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Team maps genetic evolution of T-ALL subtype
Single-cell analysis has revealed key genetic events in a type of T-cell acute lymphoblastic leukemia (T-ALL), according to researchers.
The team tracked the branching pattern of evolution in STIL-TAL1-positive T-ALL and identified mutations that may trigger development of the disease.
The researchers believe their findings could be used in minimal residual disease assessments as well as for the development of new targeted drugs.
Caroline Furness, MD, of Institute of Cancer Research in London, UK, and her colleagues described this research in Leukemia.
To determine the sequence of mutational events in STIL-TAL1-positive T-ALL, the researchers examined individual leukemia cells from 19 children and young adults with the disease, as well as 1 cell line with the STIL-TAL1 rearrangement (RPMI 8402).
The team found the STIL-TAL1 gene fusion and inactivation of the CDKN2A gene occurred very early in leukemia development.
The researchers said it was difficult to tell whether STIL-TAL1 fusion or CDKN2A loss are initiating events in this disease, and it isn’t clear which mutational event occurs first.
However, the team believes the STIL-TAL1 fusion is likely a founder or truncal event for this type of leukemia, so targeting the TAL1 regulatory complex could be an effective way to treat the disease.
The researchers also identified mutations in NOTCH1 and PTEN as secondary subclonal events.
Half of the samples examined had errors affecting PTEN, which suggests these events are key to maintaining leukemia growth and survival in STIL-TAL1-positive T-ALL, according to the researchers.
“We need to understand how cancers evolve and unpick which mutations are key to triggering cancer development and which are important for driving its growth and spread,” Dr Furness said.
“Our study uncovered these crucial mutations in a type of leukemia that accounts for around a quarter of cases of T-cell leukemia in children and young adults. This will help us to develop more effective treatments, especially in those children who relapse, and kinder treatments that won’t cause life-long side effects.”
Single-cell analysis has revealed key genetic events in a type of T-cell acute lymphoblastic leukemia (T-ALL), according to researchers.
The team tracked the branching pattern of evolution in STIL-TAL1-positive T-ALL and identified mutations that may trigger development of the disease.
The researchers believe their findings could be used in minimal residual disease assessments as well as for the development of new targeted drugs.
Caroline Furness, MD, of Institute of Cancer Research in London, UK, and her colleagues described this research in Leukemia.
To determine the sequence of mutational events in STIL-TAL1-positive T-ALL, the researchers examined individual leukemia cells from 19 children and young adults with the disease, as well as 1 cell line with the STIL-TAL1 rearrangement (RPMI 8402).
The team found the STIL-TAL1 gene fusion and inactivation of the CDKN2A gene occurred very early in leukemia development.
The researchers said it was difficult to tell whether STIL-TAL1 fusion or CDKN2A loss are initiating events in this disease, and it isn’t clear which mutational event occurs first.
However, the team believes the STIL-TAL1 fusion is likely a founder or truncal event for this type of leukemia, so targeting the TAL1 regulatory complex could be an effective way to treat the disease.
The researchers also identified mutations in NOTCH1 and PTEN as secondary subclonal events.
Half of the samples examined had errors affecting PTEN, which suggests these events are key to maintaining leukemia growth and survival in STIL-TAL1-positive T-ALL, according to the researchers.
“We need to understand how cancers evolve and unpick which mutations are key to triggering cancer development and which are important for driving its growth and spread,” Dr Furness said.
“Our study uncovered these crucial mutations in a type of leukemia that accounts for around a quarter of cases of T-cell leukemia in children and young adults. This will help us to develop more effective treatments, especially in those children who relapse, and kinder treatments that won’t cause life-long side effects.”
Single-cell analysis has revealed key genetic events in a type of T-cell acute lymphoblastic leukemia (T-ALL), according to researchers.
The team tracked the branching pattern of evolution in STIL-TAL1-positive T-ALL and identified mutations that may trigger development of the disease.
The researchers believe their findings could be used in minimal residual disease assessments as well as for the development of new targeted drugs.
Caroline Furness, MD, of Institute of Cancer Research in London, UK, and her colleagues described this research in Leukemia.
To determine the sequence of mutational events in STIL-TAL1-positive T-ALL, the researchers examined individual leukemia cells from 19 children and young adults with the disease, as well as 1 cell line with the STIL-TAL1 rearrangement (RPMI 8402).
The team found the STIL-TAL1 gene fusion and inactivation of the CDKN2A gene occurred very early in leukemia development.
The researchers said it was difficult to tell whether STIL-TAL1 fusion or CDKN2A loss are initiating events in this disease, and it isn’t clear which mutational event occurs first.
However, the team believes the STIL-TAL1 fusion is likely a founder or truncal event for this type of leukemia, so targeting the TAL1 regulatory complex could be an effective way to treat the disease.
The researchers also identified mutations in NOTCH1 and PTEN as secondary subclonal events.
Half of the samples examined had errors affecting PTEN, which suggests these events are key to maintaining leukemia growth and survival in STIL-TAL1-positive T-ALL, according to the researchers.
“We need to understand how cancers evolve and unpick which mutations are key to triggering cancer development and which are important for driving its growth and spread,” Dr Furness said.
“Our study uncovered these crucial mutations in a type of leukemia that accounts for around a quarter of cases of T-cell leukemia in children and young adults. This will help us to develop more effective treatments, especially in those children who relapse, and kinder treatments that won’t cause life-long side effects.”
Melanoma in young children may be biologically distinct from that in teens
Pediatric melanomas appear to be more progressive in adolescents than in young children, based on data from a retrospective study of 32 cases.
Few young children with melanoma die, despite a greater likelihood of thicker tumors, lymph node metastasis, and later diagnosis, which suggests that melanoma in young children may be biologically distinct from melanoma in adolescents, wrote Diana W. Bartenstein, of Harvard University Medical School, Boston, and her colleagues.
Overall, significantly more children than adolescents had spitzoid melanoma (50% vs. 10%, P = .01). In addition, children were more likely than adolescents to present with stage 3 or 4 cancer (58% vs. 25%) and with Clark level IV and V tumors (42% vs. 35%), although these differences were not significant. The median Breslow thickness of lesions was greater in children than in adolescents (3.5 mm vs. 1.5 mm) as was the median mitotic index (5 mitotic figures per mm2 vs. 2 mitotic figures per mm2) and children were more likely than adolescents to have neural invasion, but these differences were not significant either.
During the study period of more than 20 years, none of the children younger than 11 years died, compared with four deaths in adolescents, a statistically significant difference (P = .04). The follow-up for surviving individuals ranged from 9-37 months with a median of 44 months.
The study findings were limited by several factors including the small sample size and difficulty in assessing spitzoid tumors, the researchers noted.
However, “these results support the hypothesis that melanoma in young children may be biologically distinct from melanoma in adults,” they said. “Alternatively, melanoma subtype may drive survival differences between children and adolescents.”
No conflicts of interest were reported. The study was supported by the Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship and the Society for Pediatric Dermatology and Pediatric Dermatology Research Alliance.
SOURCE: Bartenstein DW et al. Pediatr Dermatol. 2018 Mar 23. doi: 10.1111/pde.13454.
Pediatric melanomas appear to be more progressive in adolescents than in young children, based on data from a retrospective study of 32 cases.
Few young children with melanoma die, despite a greater likelihood of thicker tumors, lymph node metastasis, and later diagnosis, which suggests that melanoma in young children may be biologically distinct from melanoma in adolescents, wrote Diana W. Bartenstein, of Harvard University Medical School, Boston, and her colleagues.
Overall, significantly more children than adolescents had spitzoid melanoma (50% vs. 10%, P = .01). In addition, children were more likely than adolescents to present with stage 3 or 4 cancer (58% vs. 25%) and with Clark level IV and V tumors (42% vs. 35%), although these differences were not significant. The median Breslow thickness of lesions was greater in children than in adolescents (3.5 mm vs. 1.5 mm) as was the median mitotic index (5 mitotic figures per mm2 vs. 2 mitotic figures per mm2) and children were more likely than adolescents to have neural invasion, but these differences were not significant either.
During the study period of more than 20 years, none of the children younger than 11 years died, compared with four deaths in adolescents, a statistically significant difference (P = .04). The follow-up for surviving individuals ranged from 9-37 months with a median of 44 months.
The study findings were limited by several factors including the small sample size and difficulty in assessing spitzoid tumors, the researchers noted.
However, “these results support the hypothesis that melanoma in young children may be biologically distinct from melanoma in adults,” they said. “Alternatively, melanoma subtype may drive survival differences between children and adolescents.”
No conflicts of interest were reported. The study was supported by the Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship and the Society for Pediatric Dermatology and Pediatric Dermatology Research Alliance.
SOURCE: Bartenstein DW et al. Pediatr Dermatol. 2018 Mar 23. doi: 10.1111/pde.13454.
Pediatric melanomas appear to be more progressive in adolescents than in young children, based on data from a retrospective study of 32 cases.
Few young children with melanoma die, despite a greater likelihood of thicker tumors, lymph node metastasis, and later diagnosis, which suggests that melanoma in young children may be biologically distinct from melanoma in adolescents, wrote Diana W. Bartenstein, of Harvard University Medical School, Boston, and her colleagues.
