Pediatrics

An 8-year-old girl who was infected with SARS-CoV-2 died after developing an extremely rare condition known as acute fulminant cerebral edema (AFCE), according to pediatric neurologists who are urging colleagues to watch out for similar cases.

At least one other child in the United States has died after becoming infected with the virus and developing cerebral edema. “The rapid and devastating clinical course in both of these cases highlights the need for early recognition of a cerebral edema and AFCE as potential complications of COVID-19 in pediatric patients,” the neurologists wrote.

The case was highlighted in a poster presented at the annual meeting of the Child Neurology Society and in a report published earlier this year in Child Neurology Open.

According to pediatric neurologist Timothy Gershon, MD, PhD , of the University of North Carolina at Chapel Hill, the child appeared in clinic in July 2020. She had been healthy but was suffering from 1 day of fever, seizure-like activity (generalized convulsions and drooling), anorexia, and lethargy.

The girl, who was subsequently diagnosed with COVID-19, deteriorated in the hospital. “She received IV dexamethasone in attempts to reduce cerebral edema,” the neurologists wrote. “Regarding immunomodulatory therapy, she received intravenous immunoglobulin (2 g/kg), anakinra, and hydrocortisone; despite approval for remdesivir and COVID-19 convalescent plasma, these were ultimately withheld due to poor prognosis.”

Brain death examinations at 24 and 48 hours after cardiac arrest were consistent with brain death, they reported.

Neurologists believe the patient suffered from AFCE, “an often fatal pediatric clinical entity consisting of fever, encephalopathy, and new-onset seizures followed by rapid, diffuse, and medically-refractory cerebral edema.” They add that “AFCE occurs as a rare complication of a variety of common pediatric infections, and a CNS [central nervous system] pathogen is identified in only a minority of cases, suggesting a para-infectious mechanism of edema.”

Neurologists offered a case definition of the “recently recognized” AFCE earlier this year.

“This was an extremely rare rapid progression to cerebral edema. I think it was related to the patient’s COVID infection, but why this patient got it and others don’t is unknown,” Dr. Gershon said in an interview. “The full spectrum of neurological complications of COVID were not yet known [at the time]. We didn’t know, and still don’t know, what the causative links are between COVID and suddenly having seizures and brain swelling.”

He said he’d treat a similar patient differently now and give dexamethasone earlier in the clinical course, although “there is no data to tell us if any therapy could have reversed it.” Specifically, he said, “I’d give dexamethasone at the first sign of brain involvement, using the dosing recommended for cerebral edema, and try to get the MRI earlier in the course.”

Dr. Gershon and colleagues noted another case of fatal cerebral edema in a child, a 7-year-old boy who was treated in New York state. That case “shows that fatal cerebral edema may complicate pediatric multisystem inflammatory syndrome,” they wrote.

Pediatric critical care specialist Preetha Krishnan, MD, of Randall Children’s Hospital at Legacy Emanuel in Portland, Ore., helped develop the new definition of AFCE. In an interview, she said AFCE is difficult to diagnose because the signs/symptoms – such as fever, altered sensorium, and seizures – are found in other conditions such as febrile status epilepticus with a viral illness. 
“The key to recognition of AFCE is that unlike other disease processes, these children have rapid neurologic progression,” she said. “In addition, many of our AFCE patients also had vomiting and/or headache, which in retrospect was likely an indication of elevated ICP [intracranial pressure] rather than viral infection.”
She added that “if a child with fever, seizures, and encephalopathy has cerebral edema on imaging and/or has neurologic progression, AFCE should be considered. Most of our cases of AFCE had fulminant progression within the first 3 days of their head imaging noting cerebral edema. There are other neurologic diseases, such as acute necrotizing encephalopathy of childhood, that also have progressive signs/symptoms, but head imaging and lab work should help differentiate many of these etiologies.”
In regard to treatment, she said, “our unit would likely err on the side of providing as much neuroprotective measures as is reasonable, such as maintaining normothermia, consideration of hyperosmolar therapy, maintaining normocarbia and normoxemia, managing seizures, etc. I would recommend getting the entire neurocritical care team involved in the management discussion. This varies by center, but will likely include neurology, ID [infectious disease], possibly neurosurgery, and PICU.”
As for the new case report, Krishnan said COVID-19 has been linked to neurologic complications, “so it does not surprise me that AFCE is part of the neurologic spectrum of disease.”
No funding was reported, and the authors report no relevant disclosures. Dr. Krishnan has no disclosures.

An 8-year-old girl who was infected with SARS-CoV-2 died after developing an extremely rare condition known as acute fulminant cerebral edema (AFCE), according to pediatric neurologists who are urging colleagues to watch out for similar cases.

At least one other child in the United States has died after becoming infected with the virus and developing cerebral edema. “The rapid and devastating clinical course in both of these cases highlights the need for early recognition of a cerebral edema and AFCE as potential complications of COVID-19 in pediatric patients,” the neurologists wrote.

The case was highlighted in a poster presented at the annual meeting of the Child Neurology Society and in a report published earlier this year in Child Neurology Open.

