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Zika virus persists in serum for more than 2 months in newborns
Zika virus infections can persist for more than 2 months after birth in congenitally infected infants, indicating that viral shedding of Zika can take several weeks, according to an Aug. 24, 2016 research letter to the New England Journal of Medicine.
The case study described in the letter involves a male child born after 40 weeks’ gestation in Brazil to a mother who presented with Zika-like symptoms during the 26th week of pregnancy. The child was born with microcephaly – head circumference of 32.5 centimeters – but no signs of neurological abnormalities during the initial postnatal physical examination. Additionally, cerebrospinal fluid, ophthalmologic, and otoacoustic analyses were all deemed normal.
However, low brain parenchyma in the frontal and parietal lobes, along with calcification in the subcortical area and compensatory dilatation of the infratentorial supraventricular system was found via MRI. Furthermore, testing of serum, saliva, and urine at 54 days of age via quantitative real-time polymerase chain reaction assay came back positive for Zika virus. Serum tested at 67 days postbirth also was positive for Zika virus. Testing at day 216, however, showed no signs of Zika virus in serum.
“When the infant was examined on day 54, he had no obvious illness or evidence of any immunocompromising condition,” wrote lead author Danielle B.L. Oliveira, PhD, of the Universidade de São Paulo and her colleagues. “However, by 6 months of age, he showed neuropsychomotor developmental delay, with global hypertonia and spastic hemiplegia, with the right dominant side more severely affected.”
The report comes on the heels of a Florida Department of Health (DOH) announcement that the Zika virus has been found in a pregnant woman residing in Pinellas County, the first such case in that area, making it the third region of Florida in which Zika virus infection has been discovered. As of now, it is the only case of Zika virus in that area.
“DOH has begun door-to-door outreach in Pinellas County and mosquito abatement and reduction activities are also taking place,” the DOH announced in a statement. “DOH still believes ongoing transmission is only taking place within the small identified areas in Wynwood and Miami Beach in Miami-Dade County.”
Zika virus infections can persist for more than 2 months after birth in congenitally infected infants, indicating that viral shedding of Zika can take several weeks, according to an Aug. 24, 2016 research letter to the New England Journal of Medicine.
The case study described in the letter involves a male child born after 40 weeks’ gestation in Brazil to a mother who presented with Zika-like symptoms during the 26th week of pregnancy. The child was born with microcephaly – head circumference of 32.5 centimeters – but no signs of neurological abnormalities during the initial postnatal physical examination. Additionally, cerebrospinal fluid, ophthalmologic, and otoacoustic analyses were all deemed normal.
However, low brain parenchyma in the frontal and parietal lobes, along with calcification in the subcortical area and compensatory dilatation of the infratentorial supraventricular system was found via MRI. Furthermore, testing of serum, saliva, and urine at 54 days of age via quantitative real-time polymerase chain reaction assay came back positive for Zika virus. Serum tested at 67 days postbirth also was positive for Zika virus. Testing at day 216, however, showed no signs of Zika virus in serum.
“When the infant was examined on day 54, he had no obvious illness or evidence of any immunocompromising condition,” wrote lead author Danielle B.L. Oliveira, PhD, of the Universidade de São Paulo and her colleagues. “However, by 6 months of age, he showed neuropsychomotor developmental delay, with global hypertonia and spastic hemiplegia, with the right dominant side more severely affected.”
The report comes on the heels of a Florida Department of Health (DOH) announcement that the Zika virus has been found in a pregnant woman residing in Pinellas County, the first such case in that area, making it the third region of Florida in which Zika virus infection has been discovered. As of now, it is the only case of Zika virus in that area.
“DOH has begun door-to-door outreach in Pinellas County and mosquito abatement and reduction activities are also taking place,” the DOH announced in a statement. “DOH still believes ongoing transmission is only taking place within the small identified areas in Wynwood and Miami Beach in Miami-Dade County.”
Zika virus infections can persist for more than 2 months after birth in congenitally infected infants, indicating that viral shedding of Zika can take several weeks, according to an Aug. 24, 2016 research letter to the New England Journal of Medicine.
The case study described in the letter involves a male child born after 40 weeks’ gestation in Brazil to a mother who presented with Zika-like symptoms during the 26th week of pregnancy. The child was born with microcephaly – head circumference of 32.5 centimeters – but no signs of neurological abnormalities during the initial postnatal physical examination. Additionally, cerebrospinal fluid, ophthalmologic, and otoacoustic analyses were all deemed normal.
However, low brain parenchyma in the frontal and parietal lobes, along with calcification in the subcortical area and compensatory dilatation of the infratentorial supraventricular system was found via MRI. Furthermore, testing of serum, saliva, and urine at 54 days of age via quantitative real-time polymerase chain reaction assay came back positive for Zika virus. Serum tested at 67 days postbirth also was positive for Zika virus. Testing at day 216, however, showed no signs of Zika virus in serum.
“When the infant was examined on day 54, he had no obvious illness or evidence of any immunocompromising condition,” wrote lead author Danielle B.L. Oliveira, PhD, of the Universidade de São Paulo and her colleagues. “However, by 6 months of age, he showed neuropsychomotor developmental delay, with global hypertonia and spastic hemiplegia, with the right dominant side more severely affected.”
The report comes on the heels of a Florida Department of Health (DOH) announcement that the Zika virus has been found in a pregnant woman residing in Pinellas County, the first such case in that area, making it the third region of Florida in which Zika virus infection has been discovered. As of now, it is the only case of Zika virus in that area.
“DOH has begun door-to-door outreach in Pinellas County and mosquito abatement and reduction activities are also taking place,” the DOH announced in a statement. “DOH still believes ongoing transmission is only taking place within the small identified areas in Wynwood and Miami Beach in Miami-Dade County.”
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Hospital medicine
It is important to step back occasionally to survey where one has been and to plot a new heading. In an online Aug. 10, 2016, release, the New England Journal of Medicine posted two opinion pieces that provide perspective on hospital medicine. As is often the case when journalism presents two opinions, the viewpoints represent opposite ends of a spectrum and the truth lies somewhere in between.
In one essay, Robert Wachter, MD, and Lee Goldman, MD, highlight the successful growth of hospital medicine (N Eng J Med. 2016, Aug 10. doi: 10.1056/NEJMp1607958). In just 2 decades, more than 50,000 physicians have changed their focus to the care of inpatients. The authors state that “many stars had to align” for hospital medicine to grow as rapidly as it has. I would argue instead that many talented leaders of the field have moved heaven and earth to create that alignment and birth this field.
In the other essay, Richard Gunderman, MD, focuses on what he sees as having been lost in this evolution (N Eng J Med. 2016, Aug 10. doi: 10.1056/NEJMp1608289). I believe Dr. Gunderman’s viewpoint nostalgically longs for the good old days and a model of an interpersonal doctor-patient relationship that never really existed for a large portion of the population. If you were wealthy, lived most of your life in one location, and had only intermittent or common diseases, then perhaps you had a trusted general internist to provide your medical care and provide the emotional reassurance that nourished both patient and doctor. But in modern medicine, that scenario is uncommon. With large group practices, there is only a small chance that your personal physician will be on call on the night of your admission to a hospital. The next day, as test results and specialty consults trickle in, that personal physician will be trapped in a busy outpatient clinic and not truly available at hospital bedside in “your moment of greatest need,” as Dr. Gunderman phrased it. When your personal physician finally does make rounds, s/he will find the hospital environment inefficient and repeating the same small mistakes that happened to his/her last patient.
I’ve been writing about and teaching professionalism for years. I agree with Dr. Gunderman about the importance of a doctor-patient relationship. I believe reducing physicians to being automatons in a hospital assembly line would be a bad idea. But this essay’s rose-colored and sienna-colored portrait of that relationship is not helpful guidance in the modern world. Surveyors and navigators need sharp, clear vision.
Trade-offs are being made. Many pediatricians in affluent communities do have the opportunity to establish long-term relationships with families, sometimes for multiple generations of children. Those relationships attract medical students into pediatrics and family medicine. I was fortunate enough to establish many of those relationships when I practiced outpatient pediatrics. During my last interstate move, the man packing the picture frames was amused to find amidst my many diplomas a framed crayon drawing. It was a gift to me from a young patient. I told the mover that I would be sadder to have that drawing damaged than if a diploma was damaged in the move. So he wrapped it with extra padding.
Those bonds established with families make up the emotional sustenance throughout a career that justifies the years of sacrifice spent becoming a physician. There is no doubt that it is easier to form those bonds in outpatient pediatrics. At a community hospital, with 7 days on/7 days off scheduling, I usually provide care for the entire hospitalization of a child. That provides emotional satisfaction for both the parents and for me as a physician in ways that 12-hour shifts usually don’t.
The diminishment of those relationships needs to be acknowledged, but not to the exclusion of what a hospitalist can provide. When I practiced general pediatrics and only admitted 1 or 2 children each week, I was often frustrated by inefficiency and errors in the hospital, but I had little recourse for changing it. As a hospitalist admitting 500 patients per year, I can perform problem solving and devote resources to continuously improve the quality and safety of inpatient care. I provide those improvements to all patients admitted to the hospital, whether they have a medical home or not. That fosters social justice. As a function-over-fashion person, that success is emotionally rewarding, too.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@frontlinemedcom.com.
It is important to step back occasionally to survey where one has been and to plot a new heading. In an online Aug. 10, 2016, release, the New England Journal of Medicine posted two opinion pieces that provide perspective on hospital medicine. As is often the case when journalism presents two opinions, the viewpoints represent opposite ends of a spectrum and the truth lies somewhere in between.
In one essay, Robert Wachter, MD, and Lee Goldman, MD, highlight the successful growth of hospital medicine (N Eng J Med. 2016, Aug 10. doi: 10.1056/NEJMp1607958). In just 2 decades, more than 50,000 physicians have changed their focus to the care of inpatients. The authors state that “many stars had to align” for hospital medicine to grow as rapidly as it has. I would argue instead that many talented leaders of the field have moved heaven and earth to create that alignment and birth this field.
In the other essay, Richard Gunderman, MD, focuses on what he sees as having been lost in this evolution (N Eng J Med. 2016, Aug 10. doi: 10.1056/NEJMp1608289). I believe Dr. Gunderman’s viewpoint nostalgically longs for the good old days and a model of an interpersonal doctor-patient relationship that never really existed for a large portion of the population. If you were wealthy, lived most of your life in one location, and had only intermittent or common diseases, then perhaps you had a trusted general internist to provide your medical care and provide the emotional reassurance that nourished both patient and doctor. But in modern medicine, that scenario is uncommon. With large group practices, there is only a small chance that your personal physician will be on call on the night of your admission to a hospital. The next day, as test results and specialty consults trickle in, that personal physician will be trapped in a busy outpatient clinic and not truly available at hospital bedside in “your moment of greatest need,” as Dr. Gunderman phrased it. When your personal physician finally does make rounds, s/he will find the hospital environment inefficient and repeating the same small mistakes that happened to his/her last patient.
I’ve been writing about and teaching professionalism for years. I agree with Dr. Gunderman about the importance of a doctor-patient relationship. I believe reducing physicians to being automatons in a hospital assembly line would be a bad idea. But this essay’s rose-colored and sienna-colored portrait of that relationship is not helpful guidance in the modern world. Surveyors and navigators need sharp, clear vision.
Trade-offs are being made. Many pediatricians in affluent communities do have the opportunity to establish long-term relationships with families, sometimes for multiple generations of children. Those relationships attract medical students into pediatrics and family medicine. I was fortunate enough to establish many of those relationships when I practiced outpatient pediatrics. During my last interstate move, the man packing the picture frames was amused to find amidst my many diplomas a framed crayon drawing. It was a gift to me from a young patient. I told the mover that I would be sadder to have that drawing damaged than if a diploma was damaged in the move. So he wrapped it with extra padding.
Those bonds established with families make up the emotional sustenance throughout a career that justifies the years of sacrifice spent becoming a physician. There is no doubt that it is easier to form those bonds in outpatient pediatrics. At a community hospital, with 7 days on/7 days off scheduling, I usually provide care for the entire hospitalization of a child. That provides emotional satisfaction for both the parents and for me as a physician in ways that 12-hour shifts usually don’t.
The diminishment of those relationships needs to be acknowledged, but not to the exclusion of what a hospitalist can provide. When I practiced general pediatrics and only admitted 1 or 2 children each week, I was often frustrated by inefficiency and errors in the hospital, but I had little recourse for changing it. As a hospitalist admitting 500 patients per year, I can perform problem solving and devote resources to continuously improve the quality and safety of inpatient care. I provide those improvements to all patients admitted to the hospital, whether they have a medical home or not. That fosters social justice. As a function-over-fashion person, that success is emotionally rewarding, too.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@frontlinemedcom.com.
It is important to step back occasionally to survey where one has been and to plot a new heading. In an online Aug. 10, 2016, release, the New England Journal of Medicine posted two opinion pieces that provide perspective on hospital medicine. As is often the case when journalism presents two opinions, the viewpoints represent opposite ends of a spectrum and the truth lies somewhere in between.
In one essay, Robert Wachter, MD, and Lee Goldman, MD, highlight the successful growth of hospital medicine (N Eng J Med. 2016, Aug 10. doi: 10.1056/NEJMp1607958). In just 2 decades, more than 50,000 physicians have changed their focus to the care of inpatients. The authors state that “many stars had to align” for hospital medicine to grow as rapidly as it has. I would argue instead that many talented leaders of the field have moved heaven and earth to create that alignment and birth this field.
