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Doug Brunk is a San Diego-based award-winning reporter who began covering health care in 1991. Before joining the company, he wrote for the health sciences division of Columbia University and was an associate editor at Contemporary Long Term Care magazine when it won a Jesse H. Neal Award. His work has been syndicated by the Los Angeles Times and he is the author of two books related to the University of Kentucky Wildcats men's basketball program. Doug has a master’s degree in magazine journalism from the S.I. Newhouse School of Public Communications at Syracuse University. Follow him on Twitter @dougbrunk.
Risk of infections low among kids receiving systemic meds for psoriasis, study finds
.
Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.
“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”
Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.
Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.
Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”
She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”
Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.
.
Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.
“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”
Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.
Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.
Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”
She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”
Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.
.
Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.
“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”
Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.
Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.
Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”
She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”
Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.
FROM JAMA DERMATOLOGY
Dermoscopy, other modalities for improving melanoma diagnoses reviewed
San Diego – .
“I don’t think that’s going to change in the short term,” Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, said at the annual Cutaneous Malignancy Update. “But I do think we can supplement that with other modalities that will improve the clinical examination and help dermatopathologists as they assess and evaluate these lesions,” he said, adding: “The reality is, histopathology, while it may be the gold standard, is not necessarily a consistently reproducible evaluation. That raises the question: What can we do better?”
According to Dr. Blalock, the future may include more routine use of noninvasive genetic molecular assays to assist with the diagnostics challenges linked to the visual image and pattern recognition approach of detecting cutaneous melanoma. For example, a two-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions obtained noninvasively via adhesive patch biopsy.
“Today, you can pick up a kit from your local pharmacy that can tell you a bit about broad genetic susceptibilities,” he said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. He predicted that using adhesive patch biopsies to assess suspicious melanocytic lesions “is likely the wave of the future.” This may increase patient understanding “as to the types of risks they have, the different lesions they have, and minimize invasive disease, but it also will pose different challenges for us when it comes to deploying patient-centered health care. For example, in a patient with multiple different lesions, how are you going to keep track of them all?”
Dermoscopy
In Dr. Blalock’s clinical opinion, dermoscopy improves the sensitivity of human visual detection of melanoma and may allow detection before a lesion displays classical features described with the “ABCDE rule.” However, the learning curve for dermoscopy is steep, he added, and whether the technique should be considered a first-line tool or as a supplement to other methods of examining cutaneous lesions remains a matter of debate.
“Dermoscopy is our version of the stethoscope,” he said. “We need to figure out when we’re going to use it. Should we be using it all of the time or only some of the time? Based on the clinical setting, maybe it’s a personal choice, but this can be a helpful skill and art in your practice if you’re willing to take the time to learn.”
In 2007, the International Dermoscopy Society (IDS) established a proposal for the standardization and recommended criteria necessary to effectively convey dermoscopic findings to consulting physicians and colleagues. The document includes 10 points categorized as either recommended or optional for a standardized dermoscopy report.
“The first step is to assess the lesion to determine whether or not it’s melanocytic in the first place,” said Dr. Blalock. “There are many different features – the mile-high [global features] evaluation of the lesions – then more specific local features that may clue you in to specific diagnoses,” he noted. “Once we get past that first step of determining that a lesion is melanocytic, it’s not enough to stop there, because we don’t want to biopsy every single lesion that’s melanocytic,” so there is a need to determine which ones require intervention, which is where dermoscopy “gets trickier and a little more challenging.”
According to the IDS, a standard dermoscopy report should include the patient’s age, relevant history pertaining to the lesion, pertinent personal and family history (recommended); clinical description of the lesion (recommended); the two-step method of dermoscopy differentiating melanocytic from nonmelanocytic tumors (recommended); and the use of standardized terms to describe structures as defined by the Dermoscopy Consensus Report published in 2003.
For new terms, the document states, “it would be helpful” for the physician to provide a working definition (recommended); the dermoscopic algorithm used should be mentioned (optional); information on the imaging equipment and magnification (recommended); clinical and dermoscopic images of the tumor (recommended); a diagnosis or differential diagnosis (recommended); decision concerning management (recommended), and specific comments for the pathologist when excision and histopathologic examination are recommended (optional).
The 2007 IDS document also includes a proposed seven-point checklist to differentiate between benign and melanocytic lesions on dermoscopy. Three major criteria are worth two points each: The presence of an atypical pigment network, gray-blue areas (commonly known as the veil), and an atypical vascular pattern. Four minor criteria are worth one point each: Irregular streaks, irregular dots/globules, irregular pigmentation, and regression structures. A minimum total score of 3 is required to establish a diagnosis of melanoma.
Another diagnostic technique, digital mole mapping, involves the use of photography to detect new or changing lesions. Dr. Blalock described this approach as rife with limitations, including variations in quality, challenges of storing and maintaining records, cost, time required to evaluate them, and determining which patients are appropriate candidates.
Other techniques being evaluated include computer algorithms to help dermatologists determine the diagnosis of melanoma from dermoscopic images, electrical impedance spectroscopy for noninvasive evaluation of atypical pigmented lesions, and ultrasound for staging of cutaneous malignant tumors.
Ultimately, “I think we’ll have multiple tools in our belt,” Dr. Blalock said, adding, “How do we pull them out at the right time to improve the lives of our patients? Are we going to use ultrasound? Dermoscopy? Integrate them with some of the genetic findings?”
Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.
San Diego – .
“I don’t think that’s going to change in the short term,” Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, said at the annual Cutaneous Malignancy Update. “But I do think we can supplement that with other modalities that will improve the clinical examination and help dermatopathologists as they assess and evaluate these lesions,” he said, adding: “The reality is, histopathology, while it may be the gold standard, is not necessarily a consistently reproducible evaluation. That raises the question: What can we do better?”
According to Dr. Blalock, the future may include more routine use of noninvasive genetic molecular assays to assist with the diagnostics challenges linked to the visual image and pattern recognition approach of detecting cutaneous melanoma. For example, a two-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions obtained noninvasively via adhesive patch biopsy.
“Today, you can pick up a kit from your local pharmacy that can tell you a bit about broad genetic susceptibilities,” he said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. He predicted that using adhesive patch biopsies to assess suspicious melanocytic lesions “is likely the wave of the future.” This may increase patient understanding “as to the types of risks they have, the different lesions they have, and minimize invasive disease, but it also will pose different challenges for us when it comes to deploying patient-centered health care. For example, in a patient with multiple different lesions, how are you going to keep track of them all?”
Dermoscopy
In Dr. Blalock’s clinical opinion, dermoscopy improves the sensitivity of human visual detection of melanoma and may allow detection before a lesion displays classical features described with the “ABCDE rule.” However, the learning curve for dermoscopy is steep, he added, and whether the technique should be considered a first-line tool or as a supplement to other methods of examining cutaneous lesions remains a matter of debate.
“Dermoscopy is our version of the stethoscope,” he said. “We need to figure out when we’re going to use it. Should we be using it all of the time or only some of the time? Based on the clinical setting, maybe it’s a personal choice, but this can be a helpful skill and art in your practice if you’re willing to take the time to learn.”
In 2007, the International Dermoscopy Society (IDS) established a proposal for the standardization and recommended criteria necessary to effectively convey dermoscopic findings to consulting physicians and colleagues. The document includes 10 points categorized as either recommended or optional for a standardized dermoscopy report.
“The first step is to assess the lesion to determine whether or not it’s melanocytic in the first place,” said Dr. Blalock. “There are many different features – the mile-high [global features] evaluation of the lesions – then more specific local features that may clue you in to specific diagnoses,” he noted. “Once we get past that first step of determining that a lesion is melanocytic, it’s not enough to stop there, because we don’t want to biopsy every single lesion that’s melanocytic,” so there is a need to determine which ones require intervention, which is where dermoscopy “gets trickier and a little more challenging.”
According to the IDS, a standard dermoscopy report should include the patient’s age, relevant history pertaining to the lesion, pertinent personal and family history (recommended); clinical description of the lesion (recommended); the two-step method of dermoscopy differentiating melanocytic from nonmelanocytic tumors (recommended); and the use of standardized terms to describe structures as defined by the Dermoscopy Consensus Report published in 2003.
For new terms, the document states, “it would be helpful” for the physician to provide a working definition (recommended); the dermoscopic algorithm used should be mentioned (optional); information on the imaging equipment and magnification (recommended); clinical and dermoscopic images of the tumor (recommended); a diagnosis or differential diagnosis (recommended); decision concerning management (recommended), and specific comments for the pathologist when excision and histopathologic examination are recommended (optional).
The 2007 IDS document also includes a proposed seven-point checklist to differentiate between benign and melanocytic lesions on dermoscopy. Three major criteria are worth two points each: The presence of an atypical pigment network, gray-blue areas (commonly known as the veil), and an atypical vascular pattern. Four minor criteria are worth one point each: Irregular streaks, irregular dots/globules, irregular pigmentation, and regression structures. A minimum total score of 3 is required to establish a diagnosis of melanoma.
Another diagnostic technique, digital mole mapping, involves the use of photography to detect new or changing lesions. Dr. Blalock described this approach as rife with limitations, including variations in quality, challenges of storing and maintaining records, cost, time required to evaluate them, and determining which patients are appropriate candidates.
Other techniques being evaluated include computer algorithms to help dermatologists determine the diagnosis of melanoma from dermoscopic images, electrical impedance spectroscopy for noninvasive evaluation of atypical pigmented lesions, and ultrasound for staging of cutaneous malignant tumors.
Ultimately, “I think we’ll have multiple tools in our belt,” Dr. Blalock said, adding, “How do we pull them out at the right time to improve the lives of our patients? Are we going to use ultrasound? Dermoscopy? Integrate them with some of the genetic findings?”
Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.
San Diego – .
“I don’t think that’s going to change in the short term,” Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, said at the annual Cutaneous Malignancy Update. “But I do think we can supplement that with other modalities that will improve the clinical examination and help dermatopathologists as they assess and evaluate these lesions,” he said, adding: “The reality is, histopathology, while it may be the gold standard, is not necessarily a consistently reproducible evaluation. That raises the question: What can we do better?”
According to Dr. Blalock, the future may include more routine use of noninvasive genetic molecular assays to assist with the diagnostics challenges linked to the visual image and pattern recognition approach of detecting cutaneous melanoma. For example, a two-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions obtained noninvasively via adhesive patch biopsy.
“Today, you can pick up a kit from your local pharmacy that can tell you a bit about broad genetic susceptibilities,” he said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. He predicted that using adhesive patch biopsies to assess suspicious melanocytic lesions “is likely the wave of the future.” This may increase patient understanding “as to the types of risks they have, the different lesions they have, and minimize invasive disease, but it also will pose different challenges for us when it comes to deploying patient-centered health care. For example, in a patient with multiple different lesions, how are you going to keep track of them all?”
Dermoscopy
In Dr. Blalock’s clinical opinion, dermoscopy improves the sensitivity of human visual detection of melanoma and may allow detection before a lesion displays classical features described with the “ABCDE rule.” However, the learning curve for dermoscopy is steep, he added, and whether the technique should be considered a first-line tool or as a supplement to other methods of examining cutaneous lesions remains a matter of debate.
“Dermoscopy is our version of the stethoscope,” he said. “We need to figure out when we’re going to use it. Should we be using it all of the time or only some of the time? Based on the clinical setting, maybe it’s a personal choice, but this can be a helpful skill and art in your practice if you’re willing to take the time to learn.”
In 2007, the International Dermoscopy Society (IDS) established a proposal for the standardization and recommended criteria necessary to effectively convey dermoscopic findings to consulting physicians and colleagues. The document includes 10 points categorized as either recommended or optional for a standardized dermoscopy report.
“The first step is to assess the lesion to determine whether or not it’s melanocytic in the first place,” said Dr. Blalock. “There are many different features – the mile-high [global features] evaluation of the lesions – then more specific local features that may clue you in to specific diagnoses,” he noted. “Once we get past that first step of determining that a lesion is melanocytic, it’s not enough to stop there, because we don’t want to biopsy every single lesion that’s melanocytic,” so there is a need to determine which ones require intervention, which is where dermoscopy “gets trickier and a little more challenging.”
According to the IDS, a standard dermoscopy report should include the patient’s age, relevant history pertaining to the lesion, pertinent personal and family history (recommended); clinical description of the lesion (recommended); the two-step method of dermoscopy differentiating melanocytic from nonmelanocytic tumors (recommended); and the use of standardized terms to describe structures as defined by the Dermoscopy Consensus Report published in 2003.