According to pediatric neurologist Timothy Gershon, MD, PhD , of the University of North Carolina at Chapel Hill, the child appeared in clinic in July 2020. She had been healthy but was suffering from 1 day of fever, seizure-like activity (generalized convulsions and drooling), anorexia, and lethargy.

The girl, who was subsequently diagnosed with COVID-19, deteriorated in the hospital. “She received IV dexamethasone in attempts to reduce cerebral edema,” the neurologists wrote. “Regarding immunomodulatory therapy, she received intravenous immunoglobulin (2 g/kg), anakinra, and hydrocortisone; despite approval for remdesivir and COVID-19 convalescent plasma, these were ultimately withheld due to poor prognosis.”

Brain death examinations at 24 and 48 hours after cardiac arrest were consistent with brain death, they reported.

Neurologists believe the patient suffered from AFCE, “an often fatal pediatric clinical entity consisting of fever, encephalopathy, and new-onset seizures followed by rapid, diffuse, and medically-refractory cerebral edema.” They add that “AFCE occurs as a rare complication of a variety of common pediatric infections, and a CNS [central nervous system] pathogen is identified in only a minority of cases, suggesting a para-infectious mechanism of edema.”

Neurologists offered a case definition of the “recently recognized” AFCE earlier this year.

“This was an extremely rare rapid progression to cerebral edema. I think it was related to the patient’s COVID infection, but why this patient got it and others don’t is unknown,” Dr. Gershon said in an interview. “The full spectrum of neurological complications of COVID were not yet known [at the time]. We didn’t know, and still don’t know, what the causative links are between COVID and suddenly having seizures and brain swelling.”

He said he’d treat a similar patient differently now and give dexamethasone earlier in the clinical course, although “there is no data to tell us if any therapy could have reversed it.” Specifically, he said, “I’d give dexamethasone at the first sign of brain involvement, using the dosing recommended for cerebral edema, and try to get the MRI earlier in the course.”

Dr. Gershon and colleagues noted another case of fatal cerebral edema in a child, a 7-year-old boy who was treated in New York state. That case “shows that fatal cerebral edema may complicate pediatric multisystem inflammatory syndrome,” they wrote.

Pediatric critical care specialist Preetha Krishnan, MD, of Randall Children’s Hospital at Legacy Emanuel in Portland, Ore., helped develop the new definition of AFCE. In an interview, she said AFCE is difficult to diagnose because the signs/symptoms – such as fever, altered sensorium, and seizures – are found in other conditions such as febrile status epilepticus with a viral illness. 
“The key to recognition of AFCE is that unlike other disease processes, these children have rapid neurologic progression,” she said. “In addition, many of our AFCE patients also had vomiting and/or headache, which in retrospect was likely an indication of elevated ICP [intracranial pressure] rather than viral infection.”
She added that “if a child with fever, seizures, and encephalopathy has cerebral edema on imaging and/or has neurologic progression, AFCE should be considered. Most of our cases of AFCE had fulminant progression within the first 3 days of their head imaging noting cerebral edema. There are other neurologic diseases, such as acute necrotizing encephalopathy of childhood, that also have progressive signs/symptoms, but head imaging and lab work should help differentiate many of these etiologies.”
In regard to treatment, she said, “our unit would likely err on the side of providing as much neuroprotective measures as is reasonable, such as maintaining normothermia, consideration of hyperosmolar therapy, maintaining normocarbia and normoxemia, managing seizures, etc. I would recommend getting the entire neurocritical care team involved in the management discussion. This varies by center, but will likely include neurology, ID [infectious disease], possibly neurosurgery, and PICU.”
As for the new case report, Krishnan said COVID-19 has been linked to neurologic complications, “so it does not surprise me that AFCE is part of the neurologic spectrum of disease.”
No funding was reported, and the authors report no relevant disclosures. Dr. Krishnan has no disclosures.

An 8-year-old girl who was infected with SARS-CoV-2 died after developing an extremely rare condition known as acute fulminant cerebral edema (AFCE), according to pediatric neurologists who are urging colleagues to watch out for similar cases.

At least one other child in the United States has died after becoming infected with the virus and developing cerebral edema. “The rapid and devastating clinical course in both of these cases highlights the need for early recognition of a cerebral edema and AFCE as potential complications of COVID-19 in pediatric patients,” the neurologists wrote.

The case was highlighted in a poster presented at the annual meeting of the Child Neurology Society and in a report published earlier this year in Child Neurology Open.

According to pediatric neurologist Timothy Gershon, MD, PhD , of the University of North Carolina at Chapel Hill, the child appeared in clinic in July 2020. She had been healthy but was suffering from 1 day of fever, seizure-like activity (generalized convulsions and drooling), anorexia, and lethargy.

The girl, who was subsequently diagnosed with COVID-19, deteriorated in the hospital. “She received IV dexamethasone in attempts to reduce cerebral edema,” the neurologists wrote. “Regarding immunomodulatory therapy, she received intravenous immunoglobulin (2 g/kg), anakinra, and hydrocortisone; despite approval for remdesivir and COVID-19 convalescent plasma, these were ultimately withheld due to poor prognosis.”

