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Two phase 3 trials show benefits of dupilumab for prurigo nodularis
The results, which were published online in Nature Medicine, were the basis for the FDA approval of dupilumab (Dupixent) for adults with PN in September 2022, the first treatment approved for treating PN in the United States.
“These positive studies support the involvement of type 2 cytokines in driving PN disease pathogenesis and the targeting of the [interleukin]-4/IL-13 axis as a novel therapeutic paradigm for patients with PN,” wrote the researchers, who were led by principal investigator Gil Yosipovitch, MD, professor of dermatology at the University of Miami, Fla. Dupilumab, an IL-4 receptor alpha antagonist, blocks the shared receptor component (IL-4R alpha) for IL-4 and IL-13.
For the two phase 3 trials, which were called LIBERTY-PN PRIME and PRIME2 and were sponsored by Sanofi and Regeneron Pharmaceuticals, researchers randomized adults with PN with 20 or more nodules and severe itch uncontrolled with topical therapies 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, which was measured by the proportion of patients with a 4-point or greater reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included a reduction in the number of nodules to 5 or fewer at week 24.
PRIME and PRIME2 enrolled 151 and 160 patients, respectively. In PRIME, 60% of patients in the dupilumab arm achieved a 4-point or greater reduction in the WI-NRS at week 24, compared with 18.4% of patients in the placebo arm (P < .001). In PRIME2, 37.2% of patients in the dupilumab arm achieved a 4-point or greater reduction in the WI-NRS at week 12, compared with 22% of patients in the placebo arm (P = .022).
The researchers also reported that, from an initial baseline of 20 to greater than 100 nodules, 32.0% of dupilumab-treated patients in PRIME and 25.6% in PRIME2 showed a reduction to 5 nodules or fewer, which corresponded to a response of “clear” or “almost clear” skin at week 12, compared with 11.8% and 12.2% of placebo-treated patients, respectively. This treatment effect on skin lesions continued to improve after week 12, with 48% of dupilumab-treated patients in PRIME and 44.9% in PRIME2 having five nodules or fewer at week 24, compared with 18.4% and 15.9% of placebo-treated patients, respectively. Safety was consistent with the known dupilumab safety profile.
“Validation is the first success of this paper,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study. “While both the safety and efficacy of dupilumab in these two phase 3 programs is the meat of the matter, nuanced highlights for me include the rigid nature of the exclusion criteria to ensure a study population that truly has PN as a stand-alone disease, rather than a secondary finding as we once believed to be the entire story. I think it’s important for us to recognize that it’s not one or the other, rather there is both ‘primary’ prurigo nodularis, and then there is secondary prurigo nodularis associated with something else [a wide range of underlying medical conditions], just like we divide primary and secondary hyperhidrosis.”
Dr. Yosipovitch reported having competing interests with several pharmaceutical companies, including Regeneron and Sanofi. Dr. Friedman disclosed that he is a consultant to and a speaker for Regeneron.
The results, which were published online in Nature Medicine, were the basis for the FDA approval of dupilumab (Dupixent) for adults with PN in September 2022, the first treatment approved for treating PN in the United States.
“These positive studies support the involvement of type 2 cytokines in driving PN disease pathogenesis and the targeting of the [interleukin]-4/IL-13 axis as a novel therapeutic paradigm for patients with PN,” wrote the researchers, who were led by principal investigator Gil Yosipovitch, MD, professor of dermatology at the University of Miami, Fla. Dupilumab, an IL-4 receptor alpha antagonist, blocks the shared receptor component (IL-4R alpha) for IL-4 and IL-13.
For the two phase 3 trials, which were called LIBERTY-PN PRIME and PRIME2 and were sponsored by Sanofi and Regeneron Pharmaceuticals, researchers randomized adults with PN with 20 or more nodules and severe itch uncontrolled with topical therapies 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, which was measured by the proportion of patients with a 4-point or greater reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included a reduction in the number of nodules to 5 or fewer at week 24.
PRIME and PRIME2 enrolled 151 and 160 patients, respectively. In PRIME, 60% of patients in the dupilumab arm achieved a 4-point or greater reduction in the WI-NRS at week 24, compared with 18.4% of patients in the placebo arm (P < .001). In PRIME2, 37.2% of patients in the dupilumab arm achieved a 4-point or greater reduction in the WI-NRS at week 12, compared with 22% of patients in the placebo arm (P = .022).
The researchers also reported that, from an initial baseline of 20 to greater than 100 nodules, 32.0% of dupilumab-treated patients in PRIME and 25.6% in PRIME2 showed a reduction to 5 nodules or fewer, which corresponded to a response of “clear” or “almost clear” skin at week 12, compared with 11.8% and 12.2% of placebo-treated patients, respectively. This treatment effect on skin lesions continued to improve after week 12, with 48% of dupilumab-treated patients in PRIME and 44.9% in PRIME2 having five nodules or fewer at week 24, compared with 18.4% and 15.9% of placebo-treated patients, respectively. Safety was consistent with the known dupilumab safety profile.
“Validation is the first success of this paper,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study. “While both the safety and efficacy of dupilumab in these two phase 3 programs is the meat of the matter, nuanced highlights for me include the rigid nature of the exclusion criteria to ensure a study population that truly has PN as a stand-alone disease, rather than a secondary finding as we once believed to be the entire story. I think it’s important for us to recognize that it’s not one or the other, rather there is both ‘primary’ prurigo nodularis, and then there is secondary prurigo nodularis associated with something else [a wide range of underlying medical conditions], just like we divide primary and secondary hyperhidrosis.”
Dr. Yosipovitch reported having competing interests with several pharmaceutical companies, including Regeneron and Sanofi. Dr. Friedman disclosed that he is a consultant to and a speaker for Regeneron.
The results, which were published online in Nature Medicine, were the basis for the FDA approval of dupilumab (Dupixent) for adults with PN in September 2022, the first treatment approved for treating PN in the United States.
“These positive studies support the involvement of type 2 cytokines in driving PN disease pathogenesis and the targeting of the [interleukin]-4/IL-13 axis as a novel therapeutic paradigm for patients with PN,” wrote the researchers, who were led by principal investigator Gil Yosipovitch, MD, professor of dermatology at the University of Miami, Fla. Dupilumab, an IL-4 receptor alpha antagonist, blocks the shared receptor component (IL-4R alpha) for IL-4 and IL-13.
For the two phase 3 trials, which were called LIBERTY-PN PRIME and PRIME2 and were sponsored by Sanofi and Regeneron Pharmaceuticals, researchers randomized adults with PN with 20 or more nodules and severe itch uncontrolled with topical therapies 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, which was measured by the proportion of patients with a 4-point or greater reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included a reduction in the number of nodules to 5 or fewer at week 24.
PRIME and PRIME2 enrolled 151 and 160 patients, respectively. In PRIME, 60% of patients in the dupilumab arm achieved a 4-point or greater reduction in the WI-NRS at week 24, compared with 18.4% of patients in the placebo arm (P < .001). In PRIME2, 37.2% of patients in the dupilumab arm achieved a 4-point or greater reduction in the WI-NRS at week 12, compared with 22% of patients in the placebo arm (P = .022).
The researchers also reported that, from an initial baseline of 20 to greater than 100 nodules, 32.0% of dupilumab-treated patients in PRIME and 25.6% in PRIME2 showed a reduction to 5 nodules or fewer, which corresponded to a response of “clear” or “almost clear” skin at week 12, compared with 11.8% and 12.2% of placebo-treated patients, respectively. This treatment effect on skin lesions continued to improve after week 12, with 48% of dupilumab-treated patients in PRIME and 44.9% in PRIME2 having five nodules or fewer at week 24, compared with 18.4% and 15.9% of placebo-treated patients, respectively. Safety was consistent with the known dupilumab safety profile.
“Validation is the first success of this paper,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study. “While both the safety and efficacy of dupilumab in these two phase 3 programs is the meat of the matter, nuanced highlights for me include the rigid nature of the exclusion criteria to ensure a study population that truly has PN as a stand-alone disease, rather than a secondary finding as we once believed to be the entire story. I think it’s important for us to recognize that it’s not one or the other, rather there is both ‘primary’ prurigo nodularis, and then there is secondary prurigo nodularis associated with something else [a wide range of underlying medical conditions], just like we divide primary and secondary hyperhidrosis.”
Dr. Yosipovitch reported having competing interests with several pharmaceutical companies, including Regeneron and Sanofi. Dr. Friedman disclosed that he is a consultant to and a speaker for Regeneron.
FROM NATURE MEDICINE
Itchy pustules over hair follicles
A potassium hydroxide (KOH) preparation of pus and dry superficial skin taken from 1 of the pustules revealed multiple hyphae and confirmed a diagnosis of nodular granulomatous perifolliculitis, also called Majocchi granuloma.
Majocchi granuloma is a reactive process of inflammation caused by infection of the follicular unit(s) by a dermatophyte—most often the same Trichophyton species responsible for more superficial tinea. On exam, there may be a solitary papule, pustule, or nodule. More often, there are multiple papules and pustules grouped within an annular plaque in hair-bearing areas on the head, trunk, or extremities. Majocchi granuloma can occur in patients who are healthy and those who are immunosuppressed.1 It can also occur when a topical steroid is applied to unsuspected tinea, as occurred here. In this case, the patient was accustomed to having multiple skin plaques of psoriasis and assumed this was a stubborn manifestation of that.
Because the infection penetrates deeper than most topical therapies can effectively reach at adequate concentrations, systemic medications are the treatments of choice. Terbinafine, itraconazole, and fluconazole are all effective options but need to be used for several weeks to be effective.
This patient received terbinafine 250 mg/d for 6 weeks and the pustules cleared completely. He continued with his other psoriasis medications throughout his treatment.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.
1. İlkit M, Durdu M, Karakaş M. Majocchi’s granuloma: a symptom complex caused by fungal pathogens. Med Mycol. 2012;50:449-457. doi: 10.3109/13693786.2012.669503
A potassium hydroxide (KOH) preparation of pus and dry superficial skin taken from 1 of the pustules revealed multiple hyphae and confirmed a diagnosis of nodular granulomatous perifolliculitis, also called Majocchi granuloma.
Majocchi granuloma is a reactive process of inflammation caused by infection of the follicular unit(s) by a dermatophyte—most often the same Trichophyton species responsible for more superficial tinea. On exam, there may be a solitary papule, pustule, or nodule. More often, there are multiple papules and pustules grouped within an annular plaque in hair-bearing areas on the head, trunk, or extremities. Majocchi granuloma can occur in patients who are healthy and those who are immunosuppressed.1 It can also occur when a topical steroid is applied to unsuspected tinea, as occurred here. In this case, the patient was accustomed to having multiple skin plaques of psoriasis and assumed this was a stubborn manifestation of that.
Because the infection penetrates deeper than most topical therapies can effectively reach at adequate concentrations, systemic medications are the treatments of choice. Terbinafine, itraconazole, and fluconazole are all effective options but need to be used for several weeks to be effective.
This patient received terbinafine 250 mg/d for 6 weeks and the pustules cleared completely. He continued with his other psoriasis medications throughout his treatment.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.
A potassium hydroxide (KOH) preparation of pus and dry superficial skin taken from 1 of the pustules revealed multiple hyphae and confirmed a diagnosis of nodular granulomatous perifolliculitis, also called Majocchi granuloma.
Majocchi granuloma is a reactive process of inflammation caused by infection of the follicular unit(s) by a dermatophyte—most often the same Trichophyton species responsible for more superficial tinea. On exam, there may be a solitary papule, pustule, or nodule. More often, there are multiple papules and pustules grouped within an annular plaque in hair-bearing areas on the head, trunk, or extremities. Majocchi granuloma can occur in patients who are healthy and those who are immunosuppressed.1 It can also occur when a topical steroid is applied to unsuspected tinea, as occurred here. In this case, the patient was accustomed to having multiple skin plaques of psoriasis and assumed this was a stubborn manifestation of that.
Because the infection penetrates deeper than most topical therapies can effectively reach at adequate concentrations, systemic medications are the treatments of choice. Terbinafine, itraconazole, and fluconazole are all effective options but need to be used for several weeks to be effective.
This patient received terbinafine 250 mg/d for 6 weeks and the pustules cleared completely. He continued with his other psoriasis medications throughout his treatment.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.
1. İlkit M, Durdu M, Karakaş M. Majocchi’s granuloma: a symptom complex caused by fungal pathogens. Med Mycol. 2012;50:449-457. doi: 10.3109/13693786.2012.669503
1. İlkit M, Durdu M, Karakaş M. Majocchi’s granuloma: a symptom complex caused by fungal pathogens. Med Mycol. 2012;50:449-457. doi: 10.3109/13693786.2012.669503
Study shifts burden of IgG4-related disease to women
The incidence and prevalence of IgG4-related disease each rose considerably from 2015 to 2019 in the United States, and the risk of death in those with the immune-mediated condition is about 2.5 times higher than those who are not affected, based on an analysis of claims data from commercially insured adults.
The first population-based study of IgG4-RD incidence, prevalence, and mortality establishes “key benchmarks for informing the diagnosis and management of patients” with a condition “that causes fibrosing inflammatory lesions at nearly any anatomic site,” and wasn’t initially described until 2001, Zachary S. Wallace, MD, and associates said in Annals of the Rheumatic Diseases.