For new terms, the document states, “it would be helpful” for the physician to provide a working definition (recommended); the dermoscopic algorithm used should be mentioned (optional); information on the imaging equipment and magnification (recommended); clinical and dermoscopic images of the tumor (recommended); a diagnosis or differential diagnosis (recommended); decision concerning management (recommended), and specific comments for the pathologist when excision and histopathologic examination are recommended (optional).
The 2007 IDS document also includes a proposed seven-point checklist to differentiate between benign and melanocytic lesions on dermoscopy. Three major criteria are worth two points each: The presence of an atypical pigment network, gray-blue areas (commonly known as the veil), and an atypical vascular pattern. Four minor criteria are worth one point each: Irregular streaks, irregular dots/globules, irregular pigmentation, and regression structures. A minimum total score of 3 is required to establish a diagnosis of melanoma.
Another diagnostic technique, digital mole mapping, involves the use of photography to detect new or changing lesions. Dr. Blalock described this approach as rife with limitations, including variations in quality, challenges of storing and maintaining records, cost, time required to evaluate them, and determining which patients are appropriate candidates.
Other techniques being evaluated include computer algorithms to help dermatologists determine the diagnosis of melanoma from dermoscopic images, electrical impedance spectroscopy for noninvasive evaluation of atypical pigmented lesions, and ultrasound for staging of cutaneous malignant tumors.
Ultimately, “I think we’ll have multiple tools in our belt,” Dr. Blalock said, adding, “How do we pull them out at the right time to improve the lives of our patients? Are we going to use ultrasound? Dermoscopy? Integrate them with some of the genetic findings?”
Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.
AT MELANOMA 2023
Dermatopathologist reflects on the early history of melanoma
SAN DIEGO – Evidence of melanoma in the ancient past is rare, but according to James W. Patterson, MD, .
“Radiocarbon dating indicated that these mummies were 2,400 years old,” Dr. Patterson, professor emeritus of pathology and dermatology at the University of Virginia, Charlottesville, said at the annual Cutaneous Malignancy Update.
John Hunter, a famous British surgeon who lived from 1728 to 1793, had the first known reported encounter with melanoma in 1787. “He thought it was a form of cancerous fungus,” said Dr. Patterson, a former president of the American Board of Dermatology. “That tumor was preserved in the Hunterian Museum of the Royal College of Surgeons in London, and in 1968 it was reexamined and turned out to be melanoma.”
René Laënnec, the French physician who invented the stethoscope in 1816, is believed to be the first person to lecture on melanoma while a medical student in 1804. The lecture was published about a year later. He originated the term “melanose” (becoming black), a French word derived from the Greek language, to describe metastatic melanoma and reported metastasis to the lungs. During the early part of his career, Dr. Laënnec had studied dissection in the laboratory of the French anatomist and military surgeon Guillaume Dupuytren, best known for his description of Dupuytren’s contracture. Dr. Dupuytren took exception to Dr. Laënnec’s publication about melanoma and called foul.
“As sometimes happens these days, there was some rivalry between these two outstanding physicians of their time,” Dr. Patterson said at the meeting, hosted by Scripps MD Anderson Cancer Center. “Dupuytren was unhappy that Laënnec took credit for this because he claimed credit for originally describing melanoma. He claimed that Laënnec stole the idea from his lectures. I’m not sure that issue was ever resolved.”
In 1820, William Norris, a general practitioner from Stourbridge, England, published the first English language report of melanoma in the Edinburgh Medical and Surgical Journal. “The report was titled ‘A case of fungoid disease,’ so it appears that melanoma was often regarded as a fungal infection back then,” Dr. Patterson said. In the report, Dr. Norris described the tumor in a 59-year-old man as “nearly half the size of a hen’s egg, of a deep brown color, of a firm and fleshy feel, [and] ulcerated on its surface.” Dr. Norris authored a later work titled “Eight cases of melanosis, with pathological and therapeutical remarks on that disease.”
In 1840, a full 2 decades following the first published report from Dr. Norris, the British surgeon Samuel Cooper published a book titled “First Lines of Theory and Practice of Surgery,” in which he described patients with advanced stage melanoma as untreatable and postulated that the only chance for survival was early removal of the tumor.
Dr. Patterson reported having no relevant disclosures.
SAN DIEGO – Evidence of melanoma in the ancient past is rare, but according to James W. Patterson, MD, .
“Radiocarbon dating indicated that these mummies were 2,400 years old,” Dr. Patterson, professor emeritus of pathology and dermatology at the University of Virginia, Charlottesville, said at the annual Cutaneous Malignancy Update.
John Hunter, a famous British surgeon who lived from 1728 to 1793, had the first known reported encounter with melanoma in 1787. “He thought it was a form of cancerous fungus,” said Dr. Patterson, a former president of the American Board of Dermatology. “That tumor was preserved in the Hunterian Museum of the Royal College of Surgeons in London, and in 1968 it was reexamined and turned out to be melanoma.”
René Laënnec, the French physician who invented the stethoscope in 1816, is believed to be the first person to lecture on melanoma while a medical student in 1804. The lecture was published about a year later. He originated the term “melanose” (becoming black), a French word derived from the Greek language, to describe metastatic melanoma and reported metastasis to the lungs. During the early part of his career, Dr. Laënnec had studied dissection in the laboratory of the French anatomist and military surgeon Guillaume Dupuytren, best known for his description of Dupuytren’s contracture. Dr. Dupuytren took exception to Dr. Laënnec’s publication about melanoma and called foul.
“As sometimes happens these days, there was some rivalry between these two outstanding physicians of their time,” Dr. Patterson said at the meeting, hosted by Scripps MD Anderson Cancer Center. “Dupuytren was unhappy that Laënnec took credit for this because he claimed credit for originally describing melanoma. He claimed that Laënnec stole the idea from his lectures. I’m not sure that issue was ever resolved.”
In 1820, William Norris, a general practitioner from Stourbridge, England, published the first English language report of melanoma in the Edinburgh Medical and Surgical Journal. “The report was titled ‘A case of fungoid disease,’ so it appears that melanoma was often regarded as a fungal infection back then,” Dr. Patterson said. In the report, Dr. Norris described the tumor in a 59-year-old man as “nearly half the size of a hen’s egg, of a deep brown color, of a firm and fleshy feel, [and] ulcerated on its surface.” Dr. Norris authored a later work titled “Eight cases of melanosis, with pathological and therapeutical remarks on that disease.”
In 1840, a full 2 decades following the first published report from Dr. Norris, the British surgeon Samuel Cooper published a book titled “First Lines of Theory and Practice of Surgery,” in which he described patients with advanced stage melanoma as untreatable and postulated that the only chance for survival was early removal of the tumor.
Dr. Patterson reported having no relevant disclosures.
SAN DIEGO – Evidence of melanoma in the ancient past is rare, but according to James W. Patterson, MD, .
“Radiocarbon dating indicated that these mummies were 2,400 years old,” Dr. Patterson, professor emeritus of pathology and dermatology at the University of Virginia, Charlottesville, said at the annual Cutaneous Malignancy Update.
John Hunter, a famous British surgeon who lived from 1728 to 1793, had the first known reported encounter with melanoma in 1787. “He thought it was a form of cancerous fungus,” said Dr. Patterson, a former president of the American Board of Dermatology. “That tumor was preserved in the Hunterian Museum of the Royal College of Surgeons in London, and in 1968 it was reexamined and turned out to be melanoma.”
René Laënnec, the French physician who invented the stethoscope in 1816, is believed to be the first person to lecture on melanoma while a medical student in 1804. The lecture was published about a year later. He originated the term “melanose” (becoming black), a French word derived from the Greek language, to describe metastatic melanoma and reported metastasis to the lungs. During the early part of his career, Dr. Laënnec had studied dissection in the laboratory of the French anatomist and military surgeon Guillaume Dupuytren, best known for his description of Dupuytren’s contracture. Dr. Dupuytren took exception to Dr. Laënnec’s publication about melanoma and called foul.
“As sometimes happens these days, there was some rivalry between these two outstanding physicians of their time,” Dr. Patterson said at the meeting, hosted by Scripps MD Anderson Cancer Center. “Dupuytren was unhappy that Laënnec took credit for this because he claimed credit for originally describing melanoma. He claimed that Laënnec stole the idea from his lectures. I’m not sure that issue was ever resolved.”
In 1820, William Norris, a general practitioner from Stourbridge, England, published the first English language report of melanoma in the Edinburgh Medical and Surgical Journal. “The report was titled ‘A case of fungoid disease,’ so it appears that melanoma was often regarded as a fungal infection back then,” Dr. Patterson said. In the report, Dr. Norris described the tumor in a 59-year-old man as “nearly half the size of a hen’s egg, of a deep brown color, of a firm and fleshy feel, [and] ulcerated on its surface.” Dr. Norris authored a later work titled “Eight cases of melanosis, with pathological and therapeutical remarks on that disease.”
In 1840, a full 2 decades following the first published report from Dr. Norris, the British surgeon Samuel Cooper published a book titled “First Lines of Theory and Practice of Surgery,” in which he described patients with advanced stage melanoma as untreatable and postulated that the only chance for survival was early removal of the tumor.
Dr. Patterson reported having no relevant disclosures.
AT MELANOMA 2023
How should PRAME be used to evaluate melanocytic lesions?
SAN DIEGO – , according to Cora Humberson, MD.
“I’m a fan, but there are issues with it,” Dr. Humberson, dermatopathology coordinator in the department of pathology at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “It’s all in how you use it.”
PRAME is part of the cancer/testis (CT) antigens, of which more than 40 have now been identified. They are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumor types, including melanoma and carcinomas of the bladder, lung, and liver. “The biological function of these antigens is not fully understood, but they may act as a repressor of retinoic acid, potentially inhibiting differentiation, inhibiting proliferation arrest – things that we associate with malignancy,” she said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “These immunogenic proteins are being pursued as targets for therapeutic cancer vaccines,” she noted.
CT antigens are also being evaluated for their role in oncogenesis, she added. Recapitulation of portions of the germline gene-expression might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, and metastatic capacity.
According to Dr. Humberson, PRAME can be used to differentiate comingled nevus and melanoma, to distinguish between nevoid melanoma and nevus, and for melanoma margin assessment in sun-damaged skin. One potential pitfall is that sun-damaged melanocytes may express PRAME. “The older the person and the more sun damage [they have], the more likely you are to see this, but the melanocytes won’t be grouped, they’ll be scattered,” she said.
Another pitfall is that less than 15% of nevi may express PRAME. “PRAME can be expressed in scars, so if you’re looking at a spindle cell lesion, be aware that you might be looking at a scar if you’re seeing PRAME expression,” she added. She also noted that PRAME immunohistochemistry (IHC) expression is not a prognostic biomarker in thin melanomas.
If fewer than 25% of cells in a melanocytic lesion express PRAME, most published assessments of PRAME IHC favor nevi as the diagnosis. “If more than 75% are expressing it, it favors melanoma,” Dr. Humberson said. “There’s a big category in between. It’s not that 30% is more likely benign or that 60% is more likely malignant; you can’t really depend upon [PRAME] if you’re in this range.”
A diagnostic accuracy study found that when more than 75% of cells express PRAME, the marker has a sensitivity of 0.63 and a specificity of 0.97.
Selected PRAME-related published references she recommended include: J Cutan Pathol. 2021;48(9):1115-23; Diagnostics. 2022 Sep 9; 12(9):2197, and J Cutan Pathol. 2022;49(9):829-32.
Dr. Humberson reported having no relevant disclosures.
SAN DIEGO – , according to Cora Humberson, MD.
“I’m a fan, but there are issues with it,” Dr. Humberson, dermatopathology coordinator in the department of pathology at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “It’s all in how you use it.”
PRAME is part of the cancer/testis (CT) antigens, of which more than 40 have now been identified. They are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumor types, including melanoma and carcinomas of the bladder, lung, and liver. “The biological function of these antigens is not fully understood, but they may act as a repressor of retinoic acid, potentially inhibiting differentiation, inhibiting proliferation arrest – things that we associate with malignancy,” she said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “These immunogenic proteins are being pursued as targets for therapeutic cancer vaccines,” she noted.
CT antigens are also being evaluated for their role in oncogenesis, she added. Recapitulation of portions of the germline gene-expression might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, and metastatic capacity.
According to Dr. Humberson, PRAME can be used to differentiate comingled nevus and melanoma, to distinguish between nevoid melanoma and nevus, and for melanoma margin assessment in sun-damaged skin. One potential pitfall is that sun-damaged melanocytes may express PRAME. “The older the person and the more sun damage [they have], the more likely you are to see this, but the melanocytes won’t be grouped, they’ll be scattered,” she said.
