Expert provides antibiotic stewardship tips for dermatologists

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– Dermatologists prescribe more antibiotics than any other physician group, a statistic that George G. Zhanel, PhD, would like to see go by the wayside.

Dr. George G. Zhanel a microbiologist at the College of Medicine, University of Manitoba, Winnipeg, Canada
Dr. George G. Zhanel

After all, the World Health Organization projects that the number of annual deaths in North America attributable to antibiotic resistance will reach 317,000 by the year 2050.

“It doesn’t really matter where you are in the world – we’re going to have a lot of deaths due to infections caused by antibiotic-resistant organisms,” Dr. Zhanel, a microbiologist at the College of Medicine, University of Manitoba, Winnipeg, Canada, said at the annual meeting of the Society for Pediatric Dermatology. “Many of us are very concerned about this. Countries have put together an optimal action plan. What are we going to do about this? The plans are quite similar from country to country. They talk about surveillance, finding where these pathogens are. They talk about infection control such as washing your hands in the clinic so you’re not moving antibiotic-resistant organisms around. They talk about diagnostic and treatment guidelines, new antibiotic therapies, probiotics, and vaccination strategies. My own group is doing research on all of these areas, but today I’m going to focus on antibiotic stewardship: Using antibiotics wisely, trying to optimize efficacy while trying to minimize the development of resistant organisms.”

Dr. Zhanel, who is also director of the Canadian Antimicrobial Resistance Alliance (CARA) at the College of Medicine, University of Manitoba, described dermatologists as “big players” when it comes to antibiotic use. According to a 2016 report from the Scientific Panel on Antibiotic Use in Dermatology, dermatologists order 8.2 million oral antibiotic prescriptions each year, which is more common than any other physician group based on the prescribing rate per clinician (J Clin Aesthet Dermatol. 2016;9[4]:18-24). In addition, the prescribed duration of antibiotic therapy is often markedly longer with therapies treated by dermatologists, especially acne and rosacea. One study of general practitioners in the United Kingdom found that the mean duration of oral antibiotic use for treating acne was 175 days (J Am Acad Dermatol 2016;75:1142-50). “For some patients it went on much longer,” said Dr. Zhanel, who was not affiliated with the study.

“You are important players when it comes to antibiotics. How you use them and if you use them wisely impacts not only your patients, but the world.”

The correlation between antibiotic use and resistance is widely established, he continued. “We have known for 30 to 40 years that if you treat patients with tetracyclines, the Staphylococcus epidermidis that we all have on our skin develop tetracycline resistance,” he said. “The tetracycline resistance genes from S. epidermidis can then transfer to putative pathogens such as Staphylococcus aureus, and potentially [methicillin-resistant S. aureus]. That’s why we need to try to minimize oral tetracycline exposure on the normal microbiome.” In addition, tetracycline use can help create multidrug resistant organisms.

Next, Dr. Zhanel discussed potential solutions to antimicrobial usage/resistance in dermatology. According to recent guidelines on the care for the management of acne vulgaris, systemic antibiotic use should be limited to the shortest possible duration, typically 90 days (J Am Acad Dermatol. 2016;74[5]:945-73). A common treatment for moderate to-severe acne is to combine a topical retinoid with an oral or topical antimicrobial (J Am Acad Dermatol. 2009;60(5 suppl):S1-S50). If the addition of an oral antibiotic is required, limit its use to 3 or 4 months and co-prescribe with a product that contains benzoyl peroxide (BPO), or use as a washout. “Ideally, that’s your exit strategy,” he said. “Once you finish the oral antibiotic, in about 3 months if possible, continue with the topical retinoids plus BPO to maintain that particular remission.”

Why add benzoyl peroxide to topical retinoids for maintenance therapy? “Benzoyl peroxide and topical retinoids affect multiple targets in your acne strategy, and when you use them together they are powerful,” Dr. Zhanel said. He advises dermatologists not to prescribe oral or topical clindamycin unless they have to, because that drug is one of the main drivers of Clostridium difficile infection.

Dr. Zhanel’s stewardship tips for topical antibiotics involve not using topical tetracyclines/clindamycin/macrolides, in favor of using a topical antimicrobial such as BPO. “We think that benzoyl peroxide is less likely to drive resistance than are the traditional topical antibiotics like tetracyclines and clindamycin,” he said. “Use topical retinoids and benzoyl peroxide, if possible.”

Subtherapeutic oral doses of tetracyclines such as doxycycline 40 mg modified release “look very powerful for treating rosacea and do not affect the normal microbiome or select for resistance,” he said. In the meantime, Dr. Zhanel and other researchers are working to develop narrow spectrum tetracyclines with less impact on the GI flora, such as sarecycline. “So there is the potential for more eco-friendly tetracyclines,” he said.

Going forward, many questions remain about optimal antibiotic stewardship in dermatology, Dr. Zhanel said. For example, if you combine a topical antibiotic with benzoyl peroxide, are you less likely to get resistance to that topical antibiotic? “I think the answer is yes, but the literature isn’t very strong on that,” he said. “Also, is benzoyl peroxide plus a topical retinoid better than benzoyl peroxide plus a topical antibiotic in terms of resistance? I think the answer is yes, but again there is very little data on this.”

Dr. Zhanel disclosed having numerous financial ties to the pharmaceutical industry.

dbrunk@mdedge.com

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– Dermatologists prescribe more antibiotics than any other physician group, a statistic that George G. Zhanel, PhD, would like to see go by the wayside.

Dr. George G. Zhanel a microbiologist at the College of Medicine, University of Manitoba, Winnipeg, Canada
Dr. George G. Zhanel

After all, the World Health Organization projects that the number of annual deaths in North America attributable to antibiotic resistance will reach 317,000 by the year 2050.

“It doesn’t really matter where you are in the world – we’re going to have a lot of deaths due to infections caused by antibiotic-resistant organisms,” Dr. Zhanel, a microbiologist at the College of Medicine, University of Manitoba, Winnipeg, Canada, said at the annual meeting of the Society for Pediatric Dermatology. “Many of us are very concerned about this. Countries have put together an optimal action plan. What are we going to do about this? The plans are quite similar from country to country. They talk about surveillance, finding where these pathogens are. They talk about infection control such as washing your hands in the clinic so you’re not moving antibiotic-resistant organisms around. They talk about diagnostic and treatment guidelines, new antibiotic therapies, probiotics, and vaccination strategies. My own group is doing research on all of these areas, but today I’m going to focus on antibiotic stewardship: Using antibiotics wisely, trying to optimize efficacy while trying to minimize the development of resistant organisms.”

Dr. Zhanel, who is also director of the Canadian Antimicrobial Resistance Alliance (CARA) at the College of Medicine, University of Manitoba, described dermatologists as “big players” when it comes to antibiotic use. According to a 2016 report from the Scientific Panel on Antibiotic Use in Dermatology, dermatologists order 8.2 million oral antibiotic prescriptions each year, which is more common than any other physician group based on the prescribing rate per clinician (J Clin Aesthet Dermatol. 2016;9[4]:18-24). In addition, the prescribed duration of antibiotic therapy is often markedly longer with therapies treated by dermatologists, especially acne and rosacea. One study of general practitioners in the United Kingdom found that the mean duration of oral antibiotic use for treating acne was 175 days (J Am Acad Dermatol 2016;75:1142-50). “For some patients it went on much longer,” said Dr. Zhanel, who was not affiliated with the study.

“You are important players when it comes to antibiotics. How you use them and if you use them wisely impacts not only your patients, but the world.”

The correlation between antibiotic use and resistance is widely established, he continued. “We have known for 30 to 40 years that if you treat patients with tetracyclines, the Staphylococcus epidermidis that we all have on our skin develop tetracycline resistance,” he said. “The tetracycline resistance genes from S. epidermidis can then transfer to putative pathogens such as Staphylococcus aureus, and potentially [methicillin-resistant S. aureus]. That’s why we need to try to minimize oral tetracycline exposure on the normal microbiome.” In addition, tetracycline use can help create multidrug resistant organisms.

Next, Dr. Zhanel discussed potential solutions to antimicrobial usage/resistance in dermatology. According to recent guidelines on the care for the management of acne vulgaris, systemic antibiotic use should be limited to the shortest possible duration, typically 90 days (J Am Acad Dermatol. 2016;74[5]:945-73). A common treatment for moderate to-severe acne is to combine a topical retinoid with an oral or topical antimicrobial (J Am Acad Dermatol. 2009;60(5 suppl):S1-S50). If the addition of an oral antibiotic is required, limit its use to 3 or 4 months and co-prescribe with a product that contains benzoyl peroxide (BPO), or use as a washout. “Ideally, that’s your exit strategy,” he said. “Once you finish the oral antibiotic, in about 3 months if possible, continue with the topical retinoids plus BPO to maintain that particular remission.”

Why add benzoyl peroxide to topical retinoids for maintenance therapy? “Benzoyl peroxide and topical retinoids affect multiple targets in your acne strategy, and when you use them together they are powerful,” Dr. Zhanel said. He advises dermatologists not to prescribe oral or topical clindamycin unless they have to, because that drug is one of the main drivers of Clostridium difficile infection.

Dr. Zhanel’s stewardship tips for topical antibiotics involve not using topical tetracyclines/clindamycin/macrolides, in favor of using a topical antimicrobial such as BPO. “We think that benzoyl peroxide is less likely to drive resistance than are the traditional topical antibiotics like tetracyclines and clindamycin,” he said. “Use topical retinoids and benzoyl peroxide, if possible.”

Subtherapeutic oral doses of tetracyclines such as doxycycline 40 mg modified release “look very powerful for treating rosacea and do not affect the normal microbiome or select for resistance,” he said. In the meantime, Dr. Zhanel and other researchers are working to develop narrow spectrum tetracyclines with less impact on the GI flora, such as sarecycline. “So there is the potential for more eco-friendly tetracyclines,” he said.

Going forward, many questions remain about optimal antibiotic stewardship in dermatology, Dr. Zhanel said. For example, if you combine a topical antibiotic with benzoyl peroxide, are you less likely to get resistance to that topical antibiotic? “I think the answer is yes, but the literature isn’t very strong on that,” he said. “Also, is benzoyl peroxide plus a topical retinoid better than benzoyl peroxide plus a topical antibiotic in terms of resistance? I think the answer is yes, but again there is very little data on this.”

Dr. Zhanel disclosed having numerous financial ties to the pharmaceutical industry.

dbrunk@mdedge.com

– Dermatologists prescribe more antibiotics than any other physician group, a statistic that George G. Zhanel, PhD, would like to see go by the wayside.

Dr. George G. Zhanel a microbiologist at the College of Medicine, University of Manitoba, Winnipeg, Canada
Dr. George G. Zhanel

After all, the World Health Organization projects that the number of annual deaths in North America attributable to antibiotic resistance will reach 317,000 by the year 2050.

“It doesn’t really matter where you are in the world – we’re going to have a lot of deaths due to infections caused by antibiotic-resistant organisms,” Dr. Zhanel, a microbiologist at the College of Medicine, University of Manitoba, Winnipeg, Canada, said at the annual meeting of the Society for Pediatric Dermatology. “Many of us are very concerned about this. Countries have put together an optimal action plan. What are we going to do about this? The plans are quite similar from country to country. They talk about surveillance, finding where these pathogens are. They talk about infection control such as washing your hands in the clinic so you’re not moving antibiotic-resistant organisms around. They talk about diagnostic and treatment guidelines, new antibiotic therapies, probiotics, and vaccination strategies. My own group is doing research on all of these areas, but today I’m going to focus on antibiotic stewardship: Using antibiotics wisely, trying to optimize efficacy while trying to minimize the development of resistant organisms.”

Dr. Zhanel, who is also director of the Canadian Antimicrobial Resistance Alliance (CARA) at the College of Medicine, University of Manitoba, described dermatologists as “big players” when it comes to antibiotic use. According to a 2016 report from the Scientific Panel on Antibiotic Use in Dermatology, dermatologists order 8.2 million oral antibiotic prescriptions each year, which is more common than any other physician group based on the prescribing rate per clinician (J Clin Aesthet Dermatol. 2016;9[4]:18-24). In addition, the prescribed duration of antibiotic therapy is often markedly longer with therapies treated by dermatologists, especially acne and rosacea. One study of general practitioners in the United Kingdom found that the mean duration of oral antibiotic use for treating acne was 175 days (J Am Acad Dermatol 2016;75:1142-50). “For some patients it went on much longer,” said Dr. Zhanel, who was not affiliated with the study.

“You are important players when it comes to antibiotics. How you use them and if you use them wisely impacts not only your patients, but the world.”

The correlation between antibiotic use and resistance is widely established, he continued. “We have known for 30 to 40 years that if you treat patients with tetracyclines, the Staphylococcus epidermidis that we all have on our skin develop tetracycline resistance,” he said. “The tetracycline resistance genes from S. epidermidis can then transfer to putative pathogens such as Staphylococcus aureus, and potentially [methicillin-resistant S. aureus]. That’s why we need to try to minimize oral tetracycline exposure on the normal microbiome.” In addition, tetracycline use can help create multidrug resistant organisms.

Next, Dr. Zhanel discussed potential solutions to antimicrobial usage/resistance in dermatology. According to recent guidelines on the care for the management of acne vulgaris, systemic antibiotic use should be limited to the shortest possible duration, typically 90 days (J Am Acad Dermatol. 2016;74[5]:945-73). A common treatment for moderate to-severe acne is to combine a topical retinoid with an oral or topical antimicrobial (J Am Acad Dermatol. 2009;60(5 suppl):S1-S50). If the addition of an oral antibiotic is required, limit its use to 3 or 4 months and co-prescribe with a product that contains benzoyl peroxide (BPO), or use as a washout. “Ideally, that’s your exit strategy,” he said. “Once you finish the oral antibiotic, in about 3 months if possible, continue with the topical retinoids plus BPO to maintain that particular remission.”

Why add benzoyl peroxide to topical retinoids for maintenance therapy? “Benzoyl peroxide and topical retinoids affect multiple targets in your acne strategy, and when you use them together they are powerful,” Dr. Zhanel said. He advises dermatologists not to prescribe oral or topical clindamycin unless they have to, because that drug is one of the main drivers of Clostridium difficile infection.

Dr. Zhanel’s stewardship tips for topical antibiotics involve not using topical tetracyclines/clindamycin/macrolides, in favor of using a topical antimicrobial such as BPO. “We think that benzoyl peroxide is less likely to drive resistance than are the traditional topical antibiotics like tetracyclines and clindamycin,” he said. “Use topical retinoids and benzoyl peroxide, if possible.”

Subtherapeutic oral doses of tetracyclines such as doxycycline 40 mg modified release “look very powerful for treating rosacea and do not affect the normal microbiome or select for resistance,” he said. In the meantime, Dr. Zhanel and other researchers are working to develop narrow spectrum tetracyclines with less impact on the GI flora, such as sarecycline. “So there is the potential for more eco-friendly tetracyclines,” he said.

Going forward, many questions remain about optimal antibiotic stewardship in dermatology, Dr. Zhanel said. For example, if you combine a topical antibiotic with benzoyl peroxide, are you less likely to get resistance to that topical antibiotic? “I think the answer is yes, but the literature isn’t very strong on that,” he said. “Also, is benzoyl peroxide plus a topical retinoid better than benzoyl peroxide plus a topical antibiotic in terms of resistance? I think the answer is yes, but again there is very little data on this.”

Dr. Zhanel disclosed having numerous financial ties to the pharmaceutical industry.

dbrunk@mdedge.com

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Certain skin conditions signal potential overgrowth disorder

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Mosaicism makes everything in genetics more challenging, but it also enables researchers to understand how genes and cell pathways work in cancer and during human development, Leslie G. Biesecker, MD said at the annual meeting of the Society for Pediatric Dermatology.

Dr. Leslie G. Biesecker
Dr. Leslie G. Biesecker

Dr. Biesecker, senior investigator and head of the clinical genomics section of the National Human Genome Research Institute’s Medical Genomics and Metabolic Genetics Branch, discussed mosaicism and a number of overgrowth syndromes that he and his associates have been studying that have clinical relevance for pediatric dermatologists. He noted that mosaicism can affect any tissue, anywhere, in any pattern. “If an affected cell cannot survive gametogenesis, fertilization, or survive early development, this generates Happle-type mosaicism,” explained Dr. Biesecker, who is trained in pediatrics and in clinical and molecular genetics.