In the other essay, Richard Gunderman, MD, focuses on what he sees as having been lost in this evolution (N Eng J Med. 2016, Aug 10. doi: 10.1056/NEJMp1608289). I believe Dr. Gunderman’s viewpoint nostalgically longs for the good old days and a model of an interpersonal doctor-patient relationship that never really existed for a large portion of the population. If you were wealthy, lived most of your life in one location, and had only intermittent or common diseases, then perhaps you had a trusted general internist to provide your medical care and provide the emotional reassurance that nourished both patient and doctor. But in modern medicine, that scenario is uncommon. With large group practices, there is only a small chance that your personal physician will be on call on the night of your admission to a hospital. The next day, as test results and specialty consults trickle in, that personal physician will be trapped in a busy outpatient clinic and not truly available at hospital bedside in “your moment of greatest need,” as Dr. Gunderman phrased it. When your personal physician finally does make rounds, s/he will find the hospital environment inefficient and repeating the same small mistakes that happened to his/her last patient.
I’ve been writing about and teaching professionalism for years. I agree with Dr. Gunderman about the importance of a doctor-patient relationship. I believe reducing physicians to being automatons in a hospital assembly line would be a bad idea. But this essay’s rose-colored and sienna-colored portrait of that relationship is not helpful guidance in the modern world. Surveyors and navigators need sharp, clear vision.
Trade-offs are being made. Many pediatricians in affluent communities do have the opportunity to establish long-term relationships with families, sometimes for multiple generations of children. Those relationships attract medical students into pediatrics and family medicine. I was fortunate enough to establish many of those relationships when I practiced outpatient pediatrics. During my last interstate move, the man packing the picture frames was amused to find amidst my many diplomas a framed crayon drawing. It was a gift to me from a young patient. I told the mover that I would be sadder to have that drawing damaged than if a diploma was damaged in the move. So he wrapped it with extra padding.
Those bonds established with families make up the emotional sustenance throughout a career that justifies the years of sacrifice spent becoming a physician. There is no doubt that it is easier to form those bonds in outpatient pediatrics. At a community hospital, with 7 days on/7 days off scheduling, I usually provide care for the entire hospitalization of a child. That provides emotional satisfaction for both the parents and for me as a physician in ways that 12-hour shifts usually don’t.
The diminishment of those relationships needs to be acknowledged, but not to the exclusion of what a hospitalist can provide. When I practiced general pediatrics and only admitted 1 or 2 children each week, I was often frustrated by inefficiency and errors in the hospital, but I had little recourse for changing it. As a hospitalist admitting 500 patients per year, I can perform problem solving and devote resources to continuously improve the quality and safety of inpatient care. I provide those improvements to all patients admitted to the hospital, whether they have a medical home or not. That fosters social justice. As a function-over-fashion person, that success is emotionally rewarding, too.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@frontlinemedcom.com.
U.S. breastfeeding rates rise for newborns
More than 80% of mothers in the United States started breastfeeding their infants at birth in 2013, 52% were breastfeeding at 6 months, and 30% were breastfeeding at 12 months, according to a breastfeeding report card from the Centers for Disease Control and Prevention.
Overall, 29 states, including Washington, D.C., and Puerto Rico, have met the Healthy People 2020 objective of 81.9% of infants who have ever been breastfed. However, only 12 states met the breastfeeding goal of 60.6% of infants breastfeeding at 6 months of age.
“High breastfeeding initiation rates show that most mothers in the U.S. want to breastfeed and are trying to do so,” according to the report. But the lower rates at 6 and 12 months “suggest that mothers, in part, may not be getting the support they need, such as from health care providers, family members, and employers.”
In the report, CDC officials call on states to use their breastfeeding statistics as a call to action for goals including monitoring breastfeeding progress, sharing success stories from effective hospital and community programs, building state profiles of community breastfeeding support, and identifying ways to increase breastfeeding rates through maternity care programs and peer and professional support networks.
The 2016 Breastfeeding Report Card included data from all 50 states, the District of Columbia, and Puerto Rico. The data were taken from the U.S. National Immunization Surveys from 2014 and 2015 and referred to infants born in 2013. “Since breastfeeding data are obtained by maternal recall when children are between 19 and 35 months of age, breastfeeding rates are analyzed by birth cohort rather than survey year,” the researchers noted.
Read the complete findings on the CDC website.
More than 80% of mothers in the United States started breastfeeding their infants at birth in 2013, 52% were breastfeeding at 6 months, and 30% were breastfeeding at 12 months, according to a breastfeeding report card from the Centers for Disease Control and Prevention.
Overall, 29 states, including Washington, D.C., and Puerto Rico, have met the Healthy People 2020 objective of 81.9% of infants who have ever been breastfed. However, only 12 states met the breastfeeding goal of 60.6% of infants breastfeeding at 6 months of age.
“High breastfeeding initiation rates show that most mothers in the U.S. want to breastfeed and are trying to do so,” according to the report. But the lower rates at 6 and 12 months “suggest that mothers, in part, may not be getting the support they need, such as from health care providers, family members, and employers.”
In the report, CDC officials call on states to use their breastfeeding statistics as a call to action for goals including monitoring breastfeeding progress, sharing success stories from effective hospital and community programs, building state profiles of community breastfeeding support, and identifying ways to increase breastfeeding rates through maternity care programs and peer and professional support networks.
The 2016 Breastfeeding Report Card included data from all 50 states, the District of Columbia, and Puerto Rico. The data were taken from the U.S. National Immunization Surveys from 2014 and 2015 and referred to infants born in 2013. “Since breastfeeding data are obtained by maternal recall when children are between 19 and 35 months of age, breastfeeding rates are analyzed by birth cohort rather than survey year,” the researchers noted.
Read the complete findings on the CDC website.
More than 80% of mothers in the United States started breastfeeding their infants at birth in 2013, 52% were breastfeeding at 6 months, and 30% were breastfeeding at 12 months, according to a breastfeeding report card from the Centers for Disease Control and Prevention.
Overall, 29 states, including Washington, D.C., and Puerto Rico, have met the Healthy People 2020 objective of 81.9% of infants who have ever been breastfed. However, only 12 states met the breastfeeding goal of 60.6% of infants breastfeeding at 6 months of age.
“High breastfeeding initiation rates show that most mothers in the U.S. want to breastfeed and are trying to do so,” according to the report. But the lower rates at 6 and 12 months “suggest that mothers, in part, may not be getting the support they need, such as from health care providers, family members, and employers.”
In the report, CDC officials call on states to use their breastfeeding statistics as a call to action for goals including monitoring breastfeeding progress, sharing success stories from effective hospital and community programs, building state profiles of community breastfeeding support, and identifying ways to increase breastfeeding rates through maternity care programs and peer and professional support networks.
The 2016 Breastfeeding Report Card included data from all 50 states, the District of Columbia, and Puerto Rico. The data were taken from the U.S. National Immunization Surveys from 2014 and 2015 and referred to infants born in 2013. “Since breastfeeding data are obtained by maternal recall when children are between 19 and 35 months of age, breastfeeding rates are analyzed by birth cohort rather than survey year,” the researchers noted.
Read the complete findings on the CDC website.
Rotavirus vaccine again linked to small increase in risk of intussusception hospitalization
The first dose of rotavirus vaccine was again linked to a small, short-term increase in the risk of hospitalization for intussusception, but the benefits of the vaccine exceed this risk, according to a report.
In absolute numbers, there were an estimated 7 to 26 more intussusception cases per year among U.S. children aged 8-11 weeks during the postvaccine era, compared with the prevaccine era, said Jacqueline E. Tate, PhD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, and her associates.
The increased risk did not extend to older children, which “is consistent with other U.S. studies,” the investigators said. “[Given] the magnitude of the declines in rotavirus disease compared with the small increased risk of intussusception, the public health benefits of rotavirus vaccination far exceed the increased risk of intussusception.”
Human rotavirus vaccines have been linked to rare events of intussusception since at least 1999, when Rotashield was withdrawn from the market for this reason. The next two rotavirus vaccines to receive Food and Drug Administration approval, RotaTeq and Rotarix, were not linked to intussusception in large trials or early postmarketing studies, but were estimated to cause 1-5 excess cases of intussusception per 100,000 population in more recent studies. Furthermore, a prior analysis of U.S. hospital discharge data found a small increase in the risk of intussusception hospitalization among 8- to 11-week-olds between 2007 to 2009, compared with baseline data from the prevaccine era, the investigators noted (Pediatrics. 2016 Aug 24. doi: 10.1542/peds.2016-1082).
To build on that analysis, they calculated rates of intussusception between 2000 and 2013 overall and among recommended age windows for rotavirus vaccination, which are 6-14 weeks for the first dose, 15-24 weeks for the second dose, and 25-34 weeks for the third dose. For consistency, they also looked at hospitalization rates among children aged 8-11 weeks.
The investigators identified 15,231 intussusception hospitalizations among children under 1 year of age during the study from 2000-2013. There were no overall trends in intussusception hospitalizations for all children under 1 year of age or subgroups of children aged 15-24 weeks or 25-34 weeks. Among children aged 8-11 weeks, intussusception hospitalization rates did rise significantly during the postvaccine era, compared with the prevaccine era for all years except 2011 and 2013. Excluding those two years, annual rates of intussusception hospitalizations among 8- to 11-week-olds were 46%-101% higher (16.7 to 22.9 hospitalizations per 100,000 population) during the postvaccine era than during the prevaccine era (11.4 hospitalizations per 100,000 population).
These results are “consistent with other U.S. studies that have been able to associate an increased risk of intussusception in the first week after the first dose of vaccine,” the researchers concluded. The advent of rotavirus vaccination prevented more than 176,000 hospitalizations, 242,000 emergency department visits, and 1.1 million outpatient visits from 2007 to 2011 (JAMA. 2015;313(22):2282-4), they noted.
The investigators reported no external funding sources and had no disclosures.
The first dose of rotavirus vaccine was again linked to a small, short-term increase in the risk of hospitalization for intussusception, but the benefits of the vaccine exceed this risk, according to a report.
In absolute numbers, there were an estimated 7 to 26 more intussusception cases per year among U.S. children aged 8-11 weeks during the postvaccine era, compared with the prevaccine era, said Jacqueline E. Tate, PhD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, and her associates.
The increased risk did not extend to older children, which “is consistent with other U.S. studies,” the investigators said. “[Given] the magnitude of the declines in rotavirus disease compared with the small increased risk of intussusception, the public health benefits of rotavirus vaccination far exceed the increased risk of intussusception.”
Human rotavirus vaccines have been linked to rare events of intussusception since at least 1999, when Rotashield was withdrawn from the market for this reason. The next two rotavirus vaccines to receive Food and Drug Administration approval, RotaTeq and Rotarix, were not linked to intussusception in large trials or early postmarketing studies, but were estimated to cause 1-5 excess cases of intussusception per 100,000 population in more recent studies. Furthermore, a prior analysis of U.S. hospital discharge data found a small increase in the risk of intussusception hospitalization among 8- to 11-week-olds between 2007 to 2009, compared with baseline data from the prevaccine era, the investigators noted (Pediatrics. 2016 Aug 24. doi: 10.1542/peds.2016-1082).
To build on that analysis, they calculated rates of intussusception between 2000 and 2013 overall and among recommended age windows for rotavirus vaccination, which are 6-14 weeks for the first dose, 15-24 weeks for the second dose, and 25-34 weeks for the third dose. For consistency, they also looked at hospitalization rates among children aged 8-11 weeks.
The investigators identified 15,231 intussusception hospitalizations among children under 1 year of age during the study from 2000-2013. There were no overall trends in intussusception hospitalizations for all children under 1 year of age or subgroups of children aged 15-24 weeks or 25-34 weeks. Among children aged 8-11 weeks, intussusception hospitalization rates did rise significantly during the postvaccine era, compared with the prevaccine era for all years except 2011 and 2013. Excluding those two years, annual rates of intussusception hospitalizations among 8- to 11-week-olds were 46%-101% higher (16.7 to 22.9 hospitalizations per 100,000 population) during the postvaccine era than during the prevaccine era (11.4 hospitalizations per 100,000 population).
These results are “consistent with other U.S. studies that have been able to associate an increased risk of intussusception in the first week after the first dose of vaccine,” the researchers concluded. The advent of rotavirus vaccination prevented more than 176,000 hospitalizations, 242,000 emergency department visits, and 1.1 million outpatient visits from 2007 to 2011 (JAMA. 2015;313(22):2282-4), they noted.
The investigators reported no external funding sources and had no disclosures.
The first dose of rotavirus vaccine was again linked to a small, short-term increase in the risk of hospitalization for intussusception, but the benefits of the vaccine exceed this risk, according to a report.
In absolute numbers, there were an estimated 7 to 26 more intussusception cases per year among U.S. children aged 8-11 weeks during the postvaccine era, compared with the prevaccine era, said Jacqueline E. Tate, PhD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, and her associates.
The increased risk did not extend to older children, which “is consistent with other U.S. studies,” the investigators said. “[Given] the magnitude of the declines in rotavirus disease compared with the small increased risk of intussusception, the public health benefits of rotavirus vaccination far exceed the increased risk of intussusception.”
Human rotavirus vaccines have been linked to rare events of intussusception since at least 1999, when Rotashield was withdrawn from the market for this reason. The next two rotavirus vaccines to receive Food and Drug Administration approval, RotaTeq and Rotarix, were not linked to intussusception in large trials or early postmarketing studies, but were estimated to cause 1-5 excess cases of intussusception per 100,000 population in more recent studies. Furthermore, a prior analysis of U.S. hospital discharge data found a small increase in the risk of intussusception hospitalization among 8- to 11-week-olds between 2007 to 2009, compared with baseline data from the prevaccine era, the investigators noted (Pediatrics. 2016 Aug 24. doi: 10.1542/peds.2016-1082).