The increases in incidence and prevalence likely reflected increased disease awareness, they suggested. Overall U.S. incidence was 1.2 per 100,000 person-years for the 5-year period of 2015-2019, rising 86% from 0.78 per 100,000 person-years to 1.45 in 2018 before dropping to 1.39 in 2019. The change in prevalence was even greater, increasing 122% from 2.41 per 100,000 persons in 2015 to 5.34 per 100,000 in 2019, the investigators said.
Previous studies had indicated that the majority of patients with IgG4-RD were male, but the current study, using Optum’s Clinformatics Data Mart, which includes commercial health plan and Medicare Advantage members in all 50 states, showed that both incidence and prevalence (see graph) were higher among women, noted Dr. Wallace of Massachusetts General Hospital, Boston, and associates. They identified 524 patients (57.6% female) in the database who met the criteria for IgG4-RD from Jan. 1, 2010, to Dec. 31, 2019.
Incidence over the course of the study “was similar in patients identified as Asian or White but lower in those identified as Black or Hispanic,” they noted, adding that “the prevalence of IgG4-RD during this period reflected similar trends.” A jump in prevalence from 2018 to 2019, however, left White patients with a much higher rate (6.13 per 100,000 persons) than Asian patients (4.54 per 100,000), Black patients (3.42), and Hispanic patients (3.02).
For the mortality analysis, 516 patients with IgG4-RD were age-, sex-, and race-matched with 5,160 patients without IgG4-RD. Mortality was 3.42 and 1.46 per 100 person-years, respectively, over the 5.5 years of follow-up, so IgG4-RD was associated with a 2.5-fold higher risk of death. “The association of IgG4-RD with a higher risk of death was observed across the age spectrum and among both male and female patients,” the researchers said.
“Clinicians across specialties should be aware of IgG4-RD given the incidence, prevalence, and excess risk of death associated with this condition. ... Additional studies are urgently needed to define optimal management strategies to improve survival,” they wrote.
The study was supported by a grant to Massachusetts General Hospital from Sanofi, and Dr. Wallace received funding from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Rheumatology Research Foundation. He has received research support and consulting fees from several companies, and four coinvestigators are employees of Sanofi.
The incidence and prevalence of IgG4-related disease each rose considerably from 2015 to 2019 in the United States, and the risk of death in those with the immune-mediated condition is about 2.5 times higher than those who are not affected, based on an analysis of claims data from commercially insured adults.
The first population-based study of IgG4-RD incidence, prevalence, and mortality establishes “key benchmarks for informing the diagnosis and management of patients” with a condition “that causes fibrosing inflammatory lesions at nearly any anatomic site,” and wasn’t initially described until 2001, Zachary S. Wallace, MD, and associates said in Annals of the Rheumatic Diseases.
The increases in incidence and prevalence likely reflected increased disease awareness, they suggested. Overall U.S. incidence was 1.2 per 100,000 person-years for the 5-year period of 2015-2019, rising 86% from 0.78 per 100,000 person-years to 1.45 in 2018 before dropping to 1.39 in 2019. The change in prevalence was even greater, increasing 122% from 2.41 per 100,000 persons in 2015 to 5.34 per 100,000 in 2019, the investigators said.
Previous studies had indicated that the majority of patients with IgG4-RD were male, but the current study, using Optum’s Clinformatics Data Mart, which includes commercial health plan and Medicare Advantage members in all 50 states, showed that both incidence and prevalence (see graph) were higher among women, noted Dr. Wallace of Massachusetts General Hospital, Boston, and associates. They identified 524 patients (57.6% female) in the database who met the criteria for IgG4-RD from Jan. 1, 2010, to Dec. 31, 2019.
Incidence over the course of the study “was similar in patients identified as Asian or White but lower in those identified as Black or Hispanic,” they noted, adding that “the prevalence of IgG4-RD during this period reflected similar trends.” A jump in prevalence from 2018 to 2019, however, left White patients with a much higher rate (6.13 per 100,000 persons) than Asian patients (4.54 per 100,000), Black patients (3.42), and Hispanic patients (3.02).
For the mortality analysis, 516 patients with IgG4-RD were age-, sex-, and race-matched with 5,160 patients without IgG4-RD. Mortality was 3.42 and 1.46 per 100 person-years, respectively, over the 5.5 years of follow-up, so IgG4-RD was associated with a 2.5-fold higher risk of death. “The association of IgG4-RD with a higher risk of death was observed across the age spectrum and among both male and female patients,” the researchers said.
“Clinicians across specialties should be aware of IgG4-RD given the incidence, prevalence, and excess risk of death associated with this condition. ... Additional studies are urgently needed to define optimal management strategies to improve survival,” they wrote.
The study was supported by a grant to Massachusetts General Hospital from Sanofi, and Dr. Wallace received funding from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Rheumatology Research Foundation. He has received research support and consulting fees from several companies, and four coinvestigators are employees of Sanofi.
The incidence and prevalence of IgG4-related disease each rose considerably from 2015 to 2019 in the United States, and the risk of death in those with the immune-mediated condition is about 2.5 times higher than those who are not affected, based on an analysis of claims data from commercially insured adults.
The first population-based study of IgG4-RD incidence, prevalence, and mortality establishes “key benchmarks for informing the diagnosis and management of patients” with a condition “that causes fibrosing inflammatory lesions at nearly any anatomic site,” and wasn’t initially described until 2001, Zachary S. Wallace, MD, and associates said in Annals of the Rheumatic Diseases.
The increases in incidence and prevalence likely reflected increased disease awareness, they suggested. Overall U.S. incidence was 1.2 per 100,000 person-years for the 5-year period of 2015-2019, rising 86% from 0.78 per 100,000 person-years to 1.45 in 2018 before dropping to 1.39 in 2019. The change in prevalence was even greater, increasing 122% from 2.41 per 100,000 persons in 2015 to 5.34 per 100,000 in 2019, the investigators said.
Previous studies had indicated that the majority of patients with IgG4-RD were male, but the current study, using Optum’s Clinformatics Data Mart, which includes commercial health plan and Medicare Advantage members in all 50 states, showed that both incidence and prevalence (see graph) were higher among women, noted Dr. Wallace of Massachusetts General Hospital, Boston, and associates. They identified 524 patients (57.6% female) in the database who met the criteria for IgG4-RD from Jan. 1, 2010, to Dec. 31, 2019.
Incidence over the course of the study “was similar in patients identified as Asian or White but lower in those identified as Black or Hispanic,” they noted, adding that “the prevalence of IgG4-RD during this period reflected similar trends.” A jump in prevalence from 2018 to 2019, however, left White patients with a much higher rate (6.13 per 100,000 persons) than Asian patients (4.54 per 100,000), Black patients (3.42), and Hispanic patients (3.02).
For the mortality analysis, 516 patients with IgG4-RD were age-, sex-, and race-matched with 5,160 patients without IgG4-RD. Mortality was 3.42 and 1.46 per 100 person-years, respectively, over the 5.5 years of follow-up, so IgG4-RD was associated with a 2.5-fold higher risk of death. “The association of IgG4-RD with a higher risk of death was observed across the age spectrum and among both male and female patients,” the researchers said.
“Clinicians across specialties should be aware of IgG4-RD given the incidence, prevalence, and excess risk of death associated with this condition. ... Additional studies are urgently needed to define optimal management strategies to improve survival,” they wrote.
The study was supported by a grant to Massachusetts General Hospital from Sanofi, and Dr. Wallace received funding from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Rheumatology Research Foundation. He has received research support and consulting fees from several companies, and four coinvestigators are employees of Sanofi.
FROM ANNALS OF THE RHEUMATIC DISEASES
1,726-nm lasers poised to revolutionize acne treatment, expert predicts
PHOENIX – When Jeffrey Dover, MD, addressed audience members gathered for a session on cutting-edge technologies at the annual conference of the American Society for Laser Medicine and Surgery, he reflected on a conversation he had with R. Rox Anderson, MD, almost 40 years ago, about eventually finding a cure for acne.
“Despite the fact that we have over-the-counter therapies, prescription therapies, and all kinds of devices available to treat acne, there are still barriers to care that get in the way of treatment,” said Dr. Dover, director of SkinCare Physicians in Chestnut Hill, Mass. “If we had a device based on innovative light science that could meet the needs of the acne patient to get rid of these barriers, wouldn’t that be something wonderful?”
The answer to this question, he said, is now “yes,” because of advances in lasers that target sebaceous glands.
In a seminal paper published in 2012, Fernanda H. Sakamoto, MD, PhD, Dr. Anderson, and colleagues demonstrated the potential for a free electron laser to target sebaceous glands . Following several years of refinement, Dr. Dover said.
“With the 1,726-nm laser, there is some selective absorption in sebum in skin, which beats out absorption in the other chromophores,” he said. “But it’s not a big difference like it is, for example, for pulsed-dye lasers and vascular targets. ... This means that the therapeutic window is relatively small and protecting the rest of the epidermis and dermis is crucial to be able to target these lesions or the sebaceous gland without unnecessary damage. If we can protect the epidermis and heat just the sebaceous glands, we should be able to get Accutane-like results if we get durability [by] shrinking sebaceous glands.”
Effective cooling, whether contact cooling, bulk cooling, or air cooling, is crucial to success, he continued. “It’s got to be robust and highly specific to protect the skin, so you don’t end up with side effects that are worse than the disease.”
The AviClear laser delivers seven 3-mm spots, which takes into account the thermal relaxation times of the sebaceous glands. The algorithm delivers a treatment imprint at roughly 0.3 Hz and a 1.5-mm depth of penetration, and the device relies on contact cooling. In pivotal data submitted to the FDA, 104 individuals with moderate to severe acne received three treatments with the AviClear 1 month apart, with follow-up at 1, 3, 6, and 12 months post treatment. They had no other treatment regimens, and the primary endpoint was the percentage of patients who achieved a 50% reduction in inflammatory lesion count 3 months after the final treatment. The secondary endpoint was an Investigator’s Global Assessment (IGA) improvement of 2 or greater.
Dr. Dover, who helped design the study, said that, at 3 months, 80% of those treated achieved a 50% or greater reduction in inflammatory lesion count (P < .001). As for secondary endpoints, 36% of individuals were assessed as having clear or almost clear skin; 47% achieved a 2-point or greater improvement in IGA score, compared with baseline, and 87% achieved a 1-point or greater improvement in IGA score, compared with baseline. By 6 months, 88% of individuals achieved a 50% or greater reduction in inflammatory lesion count; this improved to 92% by 12 months (P < .001).
“All of these procedures were done with no topical anesthetic, no intralesional anesthetic, and they tolerated these quite well,” he said. “There was no down time that required medical intervention after the treatments. All posttreatment erythema and swelling resolved quickly,” and 75% of the patients were “very satisfied” with the treatments.
The Accure Laser System features a proprietary technology that precisely controls thermal gradient depth. “So instead of guessing whether you are delivering the correct amount of heat, it actually tells you,” said Dr. Dover, a past president of the ASLMS and the American Society for Dermatologic Surgery. “It correlates surface and at-depth temperatures, and there’s an infrared camera for real-time accurate temperature monitoring.” The device features highly controlled air cooling and a pulsing pattern that ensures treatment of sebaceous glands of all sizes and at all depths. The clinical end marker is peak epidermal temperature.
In a study supported by Accure, the manufacturer, researchers evaluated the efficacy of the Accure Laser System in 35 subjects with types I to VI skin, who received four monthly treatments 30-45 minutes each, and were followed 12, 26, 39, and 52 weeks following their last treatment. To date, data out to 52 weeks is available for 17 study participants. According to Dr. Dover, the researchers found 80% clearance at 12 weeks following the last treatment, with continued improvement at 52 weeks. One hundred percent of subjects responded. Side effects included erythema, edema, crusting, blisters, and inflammatory papules. “None of these were medically significant,” he said.
As dermatologists begin to incorporate the AviClear and Accure devices into their practices, Dr. Dover said that he is reminded of the conversation he had some 40 years ago with Dr. Anderson about finding a cure for acne, and he feels a bit awestruck. “These 1,726-nm lasers are effective for treating acne. I personally think they are going to revolutionize the way we treat at least some of our patients with acne. They may both be effective for treating facial acne scars. Time will tell. Further study of both scarring and acne are needed to fully categorize the benefit and to optimize treatments.”
To date no direct clinical comparisons have been made between the AviClear and Accure devices.
Dr. Dover reported that he is a consultant for Cutera, the manufacturer for AviClear. He also performs research for the company.
PHOENIX – When Jeffrey Dover, MD, addressed audience members gathered for a session on cutting-edge technologies at the annual conference of the American Society for Laser Medicine and Surgery, he reflected on a conversation he had with R. Rox Anderson, MD, almost 40 years ago, about eventually finding a cure for acne.
“Despite the fact that we have over-the-counter therapies, prescription therapies, and all kinds of devices available to treat acne, there are still barriers to care that get in the way of treatment,” said Dr. Dover, director of SkinCare Physicians in Chestnut Hill, Mass. “If we had a device based on innovative light science that could meet the needs of the acne patient to get rid of these barriers, wouldn’t that be something wonderful?”
The answer to this question, he said, is now “yes,” because of advances in lasers that target sebaceous glands.
In a seminal paper published in 2012, Fernanda H. Sakamoto, MD, PhD, Dr. Anderson, and colleagues demonstrated the potential for a free electron laser to target sebaceous glands . Following several years of refinement, Dr. Dover said.
“With the 1,726-nm laser, there is some selective absorption in sebum in skin, which beats out absorption in the other chromophores,” he said. “But it’s not a big difference like it is, for example, for pulsed-dye lasers and vascular targets. ... This means that the therapeutic window is relatively small and protecting the rest of the epidermis and dermis is crucial to be able to target these lesions or the sebaceous gland without unnecessary damage. If we can protect the epidermis and heat just the sebaceous glands, we should be able to get Accutane-like results if we get durability [by] shrinking sebaceous glands.”