Brain death examinations at 24 and 48 hours after cardiac arrest were consistent with brain death, they reported.

Neurologists believe the patient suffered from AFCE, “an often fatal pediatric clinical entity consisting of fever, encephalopathy, and new-onset seizures followed by rapid, diffuse, and medically-refractory cerebral edema.” They add that “AFCE occurs as a rare complication of a variety of common pediatric infections, and a CNS [central nervous system] pathogen is identified in only a minority of cases, suggesting a para-infectious mechanism of edema.”

Neurologists offered a case definition of the “recently recognized” AFCE earlier this year.

“This was an extremely rare rapid progression to cerebral edema. I think it was related to the patient’s COVID infection, but why this patient got it and others don’t is unknown,” Dr. Gershon said in an interview. “The full spectrum of neurological complications of COVID were not yet known [at the time]. We didn’t know, and still don’t know, what the causative links are between COVID and suddenly having seizures and brain swelling.”

He said he’d treat a similar patient differently now and give dexamethasone earlier in the clinical course, although “there is no data to tell us if any therapy could have reversed it.” Specifically, he said, “I’d give dexamethasone at the first sign of brain involvement, using the dosing recommended for cerebral edema, and try to get the MRI earlier in the course.”

Dr. Gershon and colleagues noted another case of fatal cerebral edema in a child, a 7-year-old boy who was treated in New York state. That case “shows that fatal cerebral edema may complicate pediatric multisystem inflammatory syndrome,” they wrote.

Pediatric critical care specialist Preetha Krishnan, MD, of Randall Children’s Hospital at Legacy Emanuel in Portland, Ore., helped develop the new definition of AFCE. In an interview, she said AFCE is difficult to diagnose because the signs/symptoms – such as fever, altered sensorium, and seizures – are found in other conditions such as febrile status epilepticus with a viral illness. 
“The key to recognition of AFCE is that unlike other disease processes, these children have rapid neurologic progression,” she said. “In addition, many of our AFCE patients also had vomiting and/or headache, which in retrospect was likely an indication of elevated ICP [intracranial pressure] rather than viral infection.”
She added that “if a child with fever, seizures, and encephalopathy has cerebral edema on imaging and/or has neurologic progression, AFCE should be considered. Most of our cases of AFCE had fulminant progression within the first 3 days of their head imaging noting cerebral edema. There are other neurologic diseases, such as acute necrotizing encephalopathy of childhood, that also have progressive signs/symptoms, but head imaging and lab work should help differentiate many of these etiologies.”
In regard to treatment, she said, “our unit would likely err on the side of providing as much neuroprotective measures as is reasonable, such as maintaining normothermia, consideration of hyperosmolar therapy, maintaining normocarbia and normoxemia, managing seizures, etc. I would recommend getting the entire neurocritical care team involved in the management discussion. This varies by center, but will likely include neurology, ID [infectious disease], possibly neurosurgery, and PICU.”
As for the new case report, Krishnan said COVID-19 has been linked to neurologic complications, “so it does not surprise me that AFCE is part of the neurologic spectrum of disease.”
No funding was reported, and the authors report no relevant disclosures. Dr. Krishnan has no disclosures.

Newborns of pregnant women who were treated with selective serotonin reuptake inhibitors during the third trimester are almost three times as likely to develop neonatal encephalopathy (NE), although the overall risk remains extremely low, a new study finds.

The findings were presented in a poster at the 50th annual meeting of the Child Neurology Society.

“Our work showed that neonates exposed to SSRI in utero had higher risks of neonatal encephalopathy even when adjusting for confounders such as maternal mental health disorders and age. SSRIs could cause side effects such as encephalopathy in neonates, and these risks need to be balanced carefully with the potential benefits of treatment to the mother,” study lead author Marie Cornet, MD, a neonatology fellow with Benioff Children’s Hospital at the University of California, San Francisco, said in an interview.

According to Dr. Cornet, “we know that SSRI exposure in utero is associated with increased risks of respiratory distress at birth, need for positive-pressure ventilation, and an abnormal neurologic exam.” The researchers launched the new study to determine if the estimated 4%-8% of pregnant women who take SSRIs may be putting their newborns at greater risk of NE.

The researchers retrospectively tracked 305,426 infants who were born in the Kaiser Permanente Northern California health system (≥35 weeks) from 2011 to 2019. The mothers had an average age of 31 years, and approximately 34.7% were White, 34.7% of unknown race, 23.3% Asian, and 6.2% Black.

The researchers defined NE as a “5-minute APGAR score <7 and abnormal level of consciousness, activity, tone, or reflexes.”

A total of 8,024 infants (2.6%) had mothers who used SSRIs in the third trimester, and 510 (0.17%) were determined to have had NE.

After adjustment for maternal depression or anxiety, maternal age, race, and hospital, exposed neonates had 2.7 times higher odds of NE (odds ratio, 2.7).