Another pitfall is that less than 15% of nevi may express PRAME. “PRAME can be expressed in scars, so if you’re looking at a spindle cell lesion, be aware that you might be looking at a scar if you’re seeing PRAME expression,” she added. She also noted that PRAME immunohistochemistry (IHC) expression is not a prognostic biomarker in thin melanomas.
If fewer than 25% of cells in a melanocytic lesion express PRAME, most published assessments of PRAME IHC favor nevi as the diagnosis. “If more than 75% are expressing it, it favors melanoma,” Dr. Humberson said. “There’s a big category in between. It’s not that 30% is more likely benign or that 60% is more likely malignant; you can’t really depend upon [PRAME] if you’re in this range.”
A diagnostic accuracy study found that when more than 75% of cells express PRAME, the marker has a sensitivity of 0.63 and a specificity of 0.97.
Selected PRAME-related published references she recommended include: J Cutan Pathol. 2021;48(9):1115-23; Diagnostics. 2022 Sep 9; 12(9):2197, and J Cutan Pathol. 2022;49(9):829-32.
Dr. Humberson reported having no relevant disclosures.
SAN DIEGO – , according to Cora Humberson, MD.
“I’m a fan, but there are issues with it,” Dr. Humberson, dermatopathology coordinator in the department of pathology at Scripps MD Anderson Cancer Center, San Diego, said at the annual Cutaneous Malignancy Update. “It’s all in how you use it.”
PRAME is part of the cancer/testis (CT) antigens, of which more than 40 have now been identified. They are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumor types, including melanoma and carcinomas of the bladder, lung, and liver. “The biological function of these antigens is not fully understood, but they may act as a repressor of retinoic acid, potentially inhibiting differentiation, inhibiting proliferation arrest – things that we associate with malignancy,” she said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. “These immunogenic proteins are being pursued as targets for therapeutic cancer vaccines,” she noted.
CT antigens are also being evaluated for their role in oncogenesis, she added. Recapitulation of portions of the germline gene-expression might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, and metastatic capacity.
According to Dr. Humberson, PRAME can be used to differentiate comingled nevus and melanoma, to distinguish between nevoid melanoma and nevus, and for melanoma margin assessment in sun-damaged skin. One potential pitfall is that sun-damaged melanocytes may express PRAME. “The older the person and the more sun damage [they have], the more likely you are to see this, but the melanocytes won’t be grouped, they’ll be scattered,” she said.
Another pitfall is that less than 15% of nevi may express PRAME. “PRAME can be expressed in scars, so if you’re looking at a spindle cell lesion, be aware that you might be looking at a scar if you’re seeing PRAME expression,” she added. She also noted that PRAME immunohistochemistry (IHC) expression is not a prognostic biomarker in thin melanomas.
If fewer than 25% of cells in a melanocytic lesion express PRAME, most published assessments of PRAME IHC favor nevi as the diagnosis. “If more than 75% are expressing it, it favors melanoma,” Dr. Humberson said. “There’s a big category in between. It’s not that 30% is more likely benign or that 60% is more likely malignant; you can’t really depend upon [PRAME] if you’re in this range.”
A diagnostic accuracy study found that when more than 75% of cells express PRAME, the marker has a sensitivity of 0.63 and a specificity of 0.97.
Selected PRAME-related published references she recommended include: J Cutan Pathol. 2021;48(9):1115-23; Diagnostics. 2022 Sep 9; 12(9):2197, and J Cutan Pathol. 2022;49(9):829-32.
Dr. Humberson reported having no relevant disclosures.
AT MELANOMA 2023
Long-pulsed 1,064 nm Nd:YAG for nonaggressive BCC ‘effective and easy’
SAN DIEGO – After Arisa E. Ortiz, MD, and colleagues published results of a multicenter study reporting that one treatment with the long-pulsed 1,064-nm Nd:YAG laser cleared nonaggressive basal cell carcinoma (BCC) on the trunk and extremities in 90% of patients, she heard from colleagues who were skeptical of the approach.
Maybe it’s just the biopsy alone that’s clearing these tumors, some told her. Others postulated that since the energy was delivered with a 5- to 6-mm spot size at a fluence of 125-140 J/cm2 and a 7- to 10-ms pulse duration, bulk heating likely disrupted the tumors. However, treatments were generally well tolerated, required no anesthesia, and caused no significant adverse events.
“It’s almost scarless,” Dr. Ortiz, director of laser and cosmetic dermatology at the University of California, San Diego, said at the annual Masters of Aesthetics Symposium. “Sometimes the treatment does leave a mark, but I think the scars are always acceptable. We do have good histologic evidence that we can penetrate 2.15 mm, which is a lot deeper than what the pulsed-dye laser or other superficial wavelengths are able to penetrate.”
Data is well powered to reject the null hypothesis that laser treatment does not have an effect on nodular and superficial BCC lesions, she continued, noting that it is at least comparable if not superior with clearance rates reported for methyl aminolevulinate–PDT (73%), imiquimod cream (83%), and fluorouracil cream (80%). “Maybe we’re not specifically targeting the vasculature [with this approach], but we did some optical coherence tomography imaging and saw that the blood vessels in the tumor were coagulated while the vasculature in the surrounding normal skin were spared,” said Dr. Ortiz, who is also vice president of the American Society for Laser Medicine and Surgery.
In a more recent analysis, she and her colleagues retrospectively analyzed long-term outcomes in 11 patients with BCC who had 16 lesions treated with the 1,064-nm Nd:YAG laser. At a mean of 9 months, 100% of lesions remained clear as determined by clinical observation.
In a subsequent, as yet unpublished study, she and her collaborators followed 34 patients with BCC one year following laser treatment. “Of these, 33 had no recurrence at 1-year follow-up,” Dr. Ortiz said, noting that the one patient with a recurrence was on a biologic agent for Crohn’s disease.
One key advantage of using the long-pulsed 1,064-nm Nd:YAG laser for nonaggressive BCC is the potential for one treatment visit. “They don’t have to come back for suture removal,” she said. “It’s a quick procedure, takes only about 5 minutes. There’s no limitation on activity and there’s minimal wound care, light ointment, and a band-aid; that’s it.”
In addition, she said, there is a lower risk of complications, infections, and bleeding, and there is minimal scarring. It is “also an alternative for treating patients with multiple tumors or those who are poor surgical candidates, such as the elderly and those with Gorlin syndrome.”
Dr. Ortiz avoids treating aggressive subtypes “because we don’t know what margin to treat,” she added. “Avoid the face. I do make some exceptions for patients if they’re elderly or if they’ve had multiple tumors. Monitor for recurrence like you would using any other modality.”
She uses lidocaine without epinephrine to avoid vasoconstriction and treats with the 1,064-nm Nd:YAG laser as follows: a 5-mm spot size, a fluence of 140 J/cm2, and a pulse duration of 8 ms, with no cooling, which are the settings for the Excel V Laser System, she noted. “If you’re using a different Nd:YAG laser, your pulse duration may vary. I do let the device cool in between pulses to avoid bulk heating.”
The immediate endpoint to strive for is slight greying and slight contraction, and the procedure is covered by insurance, billed as malignant destruction/EDC (CPT codes 17260-17266 trunk and 17280-17283 face). “I do biopsy prior to treatment,” she said. “I like the biopsy to be healed when I’m using the laser, so I’ll treat them about a month later.”
As for future directions, Dr. Ortiz and colleagues plan to evaluate the use of gold nanoparticles to more selectively target BCC during treatment with the 1,064-nm Nd:YAG laser. For now, she sees no downside of the procedure for proper candidates. “I do think that patients really like it,” she said. “It’s effective and easy.”
Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies. She is also cochair of the MOAS.
SAN DIEGO – After Arisa E. Ortiz, MD, and colleagues published results of a multicenter study reporting that one treatment with the long-pulsed 1,064-nm Nd:YAG laser cleared nonaggressive basal cell carcinoma (BCC) on the trunk and extremities in 90% of patients, she heard from colleagues who were skeptical of the approach.
Maybe it’s just the biopsy alone that’s clearing these tumors, some told her. Others postulated that since the energy was delivered with a 5- to 6-mm spot size at a fluence of 125-140 J/cm2 and a 7- to 10-ms pulse duration, bulk heating likely disrupted the tumors. However, treatments were generally well tolerated, required no anesthesia, and caused no significant adverse events.
“It’s almost scarless,” Dr. Ortiz, director of laser and cosmetic dermatology at the University of California, San Diego, said at the annual Masters of Aesthetics Symposium. “Sometimes the treatment does leave a mark, but I think the scars are always acceptable. We do have good histologic evidence that we can penetrate 2.15 mm, which is a lot deeper than what the pulsed-dye laser or other superficial wavelengths are able to penetrate.”
Data is well powered to reject the null hypothesis that laser treatment does not have an effect on nodular and superficial BCC lesions, she continued, noting that it is at least comparable if not superior with clearance rates reported for methyl aminolevulinate–PDT (73%), imiquimod cream (83%), and fluorouracil cream (80%). “Maybe we’re not specifically targeting the vasculature [with this approach], but we did some optical coherence tomography imaging and saw that the blood vessels in the tumor were coagulated while the vasculature in the surrounding normal skin were spared,” said Dr. Ortiz, who is also vice president of the American Society for Laser Medicine and Surgery.
In a more recent analysis, she and her colleagues retrospectively analyzed long-term outcomes in 11 patients with BCC who had 16 lesions treated with the 1,064-nm Nd:YAG laser. At a mean of 9 months, 100% of lesions remained clear as determined by clinical observation.
In a subsequent, as yet unpublished study, she and her collaborators followed 34 patients with BCC one year following laser treatment. “Of these, 33 had no recurrence at 1-year follow-up,” Dr. Ortiz said, noting that the one patient with a recurrence was on a biologic agent for Crohn’s disease.
One key advantage of using the long-pulsed 1,064-nm Nd:YAG laser for nonaggressive BCC is the potential for one treatment visit. “They don’t have to come back for suture removal,” she said. “It’s a quick procedure, takes only about 5 minutes. There’s no limitation on activity and there’s minimal wound care, light ointment, and a band-aid; that’s it.”
In addition, she said, there is a lower risk of complications, infections, and bleeding, and there is minimal scarring. It is “also an alternative for treating patients with multiple tumors or those who are poor surgical candidates, such as the elderly and those with Gorlin syndrome.”
Dr. Ortiz avoids treating aggressive subtypes “because we don’t know what margin to treat,” she added. “Avoid the face. I do make some exceptions for patients if they’re elderly or if they’ve had multiple tumors. Monitor for recurrence like you would using any other modality.”
She uses lidocaine without epinephrine to avoid vasoconstriction and treats with the 1,064-nm Nd:YAG laser as follows: a 5-mm spot size, a fluence of 140 J/cm2, and a pulse duration of 8 ms, with no cooling, which are the settings for the Excel V Laser System, she noted. “If you’re using a different Nd:YAG laser, your pulse duration may vary. I do let the device cool in between pulses to avoid bulk heating.”
The immediate endpoint to strive for is slight greying and slight contraction, and the procedure is covered by insurance, billed as malignant destruction/EDC (CPT codes 17260-17266 trunk and 17280-17283 face). “I do biopsy prior to treatment,” she said. “I like the biopsy to be healed when I’m using the laser, so I’ll treat them about a month later.”
As for future directions, Dr. Ortiz and colleagues plan to evaluate the use of gold nanoparticles to more selectively target BCC during treatment with the 1,064-nm Nd:YAG laser. For now, she sees no downside of the procedure for proper candidates. “I do think that patients really like it,” she said. “It’s effective and easy.”
Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies. She is also cochair of the MOAS.
SAN DIEGO – After Arisa E. Ortiz, MD, and colleagues published results of a multicenter study reporting that one treatment with the long-pulsed 1,064-nm Nd:YAG laser cleared nonaggressive basal cell carcinoma (BCC) on the trunk and extremities in 90% of patients, she heard from colleagues who were skeptical of the approach.
Maybe it’s just the biopsy alone that’s clearing these tumors, some told her. Others postulated that since the energy was delivered with a 5- to 6-mm spot size at a fluence of 125-140 J/cm2 and a 7- to 10-ms pulse duration, bulk heating likely disrupted the tumors. However, treatments were generally well tolerated, required no anesthesia, and caused no significant adverse events.
“It’s almost scarless,” Dr. Ortiz, director of laser and cosmetic dermatology at the University of California, San Diego, said at the annual Masters of Aesthetics Symposium. “Sometimes the treatment does leave a mark, but I think the scars are always acceptable. We do have good histologic evidence that we can penetrate 2.15 mm, which is a lot deeper than what the pulsed-dye laser or other superficial wavelengths are able to penetrate.”