Effective cooling, whether contact cooling, bulk cooling, or air cooling, is crucial to success, he continued. “It’s got to be robust and highly specific to protect the skin, so you don’t end up with side effects that are worse than the disease.”
The AviClear laser delivers seven 3-mm spots, which takes into account the thermal relaxation times of the sebaceous glands. The algorithm delivers a treatment imprint at roughly 0.3 Hz and a 1.5-mm depth of penetration, and the device relies on contact cooling. In pivotal data submitted to the FDA, 104 individuals with moderate to severe acne received three treatments with the AviClear 1 month apart, with follow-up at 1, 3, 6, and 12 months post treatment. They had no other treatment regimens, and the primary endpoint was the percentage of patients who achieved a 50% reduction in inflammatory lesion count 3 months after the final treatment. The secondary endpoint was an Investigator’s Global Assessment (IGA) improvement of 2 or greater.
Dr. Dover, who helped design the study, said that, at 3 months, 80% of those treated achieved a 50% or greater reduction in inflammatory lesion count (P < .001). As for secondary endpoints, 36% of individuals were assessed as having clear or almost clear skin; 47% achieved a 2-point or greater improvement in IGA score, compared with baseline, and 87% achieved a 1-point or greater improvement in IGA score, compared with baseline. By 6 months, 88% of individuals achieved a 50% or greater reduction in inflammatory lesion count; this improved to 92% by 12 months (P < .001).
“All of these procedures were done with no topical anesthetic, no intralesional anesthetic, and they tolerated these quite well,” he said. “There was no down time that required medical intervention after the treatments. All posttreatment erythema and swelling resolved quickly,” and 75% of the patients were “very satisfied” with the treatments.
The Accure Laser System features a proprietary technology that precisely controls thermal gradient depth. “So instead of guessing whether you are delivering the correct amount of heat, it actually tells you,” said Dr. Dover, a past president of the ASLMS and the American Society for Dermatologic Surgery. “It correlates surface and at-depth temperatures, and there’s an infrared camera for real-time accurate temperature monitoring.” The device features highly controlled air cooling and a pulsing pattern that ensures treatment of sebaceous glands of all sizes and at all depths. The clinical end marker is peak epidermal temperature.
In a study supported by Accure, the manufacturer, researchers evaluated the efficacy of the Accure Laser System in 35 subjects with types I to VI skin, who received four monthly treatments 30-45 minutes each, and were followed 12, 26, 39, and 52 weeks following their last treatment. To date, data out to 52 weeks is available for 17 study participants. According to Dr. Dover, the researchers found 80% clearance at 12 weeks following the last treatment, with continued improvement at 52 weeks. One hundred percent of subjects responded. Side effects included erythema, edema, crusting, blisters, and inflammatory papules. “None of these were medically significant,” he said.
As dermatologists begin to incorporate the AviClear and Accure devices into their practices, Dr. Dover said that he is reminded of the conversation he had some 40 years ago with Dr. Anderson about finding a cure for acne, and he feels a bit awestruck. “These 1,726-nm lasers are effective for treating acne. I personally think they are going to revolutionize the way we treat at least some of our patients with acne. They may both be effective for treating facial acne scars. Time will tell. Further study of both scarring and acne are needed to fully categorize the benefit and to optimize treatments.”
To date no direct clinical comparisons have been made between the AviClear and Accure devices.
Dr. Dover reported that he is a consultant for Cutera, the manufacturer for AviClear. He also performs research for the company.
PHOENIX – When Jeffrey Dover, MD, addressed audience members gathered for a session on cutting-edge technologies at the annual conference of the American Society for Laser Medicine and Surgery, he reflected on a conversation he had with R. Rox Anderson, MD, almost 40 years ago, about eventually finding a cure for acne.
“Despite the fact that we have over-the-counter therapies, prescription therapies, and all kinds of devices available to treat acne, there are still barriers to care that get in the way of treatment,” said Dr. Dover, director of SkinCare Physicians in Chestnut Hill, Mass. “If we had a device based on innovative light science that could meet the needs of the acne patient to get rid of these barriers, wouldn’t that be something wonderful?”
The answer to this question, he said, is now “yes,” because of advances in lasers that target sebaceous glands.
In a seminal paper published in 2012, Fernanda H. Sakamoto, MD, PhD, Dr. Anderson, and colleagues demonstrated the potential for a free electron laser to target sebaceous glands . Following several years of refinement, Dr. Dover said.
“With the 1,726-nm laser, there is some selective absorption in sebum in skin, which beats out absorption in the other chromophores,” he said. “But it’s not a big difference like it is, for example, for pulsed-dye lasers and vascular targets. ... This means that the therapeutic window is relatively small and protecting the rest of the epidermis and dermis is crucial to be able to target these lesions or the sebaceous gland without unnecessary damage. If we can protect the epidermis and heat just the sebaceous glands, we should be able to get Accutane-like results if we get durability [by] shrinking sebaceous glands.”
Effective cooling, whether contact cooling, bulk cooling, or air cooling, is crucial to success, he continued. “It’s got to be robust and highly specific to protect the skin, so you don’t end up with side effects that are worse than the disease.”
The AviClear laser delivers seven 3-mm spots, which takes into account the thermal relaxation times of the sebaceous glands. The algorithm delivers a treatment imprint at roughly 0.3 Hz and a 1.5-mm depth of penetration, and the device relies on contact cooling. In pivotal data submitted to the FDA, 104 individuals with moderate to severe acne received three treatments with the AviClear 1 month apart, with follow-up at 1, 3, 6, and 12 months post treatment. They had no other treatment regimens, and the primary endpoint was the percentage of patients who achieved a 50% reduction in inflammatory lesion count 3 months after the final treatment. The secondary endpoint was an Investigator’s Global Assessment (IGA) improvement of 2 or greater.
Dr. Dover, who helped design the study, said that, at 3 months, 80% of those treated achieved a 50% or greater reduction in inflammatory lesion count (P < .001). As for secondary endpoints, 36% of individuals were assessed as having clear or almost clear skin; 47% achieved a 2-point or greater improvement in IGA score, compared with baseline, and 87% achieved a 1-point or greater improvement in IGA score, compared with baseline. By 6 months, 88% of individuals achieved a 50% or greater reduction in inflammatory lesion count; this improved to 92% by 12 months (P < .001).
“All of these procedures were done with no topical anesthetic, no intralesional anesthetic, and they tolerated these quite well,” he said. “There was no down time that required medical intervention after the treatments. All posttreatment erythema and swelling resolved quickly,” and 75% of the patients were “very satisfied” with the treatments.
The Accure Laser System features a proprietary technology that precisely controls thermal gradient depth. “So instead of guessing whether you are delivering the correct amount of heat, it actually tells you,” said Dr. Dover, a past president of the ASLMS and the American Society for Dermatologic Surgery. “It correlates surface and at-depth temperatures, and there’s an infrared camera for real-time accurate temperature monitoring.” The device features highly controlled air cooling and a pulsing pattern that ensures treatment of sebaceous glands of all sizes and at all depths. The clinical end marker is peak epidermal temperature.
In a study supported by Accure, the manufacturer, researchers evaluated the efficacy of the Accure Laser System in 35 subjects with types I to VI skin, who received four monthly treatments 30-45 minutes each, and were followed 12, 26, 39, and 52 weeks following their last treatment. To date, data out to 52 weeks is available for 17 study participants. According to Dr. Dover, the researchers found 80% clearance at 12 weeks following the last treatment, with continued improvement at 52 weeks. One hundred percent of subjects responded. Side effects included erythema, edema, crusting, blisters, and inflammatory papules. “None of these were medically significant,” he said.
As dermatologists begin to incorporate the AviClear and Accure devices into their practices, Dr. Dover said that he is reminded of the conversation he had some 40 years ago with Dr. Anderson about finding a cure for acne, and he feels a bit awestruck. “These 1,726-nm lasers are effective for treating acne. I personally think they are going to revolutionize the way we treat at least some of our patients with acne. They may both be effective for treating facial acne scars. Time will tell. Further study of both scarring and acne are needed to fully categorize the benefit and to optimize treatments.”
To date no direct clinical comparisons have been made between the AviClear and Accure devices.
Dr. Dover reported that he is a consultant for Cutera, the manufacturer for AviClear. He also performs research for the company.
AT ASLMS 2023
Contact allergens lurk in diabetes devices
in a presentation at the annual meeting of the American Contact Dermatitis Society.
Advanced technologies used for the management of diabetes fall into three main categories, said Dr. Chen, of the department of dermatology, Stanford University, Redwood City, Calif. Continuous glucose monitoring (CGM) devices, which are worn on the body, collect glucose measurements. Continuous subcutaneous insulin infusion (CSII) devices are attached to the body via an infusion set and are now available as tubing-free patch pumps that are attached directly to the skin via a catheter. Glucose-responsive insulin delivery systems combine the sensing and delivery features of the other two types of devices.
Once thought to be rare, reports of skin complications related to diabetes devices have been increasing in recent years, she said. Some reports suggest that at any given time, skin complications may affect as many as one quarter to one half of patients who use these devices, “so this is an important issue,” she emphasized. “Skin reactions are a major factor in device discontinuation, so we as clinicians need to be really proactive about treating these reactions.”
Risk factors for skin complications related to diabetes devices include sensitization to the adhesive used with the devices, as well as prolonged exposure to the device, Dr. Chen said. Younger age also appears to be a risk factor, as is a compromised skin barrier in the area where the device is used.
Unfortunately, obtaining details on the specific adhesives and the raw materials used in these devices, so as to customize patch testing, remains a challenge, she said. “Patch testing initially was often negative to commercially available allergens, even while patients were testing positive to pieces of device adhesive,” she noted.
Consider isobornyl acrylate
An article published in 2017 in Contact Dermatitis was “a major breakthrough” in that it identified isobornyl acrylate (IBOA) as an allergen in connection with the Freestyle Libre, a CGM device that was relatively new at the time. The finding was serendipitous, Dr. Chen said. A patient being treated for suspected allergic contact dermatitis in connection with use of a Freestyle Libre device was tested for IBOA accidentally, after the nurse administering the patch test thought that this was part of the standard acrylate series, she explained.
Subsequently, researchers identified 15 patients who had experienced reactions to the Freestyle Libre; 12 of 13 patients who were patch tested for IBOA tested positive. IBOA was found throughout the device, particularly where the top and bottom plastic components were connected, Dr. Chen said. This suggested that the IBOA was in the device housing and had diffused into the adhesive that attached the device to the skin.
An article published in 2018 in the Journal of Diabetes Science described three patients who developed severe allergic contact dermatitis from IBOA while using a CGM device, Dr. Chen said. The investigators confirmed that there were no reactions to the adhesive itself, again suggesting that IBOA had diffused into the adhesive from other parts of the device.
Although the authors were bound by a confidentiality agreement regarding the individual adhesive components, “the authors noted most of the acrylates in the adhesive were not present in commercially available acrylate series for patch testing,” she said.
IBOA, the ACDS’ Allergen of the Year in 2020, is common in sealants, glues, and adhesives, Dr. Chen said. Although IBOA had been reported infrequently as an allergen, it has now been identified as a “potential culprit” behind skin reactions in many diabetes devices, including CSII and CGM devices, she added.
In addition, N,N-dimethylacrylamide (DMAA) is an allergen that has been identified in several diabetes devices and often occurs with IBOA in medical-grade UV-cured adhesives, Dr. Chen noted. Other allergens identified in diabetes devices include colophony, which is present in many adhesives, as well as other acrylates and epoxy resin.
Diabetes devices are constantly evolving. IBOA is no longer found in Freestyle Libre devices. It is important that clinicians stay up to date with the medical literature and advocate for partnership with device manufacturers, she emphasized.
Patch testing
When diabetes devices are suspected as the source of allergic contact dermatitis, a minimum of a baseline series that contains colophony at a concentration of 20% in petrolatum should be carried out, Dr. Chen said. Commercialized patch test trays, which include plastics, glues, acrylates, epoxy resins/isocyanates, and colophony derivatives, should be ideal. “Personal-care products should be included if they are potentially relevant,” she added.
Dr. Chen shared tables published in Contact Dermatitis in 2021 with examples of screening test series. She said to consider including screening for other allergens more recently discovered in diabetes devices, including 2,2’-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate (MBPA) 1.5% pet; dipropylene glycol diacrylate (DPGDA) 0.1% pet; and butylated hydroxytoluene (BHT) 2% pet.
Testing for monomethyl ether of hydroquinone should also be considered; this may be included in the test preparations for IBOA and DMAA.
Management strategies
For patients who experience skin reactions to their diabetes devices, consideration may given to relocating the device to another area of skin or changing sensors more frequently, according to Dr. Chen.
For some patients, the reaction can be managed with corticosteroid cream, ointment, solution, or nasal spray. Topical antibiotics or topical antihistamines can be helpful, as can barrier dressings, solutions, or sprays, she said. The best solution is to change to a device that does not have the culprit allergen, “but that is difficult, since we don’t know what is in these devices,” she added. Good alternatives include the Eversense CGM device or devices that have been demonstrated not to contain IBOA, such as the Freestyle Libre 2 or the newer version of the Omnipod, an insulin delivery system
Looking ahead, Dr. Chen said that “mandatory labeling is needed, as devices with the same name may have different compositions, depending on the date of manufacture.” Allergens relevant to people with diabetes are constantly evolving, and many are still unidentified, so clinicians and manufacturers need to work together to identify the culprit allergens and their sources, she said.