Each 25 mg per day increase in the dose of SSRIs, as equalized to doses of sertraline (Zoloft), was linked to a significant 31% increase in the odds of developing NE (OR, 1.31).

The study doesn’t examine the benefits of SSRI treatment in pregnancy. Those taking SSRIs were much more likely to have depression during pregnancy (76.5% vs. 13.5%) and anxiety (56.7% vs. 6.9%), compared with those who did not take the drug.

The possible connection between SSRIs and NE is unclear. “SSRIs may contribute to NE by a withdrawal mechanism or by a toxicity mechanism. It is also possible that SSRIs themselves are not responsible for encephalopathy, or that the severity of maternal mental health is itself responsible for increased neonatal encephalopathy,” Dr. Cornet said. “However, we believe we adjusted our results thoroughly for that. Furthermore, in this cohort, neonates born from mothers with untreated depression were not at higher risk of encephalopathy than neonates born to mothers without depression.”

She added: “When infants have acidosis or require prolonged resuscitation after birth, they get treated with therapeutic hypothermia. This invasive treatment was shown to decrease mortality and morbidity in neonates with hypoxic-ischemic encephalopathy. However, therapeutic hypothermia may not be helpful in infants with encephalopathy due to other causes than acute hypoxia-ischemia, such as infection, inflammation, genetic conditions, or exposure to toxins. In the case of SSRIs, our results show that, while neonates often have encephalopathy, this encephalopathy is often mild and self-resolved. We did not see a statistically significant increase in acidosis or treatment with therapeutic hypothermia.”

In the future neurologists should consider SSRI use as a potential cause in cases of NE, Dr. Cornet said. “If there are no signs of hypoxic-ischemic encephalopathy – no evidence of acidosis, acute perinatal event – treatment with therapeutic hypothermia may not be indicated.”

Dr. Cornet said more research is in the works. “Studying the long-term side effect of SSRIs on neonatal brain development and injury is essential,” she said. “We plan to compare brain injury in neonates exposed and unexposed to SSRIs and examine long-term outcomes to assess if the effect of SSRI exposure is transient or has a lasting impact.”

This study was funded by the Thrasher Early Career Research Grant and by the Newborn Brain Research Innovation Award at UCSF. The authors have no relevant disclosures.
 

Newborns of pregnant women who were treated with selective serotonin reuptake inhibitors during the third trimester are almost three times as likely to develop neonatal encephalopathy (NE), although the overall risk remains extremely low, a new study finds.

The findings were presented in a poster at the 50th annual meeting of the Child Neurology Society.

“Our work showed that neonates exposed to SSRI in utero had higher risks of neonatal encephalopathy even when adjusting for confounders such as maternal mental health disorders and age. SSRIs could cause side effects such as encephalopathy in neonates, and these risks need to be balanced carefully with the potential benefits of treatment to the mother,” study lead author Marie Cornet, MD, a neonatology fellow with Benioff Children’s Hospital at the University of California, San Francisco, said in an interview.

According to Dr. Cornet, “we know that SSRI exposure in utero is associated with increased risks of respiratory distress at birth, need for positive-pressure ventilation, and an abnormal neurologic exam.” The researchers launched the new study to determine if the estimated 4%-8% of pregnant women who take SSRIs may be putting their newborns at greater risk of NE.

The researchers retrospectively tracked 305,426 infants who were born in the Kaiser Permanente Northern California health system (≥35 weeks) from 2011 to 2019. The mothers had an average age of 31 years, and approximately 34.7% were White, 34.7% of unknown race, 23.3% Asian, and 6.2% Black.

The researchers defined NE as a “5-minute APGAR score <7 and abnormal level of consciousness, activity, tone, or reflexes.”

A total of 8,024 infants (2.6%) had mothers who used SSRIs in the third trimester, and 510 (0.17%) were determined to have had NE.

After adjustment for maternal depression or anxiety, maternal age, race, and hospital, exposed neonates had 2.7 times higher odds of NE (odds ratio, 2.7).

Each 25 mg per day increase in the dose of SSRIs, as equalized to doses of sertraline (Zoloft), was linked to a significant 31% increase in the odds of developing NE (OR, 1.31).

The study doesn’t examine the benefits of SSRI treatment in pregnancy. Those taking SSRIs were much more likely to have depression during pregnancy (76.5% vs. 13.5%) and anxiety (56.7% vs. 6.9%), compared with those who did not take the drug.

The possible connection between SSRIs and NE is unclear. “SSRIs may contribute to NE by a withdrawal mechanism or by a toxicity mechanism. It is also possible that SSRIs themselves are not responsible for encephalopathy, or that the severity of maternal mental health is itself responsible for increased neonatal encephalopathy,” Dr. Cornet said. “However, we believe we adjusted our results thoroughly for that. Furthermore, in this cohort, neonates born from mothers with untreated depression were not at higher risk of encephalopathy than neonates born to mothers without depression.”