To build on that analysis, they calculated rates of intussusception between 2000 and 2013 overall and among recommended age windows for rotavirus vaccination, which are 6-14 weeks for the first dose, 15-24 weeks for the second dose, and 25-34 weeks for the third dose. For consistency, they also looked at hospitalization rates among children aged 8-11 weeks.
The investigators identified 15,231 intussusception hospitalizations among children under 1 year of age during the study from 2000-2013. There were no overall trends in intussusception hospitalizations for all children under 1 year of age or subgroups of children aged 15-24 weeks or 25-34 weeks. Among children aged 8-11 weeks, intussusception hospitalization rates did rise significantly during the postvaccine era, compared with the prevaccine era for all years except 2011 and 2013. Excluding those two years, annual rates of intussusception hospitalizations among 8- to 11-week-olds were 46%-101% higher (16.7 to 22.9 hospitalizations per 100,000 population) during the postvaccine era than during the prevaccine era (11.4 hospitalizations per 100,000 population).
These results are “consistent with other U.S. studies that have been able to associate an increased risk of intussusception in the first week after the first dose of vaccine,” the researchers concluded. The advent of rotavirus vaccination prevented more than 176,000 hospitalizations, 242,000 emergency department visits, and 1.1 million outpatient visits from 2007 to 2011 (JAMA. 2015;313(22):2282-4), they noted.
The investigators reported no external funding sources and had no disclosures.
FROM PEDIATRICS
Key clinical point: The first dose of rotavirus vaccination is associated with a slight increase in risk of hospitalization for intussusception.
Major finding: Among 8-week-old infants to 11-week-old infants, rates of intussusception hospitalizations were significantly (46% to 101%) higher than in the prevaccine era for all postvaccine years except 2011 and 2013.
Data source: An analysis of hospitalization data from 2000 through 2013 from the State Inpatient Database, which covers 26 U.S. states.
Disclosures: The investigators had no external funding sources and no disclosures.
Food allergy testing only rarely needed for AD patients
BOSTON – Between 15% and 30% of children with moderate to severe atopic dermatitis also have food allergies, but the allergies are a trigger for AD in only a small subset of patients, according to Mercedes E. Gonzalez, MD.
In most cases, allergy testing is not indicated, she said at the American Academy of Dermatology summer meeting.
She described a scenario involving a parent who is concerned that a food allergy is causing her child’s AD. The child has had no hives, no lip swelling, and no other signs of immediate hypersensitivity. In such a case, the best approach is to treat with topical therapies and follow the patient clinically.
“Allergy testing independent of history is not recommended,” she said.
However, in cases involving a significant concern about food allergy, such as the presence of hives or urticaria, or when the child has severe dermatitis that is not improving with optimized topical therapies, an assessment can be undertaken, said Dr. Gonzalez of the University of Miami.
She recommended limited food allergy testing – for common culprits such as cow’s milk, eggs, wheat, soy, and peanuts – in children younger than age 5 years with moderate to severe AD, if the AD persists despite optimized topical treatment and/or a history of immediate and reproducible reaction after ingestion of a specific food.
Food elimination diets based solely on the findings of food allergy test results are not recommended for managing AD, she noted.
If a patient has true immunoglobulin E–mediated allergy they should practice avoidance to prevent potential serious health sequelae, Dr. Gonzalez said.
When testing is done, keep in mind that skin prick tests and serum-specific IgE levels have high negative predictive values above 95%, but low specificity and positive predictive values of 40%-60%, she pointed out. Positive tests should be verified with a food elimination diet or oral food challenge.
Also, most children develop tolerance to the foods over time and should be retested, Dr. Gonzalez said.
Early peanut introduction advised in infants with AD
There is no need to delay the introduction of peanuts into the diet of an infant at high risk for atopic dermatitis, Dr. Gonzalez said.
A 2015 consensus communication from the American Academy of Pediatrics and numerous other organizations, including the American Academy of Allergy, Asthma & Immunology and the Society of Pediatric Dermatology, offering interim guidance on the topic calls for introduction of peanut products into the diets of high-risk infants in countries where peanut allergy is present, she said.
High-risk infants were defined in the study as those with egg allergy and/or severe eczema.
The guidance, which the AAP “endorses and accepts as its policy” pending more formal guidelines currently in development, was based largely on findings from the LEAP (Learn Early About Peanut Allergy) trial – a 5-year randomized, controlled trial of 640 high-risk infants aged 4-11 months. The trial showed that 17.2% of infants who avoided peanuts had peanut allergy at 5 years, compared with 3.2% of those with peanut consumption three times weekly, a relative risk reduction of 81% (N Engl J Med. 2015; 372:803-13).
In infants with egg allergy or severe eczema, an evaluation by an allergist or dermatologist familiar with the guidance may be warranted to assist in implementing the suggestions, Dr. Gonzalez said.
Dr. Gonzalez reported receiving honoraria for serving as a speaker and/or advisory board member for Pierre Fabre Dermatologie, Anacor Pharmaceuticals, Encore Dermatology, and PuraCap Pharmaceutical.
BOSTON – Between 15% and 30% of children with moderate to severe atopic dermatitis also have food allergies, but the allergies are a trigger for AD in only a small subset of patients, according to Mercedes E. Gonzalez, MD.
In most cases, allergy testing is not indicated, she said at the American Academy of Dermatology summer meeting.
She described a scenario involving a parent who is concerned that a food allergy is causing her child’s AD. The child has had no hives, no lip swelling, and no other signs of immediate hypersensitivity. In such a case, the best approach is to treat with topical therapies and follow the patient clinically.
“Allergy testing independent of history is not recommended,” she said.
However, in cases involving a significant concern about food allergy, such as the presence of hives or urticaria, or when the child has severe dermatitis that is not improving with optimized topical therapies, an assessment can be undertaken, said Dr. Gonzalez of the University of Miami.
She recommended limited food allergy testing – for common culprits such as cow’s milk, eggs, wheat, soy, and peanuts – in children younger than age 5 years with moderate to severe AD, if the AD persists despite optimized topical treatment and/or a history of immediate and reproducible reaction after ingestion of a specific food.
Food elimination diets based solely on the findings of food allergy test results are not recommended for managing AD, she noted.
If a patient has true immunoglobulin E–mediated allergy they should practice avoidance to prevent potential serious health sequelae, Dr. Gonzalez said.
When testing is done, keep in mind that skin prick tests and serum-specific IgE levels have high negative predictive values above 95%, but low specificity and positive predictive values of 40%-60%, she pointed out. Positive tests should be verified with a food elimination diet or oral food challenge.
Also, most children develop tolerance to the foods over time and should be retested, Dr. Gonzalez said.
Early peanut introduction advised in infants with AD
There is no need to delay the introduction of peanuts into the diet of an infant at high risk for atopic dermatitis, Dr. Gonzalez said.
A 2015 consensus communication from the American Academy of Pediatrics and numerous other organizations, including the American Academy of Allergy, Asthma & Immunology and the Society of Pediatric Dermatology, offering interim guidance on the topic calls for introduction of peanut products into the diets of high-risk infants in countries where peanut allergy is present, she said.
High-risk infants were defined in the study as those with egg allergy and/or severe eczema.
The guidance, which the AAP “endorses and accepts as its policy” pending more formal guidelines currently in development, was based largely on findings from the LEAP (Learn Early About Peanut Allergy) trial – a 5-year randomized, controlled trial of 640 high-risk infants aged 4-11 months. The trial showed that 17.2% of infants who avoided peanuts had peanut allergy at 5 years, compared with 3.2% of those with peanut consumption three times weekly, a relative risk reduction of 81% (N Engl J Med. 2015; 372:803-13).
In infants with egg allergy or severe eczema, an evaluation by an allergist or dermatologist familiar with the guidance may be warranted to assist in implementing the suggestions, Dr. Gonzalez said.
Dr. Gonzalez reported receiving honoraria for serving as a speaker and/or advisory board member for Pierre Fabre Dermatologie, Anacor Pharmaceuticals, Encore Dermatology, and PuraCap Pharmaceutical.
BOSTON – Between 15% and 30% of children with moderate to severe atopic dermatitis also have food allergies, but the allergies are a trigger for AD in only a small subset of patients, according to Mercedes E. Gonzalez, MD.
In most cases, allergy testing is not indicated, she said at the American Academy of Dermatology summer meeting.
She described a scenario involving a parent who is concerned that a food allergy is causing her child’s AD. The child has had no hives, no lip swelling, and no other signs of immediate hypersensitivity. In such a case, the best approach is to treat with topical therapies and follow the patient clinically.
“Allergy testing independent of history is not recommended,” she said.
However, in cases involving a significant concern about food allergy, such as the presence of hives or urticaria, or when the child has severe dermatitis that is not improving with optimized topical therapies, an assessment can be undertaken, said Dr. Gonzalez of the University of Miami.
She recommended limited food allergy testing – for common culprits such as cow’s milk, eggs, wheat, soy, and peanuts – in children younger than age 5 years with moderate to severe AD, if the AD persists despite optimized topical treatment and/or a history of immediate and reproducible reaction after ingestion of a specific food.
Food elimination diets based solely on the findings of food allergy test results are not recommended for managing AD, she noted.
If a patient has true immunoglobulin E–mediated allergy they should practice avoidance to prevent potential serious health sequelae, Dr. Gonzalez said.
When testing is done, keep in mind that skin prick tests and serum-specific IgE levels have high negative predictive values above 95%, but low specificity and positive predictive values of 40%-60%, she pointed out. Positive tests should be verified with a food elimination diet or oral food challenge.
Also, most children develop tolerance to the foods over time and should be retested, Dr. Gonzalez said.
Early peanut introduction advised in infants with AD
There is no need to delay the introduction of peanuts into the diet of an infant at high risk for atopic dermatitis, Dr. Gonzalez said.
A 2015 consensus communication from the American Academy of Pediatrics and numerous other organizations, including the American Academy of Allergy, Asthma & Immunology and the Society of Pediatric Dermatology, offering interim guidance on the topic calls for introduction of peanut products into the diets of high-risk infants in countries where peanut allergy is present, she said.
High-risk infants were defined in the study as those with egg allergy and/or severe eczema.
The guidance, which the AAP “endorses and accepts as its policy” pending more formal guidelines currently in development, was based largely on findings from the LEAP (Learn Early About Peanut Allergy) trial – a 5-year randomized, controlled trial of 640 high-risk infants aged 4-11 months. The trial showed that 17.2% of infants who avoided peanuts had peanut allergy at 5 years, compared with 3.2% of those with peanut consumption three times weekly, a relative risk reduction of 81% (N Engl J Med. 2015; 372:803-13).
In infants with egg allergy or severe eczema, an evaluation by an allergist or dermatologist familiar with the guidance may be warranted to assist in implementing the suggestions, Dr. Gonzalez said.
Dr. Gonzalez reported receiving honoraria for serving as a speaker and/or advisory board member for Pierre Fabre Dermatologie, Anacor Pharmaceuticals, Encore Dermatology, and PuraCap Pharmaceutical.
EXPERT ANALYSIS FROM AAD SUMMER ACADEMY 2016
Most sepsis cases begin outside of the hospital
Sepsis is a medical emergency that begins outside of the hospital in 79% of cases. In addition, 72% of patients with sepsis had recently used healthcare services or had chronic diseases that required frequent medical care.
Those are key findings from a special report in Morbidity and Mortality Weekly Report published by the U.S. Centers for Disease Control and Prevention (Morb Mortal Wkly Rep. 2016 Aug 23. doi: 10.15585/mmwr.mm6533e1).
“The treatment of sepsis is a race against time,” CDC Director Tom Frieden, MD, said during a media teleconference about the report. “We can protect more people from sepsis by informing patients and their families, treating infections promptly, and acting fast when sepsis does occur.”
Each year, between 1 and 3 million people in the United States are diagnosed with sepsis, a syndrome marked by the body’s overwhelming and life-threatening response to an infection, Dr. Frieden said. Of these, 15%-30% will die from the condition, for which there is no blood test. “Health care providers are on the front lines of both sepsis prevention and early recognition,” he emphasized. “Prevention really is possible.” For example, he continued, if a patient with diabetes visits their regular doctor and is found to have increased blood sugar and a small wound on their foot, “this is a prime opportunity to think about infection and reduce the risk of sepsis. In addition to treating the infection, the clinician can inform the patient and family members about how to care for the wound, how to recognize the signs that the infection may be getting worse, and when to seek additional medical care. If the infection gets worse the patient could be at risk for sepsis. Taking the opportunity to both treat and inform patients could save their life, and helping patients know to ask, ‘Could this be sepsis?’ empowers patients and families and could save lives.”
In an effort to describe the characteristics of patients with sepsis, researchers from the CDC and from New York State conducted a retrospective review of medical records from 246 adults and 79 children with sepsis who were treated at four New York hospitals. They found that sepsis most often occurs in patients older than age 65 years and in infants younger than 1 year of age, and the median hospital length of stay is 10 days. Six key signs and symptoms of sepsis were shivering or feeling cold; pain or discomfort; clammy or sweaty skin; being confused or disoriented; shortness of breath, and having a rapid heartbeat. “People with chronic diseases such as diabetes or weakened immune systems from things like tobacco use are at higher risk of sepsis,” Dr. Frieden said. “But even healthy people can develop sepsis from an infection, especially if it’s not treated properly and promptly.”
The four types of infections most commonly associated with sepsis include those involving the lungs, urinary tract, skin, and intestines, while the most common germs that can cause sepsis are Staphylococcus aureus, Escherichia coli (E. coli), and some types of Streptococcus. Infection prevention strategies such as increasing vaccination rates for pneumococcal disease and for influenza are likely to reduce the incidence of sepsis, according to the report. “We could also improve infections by improving handwashing at health care facilities as well as in the community,” Dr. Frieden added. “We can [also] improve recognition of sepsis both in the community and in health care facilities and act fast if sepsis is suspected in a patient. We’ve been able to reduce the rates of some infections that cause sepsis in health care facilities by half, but preventing more infections and stopping the spread of antibiotic resistant infections will protect even more patients from sepsis.”