Dr. Chen has served as principal investigator or subinvestigator for Amgen, AbbVie, and Sanofi Regeneron and as a consultant for Purity Brands.
A version of this article first appeared on Medscape.com.
in a presentation at the annual meeting of the American Contact Dermatitis Society.
Advanced technologies used for the management of diabetes fall into three main categories, said Dr. Chen, of the department of dermatology, Stanford University, Redwood City, Calif. Continuous glucose monitoring (CGM) devices, which are worn on the body, collect glucose measurements. Continuous subcutaneous insulin infusion (CSII) devices are attached to the body via an infusion set and are now available as tubing-free patch pumps that are attached directly to the skin via a catheter. Glucose-responsive insulin delivery systems combine the sensing and delivery features of the other two types of devices.
Once thought to be rare, reports of skin complications related to diabetes devices have been increasing in recent years, she said. Some reports suggest that at any given time, skin complications may affect as many as one quarter to one half of patients who use these devices, “so this is an important issue,” she emphasized. “Skin reactions are a major factor in device discontinuation, so we as clinicians need to be really proactive about treating these reactions.”
Risk factors for skin complications related to diabetes devices include sensitization to the adhesive used with the devices, as well as prolonged exposure to the device, Dr. Chen said. Younger age also appears to be a risk factor, as is a compromised skin barrier in the area where the device is used.
Unfortunately, obtaining details on the specific adhesives and the raw materials used in these devices, so as to customize patch testing, remains a challenge, she said. “Patch testing initially was often negative to commercially available allergens, even while patients were testing positive to pieces of device adhesive,” she noted.
Consider isobornyl acrylate
An article published in 2017 in Contact Dermatitis was “a major breakthrough” in that it identified isobornyl acrylate (IBOA) as an allergen in connection with the Freestyle Libre, a CGM device that was relatively new at the time. The finding was serendipitous, Dr. Chen said. A patient being treated for suspected allergic contact dermatitis in connection with use of a Freestyle Libre device was tested for IBOA accidentally, after the nurse administering the patch test thought that this was part of the standard acrylate series, she explained.
Subsequently, researchers identified 15 patients who had experienced reactions to the Freestyle Libre; 12 of 13 patients who were patch tested for IBOA tested positive. IBOA was found throughout the device, particularly where the top and bottom plastic components were connected, Dr. Chen said. This suggested that the IBOA was in the device housing and had diffused into the adhesive that attached the device to the skin.
An article published in 2018 in the Journal of Diabetes Science described three patients who developed severe allergic contact dermatitis from IBOA while using a CGM device, Dr. Chen said. The investigators confirmed that there were no reactions to the adhesive itself, again suggesting that IBOA had diffused into the adhesive from other parts of the device.
Although the authors were bound by a confidentiality agreement regarding the individual adhesive components, “the authors noted most of the acrylates in the adhesive were not present in commercially available acrylate series for patch testing,” she said.
IBOA, the ACDS’ Allergen of the Year in 2020, is common in sealants, glues, and adhesives, Dr. Chen said. Although IBOA had been reported infrequently as an allergen, it has now been identified as a “potential culprit” behind skin reactions in many diabetes devices, including CSII and CGM devices, she added.
In addition, N,N-dimethylacrylamide (DMAA) is an allergen that has been identified in several diabetes devices and often occurs with IBOA in medical-grade UV-cured adhesives, Dr. Chen noted. Other allergens identified in diabetes devices include colophony, which is present in many adhesives, as well as other acrylates and epoxy resin.
Diabetes devices are constantly evolving. IBOA is no longer found in Freestyle Libre devices. It is important that clinicians stay up to date with the medical literature and advocate for partnership with device manufacturers, she emphasized.
Patch testing
When diabetes devices are suspected as the source of allergic contact dermatitis, a minimum of a baseline series that contains colophony at a concentration of 20% in petrolatum should be carried out, Dr. Chen said. Commercialized patch test trays, which include plastics, glues, acrylates, epoxy resins/isocyanates, and colophony derivatives, should be ideal. “Personal-care products should be included if they are potentially relevant,” she added.
Dr. Chen shared tables published in Contact Dermatitis in 2021 with examples of screening test series. She said to consider including screening for other allergens more recently discovered in diabetes devices, including 2,2’-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate (MBPA) 1.5% pet; dipropylene glycol diacrylate (DPGDA) 0.1% pet; and butylated hydroxytoluene (BHT) 2% pet.
Testing for monomethyl ether of hydroquinone should also be considered; this may be included in the test preparations for IBOA and DMAA.
Management strategies
For patients who experience skin reactions to their diabetes devices, consideration may given to relocating the device to another area of skin or changing sensors more frequently, according to Dr. Chen.
For some patients, the reaction can be managed with corticosteroid cream, ointment, solution, or nasal spray. Topical antibiotics or topical antihistamines can be helpful, as can barrier dressings, solutions, or sprays, she said. The best solution is to change to a device that does not have the culprit allergen, “but that is difficult, since we don’t know what is in these devices,” she added. Good alternatives include the Eversense CGM device or devices that have been demonstrated not to contain IBOA, such as the Freestyle Libre 2 or the newer version of the Omnipod, an insulin delivery system
Looking ahead, Dr. Chen said that “mandatory labeling is needed, as devices with the same name may have different compositions, depending on the date of manufacture.” Allergens relevant to people with diabetes are constantly evolving, and many are still unidentified, so clinicians and manufacturers need to work together to identify the culprit allergens and their sources, she said.
Dr. Chen has served as principal investigator or subinvestigator for Amgen, AbbVie, and Sanofi Regeneron and as a consultant for Purity Brands.
A version of this article first appeared on Medscape.com.
in a presentation at the annual meeting of the American Contact Dermatitis Society.
Advanced technologies used for the management of diabetes fall into three main categories, said Dr. Chen, of the department of dermatology, Stanford University, Redwood City, Calif. Continuous glucose monitoring (CGM) devices, which are worn on the body, collect glucose measurements. Continuous subcutaneous insulin infusion (CSII) devices are attached to the body via an infusion set and are now available as tubing-free patch pumps that are attached directly to the skin via a catheter. Glucose-responsive insulin delivery systems combine the sensing and delivery features of the other two types of devices.
Once thought to be rare, reports of skin complications related to diabetes devices have been increasing in recent years, she said. Some reports suggest that at any given time, skin complications may affect as many as one quarter to one half of patients who use these devices, “so this is an important issue,” she emphasized. “Skin reactions are a major factor in device discontinuation, so we as clinicians need to be really proactive about treating these reactions.”
Risk factors for skin complications related to diabetes devices include sensitization to the adhesive used with the devices, as well as prolonged exposure to the device, Dr. Chen said. Younger age also appears to be a risk factor, as is a compromised skin barrier in the area where the device is used.
Unfortunately, obtaining details on the specific adhesives and the raw materials used in these devices, so as to customize patch testing, remains a challenge, she said. “Patch testing initially was often negative to commercially available allergens, even while patients were testing positive to pieces of device adhesive,” she noted.
Consider isobornyl acrylate
An article published in 2017 in Contact Dermatitis was “a major breakthrough” in that it identified isobornyl acrylate (IBOA) as an allergen in connection with the Freestyle Libre, a CGM device that was relatively new at the time. The finding was serendipitous, Dr. Chen said. A patient being treated for suspected allergic contact dermatitis in connection with use of a Freestyle Libre device was tested for IBOA accidentally, after the nurse administering the patch test thought that this was part of the standard acrylate series, she explained.
Subsequently, researchers identified 15 patients who had experienced reactions to the Freestyle Libre; 12 of 13 patients who were patch tested for IBOA tested positive. IBOA was found throughout the device, particularly where the top and bottom plastic components were connected, Dr. Chen said. This suggested that the IBOA was in the device housing and had diffused into the adhesive that attached the device to the skin.
An article published in 2018 in the Journal of Diabetes Science described three patients who developed severe allergic contact dermatitis from IBOA while using a CGM device, Dr. Chen said. The investigators confirmed that there were no reactions to the adhesive itself, again suggesting that IBOA had diffused into the adhesive from other parts of the device.
Although the authors were bound by a confidentiality agreement regarding the individual adhesive components, “the authors noted most of the acrylates in the adhesive were not present in commercially available acrylate series for patch testing,” she said.
IBOA, the ACDS’ Allergen of the Year in 2020, is common in sealants, glues, and adhesives, Dr. Chen said. Although IBOA had been reported infrequently as an allergen, it has now been identified as a “potential culprit” behind skin reactions in many diabetes devices, including CSII and CGM devices, she added.
In addition, N,N-dimethylacrylamide (DMAA) is an allergen that has been identified in several diabetes devices and often occurs with IBOA in medical-grade UV-cured adhesives, Dr. Chen noted. Other allergens identified in diabetes devices include colophony, which is present in many adhesives, as well as other acrylates and epoxy resin.
Diabetes devices are constantly evolving. IBOA is no longer found in Freestyle Libre devices. It is important that clinicians stay up to date with the medical literature and advocate for partnership with device manufacturers, she emphasized.
Patch testing
When diabetes devices are suspected as the source of allergic contact dermatitis, a minimum of a baseline series that contains colophony at a concentration of 20% in petrolatum should be carried out, Dr. Chen said. Commercialized patch test trays, which include plastics, glues, acrylates, epoxy resins/isocyanates, and colophony derivatives, should be ideal. “Personal-care products should be included if they are potentially relevant,” she added.
Dr. Chen shared tables published in Contact Dermatitis in 2021 with examples of screening test series. She said to consider including screening for other allergens more recently discovered in diabetes devices, including 2,2’-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate (MBPA) 1.5% pet; dipropylene glycol diacrylate (DPGDA) 0.1% pet; and butylated hydroxytoluene (BHT) 2% pet.
Testing for monomethyl ether of hydroquinone should also be considered; this may be included in the test preparations for IBOA and DMAA.
Management strategies
For patients who experience skin reactions to their diabetes devices, consideration may given to relocating the device to another area of skin or changing sensors more frequently, according to Dr. Chen.
For some patients, the reaction can be managed with corticosteroid cream, ointment, solution, or nasal spray. Topical antibiotics or topical antihistamines can be helpful, as can barrier dressings, solutions, or sprays, she said. The best solution is to change to a device that does not have the culprit allergen, “but that is difficult, since we don’t know what is in these devices,” she added. Good alternatives include the Eversense CGM device or devices that have been demonstrated not to contain IBOA, such as the Freestyle Libre 2 or the newer version of the Omnipod, an insulin delivery system
Looking ahead, Dr. Chen said that “mandatory labeling is needed, as devices with the same name may have different compositions, depending on the date of manufacture.” Allergens relevant to people with diabetes are constantly evolving, and many are still unidentified, so clinicians and manufacturers need to work together to identify the culprit allergens and their sources, she said.
Dr. Chen has served as principal investigator or subinvestigator for Amgen, AbbVie, and Sanofi Regeneron and as a consultant for Purity Brands.
A version of this article first appeared on Medscape.com.
FROM ACDS 2023
Beware the hidden allergens in nutritional supplements
, Alison Ehrlich, MD, said at the annual meeting of the American Contact Dermatitis Society.
Allergens may be hidden in a range of supplement products, from colorings in vitamin C powders to some vitamins used in hair products and other products.
“In general, our patients do not tell us what supplements they are taking,” said Dr. Ehrlich, a dermatologist who practices in Washington, D.C. Antiaging, sleep, and weight loss/weight control supplements are among the most popular, she said.
Surveys have shown that many patients do not discuss supplement use with their health care providers, in part because they believe their providers would disapprove of supplement use, and patients are not educated about supplements, she said. “This is definitely an area that we should try to learn more about,” she added.
Current regulations regarding dietary supplements stem from the Dietary Supplement Health and Education Act of 1994, which defined dietary supplements as distinct from meals but regulated them as a category of food, not as medications. Dietary supplements can be vitamins, minerals, herbs, and extracts, Dr. Ehrlich said.
“There is not a lot of safety wrapped around how supplements come onto the market,” she explained. “It is not the manufacturer’s responsibility to test these products and make sure they are safe. When they get pulled off the market, it is because safety reports are getting back to the FDA.”
Consequently, a detailed history of supplement use is important, as it may reveal possible allergens as the cause of previously unidentified reactions, she said.
Dr. Ehrlich shared a case involving a patient who claimed to have had a reaction to a “Prevage-like” product that was labeled as a crepe repair cream. Listed among the product’s ingredients was idebenone, a synthetic version of the popular antioxidant known as Coenzyme Q.
Be wary of vitamins
Another potential source of allergy is vitamin C supplements, which became especially popular during the pandemic as people sought additional immune system support, Dr. Ehrlich noted. “What kind of vitamin C product our patients are taking is important,” she said. For example, some vitamin C powders contain coloring agents, such as carmine. Some also contain gelatin, which may cause an allergic reaction in individuals with alpha-gal syndrome, she added.
In general, water-soluble vitamins such as vitamins B1 to B9, B12, and C are more likely to cause an immediate reaction, Dr. Ehrlich said. Fat-soluble vitamins, such as vitamins A, D, E, and K, are more likely to cause a delayed reaction of allergic contact dermatitis.