Data is well powered to reject the null hypothesis that laser treatment does not have an effect on nodular and superficial BCC lesions, she continued, noting that it is at least comparable if not superior with clearance rates reported for methyl aminolevulinate–PDT (73%), imiquimod cream (83%), and fluorouracil cream (80%). “Maybe we’re not specifically targeting the vasculature [with this approach], but we did some optical coherence tomography imaging and saw that the blood vessels in the tumor were coagulated while the vasculature in the surrounding normal skin were spared,” said Dr. Ortiz, who is also vice president of the American Society for Laser Medicine and Surgery.
In a more recent analysis, she and her colleagues retrospectively analyzed long-term outcomes in 11 patients with BCC who had 16 lesions treated with the 1,064-nm Nd:YAG laser. At a mean of 9 months, 100% of lesions remained clear as determined by clinical observation.
In a subsequent, as yet unpublished study, she and her collaborators followed 34 patients with BCC one year following laser treatment. “Of these, 33 had no recurrence at 1-year follow-up,” Dr. Ortiz said, noting that the one patient with a recurrence was on a biologic agent for Crohn’s disease.
One key advantage of using the long-pulsed 1,064-nm Nd:YAG laser for nonaggressive BCC is the potential for one treatment visit. “They don’t have to come back for suture removal,” she said. “It’s a quick procedure, takes only about 5 minutes. There’s no limitation on activity and there’s minimal wound care, light ointment, and a band-aid; that’s it.”
In addition, she said, there is a lower risk of complications, infections, and bleeding, and there is minimal scarring. It is “also an alternative for treating patients with multiple tumors or those who are poor surgical candidates, such as the elderly and those with Gorlin syndrome.”
Dr. Ortiz avoids treating aggressive subtypes “because we don’t know what margin to treat,” she added. “Avoid the face. I do make some exceptions for patients if they’re elderly or if they’ve had multiple tumors. Monitor for recurrence like you would using any other modality.”
She uses lidocaine without epinephrine to avoid vasoconstriction and treats with the 1,064-nm Nd:YAG laser as follows: a 5-mm spot size, a fluence of 140 J/cm2, and a pulse duration of 8 ms, with no cooling, which are the settings for the Excel V Laser System, she noted. “If you’re using a different Nd:YAG laser, your pulse duration may vary. I do let the device cool in between pulses to avoid bulk heating.”
The immediate endpoint to strive for is slight greying and slight contraction, and the procedure is covered by insurance, billed as malignant destruction/EDC (CPT codes 17260-17266 trunk and 17280-17283 face). “I do biopsy prior to treatment,” she said. “I like the biopsy to be healed when I’m using the laser, so I’ll treat them about a month later.”
As for future directions, Dr. Ortiz and colleagues plan to evaluate the use of gold nanoparticles to more selectively target BCC during treatment with the 1,064-nm Nd:YAG laser. For now, she sees no downside of the procedure for proper candidates. “I do think that patients really like it,” she said. “It’s effective and easy.”
Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies. She is also cochair of the MOAS.
AT MOAS 2022
Age-related atopic dermatitis phenotypes evaluated in study
, while older adults tend to present with less flexural eczema and the fewest associated signs.
Those are key findings from a study conducted at a single academic medical center, which aimed to identify the age-related clinical phenotypes of AD.
“Previous studies have found differences in the clinical characteristics of AD depending on age of AD onset, ethnic background, and AD severity,” senior author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the department of dermatology at George Washington University, Washington, and his coauthor wrote in the study, which was published online in JAAD International. “However, none have prospectively compared the clinical characteristics and associated signs by age group. Improved understanding of the clinical phenotypes of AD may help guide choice of treatment and improve health outcomes,” they added.
Along with coauthor Sheena Chatrath, a dermatology research fellow in the department, Dr. Silverberg prospectively reviewed self-reported questionnaires that were completed by 380 patients prior to their visit at GWU’s eczema clinic between 2013 and 2019. Questions included age of AD onset, sociodemographics, Visual Analog Scale (VAS) itch and sleep for Scoring AD, and Numeric Rating Scale (NRS) for skin pain and itch. The researchers used the Eczema Area Severity Index to assess AD severity and a dermatologist conducted full body skin exams, noting the distribution of AD involvement as well as associated signs.
Of the 380 patients, 6.1% were younger than aged 18 years, 46.3% were young adults aged 18-39 years, and 47.6% were older adults 40 years of age and older.
Compared with pediatric patients, both young and older adults were less likely to experience AD on the ankles (adjusted odds ratio [aOR], 0.41 and 0.43, respectively), moderate to severe AD lesions on flexures (aOR, 0.47 and 0.30), pityriasis alba (aOR, 0.24 and 0.07), oozing lesions (aOR, 0.44 and 0.35), and moderate to severe excoriations (aOR, 0.49 and 0.44).
In children, severe itch was more common, reported in 47.1%, compared with 43.4% of the young adults and 38.6% of the older adults, and itch was less severe among the young and older adults. “Interestingly, despite increased itch in pediatric patients, we found no difference in the severity of skin pain across all age groups,” the researchers wrote. “Moreover, pediatric patients reported skin pain less often than adult patients. This may be due to age-related differences of pain perception.”
In other findings, compared with pediatric patients, young adults were more likely to experience AD around the eyes (aOR, 2.92), while older adults were less likely to experience AD on elbows (aOR, 0.34), nipples (aOR, 0.40), knees (aOR, 0.27), and less likely to have keratosis pilaris (aOR, 0.38), and lichenification (aOR, 0.47).
Dr. Silverberg and Ms. Chatrath used latent class analysis to identify four classes for distribution of AD lesions. In this model, class 1 had low probabilities of AD involvement at all sites examined and class 2 had low probabilities of scalp, face, and foot involvement, and intermediate probability of all other AD sites. Class 3 had low probabilities of hand and foot involvement, high probability of facial erythema, and intermediate probability of all other AD signs, while class 4 had intermediate probability of postauricular and foot involvement, and high probability of all other AD sites examined.
“Pediatric patients were most commonly in class 4 (33.3%), followed by class 1 and 2 (26.7%), and least commonly in class 3 (13.3%),” the authors wrote. “In young adults, class 4 and 1 were most common (32.4% and 29.4%), followed by class 2 (27.9%), and least commonly class 3 (10.3%). In older adults, class 1 was most common (40.3%), followed by class 4 (23.6%), and least commonly classes 2 and 3 (18.1%).”
The researchers also used latent class analysis to identify four classes for the signs and symptoms of AD. In this model, class 1 had zero-low probability of all AD signs and class 2 had low probability of all AD signs. Class 3 had high probability of oozing lesions and low probability of all other signs, while class 4 had high probability of xerosis, intermediate probability of ichthyosis and palmar hyperlinearity, and low probability of all other AD signs.
In all three groups, the most common class was class 1 (85.6% of older adults, 81.8% of younger adults, and 82.6% of pediatric patients). Among the pediatric patients, they wrote, “class 3 was the second most common (8.7%), followed by class 2 and 4 (4.4%).” Among the young adults, 9.7% were in class 2, 5.7% were in class 4, and 2.8% were in class 3; and among the older adults, 8.3% were in class 4, 4.4% were in class 2, and 1.67% were in class 3.
Zelma Chiesa Fuxench, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who was asked to comment on the study, said that while AD is traditionally largely thought of as a disease of children primarily involving the flexural areas, “this study provides additional evidence to support that AD is more than just a disease of childhood with a fixed clinical presentation, but is a heterogeneous disease whose clinical presentation varies across different population groups.”
While the study provides insight into the clinical differences that may be observed across AD groups, “care must be taken when interpreting these results as the study was done in a single center with observations collected during one single visit,” she added. “AD is not a ‘static’ disease; its presentation can stay the same in one patient but can vary even in another patient throughout their lifetime. Therefore, studies of a more prospective nature that evaluate the change in clinical presentation using multiple measures throughout time in these individuals would be a step forward to better understand if these phenotypic differences truly exist and, as such, what implications could they have for treatment selection.”
This study was supported by grants from the Agency for Healthcare Research and Quality and the Dermatology Foundation. The researchers reported having no disclosures. Dr. Chiesa Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.
, while older adults tend to present with less flexural eczema and the fewest associated signs.
Those are key findings from a study conducted at a single academic medical center, which aimed to identify the age-related clinical phenotypes of AD.
“Previous studies have found differences in the clinical characteristics of AD depending on age of AD onset, ethnic background, and AD severity,” senior author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the department of dermatology at George Washington University, Washington, and his coauthor wrote in the study, which was published online in JAAD International. “However, none have prospectively compared the clinical characteristics and associated signs by age group. Improved understanding of the clinical phenotypes of AD may help guide choice of treatment and improve health outcomes,” they added.
Along with coauthor Sheena Chatrath, a dermatology research fellow in the department, Dr. Silverberg prospectively reviewed self-reported questionnaires that were completed by 380 patients prior to their visit at GWU’s eczema clinic between 2013 and 2019. Questions included age of AD onset, sociodemographics, Visual Analog Scale (VAS) itch and sleep for Scoring AD, and Numeric Rating Scale (NRS) for skin pain and itch. The researchers used the Eczema Area Severity Index to assess AD severity and a dermatologist conducted full body skin exams, noting the distribution of AD involvement as well as associated signs.
Of the 380 patients, 6.1% were younger than aged 18 years, 46.3% were young adults aged 18-39 years, and 47.6% were older adults 40 years of age and older.
Compared with pediatric patients, both young and older adults were less likely to experience AD on the ankles (adjusted odds ratio [aOR], 0.41 and 0.43, respectively), moderate to severe AD lesions on flexures (aOR, 0.47 and 0.30), pityriasis alba (aOR, 0.24 and 0.07), oozing lesions (aOR, 0.44 and 0.35), and moderate to severe excoriations (aOR, 0.49 and 0.44).
In children, severe itch was more common, reported in 47.1%, compared with 43.4% of the young adults and 38.6% of the older adults, and itch was less severe among the young and older adults. “Interestingly, despite increased itch in pediatric patients, we found no difference in the severity of skin pain across all age groups,” the researchers wrote. “Moreover, pediatric patients reported skin pain less often than adult patients. This may be due to age-related differences of pain perception.”
In other findings, compared with pediatric patients, young adults were more likely to experience AD around the eyes (aOR, 2.92), while older adults were less likely to experience AD on elbows (aOR, 0.34), nipples (aOR, 0.40), knees (aOR, 0.27), and less likely to have keratosis pilaris (aOR, 0.38), and lichenification (aOR, 0.47).
Dr. Silverberg and Ms. Chatrath used latent class analysis to identify four classes for distribution of AD lesions. In this model, class 1 had low probabilities of AD involvement at all sites examined and class 2 had low probabilities of scalp, face, and foot involvement, and intermediate probability of all other AD sites. Class 3 had low probabilities of hand and foot involvement, high probability of facial erythema, and intermediate probability of all other AD signs, while class 4 had intermediate probability of postauricular and foot involvement, and high probability of all other AD sites examined.
“Pediatric patients were most commonly in class 4 (33.3%), followed by class 1 and 2 (26.7%), and least commonly in class 3 (13.3%),” the authors wrote. “In young adults, class 4 and 1 were most common (32.4% and 29.4%), followed by class 2 (27.9%), and least commonly class 3 (10.3%). In older adults, class 1 was most common (40.3%), followed by class 4 (23.6%), and least commonly classes 2 and 3 (18.1%).”
The researchers also used latent class analysis to identify four classes for the signs and symptoms of AD. In this model, class 1 had zero-low probability of all AD signs and class 2 had low probability of all AD signs. Class 3 had high probability of oozing lesions and low probability of all other signs, while class 4 had high probability of xerosis, intermediate probability of ichthyosis and palmar hyperlinearity, and low probability of all other AD signs.
In all three groups, the most common class was class 1 (85.6% of older adults, 81.8% of younger adults, and 82.6% of pediatric patients). Among the pediatric patients, they wrote, “class 3 was the second most common (8.7%), followed by class 2 and 4 (4.4%).” Among the young adults, 9.7% were in class 2, 5.7% were in class 4, and 2.8% were in class 3; and among the older adults, 8.3% were in class 4, 4.4% were in class 2, and 1.67% were in class 3.
Zelma Chiesa Fuxench, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who was asked to comment on the study, said that while AD is traditionally largely thought of as a disease of children primarily involving the flexural areas, “this study provides additional evidence to support that AD is more than just a disease of childhood with a fixed clinical presentation, but is a heterogeneous disease whose clinical presentation varies across different population groups.”