“This is characterized by patchy manifestations, and no parent-to-child transmission or recurrence. You must always be careful here, though, because Mother Nature does what she wants to. Mosaic mutations can happen more than once, but it’s a very unlikely outcome. Happle-type mosaicism is also characterized by discordant monozygotic twins,” he noted.

The prototype for Happle-type mosaicism is Proteus syndrome, formerly known as Elephant Man disease, which is caused by a mutation in the AKT1 gene. Patients with Proteus syndrome undergo severe, relentless overgrowth, and about 25% of them die during childhood. “If you see one of these patients, you have a serious clinical problem on your hands,” he said. “There is enormous individual variability, but it is ultra rare.”


Dermatologic lesions that are characteristic of Proteus syndrome include cerebriform connective tissue nevus, which typically presents on the hands and feet. “A wide range of vascular malformations have also been associated with this, even patients with arteriovenous malformations,” Dr. Biesecker said. “They are a serious problem.” Linear verrucous epidermal nevus is another characteristic lesion of Proteus syndrome. It can present in a number of ways and in various body sites. “The natural history of these lesions is important,” he commented. “Over time, are they stable, or do they spread and expand over time? These lesions do not ever spontaneously regress. This does enable molecular diagnosis, but don’t bother sampling their blood, because it will be negative. You have to have a biopsy sample.”

Overgrowth syndromes that do not meet criteria for Proteus syndrome fall into a category known as PIK3CA-related overgrowth spectrum, which Dr. Biesecker characterized as “a bunch of clinical designations all caused by the same underlying somatic mutation in a gene called PIK3CA. There is an enormous variability in these patients, ranging from those who have profound overgrowth, including malformations, truncal overgrowth, and vascular malformations, and digital overgrowth in all sorts of patterns. We designate this as PIK3CA-related overgrowth spectrum (PROS), because we can’t clinically separate these things from one another.”

These conditions include what used to be called CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal/spinal anomalies), facial infiltrating lipomatosis, and megalencephaly-capillary malformation syndrome. PROS is about 100 times more common than Proteus syndrome. “There are no rational boundaries to distinguish these entities,” Dr. Biesecker said. “They are rationalized under a combined clinical-molecular PROS framework, meaning that the molecular diagnosis is absolutely key to correctly diagnosing these patients.”

In this way, mosaicism challenges the traditional concept of diagnosing overgrowth disorders. “What we thought were separate disorders are in fact many manifestations of a single disorder,” he continued. “When I was doing my genetics training, we were taught that it would turn out that there was one gene for every disease, and one disease for every gene. That is completely wrong; it’s much more complicated than that. Mosaicism is also important for us as biologists, because it gives us a window into biology we otherwise would not see. Without a mosaicism, Proteus syndrome cannot exist biologically. So if I want to understand that gene product, I have to study patients who are mosaics. Mosaicism can happen in any tissue, whether it’s visible or not.”

Dr. Biesecker, who has been elected to serve as president of the American Society of Human Genetics for 2019, noted that most of the gene mutations that cause overgrowth disorders are the same ones implicated in cancer. “It makes sense, because cancer is a disorder of uncontrolled proliferation and differentiation,” he said. “These overgrowth disorders are similar but less severe manifestations of the same problem. It turns out that these mosaic patients are single gene model systems of cancer biology.” Therefore, when a drug company develops an anti-cancer drug, he continued, it also can be useful for PROS or Proteus syndrome. It’s much easier to inhibit a protein that’s overactive than it is to replace the activity of a gene that has lost its function.

But in PROS and Proteus, “we have very different treatment objectives than oncologists do,” he said. “Our goal is to reduce the signaling caused by these mutations; we do not want to kill the cells. Some of my patients with these disorders have pretty close to 50% of cells in their body carrying these mutations. If I were thinking like an oncologist, the oncologist wants to kill cancer cells; that’s their objective. If I were to kill all of the mutant cells in my patients, I’m certain that would kill them.”

One promising development is the investigational oral agent ARQ 092, which is an inhibitor of AKT1. Dr. Biesecker and his colleagues at the NIH have been working to figure out what dosing should be used in humans based on mouse data, lab data, and data from cancer patients. They started with about one-twelvth the dose that oncologists use. After treating the first patient with overgrowth syndrome, on day 15 that person’s AKT1 level dropped to about 20% of normal, while on day 75 it moved to around 60% of normal. “We are right in that zone where we want to drive the activity of that protein to about half of what it should be,” Dr. Biesecker said. He and his colleagues also have observed regression of lesions in a patient with cerebriform connective tissue nevus who was treated with ARQ 092. “We’ve never seen this before.”

Dr. Biesecker disclosed that he is a member of the Illumina medical ethics board. He has received royalties from Genentech and in-kind research support from ArQule and Pfizer.

dbrunk@mdedge.com

 

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Mosaicism makes everything in genetics more challenging, but it also enables researchers to understand how genes and cell pathways work in cancer and during human development, Leslie G. Biesecker, MD said at the annual meeting of the Society for Pediatric Dermatology.

Dr. Leslie G. Biesecker
Dr. Leslie G. Biesecker

Dr. Biesecker, senior investigator and head of the clinical genomics section of the National Human Genome Research Institute’s Medical Genomics and Metabolic Genetics Branch, discussed mosaicism and a number of overgrowth syndromes that he and his associates have been studying that have clinical relevance for pediatric dermatologists. He noted that mosaicism can affect any tissue, anywhere, in any pattern. “If an affected cell cannot survive gametogenesis, fertilization, or survive early development, this generates Happle-type mosaicism,” explained Dr. Biesecker, who is trained in pediatrics and in clinical and molecular genetics.

“This is characterized by patchy manifestations, and no parent-to-child transmission or recurrence. You must always be careful here, though, because Mother Nature does what she wants to. Mosaic mutations can happen more than once, but it’s a very unlikely outcome. Happle-type mosaicism is also characterized by discordant monozygotic twins,” he noted.

The prototype for Happle-type mosaicism is Proteus syndrome, formerly known as Elephant Man disease, which is caused by a mutation in the AKT1 gene. Patients with Proteus syndrome undergo severe, relentless overgrowth, and about 25% of them die during childhood. “If you see one of these patients, you have a serious clinical problem on your hands,” he said. “There is enormous individual variability, but it is ultra rare.”


Dermatologic lesions that are characteristic of Proteus syndrome include cerebriform connective tissue nevus, which typically presents on the hands and feet. “A wide range of vascular malformations have also been associated with this, even patients with arteriovenous malformations,” Dr. Biesecker said. “They are a serious problem.” Linear verrucous epidermal nevus is another characteristic lesion of Proteus syndrome. It can present in a number of ways and in various body sites. “The natural history of these lesions is important,” he commented. “Over time, are they stable, or do they spread and expand over time? These lesions do not ever spontaneously regress. This does enable molecular diagnosis, but don’t bother sampling their blood, because it will be negative. You have to have a biopsy sample.”

Overgrowth syndromes that do not meet criteria for Proteus syndrome fall into a category known as PIK3CA-related overgrowth spectrum, which Dr. Biesecker characterized as “a bunch of clinical designations all caused by the same underlying somatic mutation in a gene called PIK3CA. There is an enormous variability in these patients, ranging from those who have profound overgrowth, including malformations, truncal overgrowth, and vascular malformations, and digital overgrowth in all sorts of patterns. We designate this as PIK3CA-related overgrowth spectrum (PROS), because we can’t clinically separate these things from one another.”

These conditions include what used to be called CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal/spinal anomalies), facial infiltrating lipomatosis, and megalencephaly-capillary malformation syndrome. PROS is about 100 times more common than Proteus syndrome. “There are no rational boundaries to distinguish these entities,” Dr. Biesecker said. “They are rationalized under a combined clinical-molecular PROS framework, meaning that the molecular diagnosis is absolutely key to correctly diagnosing these patients.”

In this way, mosaicism challenges the traditional concept of diagnosing overgrowth disorders. “What we thought were separate disorders are in fact many manifestations of a single disorder,” he continued. “When I was doing my genetics training, we were taught that it would turn out that there was one gene for every disease, and one disease for every gene. That is completely wrong; it’s much more complicated than that. Mosaicism is also important for us as biologists, because it gives us a window into biology we otherwise would not see. Without a mosaicism, Proteus syndrome cannot exist biologically. So if I want to understand that gene product, I have to study patients who are mosaics. Mosaicism can happen in any tissue, whether it’s visible or not.”

Dr. Biesecker, who has been elected to serve as president of the American Society of Human Genetics for 2019, noted that most of the gene mutations that cause overgrowth disorders are the same ones implicated in cancer. “It makes sense, because cancer is a disorder of uncontrolled proliferation and differentiation,” he said. “These overgrowth disorders are similar but less severe manifestations of the same problem. It turns out that these mosaic patients are single gene model systems of cancer biology.” Therefore, when a drug company develops an anti-cancer drug, he continued, it also can be useful for PROS or Proteus syndrome. It’s much easier to inhibit a protein that’s overactive than it is to replace the activity of a gene that has lost its function.

But in PROS and Proteus, “we have very different treatment objectives than oncologists do,” he said. “Our goal is to reduce the signaling caused by these mutations; we do not want to kill the cells. Some of my patients with these disorders have pretty close to 50% of cells in their body carrying these mutations. If I were thinking like an oncologist, the oncologist wants to kill cancer cells; that’s their objective. If I were to kill all of the mutant cells in my patients, I’m certain that would kill them.”

One promising development is the investigational oral agent ARQ 092, which is an inhibitor of AKT1. Dr. Biesecker and his colleagues at the NIH have been working to figure out what dosing should be used in humans based on mouse data, lab data, and data from cancer patients. They started with about one-twelvth the dose that oncologists use. After treating the first patient with overgrowth syndrome, on day 15 that person’s AKT1 level dropped to about 20% of normal, while on day 75 it moved to around 60% of normal. “We are right in that zone where we want to drive the activity of that protein to about half of what it should be,” Dr. Biesecker said. He and his colleagues also have observed regression of lesions in a patient with cerebriform connective tissue nevus who was treated with ARQ 092. “We’ve never seen this before.”

Dr. Biesecker disclosed that he is a member of the Illumina medical ethics board. He has received royalties from Genentech and in-kind research support from ArQule and Pfizer.

dbrunk@mdedge.com

 

Mosaicism makes everything in genetics more challenging, but it also enables researchers to understand how genes and cell pathways work in cancer and during human development, Leslie G. Biesecker, MD said at the annual meeting of the Society for Pediatric Dermatology.

Dr. Leslie G. Biesecker
Dr. Leslie G. Biesecker

Dr. Biesecker, senior investigator and head of the clinical genomics section of the National Human Genome Research Institute’s Medical Genomics and Metabolic Genetics Branch, discussed mosaicism and a number of overgrowth syndromes that he and his associates have been studying that have clinical relevance for pediatric dermatologists. He noted that mosaicism can affect any tissue, anywhere, in any pattern. “If an affected cell cannot survive gametogenesis, fertilization, or survive early development, this generates Happle-type mosaicism,” explained Dr. Biesecker, who is trained in pediatrics and in clinical and molecular genetics.

“This is characterized by patchy manifestations, and no parent-to-child transmission or recurrence. You must always be careful here, though, because Mother Nature does what she wants to. Mosaic mutations can happen more than once, but it’s a very unlikely outcome. Happle-type mosaicism is also characterized by discordant monozygotic twins,” he noted.

The prototype for Happle-type mosaicism is Proteus syndrome, formerly known as Elephant Man disease, which is caused by a mutation in the AKT1 gene. Patients with Proteus syndrome undergo severe, relentless overgrowth, and about 25% of them die during childhood. “If you see one of these patients, you have a serious clinical problem on your hands,” he said. “There is enormous individual variability, but it is ultra rare.”


Dermatologic lesions that are characteristic of Proteus syndrome include cerebriform connective tissue nevus, which typically presents on the hands and feet. “A wide range of vascular malformations have also been associated with this, even patients with arteriovenous malformations,” Dr. Biesecker said. “They are a serious problem.” Linear verrucous epidermal nevus is another characteristic lesion of Proteus syndrome. It can present in a number of ways and in various body sites. “The natural history of these lesions is important,” he commented. “Over time, are they stable, or do they spread and expand over time? These lesions do not ever spontaneously regress. This does enable molecular diagnosis, but don’t bother sampling their blood, because it will be negative. You have to have a biopsy sample.”

Overgrowth syndromes that do not meet criteria for Proteus syndrome fall into a category known as PIK3CA-related overgrowth spectrum, which Dr. Biesecker characterized as “a bunch of clinical designations all caused by the same underlying somatic mutation in a gene called PIK3CA. There is an enormous variability in these patients, ranging from those who have profound overgrowth, including malformations, truncal overgrowth, and vascular malformations, and digital overgrowth in all sorts of patterns. We designate this as PIK3CA-related overgrowth spectrum (PROS), because we can’t clinically separate these things from one another.”

These conditions include what used to be called CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal/spinal anomalies), facial infiltrating lipomatosis, and megalencephaly-capillary malformation syndrome. PROS is about 100 times more common than Proteus syndrome. “There are no rational boundaries to distinguish these entities,” Dr. Biesecker said. “They are rationalized under a combined clinical-molecular PROS framework, meaning that the molecular diagnosis is absolutely key to correctly diagnosing these patients.”

In this way, mosaicism challenges the traditional concept of diagnosing overgrowth disorders. “What we thought were separate disorders are in fact many manifestations of a single disorder,” he continued. “When I was doing my genetics training, we were taught that it would turn out that there was one gene for every disease, and one disease for every gene. That is completely wrong; it’s much more complicated than that. Mosaicism is also important for us as biologists, because it gives us a window into biology we otherwise would not see. Without a mosaicism, Proteus syndrome cannot exist biologically. So if I want to understand that gene product, I have to study patients who are mosaics. Mosaicism can happen in any tissue, whether it’s visible or not.”

Dr. Biesecker, who has been elected to serve as president of the American Society of Human Genetics for 2019, noted that most of the gene mutations that cause overgrowth disorders are the same ones implicated in cancer. “It makes sense, because cancer is a disorder of uncontrolled proliferation and differentiation,” he said. “These overgrowth disorders are similar but less severe manifestations of the same problem. It turns out that these mosaic patients are single gene model systems of cancer biology.” Therefore, when a drug company develops an anti-cancer drug, he continued, it also can be useful for PROS or Proteus syndrome. It’s much easier to inhibit a protein that’s overactive than it is to replace the activity of a gene that has lost its function.

But in PROS and Proteus, “we have very different treatment objectives than oncologists do,” he said. “Our goal is to reduce the signaling caused by these mutations; we do not want to kill the cells. Some of my patients with these disorders have pretty close to 50% of cells in their body carrying these mutations. If I were thinking like an oncologist, the oncologist wants to kill cancer cells; that’s their objective. If I were to kill all of the mutant cells in my patients, I’m certain that would kill them.”

One promising development is the investigational oral agent ARQ 092, which is an inhibitor of AKT1. Dr. Biesecker and his colleagues at the NIH have been working to figure out what dosing should be used in humans based on mouse data, lab data, and data from cancer patients. They started with about one-twelvth the dose that oncologists use. After treating the first patient with overgrowth syndrome, on day 15 that person’s AKT1 level dropped to about 20% of normal, while on day 75 it moved to around 60% of normal. “We are right in that zone where we want to drive the activity of that protein to about half of what it should be,” Dr. Biesecker said. He and his colleagues also have observed regression of lesions in a patient with cerebriform connective tissue nevus who was treated with ARQ 092. “We’ve never seen this before.”

Dr. Biesecker disclosed that he is a member of the Illumina medical ethics board. He has received royalties from Genentech and in-kind research support from ArQule and Pfizer.

dbrunk@mdedge.com

 

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JAK inhibitors emerge as promising alopecia treatment

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– After Brett King, MD, PhD, and his wife and collaborator, Brittany G. Craiglow, MD, published an index case of oral tofacitinib reversing alopecia universalis in a 25-year-old male patient back in 2014 (J Invest Dermatol. 2014;134:2988-90), they received hundreds of e-mails and phone calls from clinicians and patients.

“We also received quite a bit of media attention from around the world,” Dr. King recalled at the annual meeting of the Society for Pediatric Dermatology.

After all, alopecia areata and its variants affect 1%-2% of the population and have a marked impact on health-related quality of life, with high rates of concomitant generalized anxiety disorder and major depressive disorder. “The health-related quality of life is similar to that of atopic dermatitis and psoriasis, and there are no reliably effective therapies, especially for severe disease,” he said. “If treating atopic dermatitis and psoriasis with systemic agents is appropriate, then certainly treating alopecia areata is, too.

