reaction gene expression analysis showed a significant decrease in MMP-1 gene expression at both 4 and 24 hours after the UV injury on the treated side.

In another study, LED treatment was effective compared with control for speeding the healing process of laser treatment–related burns. In nine patients with second-degree burns from nonablative laser devices, LED therapy once daily for 1 week was associated with 50% faster healing based on both patient and physician accounts.

LED treatment also was shown in a pilot study to accelerate re-epithelialization of a forearm injury induced by a CO₂ laser; identical test sites were treated with daily dressing changes and polysporin ointment, but the site with faster re-epithelialization had also received the LED treatment (a computer pattern generator was used to deliver the identical CO₂ treatment to both sites).

Psoriasis

LLLT also shows promise for the treatment of plaque psoriasis. In a preliminary study, the combined use of sequential NIR (830 nm) and visible red light (630 nm) led to resolution of psoriasis in patients who were resistant to conventional therapy. The patients received treatment in two 20-minute sessions, 48 hours apart, for 4 or 5 weeks. No adverse side effects occurred.

Despite the variety of potential applications for the technology, LLLT remains somewhat controversial due to "uncertainties about the fundamental molecular and cellular mechanisms responsible for transducing signals from the photons incident on the cells to the biological effects that take place in the irradiated tissue" and because "there are significant variations in terms of dosimetry parameter: wavelength, irradiance or power density, pulse structure, coherence, polarization, energy, fluence, irradiation time, contact versus noncontact application, and repetition regimen," the researchers said.

They noted, however, that problems that have been experienced with LLLT – as well as negative study results – could be the result of inappropriate parameters, skin preparation, and/or device maintenance.

"LLLT appears to have a wide range of applications in dermatology, especially in indications where stimulation of healing, reduction of inflammation, reduction of cell death, and skin rejuvenation are required," they noted, but added that the lack of agreement on important parameters (particularly whether red, NIR, or a combination of both is optimal for a given application) has created a credibility gap that must be overcome before LLLT is routinely applied in every dermatologist’s office.

Once LLLT does become so widely accepted, however, it may be time for dermatologists to move on to the next big thing, Dr. Alam said in his article on the future of procedural dermatology.

"For several decades, dermatologists have worked closely with start-up companies to commercialize new devices and technologies ... when new toxins, fillers, and energy devices have been marketed, dermatologists have been early adopters," he said. "Over time, each device or procedure has diminished in cost and exclusivity as other physicians and nonphysicians have entered the market, and dermatologists have moved on to greener pastures. In all likelihood, this cycle will continue," he noted. "Dermatologists cannot prevent the dissemination of stable technologies, but they can continue to innovate and create new ones."

In fact, he added, continued success in this arena will rest largely on clinicians’ ability to nurture innovation to ensure a healthy pipeline of novel technologies.

The authors of the articles had no financial conflicts to disclose.

Noninvasive procedural dermatology has evolved at a dizzying pace, and continues to do so.

In addition to an array of procedures for skin tightening, skin resurfacing, and fat reduction, emerging technologies such as complex feedback devices, nanotechnology, and stem cell–based therapies promise to keep dermatology at the forefront of the cosmetic and esthetic realm, according to Dr. Murad Alam.

In an article featured in the March issue of Seminars in Cutaneous Medicine and Surgery, Dr. Alam of Northwestern University, Chicago, makes several predictions about the future of these technologies (Semin. Cutan. Med. Surg. 2013;32:61-63).

For example, like modern vehicles equipped with computer chips that can change steering and braking in response to environmental conditions, dermatologic devices will soon include technology that uses precise feedback to make automated setting changes, he said.

"Over time, the reduced cost of microelectronics, feedback controls, and computing power is simplifying the capacity of devices to analyze intraoperative information and adjust the procedure to compensate. For instance, certain laser and energy devices already have tips that are able to sense the temperature in the microenvironment and adjust power output to maintain site-specific temperature within a narrow band," he explained.

This technology could increase effectiveness and improve the safety of devices by reducing the level of operator time and expertise needed, and by making setting changes faster than humanly possible.

Autonomous nanotechnology devices are another advance described by Dr. Alam.

Miniaturization will become more feasible and affordable, and eventually devices will become "so exceedingly small that they will be mostly disposable and deployed in large numbers to the treatment site," he said.

The concept of hundreds of minuscule machines deployed to resurface skin or repair a wound may sound like science fiction, but the rapid advances in nanotechnology could make it a reality that could lead to the creation of new procedures such as ways to treat scars that can’t be corrected using currently available technologies, he added.

Dr. Alam’s other predictions for the future of noninvasive procedural dermatology included:

• Optimization of minimally invasive procedures for fat reduction and skin tightening, which currently provide only mild to modest results and longevity.

• The use of stem cells for augmentation of tissue layers, which could provide genuine rejuvenation rather than simply repair and concealment.

• The improvement of artificial dermal substitutes that can develop many of the functions of live skin, and can be grafted without inducing contractures.

• The development of rapid treatments for pigmentation using nanotechnology and cellular therapies, which will allow for precise melanocyte and melanosome transfer and automatic recoloration of discolored skin.