Dr. Ehrlich described some unusual reactions to vitamins that have been reported, including a systemic allergy associated with vitamin B1 (thiamine), burning mouth syndrome associated with vitamin B3 (nicotinate), contact urticaria associated with vitamin B5 (panthenol), systemic allergy and generalized ACD associated with vitamin E (tocopherol), and erythema multiforme–like ACD associated with vitamin K1.
Notably, vitamin B5 has been associated with ACD as an ingredient in hair products, moisturizers, and wound care products, as well as B-complex vitamins and fortified foods, Dr. Ehrlich said.
Herbs and spices can act as allergens as well. Turmeric is a spice that has become a popular supplement ingredient, she said. Turmeric and curcumin (found in turmeric) can be used as a dye for its yellow color as well as a flavoring but has been associated with allergic reactions. Another popular herbal supplement, ginkgo biloba, has been marketed as a product that improves memory and cognition. It is available in pill form and in herbal teas.
“It’s really important to think about what herbal products our patients are taking, and not just in pill form,” Dr. Ehrlich said. “We need to expand our thoughts on what the herbs are in.”
Consider food additives as allergens
Food additives, in the form of colorants, preservatives, or flavoring agents, can cause allergic reactions, Dr. Ehrlich noted.
The question of whether food-additive contact sensitivity has a role in the occurrence of atopic dermatitis (AD) in children remains unclear, she said. However, a study published in 2020 found that 62% of children with AD had positive patch test reactions to at least one food-additive allergen, compared with 20% of children without AD. The additives responsible for the most reactions were azorubine (24.4%); formic acid (15.6%); and carmine, cochineal red, and amaranth (13.3% for each).
Common colorant culprits in allergic reactions include carmine, annatto, tartrazine, and spices (such as paprika and saffron), Dr. Ehrlich said. Carmine is used in meat to prevent photo-oxidation and to preserve a red color, and it has other uses as well, she said. Carmine has been associated with ACD, AD flares, and immediate hypersensitivity. Annatto is used in foods, including processed foods, butter, and cheese, to provide a yellow color. It is also found in some lipsticks and has been associated with urticaria and angioedema, she noted.
Food preservatives that have been associated with allergic reactions include butylated hydroxyanisole and sulfites, Dr. Ehrlich said. Sulfites are used to prevent food from turning brown, and it may be present in dried fruit, fruit juice, molasses, pickled foods, vinegar, and wine.
Reports of ACD in response to sodium metabisulfite have been increasing, she noted. Other sulfite reactions may occur with exposure to other products, such as cosmetics, body washes, and swimming pool water, she said.
Awareness of allergens in supplements is important “because the number of our patients taking supplements for different reasons is increasing” and allergens in supplements could account for flares, Dr. Ehrlich said. Clinicians should encourage patients to tell them what supplements they use. Clinicians should review the ingredients in these supplements with their patients to identify potential allergens that may be causing reactions, she advised.
Dr. Ehrlich has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, Alison Ehrlich, MD, said at the annual meeting of the American Contact Dermatitis Society.
Allergens may be hidden in a range of supplement products, from colorings in vitamin C powders to some vitamins used in hair products and other products.
“In general, our patients do not tell us what supplements they are taking,” said Dr. Ehrlich, a dermatologist who practices in Washington, D.C. Antiaging, sleep, and weight loss/weight control supplements are among the most popular, she said.
Surveys have shown that many patients do not discuss supplement use with their health care providers, in part because they believe their providers would disapprove of supplement use, and patients are not educated about supplements, she said. “This is definitely an area that we should try to learn more about,” she added.
Current regulations regarding dietary supplements stem from the Dietary Supplement Health and Education Act of 1994, which defined dietary supplements as distinct from meals but regulated them as a category of food, not as medications. Dietary supplements can be vitamins, minerals, herbs, and extracts, Dr. Ehrlich said.
“There is not a lot of safety wrapped around how supplements come onto the market,” she explained. “It is not the manufacturer’s responsibility to test these products and make sure they are safe. When they get pulled off the market, it is because safety reports are getting back to the FDA.”
Consequently, a detailed history of supplement use is important, as it may reveal possible allergens as the cause of previously unidentified reactions, she said.
Dr. Ehrlich shared a case involving a patient who claimed to have had a reaction to a “Prevage-like” product that was labeled as a crepe repair cream. Listed among the product’s ingredients was idebenone, a synthetic version of the popular antioxidant known as Coenzyme Q.
Be wary of vitamins
Another potential source of allergy is vitamin C supplements, which became especially popular during the pandemic as people sought additional immune system support, Dr. Ehrlich noted. “What kind of vitamin C product our patients are taking is important,” she said. For example, some vitamin C powders contain coloring agents, such as carmine. Some also contain gelatin, which may cause an allergic reaction in individuals with alpha-gal syndrome, she added.
In general, water-soluble vitamins such as vitamins B1 to B9, B12, and C are more likely to cause an immediate reaction, Dr. Ehrlich said. Fat-soluble vitamins, such as vitamins A, D, E, and K, are more likely to cause a delayed reaction of allergic contact dermatitis.
Dr. Ehrlich described some unusual reactions to vitamins that have been reported, including a systemic allergy associated with vitamin B1 (thiamine), burning mouth syndrome associated with vitamin B3 (nicotinate), contact urticaria associated with vitamin B5 (panthenol), systemic allergy and generalized ACD associated with vitamin E (tocopherol), and erythema multiforme–like ACD associated with vitamin K1.
Notably, vitamin B5 has been associated with ACD as an ingredient in hair products, moisturizers, and wound care products, as well as B-complex vitamins and fortified foods, Dr. Ehrlich said.
Herbs and spices can act as allergens as well. Turmeric is a spice that has become a popular supplement ingredient, she said. Turmeric and curcumin (found in turmeric) can be used as a dye for its yellow color as well as a flavoring but has been associated with allergic reactions. Another popular herbal supplement, ginkgo biloba, has been marketed as a product that improves memory and cognition. It is available in pill form and in herbal teas.
“It’s really important to think about what herbal products our patients are taking, and not just in pill form,” Dr. Ehrlich said. “We need to expand our thoughts on what the herbs are in.”
Consider food additives as allergens
Food additives, in the form of colorants, preservatives, or flavoring agents, can cause allergic reactions, Dr. Ehrlich noted.
The question of whether food-additive contact sensitivity has a role in the occurrence of atopic dermatitis (AD) in children remains unclear, she said. However, a study published in 2020 found that 62% of children with AD had positive patch test reactions to at least one food-additive allergen, compared with 20% of children without AD. The additives responsible for the most reactions were azorubine (24.4%); formic acid (15.6%); and carmine, cochineal red, and amaranth (13.3% for each).
Common colorant culprits in allergic reactions include carmine, annatto, tartrazine, and spices (such as paprika and saffron), Dr. Ehrlich said. Carmine is used in meat to prevent photo-oxidation and to preserve a red color, and it has other uses as well, she said. Carmine has been associated with ACD, AD flares, and immediate hypersensitivity. Annatto is used in foods, including processed foods, butter, and cheese, to provide a yellow color. It is also found in some lipsticks and has been associated with urticaria and angioedema, she noted.
Food preservatives that have been associated with allergic reactions include butylated hydroxyanisole and sulfites, Dr. Ehrlich said. Sulfites are used to prevent food from turning brown, and it may be present in dried fruit, fruit juice, molasses, pickled foods, vinegar, and wine.
Reports of ACD in response to sodium metabisulfite have been increasing, she noted. Other sulfite reactions may occur with exposure to other products, such as cosmetics, body washes, and swimming pool water, she said.
Awareness of allergens in supplements is important “because the number of our patients taking supplements for different reasons is increasing” and allergens in supplements could account for flares, Dr. Ehrlich said. Clinicians should encourage patients to tell them what supplements they use. Clinicians should review the ingredients in these supplements with their patients to identify potential allergens that may be causing reactions, she advised.
Dr. Ehrlich has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, Alison Ehrlich, MD, said at the annual meeting of the American Contact Dermatitis Society.
Allergens may be hidden in a range of supplement products, from colorings in vitamin C powders to some vitamins used in hair products and other products.
“In general, our patients do not tell us what supplements they are taking,” said Dr. Ehrlich, a dermatologist who practices in Washington, D.C. Antiaging, sleep, and weight loss/weight control supplements are among the most popular, she said.
Surveys have shown that many patients do not discuss supplement use with their health care providers, in part because they believe their providers would disapprove of supplement use, and patients are not educated about supplements, she said. “This is definitely an area that we should try to learn more about,” she added.
Current regulations regarding dietary supplements stem from the Dietary Supplement Health and Education Act of 1994, which defined dietary supplements as distinct from meals but regulated them as a category of food, not as medications. Dietary supplements can be vitamins, minerals, herbs, and extracts, Dr. Ehrlich said.
“There is not a lot of safety wrapped around how supplements come onto the market,” she explained. “It is not the manufacturer’s responsibility to test these products and make sure they are safe. When they get pulled off the market, it is because safety reports are getting back to the FDA.”
Consequently, a detailed history of supplement use is important, as it may reveal possible allergens as the cause of previously unidentified reactions, she said.
Dr. Ehrlich shared a case involving a patient who claimed to have had a reaction to a “Prevage-like” product that was labeled as a crepe repair cream. Listed among the product’s ingredients was idebenone, a synthetic version of the popular antioxidant known as Coenzyme Q.
Be wary of vitamins
Another potential source of allergy is vitamin C supplements, which became especially popular during the pandemic as people sought additional immune system support, Dr. Ehrlich noted. “What kind of vitamin C product our patients are taking is important,” she said. For example, some vitamin C powders contain coloring agents, such as carmine. Some also contain gelatin, which may cause an allergic reaction in individuals with alpha-gal syndrome, she added.
In general, water-soluble vitamins such as vitamins B1 to B9, B12, and C are more likely to cause an immediate reaction, Dr. Ehrlich said. Fat-soluble vitamins, such as vitamins A, D, E, and K, are more likely to cause a delayed reaction of allergic contact dermatitis.
Dr. Ehrlich described some unusual reactions to vitamins that have been reported, including a systemic allergy associated with vitamin B1 (thiamine), burning mouth syndrome associated with vitamin B3 (nicotinate), contact urticaria associated with vitamin B5 (panthenol), systemic allergy and generalized ACD associated with vitamin E (tocopherol), and erythema multiforme–like ACD associated with vitamin K1.
Notably, vitamin B5 has been associated with ACD as an ingredient in hair products, moisturizers, and wound care products, as well as B-complex vitamins and fortified foods, Dr. Ehrlich said.
Herbs and spices can act as allergens as well. Turmeric is a spice that has become a popular supplement ingredient, she said. Turmeric and curcumin (found in turmeric) can be used as a dye for its yellow color as well as a flavoring but has been associated with allergic reactions. Another popular herbal supplement, ginkgo biloba, has been marketed as a product that improves memory and cognition. It is available in pill form and in herbal teas.
“It’s really important to think about what herbal products our patients are taking, and not just in pill form,” Dr. Ehrlich said. “We need to expand our thoughts on what the herbs are in.”
Consider food additives as allergens
Food additives, in the form of colorants, preservatives, or flavoring agents, can cause allergic reactions, Dr. Ehrlich noted.
The question of whether food-additive contact sensitivity has a role in the occurrence of atopic dermatitis (AD) in children remains unclear, she said. However, a study published in 2020 found that 62% of children with AD had positive patch test reactions to at least one food-additive allergen, compared with 20% of children without AD. The additives responsible for the most reactions were azorubine (24.4%); formic acid (15.6%); and carmine, cochineal red, and amaranth (13.3% for each).
Common colorant culprits in allergic reactions include carmine, annatto, tartrazine, and spices (such as paprika and saffron), Dr. Ehrlich said. Carmine is used in meat to prevent photo-oxidation and to preserve a red color, and it has other uses as well, she said. Carmine has been associated with ACD, AD flares, and immediate hypersensitivity. Annatto is used in foods, including processed foods, butter, and cheese, to provide a yellow color. It is also found in some lipsticks and has been associated with urticaria and angioedema, she noted.
Food preservatives that have been associated with allergic reactions include butylated hydroxyanisole and sulfites, Dr. Ehrlich said. Sulfites are used to prevent food from turning brown, and it may be present in dried fruit, fruit juice, molasses, pickled foods, vinegar, and wine.
Reports of ACD in response to sodium metabisulfite have been increasing, she noted. Other sulfite reactions may occur with exposure to other products, such as cosmetics, body washes, and swimming pool water, she said.
Awareness of allergens in supplements is important “because the number of our patients taking supplements for different reasons is increasing” and allergens in supplements could account for flares, Dr. Ehrlich said. Clinicians should encourage patients to tell them what supplements they use. Clinicians should review the ingredients in these supplements with their patients to identify potential allergens that may be causing reactions, she advised.
Dr. Ehrlich has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACDS 2023
Controlled hyperthermia: Novel treatment of BCCs without surgery continues to be refined
PHOENIX – .
“For 2,000 years, it’s been known that heat can kill cancers,” an apoptotic reaction “rather than a destructive reaction coming from excessive heat,” Christopher B. Zachary, MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the study was presented during an abstract session.
Dr. Zachary, professor and chair emeritus of the department of dermatology at the University of California, Irvine, and colleagues, evaluated a novel, noninvasive technique of controlled hyperthermia and mapping protocol (CHAMP) designed to help clinicians with margin assessment and treatment of superficial and nodular BCCs. For this prospective study, which was first described at the 2022 ASLMS annual conference and is being conducted at three centers, 73 patients with biopsy-proven superficial and nodular BCCs have been scanned with the VivoSight Dx optical coherence tomography (OCT) device to map BCC tumor margins.