Overall, significantly more children than adolescents had spitzoid melanoma (50% vs. 10%, P = .01). In addition, children were more likely than adolescents to present with stage 3 or 4 cancer (58% vs. 25%) and with Clark level IV and V tumors (42% vs. 35%), although these differences were not significant. The median Breslow thickness of lesions was greater in children than in adolescents (3.5 mm vs. 1.5 mm) as was the median mitotic index (5 mitotic figures per mm2 vs. 2 mitotic figures per mm2) and children were more likely than adolescents to have neural invasion, but these differences were not significant either.
During the study period of more than 20 years, none of the children younger than 11 years died, compared with four deaths in adolescents, a statistically significant difference (P = .04). The follow-up for surviving individuals ranged from 9-37 months with a median of 44 months.
The study findings were limited by several factors including the small sample size and difficulty in assessing spitzoid tumors, the researchers noted.
However, “these results support the hypothesis that melanoma in young children may be biologically distinct from melanoma in adults,” they said. “Alternatively, melanoma subtype may drive survival differences between children and adolescents.”
No conflicts of interest were reported. The study was supported by the Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship and the Society for Pediatric Dermatology and Pediatric Dermatology Research Alliance.
SOURCE: Bartenstein DW et al. Pediatr Dermatol. 2018 Mar 23. doi: 10.1111/pde.13454.
FROM PEDIATRIC DERMATOLOGY
Key clinical point:
Major finding: Significantly more children than adolescents had spitzoid melanoma (50% vs. 10%, P = .01).
Study details: A retrospective cohort study of 32 children and adolescents with melanoma.
Disclosures: The study was supported by the Alpha Omega Alpha–Carolyn L. Kuckein Student Research Fellowship and the Society for Pediatric Dermatology and Pediatric Dermatology Research Alliance. No conflicts of interest were reported.
Source: Bartenstein DW et al. Pediatr Dermatol. 2018 Mar 23. doi: 10.1111/pde.13454.
Consider hydroxychloroquine in treating pediatric alopecia areata
according to Duri Yun, MD, of the University of Chicago Medicine, and associates.
In a retrospective review published in Pediatric Dermatology, nine children aged 6-16 years with AA and diverse ethnicities were treated with hydroxychloroquine between July 1, 2013, and July 1, 2015; all had failed multiple previous treatment modalities. In patient 1, hydroxychloroquine therapy was initiated, fine hair regrowth occurred after 5 months of therapy and was maintained, with dosage tapered to 200 mg once daily after 1 year. After 2 years of therapy, hair had nearly completely regrown. Similar results occurred in patient 2, who had nearly complete hair loss within 2 weeks of initiating hydroxychloroquine. Steady regrowth continued to near-complete regrowth after 1 year of treatment, when dosage was tapered to 200 mg once daily.
Four patients (44%) had no evidence of regrowth after 4-6 months of hydroxychloroquine therapy so they discontinued therapy. The most common adverse events while taking hydroxychloroquine were abdominal pain in two patients (22%) and headache in two patients (22%).
“In the context of children with severe AA failing multiple first-line therapies, our findings suggest that there may be a subgroup that benefits from therapy with hydroxychloroquine,” the researchers concluded. “Determining which factors might predict response to various therapies will come from combined efforts to conduct well-controlled clinical trials of treatments for AA.”
SOURCE: Yun D et al., Pediatr Dermatol. 2018 Mar 25. doi: 10.1111/pde.13451.
according to Duri Yun, MD, of the University of Chicago Medicine, and associates.
In a retrospective review published in Pediatric Dermatology, nine children aged 6-16 years with AA and diverse ethnicities were treated with hydroxychloroquine between July 1, 2013, and July 1, 2015; all had failed multiple previous treatment modalities. In patient 1, hydroxychloroquine therapy was initiated, fine hair regrowth occurred after 5 months of therapy and was maintained, with dosage tapered to 200 mg once daily after 1 year. After 2 years of therapy, hair had nearly completely regrown. Similar results occurred in patient 2, who had nearly complete hair loss within 2 weeks of initiating hydroxychloroquine. Steady regrowth continued to near-complete regrowth after 1 year of treatment, when dosage was tapered to 200 mg once daily.
Four patients (44%) had no evidence of regrowth after 4-6 months of hydroxychloroquine therapy so they discontinued therapy. The most common adverse events while taking hydroxychloroquine were abdominal pain in two patients (22%) and headache in two patients (22%).
“In the context of children with severe AA failing multiple first-line therapies, our findings suggest that there may be a subgroup that benefits from therapy with hydroxychloroquine,” the researchers concluded. “Determining which factors might predict response to various therapies will come from combined efforts to conduct well-controlled clinical trials of treatments for AA.”
SOURCE: Yun D et al., Pediatr Dermatol. 2018 Mar 25. doi: 10.1111/pde.13451.
according to Duri Yun, MD, of the University of Chicago Medicine, and associates.
In a retrospective review published in Pediatric Dermatology, nine children aged 6-16 years with AA and diverse ethnicities were treated with hydroxychloroquine between July 1, 2013, and July 1, 2015; all had failed multiple previous treatment modalities. In patient 1, hydroxychloroquine therapy was initiated, fine hair regrowth occurred after 5 months of therapy and was maintained, with dosage tapered to 200 mg once daily after 1 year. After 2 years of therapy, hair had nearly completely regrown. Similar results occurred in patient 2, who had nearly complete hair loss within 2 weeks of initiating hydroxychloroquine. Steady regrowth continued to near-complete regrowth after 1 year of treatment, when dosage was tapered to 200 mg once daily.
Four patients (44%) had no evidence of regrowth after 4-6 months of hydroxychloroquine therapy so they discontinued therapy. The most common adverse events while taking hydroxychloroquine were abdominal pain in two patients (22%) and headache in two patients (22%).
“In the context of children with severe AA failing multiple first-line therapies, our findings suggest that there may be a subgroup that benefits from therapy with hydroxychloroquine,” the researchers concluded. “Determining which factors might predict response to various therapies will come from combined efforts to conduct well-controlled clinical trials of treatments for AA.”
SOURCE: Yun D et al., Pediatr Dermatol. 2018 Mar 25. doi: 10.1111/pde.13451.
FROM PEDIATRIC DERMATOLOGY
Homework
How do you feel about homework? Do you think your school-age patients are given too much homework? Would they be better off spending their after-school time at home in free play or exploring nonacademic interests? Or, do you feel the school day is too short to adequately cover what a well-educated child needs to know? Doesn’t homework foster good independent work habits and discipline?
Do you have fond memories of doing homework? Are you glad those days of bringing home an hour or 3 of extra work are behind you? Maybe they aren’t behind you. Are you still spending an hour or more getting stuff done at home you didn’t get done in the office?
Primary care pediatrics has never promised its practitioners that they will arrive at home at the end of the workday free of unfinished business. If you have after-hours call responsibilities, there always have been phone calls, decisions to make, and trips to EDs and delivery rooms. Even if you are fortunate enough to not have after-hours call responsibilities, there are certainly evenings when you are nagged by second thoughts and worries about troublesome patients you have seen during the day. Did you make the correct diagnosis or forget to order a critical lab test?
This kind of homework is expected. It’s what you signed up for. But with experience, you learn how to provide better anticipatory guidance that can decrease the number of after-hours calls. You can minimize, but never eliminate, second-guessing by learning to make wiser diagnostic and therapeutic decisions.
However, arriving home with a laptop or notebook loaded with unfinished electronic health records and work-related emails is not what you thought primary care pediatrics was about ... and it didn’t used to be. For the first 35 years of practice, when I saw my last patient, my office work was over. If I wasn’t on call, I could enjoy the entire evening with my family uninterrupted.
But change happens. Coincident with the launch of a new computer system, my workday became an hour longer so that I could complete my electronic office notes before I went home. For some of my colleagues, this unwelcome addition ran more than an hour and a half or 2 hours, and many of them leapt at the practice administrator’s offer to link their home computers with our new office EHR. Buried in what sounded like a good deal to them, I could hear the creaky opening of a Pandora’s box.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
How do you feel about homework? Do you think your school-age patients are given too much homework? Would they be better off spending their after-school time at home in free play or exploring nonacademic interests? Or, do you feel the school day is too short to adequately cover what a well-educated child needs to know? Doesn’t homework foster good independent work habits and discipline?
Do you have fond memories of doing homework? Are you glad those days of bringing home an hour or 3 of extra work are behind you? Maybe they aren’t behind you. Are you still spending an hour or more getting stuff done at home you didn’t get done in the office?
Primary care pediatrics has never promised its practitioners that they will arrive at home at the end of the workday free of unfinished business. If you have after-hours call responsibilities, there always have been phone calls, decisions to make, and trips to EDs and delivery rooms. Even if you are fortunate enough to not have after-hours call responsibilities, there are certainly evenings when you are nagged by second thoughts and worries about troublesome patients you have seen during the day. Did you make the correct diagnosis or forget to order a critical lab test?
This kind of homework is expected. It’s what you signed up for. But with experience, you learn how to provide better anticipatory guidance that can decrease the number of after-hours calls. You can minimize, but never eliminate, second-guessing by learning to make wiser diagnostic and therapeutic decisions.