Mitchell Levy, MD, founding member of the Surviving Sepsis Campaign, said during the teleconference that clinicians have made “tremendous progress in sepsis,” despite current challenges. “First, we now understand the importance of early identification and treatment of sepsis,” he said. “Second, we have seen improved survival through routine screening and treatment that is integrated into the work flow of hospitals. And third, frontline health care providers really do make a difference. What’s clear is that we need to expand these successes to other parts of hospitals and to other care locations.”
Forthcoming free CDC webinars related to sepsis for health care providers include one on Sept. 13 at 3 p.m., ET, entitled “Advances in Sepsis: Protecting Patients Throughout the Lifespan.” Another webinar will be offered on Sept. 22 at 2 p.m., ET, entitled “Empowering Nurses for Early Sepsis Recognition.”
Sepsis is a medical emergency that begins outside of the hospital in 79% of cases. In addition, 72% of patients with sepsis had recently used healthcare services or had chronic diseases that required frequent medical care.
Those are key findings from a special report in Morbidity and Mortality Weekly Report published by the U.S. Centers for Disease Control and Prevention (Morb Mortal Wkly Rep. 2016 Aug 23. doi: 10.15585/mmwr.mm6533e1).
“The treatment of sepsis is a race against time,” CDC Director Tom Frieden, MD, said during a media teleconference about the report. “We can protect more people from sepsis by informing patients and their families, treating infections promptly, and acting fast when sepsis does occur.”
Each year, between 1 and 3 million people in the United States are diagnosed with sepsis, a syndrome marked by the body’s overwhelming and life-threatening response to an infection, Dr. Frieden said. Of these, 15%-30% will die from the condition, for which there is no blood test. “Health care providers are on the front lines of both sepsis prevention and early recognition,” he emphasized. “Prevention really is possible.” For example, he continued, if a patient with diabetes visits their regular doctor and is found to have increased blood sugar and a small wound on their foot, “this is a prime opportunity to think about infection and reduce the risk of sepsis. In addition to treating the infection, the clinician can inform the patient and family members about how to care for the wound, how to recognize the signs that the infection may be getting worse, and when to seek additional medical care. If the infection gets worse the patient could be at risk for sepsis. Taking the opportunity to both treat and inform patients could save their life, and helping patients know to ask, ‘Could this be sepsis?’ empowers patients and families and could save lives.”
In an effort to describe the characteristics of patients with sepsis, researchers from the CDC and from New York State conducted a retrospective review of medical records from 246 adults and 79 children with sepsis who were treated at four New York hospitals. They found that sepsis most often occurs in patients older than age 65 years and in infants younger than 1 year of age, and the median hospital length of stay is 10 days. Six key signs and symptoms of sepsis were shivering or feeling cold; pain or discomfort; clammy or sweaty skin; being confused or disoriented; shortness of breath, and having a rapid heartbeat. “People with chronic diseases such as diabetes or weakened immune systems from things like tobacco use are at higher risk of sepsis,” Dr. Frieden said. “But even healthy people can develop sepsis from an infection, especially if it’s not treated properly and promptly.”
The four types of infections most commonly associated with sepsis include those involving the lungs, urinary tract, skin, and intestines, while the most common germs that can cause sepsis are Staphylococcus aureus, Escherichia coli (E. coli), and some types of Streptococcus. Infection prevention strategies such as increasing vaccination rates for pneumococcal disease and for influenza are likely to reduce the incidence of sepsis, according to the report. “We could also improve infections by improving handwashing at health care facilities as well as in the community,” Dr. Frieden added. “We can [also] improve recognition of sepsis both in the community and in health care facilities and act fast if sepsis is suspected in a patient. We’ve been able to reduce the rates of some infections that cause sepsis in health care facilities by half, but preventing more infections and stopping the spread of antibiotic resistant infections will protect even more patients from sepsis.”
Mitchell Levy, MD, founding member of the Surviving Sepsis Campaign, said during the teleconference that clinicians have made “tremendous progress in sepsis,” despite current challenges. “First, we now understand the importance of early identification and treatment of sepsis,” he said. “Second, we have seen improved survival through routine screening and treatment that is integrated into the work flow of hospitals. And third, frontline health care providers really do make a difference. What’s clear is that we need to expand these successes to other parts of hospitals and to other care locations.”
Forthcoming free CDC webinars related to sepsis for health care providers include one on Sept. 13 at 3 p.m., ET, entitled “Advances in Sepsis: Protecting Patients Throughout the Lifespan.” Another webinar will be offered on Sept. 22 at 2 p.m., ET, entitled “Empowering Nurses for Early Sepsis Recognition.”
Sepsis is a medical emergency that begins outside of the hospital in 79% of cases. In addition, 72% of patients with sepsis had recently used healthcare services or had chronic diseases that required frequent medical care.
Those are key findings from a special report in Morbidity and Mortality Weekly Report published by the U.S. Centers for Disease Control and Prevention (Morb Mortal Wkly Rep. 2016 Aug 23. doi: 10.15585/mmwr.mm6533e1).
“The treatment of sepsis is a race against time,” CDC Director Tom Frieden, MD, said during a media teleconference about the report. “We can protect more people from sepsis by informing patients and their families, treating infections promptly, and acting fast when sepsis does occur.”
Each year, between 1 and 3 million people in the United States are diagnosed with sepsis, a syndrome marked by the body’s overwhelming and life-threatening response to an infection, Dr. Frieden said. Of these, 15%-30% will die from the condition, for which there is no blood test. “Health care providers are on the front lines of both sepsis prevention and early recognition,” he emphasized. “Prevention really is possible.” For example, he continued, if a patient with diabetes visits their regular doctor and is found to have increased blood sugar and a small wound on their foot, “this is a prime opportunity to think about infection and reduce the risk of sepsis. In addition to treating the infection, the clinician can inform the patient and family members about how to care for the wound, how to recognize the signs that the infection may be getting worse, and when to seek additional medical care. If the infection gets worse the patient could be at risk for sepsis. Taking the opportunity to both treat and inform patients could save their life, and helping patients know to ask, ‘Could this be sepsis?’ empowers patients and families and could save lives.”
In an effort to describe the characteristics of patients with sepsis, researchers from the CDC and from New York State conducted a retrospective review of medical records from 246 adults and 79 children with sepsis who were treated at four New York hospitals. They found that sepsis most often occurs in patients older than age 65 years and in infants younger than 1 year of age, and the median hospital length of stay is 10 days. Six key signs and symptoms of sepsis were shivering or feeling cold; pain or discomfort; clammy or sweaty skin; being confused or disoriented; shortness of breath, and having a rapid heartbeat. “People with chronic diseases such as diabetes or weakened immune systems from things like tobacco use are at higher risk of sepsis,” Dr. Frieden said. “But even healthy people can develop sepsis from an infection, especially if it’s not treated properly and promptly.”
The four types of infections most commonly associated with sepsis include those involving the lungs, urinary tract, skin, and intestines, while the most common germs that can cause sepsis are Staphylococcus aureus, Escherichia coli (E. coli), and some types of Streptococcus. Infection prevention strategies such as increasing vaccination rates for pneumococcal disease and for influenza are likely to reduce the incidence of sepsis, according to the report. “We could also improve infections by improving handwashing at health care facilities as well as in the community,” Dr. Frieden added. “We can [also] improve recognition of sepsis both in the community and in health care facilities and act fast if sepsis is suspected in a patient. We’ve been able to reduce the rates of some infections that cause sepsis in health care facilities by half, but preventing more infections and stopping the spread of antibiotic resistant infections will protect even more patients from sepsis.”
Mitchell Levy, MD, founding member of the Surviving Sepsis Campaign, said during the teleconference that clinicians have made “tremendous progress in sepsis,” despite current challenges. “First, we now understand the importance of early identification and treatment of sepsis,” he said. “Second, we have seen improved survival through routine screening and treatment that is integrated into the work flow of hospitals. And third, frontline health care providers really do make a difference. What’s clear is that we need to expand these successes to other parts of hospitals and to other care locations.”
Forthcoming free CDC webinars related to sepsis for health care providers include one on Sept. 13 at 3 p.m., ET, entitled “Advances in Sepsis: Protecting Patients Throughout the Lifespan.” Another webinar will be offered on Sept. 22 at 2 p.m., ET, entitled “Empowering Nurses for Early Sepsis Recognition.”
FROM MORBIDITY AND MORTALITY WEEKLY REPORT
Key clinical point: Sepsis is a significant public health and clinical management challenge.
Major finding: Sepsis begins outside of the hospital in 79% of cases.
Data source: A retrospective review of medical records from 246 adults and 79 children with sepsis who were treated at four New York hospitals.
Disclosures: The researchers reported having no financial disclosures.
Brief resolved unexplained events (formerly apparent life-threatening events) and evaluation of lower-risk infants
In this new clinical practice guideline, the American Academy of Pediatrics has recommended that the term “apparent life-threatening events” (ALTEs) be replaced with a new term, “brief resolved unexplained events” (BRUEs). ALTE, proposed in 1986 to replace the term near-SIDS (sudden infant death syndrome), has been defined as an episode that is frightening to the observer and characterized by some combination of apnea, color change, marked change in muscle tone, and/or choking or gagging. Many of these children undergo a comprehensive work-up in addition to the initial history and physical. Children may be admitted for observation, and the admission often includes further evaluation with cardiorespiratory monitoring, labs, and occasionally specialized studies. These tests are usually normal, and patients are discharged home, leaving families to continue to worry that there is an undetected underlying problem.
The ALTE definition is often vague in determination and dependent on a subjective report from caregivers and their perception of the severity of the event. The new term BRUE is based on more stringent, objective criteria. BRUE is defined as occurring in children less than 1 year of age, where an observer reports a sudden, brief now-resolved episode with one or more of the following:
• Cyanosis or pallor.
• Absent, decreased, or irregular breathing.
• A marked change in tone (hypertonia or hypotonia).
• An altered level of responsiveness.
• No explanation for a qualifying event after an appropriate history and physical are conducted.
The BRUE definition differs from that of an ALTE. First, the “life-threatening” qualifier has been removed from both the title and diagnostic criteria. This allows providers to approach the patient with more objectivity, and allows clinical decision making to stem from the evaluation of the child rather than the perceived severity of the event.
“Color change” has been more strictly defined to be only cyanosis or pallor. In the ALTE definition, redness or rubor was an acceptable criterion for diagnosis; however, this is a common finding in healthy newborns.
“Change in muscle tone” has been more specifically defined and must be characterized as hypertonia or hypotonia. Characterizing the change in tone assists providers in investigating specific underlying causes. “Altered level of responsiveness” is a new criterion.
There is a notable absence of “choking or gagging” from the BRUE definition. These are often signs of reflux and upper respiratory infections in the infant. By the very nature of the definition, if a child is diagnosed with an underlying illness, this excludes the diagnosis of BRUE.
Identifying risk factors for repeat events
In addition to using new criteria for diagnosis, providers are also able to characterize infants as higher risk and lower risk. If a child truly has a BRUE, he/she may be diagnosed as higher risk or lower risk for a recurrent episode or SIDS.
A lower-risk infant has the following characteristics:
• Over 60 days old.
• Gestational age greater than 32 weeks; postconception age over 45 weeks.
• First BRUE.
• Duration of event under 1 minute.
• No CPR required by a trained medical provider (not parents).
• No concerning history and physical findings.
Children who are identified as being at higher risk would benefit from further work-up beyond a thorough history and physical. Additional testing may reveal the underlying cause of the episode (congenital cardiac disease, underlying metabolic disorder, abuse), thereby excluding the diagnosis of BRUE. By further characterizing the diagnosis, the new definition allows providers to avoid unnecessary studies in otherwise healthy children.
Key action statements and recommendations
Action statements are recommended for the evaluation of children who are classified as lower risk with BRUE. While not all the action statements can be covered in this review, for lower-risk individuals, clinicians:
• Do not need to admit infants solely for cardiorespiratory monitoring.
• Should not start home cardiorespiratory monitoring, obtain an overnight polysomnogram, a chest radiograph, or an echocardiogram.
• Assess for risk factors in order to detect any possible child abuse.
• Should not obtain neuroimaging to detect neurologic disorders or child abuse, and should not perform an EEG to detect a neurologic disorder.
• Are strongly recommended to refrain from doing a WBC, blood culture, or lumbar puncture with cerebrospinal fluid studies to rule out an occult bacterial infection.
• Should avoid doing an extensive work-up for underlying gastroesophageal reflux (e.g., upper gastrointestinal tract series, endoscopy, pH probe, ultrasound).
• Are encouraged to educate parents and families about BRUEs, and offer resources for CPR training for families and caregivers.
Limitations
While there are many benefits to these new guidelines, there are challenges. ALTE is ingrained in clinical practice, and it may take time for a uniform acceptance of the change in terminology and criteria. Additional limitations come with the lack of evidence of outcomes and impact, as all studies available are based on ALTE criteria, and data will lag in evaluating the utility of conceptualizing events as BRUEs.
The bottom line
BRUE has been proposed to replace the term ALTE for an unexplained witnessed event as defined above. BRUEs differ from ALTEs in that the criteria are more strictly defined, and they allow providers to stratify children as lower risk or higher risk for a recurrent episode or SIDS. By identifying a child’s risk, providers are able to appropriately utilize resources to refrain from doing an extensive medical work-up in a child who is otherwise healthy and low risk for a serious event.