Currently available Janus kinase (JAK) inhibitors include tofacitinib (Xeljanz), ruxolitinib (Jakafi), and baricitinib (Olumiant). “These medicines are not [Food and Drug Administration] approved for alopecia areata, though tofacitinib was recently approved for psoriatic arthritis, and so we have formal entry of this medicine into dermatology for the first time,” said Dr. King, who is a dermatologist at Yale University, New Haven, Conn.


Potential adverse effects of JAKs include nasopharyngitis, headache, diarrhea, elevated cholesterol, uncommonly herpes zoster, cytopenias, transaminitis, and rarely non-melanoma skin cancer, solid organ malignancy and lymphoma, and GI perforation. Tofacitinib has an FDA black box warning regarding serious infections and malignancies, and baricitinib has these plus an additional warning about thrombosis.

In an open label, two-center trial that followed the index patient report, Dr. King and his associates enrolled 66 patients aged 19-35 years who had greater than 50% scalp hair loss for at least 6 months to receive tofacitinib 5 mg twice daily for 3 months (JCI Insight. 2016; 1[15]:e89776). A primary outcome of interest was regrowth of hair as measured by the percent change in Severity of Alopecia Tool (SALT) score. A SALT score of 100 indicates baldness, while a score of zero indicates no hair loss. Following 3 months of treatment, 32% of patients had a greater than 50% change in their SALT score, 32% had a change in the range of 5%-50%, while 36% had a change that was less than 5%.

“One of the interesting findings was that long duration of current episode of complete scalp hair loss was a negative predictor of treatment response, especially for those who have had hair loss greater than 10 years,” Dr. King said. Adverse events were “pretty bland,” with the most common being upper respiratory infection (17%), headache (8%), abdominal pain (8%), and acne (8%). Weight gain occurred in 1.5% of patients.

Next, Dr. King and colleagues reviewed the records of 90 patients aged 18 years or older who were treated with tofacitinib for at least 4 months (J Am Acad Dermatol. 2017;76[1]:22-8). Patients had greater than 40% scalp hair loss, and the tofacitinib dose was up to 10 mg per day at the discretion of the physician. “About 43% of patients were treated with tofacitinib 5 mg” twice daily, Dr. King said. “Other patients had higher doses or the addition of prednisone for three doses to see if that would help.”

After treatment, 20% of patients had a greater than 90% change in their SALT score (complete scalp hair regrowth), while 38.4% had a change that ranged from 51%-90%. At the same time, 18% had a change in their SALT score that ranged from 6%-50%, while 23% had a change that was 5% or less. As observed in the earlier trial, researchers saw a negative correlation between duration of current episode of hair loss and latest percent change in SALT score.

“We believe that you have to catch people before they get to more than 10 years of complete scalp hair loss,” Dr. King said. “This is important for the pediatric age group. I just saw somebody who’s 13, and they’ve been bald for 8 years. You might make the argument that this person deserves treatment, at least for a period of time long enough to regrow their hair in order to reset the clock.”

The most common adverse events were acne and weight gain.

In a separate analysis, Dr. King, Dr. Craiglow, and Lucy Y. Liu, evaluated the use of tofacitinib for at least 2 months in 13 alopecia areata patients aged 12-17 years (J Am Acad Dermatol. 2017;76[1]:29-32). They limited the analysis to those who had greater than 20% scalp hair loss, alopecia totalis, or alopecia universalis that was stable or worsening for 6 months or longer. Of the 13 patients, 9 (69%) were responders. Of the four non-responders, one had a very long duration of baldness. The percent change in SALT score was 93% overall, including 100% in the responder group over a median of 5 months and just 1% in the non-responder group over a median of 4 months. “This does not work every time,” Dr. King said.

While some preliminary studies of topical JAK inhibitors for alopecia areata show promise, it remains unclear if this approach will translate in a clinically meaningful way, he said. Clinical trials are currently under way.

Dr. King disclosed that he has received honoraria or consulting fees from Aclaris Therapeutics, Celgene, Concert Pharmaceuticals, Eli Lilly, Pfizer, Regeneron Pharmaceuticals, and Dermavant Sciences. He has also received funding support from The Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research.

dbrunk@mdedge.com

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– After Brett King, MD, PhD, and his wife and collaborator, Brittany G. Craiglow, MD, published an index case of oral tofacitinib reversing alopecia universalis in a 25-year-old male patient back in 2014 (J Invest Dermatol. 2014;134:2988-90), they received hundreds of e-mails and phone calls from clinicians and patients.

“We also received quite a bit of media attention from around the world,” Dr. King recalled at the annual meeting of the Society for Pediatric Dermatology.

After all, alopecia areata and its variants affect 1%-2% of the population and have a marked impact on health-related quality of life, with high rates of concomitant generalized anxiety disorder and major depressive disorder. “The health-related quality of life is similar to that of atopic dermatitis and psoriasis, and there are no reliably effective therapies, especially for severe disease,” he said. “If treating atopic dermatitis and psoriasis with systemic agents is appropriate, then certainly treating alopecia areata is, too.

Currently available Janus kinase (JAK) inhibitors include tofacitinib (Xeljanz), ruxolitinib (Jakafi), and baricitinib (Olumiant). “These medicines are not [Food and Drug Administration] approved for alopecia areata, though tofacitinib was recently approved for psoriatic arthritis, and so we have formal entry of this medicine into dermatology for the first time,” said Dr. King, who is a dermatologist at Yale University, New Haven, Conn.


Potential adverse effects of JAKs include nasopharyngitis, headache, diarrhea, elevated cholesterol, uncommonly herpes zoster, cytopenias, transaminitis, and rarely non-melanoma skin cancer, solid organ malignancy and lymphoma, and GI perforation. Tofacitinib has an FDA black box warning regarding serious infections and malignancies, and baricitinib has these plus an additional warning about thrombosis.

In an open label, two-center trial that followed the index patient report, Dr. King and his associates enrolled 66 patients aged 19-35 years who had greater than 50% scalp hair loss for at least 6 months to receive tofacitinib 5 mg twice daily for 3 months (JCI Insight. 2016; 1[15]:e89776). A primary outcome of interest was regrowth of hair as measured by the percent change in Severity of Alopecia Tool (SALT) score. A SALT score of 100 indicates baldness, while a score of zero indicates no hair loss. Following 3 months of treatment, 32% of patients had a greater than 50% change in their SALT score, 32% had a change in the range of 5%-50%, while 36% had a change that was less than 5%.

“One of the interesting findings was that long duration of current episode of complete scalp hair loss was a negative predictor of treatment response, especially for those who have had hair loss greater than 10 years,” Dr. King said. Adverse events were “pretty bland,” with the most common being upper respiratory infection (17%), headache (8%), abdominal pain (8%), and acne (8%). Weight gain occurred in 1.5% of patients.

Next, Dr. King and colleagues reviewed the records of 90 patients aged 18 years or older who were treated with tofacitinib for at least 4 months (J Am Acad Dermatol. 2017;76[1]:22-8). Patients had greater than 40% scalp hair loss, and the tofacitinib dose was up to 10 mg per day at the discretion of the physician. “About 43% of patients were treated with tofacitinib 5 mg” twice daily, Dr. King said. “Other patients had higher doses or the addition of prednisone for three doses to see if that would help.”

After treatment, 20% of patients had a greater than 90% change in their SALT score (complete scalp hair regrowth), while 38.4% had a change that ranged from 51%-90%. At the same time, 18% had a change in their SALT score that ranged from 6%-50%, while 23% had a change that was 5% or less. As observed in the earlier trial, researchers saw a negative correlation between duration of current episode of hair loss and latest percent change in SALT score.

“We believe that you have to catch people before they get to more than 10 years of complete scalp hair loss,” Dr. King said. “This is important for the pediatric age group. I just saw somebody who’s 13, and they’ve been bald for 8 years. You might make the argument that this person deserves treatment, at least for a period of time long enough to regrow their hair in order to reset the clock.”

The most common adverse events were acne and weight gain.

In a separate analysis, Dr. King, Dr. Craiglow, and Lucy Y. Liu, evaluated the use of tofacitinib for at least 2 months in 13 alopecia areata patients aged 12-17 years (J Am Acad Dermatol. 2017;76[1]:29-32). They limited the analysis to those who had greater than 20% scalp hair loss, alopecia totalis, or alopecia universalis that was stable or worsening for 6 months or longer. Of the 13 patients, 9 (69%) were responders. Of the four non-responders, one had a very long duration of baldness. The percent change in SALT score was 93% overall, including 100% in the responder group over a median of 5 months and just 1% in the non-responder group over a median of 4 months. “This does not work every time,” Dr. King said.

While some preliminary studies of topical JAK inhibitors for alopecia areata show promise, it remains unclear if this approach will translate in a clinically meaningful way, he said. Clinical trials are currently under way.

Dr. King disclosed that he has received honoraria or consulting fees from Aclaris Therapeutics, Celgene, Concert Pharmaceuticals, Eli Lilly, Pfizer, Regeneron Pharmaceuticals, and Dermavant Sciences. He has also received funding support from The Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research.

dbrunk@mdedge.com

– After Brett King, MD, PhD, and his wife and collaborator, Brittany G. Craiglow, MD, published an index case of oral tofacitinib reversing alopecia universalis in a 25-year-old male patient back in 2014 (J Invest Dermatol. 2014;134:2988-90), they received hundreds of e-mails and phone calls from clinicians and patients.

“We also received quite a bit of media attention from around the world,” Dr. King recalled at the annual meeting of the Society for Pediatric Dermatology.

After all, alopecia areata and its variants affect 1%-2% of the population and have a marked impact on health-related quality of life, with high rates of concomitant generalized anxiety disorder and major depressive disorder. “The health-related quality of life is similar to that of atopic dermatitis and psoriasis, and there are no reliably effective therapies, especially for severe disease,” he said. “If treating atopic dermatitis and psoriasis with systemic agents is appropriate, then certainly treating alopecia areata is, too.

Currently available Janus kinase (JAK) inhibitors include tofacitinib (Xeljanz), ruxolitinib (Jakafi), and baricitinib (Olumiant). “These medicines are not [Food and Drug Administration] approved for alopecia areata, though tofacitinib was recently approved for psoriatic arthritis, and so we have formal entry of this medicine into dermatology for the first time,” said Dr. King, who is a dermatologist at Yale University, New Haven, Conn.


Potential adverse effects of JAKs include nasopharyngitis, headache, diarrhea, elevated cholesterol, uncommonly herpes zoster, cytopenias, transaminitis, and rarely non-melanoma skin cancer, solid organ malignancy and lymphoma, and GI perforation. Tofacitinib has an FDA black box warning regarding serious infections and malignancies, and baricitinib has these plus an additional warning about thrombosis.

In an open label, two-center trial that followed the index patient report, Dr. King and his associates enrolled 66 patients aged 19-35 years who had greater than 50% scalp hair loss for at least 6 months to receive tofacitinib 5 mg twice daily for 3 months (JCI Insight. 2016; 1[15]:e89776). A primary outcome of interest was regrowth of hair as measured by the percent change in Severity of Alopecia Tool (SALT) score. A SALT score of 100 indicates baldness, while a score of zero indicates no hair loss. Following 3 months of treatment, 32% of patients had a greater than 50% change in their SALT score, 32% had a change in the range of 5%-50%, while 36% had a change that was less than 5%.

“One of the interesting findings was that long duration of current episode of complete scalp hair loss was a negative predictor of treatment response, especially for those who have had hair loss greater than 10 years,” Dr. King said. Adverse events were “pretty bland,” with the most common being upper respiratory infection (17%), headache (8%), abdominal pain (8%), and acne (8%). Weight gain occurred in 1.5% of patients.

Next, Dr. King and colleagues reviewed the records of 90 patients aged 18 years or older who were treated with tofacitinib for at least 4 months (J Am Acad Dermatol. 2017;76[1]:22-8). Patients had greater than 40% scalp hair loss, and the tofacitinib dose was up to 10 mg per day at the discretion of the physician. “About 43% of patients were treated with tofacitinib 5 mg” twice daily, Dr. King said. “Other patients had higher doses or the addition of prednisone for three doses to see if that would help.”

After treatment, 20% of patients had a greater than 90% change in their SALT score (complete scalp hair regrowth), while 38.4% had a change that ranged from 51%-90%. At the same time, 18% had a change in their SALT score that ranged from 6%-50%, while 23% had a change that was 5% or less. As observed in the earlier trial, researchers saw a negative correlation between duration of current episode of hair loss and latest percent change in SALT score.

“We believe that you have to catch people before they get to more than 10 years of complete scalp hair loss,” Dr. King said. “This is important for the pediatric age group. I just saw somebody who’s 13, and they’ve been bald for 8 years. You might make the argument that this person deserves treatment, at least for a period of time long enough to regrow their hair in order to reset the clock.”

The most common adverse events were acne and weight gain.

In a separate analysis, Dr. King, Dr. Craiglow, and Lucy Y. Liu, evaluated the use of tofacitinib for at least 2 months in 13 alopecia areata patients aged 12-17 years (J Am Acad Dermatol. 2017;76[1]:29-32). They limited the analysis to those who had greater than 20% scalp hair loss, alopecia totalis, or alopecia universalis that was stable or worsening for 6 months or longer. Of the 13 patients, 9 (69%) were responders. Of the four non-responders, one had a very long duration of baldness. The percent change in SALT score was 93% overall, including 100% in the responder group over a median of 5 months and just 1% in the non-responder group over a median of 4 months. “This does not work every time,” Dr. King said.

While some preliminary studies of topical JAK inhibitors for alopecia areata show promise, it remains unclear if this approach will translate in a clinically meaningful way, he said. Clinical trials are currently under way.

Dr. King disclosed that he has received honoraria or consulting fees from Aclaris Therapeutics, Celgene, Concert Pharmaceuticals, Eli Lilly, Pfizer, Regeneron Pharmaceuticals, and Dermavant Sciences. He has also received funding support from The Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research.

dbrunk@mdedge.com

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Poor gut health tied to increased systemic disease risk

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Strong associations exist between intestinal dysbiosis and a wide variety of gut and systemic diseases, according to Mark A. Underwood, MD.

Dr. Mark A. Underwood
Doug Brunk/MDedge News
Dr. Mark A. Underwood

“Antibiotic exposure changes the composition of the intestinal microbiota,” he said at the annual meeting of the Society for Pediatric Dermatology. “That clearly causes both antibiotic-associated diarrhea and Clostridium difficile colitis. The bigger question is, is it possible that intestinal dysbiosis is related to a whole bunch of other systemic diseases? In other words, does an insult during a critical window of development cause changes in the intestinal microbiota that can lead to systemic diseases in the brain, the lung, the liver, or the immune system?”

According Dr. Underwood, a pediatrician who is chief of the division of neonatology at the University of California, Davis, the prevalence of dysbiosis is increasing worldwide, particularly in developed countries, where Bifidobacteria are decreasing and Enterobacteriaceae are increasing. “Those changes are associated with gut permeability and alterations in both local and systemic inflammation, and the risk for a number of diseases, including atopic dermatitis,” he said. Key reasons for the increasing prevalence of dysbiosis, he continued, include the use of antibiotics, cesarean section delivery, formula feeding, changes in hygiene that alter the intestinal biota, the high-fat, high-sugar Western diet, and a loss of vertical and horizontal transmission over generations.

In an effort to evaluate the association between early childhood antibiotic use with allergic diseases in later childhood, Japanese researchers followed 1,200 infants to the age of 5 years (Ann Allergy Asthma Immunol. 2017;119:54-8). They found that antibiotic exposure within the first 2 years of life was associated with an increased risk of asthma (adjusted odds ratio 1.72), allergic rhinitis (adjusted OR 1.65), and atopic dermatitis (adjusted OR 1.40). In a more recent, smaller prospective study, 436 Dutch infants were followed to 1 year of age (Pediatr Allergy Immunol. 2018;29[2]:151-8). The researchers found that antibiotic exposure within the first week of life was associated with allergic sensitization (adjusted OR 3.26), colic (adjusted OR 1.66), and wheezing (adjusted OR 1.56).

In a study of 44 term infants with a family history of allergy, changes in the fecal microbiota, especially colonization with Ruminococcus gnavus, preceded the onset of allergic symptoms (Gastroenterol. 2018;154[1]:154-67). The same researchers observed similar findings in an animal model.