However, arriving home with a laptop or notebook loaded with unfinished electronic health records and work-related emails is not what you thought primary care pediatrics was about ... and it didn’t used to be. For the first 35 years of practice, when I saw my last patient, my office work was over. If I wasn’t on call, I could enjoy the entire evening with my family uninterrupted.
But change happens. Coincident with the launch of a new computer system, my workday became an hour longer so that I could complete my electronic office notes before I went home. For some of my colleagues, this unwelcome addition ran more than an hour and a half or 2 hours, and many of them leapt at the practice administrator’s offer to link their home computers with our new office EHR. Buried in what sounded like a good deal to them, I could hear the creaky opening of a Pandora’s box.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
How do you feel about homework? Do you think your school-age patients are given too much homework? Would they be better off spending their after-school time at home in free play or exploring nonacademic interests? Or, do you feel the school day is too short to adequately cover what a well-educated child needs to know? Doesn’t homework foster good independent work habits and discipline?
Do you have fond memories of doing homework? Are you glad those days of bringing home an hour or 3 of extra work are behind you? Maybe they aren’t behind you. Are you still spending an hour or more getting stuff done at home you didn’t get done in the office?
Primary care pediatrics has never promised its practitioners that they will arrive at home at the end of the workday free of unfinished business. If you have after-hours call responsibilities, there always have been phone calls, decisions to make, and trips to EDs and delivery rooms. Even if you are fortunate enough to not have after-hours call responsibilities, there are certainly evenings when you are nagged by second thoughts and worries about troublesome patients you have seen during the day. Did you make the correct diagnosis or forget to order a critical lab test?
This kind of homework is expected. It’s what you signed up for. But with experience, you learn how to provide better anticipatory guidance that can decrease the number of after-hours calls. You can minimize, but never eliminate, second-guessing by learning to make wiser diagnostic and therapeutic decisions.
However, arriving home with a laptop or notebook loaded with unfinished electronic health records and work-related emails is not what you thought primary care pediatrics was about ... and it didn’t used to be. For the first 35 years of practice, when I saw my last patient, my office work was over. If I wasn’t on call, I could enjoy the entire evening with my family uninterrupted.
But change happens. Coincident with the launch of a new computer system, my workday became an hour longer so that I could complete my electronic office notes before I went home. For some of my colleagues, this unwelcome addition ran more than an hour and a half or 2 hours, and many of them leapt at the practice administrator’s offer to link their home computers with our new office EHR. Buried in what sounded like a good deal to them, I could hear the creaky opening of a Pandora’s box.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
Debunking Atopic Dermatitis Myths: Do Most Children Outgrow Atopic Dermatitis?
Myth: Children eventually outgrow atopic dermatitis and therefore do not need treatment
The negative impact of atopic dermatitis (AD) on quality of life in the pediatric population often prompts parents/guardians to inquire about whether a child with AD will ever outgrow their disease. If remission is expected as the child gets older, many may question if it is necessary to pursue treatment or just let the disease run its course. Although AD often is reported to resolve soon after the first decade of life, symptoms can persist well into the second decade and beyond, suggesting that AD may be a lifelong disease with periods of waxing and waning symptoms that require persistent treatment throughout the patient’s life.
A 2014 study included 7157 children with AD (mean age of disease onset, 1.7 years) who were enrolled in the Pediatric Eczema Elective Registry (PEER) program between the ages of 2 and 17 years with measurement of disease activity at regular 6-month intervals for up to 5 years. The study results indicated that more than 80% of patients at every age (age range, 2–26 years) had symptoms of AD and/or were using medication to treat their disease, and the majority (64%) of patients had never reported a 6-month period during which they achieved clearance of symptoms without medication. At the age of 20 years, 50% of patients reported at least 1 lifetime 6-month period during which they were both symptom and treatment free. In another study of adolescents with AD who also had AD in childhood (N=82), 48% of patients remained in the same AD severity grades and 13% deteriorated from childhood to adolescence; only 39% of patients showed improvement in disease severity from childhood to adolescence. The findings of these reports are contradictory to conventional clinical teaching, which indicates that AD generally resolves by age 12 in 50% to 70% of children.
Even though some children with AD may experience periods of disease clearance, these findings often do not persist and should not be confused with a permanent remission. Most patients require continued treatment with medications to achieve relief of symptoms. Therefore, physicians should not assure parents/guardians that a child can outgrow AD; rather, they should educate pediatric patients and their caregivers about the potentially lifelong disease course and encourage early intervention to mitigate symptoms and manage comorbidities as the patient ages.
Hon KL, Tsang YCK, Poon TCW, et al. Predicating eczema severity beyond childhood. World J Pediatr. 2016;12:44-48.
Margolis JS, Abuabara K, Bilker W, et al. Persistence of mild to moderate atopic dermatitis [published online April 2, 2014]. JAMA Dermatol. 2014;150:593-600.
Myth: Children eventually outgrow atopic dermatitis and therefore do not need treatment
The negative impact of atopic dermatitis (AD) on quality of life in the pediatric population often prompts parents/guardians to inquire about whether a child with AD will ever outgrow their disease. If remission is expected as the child gets older, many may question if it is necessary to pursue treatment or just let the disease run its course. Although AD often is reported to resolve soon after the first decade of life, symptoms can persist well into the second decade and beyond, suggesting that AD may be a lifelong disease with periods of waxing and waning symptoms that require persistent treatment throughout the patient’s life.
A 2014 study included 7157 children with AD (mean age of disease onset, 1.7 years) who were enrolled in the Pediatric Eczema Elective Registry (PEER) program between the ages of 2 and 17 years with measurement of disease activity at regular 6-month intervals for up to 5 years. The study results indicated that more than 80% of patients at every age (age range, 2–26 years) had symptoms of AD and/or were using medication to treat their disease, and the majority (64%) of patients had never reported a 6-month period during which they achieved clearance of symptoms without medication. At the age of 20 years, 50% of patients reported at least 1 lifetime 6-month period during which they were both symptom and treatment free. In another study of adolescents with AD who also had AD in childhood (N=82), 48% of patients remained in the same AD severity grades and 13% deteriorated from childhood to adolescence; only 39% of patients showed improvement in disease severity from childhood to adolescence. The findings of these reports are contradictory to conventional clinical teaching, which indicates that AD generally resolves by age 12 in 50% to 70% of children.
Even though some children with AD may experience periods of disease clearance, these findings often do not persist and should not be confused with a permanent remission. Most patients require continued treatment with medications to achieve relief of symptoms. Therefore, physicians should not assure parents/guardians that a child can outgrow AD; rather, they should educate pediatric patients and their caregivers about the potentially lifelong disease course and encourage early intervention to mitigate symptoms and manage comorbidities as the patient ages.
Myth: Children eventually outgrow atopic dermatitis and therefore do not need treatment
The negative impact of atopic dermatitis (AD) on quality of life in the pediatric population often prompts parents/guardians to inquire about whether a child with AD will ever outgrow their disease. If remission is expected as the child gets older, many may question if it is necessary to pursue treatment or just let the disease run its course. Although AD often is reported to resolve soon after the first decade of life, symptoms can persist well into the second decade and beyond, suggesting that AD may be a lifelong disease with periods of waxing and waning symptoms that require persistent treatment throughout the patient’s life.
A 2014 study included 7157 children with AD (mean age of disease onset, 1.7 years) who were enrolled in the Pediatric Eczema Elective Registry (PEER) program between the ages of 2 and 17 years with measurement of disease activity at regular 6-month intervals for up to 5 years. The study results indicated that more than 80% of patients at every age (age range, 2–26 years) had symptoms of AD and/or were using medication to treat their disease, and the majority (64%) of patients had never reported a 6-month period during which they achieved clearance of symptoms without medication. At the age of 20 years, 50% of patients reported at least 1 lifetime 6-month period during which they were both symptom and treatment free. In another study of adolescents with AD who also had AD in childhood (N=82), 48% of patients remained in the same AD severity grades and 13% deteriorated from childhood to adolescence; only 39% of patients showed improvement in disease severity from childhood to adolescence. The findings of these reports are contradictory to conventional clinical teaching, which indicates that AD generally resolves by age 12 in 50% to 70% of children.
Even though some children with AD may experience periods of disease clearance, these findings often do not persist and should not be confused with a permanent remission. Most patients require continued treatment with medications to achieve relief of symptoms. Therefore, physicians should not assure parents/guardians that a child can outgrow AD; rather, they should educate pediatric patients and their caregivers about the potentially lifelong disease course and encourage early intervention to mitigate symptoms and manage comorbidities as the patient ages.
Hon KL, Tsang YCK, Poon TCW, et al. Predicating eczema severity beyond childhood. World J Pediatr. 2016;12:44-48.
Margolis JS, Abuabara K, Bilker W, et al. Persistence of mild to moderate atopic dermatitis [published online April 2, 2014]. JAMA Dermatol. 2014;150:593-600.
Hon KL, Tsang YCK, Poon TCW, et al. Predicating eczema severity beyond childhood. World J Pediatr. 2016;12:44-48.