The BCCs were treated with the Sciton 1,064-nm Er:YAG laser equipped with a 4-mm beam diameter scan pattern with no overlap and an 8-millisecond pulse duration, randomized to either standard 120-140 J/cm2 pulses until tissue graying and contraction was observed, or the CHAMP controlled hyperthermia technique using repeated 25 J/cm2 pulses under thermal camera imaging to maintain a consistent temperature of 55º C for 60 seconds. Patients were rescanned by OCT at 3 to 12 months for any signs of residual tumor and if positive, were retreated. Finally, lesions were excised for evidence of histological clearance.
To date, 48 patients have completed the study. Among the 26 patients treated with the CHAMP method, 22 (84.6%) were histologically clear, as were 19 of the 22 (86.4%) in the standard treatment group. Ulceration was uncommon with the CHAMP method, and patients healed with modest erythema, Dr. Zachary said.
Pretreatment OCT mapping of BCCs indicated that tumors extended beyond their 5-mm clinical margins in 11 cases (15%). “This will be of interest to those who treat BCCs by Mohs or standard excision,” he said. Increased vascularity measured by dynamic OCT was noted in most CHAMP patients immediately after irradiation, which suggests that apoptosis was the primary mechanism of tumor response instead of vascular destruction.
“The traditional technique for using the long pulsed 1,064-nm Er:YAG laser to cause damage and destruction of BCC is 120-140 J/cm2 at one or two passes until you get to an endpoint of graying and contraction of tissue,” Dr. Zachary said. “That’s opposed to the ‘Low and Slow’ approach [where you use] multiple pulses at 25 J/cm2 until you achieve an optimal time and temperature. If you treat above 60º C, you tend to get epidermal blistering, prolonged healing, and interestingly, absence of pain. I think that’s because you kill off the nerve fibers. With the low fluence multiple scan technique, you’re going for an even flat-top heating.”
Currently, he and his colleagues consider 55 degrees at 60 seconds as “the optimal parameters,” he said, but “it could be 45 degrees at 90 seconds or two minutes. We don’t know yet.”
In an interview at the meeting, one of the abstract session moderators, Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, said that he was encouraged by the study results as investigations into effective, noninvasive treatment of BCC continue to move forward. “Details matter such as the temperature [of energy delivery] and noninvasive imaging to delineate the appropriate margins,” said Dr. Avram, who has conducted research on the 1,064-nm long-pulsed Nd:YAG laser as an alternative treatment for nonfacial BCCs in patients who are poor surgical candidates.
“Hopefully, at some point,” he said, such approaches will “become the standard of care for many BCCs that we are now treating surgically. I don’t think this will happen in the next 3 years, but I think in the long term, it will emerge as the treatment of choice.”
The study is being funded by Michelson Diagnostics. Sciton provided the long-pulsed 1,064-nm lasers devices being used in the trial. Dr. Zachary reported having no relevant disclosures. Dr. Avram disclosed that he has received consulting fees from Sciton.
PHOENIX – .
“For 2,000 years, it’s been known that heat can kill cancers,” an apoptotic reaction “rather than a destructive reaction coming from excessive heat,” Christopher B. Zachary, MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the study was presented during an abstract session.
Dr. Zachary, professor and chair emeritus of the department of dermatology at the University of California, Irvine, and colleagues, evaluated a novel, noninvasive technique of controlled hyperthermia and mapping protocol (CHAMP) designed to help clinicians with margin assessment and treatment of superficial and nodular BCCs. For this prospective study, which was first described at the 2022 ASLMS annual conference and is being conducted at three centers, 73 patients with biopsy-proven superficial and nodular BCCs have been scanned with the VivoSight Dx optical coherence tomography (OCT) device to map BCC tumor margins.
The BCCs were treated with the Sciton 1,064-nm Er:YAG laser equipped with a 4-mm beam diameter scan pattern with no overlap and an 8-millisecond pulse duration, randomized to either standard 120-140 J/cm2 pulses until tissue graying and contraction was observed, or the CHAMP controlled hyperthermia technique using repeated 25 J/cm2 pulses under thermal camera imaging to maintain a consistent temperature of 55º C for 60 seconds. Patients were rescanned by OCT at 3 to 12 months for any signs of residual tumor and if positive, were retreated. Finally, lesions were excised for evidence of histological clearance.
To date, 48 patients have completed the study. Among the 26 patients treated with the CHAMP method, 22 (84.6%) were histologically clear, as were 19 of the 22 (86.4%) in the standard treatment group. Ulceration was uncommon with the CHAMP method, and patients healed with modest erythema, Dr. Zachary said.
Pretreatment OCT mapping of BCCs indicated that tumors extended beyond their 5-mm clinical margins in 11 cases (15%). “This will be of interest to those who treat BCCs by Mohs or standard excision,” he said. Increased vascularity measured by dynamic OCT was noted in most CHAMP patients immediately after irradiation, which suggests that apoptosis was the primary mechanism of tumor response instead of vascular destruction.
“The traditional technique for using the long pulsed 1,064-nm Er:YAG laser to cause damage and destruction of BCC is 120-140 J/cm2 at one or two passes until you get to an endpoint of graying and contraction of tissue,” Dr. Zachary said. “That’s opposed to the ‘Low and Slow’ approach [where you use] multiple pulses at 25 J/cm2 until you achieve an optimal time and temperature. If you treat above 60º C, you tend to get epidermal blistering, prolonged healing, and interestingly, absence of pain. I think that’s because you kill off the nerve fibers. With the low fluence multiple scan technique, you’re going for an even flat-top heating.”
Currently, he and his colleagues consider 55 degrees at 60 seconds as “the optimal parameters,” he said, but “it could be 45 degrees at 90 seconds or two minutes. We don’t know yet.”
In an interview at the meeting, one of the abstract session moderators, Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, said that he was encouraged by the study results as investigations into effective, noninvasive treatment of BCC continue to move forward. “Details matter such as the temperature [of energy delivery] and noninvasive imaging to delineate the appropriate margins,” said Dr. Avram, who has conducted research on the 1,064-nm long-pulsed Nd:YAG laser as an alternative treatment for nonfacial BCCs in patients who are poor surgical candidates.
“Hopefully, at some point,” he said, such approaches will “become the standard of care for many BCCs that we are now treating surgically. I don’t think this will happen in the next 3 years, but I think in the long term, it will emerge as the treatment of choice.”
The study is being funded by Michelson Diagnostics. Sciton provided the long-pulsed 1,064-nm lasers devices being used in the trial. Dr. Zachary reported having no relevant disclosures. Dr. Avram disclosed that he has received consulting fees from Sciton.
PHOENIX – .
“For 2,000 years, it’s been known that heat can kill cancers,” an apoptotic reaction “rather than a destructive reaction coming from excessive heat,” Christopher B. Zachary, MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the study was presented during an abstract session.
Dr. Zachary, professor and chair emeritus of the department of dermatology at the University of California, Irvine, and colleagues, evaluated a novel, noninvasive technique of controlled hyperthermia and mapping protocol (CHAMP) designed to help clinicians with margin assessment and treatment of superficial and nodular BCCs. For this prospective study, which was first described at the 2022 ASLMS annual conference and is being conducted at three centers, 73 patients with biopsy-proven superficial and nodular BCCs have been scanned with the VivoSight Dx optical coherence tomography (OCT) device to map BCC tumor margins.
The BCCs were treated with the Sciton 1,064-nm Er:YAG laser equipped with a 4-mm beam diameter scan pattern with no overlap and an 8-millisecond pulse duration, randomized to either standard 120-140 J/cm2 pulses until tissue graying and contraction was observed, or the CHAMP controlled hyperthermia technique using repeated 25 J/cm2 pulses under thermal camera imaging to maintain a consistent temperature of 55º C for 60 seconds. Patients were rescanned by OCT at 3 to 12 months for any signs of residual tumor and if positive, were retreated. Finally, lesions were excised for evidence of histological clearance.
To date, 48 patients have completed the study. Among the 26 patients treated with the CHAMP method, 22 (84.6%) were histologically clear, as were 19 of the 22 (86.4%) in the standard treatment group. Ulceration was uncommon with the CHAMP method, and patients healed with modest erythema, Dr. Zachary said.
Pretreatment OCT mapping of BCCs indicated that tumors extended beyond their 5-mm clinical margins in 11 cases (15%). “This will be of interest to those who treat BCCs by Mohs or standard excision,” he said. Increased vascularity measured by dynamic OCT was noted in most CHAMP patients immediately after irradiation, which suggests that apoptosis was the primary mechanism of tumor response instead of vascular destruction.
“The traditional technique for using the long pulsed 1,064-nm Er:YAG laser to cause damage and destruction of BCC is 120-140 J/cm2 at one or two passes until you get to an endpoint of graying and contraction of tissue,” Dr. Zachary said. “That’s opposed to the ‘Low and Slow’ approach [where you use] multiple pulses at 25 J/cm2 until you achieve an optimal time and temperature. If you treat above 60º C, you tend to get epidermal blistering, prolonged healing, and interestingly, absence of pain. I think that’s because you kill off the nerve fibers. With the low fluence multiple scan technique, you’re going for an even flat-top heating.”
Currently, he and his colleagues consider 55 degrees at 60 seconds as “the optimal parameters,” he said, but “it could be 45 degrees at 90 seconds or two minutes. We don’t know yet.”
In an interview at the meeting, one of the abstract session moderators, Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, said that he was encouraged by the study results as investigations into effective, noninvasive treatment of BCC continue to move forward. “Details matter such as the temperature [of energy delivery] and noninvasive imaging to delineate the appropriate margins,” said Dr. Avram, who has conducted research on the 1,064-nm long-pulsed Nd:YAG laser as an alternative treatment for nonfacial BCCs in patients who are poor surgical candidates.
“Hopefully, at some point,” he said, such approaches will “become the standard of care for many BCCs that we are now treating surgically. I don’t think this will happen in the next 3 years, but I think in the long term, it will emerge as the treatment of choice.”
The study is being funded by Michelson Diagnostics. Sciton provided the long-pulsed 1,064-nm lasers devices being used in the trial. Dr. Zachary reported having no relevant disclosures. Dr. Avram disclosed that he has received consulting fees from Sciton.
AT ASLMS 2023
COVID-19 and psoriasis: Is there a link?
.
Psoriasis has several well-established triggers, including stress, skin injury, cold or warm air, and allergies. Illnesses like strep throat can also cause a psoriasis flare in some people – and it appears COVID may also do so. “Psoriasis flares have long been associated with bacterial and viral infections, particularly a form of psoriasis called guttate, which is characterized by tons of tiny red scaly bumps all over the body,” said Joel M. Gelfand, MD, a professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia. “Infection with COVID-19 has been associated with flares of guttate and pustular psoriasis, and even psoriasis that affects 100% of the skin ... in many published case reports.”
Israeli researchers recently found that psoriasis patients have a slightly higher risk of getting COVID, although they are not at higher risk of hospitalization or death, which could be related to treatment with immune-modulating therapy, which can increase their risk of infections.
How could COVID cause psoriasis to flare?
Psoriasis is an autoimmune condition, and inflammation can cause symptoms.
Investigators for a study from Albany (N.Y.) Medical College and Weirton (Pa.) Medical Center found that people in the study who were already diagnosed with the skin condition had an unexpected flare within a week to a month after testing positive for COVID. New psoriasis after a COVID infection was also found. The researchers think this could be because COVID causes inflammation in the body, which negatively affects previously well-controlled psoriasis. They also think it’s possible that COVID-related inflammation could trigger a genetic tendency to have psoriasis, which may explain why it can appear for the first time after a positive test.
“A viral infection like COVID-19 can signal the release of proinflammatory factors that can appear as rashes, such as with psoriasis.” said Robert O. Carpenter, MD, director of wellness at Texas A&M University in Bryan.
What are the symptoms of COVID-related psoriasis?
The signs are the same as those of any form of psoriasis.
For a patient with psoriasis, will COVID automatically make it worse?
Not necessarily.
“Psoriasis is a common condition, so people should be aware that new psoriasis that develops may not be related to COVID-19,” said Esther Freeman MD, PhD, director of global health dermatology at Massachusetts General Hospital in Boston.
As with every aspect of COVID, doctors and scientists are still learning about how serious and widespread a problem psoriasis after COVID-19 may be. “We have seen case reports that psoriasis can flare after COVID-19,” said Dr. Freeman, who is also an associate professor of dermatology at Harvard Medical School. “I will say, this has not been a tidal wave – more like sporadic cases here and there. So I do not think psoriasis flares are a major post-COVID finding, nor do they necessarily mean you have long COVID. That being said, we know that many different infections can cause psoriasis flares, and so, in that respect, it’s not that surprising that SARS-CoV-2, like other infections, could trigger a psoriasis flare.”
Could getting COVID more than once cause psoriasis to flare? It’s possible.
“Your body can change after having COVID-19,” said Dr. Carpenter. “We don’t know the long-term implications, but having COVID-19 repeatedly can increase the risk of long COVID, which can cause many systemic changes in your body.”
Another important point: For patients who take biologics for treating psoriasis, getting vaccinated and boosted for COVID is an important step to take to help protect themselves.
Is psoriasis itself a potential symptom of COVID?
“Yes, but we don’t know the frequency at which this may occur, and a causal relationship is difficult to establish from just case reports,” said Dr. Gelfand, who’s also medical director of the clinical studies unit in the department of dermatology at his university. “Typically, if a patient presents with a flare of psoriasis, particularly guttate, pustular, or erythrodermic forms, an infectious trigger should be considered, and testing for strep and possibly COVID-19 may be appropriate.”