While the study provides insight into the clinical differences that may be observed across AD groups, “care must be taken when interpreting these results as the study was done in a single center with observations collected during one single visit,” she added. “AD is not a ‘static’ disease; its presentation can stay the same in one patient but can vary even in another patient throughout their lifetime. Therefore, studies of a more prospective nature that evaluate the change in clinical presentation using multiple measures throughout time in these individuals would be a step forward to better understand if these phenotypic differences truly exist and, as such, what implications could they have for treatment selection.”
This study was supported by grants from the Agency for Healthcare Research and Quality and the Dermatology Foundation. The researchers reported having no disclosures. Dr. Chiesa Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.
, while older adults tend to present with less flexural eczema and the fewest associated signs.
Those are key findings from a study conducted at a single academic medical center, which aimed to identify the age-related clinical phenotypes of AD.
“Previous studies have found differences in the clinical characteristics of AD depending on age of AD onset, ethnic background, and AD severity,” senior author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the department of dermatology at George Washington University, Washington, and his coauthor wrote in the study, which was published online in JAAD International. “However, none have prospectively compared the clinical characteristics and associated signs by age group. Improved understanding of the clinical phenotypes of AD may help guide choice of treatment and improve health outcomes,” they added.
Along with coauthor Sheena Chatrath, a dermatology research fellow in the department, Dr. Silverberg prospectively reviewed self-reported questionnaires that were completed by 380 patients prior to their visit at GWU’s eczema clinic between 2013 and 2019. Questions included age of AD onset, sociodemographics, Visual Analog Scale (VAS) itch and sleep for Scoring AD, and Numeric Rating Scale (NRS) for skin pain and itch. The researchers used the Eczema Area Severity Index to assess AD severity and a dermatologist conducted full body skin exams, noting the distribution of AD involvement as well as associated signs.
Of the 380 patients, 6.1% were younger than aged 18 years, 46.3% were young adults aged 18-39 years, and 47.6% were older adults 40 years of age and older.
Compared with pediatric patients, both young and older adults were less likely to experience AD on the ankles (adjusted odds ratio [aOR], 0.41 and 0.43, respectively), moderate to severe AD lesions on flexures (aOR, 0.47 and 0.30), pityriasis alba (aOR, 0.24 and 0.07), oozing lesions (aOR, 0.44 and 0.35), and moderate to severe excoriations (aOR, 0.49 and 0.44).
In children, severe itch was more common, reported in 47.1%, compared with 43.4% of the young adults and 38.6% of the older adults, and itch was less severe among the young and older adults. “Interestingly, despite increased itch in pediatric patients, we found no difference in the severity of skin pain across all age groups,” the researchers wrote. “Moreover, pediatric patients reported skin pain less often than adult patients. This may be due to age-related differences of pain perception.”
In other findings, compared with pediatric patients, young adults were more likely to experience AD around the eyes (aOR, 2.92), while older adults were less likely to experience AD on elbows (aOR, 0.34), nipples (aOR, 0.40), knees (aOR, 0.27), and less likely to have keratosis pilaris (aOR, 0.38), and lichenification (aOR, 0.47).
Dr. Silverberg and Ms. Chatrath used latent class analysis to identify four classes for distribution of AD lesions. In this model, class 1 had low probabilities of AD involvement at all sites examined and class 2 had low probabilities of scalp, face, and foot involvement, and intermediate probability of all other AD sites. Class 3 had low probabilities of hand and foot involvement, high probability of facial erythema, and intermediate probability of all other AD signs, while class 4 had intermediate probability of postauricular and foot involvement, and high probability of all other AD sites examined.
“Pediatric patients were most commonly in class 4 (33.3%), followed by class 1 and 2 (26.7%), and least commonly in class 3 (13.3%),” the authors wrote. “In young adults, class 4 and 1 were most common (32.4% and 29.4%), followed by class 2 (27.9%), and least commonly class 3 (10.3%). In older adults, class 1 was most common (40.3%), followed by class 4 (23.6%), and least commonly classes 2 and 3 (18.1%).”
The researchers also used latent class analysis to identify four classes for the signs and symptoms of AD. In this model, class 1 had zero-low probability of all AD signs and class 2 had low probability of all AD signs. Class 3 had high probability of oozing lesions and low probability of all other signs, while class 4 had high probability of xerosis, intermediate probability of ichthyosis and palmar hyperlinearity, and low probability of all other AD signs.
In all three groups, the most common class was class 1 (85.6% of older adults, 81.8% of younger adults, and 82.6% of pediatric patients). Among the pediatric patients, they wrote, “class 3 was the second most common (8.7%), followed by class 2 and 4 (4.4%).” Among the young adults, 9.7% were in class 2, 5.7% were in class 4, and 2.8% were in class 3; and among the older adults, 8.3% were in class 4, 4.4% were in class 2, and 1.67% were in class 3.
Zelma Chiesa Fuxench, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who was asked to comment on the study, said that while AD is traditionally largely thought of as a disease of children primarily involving the flexural areas, “this study provides additional evidence to support that AD is more than just a disease of childhood with a fixed clinical presentation, but is a heterogeneous disease whose clinical presentation varies across different population groups.”
While the study provides insight into the clinical differences that may be observed across AD groups, “care must be taken when interpreting these results as the study was done in a single center with observations collected during one single visit,” she added. “AD is not a ‘static’ disease; its presentation can stay the same in one patient but can vary even in another patient throughout their lifetime. Therefore, studies of a more prospective nature that evaluate the change in clinical presentation using multiple measures throughout time in these individuals would be a step forward to better understand if these phenotypic differences truly exist and, as such, what implications could they have for treatment selection.”
This study was supported by grants from the Agency for Healthcare Research and Quality and the Dermatology Foundation. The researchers reported having no disclosures. Dr. Chiesa Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.
FROM JAAD INTERNATIONAL
AAD unveils updated guidelines for topical AD treatment in adults
, and topical phosphodiesterase-4 (PDE-4) and Janus kinase (JAK) inhibitors. The guidelines also conditionally recommend the use of bathing and wet wrap therapy but recommend against the use of topical antimicrobials, antiseptics, and antihistamines.
The development updates the AAD’s 2014 recommendations for managing AD with topical therapies, published almost 9 years ago. “At that time, the only U.S. FDA–approved systemic medication for atopic dermatitis was prednisone – universally felt amongst dermatologists to be the least appropriate systemic medication for this condition, at least chronically,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the updated guidelines, told this news organization in an interview.
“Since 2017, there have been two different biologic medications approved for moderate to severe AD (dupilumab and tralokinumab) with certainly a third or more right around the corner. There have been two new oral agents approved for moderate to severe AD – upadacitinib and abrocitinib – with others on the way,” he noted. While these are not topical therapies, the purview of the newly released guidelines, he said, “there have also been new topical medications approved since that time (crisaborole and ruxolitinib). It was high time for an update.”
For the new guidelines, which were published online in the Journal of the American Academy of Dermatology, Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic review of evidence regarding the use of nonprescription topical agents such as moisturizers, bathing practices, and wet wraps, as well as topical pharmacologic modalities such as corticosteroids, calcineurin inhibitors, JAK inhibitors, PDE-4 inhibitors, antimicrobials, and antihistamines.
Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
12 recommendations
Of the 12 recommendations made for adults with AD, the work group ranked 7 as “strong” based on the evidence reviewed, and the rest as “conditional.” The “strong” recommendations include the use of moisturizers; the use of tacrolimus 0.03% or 0.1%; the use of pimecrolimus 1% cream for mild to moderate AD; use of topical steroids; intermittent use of medium-potency topical corticosteroids as maintenance therapy to reduce flares and relapse; the use of the topical PDE-4 inhibitor crisaborole, and the use of the topical JAK inhibitor ruxolitinib.
Regarding ruxolitinib cream 1.5%, the work group advised that the treatment area “should not exceed 20% body surface area, and a maximum of 60 grams should be applied per week; these stipulations are aimed at reducing systemic absorption, as black box warnings include serious infections, mortality, malignancies (for example, lymphoma), major adverse cardiovascular events, and thrombosis.”
Conditional recommendations in the guidelines include those for bathing for treatment and maintenance and the use of wet dressings, and those against the use of topical antimicrobials, topical antihistamines, and topical antiseptics.
According to Dr. Sidbury, the topic of bathing generated robust discussion among the work group members. “Though [each group member] has strong opinions and individual practice styles, they were also able to recognize that the evidence is all that matters in a project like this, which led to a ‘conditional’ recommendation regarding bathing frequency backed by ‘low’ evidence,” he said. “While this may seem like ‘guidance’ that doesn’t ‘guide,’ I would argue it informs the guideline consumer exactly where we are in terms of this question and allows them to use their best judgment and experience as their true north here.”
In the realm of topical steroids, Dr. Sidbury said that topical steroid addiction (TSA) and topical steroid withdrawal (TSW) have been a “controversial but persistent concern” from some patients and providers. “Two systematic reviews of this topic were mentioned, and it was made clear that the evidence base [for the concepts] is weak,” he said. “With that important caveat ,the guideline committee delineated both a definition of TSW/TSA and potential risk factors.”
Dr. Sidbury marveled at the potential impact of newer medicines such as crisaborole and ruxolitinib on younger AD patients as well. Crisaborole is now Food and Drug Administration approved down to 3 months of age for mild to moderate AD. “This is extraordinary and expands treatment options for all providers at an age when parents and providers are most conservative in their practice,” he said. “Ruxolitinib, also nonsteroidal, is FDA approved for mild to moderate AD down to 12 years of age. Having spent a good percentage of my practice years either being able to offer only topical steroids, or later topical steroids and topical calcineurin inhibitors like tacrolimus or pimecrolimus, having additional options is wonderful.”
In the guidelines, the work group noted that “significant gaps remain” in current understanding of various topical AD therapies. “Studies are needed which examine quality of life and other patient-important outcomes, changes to the cutaneous microbiome, as well as long term follow-up, and use in special and diverse populations (e.g., pregnancy, lactation, immunosuppression, multiple comorbidities, skin of color, pediatric),” they wrote. “Furthermore, increased use of new systemic AD treatment options (dupilumab, tralokinumab, abrocitinib, upadacitinib) in patients with moderate to severe disease may result in a selection bias toward milder disease in current and future AD topical therapy studies.”
Use of topical therapies to manage AD in pediatric patients will be covered in a forthcoming AAD guideline. The first updated AD guideline, on comorbidities associated with AD in adults, was released in January 2022.
Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Microes. Other work group members reported having financial disclosures with many pharmaceutical companies.
, and topical phosphodiesterase-4 (PDE-4) and Janus kinase (JAK) inhibitors. The guidelines also conditionally recommend the use of bathing and wet wrap therapy but recommend against the use of topical antimicrobials, antiseptics, and antihistamines.
The development updates the AAD’s 2014 recommendations for managing AD with topical therapies, published almost 9 years ago. “At that time, the only U.S. FDA–approved systemic medication for atopic dermatitis was prednisone – universally felt amongst dermatologists to be the least appropriate systemic medication for this condition, at least chronically,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the updated guidelines, told this news organization in an interview.
“Since 2017, there have been two different biologic medications approved for moderate to severe AD (dupilumab and tralokinumab) with certainly a third or more right around the corner. There have been two new oral agents approved for moderate to severe AD – upadacitinib and abrocitinib – with others on the way,” he noted. While these are not topical therapies, the purview of the newly released guidelines, he said, “there have also been new topical medications approved since that time (crisaborole and ruxolitinib). It was high time for an update.”
For the new guidelines, which were published online in the Journal of the American Academy of Dermatology, Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic review of evidence regarding the use of nonprescription topical agents such as moisturizers, bathing practices, and wet wraps, as well as topical pharmacologic modalities such as corticosteroids, calcineurin inhibitors, JAK inhibitors, PDE-4 inhibitors, antimicrobials, and antihistamines.
Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
12 recommendations
Of the 12 recommendations made for adults with AD, the work group ranked 7 as “strong” based on the evidence reviewed, and the rest as “conditional.” The “strong” recommendations include the use of moisturizers; the use of tacrolimus 0.03% or 0.1%; the use of pimecrolimus 1% cream for mild to moderate AD; use of topical steroids; intermittent use of medium-potency topical corticosteroids as maintenance therapy to reduce flares and relapse; the use of the topical PDE-4 inhibitor crisaborole, and the use of the topical JAK inhibitor ruxolitinib.
Regarding ruxolitinib cream 1.5%, the work group advised that the treatment area “should not exceed 20% body surface area, and a maximum of 60 grams should be applied per week; these stipulations are aimed at reducing systemic absorption, as black box warnings include serious infections, mortality, malignancies (for example, lymphoma), major adverse cardiovascular events, and thrombosis.”
Conditional recommendations in the guidelines include those for bathing for treatment and maintenance and the use of wet dressings, and those against the use of topical antimicrobials, topical antihistamines, and topical antiseptics.