Margolis JS, Abuabara K, Bilker W, et al. Persistence of mild to moderate atopic dermatitis [published online April 2, 2014]. JAMA Dermatol. 2014;150:593-600.
Drug nets orphan designation for SCD
The European Commission (EC) has granted orphan designation to Altemia (formerly SC411) for the treatment of pediatric patients with sickle cell disease (SCD).
Altemia gelatin capsules are designed to replenish the lipids destroyed by sickle hemoglobin.
Altemia is intended to be taken once daily to reduce vaso-occlusive crises, anemia, organ damage, and other complications of SCD.
Altemia consists of a mixture of fatty acids, primarily in the form of Ethyl Cervonate (a proprietary blend of docosahexaenoic acid and other omega-3 fatty acids), and surface active agents formulated using Advanced Lipid Technologies.
Advanced Lipid Technologies are proprietary formulation and manufacturing techniques used by Sancilio Pharmaceuticals Company, Inc. (SPCI) to create lipophilic drug products.
Last November, SPCI reported topline data from its phase 2 study of Altemia, the SCOT trial (NCT02973360). The trial included pediatric patients, ages 5 to 17, with SCD.
The study’s primary endpoint was the change from baseline in blood cell membranes’ fatty acids concentration. SPCI said Altemia showed a significant improvement in this endpoint, compared to placebo, within 4 weeks of treatment initiation.
Patients who received Altemia also had significant improvements in markers of coagulation (D-dimer), inflammation (C-reactive protein), and adhesion (E-selectin) after 8 weeks of treatment.
And patients treated with Altemia had a “clinically meaningful” reduction in vaso-occlusive events, according to SPCI.
There were no treatment-related serious adverse events reported.
Ninety-four percent of patients completed the study, and most have chosen to participate in the open-label extension phase, in which researchers will continue monitoring the safety and effectiveness of Altemia.
SPCI said additional analyses of SCOT data are ongoing, and the company plans to present detailed data from the study in journals and at upcoming scientific conferences.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Commission (EC) has granted orphan designation to Altemia (formerly SC411) for the treatment of pediatric patients with sickle cell disease (SCD).
Altemia gelatin capsules are designed to replenish the lipids destroyed by sickle hemoglobin.
Altemia is intended to be taken once daily to reduce vaso-occlusive crises, anemia, organ damage, and other complications of SCD.
Altemia consists of a mixture of fatty acids, primarily in the form of Ethyl Cervonate (a proprietary blend of docosahexaenoic acid and other omega-3 fatty acids), and surface active agents formulated using Advanced Lipid Technologies.
Advanced Lipid Technologies are proprietary formulation and manufacturing techniques used by Sancilio Pharmaceuticals Company, Inc. (SPCI) to create lipophilic drug products.
Last November, SPCI reported topline data from its phase 2 study of Altemia, the SCOT trial (NCT02973360). The trial included pediatric patients, ages 5 to 17, with SCD.
The study’s primary endpoint was the change from baseline in blood cell membranes’ fatty acids concentration. SPCI said Altemia showed a significant improvement in this endpoint, compared to placebo, within 4 weeks of treatment initiation.
Patients who received Altemia also had significant improvements in markers of coagulation (D-dimer), inflammation (C-reactive protein), and adhesion (E-selectin) after 8 weeks of treatment.
And patients treated with Altemia had a “clinically meaningful” reduction in vaso-occlusive events, according to SPCI.
There were no treatment-related serious adverse events reported.
Ninety-four percent of patients completed the study, and most have chosen to participate in the open-label extension phase, in which researchers will continue monitoring the safety and effectiveness of Altemia.
SPCI said additional analyses of SCOT data are ongoing, and the company plans to present detailed data from the study in journals and at upcoming scientific conferences.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Commission (EC) has granted orphan designation to Altemia (formerly SC411) for the treatment of pediatric patients with sickle cell disease (SCD).
Altemia gelatin capsules are designed to replenish the lipids destroyed by sickle hemoglobin.
Altemia is intended to be taken once daily to reduce vaso-occlusive crises, anemia, organ damage, and other complications of SCD.
Altemia consists of a mixture of fatty acids, primarily in the form of Ethyl Cervonate (a proprietary blend of docosahexaenoic acid and other omega-3 fatty acids), and surface active agents formulated using Advanced Lipid Technologies.
Advanced Lipid Technologies are proprietary formulation and manufacturing techniques used by Sancilio Pharmaceuticals Company, Inc. (SPCI) to create lipophilic drug products.
Last November, SPCI reported topline data from its phase 2 study of Altemia, the SCOT trial (NCT02973360). The trial included pediatric patients, ages 5 to 17, with SCD.
The study’s primary endpoint was the change from baseline in blood cell membranes’ fatty acids concentration. SPCI said Altemia showed a significant improvement in this endpoint, compared to placebo, within 4 weeks of treatment initiation.
Patients who received Altemia also had significant improvements in markers of coagulation (D-dimer), inflammation (C-reactive protein), and adhesion (E-selectin) after 8 weeks of treatment.
And patients treated with Altemia had a “clinically meaningful” reduction in vaso-occlusive events, according to SPCI.
There were no treatment-related serious adverse events reported.
Ninety-four percent of patients completed the study, and most have chosen to participate in the open-label extension phase, in which researchers will continue monitoring the safety and effectiveness of Altemia.
SPCI said additional analyses of SCOT data are ongoing, and the company plans to present detailed data from the study in journals and at upcoming scientific conferences.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
Always get culture in symptomatic children with neurogenic bladder
In the symptomatic child with neurogenic bladder at risk for urinary tract infection (UTI), urine culture should be performed regardless of the results of urinalysis, recommended Catherine S. Forster, MD, of Cincinnati Children’s Hospital Medical Center, and her associates.
In a general pediatric population, studies have found that certain uropathogens – such as Enterococcus species, Klebsiella species, and Pseudomonas aeruginosa – are less likely to be associated with pyuria than Escherichia coli.
According to the guidelines of the Infectious Disease Society of America guidelines for the diagnosis of catheter-associated UTI, pyuria is not considered diagnostic of UTI in patients who require CIC.
Children with neurogenic bladder requiring CIC often have bacteriuria and often undergo urinalyses to determine if empirical antibiotics are warranted until urine culture results are available. “Although timely initiation of antibiotics can prevent the progression of infection and decrease the risk of renal scars, unnecessary antimicrobial agents contribute to the emergence of bacterial resistance,” Dr. Forster and her associates said.
So the researchers designed a study to find out if the presence of pyuria was associated with particular uropathogens in children with neurogenic bladders.
In an analysis of 2,420 urinalysis and urine culture results from EHRs between Jan.1, 2008, and Dec. 31, 2014, for patients aged 18 years and younger with neurogenic bladders requiring CIC, the most frequently isolated uropathogen was E. coli (37%), followed by Enterococcus species (14%), Klebsiella species (11%), and various other uropathogen species (38%).
In children needing CIC for neurogenic bladder, growth of Enterococcus species on urine culture was linked with lower odds of both microscopic pyuria (0.44) and leukocyte esterase (0.45).
“With these results, we suggest that the current markers of UTI evidenced on urinalysis and urine microscopy are insufficient for predicting bacteriuria in this population,” Dr. Forster and her colleagues said, leading to their recommendation to perform a culture in symptomatic children with neurogenic bladders irrespective of urinalysis results.
Dr. Forster received a research grant from the National Institutes of Health. The investigators said they had no relevant conflicts of interest.
SOURCE: Forster CS et al. Pediatrics. 2018;141(5):e20173006.
In the symptomatic child with neurogenic bladder at risk for urinary tract infection (UTI), urine culture should be performed regardless of the results of urinalysis, recommended Catherine S. Forster, MD, of Cincinnati Children’s Hospital Medical Center, and her associates.
In a general pediatric population, studies have found that certain uropathogens – such as Enterococcus species, Klebsiella species, and Pseudomonas aeruginosa – are less likely to be associated with pyuria than Escherichia coli.
According to the guidelines of the Infectious Disease Society of America guidelines for the diagnosis of catheter-associated UTI, pyuria is not considered diagnostic of UTI in patients who require CIC.
Children with neurogenic bladder requiring CIC often have bacteriuria and often undergo urinalyses to determine if empirical antibiotics are warranted until urine culture results are available. “Although timely initiation of antibiotics can prevent the progression of infection and decrease the risk of renal scars, unnecessary antimicrobial agents contribute to the emergence of bacterial resistance,” Dr. Forster and her associates said.
So the researchers designed a study to find out if the presence of pyuria was associated with particular uropathogens in children with neurogenic bladders.
In an analysis of 2,420 urinalysis and urine culture results from EHRs between Jan.1, 2008, and Dec. 31, 2014, for patients aged 18 years and younger with neurogenic bladders requiring CIC, the most frequently isolated uropathogen was E. coli (37%), followed by Enterococcus species (14%), Klebsiella species (11%), and various other uropathogen species (38%).
In children needing CIC for neurogenic bladder, growth of Enterococcus species on urine culture was linked with lower odds of both microscopic pyuria (0.44) and leukocyte esterase (0.45).