A version of this article first appeared on Medscape.com.
.
Psoriasis has several well-established triggers, including stress, skin injury, cold or warm air, and allergies. Illnesses like strep throat can also cause a psoriasis flare in some people – and it appears COVID may also do so. “Psoriasis flares have long been associated with bacterial and viral infections, particularly a form of psoriasis called guttate, which is characterized by tons of tiny red scaly bumps all over the body,” said Joel M. Gelfand, MD, a professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia. “Infection with COVID-19 has been associated with flares of guttate and pustular psoriasis, and even psoriasis that affects 100% of the skin ... in many published case reports.”
Israeli researchers recently found that psoriasis patients have a slightly higher risk of getting COVID, although they are not at higher risk of hospitalization or death, which could be related to treatment with immune-modulating therapy, which can increase their risk of infections.
How could COVID cause psoriasis to flare?
Psoriasis is an autoimmune condition, and inflammation can cause symptoms.
Investigators for a study from Albany (N.Y.) Medical College and Weirton (Pa.) Medical Center found that people in the study who were already diagnosed with the skin condition had an unexpected flare within a week to a month after testing positive for COVID. New psoriasis after a COVID infection was also found. The researchers think this could be because COVID causes inflammation in the body, which negatively affects previously well-controlled psoriasis. They also think it’s possible that COVID-related inflammation could trigger a genetic tendency to have psoriasis, which may explain why it can appear for the first time after a positive test.
“A viral infection like COVID-19 can signal the release of proinflammatory factors that can appear as rashes, such as with psoriasis.” said Robert O. Carpenter, MD, director of wellness at Texas A&M University in Bryan.
What are the symptoms of COVID-related psoriasis?
The signs are the same as those of any form of psoriasis.
For a patient with psoriasis, will COVID automatically make it worse?
Not necessarily.
“Psoriasis is a common condition, so people should be aware that new psoriasis that develops may not be related to COVID-19,” said Esther Freeman MD, PhD, director of global health dermatology at Massachusetts General Hospital in Boston.
As with every aspect of COVID, doctors and scientists are still learning about how serious and widespread a problem psoriasis after COVID-19 may be. “We have seen case reports that psoriasis can flare after COVID-19,” said Dr. Freeman, who is also an associate professor of dermatology at Harvard Medical School. “I will say, this has not been a tidal wave – more like sporadic cases here and there. So I do not think psoriasis flares are a major post-COVID finding, nor do they necessarily mean you have long COVID. That being said, we know that many different infections can cause psoriasis flares, and so, in that respect, it’s not that surprising that SARS-CoV-2, like other infections, could trigger a psoriasis flare.”
Could getting COVID more than once cause psoriasis to flare? It’s possible.
“Your body can change after having COVID-19,” said Dr. Carpenter. “We don’t know the long-term implications, but having COVID-19 repeatedly can increase the risk of long COVID, which can cause many systemic changes in your body.”
Another important point: For patients who take biologics for treating psoriasis, getting vaccinated and boosted for COVID is an important step to take to help protect themselves.
Is psoriasis itself a potential symptom of COVID?
“Yes, but we don’t know the frequency at which this may occur, and a causal relationship is difficult to establish from just case reports,” said Dr. Gelfand, who’s also medical director of the clinical studies unit in the department of dermatology at his university. “Typically, if a patient presents with a flare of psoriasis, particularly guttate, pustular, or erythrodermic forms, an infectious trigger should be considered, and testing for strep and possibly COVID-19 may be appropriate.”
A version of this article first appeared on Medscape.com.
.
Psoriasis has several well-established triggers, including stress, skin injury, cold or warm air, and allergies. Illnesses like strep throat can also cause a psoriasis flare in some people – and it appears COVID may also do so. “Psoriasis flares have long been associated with bacterial and viral infections, particularly a form of psoriasis called guttate, which is characterized by tons of tiny red scaly bumps all over the body,” said Joel M. Gelfand, MD, a professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia. “Infection with COVID-19 has been associated with flares of guttate and pustular psoriasis, and even psoriasis that affects 100% of the skin ... in many published case reports.”
Israeli researchers recently found that psoriasis patients have a slightly higher risk of getting COVID, although they are not at higher risk of hospitalization or death, which could be related to treatment with immune-modulating therapy, which can increase their risk of infections.
How could COVID cause psoriasis to flare?
Psoriasis is an autoimmune condition, and inflammation can cause symptoms.
Investigators for a study from Albany (N.Y.) Medical College and Weirton (Pa.) Medical Center found that people in the study who were already diagnosed with the skin condition had an unexpected flare within a week to a month after testing positive for COVID. New psoriasis after a COVID infection was also found. The researchers think this could be because COVID causes inflammation in the body, which negatively affects previously well-controlled psoriasis. They also think it’s possible that COVID-related inflammation could trigger a genetic tendency to have psoriasis, which may explain why it can appear for the first time after a positive test.
“A viral infection like COVID-19 can signal the release of proinflammatory factors that can appear as rashes, such as with psoriasis.” said Robert O. Carpenter, MD, director of wellness at Texas A&M University in Bryan.
What are the symptoms of COVID-related psoriasis?
The signs are the same as those of any form of psoriasis.
For a patient with psoriasis, will COVID automatically make it worse?
Not necessarily.
“Psoriasis is a common condition, so people should be aware that new psoriasis that develops may not be related to COVID-19,” said Esther Freeman MD, PhD, director of global health dermatology at Massachusetts General Hospital in Boston.
As with every aspect of COVID, doctors and scientists are still learning about how serious and widespread a problem psoriasis after COVID-19 may be. “We have seen case reports that psoriasis can flare after COVID-19,” said Dr. Freeman, who is also an associate professor of dermatology at Harvard Medical School. “I will say, this has not been a tidal wave – more like sporadic cases here and there. So I do not think psoriasis flares are a major post-COVID finding, nor do they necessarily mean you have long COVID. That being said, we know that many different infections can cause psoriasis flares, and so, in that respect, it’s not that surprising that SARS-CoV-2, like other infections, could trigger a psoriasis flare.”
Could getting COVID more than once cause psoriasis to flare? It’s possible.
“Your body can change after having COVID-19,” said Dr. Carpenter. “We don’t know the long-term implications, but having COVID-19 repeatedly can increase the risk of long COVID, which can cause many systemic changes in your body.”
Another important point: For patients who take biologics for treating psoriasis, getting vaccinated and boosted for COVID is an important step to take to help protect themselves.
Is psoriasis itself a potential symptom of COVID?
“Yes, but we don’t know the frequency at which this may occur, and a causal relationship is difficult to establish from just case reports,” said Dr. Gelfand, who’s also medical director of the clinical studies unit in the department of dermatology at his university. “Typically, if a patient presents with a flare of psoriasis, particularly guttate, pustular, or erythrodermic forms, an infectious trigger should be considered, and testing for strep and possibly COVID-19 may be appropriate.”
A version of this article first appeared on Medscape.com.
FDA puts partial hold on investigational alopecia areata drug deuruxolitinib
The in a press release on May 2.
The announcement came after a pulmonary embolism occurred with the 12-mg twice-daily dose in one of the long-term open-label extension (OLE) studies, the company, Sun Pharmaceutical Industries, said.
The company stated that the FDA has placed the Investigational New Drug testing for deuruxolitinib on partial clinical hold, and the agency is requiring that study participants who are currently on the 12-mg twice-daily dose in the OLE studies stop taking that dose. The hold covers only the 12-mg dose.
No hold on 8-mg dose
“There have been no thrombotic events reported to date for the 8-mg b.i.d. dose and U.S. FDA has not placed the 8-mg b.i.d. dose on hold,” the company said in the statement.
The statement added, “We are taking immediate steps to transition the patients in the OLE studies to the 8-mg b.i.d. dose arm in the ongoing studies.”
The company said that no thromboembolic events were observed in the phase 2 or phase 3 trials and said that it will work closely with the FDA to address its concerns. A formal letter detailing the FDA’s concerns is expected within 30 days.
Deuruxolitinib is an investigational oral selective inhibitor of Janus kinase 1 (JAK1) and JAK2 enzymes.
The FDA has granted deuruxolitinib breakthrough therapy designation for the treatment of adult patients with moderate to severe alopecia areata as well as fast-track designation for the treatment of alopecia areata.
In March, this news organization reported from the annual meeting of the American Academy of Dermatology that, based on phase 3 studies that demonstrate robust hair growth in about one-third of patients, deuruxolitinib has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received FDA approval almost 1 year ago.
Also at the AAD annual meeting, this news organization reported that principal investigator Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., in his presentation on the results of THRIVE-AA2, one of the two phase 3 trials of deuruxolitinib, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.” Dr King also was a principal investigator in studies of baricitinib.
With one exception, labeling for baricitinib and other JAK inhibitors with dermatologic indications includes a boxed warning listing serious adverse events including the risk for major adverse cardiac events and thrombosis, including pulmonary embolism, based on the risks in a rheumatoid arthritis study.
A version of this article first appeared on Medscape.com.
The in a press release on May 2.
The announcement came after a pulmonary embolism occurred with the 12-mg twice-daily dose in one of the long-term open-label extension (OLE) studies, the company, Sun Pharmaceutical Industries, said.
The company stated that the FDA has placed the Investigational New Drug testing for deuruxolitinib on partial clinical hold, and the agency is requiring that study participants who are currently on the 12-mg twice-daily dose in the OLE studies stop taking that dose. The hold covers only the 12-mg dose.
No hold on 8-mg dose
“There have been no thrombotic events reported to date for the 8-mg b.i.d. dose and U.S. FDA has not placed the 8-mg b.i.d. dose on hold,” the company said in the statement.
The statement added, “We are taking immediate steps to transition the patients in the OLE studies to the 8-mg b.i.d. dose arm in the ongoing studies.”
The company said that no thromboembolic events were observed in the phase 2 or phase 3 trials and said that it will work closely with the FDA to address its concerns. A formal letter detailing the FDA’s concerns is expected within 30 days.
Deuruxolitinib is an investigational oral selective inhibitor of Janus kinase 1 (JAK1) and JAK2 enzymes.
The FDA has granted deuruxolitinib breakthrough therapy designation for the treatment of adult patients with moderate to severe alopecia areata as well as fast-track designation for the treatment of alopecia areata.
In March, this news organization reported from the annual meeting of the American Academy of Dermatology that, based on phase 3 studies that demonstrate robust hair growth in about one-third of patients, deuruxolitinib has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received FDA approval almost 1 year ago.
Also at the AAD annual meeting, this news organization reported that principal investigator Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., in his presentation on the results of THRIVE-AA2, one of the two phase 3 trials of deuruxolitinib, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.” Dr King also was a principal investigator in studies of baricitinib.
With one exception, labeling for baricitinib and other JAK inhibitors with dermatologic indications includes a boxed warning listing serious adverse events including the risk for major adverse cardiac events and thrombosis, including pulmonary embolism, based on the risks in a rheumatoid arthritis study.
A version of this article first appeared on Medscape.com.
The in a press release on May 2.
The announcement came after a pulmonary embolism occurred with the 12-mg twice-daily dose in one of the long-term open-label extension (OLE) studies, the company, Sun Pharmaceutical Industries, said.
The company stated that the FDA has placed the Investigational New Drug testing for deuruxolitinib on partial clinical hold, and the agency is requiring that study participants who are currently on the 12-mg twice-daily dose in the OLE studies stop taking that dose. The hold covers only the 12-mg dose.
No hold on 8-mg dose
“There have been no thrombotic events reported to date for the 8-mg b.i.d. dose and U.S. FDA has not placed the 8-mg b.i.d. dose on hold,” the company said in the statement.
The statement added, “We are taking immediate steps to transition the patients in the OLE studies to the 8-mg b.i.d. dose arm in the ongoing studies.”
The company said that no thromboembolic events were observed in the phase 2 or phase 3 trials and said that it will work closely with the FDA to address its concerns. A formal letter detailing the FDA’s concerns is expected within 30 days.
Deuruxolitinib is an investigational oral selective inhibitor of Janus kinase 1 (JAK1) and JAK2 enzymes.
The FDA has granted deuruxolitinib breakthrough therapy designation for the treatment of adult patients with moderate to severe alopecia areata as well as fast-track designation for the treatment of alopecia areata.
In March, this news organization reported from the annual meeting of the American Academy of Dermatology that, based on phase 3 studies that demonstrate robust hair growth in about one-third of patients, deuruxolitinib has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received FDA approval almost 1 year ago.
Also at the AAD annual meeting, this news organization reported that principal investigator Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., in his presentation on the results of THRIVE-AA2, one of the two phase 3 trials of deuruxolitinib, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.” Dr King also was a principal investigator in studies of baricitinib.
With one exception, labeling for baricitinib and other JAK inhibitors with dermatologic indications includes a boxed warning listing serious adverse events including the risk for major adverse cardiac events and thrombosis, including pulmonary embolism, based on the risks in a rheumatoid arthritis study.
A version of this article first appeared on Medscape.com.
Gray hair and aging: Could ‘stuck’ stem cells be to blame?
New evidence points more to a cycle wherein undifferentiated stem cells mature to perform their hair-coloring duties and then transform back to their primitive form. To accomplish this, they need to stay on the move.
When these special stem cells get “stuck” in the follicle, gray hair is the result, according to a new study reported online in Nature.