Reference
Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. Dr. Cavanaugh is a second-year resident in the Abington-Jefferson Family Medicine Residency Program.
In this new clinical practice guideline, the American Academy of Pediatrics has recommended that the term “apparent life-threatening events” (ALTEs) be replaced with a new term, “brief resolved unexplained events” (BRUEs). ALTE, proposed in 1986 to replace the term near-SIDS (sudden infant death syndrome), has been defined as an episode that is frightening to the observer and characterized by some combination of apnea, color change, marked change in muscle tone, and/or choking or gagging. Many of these children undergo a comprehensive work-up in addition to the initial history and physical. Children may be admitted for observation, and the admission often includes further evaluation with cardiorespiratory monitoring, labs, and occasionally specialized studies. These tests are usually normal, and patients are discharged home, leaving families to continue to worry that there is an undetected underlying problem.
The ALTE definition is often vague in determination and dependent on a subjective report from caregivers and their perception of the severity of the event. The new term BRUE is based on more stringent, objective criteria. BRUE is defined as occurring in children less than 1 year of age, where an observer reports a sudden, brief now-resolved episode with one or more of the following:
• Cyanosis or pallor.
• Absent, decreased, or irregular breathing.
• A marked change in tone (hypertonia or hypotonia).
• An altered level of responsiveness.
• No explanation for a qualifying event after an appropriate history and physical are conducted.
The BRUE definition differs from that of an ALTE. First, the “life-threatening” qualifier has been removed from both the title and diagnostic criteria. This allows providers to approach the patient with more objectivity, and allows clinical decision making to stem from the evaluation of the child rather than the perceived severity of the event.
“Color change” has been more strictly defined to be only cyanosis or pallor. In the ALTE definition, redness or rubor was an acceptable criterion for diagnosis; however, this is a common finding in healthy newborns.
“Change in muscle tone” has been more specifically defined and must be characterized as hypertonia or hypotonia. Characterizing the change in tone assists providers in investigating specific underlying causes. “Altered level of responsiveness” is a new criterion.
There is a notable absence of “choking or gagging” from the BRUE definition. These are often signs of reflux and upper respiratory infections in the infant. By the very nature of the definition, if a child is diagnosed with an underlying illness, this excludes the diagnosis of BRUE.
Identifying risk factors for repeat events
In addition to using new criteria for diagnosis, providers are also able to characterize infants as higher risk and lower risk. If a child truly has a BRUE, he/she may be diagnosed as higher risk or lower risk for a recurrent episode or SIDS.
A lower-risk infant has the following characteristics:
• Over 60 days old.
• Gestational age greater than 32 weeks; postconception age over 45 weeks.
• First BRUE.
• Duration of event under 1 minute.
• No CPR required by a trained medical provider (not parents).
• No concerning history and physical findings.
Children who are identified as being at higher risk would benefit from further work-up beyond a thorough history and physical. Additional testing may reveal the underlying cause of the episode (congenital cardiac disease, underlying metabolic disorder, abuse), thereby excluding the diagnosis of BRUE. By further characterizing the diagnosis, the new definition allows providers to avoid unnecessary studies in otherwise healthy children.
Key action statements and recommendations
Action statements are recommended for the evaluation of children who are classified as lower risk with BRUE. While not all the action statements can be covered in this review, for lower-risk individuals, clinicians:
• Do not need to admit infants solely for cardiorespiratory monitoring.
• Should not start home cardiorespiratory monitoring, obtain an overnight polysomnogram, a chest radiograph, or an echocardiogram.
• Assess for risk factors in order to detect any possible child abuse.
• Should not obtain neuroimaging to detect neurologic disorders or child abuse, and should not perform an EEG to detect a neurologic disorder.
• Are strongly recommended to refrain from doing a WBC, blood culture, or lumbar puncture with cerebrospinal fluid studies to rule out an occult bacterial infection.
• Should avoid doing an extensive work-up for underlying gastroesophageal reflux (e.g., upper gastrointestinal tract series, endoscopy, pH probe, ultrasound).
• Are encouraged to educate parents and families about BRUEs, and offer resources for CPR training for families and caregivers.
Limitations
While there are many benefits to these new guidelines, there are challenges. ALTE is ingrained in clinical practice, and it may take time for a uniform acceptance of the change in terminology and criteria. Additional limitations come with the lack of evidence of outcomes and impact, as all studies available are based on ALTE criteria, and data will lag in evaluating the utility of conceptualizing events as BRUEs.
The bottom line
BRUE has been proposed to replace the term ALTE for an unexplained witnessed event as defined above. BRUEs differ from ALTEs in that the criteria are more strictly defined, and they allow providers to stratify children as lower risk or higher risk for a recurrent episode or SIDS. By identifying a child’s risk, providers are able to appropriately utilize resources to refrain from doing an extensive medical work-up in a child who is otherwise healthy and low risk for a serious event.
Reference
Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. Dr. Cavanaugh is a second-year resident in the Abington-Jefferson Family Medicine Residency Program.
In this new clinical practice guideline, the American Academy of Pediatrics has recommended that the term “apparent life-threatening events” (ALTEs) be replaced with a new term, “brief resolved unexplained events” (BRUEs). ALTE, proposed in 1986 to replace the term near-SIDS (sudden infant death syndrome), has been defined as an episode that is frightening to the observer and characterized by some combination of apnea, color change, marked change in muscle tone, and/or choking or gagging. Many of these children undergo a comprehensive work-up in addition to the initial history and physical. Children may be admitted for observation, and the admission often includes further evaluation with cardiorespiratory monitoring, labs, and occasionally specialized studies. These tests are usually normal, and patients are discharged home, leaving families to continue to worry that there is an undetected underlying problem.
The ALTE definition is often vague in determination and dependent on a subjective report from caregivers and their perception of the severity of the event. The new term BRUE is based on more stringent, objective criteria. BRUE is defined as occurring in children less than 1 year of age, where an observer reports a sudden, brief now-resolved episode with one or more of the following:
• Cyanosis or pallor.
• Absent, decreased, or irregular breathing.
• A marked change in tone (hypertonia or hypotonia).
• An altered level of responsiveness.
• No explanation for a qualifying event after an appropriate history and physical are conducted.
The BRUE definition differs from that of an ALTE. First, the “life-threatening” qualifier has been removed from both the title and diagnostic criteria. This allows providers to approach the patient with more objectivity, and allows clinical decision making to stem from the evaluation of the child rather than the perceived severity of the event.
“Color change” has been more strictly defined to be only cyanosis or pallor. In the ALTE definition, redness or rubor was an acceptable criterion for diagnosis; however, this is a common finding in healthy newborns.
“Change in muscle tone” has been more specifically defined and must be characterized as hypertonia or hypotonia. Characterizing the change in tone assists providers in investigating specific underlying causes. “Altered level of responsiveness” is a new criterion.
There is a notable absence of “choking or gagging” from the BRUE definition. These are often signs of reflux and upper respiratory infections in the infant. By the very nature of the definition, if a child is diagnosed with an underlying illness, this excludes the diagnosis of BRUE.
Identifying risk factors for repeat events
In addition to using new criteria for diagnosis, providers are also able to characterize infants as higher risk and lower risk. If a child truly has a BRUE, he/she may be diagnosed as higher risk or lower risk for a recurrent episode or SIDS.
A lower-risk infant has the following characteristics:
• Over 60 days old.
• Gestational age greater than 32 weeks; postconception age over 45 weeks.
• First BRUE.
• Duration of event under 1 minute.
• No CPR required by a trained medical provider (not parents).
• No concerning history and physical findings.
Children who are identified as being at higher risk would benefit from further work-up beyond a thorough history and physical. Additional testing may reveal the underlying cause of the episode (congenital cardiac disease, underlying metabolic disorder, abuse), thereby excluding the diagnosis of BRUE. By further characterizing the diagnosis, the new definition allows providers to avoid unnecessary studies in otherwise healthy children.
Key action statements and recommendations
Action statements are recommended for the evaluation of children who are classified as lower risk with BRUE. While not all the action statements can be covered in this review, for lower-risk individuals, clinicians:
• Do not need to admit infants solely for cardiorespiratory monitoring.
• Should not start home cardiorespiratory monitoring, obtain an overnight polysomnogram, a chest radiograph, or an echocardiogram.
• Assess for risk factors in order to detect any possible child abuse.
• Should not obtain neuroimaging to detect neurologic disorders or child abuse, and should not perform an EEG to detect a neurologic disorder.
• Are strongly recommended to refrain from doing a WBC, blood culture, or lumbar puncture with cerebrospinal fluid studies to rule out an occult bacterial infection.
• Should avoid doing an extensive work-up for underlying gastroesophageal reflux (e.g., upper gastrointestinal tract series, endoscopy, pH probe, ultrasound).
• Are encouraged to educate parents and families about BRUEs, and offer resources for CPR training for families and caregivers.
Limitations
While there are many benefits to these new guidelines, there are challenges. ALTE is ingrained in clinical practice, and it may take time for a uniform acceptance of the change in terminology and criteria. Additional limitations come with the lack of evidence of outcomes and impact, as all studies available are based on ALTE criteria, and data will lag in evaluating the utility of conceptualizing events as BRUEs.
The bottom line
BRUE has been proposed to replace the term ALTE for an unexplained witnessed event as defined above. BRUEs differ from ALTEs in that the criteria are more strictly defined, and they allow providers to stratify children as lower risk or higher risk for a recurrent episode or SIDS. By identifying a child’s risk, providers are able to appropriately utilize resources to refrain from doing an extensive medical work-up in a child who is otherwise healthy and low risk for a serious event.
Reference
Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. Dr. Cavanaugh is a second-year resident in the Abington-Jefferson Family Medicine Residency Program.
Herpes Zoster in Children
Herpes zoster (HZ) is commonly seen in immunocompromised patients but is quite uncommon in immunocompetent children. Pediatric cases have been attributed to 1 of 3 primary exposures: intrauterine exposure to the varicella-zoster virus (VZV), postuterine exposure to wild-type VZV, or exposure due to vaccination with the live-attenuated strain of the virus.1
We report a case of HZ in an immunocompetent pediatric patient soon after routine VZV vaccination. We also review the literature on the incidence, clinical characteristics, and diagnostic aids for pediatric cases of HZ.
Case Report
A 15-month-old boy who was previously healthy presented with a red vesicular rash on the right upper cheek of 3 days’ duration. The patient was otherwise asymptomatic and had no constitutional symptoms. The patient’s mother reported an uncomplicated pregnancy and delivery with no history of maternal VZV infection. There was no known exposure to other individuals with VZV or a history of a similar rash. The patient was up-to-date on his immunizations, which included the VZV vaccine at 12 months of age.
Physical examination revealed vesicles and pustules with an erythematous base on the right zygoma extending to the right lateral canthus and upper eyelid in a dermatomal distribution (Figure). No lesions were present on any other area of the body. One group of vesicles was ruptured with a polyester-tipped applicator and submitted for polymerase chain reaction (PCR) analysis for suspected VZV infection. An ophthalmology evaluation revealed no ocular involvement.
Although no complications were noted on the ophthalmologist’s initial examination or at the follow-up visit, 1 month later the patient’s father noted a “cloudy change” to the right eye. The patient had several subsequent evaluations with ophthalmologists and was treated for HZ ophthalmicus with acyclovir over the following 10 months. The patient’s mother reported eventual clearance of the eye findings without permanent visual sequelae. She stated that the PCR results documenting VZV positivity were extremely helpful for the ophthalmologist in establishing a diagnosis and treatment plan.
Comment
Varicella-zoster virus is 1 of 8 viruses in the Herpesviridae family known to infect humans. It is known to cause 2 distinct disease states: varicella (chickenpox) due to a primary infection from the virus, and HZ (shingles) caused by a reactivation of the latent virus in the dorsal root ganglion, which then travels the neural pathway and manifests cutaneously along 1 to 2 dermatomes.1 This recurrence is possible in infants, children, and adults via 1 of 3 routes of exposure.
The overall incidence of HZ is lower in children compared to adults, and the risk dramatically increases in individuals older than 50 years. Evidence also shows that exposure to VZV before 1 year of age increases the lifetime risk for HZ.2,3 Children aged 1 to 18 years who were evaluated for HZ demonstrated a decreased incidence among those who were vaccinated versus those who were not.4,5 Interestingly, there was an increased incidence of HZ among children aged 1 to 2 years who had been vaccinated. Based on PCR analysis, it was noted that HZ was attributed to the vaccine-related strain of VZV in 92% of 1- to 2-year-old patients.4
There is some concern that the varicella vaccination program implemented in 1995 has led to increased rates of HZ. The literature presents mixed reports. Some studies showed an overall increased incidence of HZ,6,7 and 2 other studies showed no increase in the incidence of HZ.4,8 More recent studies have demonstrated that vaccination may have a protective effect against HZ.4-6,9 In a 2013 study in which HZ samples were tested by PCR analysis to determine the strains of VZV that were responsible for an HZ outbreak in children aged 1 to 18 years, the HZ incidence was 48 per 100,000 person-years in patients who were vaccinated versus 230 per 100,000 person-years in patients who were not vaccinated. Among the subset of patients who were vaccinated (n=118), 52% of the HZ lesions were from the wild-type strain.4
Clinical Characteristics
The typical presentation of HZ includes grouped vesicles or small bullae on an erythematous base that occur unilaterally within the distribution of a cranial or spinal sensory nerve, occasionally with overflow into the dermatomes above and below, typically without crossing the midline.8 The most frequent distributions in descending order are thoracic, cranial (mostly trigeminal), lumbar, and sacral. Pain in the dermatome may never occur, may precede, may occur during, or may even occur after the eruption. The initial presentation involves papules and plaques that develop blisters within hours of their development. Lesions continue to appear for several days and may coalesce. The lesions may become hemorrhagic, necrotic, or bullous, with or without adenopathy. Rarely, there can be pain without the associated skin eruption (zoster sine herpete). Lesions tend to crust by days 7 to 10.8
Herpes zoster typically affects children to a lesser extent than adults. The disease state often is milder in children with a decreased likelihood of postherpetic neuralgia.10 However, there are documented cases of severe sequelae secondary to zoster infection in pediatric patients, including but not limited to disseminated HZ,8 HZ ophthalmicus,11,12 Ramsay Hunt syndrome,8 and chronic encephalitis.8 In the adult population, ocular involvement will present in 33% to 50% of cases that involve the ophthalmic branch of the trigeminal nerve without clinical involvement of the nasociliary branch of the ophthalmic nerve. Involvement of the nasociliary branch will lead to ocular pathology in an estimated 76% to 100% of adult cases.13,14 It is unknown if this rate is the same in the pediatric population, but it highlights the importance of educating patients and/or guardians about possible complications. It also demonstrates the importance of including HZ in the differential diagnosis for pediatric patients presenting with papular or vesicular skin eruptions, particularly in the area of the ophthalmic branch of the trigeminal nerve.