One potential mechanism by which intestinal dysbiosis causes systemic disease is stimulation of toll-like receptor 4 (TLR4), “which is a receptor on a variety of mucosal cells that senses the presence of a microbial pathogen-associated patterns, particularly those of Gram-negative Enterobacteriaceae,” Dr. Underwood explained. Other potential mechanisms include increased intestinal permeability, an increase in the pH and decreases in short-chain fatty acids within the gut lumen, and a loss of intraluminal hypoxia. “Think of the colon as an anaerobic chamber,” he said. “The colon lumen should be very low in oxygen. It should be dominated by obligate anaerobes.”

Efforts to prevent or treat dysbiosis-related diseases include the use of probiotics and fecal transplantation. A recent Cochrane review of 8,672 patients found “moderate certainty evidence” that probiotics are effective for preventing C. difficile-associated diarrhea. The analysis included 31 randomized, controlled trials of adults who were treated either with a probiotic or with a placebo. When pooled, the risk ratio was 0.40, which represented a significant protection. In addition, a summary of 7 randomized controlled trials and 30 case series suggests that fecal microbial transplantation is superior to vancomycin for adults with recurrent C. difficile colitis (relative risk 0.23) (Aliment Pharmacol Ther. 2017;46[5]:470-93).

To date, the effect of giving probiotics to pregnant women who have a family history of allergy is less clear. One pooled analysis of such studies put the overall risk ratio at 0.74 (Mil Med. 2014;179[6]:580-92). “While I think the jury’s still out on how to best prevent atopic dermatitis in these families, it looks like there is some potential benefit in treating these moms during pregnancy with probiotics and treating the infant during the first few months of life,” Dr. Underwood said. The most effective were mixtures including one or more Lactobacillus species or L. rhamnosus, mixtures including one or more Bifidobacterium species, or B. lactis by itself. The use of probiotics also has been found to prevent necrotizing enterocolitis, sepsis, and death in premature infants (Semin Pediatr Surg. 2018;27[1]:39-46).

Dr. Underwood disclosed that he has received honoraria from Abbott and that he was a member of the scientific review board for Avexegen. He also chaired the data safety and monitoring board for Infant Bacterial Therapeutics and has received support from Evolve BioSystems to perform a clinical trial.

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Strong associations exist between intestinal dysbiosis and a wide variety of gut and systemic diseases, according to Mark A. Underwood, MD.

Dr. Mark A. Underwood
Doug Brunk/MDedge News
Dr. Mark A. Underwood

“Antibiotic exposure changes the composition of the intestinal microbiota,” he said at the annual meeting of the Society for Pediatric Dermatology. “That clearly causes both antibiotic-associated diarrhea and Clostridium difficile colitis. The bigger question is, is it possible that intestinal dysbiosis is related to a whole bunch of other systemic diseases? In other words, does an insult during a critical window of development cause changes in the intestinal microbiota that can lead to systemic diseases in the brain, the lung, the liver, or the immune system?”

According Dr. Underwood, a pediatrician who is chief of the division of neonatology at the University of California, Davis, the prevalence of dysbiosis is increasing worldwide, particularly in developed countries, where Bifidobacteria are decreasing and Enterobacteriaceae are increasing. “Those changes are associated with gut permeability and alterations in both local and systemic inflammation, and the risk for a number of diseases, including atopic dermatitis,” he said. Key reasons for the increasing prevalence of dysbiosis, he continued, include the use of antibiotics, cesarean section delivery, formula feeding, changes in hygiene that alter the intestinal biota, the high-fat, high-sugar Western diet, and a loss of vertical and horizontal transmission over generations.

In an effort to evaluate the association between early childhood antibiotic use with allergic diseases in later childhood, Japanese researchers followed 1,200 infants to the age of 5 years (Ann Allergy Asthma Immunol. 2017;119:54-8). They found that antibiotic exposure within the first 2 years of life was associated with an increased risk of asthma (adjusted odds ratio 1.72), allergic rhinitis (adjusted OR 1.65), and atopic dermatitis (adjusted OR 1.40). In a more recent, smaller prospective study, 436 Dutch infants were followed to 1 year of age (Pediatr Allergy Immunol. 2018;29[2]:151-8). The researchers found that antibiotic exposure within the first week of life was associated with allergic sensitization (adjusted OR 3.26), colic (adjusted OR 1.66), and wheezing (adjusted OR 1.56).

In a study of 44 term infants with a family history of allergy, changes in the fecal microbiota, especially colonization with Ruminococcus gnavus, preceded the onset of allergic symptoms (Gastroenterol. 2018;154[1]:154-67). The same researchers observed similar findings in an animal model.

One potential mechanism by which intestinal dysbiosis causes systemic disease is stimulation of toll-like receptor 4 (TLR4), “which is a receptor on a variety of mucosal cells that senses the presence of a microbial pathogen-associated patterns, particularly those of Gram-negative Enterobacteriaceae,” Dr. Underwood explained. Other potential mechanisms include increased intestinal permeability, an increase in the pH and decreases in short-chain fatty acids within the gut lumen, and a loss of intraluminal hypoxia. “Think of the colon as an anaerobic chamber,” he said. “The colon lumen should be very low in oxygen. It should be dominated by obligate anaerobes.”

Efforts to prevent or treat dysbiosis-related diseases include the use of probiotics and fecal transplantation. A recent Cochrane review of 8,672 patients found “moderate certainty evidence” that probiotics are effective for preventing C. difficile-associated diarrhea. The analysis included 31 randomized, controlled trials of adults who were treated either with a probiotic or with a placebo. When pooled, the risk ratio was 0.40, which represented a significant protection. In addition, a summary of 7 randomized controlled trials and 30 case series suggests that fecal microbial transplantation is superior to vancomycin for adults with recurrent C. difficile colitis (relative risk 0.23) (Aliment Pharmacol Ther. 2017;46[5]:470-93).

To date, the effect of giving probiotics to pregnant women who have a family history of allergy is less clear. One pooled analysis of such studies put the overall risk ratio at 0.74 (Mil Med. 2014;179[6]:580-92). “While I think the jury’s still out on how to best prevent atopic dermatitis in these families, it looks like there is some potential benefit in treating these moms during pregnancy with probiotics and treating the infant during the first few months of life,” Dr. Underwood said. The most effective were mixtures including one or more Lactobacillus species or L. rhamnosus, mixtures including one or more Bifidobacterium species, or B. lactis by itself. The use of probiotics also has been found to prevent necrotizing enterocolitis, sepsis, and death in premature infants (Semin Pediatr Surg. 2018;27[1]:39-46).

Dr. Underwood disclosed that he has received honoraria from Abbott and that he was a member of the scientific review board for Avexegen. He also chaired the data safety and monitoring board for Infant Bacterial Therapeutics and has received support from Evolve BioSystems to perform a clinical trial.

dbrunk@mdedge.com

 

Strong associations exist between intestinal dysbiosis and a wide variety of gut and systemic diseases, according to Mark A. Underwood, MD.

Dr. Mark A. Underwood
Doug Brunk/MDedge News
Dr. Mark A. Underwood

“Antibiotic exposure changes the composition of the intestinal microbiota,” he said at the annual meeting of the Society for Pediatric Dermatology. “That clearly causes both antibiotic-associated diarrhea and Clostridium difficile colitis. The bigger question is, is it possible that intestinal dysbiosis is related to a whole bunch of other systemic diseases? In other words, does an insult during a critical window of development cause changes in the intestinal microbiota that can lead to systemic diseases in the brain, the lung, the liver, or the immune system?”

According Dr. Underwood, a pediatrician who is chief of the division of neonatology at the University of California, Davis, the prevalence of dysbiosis is increasing worldwide, particularly in developed countries, where Bifidobacteria are decreasing and Enterobacteriaceae are increasing. “Those changes are associated with gut permeability and alterations in both local and systemic inflammation, and the risk for a number of diseases, including atopic dermatitis,” he said. Key reasons for the increasing prevalence of dysbiosis, he continued, include the use of antibiotics, cesarean section delivery, formula feeding, changes in hygiene that alter the intestinal biota, the high-fat, high-sugar Western diet, and a loss of vertical and horizontal transmission over generations.

In an effort to evaluate the association between early childhood antibiotic use with allergic diseases in later childhood, Japanese researchers followed 1,200 infants to the age of 5 years (Ann Allergy Asthma Immunol. 2017;119:54-8). They found that antibiotic exposure within the first 2 years of life was associated with an increased risk of asthma (adjusted odds ratio 1.72), allergic rhinitis (adjusted OR 1.65), and atopic dermatitis (adjusted OR 1.40). In a more recent, smaller prospective study, 436 Dutch infants were followed to 1 year of age (Pediatr Allergy Immunol. 2018;29[2]:151-8). The researchers found that antibiotic exposure within the first week of life was associated with allergic sensitization (adjusted OR 3.26), colic (adjusted OR 1.66), and wheezing (adjusted OR 1.56).

In a study of 44 term infants with a family history of allergy, changes in the fecal microbiota, especially colonization with Ruminococcus gnavus, preceded the onset of allergic symptoms (Gastroenterol. 2018;154[1]:154-67). The same researchers observed similar findings in an animal model.

One potential mechanism by which intestinal dysbiosis causes systemic disease is stimulation of toll-like receptor 4 (TLR4), “which is a receptor on a variety of mucosal cells that senses the presence of a microbial pathogen-associated patterns, particularly those of Gram-negative Enterobacteriaceae,” Dr. Underwood explained. Other potential mechanisms include increased intestinal permeability, an increase in the pH and decreases in short-chain fatty acids within the gut lumen, and a loss of intraluminal hypoxia. “Think of the colon as an anaerobic chamber,” he said. “The colon lumen should be very low in oxygen. It should be dominated by obligate anaerobes.”

Efforts to prevent or treat dysbiosis-related diseases include the use of probiotics and fecal transplantation. A recent Cochrane review of 8,672 patients found “moderate certainty evidence” that probiotics are effective for preventing C. difficile-associated diarrhea. The analysis included 31 randomized, controlled trials of adults who were treated either with a probiotic or with a placebo. When pooled, the risk ratio was 0.40, which represented a significant protection. In addition, a summary of 7 randomized controlled trials and 30 case series suggests that fecal microbial transplantation is superior to vancomycin for adults with recurrent C. difficile colitis (relative risk 0.23) (Aliment Pharmacol Ther. 2017;46[5]:470-93).

To date, the effect of giving probiotics to pregnant women who have a family history of allergy is less clear. One pooled analysis of such studies put the overall risk ratio at 0.74 (Mil Med. 2014;179[6]:580-92). “While I think the jury’s still out on how to best prevent atopic dermatitis in these families, it looks like there is some potential benefit in treating these moms during pregnancy with probiotics and treating the infant during the first few months of life,” Dr. Underwood said. The most effective were mixtures including one or more Lactobacillus species or L. rhamnosus, mixtures including one or more Bifidobacterium species, or B. lactis by itself. The use of probiotics also has been found to prevent necrotizing enterocolitis, sepsis, and death in premature infants (Semin Pediatr Surg. 2018;27[1]:39-46).

Dr. Underwood disclosed that he has received honoraria from Abbott and that he was a member of the scientific review board for Avexegen. He also chaired the data safety and monitoring board for Infant Bacterial Therapeutics and has received support from Evolve BioSystems to perform a clinical trial.

dbrunk@mdedge.com

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Orodental issues often associated with facial port-wine stains

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– Several years ago, David H. Darrow, MD, DDS, began to notice a pattern in the conversation threads on websites dedicated to support for parents of children with facial port-wine stains (PWS).

Parents were reporting that dental problems arose earlier on their child’s side of face with the PWS, and that the alveolar ridge was lower on the side of the face that harbored the lesion. “Most importantly, parents were concerned that dentists were not touching their children because they were concerned about bleeding,” Dr. Darrow said at the annual meeting of the Society for Pediatric Dermatology. A search in the medical literature for port-wine stains and oral cavity changes, did not turn up much except for a few articles on bleeding. “One said that port-wine stains or capillary malformations rarely present major problems for the oral and maxillofacial surgeon. The other said that periodontal probing should not be done, as even gentle probing can result in uncontrolled bleeding,” he noted.

This prompted Dr. Darrow, who directs the Center for Hemangiomas and Vascular Birthmarks at the Eastern Virginia Medical School, Norfolk, and coinvestigators, Megan B. Dowling, MD, and Yueqin Zhao, PhD, to characterize manifestations of PWS in the oral cavity via an anonymous paired survey of volunteers with facial PWS and their dentists who were recruited from birthmarks.com and 10 collaborating physician practices (J Am Acad Dermatol 2012;67:687-93). Volunteers ranged in age from 1 to 62 years; mean age was 29 years. A total of 30 patients participated, and most (67%) were female.


The five most common oral manifestations reported by the patients were lip hyperplasia (53%), stained gingiva (47%), malocclusion (30%), bleeding gingiva (27%), and spacing between teeth (23%). Only 3% reported bleeding from dental procedures. When the researchers evaluated the orodental findings in the paired patient-physician responses, “most of the time there was good agreement between the patient and the dentist,” Dr. Darrow said. “The only one that fell out of agreement was lip hyperplasia. That’s probably because most dentists look right past the lips and into the oral cavity.”

When the researchers examined patients who had stained gingiva versus those who did not, they found that early-stage lesions demonstrated a reddish blush of the oral mucosa and gingiva, while late-stage lesions demonstrated increased blush of the oral tissues, as well as hyperplasia of the soft tissue or bone in the affected area. “Based on our review of the literature, bleeding of gums is rarely prolonged and dental procedures are safe,” Dr. Darrow said.

The findings are important, he continued, because capillary malformations of the oral cavity may result in periodontal disease associated with gingival overgrowth. The depth of the gingival pocket should be no more than 2-3 mm. “When you have areas of inflammation and deep-pocket formation, plaque and bacteria slowly erode the connection between the tooth and the soft tissue,” he explained. “At some point, that pocket becomes so deep that it reaches down into the bone in which the tooth is anchored. As that bone is eroded, the teeth loosen and begin to fall out. The goals of therapy are prevention of periodontal disease with meticulous oral hygiene.”

Soft tissue hyperplasia may be exacerbated by medications such as calcium channel blockers, cyclosporine, and phenytoin and phenobarbital, which are sometimes used by patients with Sturge-Weber syndrome, he said.

Dr. Darrow reported having no financial disclosures.

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– Several years ago, David H. Darrow, MD, DDS, began to notice a pattern in the conversation threads on websites dedicated to support for parents of children with facial port-wine stains (PWS).

Parents were reporting that dental problems arose earlier on their child’s side of face with the PWS, and that the alveolar ridge was lower on the side of the face that harbored the lesion. “Most importantly, parents were concerned that dentists were not touching their children because they were concerned about bleeding,” Dr. Darrow said at the annual meeting of the Society for Pediatric Dermatology. A search in the medical literature for port-wine stains and oral cavity changes, did not turn up much except for a few articles on bleeding. “One said that port-wine stains or capillary malformations rarely present major problems for the oral and maxillofacial surgeon. The other said that periodontal probing should not be done, as even gentle probing can result in uncontrolled bleeding,” he noted.

This prompted Dr. Darrow, who directs the Center for Hemangiomas and Vascular Birthmarks at the Eastern Virginia Medical School, Norfolk, and coinvestigators, Megan B. Dowling, MD, and Yueqin Zhao, PhD, to characterize manifestations of PWS in the oral cavity via an anonymous paired survey of volunteers with facial PWS and their dentists who were recruited from birthmarks.com and 10 collaborating physician practices (J Am Acad Dermatol 2012;67:687-93). Volunteers ranged in age from 1 to 62 years; mean age was 29 years. A total of 30 patients participated, and most (67%) were female.


The five most common oral manifestations reported by the patients were lip hyperplasia (53%), stained gingiva (47%), malocclusion (30%), bleeding gingiva (27%), and spacing between teeth (23%). Only 3% reported bleeding from dental procedures. When the researchers evaluated the orodental findings in the paired patient-physician responses, “most of the time there was good agreement between the patient and the dentist,” Dr. Darrow said. “The only one that fell out of agreement was lip hyperplasia. That’s probably because most dentists look right past the lips and into the oral cavity.”

When the researchers examined patients who had stained gingiva versus those who did not, they found that early-stage lesions demonstrated a reddish blush of the oral mucosa and gingiva, while late-stage lesions demonstrated increased blush of the oral tissues, as well as hyperplasia of the soft tissue or bone in the affected area. “Based on our review of the literature, bleeding of gums is rarely prolonged and dental procedures are safe,” Dr. Darrow said.