While these technologies continue to emerge, plenty of others have already established their places in the dermatology arena. The many and varied applications of one of these – low-level laser therapy, or LLLT – are described in another article in the March issue of Seminars in Cutaneous Medicine and Surgery (Semin. Cutan. Med. Surg. 2013;32:42-54).

"LLLT involves exposing cells or tissue to low levels of red and near-infrared light. ... Recently, medical treatment with LLLT at various intensities has been found to stimulate or inhibit an assortment of cellular processes," wrote Dr. Pinar Avci of Massachusetts General Hospital, Boston, and his colleagues, noting that the mechanism associated with the cellular photobiostimulation by LLLT is not yet fully understood, but appears to have a wide range of effects at the molecular, cellular, and tissue levels.

Describing LLLT as "possibly the ultimate noninvasive approach to treating the skin," the researchers highlighted numerous existing or emerging applications for the technology, outlined below.

Skin rejuvenation

Many modalities developed to reverse the dermal and epidermal signs of photoaging and chronological aging depend on the removal of the epidermis and the induction of a controlled form of skin wounding to promote collagen biosynthesis and dermal matrix remodeling. Examples include retinoic acid, dermabrasion, chemical peels, and ablative laser resurfacing.

These modalities require intensive posttreatment care and prolonged down time, and are associated with a risk of numerous complications, the researchers said.

LLLT represents an alternative that is known to increase microcirculation and vascular perfusion in the skin. Data from previous studies have shown that LLLT increased collagen and improved wrinkles and skin laxity with less down time and risk than that of other treatments.

In one study, for example, 300 patients treated with only a light-emitting diode (LED) LLLT device set at 590 nm, 0.10 J/cm², were compared with 600 patients who received the LED therapy in combination with a thermal-based photorejuvenation procedure. Of those who received LED therapy alone, 90% reported softer skin and less roughness and fine lines. The changes ranged from subtle to significant.

Those who received thermal photorejuvenation laser treatment reported a reduction in posttreatment erythema and an overall impression of increased efficacy with the additional LED treatment – an effect that could be attributed to anti-inflammatory effects of LLLT, they noted.

In another study, more than 90% of 90 patients receiving eight LED treatments over 4 weeks experienced favorable results, improving by at least one Fitzpatrick photoaging category. In addition, 65% of patients experienced global improvement in facial texture, fine lines, background erythema, and pigmentation, with results peaking 4-6 months after completion.

Acne treatment

LLLT in the red to near-infrared (NIR) spectral range (630-1000 nm) and with nonthermal power (less than 200 mW) has been shown in several studies to improve acne vulgaris. In one study, a significant reduction in active acne lesions occurred after 12 twice-weekly sessions using 630 nm red-spectrum LLLT with a fluence of 12 J/cm² in conjunction with 2% topical clindamycin. No significant effects were seen using an 890-nm laser. Other studies have demonstrated that the combination of blue and red light is synergistic for treating acne.

Photoprotection

Recent suggestions that infrared exposure might have protective effects against ultraviolet light–induced skin damage are based on the theory that the exposure might trigger protective or repair responses to UV irradiation. While controversial, this view is supported by data suggesting potential mechanisms of action. For example, some data suggest a role of p53, a sensor of gene integrity involved in cell apoptosis and repair mechanisms. In one study, the response to infrared (IR) irradiation was shown to be p53 dependent, suggesting the IR irradiation prepares cells to resist and/or repair further UV-induced DNA damage. Data from another study showed that IR irradiation induced the protective protein ferritin, which is involved in skin repair.

Data from yet another study suggested that nerve growth factor (NGF) production induced by LLLT using the helium neon semiconductor laser diode (HeNe, 633 nm) might explain the photoprotective effects of LLLT. In that study, NGF – a major paracrine maintenance factor for melanocyte survival in skin, was shown to protect melanocytes from UV-induced apoptosis by upregulating the level of Bcl-2 (an antiapoptotic protein) in the cells.

Herpesvirus lesion treatment

New therapies are needed to shorten recurrent herpesvirus episodes and reduce related pain and inflammation. LLLT has been suggested as an alternative to current medications. In one study of 50 patients with recurrent perioral HSV infection, LLLT at 690 nm, 80 mW/cm², 48 J/cm² daily for 2 weeks during recurrence-free periods decreased the frequency of herpes labialis episodes, the authors said.

In another study with similar parameters, patients achieved a significant prolongation of remission intervals from 30 to 73 days.

The mechanism of action remains unclear, but an indirect effect of LLLT on cellular and humoral components of the immune system may be involved in antiviral responses, as opposed to a direct virus-inactivating effect, the researchers noted.

Vitiligo treatment

Modest efficacy seen with the low-energy HeNe laser (632 nm, 25 mW/cm²) for the treatment of 18 vitiligo patients led to speculation that LLLT could serve as an alternative effective treatment for this typically treatment-resistant condition. (Repigmentation was observed in 64%, and some follicular repigmentation was observed in the remaining patients).