Diagnosis
Herpes zoster usually is diagnosed based on its clinical presentation. Human herpesvirus 1 or 2 also may present with similar lesions and should be included in the differential diagnosis. To confirm a clinical diagnosis, additional testing may be done. A Tzanck smear historically has been the least expensive and most rapid test. Scrapings can be taken from the base of a vesicle, stained, and examined for multinucleated giant cells; however, a Tzanck smear cannot help in distinguishing herpes simplex virus from VZV. Direct fluorescent antibody testing and viral culture are less rapid but are standard tests that may help with the diagnosis. Direct fluorescent antibody testing can have a high false-negative rate, and viral cultures typically take 2 weeks for completion. These tests have largely been replaced by PCR analysis. Polymerase chain reaction has been the most sensitive test developed yet. With recent advances, real-time PCR, which can be performed within 1 hour in small hospital laboratories,15 has become more readily available and much more rapid than standard PCR. Further PCR testing can differentiate between the 2 possible infective strains (wild-type vs vaccine related).16 Real-time PCR is now commonly used as the first-line ancillary diagnostic test after physical examination.17
Conclusion
Although uncommon, HZ does occur in immunocompetent children and should be included in the differential diagnosis in children with vesicular lesions. Herpes zoster is a reactivation of VZV and initial exposure may be from the wild-type or vaccine-related strains. Clinicians must be vigilant in their evaluation of vesicular lesions in children even without known varicella exposure. Polymerase chain reaction testing can be helpful to distinguish between herpes simplex lesions and VZV. Polymerase chain reaction testing also may be of benefit to determine the strain of VZV infection.
- Myers MG, Seward JF, LaRussa PS. Varicella-zoster virus. In: Kliegman RM, Behrman RE, Jenson HB, et al, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Saunders; 2011:1104-1105.
- Terada K, Kawano S, Yoshihiro K, et al. Varicella-zoster virus (VZV) reactivation is related to the low response of VZV-specific immunity after chickenpox in infancy. J Infect Dis. 1994;169:650-652.
- Takayama N, Yamada H, Kaku H, et al. Herpes zoster in immunocompetent and immunocompromised Japanese children. Pediatr Int. 2000;42:275-279.
- Weinmann S, Chun C, Schmid DS, et al. Incidence and clinical characteristics of herpes zoster among children in the varicella vaccine era, 2005-2009. J Infect Dis. 2013;208:1859-1868.
- Civen R, Lopez AS, Zhang J, et al. Varicella outbreak epidemiology in an active surveillance site, 1995–2005. J Infect Dis. 2008;197(suppl 2):S114-S119.
- Russell ML, Dover DC, Simmonds KA, et al. Shingles in Alberta: before and after publicly funded varicella vaccination. Vaccine. 2014;32:6319-6324.
- Goldman GS, King PG. Review of the United States universal varicella vaccination program: herpes zoster incidence rates, cost-effectiveness, and vaccine efficacy based primarily on the Antelope Valley Varicella Active Surveillance Project data. Vaccine. 2013;31:1680-1694.
- Arikawa J, Asahi T, Au WY, et al. Zoster (shingles, herpes zoster). In: James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin. 11th ed. Philadelphia, PA: Saunders/Elsevier; 2011:372-376.
- Guris D, Jumaan AO, Mascola L, et al. Changing varicella epidemiology in active surveillance sites–United States, 1995-2005. J Infect Dis. 2008;197(suppl 2):S71-S75.
- Petursson G, Helgason S, Gudmundsson S, et al. Herpes zoster in children and adolescents. Pediatr Infect Dis J. 1998;17:905-908.
- Oladokun RE, Olomukoro CN, Owa AB. Disseminated herpes zoster ophthalmicus in an immunocompetent 8-year-old boy. Clin Pract. 2013;3:e16.
- Lewkonia IK, Jackson AA. Infantile herpes zoster after intrauterine exposure to varicella. Br Med J. 1973;3:149.
- Zaal MJ, Völker-Dieben HJ, D’Amaro J. Prognostic value of Hutchinson’s sign in acute herpes zoster ophthalmicus. Graefes Arch Clin Exp Ophthalmol. 2003;241:187-191.
- Harding SP, Lipton JR, Wells JC. Natural history of herpes zoster ophthalmicus: predictors of postherpetic neuralgia and ocular involvement. Br J Ophthalmol. 1987;71:353-358.
- Higashimoto Y, Ihira M, Ohta A, et al. Discriminating between varicella-zoster virus vaccine and wild-type strains by loop-mediated isothermal amplification. J Clin Microbiol. 2008;46:2665-2670.
- Harbecke R, Oxman MN, Arnold, et al. A real-time PCR assay to identify and discriminate among wild-type and vaccine strains of varicella-zoster virus and herpes simplex virus in clinical specimens, and comparison with the clinical diagnoses. J Med Virol. 2009;81:1310-1322.
- Albrecht MA. Diagnosis of varicella-zoster infection. UpToDate website. http://www.uptodate.com/contents/diagnosis-of-varicella-zoster-virus-infection. Updated July 6, 2015. Accessed July 19, 2016.
Herpes zoster (HZ) is commonly seen in immunocompromised patients but is quite uncommon in immunocompetent children. Pediatric cases have been attributed to 1 of 3 primary exposures: intrauterine exposure to the varicella-zoster virus (VZV), postuterine exposure to wild-type VZV, or exposure due to vaccination with the live-attenuated strain of the virus.1
We report a case of HZ in an immunocompetent pediatric patient soon after routine VZV vaccination. We also review the literature on the incidence, clinical characteristics, and diagnostic aids for pediatric cases of HZ.
Case Report
A 15-month-old boy who was previously healthy presented with a red vesicular rash on the right upper cheek of 3 days’ duration. The patient was otherwise asymptomatic and had no constitutional symptoms. The patient’s mother reported an uncomplicated pregnancy and delivery with no history of maternal VZV infection. There was no known exposure to other individuals with VZV or a history of a similar rash. The patient was up-to-date on his immunizations, which included the VZV vaccine at 12 months of age.
Physical examination revealed vesicles and pustules with an erythematous base on the right zygoma extending to the right lateral canthus and upper eyelid in a dermatomal distribution (Figure). No lesions were present on any other area of the body. One group of vesicles was ruptured with a polyester-tipped applicator and submitted for polymerase chain reaction (PCR) analysis for suspected VZV infection. An ophthalmology evaluation revealed no ocular involvement.
Although no complications were noted on the ophthalmologist’s initial examination or at the follow-up visit, 1 month later the patient’s father noted a “cloudy change” to the right eye. The patient had several subsequent evaluations with ophthalmologists and was treated for HZ ophthalmicus with acyclovir over the following 10 months. The patient’s mother reported eventual clearance of the eye findings without permanent visual sequelae. She stated that the PCR results documenting VZV positivity were extremely helpful for the ophthalmologist in establishing a diagnosis and treatment plan.
Comment
Varicella-zoster virus is 1 of 8 viruses in the Herpesviridae family known to infect humans. It is known to cause 2 distinct disease states: varicella (chickenpox) due to a primary infection from the virus, and HZ (shingles) caused by a reactivation of the latent virus in the dorsal root ganglion, which then travels the neural pathway and manifests cutaneously along 1 to 2 dermatomes.1 This recurrence is possible in infants, children, and adults via 1 of 3 routes of exposure.
The overall incidence of HZ is lower in children compared to adults, and the risk dramatically increases in individuals older than 50 years. Evidence also shows that exposure to VZV before 1 year of age increases the lifetime risk for HZ.2,3 Children aged 1 to 18 years who were evaluated for HZ demonstrated a decreased incidence among those who were vaccinated versus those who were not.4,5 Interestingly, there was an increased incidence of HZ among children aged 1 to 2 years who had been vaccinated. Based on PCR analysis, it was noted that HZ was attributed to the vaccine-related strain of VZV in 92% of 1- to 2-year-old patients.4
There is some concern that the varicella vaccination program implemented in 1995 has led to increased rates of HZ. The literature presents mixed reports. Some studies showed an overall increased incidence of HZ,6,7 and 2 other studies showed no increase in the incidence of HZ.4,8 More recent studies have demonstrated that vaccination may have a protective effect against HZ.4-6,9 In a 2013 study in which HZ samples were tested by PCR analysis to determine the strains of VZV that were responsible for an HZ outbreak in children aged 1 to 18 years, the HZ incidence was 48 per 100,000 person-years in patients who were vaccinated versus 230 per 100,000 person-years in patients who were not vaccinated. Among the subset of patients who were vaccinated (n=118), 52% of the HZ lesions were from the wild-type strain.4
Clinical Characteristics
The typical presentation of HZ includes grouped vesicles or small bullae on an erythematous base that occur unilaterally within the distribution of a cranial or spinal sensory nerve, occasionally with overflow into the dermatomes above and below, typically without crossing the midline.8 The most frequent distributions in descending order are thoracic, cranial (mostly trigeminal), lumbar, and sacral. Pain in the dermatome may never occur, may precede, may occur during, or may even occur after the eruption. The initial presentation involves papules and plaques that develop blisters within hours of their development. Lesions continue to appear for several days and may coalesce. The lesions may become hemorrhagic, necrotic, or bullous, with or without adenopathy. Rarely, there can be pain without the associated skin eruption (zoster sine herpete). Lesions tend to crust by days 7 to 10.8
Herpes zoster typically affects children to a lesser extent than adults. The disease state often is milder in children with a decreased likelihood of postherpetic neuralgia.10 However, there are documented cases of severe sequelae secondary to zoster infection in pediatric patients, including but not limited to disseminated HZ,8 HZ ophthalmicus,11,12 Ramsay Hunt syndrome,8 and chronic encephalitis.8 In the adult population, ocular involvement will present in 33% to 50% of cases that involve the ophthalmic branch of the trigeminal nerve without clinical involvement of the nasociliary branch of the ophthalmic nerve. Involvement of the nasociliary branch will lead to ocular pathology in an estimated 76% to 100% of adult cases.13,14 It is unknown if this rate is the same in the pediatric population, but it highlights the importance of educating patients and/or guardians about possible complications. It also demonstrates the importance of including HZ in the differential diagnosis for pediatric patients presenting with papular or vesicular skin eruptions, particularly in the area of the ophthalmic branch of the trigeminal nerve.
Diagnosis
Herpes zoster usually is diagnosed based on its clinical presentation. Human herpesvirus 1 or 2 also may present with similar lesions and should be included in the differential diagnosis. To confirm a clinical diagnosis, additional testing may be done. A Tzanck smear historically has been the least expensive and most rapid test. Scrapings can be taken from the base of a vesicle, stained, and examined for multinucleated giant cells; however, a Tzanck smear cannot help in distinguishing herpes simplex virus from VZV. Direct fluorescent antibody testing and viral culture are less rapid but are standard tests that may help with the diagnosis. Direct fluorescent antibody testing can have a high false-negative rate, and viral cultures typically take 2 weeks for completion. These tests have largely been replaced by PCR analysis. Polymerase chain reaction has been the most sensitive test developed yet. With recent advances, real-time PCR, which can be performed within 1 hour in small hospital laboratories,15 has become more readily available and much more rapid than standard PCR. Further PCR testing can differentiate between the 2 possible infective strains (wild-type vs vaccine related).16 Real-time PCR is now commonly used as the first-line ancillary diagnostic test after physical examination.17
Conclusion
Although uncommon, HZ does occur in immunocompetent children and should be included in the differential diagnosis in children with vesicular lesions. Herpes zoster is a reactivation of VZV and initial exposure may be from the wild-type or vaccine-related strains. Clinicians must be vigilant in their evaluation of vesicular lesions in children even without known varicella exposure. Polymerase chain reaction testing can be helpful to distinguish between herpes simplex lesions and VZV. Polymerase chain reaction testing also may be of benefit to determine the strain of VZV infection.
Herpes zoster (HZ) is commonly seen in immunocompromised patients but is quite uncommon in immunocompetent children. Pediatric cases have been attributed to 1 of 3 primary exposures: intrauterine exposure to the varicella-zoster virus (VZV), postuterine exposure to wild-type VZV, or exposure due to vaccination with the live-attenuated strain of the virus.1
We report a case of HZ in an immunocompetent pediatric patient soon after routine VZV vaccination. We also review the literature on the incidence, clinical characteristics, and diagnostic aids for pediatric cases of HZ.