“With these results, we suggest that the current markers of UTI evidenced on urinalysis and urine microscopy are insufficient for predicting bacteriuria in this population,” Dr. Forster and her colleagues said, leading to their recommendation to perform a culture in symptomatic children with neurogenic bladders irrespective of urinalysis results.
Dr. Forster received a research grant from the National Institutes of Health. The investigators said they had no relevant conflicts of interest.
SOURCE: Forster CS et al. Pediatrics. 2018;141(5):e20173006.
In the symptomatic child with neurogenic bladder at risk for urinary tract infection (UTI), urine culture should be performed regardless of the results of urinalysis, recommended Catherine S. Forster, MD, of Cincinnati Children’s Hospital Medical Center, and her associates.
In a general pediatric population, studies have found that certain uropathogens – such as Enterococcus species, Klebsiella species, and Pseudomonas aeruginosa – are less likely to be associated with pyuria than Escherichia coli.
According to the guidelines of the Infectious Disease Society of America guidelines for the diagnosis of catheter-associated UTI, pyuria is not considered diagnostic of UTI in patients who require CIC.
Children with neurogenic bladder requiring CIC often have bacteriuria and often undergo urinalyses to determine if empirical antibiotics are warranted until urine culture results are available. “Although timely initiation of antibiotics can prevent the progression of infection and decrease the risk of renal scars, unnecessary antimicrobial agents contribute to the emergence of bacterial resistance,” Dr. Forster and her associates said.
So the researchers designed a study to find out if the presence of pyuria was associated with particular uropathogens in children with neurogenic bladders.
In an analysis of 2,420 urinalysis and urine culture results from EHRs between Jan.1, 2008, and Dec. 31, 2014, for patients aged 18 years and younger with neurogenic bladders requiring CIC, the most frequently isolated uropathogen was E. coli (37%), followed by Enterococcus species (14%), Klebsiella species (11%), and various other uropathogen species (38%).
In children needing CIC for neurogenic bladder, growth of Enterococcus species on urine culture was linked with lower odds of both microscopic pyuria (0.44) and leukocyte esterase (0.45).
“With these results, we suggest that the current markers of UTI evidenced on urinalysis and urine microscopy are insufficient for predicting bacteriuria in this population,” Dr. Forster and her colleagues said, leading to their recommendation to perform a culture in symptomatic children with neurogenic bladders irrespective of urinalysis results.
Dr. Forster received a research grant from the National Institutes of Health. The investigators said they had no relevant conflicts of interest.
SOURCE: Forster CS et al. Pediatrics. 2018;141(5):e20173006.
FROM PEDIATRICS
Key clinical point:
Major finding: In children needing CIC for neurogenic bladder, growth of Enterococcus species on urine culture was linked with lower odds of both microscopic pyuria (0.44) and leukocyte esterase (0.45).
Study details: Assessment of 2,420 urinalyses and urine cultures in children with neurogenic bladders.
Disclosures: Dr. Forster received a research grant from the National Institutes of Health. The investigators said they had no relevant conflicts of interest.
Source: Forster CS et al. Pediatrics. 2018;141(5):e20173006.
Pediatric Dermatology Consult - March 2018
Rosacea is a chronic inflammatory skin disorder characterized by flushing, telangiectasia, erythema, papules, and pustules, most classically of the central face. Fair-skinned individuals and women are more commonly affected than are men, with age of onset typically around 30 years and older.1 In children and adolescents, rosacea is rare, especially among prepubertal children, so other papulopustular disorders should be considered when a rosacealike picture is present.2 Recurrent chalazia are seen with ocular rosacea and may be a clue to the diagnosis of acne rosacea. An individual’s subtype of rosacea also may transform with time to a different or an additional subtype.
Papulopustular rosacea (subtype II) is characterized by the presence of erythematous, dome-shaped papules distributed in crops in the central facial region. Cheeks, nasolabial folds, and the chin are most commonly affected. Pustules may or may not be present, but comedones are notably absent in an exclusively rosacea disease process. If comedones are present, a diagnosis of acne vulgaris should be considered instead of, or in addition to, rosacea. Pediatric patients with rosacea frequently present with papules and/or pustules, following the development of flushing.2
Ocular rosacea (subtype IV) may range in severity from mild blepharitis to severe keratitis and corneal vascularization. Patients may complain of a foreign body sensation. On external exam, lid margin telangiectasias, blepharitis, conjunctivitis, conjunctival injection, and recurrent chalazia may be frequently seen.3 Ocular rosacea may present without any signs of cutaneous disease; it may be the only form of rosacea (15% of patients in one study of 20 patients had only ocular rosacea)4 or may herald the development of cutaneous involvement. In fact, in children, ocular rosacea is frequently the first sign of disease. (A total of 55% of patients in the same study had both ocular and cutaneous rosacea, with ocular symptoms manifesting before the cutaneous disease). Thus an index of suspicion for rosacea should be maintained when a child presents with ocular findings.2
Other dermatitides resembling rosacea include steroid rosacea, perioral dermatitis, and idiopathic facial aseptic granuloma. Steroid rosacea, also known as iatrosacea, describes an eruption of erythema, papules, and telangiectasias that is clinically indistinguishable from rosacea.6 It results from chronic use of topical steroids, generally high potency, or abrupt withdrawal of steroids. Steroid rosacea should be treated by discontinuation of the steroid via tapered withdrawal.7 Perioral dermatitis, also known as periorificial dermatitis, may also appear rosacea-form. It usually is located around the perioral and perinasal areas, but may extend to the periocular area.8 Idiopathic facial septic granuloma describes erythematous to violaceous nodules of the cheeks and eyelid in children, with chalazia frequently present; it is thought to be associated with rosacea.9
Although the exact pathophysiology of rosacea is unknown, it is clear that the dysregulation of the innate immune system plays a key role in the pathogenesis of rosacea. Studies have found that patients with rosacea have increased expression of cathelicidin, and its activating serine protease, kallikrein.5 Interestingly, UV light, a known trigger of rosacea, induces expression of cathelicidin and its inflammatory cascade.5 Neurovascular signaling is also aberrantly upregulated; vanilloid and ankyrin receptors have been shown to be active in rosacea, and are activated by rosacea-exacerbating stimuli, such as heat, inflammation, and spices. Higher levels of Demodex folliculorum and Staphylococcus epidermis also have been consistently found on the skin of rosacea patients, compared with healthy subjects, though it is unclear what role these pathogens play in the development of rosacea.
Treatment of rosacea is very important given its profound impact on quality of life; one study found that the odds ratio for depression in individuals with rosacea is 4.81.10 Patient education is essential, and patients should be encouraged to identify specific triggers so they can minimize exposure when feasible. Common triggers include hot and cold temperature, sunlight, wind, spicy foods, alcohol, exercise, emotional stress, and certain medications such as niacin. Topical steroids frequently are exacerbating, so patients should be encouraged to avoid them and use moisturizers often, given their skin’s increased transepidermal water loss and susceptibility to irritation. In addition, sunscreens are essential to reduce inflammation from reactive oxygen species, which aggravate rosacea.11 For pharmaceutical therapeutics, topical sodium sulfacetamide, metronidazole, and azelaic acid have been shown to be effective in rosacea. For persistent erythema, topical alpha-adrenergic receptor agonists including brimonidine tartrate and oxymetazoline have been shown to reduce erythema by vasoconstricting blood vessels, although some products are associated with a rebound erythema on treatment discontinuation. For moderate to severe rosacea, low-dose oral doxycycline at anti-inflammatory doses (less than 50 mg daily) is the mainstay of therapy. Other oral antibiotics and topical permethrin have been used, and topical ivermectin 1% cream has been approved for inflammatory rosacea.11 Oral beta-blockers also have been successfully used in some patients to reduce erythema and flushing, as well as isotretinoin for refractory, severe rosacea with improvement.
Allison Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. There are no conflicts of interest or financial disclosures for Ms. Han or Dr. Eichenfield.
References
1. J Am Acad Dermatol. 2018 Jan;78(1):148-55.
2. Cutis. 2016 Jul;98(1):49-53.
3. J Eur Acad Dermatol Venereol. 2017 Oct;31(10):1732-8.
4. J Fr Ophtalmol. 2011 Dec;34(10):703-10.
5. J Am Acad Dermatol. 2015 May;72(5):749-58.
6. Indian J Dermatol. 2011 Jan;56(1):30-2.
7. Cutis, 2004. 74(2):99-103.
8. Pediatr Dermatol. 1992 Mar;9(1):22-6.
9. Pediatr Dermatol. 2015 Jul-Aug;32(4):e136-9.
10. Br J Dermatol. 2005 Dec;153(6):1176-81.
11. J Am Acad Dermatol. 2015 May;72(5):761-70.
Rosacea is a chronic inflammatory skin disorder characterized by flushing, telangiectasia, erythema, papules, and pustules, most classically of the central face. Fair-skinned individuals and women are more commonly affected than are men, with age of onset typically around 30 years and older.1 In children and adolescents, rosacea is rare, especially among prepubertal children, so other papulopustular disorders should be considered when a rosacealike picture is present.2 Recurrent chalazia are seen with ocular rosacea and may be a clue to the diagnosis of acne rosacea. An individual’s subtype of rosacea also may transform with time to a different or an additional subtype.