She added: “When infants have acidosis or require prolonged resuscitation after birth, they get treated with therapeutic hypothermia. This invasive treatment was shown to decrease mortality and morbidity in neonates with hypoxic-ischemic encephalopathy. However, therapeutic hypothermia may not be helpful in infants with encephalopathy due to other causes than acute hypoxia-ischemia, such as infection, inflammation, genetic conditions, or exposure to toxins. In the case of SSRIs, our results show that, while neonates often have encephalopathy, this encephalopathy is often mild and self-resolved. We did not see a statistically significant increase in acidosis or treatment with therapeutic hypothermia.”

In the future neurologists should consider SSRI use as a potential cause in cases of NE, Dr. Cornet said. “If there are no signs of hypoxic-ischemic encephalopathy – no evidence of acidosis, acute perinatal event – treatment with therapeutic hypothermia may not be indicated.”

Dr. Cornet said more research is in the works. “Studying the long-term side effect of SSRIs on neonatal brain development and injury is essential,” she said. “We plan to compare brain injury in neonates exposed and unexposed to SSRIs and examine long-term outcomes to assess if the effect of SSRI exposure is transient or has a lasting impact.”

This study was funded by the Thrasher Early Career Research Grant and by the Newborn Brain Research Innovation Award at UCSF. The authors have no relevant disclosures.
 

Newborns of pregnant women who were treated with selective serotonin reuptake inhibitors during the third trimester are almost three times as likely to develop neonatal encephalopathy (NE), although the overall risk remains extremely low, a new study finds.

The findings were presented in a poster at the 50th annual meeting of the Child Neurology Society.

“Our work showed that neonates exposed to SSRI in utero had higher risks of neonatal encephalopathy even when adjusting for confounders such as maternal mental health disorders and age. SSRIs could cause side effects such as encephalopathy in neonates, and these risks need to be balanced carefully with the potential benefits of treatment to the mother,” study lead author Marie Cornet, MD, a neonatology fellow with Benioff Children’s Hospital at the University of California, San Francisco, said in an interview.

According to Dr. Cornet, “we know that SSRI exposure in utero is associated with increased risks of respiratory distress at birth, need for positive-pressure ventilation, and an abnormal neurologic exam.” The researchers launched the new study to determine if the estimated 4%-8% of pregnant women who take SSRIs may be putting their newborns at greater risk of NE.

The researchers retrospectively tracked 305,426 infants who were born in the Kaiser Permanente Northern California health system (≥35 weeks) from 2011 to 2019. The mothers had an average age of 31 years, and approximately 34.7% were White, 34.7% of unknown race, 23.3% Asian, and 6.2% Black.

The researchers defined NE as a “5-minute APGAR score <7 and abnormal level of consciousness, activity, tone, or reflexes.”

A total of 8,024 infants (2.6%) had mothers who used SSRIs in the third trimester, and 510 (0.17%) were determined to have had NE.

After adjustment for maternal depression or anxiety, maternal age, race, and hospital, exposed neonates had 2.7 times higher odds of NE (odds ratio, 2.7).

Each 25 mg per day increase in the dose of SSRIs, as equalized to doses of sertraline (Zoloft), was linked to a significant 31% increase in the odds of developing NE (OR, 1.31).

The study doesn’t examine the benefits of SSRI treatment in pregnancy. Those taking SSRIs were much more likely to have depression during pregnancy (76.5% vs. 13.5%) and anxiety (56.7% vs. 6.9%), compared with those who did not take the drug.

The possible connection between SSRIs and NE is unclear. “SSRIs may contribute to NE by a withdrawal mechanism or by a toxicity mechanism. It is also possible that SSRIs themselves are not responsible for encephalopathy, or that the severity of maternal mental health is itself responsible for increased neonatal encephalopathy,” Dr. Cornet said. “However, we believe we adjusted our results thoroughly for that. Furthermore, in this cohort, neonates born from mothers with untreated depression were not at higher risk of encephalopathy than neonates born to mothers without depression.”

She added: “When infants have acidosis or require prolonged resuscitation after birth, they get treated with therapeutic hypothermia. This invasive treatment was shown to decrease mortality and morbidity in neonates with hypoxic-ischemic encephalopathy. However, therapeutic hypothermia may not be helpful in infants with encephalopathy due to other causes than acute hypoxia-ischemia, such as infection, inflammation, genetic conditions, or exposure to toxins. In the case of SSRIs, our results show that, while neonates often have encephalopathy, this encephalopathy is often mild and self-resolved. We did not see a statistically significant increase in acidosis or treatment with therapeutic hypothermia.”

In the future neurologists should consider SSRI use as a potential cause in cases of NE, Dr. Cornet said. “If there are no signs of hypoxic-ischemic encephalopathy – no evidence of acidosis, acute perinatal event – treatment with therapeutic hypothermia may not be indicated.”

Dr. Cornet said more research is in the works. “Studying the long-term side effect of SSRIs on neonatal brain development and injury is essential,” she said. “We plan to compare brain injury in neonates exposed and unexposed to SSRIs and examine long-term outcomes to assess if the effect of SSRI exposure is transient or has a lasting impact.”