The findings are important, he continued, because capillary malformations of the oral cavity may result in periodontal disease associated with gingival overgrowth. The depth of the gingival pocket should be no more than 2-3 mm. “When you have areas of inflammation and deep-pocket formation, plaque and bacteria slowly erode the connection between the tooth and the soft tissue,” he explained. “At some point, that pocket becomes so deep that it reaches down into the bone in which the tooth is anchored. As that bone is eroded, the teeth loosen and begin to fall out. The goals of therapy are prevention of periodontal disease with meticulous oral hygiene.”

Soft tissue hyperplasia may be exacerbated by medications such as calcium channel blockers, cyclosporine, and phenytoin and phenobarbital, which are sometimes used by patients with Sturge-Weber syndrome, he said.

Dr. Darrow reported having no financial disclosures.

 

– Several years ago, David H. Darrow, MD, DDS, began to notice a pattern in the conversation threads on websites dedicated to support for parents of children with facial port-wine stains (PWS).

Parents were reporting that dental problems arose earlier on their child’s side of face with the PWS, and that the alveolar ridge was lower on the side of the face that harbored the lesion. “Most importantly, parents were concerned that dentists were not touching their children because they were concerned about bleeding,” Dr. Darrow said at the annual meeting of the Society for Pediatric Dermatology. A search in the medical literature for port-wine stains and oral cavity changes, did not turn up much except for a few articles on bleeding. “One said that port-wine stains or capillary malformations rarely present major problems for the oral and maxillofacial surgeon. The other said that periodontal probing should not be done, as even gentle probing can result in uncontrolled bleeding,” he noted.

This prompted Dr. Darrow, who directs the Center for Hemangiomas and Vascular Birthmarks at the Eastern Virginia Medical School, Norfolk, and coinvestigators, Megan B. Dowling, MD, and Yueqin Zhao, PhD, to characterize manifestations of PWS in the oral cavity via an anonymous paired survey of volunteers with facial PWS and their dentists who were recruited from birthmarks.com and 10 collaborating physician practices (J Am Acad Dermatol 2012;67:687-93). Volunteers ranged in age from 1 to 62 years; mean age was 29 years. A total of 30 patients participated, and most (67%) were female.


The five most common oral manifestations reported by the patients were lip hyperplasia (53%), stained gingiva (47%), malocclusion (30%), bleeding gingiva (27%), and spacing between teeth (23%). Only 3% reported bleeding from dental procedures. When the researchers evaluated the orodental findings in the paired patient-physician responses, “most of the time there was good agreement between the patient and the dentist,” Dr. Darrow said. “The only one that fell out of agreement was lip hyperplasia. That’s probably because most dentists look right past the lips and into the oral cavity.”

When the researchers examined patients who had stained gingiva versus those who did not, they found that early-stage lesions demonstrated a reddish blush of the oral mucosa and gingiva, while late-stage lesions demonstrated increased blush of the oral tissues, as well as hyperplasia of the soft tissue or bone in the affected area. “Based on our review of the literature, bleeding of gums is rarely prolonged and dental procedures are safe,” Dr. Darrow said.

The findings are important, he continued, because capillary malformations of the oral cavity may result in periodontal disease associated with gingival overgrowth. The depth of the gingival pocket should be no more than 2-3 mm. “When you have areas of inflammation and deep-pocket formation, plaque and bacteria slowly erode the connection between the tooth and the soft tissue,” he explained. “At some point, that pocket becomes so deep that it reaches down into the bone in which the tooth is anchored. As that bone is eroded, the teeth loosen and begin to fall out. The goals of therapy are prevention of periodontal disease with meticulous oral hygiene.”

Soft tissue hyperplasia may be exacerbated by medications such as calcium channel blockers, cyclosporine, and phenytoin and phenobarbital, which are sometimes used by patients with Sturge-Weber syndrome, he said.

Dr. Darrow reported having no financial disclosures.

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Three steps are involved in assessing a vesiculopustular lesion

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– Evaluation of an infant with a vesiculopustular lesion entails a pragmatic approach, with three assessment steps, according to pediatric dermatologist Lawrence A. Schachner, MD.

Dr. Lawrence A. Schachner, University of Miami, pediatric dermatology
Dr. Lawrence A. Schachner

At the annual meeting of the Society for Pediatric Dermatology, Dr. Schachner noted that the differential diagnosis of noninfectious, usually benign neonatal vesiculopustular lesions includes acropustulosis of infancy; eosinophilic pustular folliculitis; erythema toxicum neonatorum; miliaria crystallina, rubra, or profunda; transient neonatal pustular melanosis; and neonatal sucking blisters. Noninfectious lesions that can be potentially serious include acrodermatitis enteropathica, bullous pemphigoid, epidermolysis bullosa, epidermolytic hyperkeratosis, incontinentia pigmenti, Langerhans cell histiocytosis, pemphigus vulgaris, pustular psoriasis, and urticarial pigmentosa.

Step 1 for evaluating vesiculopustular lesions involves drawing out the fluid for bacterial cultures and sensitivity, Gram stains, viral culture and/or serology, said Dr. Schachner, who directs the division of pediatric dermatology at the University of Miami.

Step 2 involves snipping off the lesion’s roof for a potassium hydroxide test to send for dermatopathology or frozen pathology.

Step 3 involves scraping the lesion’s base for viral cytology and cell identification. “If we can see a predominant cell type, that’s where the action is,” said Dr. Schachner, professor of pediatrics at the university. If cytology reveals polymorphic neutrophils, differential diagnoses include transient neonatal pustular melanosis, infantile acropustulosis, bullous impetigo, and pustular psoriasis. If cytology reveals eosinophils, differential diagnoses include eosinophilic pustular folliculitis of infancy, erythema toxicum neonatorum, incontinentia pigmenti, bullous pemphigoid, drug reactions, and arthropod bites. The presence of lymphocytes on cytology, meanwhile, may suggest a differential diagnosis miliaria or acrodermatitis enteropathica.

“When in doubt about the diagnosis, biopsy,” Dr. Schachner said. “This, to me, is a pragmatic approach.”

Dr. Schachner disclosed that he is an investigator for Astellas, Ferndale Labs, Novartis, Organogenesis, Stiefel Laboratories, Berg Pharma, Medimetrics, and Lilly. He is a consultant to Beiersdorf, Lexington, TopMD, Cutanea, Hoth Therapeutics, and Mustela.

dbrunk@mdedge.com

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– Evaluation of an infant with a vesiculopustular lesion entails a pragmatic approach, with three assessment steps, according to pediatric dermatologist Lawrence A. Schachner, MD.

Dr. Lawrence A. Schachner, University of Miami, pediatric dermatology
Dr. Lawrence A. Schachner

At the annual meeting of the Society for Pediatric Dermatology, Dr. Schachner noted that the differential diagnosis of noninfectious, usually benign neonatal vesiculopustular lesions includes acropustulosis of infancy; eosinophilic pustular folliculitis; erythema toxicum neonatorum; miliaria crystallina, rubra, or profunda; transient neonatal pustular melanosis; and neonatal sucking blisters. Noninfectious lesions that can be potentially serious include acrodermatitis enteropathica, bullous pemphigoid, epidermolysis bullosa, epidermolytic hyperkeratosis, incontinentia pigmenti, Langerhans cell histiocytosis, pemphigus vulgaris, pustular psoriasis, and urticarial pigmentosa.

Step 1 for evaluating vesiculopustular lesions involves drawing out the fluid for bacterial cultures and sensitivity, Gram stains, viral culture and/or serology, said Dr. Schachner, who directs the division of pediatric dermatology at the University of Miami.

Step 2 involves snipping off the lesion’s roof for a potassium hydroxide test to send for dermatopathology or frozen pathology.

Step 3 involves scraping the lesion’s base for viral cytology and cell identification. “If we can see a predominant cell type, that’s where the action is,” said Dr. Schachner, professor of pediatrics at the university. If cytology reveals polymorphic neutrophils, differential diagnoses include transient neonatal pustular melanosis, infantile acropustulosis, bullous impetigo, and pustular psoriasis. If cytology reveals eosinophils, differential diagnoses include eosinophilic pustular folliculitis of infancy, erythema toxicum neonatorum, incontinentia pigmenti, bullous pemphigoid, drug reactions, and arthropod bites. The presence of lymphocytes on cytology, meanwhile, may suggest a differential diagnosis miliaria or acrodermatitis enteropathica.

“When in doubt about the diagnosis, biopsy,” Dr. Schachner said. “This, to me, is a pragmatic approach.”

Dr. Schachner disclosed that he is an investigator for Astellas, Ferndale Labs, Novartis, Organogenesis, Stiefel Laboratories, Berg Pharma, Medimetrics, and Lilly. He is a consultant to Beiersdorf, Lexington, TopMD, Cutanea, Hoth Therapeutics, and Mustela.

dbrunk@mdedge.com

 

– Evaluation of an infant with a vesiculopustular lesion entails a pragmatic approach, with three assessment steps, according to pediatric dermatologist Lawrence A. Schachner, MD.

Dr. Lawrence A. Schachner, University of Miami, pediatric dermatology
Dr. Lawrence A. Schachner

At the annual meeting of the Society for Pediatric Dermatology, Dr. Schachner noted that the differential diagnosis of noninfectious, usually benign neonatal vesiculopustular lesions includes acropustulosis of infancy; eosinophilic pustular folliculitis; erythema toxicum neonatorum; miliaria crystallina, rubra, or profunda; transient neonatal pustular melanosis; and neonatal sucking blisters. Noninfectious lesions that can be potentially serious include acrodermatitis enteropathica, bullous pemphigoid, epidermolysis bullosa, epidermolytic hyperkeratosis, incontinentia pigmenti, Langerhans cell histiocytosis, pemphigus vulgaris, pustular psoriasis, and urticarial pigmentosa.

Step 1 for evaluating vesiculopustular lesions involves drawing out the fluid for bacterial cultures and sensitivity, Gram stains, viral culture and/or serology, said Dr. Schachner, who directs the division of pediatric dermatology at the University of Miami.

Step 2 involves snipping off the lesion’s roof for a potassium hydroxide test to send for dermatopathology or frozen pathology.

Step 3 involves scraping the lesion’s base for viral cytology and cell identification. “If we can see a predominant cell type, that’s where the action is,” said Dr. Schachner, professor of pediatrics at the university. If cytology reveals polymorphic neutrophils, differential diagnoses include transient neonatal pustular melanosis, infantile acropustulosis, bullous impetigo, and pustular psoriasis. If cytology reveals eosinophils, differential diagnoses include eosinophilic pustular folliculitis of infancy, erythema toxicum neonatorum, incontinentia pigmenti, bullous pemphigoid, drug reactions, and arthropod bites. The presence of lymphocytes on cytology, meanwhile, may suggest a differential diagnosis miliaria or acrodermatitis enteropathica.

“When in doubt about the diagnosis, biopsy,” Dr. Schachner said. “This, to me, is a pragmatic approach.”

Dr. Schachner disclosed that he is an investigator for Astellas, Ferndale Labs, Novartis, Organogenesis, Stiefel Laboratories, Berg Pharma, Medimetrics, and Lilly. He is a consultant to Beiersdorf, Lexington, TopMD, Cutanea, Hoth Therapeutics, and Mustela.

dbrunk@mdedge.com

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Immunosuppression often triggers skin side effects

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Fri, 01/18/2019 - 17:52

Children experience a wide range of cutaneous manifestations of immunosuppression, including atopic dermatitis (AD), skin cancer, and side effects of vemurafenib treatment.

In a presentation on the cutaneous sequelae of different immunosuppressive regimens at the annual meeting of the Society for Pediatric Dermatology, Carrie C. Coughlin, MD, opened with a discussion of AD triggered by the tumor necrosis factor (TNF) blocker infliximab, especially in the setting of therapy for Crohn’s disease. “In this patient population you often think of psoriasis as a consequence of infliximab and other TNF therapies,” said Dr. Coughlin, a pediatric dermatologist at Washington University, St. Louis. “But you can also get true atopic dermatitis with infliximab as well. Who’s more at risk for this? Patients with Crohn’s disease seem to be. Most of the literature is in adults, but there are a few series of children. In a series of children looking at cutaneous sequelae of infliximab therapy, about 20% of cutaneous eruptions were atopic dermatitis. I think it’s a great opportunity for us in dermatology to do a more research in this area.”

Some researchers have proposed that atopic disease could be a marker of over-suppression of TNF-alpha in young Crohn’s disease patients on infliximab (Inflamm Bowel Dis. 2014; 20[8]:1309-15). “One question you could ask is, could these patients actually tolerate a dose reduction?” Dr. Coughlin said. She promoted the role of dermatologists in working at managing side effects to keep patients on medications helping their GI disease, but acknowledged this is not always possible.

Dr. Carrie C. Coughlin, a pediatric dermatologist at Washington University, St. Louis
Doug Brunk/MDedge News
Dr. Carrie C. Coughlin


Atopic disease can also occur after a solid organ transplant. In fact, the incidence of new-onset food allergies after a liver transplant is 6%-30% of cases, mainly in young patients (Pediatr Transplant. 2009;13[1]:63-9, Pediatr Transplant 2013;17[3]:251-5). “There are some mechanisms, including liver presentation of antigens, that spread through portal veins that could potentially put people at risk who have liver dysfunction,” Dr. Coughlin explained. “They could potentially have a higher risk for food allergies and AD. There is also some thought that tacrolimus potentially predisposes patients to having atopic dermatitis and atopy after their transplant. When you look at the mechanism of action of tacrolimus, you see increased levels of IL-5, IL-13, and skewing of IgE levels.”

Dr. Coughlin also discussed the possibilities of development of AD after transplant being a delayed presentation of an allergic sensitization that patients already had. Younger patients are at higher risk for AD post transplant. The renal transplant population, meanwhile, generally receives the transplant at a later age, “so they may not have that delay in terms of presentation; they may have already had their allergies and grown out of them by the time they’re getting their transplant,” she said. “I think there’s more for us to investigate.”

Solid organ transplant recipients also face an increased risk of skin cancer as a long-term side effect of immunosuppressive therapy. Risk factors include fair skin, sun exposure, and remote time from transplant. “Time from transplant is a risk factor,” Dr. Coughlin said. “Longer time on immunosuppression could predispose you to a risk for skin cancer. Our patients are living longer post transplant than they used to, so they have more potential years to develop their skin cancers.” She focused on the importance of educating transplant recipients and families early about photoprotection. “It’s interesting to think about how we can continue to intervene early on to continue to decrease risk.”

Young patients exposed to voriconazole also face an increased risk for skin cancer. “We know that longer-term dosing and higher cumulative dosing puts you at higher risk,” she said. Lung transplant recipients, who are often more likely to be treated with voriconazole, are thus at higher risk.

Dr. Coughlin ended her presentation by noting that side effects of the BRAF inhibitor vemurafenib (Zelboraf) used to treat advanced melanoma in children are similar to, but not the same as, those in adults. “We see BRAF mutations in multiple different tumor types: Langerhans cell histiocytosis, gliomas, and melanoma,” she said. “Trials of vemurafenib and dabrafenib are under way in the pediatric population. Vemurafenib can cause keratosis pilaris, panniculitis, alopecia, and granulomatous dermatitis.” In her experience, she has seen more alopecia in the older teenage population, but younger patients may not be asked about this side effect as frequently.

She counsels patients to expect keratosis pilaris–like eruptions and to take sun protection seriously. “It’s important to emphasize that each time they come in,” Dr. Coughlin said. She also discussed the potential for changing nevi and treatment options for vemurafenib-associated panniculitis.

Dr. Coughlin disclosed that she is the recipient of active pilot grants from the Pediatric Dermatology Research Alliance and the SPD.
 

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Children experience a wide range of cutaneous manifestations of immunosuppression, including atopic dermatitis (AD), skin cancer, and side effects of vemurafenib treatment.

In a presentation on the cutaneous sequelae of different immunosuppressive regimens at the annual meeting of the Society for Pediatric Dermatology, Carrie C. Coughlin, MD, opened with a discussion of AD triggered by the tumor necrosis factor (TNF) blocker infliximab, especially in the setting of therapy for Crohn’s disease. “In this patient population you often think of psoriasis as a consequence of infliximab and other TNF therapies,” said Dr. Coughlin, a pediatric dermatologist at Washington University, St. Louis. “But you can also get true atopic dermatitis with infliximab as well. Who’s more at risk for this? Patients with Crohn’s disease seem to be. Most of the literature is in adults, but there are a few series of children. In a series of children looking at cutaneous sequelae of infliximab therapy, about 20% of cutaneous eruptions were atopic dermatitis. I think it’s a great opportunity for us in dermatology to do a more research in this area.”