Case Report
A 15-month-old boy who was previously healthy presented with a red vesicular rash on the right upper cheek of 3 days’ duration. The patient was otherwise asymptomatic and had no constitutional symptoms. The patient’s mother reported an uncomplicated pregnancy and delivery with no history of maternal VZV infection. There was no known exposure to other individuals with VZV or a history of a similar rash. The patient was up-to-date on his immunizations, which included the VZV vaccine at 12 months of age.
Physical examination revealed vesicles and pustules with an erythematous base on the right zygoma extending to the right lateral canthus and upper eyelid in a dermatomal distribution (Figure). No lesions were present on any other area of the body. One group of vesicles was ruptured with a polyester-tipped applicator and submitted for polymerase chain reaction (PCR) analysis for suspected VZV infection. An ophthalmology evaluation revealed no ocular involvement.
Although no complications were noted on the ophthalmologist’s initial examination or at the follow-up visit, 1 month later the patient’s father noted a “cloudy change” to the right eye. The patient had several subsequent evaluations with ophthalmologists and was treated for HZ ophthalmicus with acyclovir over the following 10 months. The patient’s mother reported eventual clearance of the eye findings without permanent visual sequelae. She stated that the PCR results documenting VZV positivity were extremely helpful for the ophthalmologist in establishing a diagnosis and treatment plan.
Comment
Varicella-zoster virus is 1 of 8 viruses in the Herpesviridae family known to infect humans. It is known to cause 2 distinct disease states: varicella (chickenpox) due to a primary infection from the virus, and HZ (shingles) caused by a reactivation of the latent virus in the dorsal root ganglion, which then travels the neural pathway and manifests cutaneously along 1 to 2 dermatomes.1 This recurrence is possible in infants, children, and adults via 1 of 3 routes of exposure.
The overall incidence of HZ is lower in children compared to adults, and the risk dramatically increases in individuals older than 50 years. Evidence also shows that exposure to VZV before 1 year of age increases the lifetime risk for HZ.2,3 Children aged 1 to 18 years who were evaluated for HZ demonstrated a decreased incidence among those who were vaccinated versus those who were not.4,5 Interestingly, there was an increased incidence of HZ among children aged 1 to 2 years who had been vaccinated. Based on PCR analysis, it was noted that HZ was attributed to the vaccine-related strain of VZV in 92% of 1- to 2-year-old patients.4
There is some concern that the varicella vaccination program implemented in 1995 has led to increased rates of HZ. The literature presents mixed reports. Some studies showed an overall increased incidence of HZ,6,7 and 2 other studies showed no increase in the incidence of HZ.4,8 More recent studies have demonstrated that vaccination may have a protective effect against HZ.4-6,9 In a 2013 study in which HZ samples were tested by PCR analysis to determine the strains of VZV that were responsible for an HZ outbreak in children aged 1 to 18 years, the HZ incidence was 48 per 100,000 person-years in patients who were vaccinated versus 230 per 100,000 person-years in patients who were not vaccinated. Among the subset of patients who were vaccinated (n=118), 52% of the HZ lesions were from the wild-type strain.4
Clinical Characteristics
The typical presentation of HZ includes grouped vesicles or small bullae on an erythematous base that occur unilaterally within the distribution of a cranial or spinal sensory nerve, occasionally with overflow into the dermatomes above and below, typically without crossing the midline.8 The most frequent distributions in descending order are thoracic, cranial (mostly trigeminal), lumbar, and sacral. Pain in the dermatome may never occur, may precede, may occur during, or may even occur after the eruption. The initial presentation involves papules and plaques that develop blisters within hours of their development. Lesions continue to appear for several days and may coalesce. The lesions may become hemorrhagic, necrotic, or bullous, with or without adenopathy. Rarely, there can be pain without the associated skin eruption (zoster sine herpete). Lesions tend to crust by days 7 to 10.8
Herpes zoster typically affects children to a lesser extent than adults. The disease state often is milder in children with a decreased likelihood of postherpetic neuralgia.10 However, there are documented cases of severe sequelae secondary to zoster infection in pediatric patients, including but not limited to disseminated HZ,8 HZ ophthalmicus,11,12 Ramsay Hunt syndrome,8 and chronic encephalitis.8 In the adult population, ocular involvement will present in 33% to 50% of cases that involve the ophthalmic branch of the trigeminal nerve without clinical involvement of the nasociliary branch of the ophthalmic nerve. Involvement of the nasociliary branch will lead to ocular pathology in an estimated 76% to 100% of adult cases.13,14 It is unknown if this rate is the same in the pediatric population, but it highlights the importance of educating patients and/or guardians about possible complications. It also demonstrates the importance of including HZ in the differential diagnosis for pediatric patients presenting with papular or vesicular skin eruptions, particularly in the area of the ophthalmic branch of the trigeminal nerve.
Diagnosis
Herpes zoster usually is diagnosed based on its clinical presentation. Human herpesvirus 1 or 2 also may present with similar lesions and should be included in the differential diagnosis. To confirm a clinical diagnosis, additional testing may be done. A Tzanck smear historically has been the least expensive and most rapid test. Scrapings can be taken from the base of a vesicle, stained, and examined for multinucleated giant cells; however, a Tzanck smear cannot help in distinguishing herpes simplex virus from VZV. Direct fluorescent antibody testing and viral culture are less rapid but are standard tests that may help with the diagnosis. Direct fluorescent antibody testing can have a high false-negative rate, and viral cultures typically take 2 weeks for completion. These tests have largely been replaced by PCR analysis. Polymerase chain reaction has been the most sensitive test developed yet. With recent advances, real-time PCR, which can be performed within 1 hour in small hospital laboratories,15 has become more readily available and much more rapid than standard PCR. Further PCR testing can differentiate between the 2 possible infective strains (wild-type vs vaccine related).16 Real-time PCR is now commonly used as the first-line ancillary diagnostic test after physical examination.17
Conclusion
Although uncommon, HZ does occur in immunocompetent children and should be included in the differential diagnosis in children with vesicular lesions. Herpes zoster is a reactivation of VZV and initial exposure may be from the wild-type or vaccine-related strains. Clinicians must be vigilant in their evaluation of vesicular lesions in children even without known varicella exposure. Polymerase chain reaction testing can be helpful to distinguish between herpes simplex lesions and VZV. Polymerase chain reaction testing also may be of benefit to determine the strain of VZV infection.
- Myers MG, Seward JF, LaRussa PS. Varicella-zoster virus. In: Kliegman RM, Behrman RE, Jenson HB, et al, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Saunders; 2011:1104-1105.
- Terada K, Kawano S, Yoshihiro K, et al. Varicella-zoster virus (VZV) reactivation is related to the low response of VZV-specific immunity after chickenpox in infancy. J Infect Dis. 1994;169:650-652.
- Takayama N, Yamada H, Kaku H, et al. Herpes zoster in immunocompetent and immunocompromised Japanese children. Pediatr Int. 2000;42:275-279.
- Weinmann S, Chun C, Schmid DS, et al. Incidence and clinical characteristics of herpes zoster among children in the varicella vaccine era, 2005-2009. J Infect Dis. 2013;208:1859-1868.
- Civen R, Lopez AS, Zhang J, et al. Varicella outbreak epidemiology in an active surveillance site, 1995–2005. J Infect Dis. 2008;197(suppl 2):S114-S119.
- Russell ML, Dover DC, Simmonds KA, et al. Shingles in Alberta: before and after publicly funded varicella vaccination. Vaccine. 2014;32:6319-6324.
- Goldman GS, King PG. Review of the United States universal varicella vaccination program: herpes zoster incidence rates, cost-effectiveness, and vaccine efficacy based primarily on the Antelope Valley Varicella Active Surveillance Project data. Vaccine. 2013;31:1680-1694.
- Arikawa J, Asahi T, Au WY, et al. Zoster (shingles, herpes zoster). In: James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin. 11th ed. Philadelphia, PA: Saunders/Elsevier; 2011:372-376.
- Guris D, Jumaan AO, Mascola L, et al. Changing varicella epidemiology in active surveillance sites–United States, 1995-2005. J Infect Dis. 2008;197(suppl 2):S71-S75.
- Petursson G, Helgason S, Gudmundsson S, et al. Herpes zoster in children and adolescents. Pediatr Infect Dis J. 1998;17:905-908.
- Oladokun RE, Olomukoro CN, Owa AB. Disseminated herpes zoster ophthalmicus in an immunocompetent 8-year-old boy. Clin Pract. 2013;3:e16.
- Lewkonia IK, Jackson AA. Infantile herpes zoster after intrauterine exposure to varicella. Br Med J. 1973;3:149.
- Zaal MJ, Völker-Dieben HJ, D’Amaro J. Prognostic value of Hutchinson’s sign in acute herpes zoster ophthalmicus. Graefes Arch Clin Exp Ophthalmol. 2003;241:187-191.
- Harding SP, Lipton JR, Wells JC. Natural history of herpes zoster ophthalmicus: predictors of postherpetic neuralgia and ocular involvement. Br J Ophthalmol. 1987;71:353-358.
- Higashimoto Y, Ihira M, Ohta A, et al. Discriminating between varicella-zoster virus vaccine and wild-type strains by loop-mediated isothermal amplification. J Clin Microbiol. 2008;46:2665-2670.
- Harbecke R, Oxman MN, Arnold, et al. A real-time PCR assay to identify and discriminate among wild-type and vaccine strains of varicella-zoster virus and herpes simplex virus in clinical specimens, and comparison with the clinical diagnoses. J Med Virol. 2009;81:1310-1322.
- Albrecht MA. Diagnosis of varicella-zoster infection. UpToDate website. http://www.uptodate.com/contents/diagnosis-of-varicella-zoster-virus-infection. Updated July 6, 2015. Accessed July 19, 2016.
- Myers MG, Seward JF, LaRussa PS. Varicella-zoster virus. In: Kliegman RM, Behrman RE, Jenson HB, et al, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Saunders; 2011:1104-1105.
- Terada K, Kawano S, Yoshihiro K, et al. Varicella-zoster virus (VZV) reactivation is related to the low response of VZV-specific immunity after chickenpox in infancy. J Infect Dis. 1994;169:650-652.
- Takayama N, Yamada H, Kaku H, et al. Herpes zoster in immunocompetent and immunocompromised Japanese children. Pediatr Int. 2000;42:275-279.
- Weinmann S, Chun C, Schmid DS, et al. Incidence and clinical characteristics of herpes zoster among children in the varicella vaccine era, 2005-2009. J Infect Dis. 2013;208:1859-1868.
- Civen R, Lopez AS, Zhang J, et al. Varicella outbreak epidemiology in an active surveillance site, 1995–2005. J Infect Dis. 2008;197(suppl 2):S114-S119.
- Russell ML, Dover DC, Simmonds KA, et al. Shingles in Alberta: before and after publicly funded varicella vaccination. Vaccine. 2014;32:6319-6324.
- Goldman GS, King PG. Review of the United States universal varicella vaccination program: herpes zoster incidence rates, cost-effectiveness, and vaccine efficacy based primarily on the Antelope Valley Varicella Active Surveillance Project data. Vaccine. 2013;31:1680-1694.
- Arikawa J, Asahi T, Au WY, et al. Zoster (shingles, herpes zoster). In: James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin. 11th ed. Philadelphia, PA: Saunders/Elsevier; 2011:372-376.
- Guris D, Jumaan AO, Mascola L, et al. Changing varicella epidemiology in active surveillance sites–United States, 1995-2005. J Infect Dis. 2008;197(suppl 2):S71-S75.
- Petursson G, Helgason S, Gudmundsson S, et al. Herpes zoster in children and adolescents. Pediatr Infect Dis J. 1998;17:905-908.
- Oladokun RE, Olomukoro CN, Owa AB. Disseminated herpes zoster ophthalmicus in an immunocompetent 8-year-old boy. Clin Pract. 2013;3:e16.
- Lewkonia IK, Jackson AA. Infantile herpes zoster after intrauterine exposure to varicella. Br Med J. 1973;3:149.
- Zaal MJ, Völker-Dieben HJ, D’Amaro J. Prognostic value of Hutchinson’s sign in acute herpes zoster ophthalmicus. Graefes Arch Clin Exp Ophthalmol. 2003;241:187-191.
- Harding SP, Lipton JR, Wells JC. Natural history of herpes zoster ophthalmicus: predictors of postherpetic neuralgia and ocular involvement. Br J Ophthalmol. 1987;71:353-358.
- Higashimoto Y, Ihira M, Ohta A, et al. Discriminating between varicella-zoster virus vaccine and wild-type strains by loop-mediated isothermal amplification. J Clin Microbiol. 2008;46:2665-2670.
- Harbecke R, Oxman MN, Arnold, et al. A real-time PCR assay to identify and discriminate among wild-type and vaccine strains of varicella-zoster virus and herpes simplex virus in clinical specimens, and comparison with the clinical diagnoses. J Med Virol. 2009;81:1310-1322.
- Albrecht MA. Diagnosis of varicella-zoster infection. UpToDate website. http://www.uptodate.com/contents/diagnosis-of-varicella-zoster-virus-infection. Updated July 6, 2015. Accessed July 19, 2016.
Practice Points
- Herpes zoster (HZ) should be included in the differential diagnosis for children presenting with vesicular lesions in a dermatomal distribution and a history of varicella exposure.
- Clinical diagnosis of HZ and herpes simplex virus can be aided by the use of viral polymerase chain reaction testing.
- Children with HZ should be monitored for the same possible complications as adults.
Predicting outcomes in relapsed BCP-ALL
Image by Vashi Donsk
Screening for genetic abnormalities can provide a more accurate prediction of outcomes in children with relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL), according to a study published in Blood.
Researchers found that mutations or deletions in TP53, NR3C1, BTG1, and NRAS were associated with inferior outcomes in relapsed BCP-ALL.