According to Dr. Sidbury, the topic of bathing generated robust discussion among the work group members. “Though [each group member] has strong opinions and individual practice styles, they were also able to recognize that the evidence is all that matters in a project like this, which led to a ‘conditional’ recommendation regarding bathing frequency backed by ‘low’ evidence,” he said. “While this may seem like ‘guidance’ that doesn’t ‘guide,’ I would argue it informs the guideline consumer exactly where we are in terms of this question and allows them to use their best judgment and experience as their true north here.”
In the realm of topical steroids, Dr. Sidbury said that topical steroid addiction (TSA) and topical steroid withdrawal (TSW) have been a “controversial but persistent concern” from some patients and providers. “Two systematic reviews of this topic were mentioned, and it was made clear that the evidence base [for the concepts] is weak,” he said. “With that important caveat ,the guideline committee delineated both a definition of TSW/TSA and potential risk factors.”
Dr. Sidbury marveled at the potential impact of newer medicines such as crisaborole and ruxolitinib on younger AD patients as well. Crisaborole is now Food and Drug Administration approved down to 3 months of age for mild to moderate AD. “This is extraordinary and expands treatment options for all providers at an age when parents and providers are most conservative in their practice,” he said. “Ruxolitinib, also nonsteroidal, is FDA approved for mild to moderate AD down to 12 years of age. Having spent a good percentage of my practice years either being able to offer only topical steroids, or later topical steroids and topical calcineurin inhibitors like tacrolimus or pimecrolimus, having additional options is wonderful.”
In the guidelines, the work group noted that “significant gaps remain” in current understanding of various topical AD therapies. “Studies are needed which examine quality of life and other patient-important outcomes, changes to the cutaneous microbiome, as well as long term follow-up, and use in special and diverse populations (e.g., pregnancy, lactation, immunosuppression, multiple comorbidities, skin of color, pediatric),” they wrote. “Furthermore, increased use of new systemic AD treatment options (dupilumab, tralokinumab, abrocitinib, upadacitinib) in patients with moderate to severe disease may result in a selection bias toward milder disease in current and future AD topical therapy studies.”
Use of topical therapies to manage AD in pediatric patients will be covered in a forthcoming AAD guideline. The first updated AD guideline, on comorbidities associated with AD in adults, was released in January 2022.
Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Microes. Other work group members reported having financial disclosures with many pharmaceutical companies.
, and topical phosphodiesterase-4 (PDE-4) and Janus kinase (JAK) inhibitors. The guidelines also conditionally recommend the use of bathing and wet wrap therapy but recommend against the use of topical antimicrobials, antiseptics, and antihistamines.
The development updates the AAD’s 2014 recommendations for managing AD with topical therapies, published almost 9 years ago. “At that time, the only U.S. FDA–approved systemic medication for atopic dermatitis was prednisone – universally felt amongst dermatologists to be the least appropriate systemic medication for this condition, at least chronically,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the updated guidelines, told this news organization in an interview.
“Since 2017, there have been two different biologic medications approved for moderate to severe AD (dupilumab and tralokinumab) with certainly a third or more right around the corner. There have been two new oral agents approved for moderate to severe AD – upadacitinib and abrocitinib – with others on the way,” he noted. While these are not topical therapies, the purview of the newly released guidelines, he said, “there have also been new topical medications approved since that time (crisaborole and ruxolitinib). It was high time for an update.”
For the new guidelines, which were published online in the Journal of the American Academy of Dermatology, Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic review of evidence regarding the use of nonprescription topical agents such as moisturizers, bathing practices, and wet wraps, as well as topical pharmacologic modalities such as corticosteroids, calcineurin inhibitors, JAK inhibitors, PDE-4 inhibitors, antimicrobials, and antihistamines.
Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
12 recommendations
Of the 12 recommendations made for adults with AD, the work group ranked 7 as “strong” based on the evidence reviewed, and the rest as “conditional.” The “strong” recommendations include the use of moisturizers; the use of tacrolimus 0.03% or 0.1%; the use of pimecrolimus 1% cream for mild to moderate AD; use of topical steroids; intermittent use of medium-potency topical corticosteroids as maintenance therapy to reduce flares and relapse; the use of the topical PDE-4 inhibitor crisaborole, and the use of the topical JAK inhibitor ruxolitinib.
Regarding ruxolitinib cream 1.5%, the work group advised that the treatment area “should not exceed 20% body surface area, and a maximum of 60 grams should be applied per week; these stipulations are aimed at reducing systemic absorption, as black box warnings include serious infections, mortality, malignancies (for example, lymphoma), major adverse cardiovascular events, and thrombosis.”
Conditional recommendations in the guidelines include those for bathing for treatment and maintenance and the use of wet dressings, and those against the use of topical antimicrobials, topical antihistamines, and topical antiseptics.
According to Dr. Sidbury, the topic of bathing generated robust discussion among the work group members. “Though [each group member] has strong opinions and individual practice styles, they were also able to recognize that the evidence is all that matters in a project like this, which led to a ‘conditional’ recommendation regarding bathing frequency backed by ‘low’ evidence,” he said. “While this may seem like ‘guidance’ that doesn’t ‘guide,’ I would argue it informs the guideline consumer exactly where we are in terms of this question and allows them to use their best judgment and experience as their true north here.”
In the realm of topical steroids, Dr. Sidbury said that topical steroid addiction (TSA) and topical steroid withdrawal (TSW) have been a “controversial but persistent concern” from some patients and providers. “Two systematic reviews of this topic were mentioned, and it was made clear that the evidence base [for the concepts] is weak,” he said. “With that important caveat ,the guideline committee delineated both a definition of TSW/TSA and potential risk factors.”
Dr. Sidbury marveled at the potential impact of newer medicines such as crisaborole and ruxolitinib on younger AD patients as well. Crisaborole is now Food and Drug Administration approved down to 3 months of age for mild to moderate AD. “This is extraordinary and expands treatment options for all providers at an age when parents and providers are most conservative in their practice,” he said. “Ruxolitinib, also nonsteroidal, is FDA approved for mild to moderate AD down to 12 years of age. Having spent a good percentage of my practice years either being able to offer only topical steroids, or later topical steroids and topical calcineurin inhibitors like tacrolimus or pimecrolimus, having additional options is wonderful.”
In the guidelines, the work group noted that “significant gaps remain” in current understanding of various topical AD therapies. “Studies are needed which examine quality of life and other patient-important outcomes, changes to the cutaneous microbiome, as well as long term follow-up, and use in special and diverse populations (e.g., pregnancy, lactation, immunosuppression, multiple comorbidities, skin of color, pediatric),” they wrote. “Furthermore, increased use of new systemic AD treatment options (dupilumab, tralokinumab, abrocitinib, upadacitinib) in patients with moderate to severe disease may result in a selection bias toward milder disease in current and future AD topical therapy studies.”
Use of topical therapies to manage AD in pediatric patients will be covered in a forthcoming AAD guideline. The first updated AD guideline, on comorbidities associated with AD in adults, was released in January 2022.
Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Microes. Other work group members reported having financial disclosures with many pharmaceutical companies.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Picosecond lasers for tattoo removal could benefit from enhancements, expert says
SAN DIEGO – When picosecond lasers hit the market about 10 years ago, they became a game-changer for tattoo removal, boasting the delivery of energy that is about threefold faster than with nanosecond lasers.
However, picosecond lasers are far from perfect even in the hands of the most experienced clinicians, according to Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford. “They have been very difficult to build from an engineering perspective,” he said at the annual Masters of Aesthetics Symposium. It took a long time for these lasers to come to the market, and they are still fairly expensive and require a lot of maintenance, he noted. In addition, “they are also not quite as ‘picosecond’ as they need to be. I think there is definitely room to improve, but this is the gold standard.”
Today, . Tattoo ink particles average about 0.1 mcm in size, and the thermal relaxation size works out to be less than 10 nanoseconds, with shorter pulses better at capturing the ink particles that are smaller than average.
Black is the most common tattoo color dermatologists treat. “For that, you can typically use a 1064, which has the highest absorption, but you can also use many of the other wavelengths,” he said. “Other colors are less common, followed by red, for which you would use a 532-nm wavelength.”
Dr. Ibrahimi underscored the importance of setting realistic expectations during consults with patients seeking options for tattoo removal. Even with picosecond laser technology, many treatments are typically required and “a good patient consultation is key to setting proper expectations,” he said. “If you promise someone results in 4 to 5 treatments like many of the device companies will say you can achieve, you’re going to have a large group of patients who are disappointed.”
The clinical endpoint to strive for during tattoo removal is whitening of the ink, which typically fades about 20 minutes after treatment. That whitening corresponds to cavitation, or the production of gas vacuoles in the cells that were holding the ink. This discovery led to a technique intended to enhance tattoo removal. In 2012, R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, and colleagues published results of a study that compared a single Q-switched laser treatment pass with four treatment passes separated by 20 minutes. After treating 18 tattoos in 12 adults, they found that the technique, known as the “R20” method, was more effective than a single-pass treatment (P < .01).
“Subsequent to this, there has been conflicting data on whether this is truly effective or not,” said Dr. Ibrahimi, who is also on the board of directors for the American Society for Dermatologic Surgery and the American Society for Laser Medicine and Surgery. “Most of us agree that one additional pass would be helpful, but when you’re doing this in the private practice setting, it’s often challenging because patients aren’t necessarily willing to pay more for more than just one pass for their tattoo removal.”
Another recent advance is use of a topical square silicone patch infused with perfluorodecalin (PFD) for use during tattoo removal, which has been shown to reduce epidermal whitening. The patch contains a fluorocarbon “that is very good at dissolving gas, and it is already widely used in medicine,” he said. When applied, “it almost instantaneously takes the whitening away; you don’t have to wait the 20 minutes to do your second pass.”
A different technology designed to speed up tattoo removal is the Resonic Rapid Acoustic Pulse device (marketed as Resonic, from Allergan Aesthetics), which is cleared by the FDA for use as an accessory to the 1064 nm Q-switched laser for black tattoo removal in patients with skin types I-III. “This uses acoustic pulses of sound waves; they’re rapid and powerful,” Dr. Ibrahimi said. “They can clear those cavitation bubbles much like the PFD patches do. It’s also thought that they further disperse the tattoo ink particles by supplementing the laser energy as well. It is also purported to alter the body’s healing response, or immune response, which is important in tattoo clearing.”
Dr. Ibrahimi disclosed that he is a member of the Advisory Board for Accure Acne, AbbVie (which owns Allergan), Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies.
SAN DIEGO – When picosecond lasers hit the market about 10 years ago, they became a game-changer for tattoo removal, boasting the delivery of energy that is about threefold faster than with nanosecond lasers.
However, picosecond lasers are far from perfect even in the hands of the most experienced clinicians, according to Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford. “They have been very difficult to build from an engineering perspective,” he said at the annual Masters of Aesthetics Symposium. It took a long time for these lasers to come to the market, and they are still fairly expensive and require a lot of maintenance, he noted. In addition, “they are also not quite as ‘picosecond’ as they need to be. I think there is definitely room to improve, but this is the gold standard.”
Today, . Tattoo ink particles average about 0.1 mcm in size, and the thermal relaxation size works out to be less than 10 nanoseconds, with shorter pulses better at capturing the ink particles that are smaller than average.
Black is the most common tattoo color dermatologists treat. “For that, you can typically use a 1064, which has the highest absorption, but you can also use many of the other wavelengths,” he said. “Other colors are less common, followed by red, for which you would use a 532-nm wavelength.”
Dr. Ibrahimi underscored the importance of setting realistic expectations during consults with patients seeking options for tattoo removal. Even with picosecond laser technology, many treatments are typically required and “a good patient consultation is key to setting proper expectations,” he said. “If you promise someone results in 4 to 5 treatments like many of the device companies will say you can achieve, you’re going to have a large group of patients who are disappointed.”
The clinical endpoint to strive for during tattoo removal is whitening of the ink, which typically fades about 20 minutes after treatment. That whitening corresponds to cavitation, or the production of gas vacuoles in the cells that were holding the ink. This discovery led to a technique intended to enhance tattoo removal. In 2012, R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, and colleagues published results of a study that compared a single Q-switched laser treatment pass with four treatment passes separated by 20 minutes. After treating 18 tattoos in 12 adults, they found that the technique, known as the “R20” method, was more effective than a single-pass treatment (P < .01).
“Subsequent to this, there has been conflicting data on whether this is truly effective or not,” said Dr. Ibrahimi, who is also on the board of directors for the American Society for Dermatologic Surgery and the American Society for Laser Medicine and Surgery. “Most of us agree that one additional pass would be helpful, but when you’re doing this in the private practice setting, it’s often challenging because patients aren’t necessarily willing to pay more for more than just one pass for their tattoo removal.”