This study was funded by the Thrasher Early Career Research Grant and by the Newborn Brain Research Innovation Award at UCSF. The authors have no relevant disclosures.
 

The common-cold viruses rhinovirus (RV) and enterovirus (EV) continued to circulate among children during the COVID-19 pandemic while there were sharp declines in influenza, respiratory syncytial virus (RSV), and other respiratory viruses, new data indicate.

Researchers used data from the Centers for Disease Control and Prevention’s New Vaccine Surveillance Network. The cases involved 37,676 children in seven geographically diverse U.S. medical centers between December 2016 and January 2021. Patients presented to emergency departments or were hospitalized with RV, EV, and other acute respiratory viruses.

The investigators found that the percentage of children in whom RV/EV was detected from March 2020 to January 2021 was similar to the percentage during the same months in 2017-2018 and 2019-2020. However, the proportion of children infected with influenza, RSV, and other respiratory viruses combined dropped significantly in comparison to the three prior seasons.

A version of this article first appeared on Medscape.com.

The common-cold viruses rhinovirus (RV) and enterovirus (EV) continued to circulate among children during the COVID-19 pandemic while there were sharp declines in influenza, respiratory syncytial virus (RSV), and other respiratory viruses, new data indicate.

Researchers used data from the Centers for Disease Control and Prevention’s New Vaccine Surveillance Network. The cases involved 37,676 children in seven geographically diverse U.S. medical centers between December 2016 and January 2021. Patients presented to emergency departments or were hospitalized with RV, EV, and other acute respiratory viruses.

The investigators found that the percentage of children in whom RV/EV was detected from March 2020 to January 2021 was similar to the percentage during the same months in 2017-2018 and 2019-2020. However, the proportion of children infected with influenza, RSV, and other respiratory viruses combined dropped significantly in comparison to the three prior seasons.

A version of this article first appeared on Medscape.com.

The common-cold viruses rhinovirus (RV) and enterovirus (EV) continued to circulate among children during the COVID-19 pandemic while there were sharp declines in influenza, respiratory syncytial virus (RSV), and other respiratory viruses, new data indicate.

Researchers used data from the Centers for Disease Control and Prevention’s New Vaccine Surveillance Network. The cases involved 37,676 children in seven geographically diverse U.S. medical centers between December 2016 and January 2021. Patients presented to emergency departments or were hospitalized with RV, EV, and other acute respiratory viruses.

The investigators found that the percentage of children in whom RV/EV was detected from March 2020 to January 2021 was similar to the percentage during the same months in 2017-2018 and 2019-2020. However, the proportion of children infected with influenza, RSV, and other respiratory viruses combined dropped significantly in comparison to the three prior seasons.

A version of this article first appeared on Medscape.com.

To the Editor:

Kikuchi-Fujimoto Disease, also called histiocytic necrotizing lymphadenitis, was described in 1972 by both Kikuchi¹ and Fujimoto et al.² Most cases are reported in Asia, with limited reports in the United States.^3-5 Kikuchi-Fujimoto disease is a rare, self-limiting condition consisting of benign lymphadenopathy and oftentimes fever and systemic symptoms. Lymph node involvement may mimic non-Hodgkin lymphoma or other reactive lymphadenopathy, rendering diagnostic accuracy challenging.⁵ Cutaneous manifestations are reported in only 16% to 40% of patients.^6,7 Herein, we describe the clinical and pathologic features of a case of Kikuchi-Fujimoto disease with cutaneous involvement in an adolescent boy.

A 13-year-old adolescent boy with no notable medical history presented to the pediatric emergency department with cervical lymphadenopathy, weight loss, intermittent fever, and an evolving rash on the face, ears, arms, and thighs of 6 weeks’ duration. The illness began with enlarged lymph nodes and erythematous macules on the face and was diagnosed by his primary care physician as lymphadenitis that was unresponsive to clindamycin. Over the subsequent weeks, the rash worsened, and he developed intermittent fevers, night sweats, abdominal pain, and nausea with a 20-pound weight loss. He presented to the emergency department 3 weeks prior to the current admission and was noted to have elevated cytomegalovirus (CMV) IgM and IgG in addition to lymphopenia and anemia. He was discharged with outpatient follow-up. The rash progressed to involve the face, ears, arms, and thighs. One day prior to the current admission, the patient’s abdominal pain worsened acutely, and he experienced several episodes of emesis. He presented to the pediatric emergency department for further evaluation, and a dermatology consultation was requested at that time.

The patient’s rash was asymptomatic. In addition to the above symptoms, he also noted frequent nosebleeds, gingival bleeding, and diffuse myalgia that was most prominent on the hands and feet; he denied diarrhea, sick contacts, recent travel, or insect bites. His vital signs were normal, and he remained afebrile throughout the hospitalization. Physical examination revealed an ill-appearing patient with sunken eyes and dry lips. He had pink, oval, scaly plaques on the cheeks, ears, and arms (Figure 1). The thighs exhibited folliculocentric erythematous papules. The ocular conjunctivae were clear, but white exudative plaques were noted on the tongue. Tender, bilateral, cervical lymphadenopathy and diffuse abdominal tenderness with guarding and hepatosplenomegaly also were present. The fingers and toes were tender upon palpation.