And screening for these abnormalities could improve upon the predictive accuracy of clinical risk factors.
“Current methods used to guide treatment for relapsed leukemia are not accurate enough, with some children believed to have a good chance of survival actually responding very poorly to chemotherapy,” said study author Anthony Moorman, PhD, of Newcastle University in Newcastle upon Tyne, UK.
“Screening patients at relapse for key genetic abnormalities that influence outcome will ensure that treatment can be personalized, thereby improving their chances of survival.”
For this study, Dr Moorman and his colleagues analyzed cytogenetic data from 427 children with relapsed BCP-ALL and screened 238 patients with a marrow relapse for certain copy number alterations and mutations.
According to univariate analysis, alterations in TP53, NR3C1 deletions, and BTG1 deletions were significantly associated with patient outcomes.
Patients with TP53 alterations had a higher risk of progression (hazard ratio [HR]=2.36, P<0.001) and death (HR=2.56, P<0.001), as did patients with deletions in NR3C1 and BTG1.
Because both NR3C1 and BTG1 are implicated in resistance to glucocorticoids and the deletions are mutually exclusive, the researchers considered the effect of the deletions together. So for patients with NR3C1 and BTG1 deletions, the HR for progression was 2.15 (P=0.002), and the HR for death was 1.91 (P=0.015).
Patients with NRAS mutations had an increased risk of progression and death as well, but this did not reach statistical significance.
The researchers also found that patients who were standard risk according to clinical characteristics but, at the time of relapse, had one or more high-risk genetic abnormalities had poorer outcomes.
Standard-risk patients with a TP53 alteration had an increased risk of death (HR=2.56, P<0.001), as did standard-risk patients with NR3C1 and BTG1 deletions (HR=1.91, P=0.015).
Standard-risk patients with NRAS mutations and high hyperdiploidy had an increased risk of progression (HR=3.17, P=0.026) and death (HR=3.41, P=0.032).
The researchers concluded that the outcomes of clinical standard-risk patients with high-risk cytogenetics were equivalent to outcomes of clinical high-risk patients.
The team therefore believes that screening BCP-ALL patients for the aforementioned genetic abnormalities at relapse will improve patient stratification and outcomes. 
Image by Vashi Donsk
Screening for genetic abnormalities can provide a more accurate prediction of outcomes in children with relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL), according to a study published in Blood.
Researchers found that mutations or deletions in TP53, NR3C1, BTG1, and NRAS were associated with inferior outcomes in relapsed BCP-ALL.
And screening for these abnormalities could improve upon the predictive accuracy of clinical risk factors.
“Current methods used to guide treatment for relapsed leukemia are not accurate enough, with some children believed to have a good chance of survival actually responding very poorly to chemotherapy,” said study author Anthony Moorman, PhD, of Newcastle University in Newcastle upon Tyne, UK.
“Screening patients at relapse for key genetic abnormalities that influence outcome will ensure that treatment can be personalized, thereby improving their chances of survival.”
For this study, Dr Moorman and his colleagues analyzed cytogenetic data from 427 children with relapsed BCP-ALL and screened 238 patients with a marrow relapse for certain copy number alterations and mutations.
According to univariate analysis, alterations in TP53, NR3C1 deletions, and BTG1 deletions were significantly associated with patient outcomes.
Patients with TP53 alterations had a higher risk of progression (hazard ratio [HR]=2.36, P<0.001) and death (HR=2.56, P<0.001), as did patients with deletions in NR3C1 and BTG1.
Because both NR3C1 and BTG1 are implicated in resistance to glucocorticoids and the deletions are mutually exclusive, the researchers considered the effect of the deletions together. So for patients with NR3C1 and BTG1 deletions, the HR for progression was 2.15 (P=0.002), and the HR for death was 1.91 (P=0.015).
Patients with NRAS mutations had an increased risk of progression and death as well, but this did not reach statistical significance.
The researchers also found that patients who were standard risk according to clinical characteristics but, at the time of relapse, had one or more high-risk genetic abnormalities had poorer outcomes.
Standard-risk patients with a TP53 alteration had an increased risk of death (HR=2.56, P<0.001), as did standard-risk patients with NR3C1 and BTG1 deletions (HR=1.91, P=0.015).
Standard-risk patients with NRAS mutations and high hyperdiploidy had an increased risk of progression (HR=3.17, P=0.026) and death (HR=3.41, P=0.032).
The researchers concluded that the outcomes of clinical standard-risk patients with high-risk cytogenetics were equivalent to outcomes of clinical high-risk patients.
The team therefore believes that screening BCP-ALL patients for the aforementioned genetic abnormalities at relapse will improve patient stratification and outcomes.
Image by Vashi Donsk
Screening for genetic abnormalities can provide a more accurate prediction of outcomes in children with relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL), according to a study published in Blood.
Researchers found that mutations or deletions in TP53, NR3C1, BTG1, and NRAS were associated with inferior outcomes in relapsed BCP-ALL.
And screening for these abnormalities could improve upon the predictive accuracy of clinical risk factors.
“Current methods used to guide treatment for relapsed leukemia are not accurate enough, with some children believed to have a good chance of survival actually responding very poorly to chemotherapy,” said study author Anthony Moorman, PhD, of Newcastle University in Newcastle upon Tyne, UK.
“Screening patients at relapse for key genetic abnormalities that influence outcome will ensure that treatment can be personalized, thereby improving their chances of survival.”
For this study, Dr Moorman and his colleagues analyzed cytogenetic data from 427 children with relapsed BCP-ALL and screened 238 patients with a marrow relapse for certain copy number alterations and mutations.
According to univariate analysis, alterations in TP53, NR3C1 deletions, and BTG1 deletions were significantly associated with patient outcomes.
Patients with TP53 alterations had a higher risk of progression (hazard ratio [HR]=2.36, P<0.001) and death (HR=2.56, P<0.001), as did patients with deletions in NR3C1 and BTG1.
Because both NR3C1 and BTG1 are implicated in resistance to glucocorticoids and the deletions are mutually exclusive, the researchers considered the effect of the deletions together. So for patients with NR3C1 and BTG1 deletions, the HR for progression was 2.15 (P=0.002), and the HR for death was 1.91 (P=0.015).
Patients with NRAS mutations had an increased risk of progression and death as well, but this did not reach statistical significance.
The researchers also found that patients who were standard risk according to clinical characteristics but, at the time of relapse, had one or more high-risk genetic abnormalities had poorer outcomes.
Standard-risk patients with a TP53 alteration had an increased risk of death (HR=2.56, P<0.001), as did standard-risk patients with NR3C1 and BTG1 deletions (HR=1.91, P=0.015).
Standard-risk patients with NRAS mutations and high hyperdiploidy had an increased risk of progression (HR=3.17, P=0.026) and death (HR=3.41, P=0.032).
The researchers concluded that the outcomes of clinical standard-risk patients with high-risk cytogenetics were equivalent to outcomes of clinical high-risk patients.
The team therefore believes that screening BCP-ALL patients for the aforementioned genetic abnormalities at relapse will improve patient stratification and outcomes.
Office-based evidence-informed tools guide obesity and eating disorder counseling
Avoid weight-based language, use motivational interviewing techniques, and promote healthy family-based lifestyle modifications to prevent and manage obesity without predisposing adolescents to eating disorders, according to new recommendations in an American Academy of Pediatrics clinical report.
Obesity and eating disorders are becoming increasingly prevalent in adolescents. In 2012, 20.5% of 12- to 19-year-olds met sex-specific body mass index (BMI) criteria for obesity, according to data from the National Health and Nutrition Examination survey. From 1999 to 2006, there was a 119% increase in hospitalizations due to eating disorders among children younger than 12 years, according to a 2011 study by the Agency for Healthcare Research and Quality.
Most adolescents who develop eating disorders are not obese, lead coauthor Neville H. Golden, MD, of Stanford (Calif.) University and his associates noted in the report by the AAP Committee on Nutrition, the Committee on Adolescence, and the Section on Obesity (Pediatrics. 2016 Aug. doi: 10.1542/peds.2016-1649).
However, in some adolescents, obesity prevention or management and initial attempts to lose weight can spiral into the development of an eating disorder, they said. “In one study in adolescents seeking treatment of an [eating disorder], 36.7% had a previous weight greater than the 85th percentile for age and sex.”
Cross-sectional and longitudinal observational studies identified dieting, body dissatisfaction, and talking about or teasing a child about his or her weight as risk factors for obesity and eating disorders. Conversely, family meals have been associated with improved dietary quality and a reduction in eating disorders among adolescent girls.
As pediatricians are often the first professional consulted by a parent when eating disorders or obesity are a concern, the investigators recommended the following office-based, evidence-informed tools to provide guidance about obesity and eating disorders:
• Discourage dieting, skipping of meals, or the use of diet pills.
• Encourage healthy eating and physical activity.
• Promote a positive body image; do not focus on body dissatisfaction as a reason for dieting.
• Encourage family meals.
• Encourage families not to talk about weight, but rather to talk about healthy eating and being active to stay healthy.
• Inquire about a history of mistreatment or bullying in overweight and obese teenagers and address this issue with patients and their families.
• Monitor weight loss in adolescents who need to lose weight.
The American Academy of Pediatrics supported this clinical report. The authors had no relevant disclosures to report.
On Twitter @jessnicolecraig
Avoid weight-based language, use motivational interviewing techniques, and promote healthy family-based lifestyle modifications to prevent and manage obesity without predisposing adolescents to eating disorders, according to new recommendations in an American Academy of Pediatrics clinical report.
Obesity and eating disorders are becoming increasingly prevalent in adolescents. In 2012, 20.5% of 12- to 19-year-olds met sex-specific body mass index (BMI) criteria for obesity, according to data from the National Health and Nutrition Examination survey. From 1999 to 2006, there was a 119% increase in hospitalizations due to eating disorders among children younger than 12 years, according to a 2011 study by the Agency for Healthcare Research and Quality.
Most adolescents who develop eating disorders are not obese, lead coauthor Neville H. Golden, MD, of Stanford (Calif.) University and his associates noted in the report by the AAP Committee on Nutrition, the Committee on Adolescence, and the Section on Obesity (Pediatrics. 2016 Aug. doi: 10.1542/peds.2016-1649).
However, in some adolescents, obesity prevention or management and initial attempts to lose weight can spiral into the development of an eating disorder, they said. “In one study in adolescents seeking treatment of an [eating disorder], 36.7% had a previous weight greater than the 85th percentile for age and sex.”
Cross-sectional and longitudinal observational studies identified dieting, body dissatisfaction, and talking about or teasing a child about his or her weight as risk factors for obesity and eating disorders. Conversely, family meals have been associated with improved dietary quality and a reduction in eating disorders among adolescent girls.
As pediatricians are often the first professional consulted by a parent when eating disorders or obesity are a concern, the investigators recommended the following office-based, evidence-informed tools to provide guidance about obesity and eating disorders:
• Discourage dieting, skipping of meals, or the use of diet pills.
• Encourage healthy eating and physical activity.
• Promote a positive body image; do not focus on body dissatisfaction as a reason for dieting.
• Encourage family meals.
• Encourage families not to talk about weight, but rather to talk about healthy eating and being active to stay healthy.
• Inquire about a history of mistreatment or bullying in overweight and obese teenagers and address this issue with patients and their families.
• Monitor weight loss in adolescents who need to lose weight.
The American Academy of Pediatrics supported this clinical report. The authors had no relevant disclosures to report.
On Twitter @jessnicolecraig
Avoid weight-based language, use motivational interviewing techniques, and promote healthy family-based lifestyle modifications to prevent and manage obesity without predisposing adolescents to eating disorders, according to new recommendations in an American Academy of Pediatrics clinical report.
Obesity and eating disorders are becoming increasingly prevalent in adolescents. In 2012, 20.5% of 12- to 19-year-olds met sex-specific body mass index (BMI) criteria for obesity, according to data from the National Health and Nutrition Examination survey. From 1999 to 2006, there was a 119% increase in hospitalizations due to eating disorders among children younger than 12 years, according to a 2011 study by the Agency for Healthcare Research and Quality.
Most adolescents who develop eating disorders are not obese, lead coauthor Neville H. Golden, MD, of Stanford (Calif.) University and his associates noted in the report by the AAP Committee on Nutrition, the Committee on Adolescence, and the Section on Obesity (Pediatrics. 2016 Aug. doi: 10.1542/peds.2016-1649).
However, in some adolescents, obesity prevention or management and initial attempts to lose weight can spiral into the development of an eating disorder, they said. “In one study in adolescents seeking treatment of an [eating disorder], 36.7% had a previous weight greater than the 85th percentile for age and sex.”
Cross-sectional and longitudinal observational studies identified dieting, body dissatisfaction, and talking about or teasing a child about his or her weight as risk factors for obesity and eating disorders. Conversely, family meals have been associated with improved dietary quality and a reduction in eating disorders among adolescent girls.
As pediatricians are often the first professional consulted by a parent when eating disorders or obesity are a concern, the investigators recommended the following office-based, evidence-informed tools to provide guidance about obesity and eating disorders:
• Discourage dieting, skipping of meals, or the use of diet pills.
• Encourage healthy eating and physical activity.
• Promote a positive body image; do not focus on body dissatisfaction as a reason for dieting.
• Encourage family meals.
• Encourage families not to talk about weight, but rather to talk about healthy eating and being active to stay healthy.
• Inquire about a history of mistreatment or bullying in overweight and obese teenagers and address this issue with patients and their families.
• Monitor weight loss in adolescents who need to lose weight.
The American Academy of Pediatrics supported this clinical report. The authors had no relevant disclosures to report.
On Twitter @jessnicolecraig
FROM PEDIATRICS