Another recent advance is use of a topical square silicone patch infused with perfluorodecalin (PFD) for use during tattoo removal, which has been shown to reduce epidermal whitening. The patch contains a fluorocarbon “that is very good at dissolving gas, and it is already widely used in medicine,” he said. When applied, “it almost instantaneously takes the whitening away; you don’t have to wait the 20 minutes to do your second pass.”
A different technology designed to speed up tattoo removal is the Resonic Rapid Acoustic Pulse device (marketed as Resonic, from Allergan Aesthetics), which is cleared by the FDA for use as an accessory to the 1064 nm Q-switched laser for black tattoo removal in patients with skin types I-III. “This uses acoustic pulses of sound waves; they’re rapid and powerful,” Dr. Ibrahimi said. “They can clear those cavitation bubbles much like the PFD patches do. It’s also thought that they further disperse the tattoo ink particles by supplementing the laser energy as well. It is also purported to alter the body’s healing response, or immune response, which is important in tattoo clearing.”
Dr. Ibrahimi disclosed that he is a member of the Advisory Board for Accure Acne, AbbVie (which owns Allergan), Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies.
SAN DIEGO – When picosecond lasers hit the market about 10 years ago, they became a game-changer for tattoo removal, boasting the delivery of energy that is about threefold faster than with nanosecond lasers.
However, picosecond lasers are far from perfect even in the hands of the most experienced clinicians, according to Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford. “They have been very difficult to build from an engineering perspective,” he said at the annual Masters of Aesthetics Symposium. It took a long time for these lasers to come to the market, and they are still fairly expensive and require a lot of maintenance, he noted. In addition, “they are also not quite as ‘picosecond’ as they need to be. I think there is definitely room to improve, but this is the gold standard.”
Today, . Tattoo ink particles average about 0.1 mcm in size, and the thermal relaxation size works out to be less than 10 nanoseconds, with shorter pulses better at capturing the ink particles that are smaller than average.
Black is the most common tattoo color dermatologists treat. “For that, you can typically use a 1064, which has the highest absorption, but you can also use many of the other wavelengths,” he said. “Other colors are less common, followed by red, for which you would use a 532-nm wavelength.”
Dr. Ibrahimi underscored the importance of setting realistic expectations during consults with patients seeking options for tattoo removal. Even with picosecond laser technology, many treatments are typically required and “a good patient consultation is key to setting proper expectations,” he said. “If you promise someone results in 4 to 5 treatments like many of the device companies will say you can achieve, you’re going to have a large group of patients who are disappointed.”
The clinical endpoint to strive for during tattoo removal is whitening of the ink, which typically fades about 20 minutes after treatment. That whitening corresponds to cavitation, or the production of gas vacuoles in the cells that were holding the ink. This discovery led to a technique intended to enhance tattoo removal. In 2012, R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, and colleagues published results of a study that compared a single Q-switched laser treatment pass with four treatment passes separated by 20 minutes. After treating 18 tattoos in 12 adults, they found that the technique, known as the “R20” method, was more effective than a single-pass treatment (P < .01).
“Subsequent to this, there has been conflicting data on whether this is truly effective or not,” said Dr. Ibrahimi, who is also on the board of directors for the American Society for Dermatologic Surgery and the American Society for Laser Medicine and Surgery. “Most of us agree that one additional pass would be helpful, but when you’re doing this in the private practice setting, it’s often challenging because patients aren’t necessarily willing to pay more for more than just one pass for their tattoo removal.”
Another recent advance is use of a topical square silicone patch infused with perfluorodecalin (PFD) for use during tattoo removal, which has been shown to reduce epidermal whitening. The patch contains a fluorocarbon “that is very good at dissolving gas, and it is already widely used in medicine,” he said. When applied, “it almost instantaneously takes the whitening away; you don’t have to wait the 20 minutes to do your second pass.”
A different technology designed to speed up tattoo removal is the Resonic Rapid Acoustic Pulse device (marketed as Resonic, from Allergan Aesthetics), which is cleared by the FDA for use as an accessory to the 1064 nm Q-switched laser for black tattoo removal in patients with skin types I-III. “This uses acoustic pulses of sound waves; they’re rapid and powerful,” Dr. Ibrahimi said. “They can clear those cavitation bubbles much like the PFD patches do. It’s also thought that they further disperse the tattoo ink particles by supplementing the laser energy as well. It is also purported to alter the body’s healing response, or immune response, which is important in tattoo clearing.”
Dr. Ibrahimi disclosed that he is a member of the Advisory Board for Accure Acne, AbbVie (which owns Allergan), Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies.
AT MOAS 2022
Study spotlights clinicopathologic features, survival outcomes of pediatric melanoma
.
“Cutaneous melanomas are rare in children and much less common in adolescents than in later life,” researchers led by Mary-Ann El Sharouni, PhD, wrote in the study, which was published online in the Journal of the American Academy of Dermatology. “Management of these young patients currently follows guidelines developed for adults. Better understanding of melanoma occurring in the first 2 decades of life is, therefore, warranted.”
Drawing from two datasets – one from the Netherlands and the other from Melanoma Institute Australia (MIA) at the University of Sydney – Dr. El Sharouni of the MIA and of the department of dermatology at University Medical Center Utrecht in the Netherlands, and colleagues, evaluated all patients younger than 20 years of age who were diagnosed with invasive melanoma between January 2000 and December 2014. The pooled cohort included 397 Dutch and 117 Australian individuals. Of these, 62 were children and 452 were adolescents. To determine melanoma subtypes, the researchers reevaluated pathology reports and used multivariate Cox models to calculate recurrence-free survival (RFS) and overall survival (OS).
The median Breslow thickness was 2.7 mm in children and 1.0 mm in adolescents. Most patients (83%) had conventional melanoma, which consisted of superficial spreading, nodular, desmoplastic, and acral lentiginous forms, while 78 had spitzoid melanoma and 8 had melanoma associated with a congenital nevus. The 10-year RFS was 91.5% in children and 86.4% in adolescents (P =.32), while the 10-year OS was 100% in children and 92.7% in adolescents (P = .09).
On multivariable analysis, which was possible only for the adolescent cohort because of the small number of children, ulceration status and anatomic site were associated with RFS and OS, whereas age, sex, mitotic index, sentinel node status, and melanoma subtype were not. Breslow thickness > 4 mm was associated with worse RFS. As for affected anatomic site, those with melanomas located on the upper and lower limbs had a better overall RFS and OS compared with those who had head or neck melanomas.
The authors acknowledged certain limitation of the analysis, including its retrospective design and the small number of children. “Our data suggest that adolescent melanomas are often similar to adult-type melanomas, whilst those which occur in young children frequently occur via different molecular mechanisms,” they concluded. “In the future it is likely that further understanding of these molecular mechanisms and ability to classify melanomas based on their molecular characteristics will assist in further refining prognostic estimates and possible guiding treatment for young patients with melanoma.”
Rebecca M. Thiede, MD, assistant program director of the division of dermatology at the University of Arizona, Tucson, who was asked to comment on the study, said that the analysis “greatly contributes to dermatology, as we are still learning the differences between melanoma in children and adolescents versus adults.
This study found that adolescents with melanoma had worse survival if mitosis were present and/or located on head/neck, which could aid in aggressiveness of treatment.”
A key strength of analysis, she continued, is the large sample size of 514 patients, “given that melanoma in this population is very rare. A limitation which [the researchers] brought up is the discrepancy of diagnosis via histopathology of melanoma in children versus adults. The study relied on the pathology report given the retrospective nature of this [analysis, and it] was based on Australian and Dutch populations, which may limit its scope in other countries.”
Dr. El Sharouni was supported by a research fellowship grant from the European Academy of Dermatology and Venereology (EADV), while two of her coauthors, Richard A. Scolyer, MD, and John F. Thompson, MD, were recipients of an Australian National Health and Medical Research Council Program Grant. The study was also supported by a research program grant from Cancer Institute New South Wales. Dr. Thiede reported having no financial disclosures.
.
“Cutaneous melanomas are rare in children and much less common in adolescents than in later life,” researchers led by Mary-Ann El Sharouni, PhD, wrote in the study, which was published online in the Journal of the American Academy of Dermatology. “Management of these young patients currently follows guidelines developed for adults. Better understanding of melanoma occurring in the first 2 decades of life is, therefore, warranted.”
Drawing from two datasets – one from the Netherlands and the other from Melanoma Institute Australia (MIA) at the University of Sydney – Dr. El Sharouni of the MIA and of the department of dermatology at University Medical Center Utrecht in the Netherlands, and colleagues, evaluated all patients younger than 20 years of age who were diagnosed with invasive melanoma between January 2000 and December 2014. The pooled cohort included 397 Dutch and 117 Australian individuals. Of these, 62 were children and 452 were adolescents. To determine melanoma subtypes, the researchers reevaluated pathology reports and used multivariate Cox models to calculate recurrence-free survival (RFS) and overall survival (OS).
The median Breslow thickness was 2.7 mm in children and 1.0 mm in adolescents. Most patients (83%) had conventional melanoma, which consisted of superficial spreading, nodular, desmoplastic, and acral lentiginous forms, while 78 had spitzoid melanoma and 8 had melanoma associated with a congenital nevus. The 10-year RFS was 91.5% in children and 86.4% in adolescents (P =.32), while the 10-year OS was 100% in children and 92.7% in adolescents (P = .09).
On multivariable analysis, which was possible only for the adolescent cohort because of the small number of children, ulceration status and anatomic site were associated with RFS and OS, whereas age, sex, mitotic index, sentinel node status, and melanoma subtype were not. Breslow thickness > 4 mm was associated with worse RFS. As for affected anatomic site, those with melanomas located on the upper and lower limbs had a better overall RFS and OS compared with those who had head or neck melanomas.
The authors acknowledged certain limitation of the analysis, including its retrospective design and the small number of children. “Our data suggest that adolescent melanomas are often similar to adult-type melanomas, whilst those which occur in young children frequently occur via different molecular mechanisms,” they concluded. “In the future it is likely that further understanding of these molecular mechanisms and ability to classify melanomas based on their molecular characteristics will assist in further refining prognostic estimates and possible guiding treatment for young patients with melanoma.”
Rebecca M. Thiede, MD, assistant program director of the division of dermatology at the University of Arizona, Tucson, who was asked to comment on the study, said that the analysis “greatly contributes to dermatology, as we are still learning the differences between melanoma in children and adolescents versus adults.
This study found that adolescents with melanoma had worse survival if mitosis were present and/or located on head/neck, which could aid in aggressiveness of treatment.”
A key strength of analysis, she continued, is the large sample size of 514 patients, “given that melanoma in this population is very rare. A limitation which [the researchers] brought up is the discrepancy of diagnosis via histopathology of melanoma in children versus adults. The study relied on the pathology report given the retrospective nature of this [analysis, and it] was based on Australian and Dutch populations, which may limit its scope in other countries.”
Dr. El Sharouni was supported by a research fellowship grant from the European Academy of Dermatology and Venereology (EADV), while two of her coauthors, Richard A. Scolyer, MD, and John F. Thompson, MD, were recipients of an Australian National Health and Medical Research Council Program Grant. The study was also supported by a research program grant from Cancer Institute New South Wales. Dr. Thiede reported having no financial disclosures.
.
“Cutaneous melanomas are rare in children and much less common in adolescents than in later life,” researchers led by Mary-Ann El Sharouni, PhD, wrote in the study, which was published online in the Journal of the American Academy of Dermatology. “Management of these young patients currently follows guidelines developed for adults. Better understanding of melanoma occurring in the first 2 decades of life is, therefore, warranted.”
Drawing from two datasets – one from the Netherlands and the other from Melanoma Institute Australia (MIA) at the University of Sydney – Dr. El Sharouni of the MIA and of the department of dermatology at University Medical Center Utrecht in the Netherlands, and colleagues, evaluated all patients younger than 20 years of age who were diagnosed with invasive melanoma between January 2000 and December 2014. The pooled cohort included 397 Dutch and 117 Australian individuals. Of these, 62 were children and 452 were adolescents. To determine melanoma subtypes, the researchers reevaluated pathology reports and used multivariate Cox models to calculate recurrence-free survival (RFS) and overall survival (OS).
The median Breslow thickness was 2.7 mm in children and 1.0 mm in adolescents. Most patients (83%) had conventional melanoma, which consisted of superficial spreading, nodular, desmoplastic, and acral lentiginous forms, while 78 had spitzoid melanoma and 8 had melanoma associated with a congenital nevus. The 10-year RFS was 91.5% in children and 86.4% in adolescents (P =.32), while the 10-year OS was 100% in children and 92.7% in adolescents (P = .09).