Some researchers have proposed that atopic disease could be a marker of over-suppression of TNF-alpha in young Crohn’s disease patients on infliximab (Inflamm Bowel Dis. 2014; 20[8]:1309-15). “One question you could ask is, could these patients actually tolerate a dose reduction?” Dr. Coughlin said. She promoted the role of dermatologists in working at managing side effects to keep patients on medications helping their GI disease, but acknowledged this is not always possible.

Dr. Carrie C. Coughlin, a pediatric dermatologist at Washington University, St. Louis
Doug Brunk/MDedge News
Dr. Carrie C. Coughlin


Atopic disease can also occur after a solid organ transplant. In fact, the incidence of new-onset food allergies after a liver transplant is 6%-30% of cases, mainly in young patients (Pediatr Transplant. 2009;13[1]:63-9, Pediatr Transplant 2013;17[3]:251-5). “There are some mechanisms, including liver presentation of antigens, that spread through portal veins that could potentially put people at risk who have liver dysfunction,” Dr. Coughlin explained. “They could potentially have a higher risk for food allergies and AD. There is also some thought that tacrolimus potentially predisposes patients to having atopic dermatitis and atopy after their transplant. When you look at the mechanism of action of tacrolimus, you see increased levels of IL-5, IL-13, and skewing of IgE levels.”

Dr. Coughlin also discussed the possibilities of development of AD after transplant being a delayed presentation of an allergic sensitization that patients already had. Younger patients are at higher risk for AD post transplant. The renal transplant population, meanwhile, generally receives the transplant at a later age, “so they may not have that delay in terms of presentation; they may have already had their allergies and grown out of them by the time they’re getting their transplant,” she said. “I think there’s more for us to investigate.”

Solid organ transplant recipients also face an increased risk of skin cancer as a long-term side effect of immunosuppressive therapy. Risk factors include fair skin, sun exposure, and remote time from transplant. “Time from transplant is a risk factor,” Dr. Coughlin said. “Longer time on immunosuppression could predispose you to a risk for skin cancer. Our patients are living longer post transplant than they used to, so they have more potential years to develop their skin cancers.” She focused on the importance of educating transplant recipients and families early about photoprotection. “It’s interesting to think about how we can continue to intervene early on to continue to decrease risk.”

Young patients exposed to voriconazole also face an increased risk for skin cancer. “We know that longer-term dosing and higher cumulative dosing puts you at higher risk,” she said. Lung transplant recipients, who are often more likely to be treated with voriconazole, are thus at higher risk.

Dr. Coughlin ended her presentation by noting that side effects of the BRAF inhibitor vemurafenib (Zelboraf) used to treat advanced melanoma in children are similar to, but not the same as, those in adults. “We see BRAF mutations in multiple different tumor types: Langerhans cell histiocytosis, gliomas, and melanoma,” she said. “Trials of vemurafenib and dabrafenib are under way in the pediatric population. Vemurafenib can cause keratosis pilaris, panniculitis, alopecia, and granulomatous dermatitis.” In her experience, she has seen more alopecia in the older teenage population, but younger patients may not be asked about this side effect as frequently.

She counsels patients to expect keratosis pilaris–like eruptions and to take sun protection seriously. “It’s important to emphasize that each time they come in,” Dr. Coughlin said. She also discussed the potential for changing nevi and treatment options for vemurafenib-associated panniculitis.

Dr. Coughlin disclosed that she is the recipient of active pilot grants from the Pediatric Dermatology Research Alliance and the SPD.
 

dbrunk@mdedge.com

Children experience a wide range of cutaneous manifestations of immunosuppression, including atopic dermatitis (AD), skin cancer, and side effects of vemurafenib treatment.

In a presentation on the cutaneous sequelae of different immunosuppressive regimens at the annual meeting of the Society for Pediatric Dermatology, Carrie C. Coughlin, MD, opened with a discussion of AD triggered by the tumor necrosis factor (TNF) blocker infliximab, especially in the setting of therapy for Crohn’s disease. “In this patient population you often think of psoriasis as a consequence of infliximab and other TNF therapies,” said Dr. Coughlin, a pediatric dermatologist at Washington University, St. Louis. “But you can also get true atopic dermatitis with infliximab as well. Who’s more at risk for this? Patients with Crohn’s disease seem to be. Most of the literature is in adults, but there are a few series of children. In a series of children looking at cutaneous sequelae of infliximab therapy, about 20% of cutaneous eruptions were atopic dermatitis. I think it’s a great opportunity for us in dermatology to do a more research in this area.”

Some researchers have proposed that atopic disease could be a marker of over-suppression of TNF-alpha in young Crohn’s disease patients on infliximab (Inflamm Bowel Dis. 2014; 20[8]:1309-15). “One question you could ask is, could these patients actually tolerate a dose reduction?” Dr. Coughlin said. She promoted the role of dermatologists in working at managing side effects to keep patients on medications helping their GI disease, but acknowledged this is not always possible.

Dr. Carrie C. Coughlin, a pediatric dermatologist at Washington University, St. Louis
Doug Brunk/MDedge News
Dr. Carrie C. Coughlin


Atopic disease can also occur after a solid organ transplant. In fact, the incidence of new-onset food allergies after a liver transplant is 6%-30% of cases, mainly in young patients (Pediatr Transplant. 2009;13[1]:63-9, Pediatr Transplant 2013;17[3]:251-5). “There are some mechanisms, including liver presentation of antigens, that spread through portal veins that could potentially put people at risk who have liver dysfunction,” Dr. Coughlin explained. “They could potentially have a higher risk for food allergies and AD. There is also some thought that tacrolimus potentially predisposes patients to having atopic dermatitis and atopy after their transplant. When you look at the mechanism of action of tacrolimus, you see increased levels of IL-5, IL-13, and skewing of IgE levels.”

Dr. Coughlin also discussed the possibilities of development of AD after transplant being a delayed presentation of an allergic sensitization that patients already had. Younger patients are at higher risk for AD post transplant. The renal transplant population, meanwhile, generally receives the transplant at a later age, “so they may not have that delay in terms of presentation; they may have already had their allergies and grown out of them by the time they’re getting their transplant,” she said. “I think there’s more for us to investigate.”

Solid organ transplant recipients also face an increased risk of skin cancer as a long-term side effect of immunosuppressive therapy. Risk factors include fair skin, sun exposure, and remote time from transplant. “Time from transplant is a risk factor,” Dr. Coughlin said. “Longer time on immunosuppression could predispose you to a risk for skin cancer. Our patients are living longer post transplant than they used to, so they have more potential years to develop their skin cancers.” She focused on the importance of educating transplant recipients and families early about photoprotection. “It’s interesting to think about how we can continue to intervene early on to continue to decrease risk.”

Young patients exposed to voriconazole also face an increased risk for skin cancer. “We know that longer-term dosing and higher cumulative dosing puts you at higher risk,” she said. Lung transplant recipients, who are often more likely to be treated with voriconazole, are thus at higher risk.

Dr. Coughlin ended her presentation by noting that side effects of the BRAF inhibitor vemurafenib (Zelboraf) used to treat advanced melanoma in children are similar to, but not the same as, those in adults. “We see BRAF mutations in multiple different tumor types: Langerhans cell histiocytosis, gliomas, and melanoma,” she said. “Trials of vemurafenib and dabrafenib are under way in the pediatric population. Vemurafenib can cause keratosis pilaris, panniculitis, alopecia, and granulomatous dermatitis.” In her experience, she has seen more alopecia in the older teenage population, but younger patients may not be asked about this side effect as frequently.

She counsels patients to expect keratosis pilaris–like eruptions and to take sun protection seriously. “It’s important to emphasize that each time they come in,” Dr. Coughlin said. She also discussed the potential for changing nevi and treatment options for vemurafenib-associated panniculitis.

Dr. Coughlin disclosed that she is the recipient of active pilot grants from the Pediatric Dermatology Research Alliance and the SPD.
 

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Study offers snapshot of esophageal strictures in EB patients

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Mon, 01/14/2019 - 10:28

 

Esophageal strictures are common complications of epidermolysis bullosa, and direct visualization of these strictures is the preferred method of diagnosis. Those are key findings from a multicenter study that lead author Elena Pope, MD, discussed at the annual meeting of the Society for Pediatric Dermatology.

Dr. Elena Pope, head of the section of dermatology at the Hospital for Sick Children, Toronto
Doug Brunk/MDedge News
Dr. Elena Pope

According to Dr. Pope, who heads the section of dermatology at the Hospital for Sick Children, Toronto, an estimated 10%-17% of epidermolysis bullosa (EB) patients experience strictures, with an overrepresentation in the recessive dystrophic EB subtype in up to 80% of cases. The risk increases with age. “What remains unknown is the best short- and long-term intervention to manage the strictures and predictors/associations for stricture-free episodes,” Dr. Pope said. “The objectives of the current study were to determine the prevalence and predisposing factors for strictures in EB, management options, patient outcomes, and predictors for recurrences and stricture-free intervals.”

She and her associates at seven centers worldwide collected data on 125 EB patients who experienced at least one episode of esophageal stricture. Data was analyzed descriptively and with ANOVA regression analysis for associations/predictors for recurrences/episode-free intervals.

The researchers evaluated 497 stricture events in the 125 patients. A slight female predominance was noted (53%), and the mean age of the first episode was 12.7 years, “which is a little bit older” than the age found in previously published data, Dr. Pope said. As expected, dystrophic EB patients made up most of the sample (98.4%); of these 123 patients, recessive dystrophic EB severe generalized subtype – approaching 50% – was the most common, followed by the recessive dystrophic EB severe intermediate subtype (almost 21%), the dominant dystrophic EB generalized subtype (7%), and other types of dystrophic EB (almost 26%).



The median body mass index percentile for age was 6.3, “so these were patients who were severely malnourished, probably as a result of their strictures as well as their underlying disease,” Dr. Pope said.

As expected, dysphagia was a presenting symptom in most patients (85.5%), while 29.8% presented with inability to swallow solids. The preferred method of evaluation was video fluoroscopy (57.7%), and less commonly with barium swallow (22.3%) or with clinical symptoms alone (0.1%). The mean number of strictures was 1.69; 76.7% were located in the cervical area, 56.7% were located in the thoracic area, and 9.7% were located in the abdominal area. Most patients (76%) had lesions that were 1 cm or longer in size.

Fluoroscopy guidance was the most common method of dilatation (in 45.2% of cases), followed by retrograde endoscopy was (33%), antegrade endoscopy (19.1%), and bougienage (0.1%). General anesthesia was used in most cases (87.6%), and corticosteroids were used around the dilatation in 90.4% of patients. The mean duration of medication use was about 5 days.

As for outcomes after dilatation, 92.2% of strictures completely resolved, 3.8% were partially resolved, 3.9% were not resolved, and 2.7% had complications. The median interval between dilatations was 7 months. Fluoroscopy-guided balloon dilatation was associated with the longest esophageal stricture-free duration (mean of 13.83 months vs. 8.75 months; P less than .001), followed by retrograde endoscopy (mean of 13.10 months vs. 7.85 months; P less than .001), and antegrade endoscopy (mean of 7.63 months vs. 11.46 months; P = .024). “I think this is interesting,” said Dr. Pope, who is also a professor of pediatrics at the University of Toronto. “I think the difference occurs because if you use the endoscopy, which a rigid tube, you can potentially cause more damage, and more long-term scarring.”

 

 

Another predictor of esophageal stricture-free episodes was systemic corticosteroid use (a mean of 25.28 months vs. 10.24 months; P less than .001) around the time of the dilatation procedure. “By using systemic steroids, you’re actually decreasing some of the inflammation associated with the trauma of the procedure decreasing the chances of strictures formation,” she said.

Dr. Pope recommended that future studies evaluate the benefit of periprocedural medical interventions on increasing the intervals between esophageal stricture occurrences.

The study was supported by an unrestricted grant from the Epidermolysis Bullosa Research Foundation. She reported having no financial disclosures.
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Esophageal strictures are common complications of epidermolysis bullosa, and direct visualization of these strictures is the preferred method of diagnosis. Those are key findings from a multicenter study that lead author Elena Pope, MD, discussed at the annual meeting of the Society for Pediatric Dermatology.

Dr. Elena Pope, head of the section of dermatology at the Hospital for Sick Children, Toronto
Doug Brunk/MDedge News
Dr. Elena Pope

According to Dr. Pope, who heads the section of dermatology at the Hospital for Sick Children, Toronto, an estimated 10%-17% of epidermolysis bullosa (EB) patients experience strictures, with an overrepresentation in the recessive dystrophic EB subtype in up to 80% of cases. The risk increases with age. “What remains unknown is the best short- and long-term intervention to manage the strictures and predictors/associations for stricture-free episodes,” Dr. Pope said. “The objectives of the current study were to determine the prevalence and predisposing factors for strictures in EB, management options, patient outcomes, and predictors for recurrences and stricture-free intervals.”

She and her associates at seven centers worldwide collected data on 125 EB patients who experienced at least one episode of esophageal stricture. Data was analyzed descriptively and with ANOVA regression analysis for associations/predictors for recurrences/episode-free intervals.

The researchers evaluated 497 stricture events in the 125 patients. A slight female predominance was noted (53%), and the mean age of the first episode was 12.7 years, “which is a little bit older” than the age found in previously published data, Dr. Pope said. As expected, dystrophic EB patients made up most of the sample (98.4%); of these 123 patients, recessive dystrophic EB severe generalized subtype – approaching 50% – was the most common, followed by the recessive dystrophic EB severe intermediate subtype (almost 21%), the dominant dystrophic EB generalized subtype (7%), and other types of dystrophic EB (almost 26%).



The median body mass index percentile for age was 6.3, “so these were patients who were severely malnourished, probably as a result of their strictures as well as their underlying disease,” Dr. Pope said.

As expected, dysphagia was a presenting symptom in most patients (85.5%), while 29.8% presented with inability to swallow solids. The preferred method of evaluation was video fluoroscopy (57.7%), and less commonly with barium swallow (22.3%) or with clinical symptoms alone (0.1%). The mean number of strictures was 1.69; 76.7% were located in the cervical area, 56.7% were located in the thoracic area, and 9.7% were located in the abdominal area. Most patients (76%) had lesions that were 1 cm or longer in size.

Fluoroscopy guidance was the most common method of dilatation (in 45.2% of cases), followed by retrograde endoscopy was (33%), antegrade endoscopy (19.1%), and bougienage (0.1%). General anesthesia was used in most cases (87.6%), and corticosteroids were used around the dilatation in 90.4% of patients. The mean duration of medication use was about 5 days.

As for outcomes after dilatation, 92.2% of strictures completely resolved, 3.8% were partially resolved, 3.9% were not resolved, and 2.7% had complications. The median interval between dilatations was 7 months. Fluoroscopy-guided balloon dilatation was associated with the longest esophageal stricture-free duration (mean of 13.83 months vs. 8.75 months; P less than .001), followed by retrograde endoscopy (mean of 13.10 months vs. 7.85 months; P less than .001), and antegrade endoscopy (mean of 7.63 months vs. 11.46 months; P = .024). “I think this is interesting,” said Dr. Pope, who is also a professor of pediatrics at the University of Toronto. “I think the difference occurs because if you use the endoscopy, which a rigid tube, you can potentially cause more damage, and more long-term scarring.”

 

 

Another predictor of esophageal stricture-free episodes was systemic corticosteroid use (a mean of 25.28 months vs. 10.24 months; P less than .001) around the time of the dilatation procedure. “By using systemic steroids, you’re actually decreasing some of the inflammation associated with the trauma of the procedure decreasing the chances of strictures formation,” she said.

Dr. Pope recommended that future studies evaluate the benefit of periprocedural medical interventions on increasing the intervals between esophageal stricture occurrences.

The study was supported by an unrestricted grant from the Epidermolysis Bullosa Research Foundation. She reported having no financial disclosures.

 

Esophageal strictures are common complications of epidermolysis bullosa, and direct visualization of these strictures is the preferred method of diagnosis. Those are key findings from a multicenter study that lead author Elena Pope, MD, discussed at the annual meeting of the Society for Pediatric Dermatology.

Dr. Elena Pope, head of the section of dermatology at the Hospital for Sick Children, Toronto
Doug Brunk/MDedge News
Dr. Elena Pope

According to Dr. Pope, who heads the section of dermatology at the Hospital for Sick Children, Toronto, an estimated 10%-17% of epidermolysis bullosa (EB) patients experience strictures, with an overrepresentation in the recessive dystrophic EB subtype in up to 80% of cases. The risk increases with age. “What remains unknown is the best short- and long-term intervention to manage the strictures and predictors/associations for stricture-free episodes,” Dr. Pope said. “The objectives of the current study were to determine the prevalence and predisposing factors for strictures in EB, management options, patient outcomes, and predictors for recurrences and stricture-free intervals.”