Laboratory workup at admission revealed the following: low white blood cell count, 2700/μL (reference range, 4500–11,000/μL); low hemoglobin, 9.6 g/dL (reference range, 14.0–17.5 g/dL); elevated aspartate aminotransferase, 91 U/L (reference range, 10–30 U/L); and elevated alanine aminotransferase, 118 U/L (reference range, 10–40 U/L). Lactate dehydrogenase (582 U/L [reference range, 100–200 U/L]), ferritin (1681 ng/mL [reference range, 15–200 ng/mL]), and C-reactive protein (6.0 mg/L [reference range, 0.08–3.1 mg/L]) also were elevated. A respiratory viral panel was unremarkable. Blood cultures were negative, and an HIV 1/2 assay was nonreactive. A chest radiograph demonstrated clear lung fields. Computed tomography of the abdomen and pelvis showed prominent mesenteric, ileocolic, and retroperitoneal lymph nodes.

The differential diagnoses at this time included acute connective tissue disease, a paraneoplastic phenomenon, cutaneous lymphoma, or an infectious etiology. A punch biopsy of the skin as well as tissue cultures were performed from a lesion on the right arm. Quantitative immunoglobulin (IgA, IgG, IgM) levels were checked, all of which were within reference range. An antinuclear antibody (ANA) assay and rheumatoid factor were normal.

The tissue cultures were negative for bacteria, fungi, and mycobacteria. Microscopic examination of the skin biopsy revealed a moderate perivascular and interstitial infiltrate of predominantly histiocytes and lymphocytes with prominent karyorrhectic debris (nuclear dust) in the upper dermis as well as focal vacuolar interface changes with scattered necrotic keratinocytes in the epidermis (Figure 2). Based on these histopathologic findings, a diagnosis of Kikuchi-Fujimoto disease was considered. To confirm the diagnosis and to rule out the possibility of lymphoma, an excisional biopsy of the cervical lymph node was performed, which showed typical histopathologic features of histiocytic necrotizing lymphadenitis.

Given the patient’s clinical presentation with arthralgia, anorexia, lymphadenitis, and hepatosplenomegaly along with histopathologic findings from both the skin and lymph node biopsies, a diagnosis of Kikuchi-Fujimoto disease was made. The patient was conservatively managed with acetaminophen and was discharged with improvement in his appetite and systemic symptoms.

He was seen for follow-up 3 months later in the outpatient clinic. He denied any recurrence of systemic symptoms but endorsed a recent shedding of hair consistent with telogen effluvium. The rash had substantially improved, though residual asymptomatic erythematous plaques remained on the right forehead and right cheek (Figure 3). He was prescribed triamcinolone acetonide cream 0.1% to apply to the active area twice daily for the following 2 to 3 weeks.

Kikuchi-Fujimoto disease presents with a wide clinical spectrum, classically with benign lymphadenopathy and fever of unknown etiology.^5,6 Lymphadenopathy most often is cervical (55%–99%)⁸ and unilateral,^4,7 but patients can present with polyadenopathy (52%).^7,8 Constitutional signs commonly include fever (35%–76%), weight loss, arthritis (5%–34%), and leukopenia (25%–74%).^4,8,9

Cutaneous findings have been described in up to 40% of cases, of which clinical presentation is variable.⁶ Lesions may include blanchable, erythematous, painful, and/or indurated plaques, nodules, or maculopapules with confluence into patches, urticaria, morbilliform lesions, erythema multiforme, eyelid edema, leukocytoclastic vasculitis, papulopustules, ulcerated gingivae, and mucositis.^6,7,10-13 Patients with skin lesions may be at an increased risk for developing systemic lupus erythematosus (SLE).⁸ Our patient presented with erythematous scaly plaques with a predominance of lesions in photodistributed locations, which clinically mimicked an underlying connective tissue disease process such as SLE.

Infectious agents such as CMV, parvovirus B19, human herpesvirus 6, human herpesvirus 8 and human T-cell lymphotropic virus 1, HIV, Yersinia enterocolitica, and Toxoplasma have all been implicated as possible causes of Kikuchi-Fujimoto disease, but studies have failed to provide convincing causal evidence.^9,14,15 Our patient had positive IgM and IgG for CMV, which may have incited his disease.