On multivariable analysis, which was possible only for the adolescent cohort because of the small number of children, ulceration status and anatomic site were associated with RFS and OS, whereas age, sex, mitotic index, sentinel node status, and melanoma subtype were not. Breslow thickness > 4 mm was associated with worse RFS. As for affected anatomic site, those with melanomas located on the upper and lower limbs had a better overall RFS and OS compared with those who had head or neck melanomas.
The authors acknowledged certain limitation of the analysis, including its retrospective design and the small number of children. “Our data suggest that adolescent melanomas are often similar to adult-type melanomas, whilst those which occur in young children frequently occur via different molecular mechanisms,” they concluded. “In the future it is likely that further understanding of these molecular mechanisms and ability to classify melanomas based on their molecular characteristics will assist in further refining prognostic estimates and possible guiding treatment for young patients with melanoma.”
Rebecca M. Thiede, MD, assistant program director of the division of dermatology at the University of Arizona, Tucson, who was asked to comment on the study, said that the analysis “greatly contributes to dermatology, as we are still learning the differences between melanoma in children and adolescents versus adults.
This study found that adolescents with melanoma had worse survival if mitosis were present and/or located on head/neck, which could aid in aggressiveness of treatment.”
A key strength of analysis, she continued, is the large sample size of 514 patients, “given that melanoma in this population is very rare. A limitation which [the researchers] brought up is the discrepancy of diagnosis via histopathology of melanoma in children versus adults. The study relied on the pathology report given the retrospective nature of this [analysis, and it] was based on Australian and Dutch populations, which may limit its scope in other countries.”
Dr. El Sharouni was supported by a research fellowship grant from the European Academy of Dermatology and Venereology (EADV), while two of her coauthors, Richard A. Scolyer, MD, and John F. Thompson, MD, were recipients of an Australian National Health and Medical Research Council Program Grant. The study was also supported by a research program grant from Cancer Institute New South Wales. Dr. Thiede reported having no financial disclosures.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Infantile hemangioma: Analysis underscores importance of early propranolol treatment
, results from a post-hoc analysis of phase 2 and 3 clinical trial data showed.
“It is widely accepted that oral propranolol should be started early to improve the success rate, but proposed thresholds have lacked supportive data,” researchers led by Christine Léauté-Labrèze, MD, of the department of dermatology at Pellegrin Children’s Hospital, Bordeaux, France, wrote in the study, which was published online in Pediatric Dermatology. In the pivotal phase 2/3 trial of propranolol of 460 infants, published in 2015, the mean initiation of treatment was 104 days, they added, but “in real-life studies, most infants are referred later than this.”
In addition, a European expert consensus panel set the ideal age for a patient to be seen by a specialist at between 3 and 5 weeks of age, while an American Academy of Pediatrics Clinical Practice Guideline set the ideal age at 1 month.
To determine factors associated with a higher success rate with oral propranolol treatment, such as age at treatment initiation, the researchers analyzed data from the pivotal phase 2-3 clinical trial of oral propranolol in IH. They used Generalized Additive Model (GAM) charts with Generalized Linear Models (GLM), then a rule discovery algorithm, to identify subgroups presenting a high probability of occurrence of the predefined outcome: success at 6 months of treatment (defined as complete or nearly complete resolution of the target hemangioma). Study coauthors were Ilona J. Frieden, MD, of the department of dermatology at the University of California, San Francisco, and director of the UCSF Birthmarks & Vascular Anomalies Center; and Alain Delarue, MD, of medical affairs at Pierre Fabre Dermatologie, Lavaur, France, which markets the pediatric formulation of propranolol approved by the Food and Drug Administration in 2014 for treating IH.
They found that patients who started oral propranolol 3 mg/kg/day before the age of 10 weeks had a success rate of 86%, while those who started treatment after 10 weeks of age had a success rate of 60%. “Our clinical experience suggested that starting early propranolol gave better results on infantile hemangiomas; however, we were surprised” by the significance of the difference, the three study authors stated in an e-mail reply to this news organization.
“It therefore seemed essential to communicate the importance of early treatment to maximize the possibilities of recovery for children. Our findings support early treatment of at-risk infantile hemangiomas, without waiting for complications such as ulceration and/or functional consequences,” they added.
In their e-mail reply, the authors stated that treatment of high-risk IH should be initiated whenever possible before 10 weeks of age. Ideally, infants should be examined by a practitioner between 2 and 5 weeks of age and referred to a specialized center if they have features of an at-risk IH. Tools such as the Infantile Hemangioma Referral Score (IHReS) and consensus guidelines such as the AAP Clinical Practice Guideline “can help guide clinicians seeing newborns and young infants to recognize which IH may need early intervention,” they stated.
For rural-based providers whose patients and their families may not live close to an expert center, the study authors especially recommend using the IHReS scoring tool, which is readily available online and “will be very helpful in assessing whether patients need referral.” For those who do, they added, “triage using photographs is an excellent way to reach out to a referral center for advice and possible urgent referral.” In addition, a recent study emphasized that telemedicine using either live interactive portals or store-and-forward can be helpful in evaluation and management of patients with IH.
Dr. Léauté-Labrèze and colleagues acknowledged certain limitations of the analysis, including the fact that it was performed post-hoc on an existing study and the challenge of translating its findings into clinical practice.
The three study authors were also authors of the 2015 NEJM study; Dr. Léauté-Labrèze was the lead author.
Dr. Léauté-Labrèze disclosed that she has served as a speaker and consultant for Pierre Fabre. Dr. Delarue is an employee of the company. Dr. Frieden reported having no disclosures relevant to the analysis.
, results from a post-hoc analysis of phase 2 and 3 clinical trial data showed.
“It is widely accepted that oral propranolol should be started early to improve the success rate, but proposed thresholds have lacked supportive data,” researchers led by Christine Léauté-Labrèze, MD, of the department of dermatology at Pellegrin Children’s Hospital, Bordeaux, France, wrote in the study, which was published online in Pediatric Dermatology. In the pivotal phase 2/3 trial of propranolol of 460 infants, published in 2015, the mean initiation of treatment was 104 days, they added, but “in real-life studies, most infants are referred later than this.”
In addition, a European expert consensus panel set the ideal age for a patient to be seen by a specialist at between 3 and 5 weeks of age, while an American Academy of Pediatrics Clinical Practice Guideline set the ideal age at 1 month.
To determine factors associated with a higher success rate with oral propranolol treatment, such as age at treatment initiation, the researchers analyzed data from the pivotal phase 2-3 clinical trial of oral propranolol in IH. They used Generalized Additive Model (GAM) charts with Generalized Linear Models (GLM), then a rule discovery algorithm, to identify subgroups presenting a high probability of occurrence of the predefined outcome: success at 6 months of treatment (defined as complete or nearly complete resolution of the target hemangioma). Study coauthors were Ilona J. Frieden, MD, of the department of dermatology at the University of California, San Francisco, and director of the UCSF Birthmarks & Vascular Anomalies Center; and Alain Delarue, MD, of medical affairs at Pierre Fabre Dermatologie, Lavaur, France, which markets the pediatric formulation of propranolol approved by the Food and Drug Administration in 2014 for treating IH.
They found that patients who started oral propranolol 3 mg/kg/day before the age of 10 weeks had a success rate of 86%, while those who started treatment after 10 weeks of age had a success rate of 60%. “Our clinical experience suggested that starting early propranolol gave better results on infantile hemangiomas; however, we were surprised” by the significance of the difference, the three study authors stated in an e-mail reply to this news organization.
“It therefore seemed essential to communicate the importance of early treatment to maximize the possibilities of recovery for children. Our findings support early treatment of at-risk infantile hemangiomas, without waiting for complications such as ulceration and/or functional consequences,” they added.
In their e-mail reply, the authors stated that treatment of high-risk IH should be initiated whenever possible before 10 weeks of age. Ideally, infants should be examined by a practitioner between 2 and 5 weeks of age and referred to a specialized center if they have features of an at-risk IH. Tools such as the Infantile Hemangioma Referral Score (IHReS) and consensus guidelines such as the AAP Clinical Practice Guideline “can help guide clinicians seeing newborns and young infants to recognize which IH may need early intervention,” they stated.
For rural-based providers whose patients and their families may not live close to an expert center, the study authors especially recommend using the IHReS scoring tool, which is readily available online and “will be very helpful in assessing whether patients need referral.” For those who do, they added, “triage using photographs is an excellent way to reach out to a referral center for advice and possible urgent referral.” In addition, a recent study emphasized that telemedicine using either live interactive portals or store-and-forward can be helpful in evaluation and management of patients with IH.
Dr. Léauté-Labrèze and colleagues acknowledged certain limitations of the analysis, including the fact that it was performed post-hoc on an existing study and the challenge of translating its findings into clinical practice.
The three study authors were also authors of the 2015 NEJM study; Dr. Léauté-Labrèze was the lead author.
Dr. Léauté-Labrèze disclosed that she has served as a speaker and consultant for Pierre Fabre. Dr. Delarue is an employee of the company. Dr. Frieden reported having no disclosures relevant to the analysis.
, results from a post-hoc analysis of phase 2 and 3 clinical trial data showed.
“It is widely accepted that oral propranolol should be started early to improve the success rate, but proposed thresholds have lacked supportive data,” researchers led by Christine Léauté-Labrèze, MD, of the department of dermatology at Pellegrin Children’s Hospital, Bordeaux, France, wrote in the study, which was published online in Pediatric Dermatology. In the pivotal phase 2/3 trial of propranolol of 460 infants, published in 2015, the mean initiation of treatment was 104 days, they added, but “in real-life studies, most infants are referred later than this.”
In addition, a European expert consensus panel set the ideal age for a patient to be seen by a specialist at between 3 and 5 weeks of age, while an American Academy of Pediatrics Clinical Practice Guideline set the ideal age at 1 month.
To determine factors associated with a higher success rate with oral propranolol treatment, such as age at treatment initiation, the researchers analyzed data from the pivotal phase 2-3 clinical trial of oral propranolol in IH. They used Generalized Additive Model (GAM) charts with Generalized Linear Models (GLM), then a rule discovery algorithm, to identify subgroups presenting a high probability of occurrence of the predefined outcome: success at 6 months of treatment (defined as complete or nearly complete resolution of the target hemangioma). Study coauthors were Ilona J. Frieden, MD, of the department of dermatology at the University of California, San Francisco, and director of the UCSF Birthmarks & Vascular Anomalies Center; and Alain Delarue, MD, of medical affairs at Pierre Fabre Dermatologie, Lavaur, France, which markets the pediatric formulation of propranolol approved by the Food and Drug Administration in 2014 for treating IH.
They found that patients who started oral propranolol 3 mg/kg/day before the age of 10 weeks had a success rate of 86%, while those who started treatment after 10 weeks of age had a success rate of 60%. “Our clinical experience suggested that starting early propranolol gave better results on infantile hemangiomas; however, we were surprised” by the significance of the difference, the three study authors stated in an e-mail reply to this news organization.
“It therefore seemed essential to communicate the importance of early treatment to maximize the possibilities of recovery for children. Our findings support early treatment of at-risk infantile hemangiomas, without waiting for complications such as ulceration and/or functional consequences,” they added.
In their e-mail reply, the authors stated that treatment of high-risk IH should be initiated whenever possible before 10 weeks of age. Ideally, infants should be examined by a practitioner between 2 and 5 weeks of age and referred to a specialized center if they have features of an at-risk IH. Tools such as the Infantile Hemangioma Referral Score (IHReS) and consensus guidelines such as the AAP Clinical Practice Guideline “can help guide clinicians seeing newborns and young infants to recognize which IH may need early intervention,” they stated.
For rural-based providers whose patients and their families may not live close to an expert center, the study authors especially recommend using the IHReS scoring tool, which is readily available online and “will be very helpful in assessing whether patients need referral.” For those who do, they added, “triage using photographs is an excellent way to reach out to a referral center for advice and possible urgent referral.” In addition, a recent study emphasized that telemedicine using either live interactive portals or store-and-forward can be helpful in evaluation and management of patients with IH.
Dr. Léauté-Labrèze and colleagues acknowledged certain limitations of the analysis, including the fact that it was performed post-hoc on an existing study and the challenge of translating its findings into clinical practice.
The three study authors were also authors of the 2015 NEJM study; Dr. Léauté-Labrèze was the lead author.
Dr. Léauté-Labrèze disclosed that she has served as a speaker and consultant for Pierre Fabre. Dr. Delarue is an employee of the company. Dr. Frieden reported having no disclosures relevant to the analysis.
FROM PEDIATRIC DERMATOLOGY