She and her associates at seven centers worldwide collected data on 125 EB patients who experienced at least one episode of esophageal stricture. Data was analyzed descriptively and with ANOVA regression analysis for associations/predictors for recurrences/episode-free intervals.

The researchers evaluated 497 stricture events in the 125 patients. A slight female predominance was noted (53%), and the mean age of the first episode was 12.7 years, “which is a little bit older” than the age found in previously published data, Dr. Pope said. As expected, dystrophic EB patients made up most of the sample (98.4%); of these 123 patients, recessive dystrophic EB severe generalized subtype – approaching 50% – was the most common, followed by the recessive dystrophic EB severe intermediate subtype (almost 21%), the dominant dystrophic EB generalized subtype (7%), and other types of dystrophic EB (almost 26%).



The median body mass index percentile for age was 6.3, “so these were patients who were severely malnourished, probably as a result of their strictures as well as their underlying disease,” Dr. Pope said.

As expected, dysphagia was a presenting symptom in most patients (85.5%), while 29.8% presented with inability to swallow solids. The preferred method of evaluation was video fluoroscopy (57.7%), and less commonly with barium swallow (22.3%) or with clinical symptoms alone (0.1%). The mean number of strictures was 1.69; 76.7% were located in the cervical area, 56.7% were located in the thoracic area, and 9.7% were located in the abdominal area. Most patients (76%) had lesions that were 1 cm or longer in size.

Fluoroscopy guidance was the most common method of dilatation (in 45.2% of cases), followed by retrograde endoscopy was (33%), antegrade endoscopy (19.1%), and bougienage (0.1%). General anesthesia was used in most cases (87.6%), and corticosteroids were used around the dilatation in 90.4% of patients. The mean duration of medication use was about 5 days.

As for outcomes after dilatation, 92.2% of strictures completely resolved, 3.8% were partially resolved, 3.9% were not resolved, and 2.7% had complications. The median interval between dilatations was 7 months. Fluoroscopy-guided balloon dilatation was associated with the longest esophageal stricture-free duration (mean of 13.83 months vs. 8.75 months; P less than .001), followed by retrograde endoscopy (mean of 13.10 months vs. 7.85 months; P less than .001), and antegrade endoscopy (mean of 7.63 months vs. 11.46 months; P = .024). “I think this is interesting,” said Dr. Pope, who is also a professor of pediatrics at the University of Toronto. “I think the difference occurs because if you use the endoscopy, which a rigid tube, you can potentially cause more damage, and more long-term scarring.”

 

 

Another predictor of esophageal stricture-free episodes was systemic corticosteroid use (a mean of 25.28 months vs. 10.24 months; P less than .001) around the time of the dilatation procedure. “By using systemic steroids, you’re actually decreasing some of the inflammation associated with the trauma of the procedure decreasing the chances of strictures formation,” she said.

Dr. Pope recommended that future studies evaluate the benefit of periprocedural medical interventions on increasing the intervals between esophageal stricture occurrences.

The study was supported by an unrestricted grant from the Epidermolysis Bullosa Research Foundation. She reported having no financial disclosures.
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Key clinical point: Esophageal strictures are common complications of patients with severe types of epidermolysis bullosa.

Major finding: Most epidermolysis bullosa patients (85.5%) presented with dysphagia, while the preferred method of evaluation was video fluoroscopy (57.7%).

Study details: A multicenter study of 497 stricture events in 125 patients with epidermolysis bullosa.

Disclosures: The study was supported by an unrestricted grant from the Epidermolysis Bullosa Research Foundation. Dr. Pope reported having no financial disclosures.

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Foster cultural competence when examining hair, scalp of ethnic patients

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Fri, 01/18/2019 - 17:51

 

– The way Susan C. Taylor, MD, sees it, rule No. 1 when examining the hair and scalp of young ethnic patients is to foster a sense of cultural competence.

At the annual meeting of the Society for Pediatric Dermatology, Dr. Taylor, a dermatologist at the University of Pennsylvania, Philadelphia, defined culturally competent care as a patient-centered approach in which clinicians establish a rapport with the patient and the caregiver. “It’s important that we ask the right questions,” she said. “In doing so, we have to be familiar with common hair care practices. It’s important that we respect our patients’ values, their goals, their health needs, and, of course, their cultural background. Finally, we have to engage in shared decision making. That’s where we can improve compliance and lead to an overall very satisfactory patient visit.”

Susan C. Taylor, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia
Dr. Susan C. Taylor

To illustrate this point, she discussed the case of a four-year-old black female with a 9-month history of bad dandruff. The child’s mother reports thick flakes that never go away. She takes pride in caring for her daughter’s hair, and shampoos it every two weeks. “She tells me that during the 2.5 hours that it takes her on Saturdays to shampoo, detangle, and comb her daughter’s hair, which she then braids or cornrows and adorns with barrettes or balls, it is a great bonding experience for the two of them,” Dr. Taylor said. “The flakes are temporarily better after she ‘greases’ her daughter’s scalp, but after 2-3 days, they are back.”

In a case like this, Dr. Taylor recommends asking the parent or caregiver to join you while you examine the scalp. This way, the focus becomes the child’s scalp, and the parent is not just staring at your expressions. “The child also observes the pediatric dermatologist and parent/caregiver working together as a team,” she said. “You also want to ask the parent to remove the hair adornments. This makes the child feel more comfortable. It also allows you to observe how the hair is being managed. Are the adornments being removed gently? Is there aggressive pulling of the hair when they take out the braids? Is the child visibly wincing in pain? If the latter two happen this is a teachable moment. You can point out, ‘It looks like Susie is in pain. Let’s do it a little more gently. That might prevent further hair breakage.’ ”

The differential diagnosis of a scaly pediatric scalp includes infrequent shampooing, seborrheic dermatitis, tinea capitis, atopic dermatitis, psoriasis, and sebopsoriasis. The type of hairstyle also factors in. For example, cornrows are a popular hair styling option among ethnic patients. “These are very popular and very time consuming and may lead to infrequent shampooing,” she said. “If they’re put in very tightly or if they have beads or other adornments, it can lead to traction alopecia.” Twists, meanwhile, can create tension on the hair, while puffs can cause traction alopecia if they’re pulled too tightly. “Although dreadlocks are more common among adolescents, we’re seeing them more commonly in young children,” she said. “They can be very long and wavy and lead to traction alopecia.”

The time required to shampoo, detangle, and style tightly coiled African American hair can be significant. For example, in children with cornrows or braids with extensions, Dr. Taylor said that it might require 30 minutes to as long as 2 or 3 hours to remove their current hairstyle, followed by shampooing and conditioning. “Detangling can take at least 15 minutes. In tightly coiled African American hair, studies have demonstrated that detangling while the hair is wet is best, because you have fewer forces on that comb and the hair is less likely to break, as opposed to detangling when the hair is dry. After the wet hair is detangled and the conditioner is rinsed out, a leave-in conditioner is often applied. Then the hair is detangled again, which can take up to an hour, followed by styling, which can take 1-3 hours. That gives you some insight as to why there can often be infrequent shampooing.”


The recommended frequency of shampooing depends on the hairstyle selected. Many children with braids and extensions will have those braids and extensions taken out every six to 12 weeks, “but that doesn’t mean that the scalp can’t be shampooed,” Dr. Taylor said. “The scalp should be shampooed more often. Economics and socioeconomic status play into the frequency of shampooing. For example, if a parent or a caregiver sends a child to a hair stylist, that can range in price from $45 to $65 or more. Time also factors in. In the black community in particular, it’s a ritual on a Saturday to get your hair done. If the parent or caregiver works on weekends, that’s going to impact the frequency of shampooing.”

Dr. Taylor underscored the importance of framing the history-taking process to avoid common pitfall questions like “Do you wash the child’s hair every day or every other day?” or “Do you use dandruff shampoo every day?” It is important to remember that “the parent’s inherent perception is of a doctor who does not have my hair probably does not understand my hair or my child’s hair,” she said. “It’s unlikely that you’re going to find a parent who shampoos their child’s hair every day or every other day. Maybe once a week, probably biweekly. It’s important to ask culturally competent questions.”

She also advises against asking about shampooing when you’re examining the child’s hair, “because there’s going to be the perception that you may think the scalp is dirty,” Dr. Taylor explained. “You probably want to ask that when gathering the history of present illness. The culturally competent question is going to be, ‘Do you wash her/his hair weekly, every other week, monthly, or does it depend on the hair style?’ ”

Body language is also important. “Don’t lean in from afar when examining the patient,” she said. “Get up close and touch the child’s hair.” If you choose to wear surgical gloves for the exam “don’t hold your hands in the surgical scrub position,” she recommended. “Hold your hands in a more neutral position. I think it’s important to touch the hair.”

Referring back to the 4-year-old black child with bad dandruff, she said that a diagnosis of seborrheic dermatitis is unlikely since that condition usually occurs during puberty. “You should have a high index of suspicion for tinea capitis,” she said. “If the patient has occipital lymphadenopathy plus scaling of the scalp or alopecia, that’s enough to presumptively treat for tinea capitis. There are studies that support that.”

For established tinea capitis, Dr. Taylor advises parents to wash barrettes and other hair adornments in hot soapy water or in the dishwasher. She also recommends disposal of hair oil, pomade, and grease and shampooing the child’s hair with ketoconazole and use a conditioner to decrease household and patient spread, which decreases transmissible fungal spores. “There’s a misperception that the application of hair oils and grease can increase the rate of tinea capitis,” she noted. “That’s not true. However, if hair grease and hair oil is applied to the scalp within one week of culture, it could produce a false negative culture.”

For established seborrheic dermatitis, antifungal shampoos including ketoconazole, ciclopirox, and selenium sulfide may be too drying for ethnic hair, “which already has a propensity to break,” she said. “Instead, we recommend a 5-10 minute scalp contact time with the shampoo and avoid contact with strands of hair. Shampoo hair strands with a conditioning shampoo followed by a conditioner to limit hair breakage. We suggest once weekly or biweekly shampooing.”

Dr. Taylor disclosed that she has advisory board and/or investigator relationships with Aclaris Therapeutics, Allergan, Beiersdorf, Croma Pharmaceuticals, Galderma, Isdin, Johnson & Johnson, and Unilever. She also acknowledged Candrice R. Heath, MD, a dermatologist based in Newark, Delaware, for her assistance with the presentation content.

dbrunk@mdedge.com







 

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– The way Susan C. Taylor, MD, sees it, rule No. 1 when examining the hair and scalp of young ethnic patients is to foster a sense of cultural competence.

At the annual meeting of the Society for Pediatric Dermatology, Dr. Taylor, a dermatologist at the University of Pennsylvania, Philadelphia, defined culturally competent care as a patient-centered approach in which clinicians establish a rapport with the patient and the caregiver. “It’s important that we ask the right questions,” she said. “In doing so, we have to be familiar with common hair care practices. It’s important that we respect our patients’ values, their goals, their health needs, and, of course, their cultural background. Finally, we have to engage in shared decision making. That’s where we can improve compliance and lead to an overall very satisfactory patient visit.”

Susan C. Taylor, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia
Dr. Susan C. Taylor

To illustrate this point, she discussed the case of a four-year-old black female with a 9-month history of bad dandruff. The child’s mother reports thick flakes that never go away. She takes pride in caring for her daughter’s hair, and shampoos it every two weeks. “She tells me that during the 2.5 hours that it takes her on Saturdays to shampoo, detangle, and comb her daughter’s hair, which she then braids or cornrows and adorns with barrettes or balls, it is a great bonding experience for the two of them,” Dr. Taylor said. “The flakes are temporarily better after she ‘greases’ her daughter’s scalp, but after 2-3 days, they are back.”

In a case like this, Dr. Taylor recommends asking the parent or caregiver to join you while you examine the scalp. This way, the focus becomes the child’s scalp, and the parent is not just staring at your expressions. “The child also observes the pediatric dermatologist and parent/caregiver working together as a team,” she said. “You also want to ask the parent to remove the hair adornments. This makes the child feel more comfortable. It also allows you to observe how the hair is being managed. Are the adornments being removed gently? Is there aggressive pulling of the hair when they take out the braids? Is the child visibly wincing in pain? If the latter two happen this is a teachable moment. You can point out, ‘It looks like Susie is in pain. Let’s do it a little more gently. That might prevent further hair breakage.’ ”

The differential diagnosis of a scaly pediatric scalp includes infrequent shampooing, seborrheic dermatitis, tinea capitis, atopic dermatitis, psoriasis, and sebopsoriasis. The type of hairstyle also factors in. For example, cornrows are a popular hair styling option among ethnic patients. “These are very popular and very time consuming and may lead to infrequent shampooing,” she said. “If they’re put in very tightly or if they have beads or other adornments, it can lead to traction alopecia.” Twists, meanwhile, can create tension on the hair, while puffs can cause traction alopecia if they’re pulled too tightly. “Although dreadlocks are more common among adolescents, we’re seeing them more commonly in young children,” she said. “They can be very long and wavy and lead to traction alopecia.”

The time required to shampoo, detangle, and style tightly coiled African American hair can be significant. For example, in children with cornrows or braids with extensions, Dr. Taylor said that it might require 30 minutes to as long as 2 or 3 hours to remove their current hairstyle, followed by shampooing and conditioning. “Detangling can take at least 15 minutes. In tightly coiled African American hair, studies have demonstrated that detangling while the hair is wet is best, because you have fewer forces on that comb and the hair is less likely to break, as opposed to detangling when the hair is dry. After the wet hair is detangled and the conditioner is rinsed out, a leave-in conditioner is often applied. Then the hair is detangled again, which can take up to an hour, followed by styling, which can take 1-3 hours. That gives you some insight as to why there can often be infrequent shampooing.”


The recommended frequency of shampooing depends on the hairstyle selected. Many children with braids and extensions will have those braids and extensions taken out every six to 12 weeks, “but that doesn’t mean that the scalp can’t be shampooed,” Dr. Taylor said. “The scalp should be shampooed more often. Economics and socioeconomic status play into the frequency of shampooing. For example, if a parent or a caregiver sends a child to a hair stylist, that can range in price from $45 to $65 or more. Time also factors in. In the black community in particular, it’s a ritual on a Saturday to get your hair done. If the parent or caregiver works on weekends, that’s going to impact the frequency of shampooing.”

Dr. Taylor underscored the importance of framing the history-taking process to avoid common pitfall questions like “Do you wash the child’s hair every day or every other day?” or “Do you use dandruff shampoo every day?” It is important to remember that “the parent’s inherent perception is of a doctor who does not have my hair probably does not understand my hair or my child’s hair,” she said. “It’s unlikely that you’re going to find a parent who shampoos their child’s hair every day or every other day. Maybe once a week, probably biweekly. It’s important to ask culturally competent questions.”

She also advises against asking about shampooing when you’re examining the child’s hair, “because there’s going to be the perception that you may think the scalp is dirty,” Dr. Taylor explained. “You probably want to ask that when gathering the history of present illness. The culturally competent question is going to be, ‘Do you wash her/his hair weekly, every other week, monthly, or does it depend on the hair style?’ ”

Body language is also important. “Don’t lean in from afar when examining the patient,” she said. “Get up close and touch the child’s hair.” If you choose to wear surgical gloves for the exam “don’t hold your hands in the surgical scrub position,” she recommended. “Hold your hands in a more neutral position. I think it’s important to touch the hair.”

Referring back to the 4-year-old black child with bad dandruff, she said that a diagnosis of seborrheic dermatitis is unlikely since that condition usually occurs during puberty. “You should have a high index of suspicion for tinea capitis,” she said. “If the patient has occipital lymphadenopathy plus scaling of the scalp or alopecia, that’s enough to presumptively treat for tinea capitis. There are studies that support that.”

For established tinea capitis, Dr. Taylor advises parents to wash barrettes and other hair adornments in hot soapy water or in the dishwasher. She also recommends disposal of hair oil, pomade, and grease and shampooing the child’s hair with ketoconazole and use a conditioner to decrease household and patient spread, which decreases transmissible fungal spores. “There’s a misperception that the application of hair oils and grease can increase the rate of tinea capitis,” she noted. “That’s not true. However, if hair grease and hair oil is applied to the scalp within one week of culture, it could produce a false negative culture.”