Papulopustular rosacea (subtype II) is characterized by the presence of erythematous, dome-shaped papules distributed in crops in the central facial region. Cheeks, nasolabial folds, and the chin are most commonly affected. Pustules may or may not be present, but comedones are notably absent in an exclusively rosacea disease process. If comedones are present, a diagnosis of acne vulgaris should be considered instead of, or in addition to, rosacea. Pediatric patients with rosacea frequently present with papules and/or pustules, following the development of flushing.2
Ocular rosacea (subtype IV) may range in severity from mild blepharitis to severe keratitis and corneal vascularization. Patients may complain of a foreign body sensation. On external exam, lid margin telangiectasias, blepharitis, conjunctivitis, conjunctival injection, and recurrent chalazia may be frequently seen.3 Ocular rosacea may present without any signs of cutaneous disease; it may be the only form of rosacea (15% of patients in one study of 20 patients had only ocular rosacea)4 or may herald the development of cutaneous involvement. In fact, in children, ocular rosacea is frequently the first sign of disease. (A total of 55% of patients in the same study had both ocular and cutaneous rosacea, with ocular symptoms manifesting before the cutaneous disease). Thus an index of suspicion for rosacea should be maintained when a child presents with ocular findings.2
Other dermatitides resembling rosacea include steroid rosacea, perioral dermatitis, and idiopathic facial aseptic granuloma. Steroid rosacea, also known as iatrosacea, describes an eruption of erythema, papules, and telangiectasias that is clinically indistinguishable from rosacea.6 It results from chronic use of topical steroids, generally high potency, or abrupt withdrawal of steroids. Steroid rosacea should be treated by discontinuation of the steroid via tapered withdrawal.7 Perioral dermatitis, also known as periorificial dermatitis, may also appear rosacea-form. It usually is located around the perioral and perinasal areas, but may extend to the periocular area.8 Idiopathic facial septic granuloma describes erythematous to violaceous nodules of the cheeks and eyelid in children, with chalazia frequently present; it is thought to be associated with rosacea.9
Although the exact pathophysiology of rosacea is unknown, it is clear that the dysregulation of the innate immune system plays a key role in the pathogenesis of rosacea. Studies have found that patients with rosacea have increased expression of cathelicidin, and its activating serine protease, kallikrein.5 Interestingly, UV light, a known trigger of rosacea, induces expression of cathelicidin and its inflammatory cascade.5 Neurovascular signaling is also aberrantly upregulated; vanilloid and ankyrin receptors have been shown to be active in rosacea, and are activated by rosacea-exacerbating stimuli, such as heat, inflammation, and spices. Higher levels of Demodex folliculorum and Staphylococcus epidermis also have been consistently found on the skin of rosacea patients, compared with healthy subjects, though it is unclear what role these pathogens play in the development of rosacea.
Treatment of rosacea is very important given its profound impact on quality of life; one study found that the odds ratio for depression in individuals with rosacea is 4.81.10 Patient education is essential, and patients should be encouraged to identify specific triggers so they can minimize exposure when feasible. Common triggers include hot and cold temperature, sunlight, wind, spicy foods, alcohol, exercise, emotional stress, and certain medications such as niacin. Topical steroids frequently are exacerbating, so patients should be encouraged to avoid them and use moisturizers often, given their skin’s increased transepidermal water loss and susceptibility to irritation. In addition, sunscreens are essential to reduce inflammation from reactive oxygen species, which aggravate rosacea.11 For pharmaceutical therapeutics, topical sodium sulfacetamide, metronidazole, and azelaic acid have been shown to be effective in rosacea. For persistent erythema, topical alpha-adrenergic receptor agonists including brimonidine tartrate and oxymetazoline have been shown to reduce erythema by vasoconstricting blood vessels, although some products are associated with a rebound erythema on treatment discontinuation. For moderate to severe rosacea, low-dose oral doxycycline at anti-inflammatory doses (less than 50 mg daily) is the mainstay of therapy. Other oral antibiotics and topical permethrin have been used, and topical ivermectin 1% cream has been approved for inflammatory rosacea.11 Oral beta-blockers also have been successfully used in some patients to reduce erythema and flushing, as well as isotretinoin for refractory, severe rosacea with improvement.
Allison Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. There are no conflicts of interest or financial disclosures for Ms. Han or Dr. Eichenfield.
References
1. J Am Acad Dermatol. 2018 Jan;78(1):148-55.
2. Cutis. 2016 Jul;98(1):49-53.
3. J Eur Acad Dermatol Venereol. 2017 Oct;31(10):1732-8.
4. J Fr Ophtalmol. 2011 Dec;34(10):703-10.
5. J Am Acad Dermatol. 2015 May;72(5):749-58.
6. Indian J Dermatol. 2011 Jan;56(1):30-2.
7. Cutis, 2004. 74(2):99-103.
8. Pediatr Dermatol. 1992 Mar;9(1):22-6.
9. Pediatr Dermatol. 2015 Jul-Aug;32(4):e136-9.
10. Br J Dermatol. 2005 Dec;153(6):1176-81.
11. J Am Acad Dermatol. 2015 May;72(5):761-70.
Rosacea is a chronic inflammatory skin disorder characterized by flushing, telangiectasia, erythema, papules, and pustules, most classically of the central face. Fair-skinned individuals and women are more commonly affected than are men, with age of onset typically around 30 years and older.1 In children and adolescents, rosacea is rare, especially among prepubertal children, so other papulopustular disorders should be considered when a rosacealike picture is present.2 Recurrent chalazia are seen with ocular rosacea and may be a clue to the diagnosis of acne rosacea. An individual’s subtype of rosacea also may transform with time to a different or an additional subtype.
Papulopustular rosacea (subtype II) is characterized by the presence of erythematous, dome-shaped papules distributed in crops in the central facial region. Cheeks, nasolabial folds, and the chin are most commonly affected. Pustules may or may not be present, but comedones are notably absent in an exclusively rosacea disease process. If comedones are present, a diagnosis of acne vulgaris should be considered instead of, or in addition to, rosacea. Pediatric patients with rosacea frequently present with papules and/or pustules, following the development of flushing.2
Ocular rosacea (subtype IV) may range in severity from mild blepharitis to severe keratitis and corneal vascularization. Patients may complain of a foreign body sensation. On external exam, lid margin telangiectasias, blepharitis, conjunctivitis, conjunctival injection, and recurrent chalazia may be frequently seen.3 Ocular rosacea may present without any signs of cutaneous disease; it may be the only form of rosacea (15% of patients in one study of 20 patients had only ocular rosacea)4 or may herald the development of cutaneous involvement. In fact, in children, ocular rosacea is frequently the first sign of disease. (A total of 55% of patients in the same study had both ocular and cutaneous rosacea, with ocular symptoms manifesting before the cutaneous disease). Thus an index of suspicion for rosacea should be maintained when a child presents with ocular findings.2
Other dermatitides resembling rosacea include steroid rosacea, perioral dermatitis, and idiopathic facial aseptic granuloma. Steroid rosacea, also known as iatrosacea, describes an eruption of erythema, papules, and telangiectasias that is clinically indistinguishable from rosacea.6 It results from chronic use of topical steroids, generally high potency, or abrupt withdrawal of steroids. Steroid rosacea should be treated by discontinuation of the steroid via tapered withdrawal.7 Perioral dermatitis, also known as periorificial dermatitis, may also appear rosacea-form. It usually is located around the perioral and perinasal areas, but may extend to the periocular area.8 Idiopathic facial septic granuloma describes erythematous to violaceous nodules of the cheeks and eyelid in children, with chalazia frequently present; it is thought to be associated with rosacea.9
Although the exact pathophysiology of rosacea is unknown, it is clear that the dysregulation of the innate immune system plays a key role in the pathogenesis of rosacea. Studies have found that patients with rosacea have increased expression of cathelicidin, and its activating serine protease, kallikrein.5 Interestingly, UV light, a known trigger of rosacea, induces expression of cathelicidin and its inflammatory cascade.5 Neurovascular signaling is also aberrantly upregulated; vanilloid and ankyrin receptors have been shown to be active in rosacea, and are activated by rosacea-exacerbating stimuli, such as heat, inflammation, and spices. Higher levels of Demodex folliculorum and Staphylococcus epidermis also have been consistently found on the skin of rosacea patients, compared with healthy subjects, though it is unclear what role these pathogens play in the development of rosacea.
Treatment of rosacea is very important given its profound impact on quality of life; one study found that the odds ratio for depression in individuals with rosacea is 4.81.10 Patient education is essential, and patients should be encouraged to identify specific triggers so they can minimize exposure when feasible. Common triggers include hot and cold temperature, sunlight, wind, spicy foods, alcohol, exercise, emotional stress, and certain medications such as niacin. Topical steroids frequently are exacerbating, so patients should be encouraged to avoid them and use moisturizers often, given their skin’s increased transepidermal water loss and susceptibility to irritation. In addition, sunscreens are essential to reduce inflammation from reactive oxygen species, which aggravate rosacea.11 For pharmaceutical therapeutics, topical sodium sulfacetamide, metronidazole, and azelaic acid have been shown to be effective in rosacea. For persistent erythema, topical alpha-adrenergic receptor agonists including brimonidine tartrate and oxymetazoline have been shown to reduce erythema by vasoconstricting blood vessels, although some products are associated with a rebound erythema on treatment discontinuation. For moderate to severe rosacea, low-dose oral doxycycline at anti-inflammatory doses (less than 50 mg daily) is the mainstay of therapy. Other oral antibiotics and topical permethrin have been used, and topical ivermectin 1% cream has been approved for inflammatory rosacea.11 Oral beta-blockers also have been successfully used in some patients to reduce erythema and flushing, as well as isotretinoin for refractory, severe rosacea with improvement.