In a subsequent study of local administration of the HeNe laser light at 3 J/cm², 1.0 mW, 632.8 nm in patients with segmental type vitiligo, marked perilesional and perifollicular repigmentation of more than 50% was observed in 60% of patients.

"Both NGF and (basic fibroblast growth factor) stimulate melanocyte migration, and deficiencies of these mediators may participate in the development of vitiligo," the researchers wrote.

Depigmentation

During tests of red and blue light for acne, researchers unexpectedly found that patients treated with both red and blue light experienced an overall decrease in melanin.

Based on instrumental measurement results, blue light exposure (415 nm, 40 mW/cm², 48 J/cm²), increased the melanin level by 6.7, whereas red light exposure (633 nm, 80 mW/cm², 96 J/cm²) decreased the melanin level by 15.5.

"This finding may have some relationship with the laser’s brightening effect of the skin tone, which 14 of 24 patients spontaneously reported after the treatment period. However, as of today, no other studies investigated or reported a similar decrease in melanin levels after red light irradiations," the researchers said.

Hypertrophic scar and keloid eradication

LLLT has shown promise for preventing hypertrophic and keloid scars in patients who undergo scar revision by surgery or CO₂ laser. The use of daily near-infrared LED (NIR-LED) treatment on one of the two bilateral sites safely reduced the risk of scar development in that lesion, compared with the untreated lesion in three patients with bilateral scars. One underwent surgical revision/excision for preauricular linear keloids that developed after a face-lift procedure, one underwent CO₂ resurfacing for hypertrophic acne scars on the chest, and one underwent CO₂ resurfacing after excision of hypertrophic scars on the back. No significant treatment-related adverse effects were reported.

LLLT may work in these types of scars through an inhibitory effect on interleukin-6 mRNA levels and the modulating of platelet derived growth factor, transforming growth factor–beta, interleukins, and MMPs, which are associated with abnormal wound healing, the researchers noted.

Burn treatment

LED exposure was shown to provide benefit for the treatment of acute sunburn in a study of 10 patients.

Treatment once or twice daily for 3 days on half of the affected area decreased symptoms of burning, redness, swelling, and peeling compared with the untreated half. Decreased MMP-1 was noted on the treated side through immunofluorescence staining in one patient, and real-time polymerase chain reaction gene expression analysis showed a significant decrease in MMP-1 gene expression at both 4 and 24 hours after the UV injury on the treated side.

In another study, LED treatment was effective compared with control for speeding the healing process of laser treatment–related burns. In nine patients with second-degree burns from nonablative laser devices, LED therapy once daily for 1 week was associated with 50% faster healing based on both patient and physician accounts.

LED treatment also was shown in a pilot study to accelerate re-epithelialization of a forearm injury induced by a CO₂ laser; identical test sites were treated with daily dressing changes and polysporin ointment, but the site with faster re-epithelialization had also received the LED treatment (a computer pattern generator was used to deliver the identical CO₂ treatment to both sites).

Psoriasis

LLLT also shows promise for the treatment of plaque psoriasis. In a preliminary study, the combined use of sequential NIR (830 nm) and visible red light (630 nm) led to resolution of psoriasis in patients who were resistant to conventional therapy. The patients received treatment in two 20-minute sessions, 48 hours apart, for 4 or 5 weeks. No adverse side effects occurred.

Despite the variety of potential applications for the technology, LLLT remains somewhat controversial due to "uncertainties about the fundamental molecular and cellular mechanisms responsible for transducing signals from the photons incident on the cells to the biological effects that take place in the irradiated tissue" and because "there are significant variations in terms of dosimetry parameter: wavelength, irradiance or power density, pulse structure, coherence, polarization, energy, fluence, irradiation time, contact versus noncontact application, and repetition regimen," the researchers said.

They noted, however, that problems that have been experienced with LLLT – as well as negative study results – could be the result of inappropriate parameters, skin preparation, and/or device maintenance.

"LLLT appears to have a wide range of applications in dermatology, especially in indications where stimulation of healing, reduction of inflammation, reduction of cell death, and skin rejuvenation are required," they noted, but added that the lack of agreement on important parameters (particularly whether red, NIR, or a combination of both is optimal for a given application) has created a credibility gap that must be overcome before LLLT is routinely applied in every dermatologist’s office.

Once LLLT does become so widely accepted, however, it may be time for dermatologists to move on to the next big thing, Dr. Alam said in his article on the future of procedural dermatology.

"For several decades, dermatologists have worked closely with start-up companies to commercialize new devices and technologies ... when new toxins, fillers, and energy devices have been marketed, dermatologists have been early adopters," he said. "Over time, each device or procedure has diminished in cost and exclusivity as other physicians and nonphysicians have entered the market, and dermatologists have moved on to greener pastures. In all likelihood, this cycle will continue," he noted. "Dermatologists cannot prevent the dissemination of stable technologies, but they can continue to innovate and create new ones."

In fact, he added, continued success in this arena will rest largely on clinicians’ ability to nurture innovation to ensure a healthy pipeline of novel technologies.

The authors of the articles had no financial conflicts to disclose.