For established seborrheic dermatitis, antifungal shampoos including ketoconazole, ciclopirox, and selenium sulfide may be too drying for ethnic hair, “which already has a propensity to break,” she said. “Instead, we recommend a 5-10 minute scalp contact time with the shampoo and avoid contact with strands of hair. Shampoo hair strands with a conditioning shampoo followed by a conditioner to limit hair breakage. We suggest once weekly or biweekly shampooing.”

Dr. Taylor disclosed that she has advisory board and/or investigator relationships with Aclaris Therapeutics, Allergan, Beiersdorf, Croma Pharmaceuticals, Galderma, Isdin, Johnson & Johnson, and Unilever. She also acknowledged Candrice R. Heath, MD, a dermatologist based in Newark, Delaware, for her assistance with the presentation content.

dbrunk@mdedge.com







 

 

– The way Susan C. Taylor, MD, sees it, rule No. 1 when examining the hair and scalp of young ethnic patients is to foster a sense of cultural competence.

At the annual meeting of the Society for Pediatric Dermatology, Dr. Taylor, a dermatologist at the University of Pennsylvania, Philadelphia, defined culturally competent care as a patient-centered approach in which clinicians establish a rapport with the patient and the caregiver. “It’s important that we ask the right questions,” she said. “In doing so, we have to be familiar with common hair care practices. It’s important that we respect our patients’ values, their goals, their health needs, and, of course, their cultural background. Finally, we have to engage in shared decision making. That’s where we can improve compliance and lead to an overall very satisfactory patient visit.”

Susan C. Taylor, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia
Dr. Susan C. Taylor

To illustrate this point, she discussed the case of a four-year-old black female with a 9-month history of bad dandruff. The child’s mother reports thick flakes that never go away. She takes pride in caring for her daughter’s hair, and shampoos it every two weeks. “She tells me that during the 2.5 hours that it takes her on Saturdays to shampoo, detangle, and comb her daughter’s hair, which she then braids or cornrows and adorns with barrettes or balls, it is a great bonding experience for the two of them,” Dr. Taylor said. “The flakes are temporarily better after she ‘greases’ her daughter’s scalp, but after 2-3 days, they are back.”

In a case like this, Dr. Taylor recommends asking the parent or caregiver to join you while you examine the scalp. This way, the focus becomes the child’s scalp, and the parent is not just staring at your expressions. “The child also observes the pediatric dermatologist and parent/caregiver working together as a team,” she said. “You also want to ask the parent to remove the hair adornments. This makes the child feel more comfortable. It also allows you to observe how the hair is being managed. Are the adornments being removed gently? Is there aggressive pulling of the hair when they take out the braids? Is the child visibly wincing in pain? If the latter two happen this is a teachable moment. You can point out, ‘It looks like Susie is in pain. Let’s do it a little more gently. That might prevent further hair breakage.’ ”

The differential diagnosis of a scaly pediatric scalp includes infrequent shampooing, seborrheic dermatitis, tinea capitis, atopic dermatitis, psoriasis, and sebopsoriasis. The type of hairstyle also factors in. For example, cornrows are a popular hair styling option among ethnic patients. “These are very popular and very time consuming and may lead to infrequent shampooing,” she said. “If they’re put in very tightly or if they have beads or other adornments, it can lead to traction alopecia.” Twists, meanwhile, can create tension on the hair, while puffs can cause traction alopecia if they’re pulled too tightly. “Although dreadlocks are more common among adolescents, we’re seeing them more commonly in young children,” she said. “They can be very long and wavy and lead to traction alopecia.”

The time required to shampoo, detangle, and style tightly coiled African American hair can be significant. For example, in children with cornrows or braids with extensions, Dr. Taylor said that it might require 30 minutes to as long as 2 or 3 hours to remove their current hairstyle, followed by shampooing and conditioning. “Detangling can take at least 15 minutes. In tightly coiled African American hair, studies have demonstrated that detangling while the hair is wet is best, because you have fewer forces on that comb and the hair is less likely to break, as opposed to detangling when the hair is dry. After the wet hair is detangled and the conditioner is rinsed out, a leave-in conditioner is often applied. Then the hair is detangled again, which can take up to an hour, followed by styling, which can take 1-3 hours. That gives you some insight as to why there can often be infrequent shampooing.”


The recommended frequency of shampooing depends on the hairstyle selected. Many children with braids and extensions will have those braids and extensions taken out every six to 12 weeks, “but that doesn’t mean that the scalp can’t be shampooed,” Dr. Taylor said. “The scalp should be shampooed more often. Economics and socioeconomic status play into the frequency of shampooing. For example, if a parent or a caregiver sends a child to a hair stylist, that can range in price from $45 to $65 or more. Time also factors in. In the black community in particular, it’s a ritual on a Saturday to get your hair done. If the parent or caregiver works on weekends, that’s going to impact the frequency of shampooing.”

Dr. Taylor underscored the importance of framing the history-taking process to avoid common pitfall questions like “Do you wash the child’s hair every day or every other day?” or “Do you use dandruff shampoo every day?” It is important to remember that “the parent’s inherent perception is of a doctor who does not have my hair probably does not understand my hair or my child’s hair,” she said. “It’s unlikely that you’re going to find a parent who shampoos their child’s hair every day or every other day. Maybe once a week, probably biweekly. It’s important to ask culturally competent questions.”

She also advises against asking about shampooing when you’re examining the child’s hair, “because there’s going to be the perception that you may think the scalp is dirty,” Dr. Taylor explained. “You probably want to ask that when gathering the history of present illness. The culturally competent question is going to be, ‘Do you wash her/his hair weekly, every other week, monthly, or does it depend on the hair style?’ ”

Body language is also important. “Don’t lean in from afar when examining the patient,” she said. “Get up close and touch the child’s hair.” If you choose to wear surgical gloves for the exam “don’t hold your hands in the surgical scrub position,” she recommended. “Hold your hands in a more neutral position. I think it’s important to touch the hair.”

Referring back to the 4-year-old black child with bad dandruff, she said that a diagnosis of seborrheic dermatitis is unlikely since that condition usually occurs during puberty. “You should have a high index of suspicion for tinea capitis,” she said. “If the patient has occipital lymphadenopathy plus scaling of the scalp or alopecia, that’s enough to presumptively treat for tinea capitis. There are studies that support that.”

For established tinea capitis, Dr. Taylor advises parents to wash barrettes and other hair adornments in hot soapy water or in the dishwasher. She also recommends disposal of hair oil, pomade, and grease and shampooing the child’s hair with ketoconazole and use a conditioner to decrease household and patient spread, which decreases transmissible fungal spores. “There’s a misperception that the application of hair oils and grease can increase the rate of tinea capitis,” she noted. “That’s not true. However, if hair grease and hair oil is applied to the scalp within one week of culture, it could produce a false negative culture.”

For established seborrheic dermatitis, antifungal shampoos including ketoconazole, ciclopirox, and selenium sulfide may be too drying for ethnic hair, “which already has a propensity to break,” she said. “Instead, we recommend a 5-10 minute scalp contact time with the shampoo and avoid contact with strands of hair. Shampoo hair strands with a conditioning shampoo followed by a conditioner to limit hair breakage. We suggest once weekly or biweekly shampooing.”

Dr. Taylor disclosed that she has advisory board and/or investigator relationships with Aclaris Therapeutics, Allergan, Beiersdorf, Croma Pharmaceuticals, Galderma, Isdin, Johnson & Johnson, and Unilever. She also acknowledged Candrice R. Heath, MD, a dermatologist based in Newark, Delaware, for her assistance with the presentation content.

dbrunk@mdedge.com







 

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Respect is key when treating dermatologic conditions in transgender youth

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– The way Stanley Vance Jr., MD, sees it, the No. 1 priority in the care of transgender youth is respecting their gender identity.

Dr. Stanley Vance Jr. of the University of California San Francisco, adolescent medicine
Dr. Stanley Vance Jr.

“This can really help with rapport and also help them continue to engage with your care,” he said at the annual meeting of the Society for Pediatric Dermatology.

One of the first steps is to establish the patient’s chosen name and pronouns. “Ask, use, and be consistent,” said Dr. Vance, an adolescent medicine specialist at the University of California, San Francisco. “Taking it to another level, you can implement system-level tools to ensure that all of your staff consistently use the chosen name and pronouns. Something we’ve found helpful is including questions about chosen name and pronouns on patient intake forms, and working with the IT department to have a place in our electronic medical record to put the chosen name and preferred pronouns.”

In a study published in the Journal of Adolescent Health, researchers found that the use of chosen names and pronouns for transgender use was associated with reduced depressive symptoms, suicidal ideation, and suicidal behavior among transgender youth.

Dr. Vance, who also holds a staff position at the UCSF Child and Adolescent Clinic, went on to discuss dermatologic considerations for gender diverse youth. In transgender females, estrogens can reduce the quantity and density of body and facial hair, “but it doesn’t necessarily get rid of the hair, so we may refer to dermatology for hair removal or hair reduction. There can also be a decrease in sebum production, which can lead to dry skin for those who are at risk.”

Transgender females often seek laser hair removal or electrolysis to aid in “blendability,” or how they perceive as being female or feminine. “We know that this can help in psychosocial outcomes for these young people,” Dr. Vance said. “Another reason why hair reduction and removal may be important is preoperatively for vaginoplasty.”

In transgender males, testosterone increases male pattern hair growth and can increase male pattern hair loss. “Minoxidil does not interact with gender-affirming hormone treatment. If finasteride needs to be considered, it may interfere with the development of secondary sex characteristics.” Testosterone also increases sebum production and can increase acne, particularly in the first 6 months to 1 year after initiation, and with increased titration. “Some transmasculine youth may need oral isotretinoin, as stopping testosterone can be psychologically damaging,” Dr. Vance said.

“Unfortunately, the iPLEDGE program requirements can be perceived as gender nonaffirming, because patients must register by the sex assigned to them at birth, they must take pregnancy tests, and there can be provider assumptions about sexuality which does not equate with gender identity.”

He recommended having “open and honest” conversations with patients about the requirements and limitations of dispensing oral isotretinoin. “Assure the patient that you will be respectful and affirming of their gender identity while they’re in your office,” Dr. Vance advised. “If the patient has a mental health provider, you can strategize with them to reduce gender dysphoria around this process. Finally, advocating to change the system can not only be helpful for the patient in front of you, but for other patients who are in the same situation.”

He concluded his presentation by describing transgender youth as “some of the most resilient young people I’ve had the pleasure of working with.

“I think that we can all work to make sure they feel supported in who they are,” he said.

Dr. Vance reported having no relevant financial disclosures.

dbrunk@mdedge.com

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– The way Stanley Vance Jr., MD, sees it, the No. 1 priority in the care of transgender youth is respecting their gender identity.

Dr. Stanley Vance Jr. of the University of California San Francisco, adolescent medicine
Dr. Stanley Vance Jr.

“This can really help with rapport and also help them continue to engage with your care,” he said at the annual meeting of the Society for Pediatric Dermatology.

One of the first steps is to establish the patient’s chosen name and pronouns. “Ask, use, and be consistent,” said Dr. Vance, an adolescent medicine specialist at the University of California, San Francisco. “Taking it to another level, you can implement system-level tools to ensure that all of your staff consistently use the chosen name and pronouns. Something we’ve found helpful is including questions about chosen name and pronouns on patient intake forms, and working with the IT department to have a place in our electronic medical record to put the chosen name and preferred pronouns.”

In a study published in the Journal of Adolescent Health, researchers found that the use of chosen names and pronouns for transgender use was associated with reduced depressive symptoms, suicidal ideation, and suicidal behavior among transgender youth.

Dr. Vance, who also holds a staff position at the UCSF Child and Adolescent Clinic, went on to discuss dermatologic considerations for gender diverse youth. In transgender females, estrogens can reduce the quantity and density of body and facial hair, “but it doesn’t necessarily get rid of the hair, so we may refer to dermatology for hair removal or hair reduction. There can also be a decrease in sebum production, which can lead to dry skin for those who are at risk.”

Transgender females often seek laser hair removal or electrolysis to aid in “blendability,” or how they perceive as being female or feminine. “We know that this can help in psychosocial outcomes for these young people,” Dr. Vance said. “Another reason why hair reduction and removal may be important is preoperatively for vaginoplasty.”

In transgender males, testosterone increases male pattern hair growth and can increase male pattern hair loss. “Minoxidil does not interact with gender-affirming hormone treatment. If finasteride needs to be considered, it may interfere with the development of secondary sex characteristics.” Testosterone also increases sebum production and can increase acne, particularly in the first 6 months to 1 year after initiation, and with increased titration. “Some transmasculine youth may need oral isotretinoin, as stopping testosterone can be psychologically damaging,” Dr. Vance said.

“Unfortunately, the iPLEDGE program requirements can be perceived as gender nonaffirming, because patients must register by the sex assigned to them at birth, they must take pregnancy tests, and there can be provider assumptions about sexuality which does not equate with gender identity.”

He recommended having “open and honest” conversations with patients about the requirements and limitations of dispensing oral isotretinoin. “Assure the patient that you will be respectful and affirming of their gender identity while they’re in your office,” Dr. Vance advised. “If the patient has a mental health provider, you can strategize with them to reduce gender dysphoria around this process. Finally, advocating to change the system can not only be helpful for the patient in front of you, but for other patients who are in the same situation.”

He concluded his presentation by describing transgender youth as “some of the most resilient young people I’ve had the pleasure of working with.

“I think that we can all work to make sure they feel supported in who they are,” he said.

Dr. Vance reported having no relevant financial disclosures.

dbrunk@mdedge.com

– The way Stanley Vance Jr., MD, sees it, the No. 1 priority in the care of transgender youth is respecting their gender identity.

Dr. Stanley Vance Jr. of the University of California San Francisco, adolescent medicine
Dr. Stanley Vance Jr.

“This can really help with rapport and also help them continue to engage with your care,” he said at the annual meeting of the Society for Pediatric Dermatology.

One of the first steps is to establish the patient’s chosen name and pronouns. “Ask, use, and be consistent,” said Dr. Vance, an adolescent medicine specialist at the University of California, San Francisco. “Taking it to another level, you can implement system-level tools to ensure that all of your staff consistently use the chosen name and pronouns. Something we’ve found helpful is including questions about chosen name and pronouns on patient intake forms, and working with the IT department to have a place in our electronic medical record to put the chosen name and preferred pronouns.”

In a study published in the Journal of Adolescent Health, researchers found that the use of chosen names and pronouns for transgender use was associated with reduced depressive symptoms, suicidal ideation, and suicidal behavior among transgender youth.

Dr. Vance, who also holds a staff position at the UCSF Child and Adolescent Clinic, went on to discuss dermatologic considerations for gender diverse youth. In transgender females, estrogens can reduce the quantity and density of body and facial hair, “but it doesn’t necessarily get rid of the hair, so we may refer to dermatology for hair removal or hair reduction. There can also be a decrease in sebum production, which can lead to dry skin for those who are at risk.”

Transgender females often seek laser hair removal or electrolysis to aid in “blendability,” or how they perceive as being female or feminine. “We know that this can help in psychosocial outcomes for these young people,” Dr. Vance said. “Another reason why hair reduction and removal may be important is preoperatively for vaginoplasty.”

In transgender males, testosterone increases male pattern hair growth and can increase male pattern hair loss. “Minoxidil does not interact with gender-affirming hormone treatment. If finasteride needs to be considered, it may interfere with the development of secondary sex characteristics.” Testosterone also increases sebum production and can increase acne, particularly in the first 6 months to 1 year after initiation, and with increased titration. “Some transmasculine youth may need oral isotretinoin, as stopping testosterone can be psychologically damaging,” Dr. Vance said.

“Unfortunately, the iPLEDGE program requirements can be perceived as gender nonaffirming, because patients must register by the sex assigned to them at birth, they must take pregnancy tests, and there can be provider assumptions about sexuality which does not equate with gender identity.”

He recommended having “open and honest” conversations with patients about the requirements and limitations of dispensing oral isotretinoin. “Assure the patient that you will be respectful and affirming of their gender identity while they’re in your office,” Dr. Vance advised. “If the patient has a mental health provider, you can strategize with them to reduce gender dysphoria around this process. Finally, advocating to change the system can not only be helpful for the patient in front of you, but for other patients who are in the same situation.”

He concluded his presentation by describing transgender youth as “some of the most resilient young people I’ve had the pleasure of working with.

“I think that we can all work to make sure they feel supported in who they are,” he said.

Dr. Vance reported having no relevant financial disclosures.

dbrunk@mdedge.com

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