Allison Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. There are no conflicts of interest or financial disclosures for Ms. Han or Dr. Eichenfield.
References
1. J Am Acad Dermatol. 2018 Jan;78(1):148-55.
2. Cutis. 2016 Jul;98(1):49-53.
3. J Eur Acad Dermatol Venereol. 2017 Oct;31(10):1732-8.
4. J Fr Ophtalmol. 2011 Dec;34(10):703-10.
5. J Am Acad Dermatol. 2015 May;72(5):749-58.
6. Indian J Dermatol. 2011 Jan;56(1):30-2.
7. Cutis, 2004. 74(2):99-103.
8. Pediatr Dermatol. 1992 Mar;9(1):22-6.
9. Pediatr Dermatol. 2015 Jul-Aug;32(4):e136-9.
10. Br J Dermatol. 2005 Dec;153(6):1176-81.
11. J Am Acad Dermatol. 2015 May;72(5):761-70.
A 16-year-old girl presented with a 6-month history of an erythematous eruption of small papules and pustules around the cheeks and nose. She states the erythema had started first, with periods of feeling flushed that became worse with sun exposure. She saw her primary care physician who prescribed topical steroids. After using the steroids, the rash became worse, and she developed papules and pustules.
Evaluating fever in the first 90 days of life
Fever in the youngest of infants creates a challenge for the pediatric clinician. Fever is a common presentation for serious bacterial infection (SBI) although most fevers are due to viral infection. However, the clinical presentation does not necessarily differ, and the risk for a poor outcome in this age group is substantial.
In the early stages of my pediatric career, most febrile infants less than 90 days of age were evaluated for sepsis, admitted, and treated with antibiotics pending culture results. Group B streptococcal sepsis or Escherichia coli sepsis were common in the first month of life, and Haemophilus influenza type B or Streptococcus pneumoniae in the second and third months of life. The approach to fever in the first 90 days has changed following both the introduction of haemophilus and pneumococcal conjugate vaccines, the experience with risk stratification criteria for identifying infants at low risk for SBI, and the recognition of urinary tract infection (UTI) as a common source of infection in this age group as well as development of criteria for diagnosis.
A further nuance was subsequently added with the introduction of rapid diagnostics for viral infection. Byington et al. found that the majority of febrile infants less than 90 days of age had viral infection with enterovirus, respiratory syncytial virus (RSV), influenza or rotavirus.1 Using the Rochester risk stratification and the presence or absence of viral infection, she demonstrated that the risk of SBI was reduced in both high- and low-risk infants in the presence of viral infection; in low risk infants with viral infection, SBI was identified in 1.8%, compared with 3.1% in those without viral infection, and in high-risk infants. 5.5% has SBI when viral infection was found, compared to 16.7% in the absence of viral infection. She also proposed risk features to identify those infected with herpes simplex virus; age less than 42 days, vesicular rash, elevated alanine transaminase (ALT) and aspartate aminotransferase (AST), CSF pleocytosis, and seizure or twitching.
Greenhow et al. reported on the experience with “serious” bacterial infection in infants less than 90 days of age receiving care at Northern California Kaiser Permanente during the period 2005-2011.2 As pictured, the majority of children have UTI, and smaller numbers have bacteremia or meningitis. A small group of children with UTI have urosepsis as well; those with urosepsis can be differentiated from those with only UTI by age (less than 21 days), clinical exam (ill appearing), and elevated C reactive protein (greater than 20 mg/L) or elevated procalcitonin (greater than 0.5 ng/mL).3 Further evaluation of procalcitonin by other groups appears to validate its role in identifying children at low risk of SBI (procalcitonin less than 0.3 ng/mL).4
Currently, studies of febrile infants less than 90 days of age demonstrate that E. coli dominates in bacteremia, UTI, and meningitis, with Group B streptococcus as the next most frequent pathogen identified.2 Increasingly ampicillin resistance has been reported among E. coli isolates from both early- and late-onset disease as well as rare isolates that are resistant to third generation cephalosporins or gentamicin. Surveillance to identify changes in antimicrobial susceptibility will need to be ongoing to ensure that current approaches for initial therapy in high-risk infants aligns with current susceptibility patterns.
Dr. Pelton is chief of the section of pediatric infectious diseases and coordinator of the maternal-child HIV program at Boston Medical Center. He said he had no relevant financial disclosures. Email him at pdnews@mdedge.com.
References
1. Pediatrics. 2004 Jun;113(6):1662-6.
2. Pediatr Infect Dis J. 2014 Jun;33(6):595-9.
3. Pediatr Infect Dis J. 2015 Jan;34(1):17-21.
4. JAMA Pediatr. 2016;170(1):17-18.
5. “AAP Proposes Update to Evaluating, Managing Febrile Infants Guideline,” The Hospitalist, 2016.
Fever in the youngest of infants creates a challenge for the pediatric clinician. Fever is a common presentation for serious bacterial infection (SBI) although most fevers are due to viral infection. However, the clinical presentation does not necessarily differ, and the risk for a poor outcome in this age group is substantial.
In the early stages of my pediatric career, most febrile infants less than 90 days of age were evaluated for sepsis, admitted, and treated with antibiotics pending culture results. Group B streptococcal sepsis or Escherichia coli sepsis were common in the first month of life, and Haemophilus influenza type B or Streptococcus pneumoniae in the second and third months of life. The approach to fever in the first 90 days has changed following both the introduction of haemophilus and pneumococcal conjugate vaccines, the experience with risk stratification criteria for identifying infants at low risk for SBI, and the recognition of urinary tract infection (UTI) as a common source of infection in this age group as well as development of criteria for diagnosis.
A further nuance was subsequently added with the introduction of rapid diagnostics for viral infection. Byington et al. found that the majority of febrile infants less than 90 days of age had viral infection with enterovirus, respiratory syncytial virus (RSV), influenza or rotavirus.1 Using the Rochester risk stratification and the presence or absence of viral infection, she demonstrated that the risk of SBI was reduced in both high- and low-risk infants in the presence of viral infection; in low risk infants with viral infection, SBI was identified in 1.8%, compared with 3.1% in those without viral infection, and in high-risk infants. 5.5% has SBI when viral infection was found, compared to 16.7% in the absence of viral infection. She also proposed risk features to identify those infected with herpes simplex virus; age less than 42 days, vesicular rash, elevated alanine transaminase (ALT) and aspartate aminotransferase (AST), CSF pleocytosis, and seizure or twitching.
Greenhow et al. reported on the experience with “serious” bacterial infection in infants less than 90 days of age receiving care at Northern California Kaiser Permanente during the period 2005-2011.2 As pictured, the majority of children have UTI, and smaller numbers have bacteremia or meningitis. A small group of children with UTI have urosepsis as well; those with urosepsis can be differentiated from those with only UTI by age (less than 21 days), clinical exam (ill appearing), and elevated C reactive protein (greater than 20 mg/L) or elevated procalcitonin (greater than 0.5 ng/mL).3 Further evaluation of procalcitonin by other groups appears to validate its role in identifying children at low risk of SBI (procalcitonin less than 0.3 ng/mL).4
Currently, studies of febrile infants less than 90 days of age demonstrate that E. coli dominates in bacteremia, UTI, and meningitis, with Group B streptococcus as the next most frequent pathogen identified.2 Increasingly ampicillin resistance has been reported among E. coli isolates from both early- and late-onset disease as well as rare isolates that are resistant to third generation cephalosporins or gentamicin. Surveillance to identify changes in antimicrobial susceptibility will need to be ongoing to ensure that current approaches for initial therapy in high-risk infants aligns with current susceptibility patterns.
Dr. Pelton is chief of the section of pediatric infectious diseases and coordinator of the maternal-child HIV program at Boston Medical Center. He said he had no relevant financial disclosures. Email him at pdnews@mdedge.com.
References
1. Pediatrics. 2004 Jun;113(6):1662-6.
2. Pediatr Infect Dis J. 2014 Jun;33(6):595-9.
3. Pediatr Infect Dis J. 2015 Jan;34(1):17-21.
4. JAMA Pediatr. 2016;170(1):17-18.
5. “AAP Proposes Update to Evaluating, Managing Febrile Infants Guideline,” The Hospitalist, 2016.
Fever in the youngest of infants creates a challenge for the pediatric clinician. Fever is a common presentation for serious bacterial infection (SBI) although most fevers are due to viral infection. However, the clinical presentation does not necessarily differ, and the risk for a poor outcome in this age group is substantial.