The regeneration cycle of melanocyte stem cells (McSCs) to melanocytes and back again can last for years. However, McSCs die sooner than do other cells nearby, such as hair follicle stem cells. This difference can explain why people go gray but still grow hair.
“It was thought that melanocyte stem cells are maintained in an undifferentiated state, instead of repeating differentiation and de-differentiation,” said the study’s senior investigator Mayumi Ito, PhD, professor in the departments of dermatology and cell biology at NYU Langone Health, New York.
The process involves different compartments in the hair follicle – the germ area is where the stem cells regenerate; the follicle bulge is where they get stuck. A different microenvironment in each location dictates how they change. This “chameleon-like” property surprised researchers.
Now that investigators figured out how gray hair might get started, a next step will be to search for a way to stop it.
The research has been performed in mice to date but could translate to humans. “Because the structure of the hair follicle is similar between mice and humans, we speculate that human melanocytes may also demonstrate the plasticity during hair regeneration,” Dr. Ito told this news organization.
Future findings could also lead to new therapies. “Our study suggests that moving melanocytes to a proper location within the hair follicle may help prevent gray hair,” Dr. Ito said.
Given the known effects of ultraviolet B (UVB) radiation on melanocytes, Dr. Ito and colleagues wanted to see what effect it might have on this cycle. So in the study, they exposed hair follicles of mice to UVB radiation and report it speeds up the process for McSCs to transform to color-producing melanocytes. They found that these McSCs can regenerate or change back to undifferentiated stem cells, so UVB radiation does not interrupt the process.
A melanoma clue?
The study also could have implications for melanoma. Unlike other tumors, melanocytes that cause cancer can self-renew even from a fully differentiated, pigmented form, the researchers note.
This makes melanomas more difficult to eliminate.
“Our study suggests normal melanocytes are very plastic and can reverse a differentiation state. Melanoma cells are known to be very plastic,” Dr. Ito said. “We consider this feature of melanoma may be related to the high plasticity of original melanocytes.”
The finding that melanocyte stem cells “are more plastic than maybe previously given credit for … certainly has implications in melanoma,” agreed Melissa Harris, PhD, associate professor, department of biology at the University of Alabama, Birmingham, when asked to comment on the study.
Small technology, big insights?
The advanced technology used by Dr. Ito and colleagues in the study included 3D-intravital imaging and single-cell RNA sequencing to track the stem cells in almost real time as they aged and moved within each hair follicle.
“This paper uses a nice mix of classic and modern techniques to help answer a question that many in the field of pigmentation biology have suspected for a long time. Not all dormant melanocyte stem cells are created equal,” Dr. Harris said.
“The one question not answered in this paper is how to reverse the dysfunction of the melanocyte stem cell ‘stuck’ in the hair bulge,” Dr. Harris added. “There are numerous clinical case studies in humans showing medicine-induced hair repigmentation, and perhaps these cases are examples of dysfunctional melanocyte stem cells becoming ‘unstuck.’ ”
‘Very interesting’ findings
The study and its results “are very interesting from a mechanistic perspective and basic science view,” said Anthony M. Rossi, MD, a private practice dermatologist and assistant attending dermatologist at Memorial Sloan Kettering Cancer Center in New York, when asked to comment on the results.
The research provides another view of how melanocyte stem cells can pigment the hair shaft, Dr. Rossi added. “It gives insight into the behavior of stem cells and how they can travel and change state, something not well-known before.”
Dr. Rossi cautioned that other mechanisms are likely taking place. He pointed out that graying of hair can actually occur after a sudden stress event, as well as with vitamin B12 deficiency, thyroid disease, vitiligo-related autoimmune destruction, neurofibromatosis, tuberous sclerosis, and alopecia areata.
The “standout concept” in this paper is that the melanocyte stem cells are stranded and are not getting the right signal from the microenvironment to amplify and appropriately migrate to provide pigment to the hair shaft, said Paradi Mirmirani, MD, a private practice dermatologist in Vallejo, Calif.
It could be challenging to find the right signaling to reverse the graying process, Dr. Mirmirani added. “But the first step is always to understand the underlying basic mechanism. It would be interesting to see if other factors such as smoking, stress … influence the melanocyte stem cells in the same way.”
Grants from the National Institutes of Health and the Department of Defense supported the study. Dr. Ito, Dr. Harris, Dr. Mirmirani, and Dr. Rossi had no relevant disclosures.
A version of this article first appeared on Medscape.com.
New evidence points more to a cycle wherein undifferentiated stem cells mature to perform their hair-coloring duties and then transform back to their primitive form. To accomplish this, they need to stay on the move.
When these special stem cells get “stuck” in the follicle, gray hair is the result, according to a new study reported online in Nature.
The regeneration cycle of melanocyte stem cells (McSCs) to melanocytes and back again can last for years. However, McSCs die sooner than do other cells nearby, such as hair follicle stem cells. This difference can explain why people go gray but still grow hair.
“It was thought that melanocyte stem cells are maintained in an undifferentiated state, instead of repeating differentiation and de-differentiation,” said the study’s senior investigator Mayumi Ito, PhD, professor in the departments of dermatology and cell biology at NYU Langone Health, New York.
The process involves different compartments in the hair follicle – the germ area is where the stem cells regenerate; the follicle bulge is where they get stuck. A different microenvironment in each location dictates how they change. This “chameleon-like” property surprised researchers.
Now that investigators figured out how gray hair might get started, a next step will be to search for a way to stop it.
The research has been performed in mice to date but could translate to humans. “Because the structure of the hair follicle is similar between mice and humans, we speculate that human melanocytes may also demonstrate the plasticity during hair regeneration,” Dr. Ito told this news organization.
Future findings could also lead to new therapies. “Our study suggests that moving melanocytes to a proper location within the hair follicle may help prevent gray hair,” Dr. Ito said.
Given the known effects of ultraviolet B (UVB) radiation on melanocytes, Dr. Ito and colleagues wanted to see what effect it might have on this cycle. So in the study, they exposed hair follicles of mice to UVB radiation and report it speeds up the process for McSCs to transform to color-producing melanocytes. They found that these McSCs can regenerate or change back to undifferentiated stem cells, so UVB radiation does not interrupt the process.
A melanoma clue?
The study also could have implications for melanoma. Unlike other tumors, melanocytes that cause cancer can self-renew even from a fully differentiated, pigmented form, the researchers note.
This makes melanomas more difficult to eliminate.
“Our study suggests normal melanocytes are very plastic and can reverse a differentiation state. Melanoma cells are known to be very plastic,” Dr. Ito said. “We consider this feature of melanoma may be related to the high plasticity of original melanocytes.”
The finding that melanocyte stem cells “are more plastic than maybe previously given credit for … certainly has implications in melanoma,” agreed Melissa Harris, PhD, associate professor, department of biology at the University of Alabama, Birmingham, when asked to comment on the study.
Small technology, big insights?
The advanced technology used by Dr. Ito and colleagues in the study included 3D-intravital imaging and single-cell RNA sequencing to track the stem cells in almost real time as they aged and moved within each hair follicle.
“This paper uses a nice mix of classic and modern techniques to help answer a question that many in the field of pigmentation biology have suspected for a long time. Not all dormant melanocyte stem cells are created equal,” Dr. Harris said.
“The one question not answered in this paper is how to reverse the dysfunction of the melanocyte stem cell ‘stuck’ in the hair bulge,” Dr. Harris added. “There are numerous clinical case studies in humans showing medicine-induced hair repigmentation, and perhaps these cases are examples of dysfunctional melanocyte stem cells becoming ‘unstuck.’ ”
‘Very interesting’ findings
The study and its results “are very interesting from a mechanistic perspective and basic science view,” said Anthony M. Rossi, MD, a private practice dermatologist and assistant attending dermatologist at Memorial Sloan Kettering Cancer Center in New York, when asked to comment on the results.
The research provides another view of how melanocyte stem cells can pigment the hair shaft, Dr. Rossi added. “It gives insight into the behavior of stem cells and how they can travel and change state, something not well-known before.”
Dr. Rossi cautioned that other mechanisms are likely taking place. He pointed out that graying of hair can actually occur after a sudden stress event, as well as with vitamin B12 deficiency, thyroid disease, vitiligo-related autoimmune destruction, neurofibromatosis, tuberous sclerosis, and alopecia areata.
The “standout concept” in this paper is that the melanocyte stem cells are stranded and are not getting the right signal from the microenvironment to amplify and appropriately migrate to provide pigment to the hair shaft, said Paradi Mirmirani, MD, a private practice dermatologist in Vallejo, Calif.
It could be challenging to find the right signaling to reverse the graying process, Dr. Mirmirani added. “But the first step is always to understand the underlying basic mechanism. It would be interesting to see if other factors such as smoking, stress … influence the melanocyte stem cells in the same way.”
Grants from the National Institutes of Health and the Department of Defense supported the study. Dr. Ito, Dr. Harris, Dr. Mirmirani, and Dr. Rossi had no relevant disclosures.
A version of this article first appeared on Medscape.com.
New evidence points more to a cycle wherein undifferentiated stem cells mature to perform their hair-coloring duties and then transform back to their primitive form. To accomplish this, they need to stay on the move.
When these special stem cells get “stuck” in the follicle, gray hair is the result, according to a new study reported online in Nature.
The regeneration cycle of melanocyte stem cells (McSCs) to melanocytes and back again can last for years. However, McSCs die sooner than do other cells nearby, such as hair follicle stem cells. This difference can explain why people go gray but still grow hair.
“It was thought that melanocyte stem cells are maintained in an undifferentiated state, instead of repeating differentiation and de-differentiation,” said the study’s senior investigator Mayumi Ito, PhD, professor in the departments of dermatology and cell biology at NYU Langone Health, New York.
The process involves different compartments in the hair follicle – the germ area is where the stem cells regenerate; the follicle bulge is where they get stuck. A different microenvironment in each location dictates how they change. This “chameleon-like” property surprised researchers.
Now that investigators figured out how gray hair might get started, a next step will be to search for a way to stop it.
The research has been performed in mice to date but could translate to humans. “Because the structure of the hair follicle is similar between mice and humans, we speculate that human melanocytes may also demonstrate the plasticity during hair regeneration,” Dr. Ito told this news organization.
Future findings could also lead to new therapies. “Our study suggests that moving melanocytes to a proper location within the hair follicle may help prevent gray hair,” Dr. Ito said.
Given the known effects of ultraviolet B (UVB) radiation on melanocytes, Dr. Ito and colleagues wanted to see what effect it might have on this cycle. So in the study, they exposed hair follicles of mice to UVB radiation and report it speeds up the process for McSCs to transform to color-producing melanocytes. They found that these McSCs can regenerate or change back to undifferentiated stem cells, so UVB radiation does not interrupt the process.
A melanoma clue?
The study also could have implications for melanoma. Unlike other tumors, melanocytes that cause cancer can self-renew even from a fully differentiated, pigmented form, the researchers note.
This makes melanomas more difficult to eliminate.
“Our study suggests normal melanocytes are very plastic and can reverse a differentiation state. Melanoma cells are known to be very plastic,” Dr. Ito said. “We consider this feature of melanoma may be related to the high plasticity of original melanocytes.”
The finding that melanocyte stem cells “are more plastic than maybe previously given credit for … certainly has implications in melanoma,” agreed Melissa Harris, PhD, associate professor, department of biology at the University of Alabama, Birmingham, when asked to comment on the study.
Small technology, big insights?
The advanced technology used by Dr. Ito and colleagues in the study included 3D-intravital imaging and single-cell RNA sequencing to track the stem cells in almost real time as they aged and moved within each hair follicle.
“This paper uses a nice mix of classic and modern techniques to help answer a question that many in the field of pigmentation biology have suspected for a long time. Not all dormant melanocyte stem cells are created equal,” Dr. Harris said.
“The one question not answered in this paper is how to reverse the dysfunction of the melanocyte stem cell ‘stuck’ in the hair bulge,” Dr. Harris added. “There are numerous clinical case studies in humans showing medicine-induced hair repigmentation, and perhaps these cases are examples of dysfunctional melanocyte stem cells becoming ‘unstuck.’ ”
‘Very interesting’ findings
The study and its results “are very interesting from a mechanistic perspective and basic science view,” said Anthony M. Rossi, MD, a private practice dermatologist and assistant attending dermatologist at Memorial Sloan Kettering Cancer Center in New York, when asked to comment on the results.
The research provides another view of how melanocyte stem cells can pigment the hair shaft, Dr. Rossi added. “It gives insight into the behavior of stem cells and how they can travel and change state, something not well-known before.”
Dr. Rossi cautioned that other mechanisms are likely taking place. He pointed out that graying of hair can actually occur after a sudden stress event, as well as with vitamin B12 deficiency, thyroid disease, vitiligo-related autoimmune destruction, neurofibromatosis, tuberous sclerosis, and alopecia areata.
The “standout concept” in this paper is that the melanocyte stem cells are stranded and are not getting the right signal from the microenvironment to amplify and appropriately migrate to provide pigment to the hair shaft, said Paradi Mirmirani, MD, a private practice dermatologist in Vallejo, Calif.
It could be challenging to find the right signaling to reverse the graying process, Dr. Mirmirani added. “But the first step is always to understand the underlying basic mechanism. It would be interesting to see if other factors such as smoking, stress … influence the melanocyte stem cells in the same way.”
Grants from the National Institutes of Health and the Department of Defense supported the study. Dr. Ito, Dr. Harris, Dr. Mirmirani, and Dr. Rossi had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM NATURE