In the early stages of my pediatric career, most febrile infants less than 90 days of age were evaluated for sepsis, admitted, and treated with antibiotics pending culture results. Group B streptococcal sepsis or Escherichia coli sepsis were common in the first month of life, and Haemophilus influenza type B or Streptococcus pneumoniae in the second and third months of life. The approach to fever in the first 90 days has changed following both the introduction of haemophilus and pneumococcal conjugate vaccines, the experience with risk stratification criteria for identifying infants at low risk for SBI, and the recognition of urinary tract infection (UTI) as a common source of infection in this age group as well as development of criteria for diagnosis.
A further nuance was subsequently added with the introduction of rapid diagnostics for viral infection. Byington et al. found that the majority of febrile infants less than 90 days of age had viral infection with enterovirus, respiratory syncytial virus (RSV), influenza or rotavirus.1 Using the Rochester risk stratification and the presence or absence of viral infection, she demonstrated that the risk of SBI was reduced in both high- and low-risk infants in the presence of viral infection; in low risk infants with viral infection, SBI was identified in 1.8%, compared with 3.1% in those without viral infection, and in high-risk infants. 5.5% has SBI when viral infection was found, compared to 16.7% in the absence of viral infection. She also proposed risk features to identify those infected with herpes simplex virus; age less than 42 days, vesicular rash, elevated alanine transaminase (ALT) and aspartate aminotransferase (AST), CSF pleocytosis, and seizure or twitching.
Greenhow et al. reported on the experience with “serious” bacterial infection in infants less than 90 days of age receiving care at Northern California Kaiser Permanente during the period 2005-2011.2 As pictured, the majority of children have UTI, and smaller numbers have bacteremia or meningitis. A small group of children with UTI have urosepsis as well; those with urosepsis can be differentiated from those with only UTI by age (less than 21 days), clinical exam (ill appearing), and elevated C reactive protein (greater than 20 mg/L) or elevated procalcitonin (greater than 0.5 ng/mL).3 Further evaluation of procalcitonin by other groups appears to validate its role in identifying children at low risk of SBI (procalcitonin less than 0.3 ng/mL).4
Currently, studies of febrile infants less than 90 days of age demonstrate that E. coli dominates in bacteremia, UTI, and meningitis, with Group B streptococcus as the next most frequent pathogen identified.2 Increasingly ampicillin resistance has been reported among E. coli isolates from both early- and late-onset disease as well as rare isolates that are resistant to third generation cephalosporins or gentamicin. Surveillance to identify changes in antimicrobial susceptibility will need to be ongoing to ensure that current approaches for initial therapy in high-risk infants aligns with current susceptibility patterns.
Dr. Pelton is chief of the section of pediatric infectious diseases and coordinator of the maternal-child HIV program at Boston Medical Center. He said he had no relevant financial disclosures. Email him at pdnews@mdedge.com.
References
1. Pediatrics. 2004 Jun;113(6):1662-6.
2. Pediatr Infect Dis J. 2014 Jun;33(6):595-9.
3. Pediatr Infect Dis J. 2015 Jan;34(1):17-21.
4. JAMA Pediatr. 2016;170(1):17-18.
5. “AAP Proposes Update to Evaluating, Managing Febrile Infants Guideline,” The Hospitalist, 2016.
Pilot study: Topical anticholinergic improved axillary hyperhidrosis in teens, young adults
Nicholas V. Nguyen, MD, of the division of dermatology, Akron Children’s Hospital, Ohio, and his associates reported.
Ten patients aged 13-24 years with moderate to severe axillary hyperhidrosis started the study and were treated with 1 g of oxybutynin 3% gel applied to each axilla every morning for 4 weeks. Of the seven patients who completed the study, four had a two-point reduction in the Hyperhidrosis Disease Severity Scale (HDSS) at week 1 and all seven achieved that endpoint at week 4. Of the five patients who also had hyperhidrosis of the palms, four had a two-point reduction in the HDSS at weeks 1 and 4; the remaining patient reported no change. Of the five patients who also had plantar hyperhidrosis, two reported a reduction at weeks 1 and 4, two reported no change, and one had no change at week 1 and experienced worse hyperhidrosis at week 4.
Safety data were available in the seven patients who completed the study and in two others, one lost to follow-up after the first week, and one patient who dropped out of the study because of a severe adverse event. Three patients reported application site irritation, but it was mild to moderate and did not require any intervention. Two patients reported xerostomia, which resolved by itself, and one reported constipation and blurry vision unrelated to the study drug.
One patient developed pyelonephritis on the sixth day of treatment, possibly related to the study drug. “This patient had a history of kidney transplantation, immunosuppression, and recurrent urinary tract infections. For these reasons, the drug should be used with caution in patients with a history of urinary retention or recurrent urinary tract infections,” Dr. Nguyen and his colleagues said.
The manufacturer discontinued the 3% formulation during enrollment, because of business reasons. A large, randomized, placebo-controlled, double-blind trial to address unanswered questions is warranted, the researchers noted. Oxybutynin 10% gel, approved for treating overactive bladder, is still commercially available.
The study was supported by a Society for Pediatric Dermatology pilot project grant and a Colorado Clinical and Translational Sciences Institute grant.
SOURCE: Nguyen NV et al. Pediatr Dermatol. 2018 Jan 15. doi: 10.1111/pde.13404.
Nicholas V. Nguyen, MD, of the division of dermatology, Akron Children’s Hospital, Ohio, and his associates reported.
Ten patients aged 13-24 years with moderate to severe axillary hyperhidrosis started the study and were treated with 1 g of oxybutynin 3% gel applied to each axilla every morning for 4 weeks. Of the seven patients who completed the study, four had a two-point reduction in the Hyperhidrosis Disease Severity Scale (HDSS) at week 1 and all seven achieved that endpoint at week 4. Of the five patients who also had hyperhidrosis of the palms, four had a two-point reduction in the HDSS at weeks 1 and 4; the remaining patient reported no change. Of the five patients who also had plantar hyperhidrosis, two reported a reduction at weeks 1 and 4, two reported no change, and one had no change at week 1 and experienced worse hyperhidrosis at week 4.
Safety data were available in the seven patients who completed the study and in two others, one lost to follow-up after the first week, and one patient who dropped out of the study because of a severe adverse event. Three patients reported application site irritation, but it was mild to moderate and did not require any intervention. Two patients reported xerostomia, which resolved by itself, and one reported constipation and blurry vision unrelated to the study drug.
One patient developed pyelonephritis on the sixth day of treatment, possibly related to the study drug. “This patient had a history of kidney transplantation, immunosuppression, and recurrent urinary tract infections. For these reasons, the drug should be used with caution in patients with a history of urinary retention or recurrent urinary tract infections,” Dr. Nguyen and his colleagues said.
The manufacturer discontinued the 3% formulation during enrollment, because of business reasons. A large, randomized, placebo-controlled, double-blind trial to address unanswered questions is warranted, the researchers noted. Oxybutynin 10% gel, approved for treating overactive bladder, is still commercially available.
The study was supported by a Society for Pediatric Dermatology pilot project grant and a Colorado Clinical and Translational Sciences Institute grant.
SOURCE: Nguyen NV et al. Pediatr Dermatol. 2018 Jan 15. doi: 10.1111/pde.13404.
Nicholas V. Nguyen, MD, of the division of dermatology, Akron Children’s Hospital, Ohio, and his associates reported.
Ten patients aged 13-24 years with moderate to severe axillary hyperhidrosis started the study and were treated with 1 g of oxybutynin 3% gel applied to each axilla every morning for 4 weeks. Of the seven patients who completed the study, four had a two-point reduction in the Hyperhidrosis Disease Severity Scale (HDSS) at week 1 and all seven achieved that endpoint at week 4. Of the five patients who also had hyperhidrosis of the palms, four had a two-point reduction in the HDSS at weeks 1 and 4; the remaining patient reported no change. Of the five patients who also had plantar hyperhidrosis, two reported a reduction at weeks 1 and 4, two reported no change, and one had no change at week 1 and experienced worse hyperhidrosis at week 4.
Safety data were available in the seven patients who completed the study and in two others, one lost to follow-up after the first week, and one patient who dropped out of the study because of a severe adverse event. Three patients reported application site irritation, but it was mild to moderate and did not require any intervention. Two patients reported xerostomia, which resolved by itself, and one reported constipation and blurry vision unrelated to the study drug.
One patient developed pyelonephritis on the sixth day of treatment, possibly related to the study drug. “This patient had a history of kidney transplantation, immunosuppression, and recurrent urinary tract infections. For these reasons, the drug should be used with caution in patients with a history of urinary retention or recurrent urinary tract infections,” Dr. Nguyen and his colleagues said.
The manufacturer discontinued the 3% formulation during enrollment, because of business reasons. A large, randomized, placebo-controlled, double-blind trial to address unanswered questions is warranted, the researchers noted. Oxybutynin 10% gel, approved for treating overactive bladder, is still commercially available.
The study was supported by a Society for Pediatric Dermatology pilot project grant and a Colorado Clinical and Translational Sciences Institute grant.
SOURCE: Nguyen NV et al. Pediatr Dermatol. 2018 Jan 15. doi: 10.1111/pde.13404.
FROM PEDIATRIC DERMATOLOGY