Definitive diagnosis of Kikuchi-Fujimoto disease is made by lymph node excisional biopsy, which histologically exhibits a histiocytic cell proliferation with paracortical foci of necrosis and abundant karyorrhectic debris.⁵ Cutaneous histologic findings that support the diagnosis are variable and may include a dermal histiocytic infiltrate, epidermal change with necrotic keratinocytes, non-neutrophilic karyorrhectic debris, basal vacuolar change, papillary dermal edema, a nonspecific superficial and deep perivascular infiltrate, and a patchy infiltration of histiocytes and lymphocytes.^6,13

Clinical and histopathological features of this disease can mimic other diseases, specifically SLE or lymphoma.⁷ An association with SLE has been suspected, though it is not well defined and more frequently is associated with cases from Asia than from Europe (28% and 9%, respectively).⁹ Patients presenting concomitantly with positive ANA, weight loss, arthralgia, and skin lesions are more likely to develop SLE.⁸ Furthermore, the cutaneous histologic finding of interface change suggests a link between the two diseases. As such, recommendations have been made for ANA screenings and follow-up of patients diagnosed with Kikuchi-Fujimoto disease for clinical evidence of autoimmune disease, particularly SLE.⁶ Although our patient did not have a positive ANA, his biopsy did demonstrate interface change, and he should be monitored for possible progression of disease in the future.

Kikuchi-Fujimoto disease differs from lymphoma, as it initially presents with rapid lymph node enlargement as opposed to the gradual enlargement seen in lymphoma. The lymph nodes in Kikuchi-Fujimoto disease often are firm and moveable compared to hard and immobile in lymphoma.³ Excisional lymph node biopsy is necessary for both confirming the diagnosis of Kikuchi-Fujimoto disease and ruling out lymphoma.⁵

Spontaneous resolution usually occurs in 1 to 4 months.^3,6 As such, observation is the most common approach to management. When patients have symptoms that limit activities or cause undue distress such as fevers, joint pains, or abdominal pain, systemic treatment options may be desired. Symptomatic treatment can be managed with a short duration of oral corticosteroids,^10,11 nonsteroidal anti-inflammatory drugs, antimalarials, and/or antipyretics.^8-15 There are no guidelines regarding systemic steroid regimens, and various treatment schedules have been successful. Systemic therapy was considered for our patient for his weight loss and abdominal pain; however, by the time of discharge the patient was tolerating oral intake and his abdominal pain had improved.

To the Editor:

Kikuchi-Fujimoto Disease, also called histiocytic necrotizing lymphadenitis, was described in 1972 by both Kikuchi¹ and Fujimoto et al.² Most cases are reported in Asia, with limited reports in the United States.^3-5 Kikuchi-Fujimoto disease is a rare, self-limiting condition consisting of benign lymphadenopathy and oftentimes fever and systemic symptoms. Lymph node involvement may mimic non-Hodgkin lymphoma or other reactive lymphadenopathy, rendering diagnostic accuracy challenging.⁵ Cutaneous manifestations are reported in only 16% to 40% of patients.^6,7 Herein, we describe the clinical and pathologic features of a case of Kikuchi-Fujimoto disease with cutaneous involvement in an adolescent boy.

A 13-year-old adolescent boy with no notable medical history presented to the pediatric emergency department with cervical lymphadenopathy, weight loss, intermittent fever, and an evolving rash on the face, ears, arms, and thighs of 6 weeks’ duration. The illness began with enlarged lymph nodes and erythematous macules on the face and was diagnosed by his primary care physician as lymphadenitis that was unresponsive to clindamycin. Over the subsequent weeks, the rash worsened, and he developed intermittent fevers, night sweats, abdominal pain, and nausea with a 20-pound weight loss. He presented to the emergency department 3 weeks prior to the current admission and was noted to have elevated cytomegalovirus (CMV) IgM and IgG in addition to lymphopenia and anemia. He was discharged with outpatient follow-up. The rash progressed to involve the face, ears, arms, and thighs. One day prior to the current admission, the patient’s abdominal pain worsened acutely, and he experienced several episodes of emesis. He presented to the pediatric emergency department for further evaluation, and a dermatology consultation was requested at that time.

The patient’s rash was asymptomatic. In addition to the above symptoms, he also noted frequent nosebleeds, gingival bleeding, and diffuse myalgia that was most prominent on the hands and feet; he denied diarrhea, sick contacts, recent travel, or insect bites. His vital signs were normal, and he remained afebrile throughout the hospitalization. Physical examination revealed an ill-appearing patient with sunken eyes and dry lips. He had pink, oval, scaly plaques on the cheeks, ears, and arms (Figure 1). The thighs exhibited folliculocentric erythematous papules. The ocular conjunctivae were clear, but white exudative plaques were noted on the tongue. Tender, bilateral, cervical lymphadenopathy and diffuse abdominal tenderness with guarding and hepatosplenomegaly also were present. The fingers and toes were tender upon palpation.

Laboratory workup at admission revealed the following: low white blood cell count, 2700/μL (reference range, 4500–11,000/μL); low hemoglobin, 9.6 g/dL (reference range, 14.0–17.5 g/dL); elevated aspartate aminotransferase, 91 U/L (reference range, 10–30 U/L); and elevated alanine aminotransferase, 118 U/L (reference range, 10–40 U/L). Lactate dehydrogenase (582 U/L [reference range, 100–200 U/L]), ferritin (1681 ng/mL [reference range, 15–200 ng/mL]), and C-reactive protein (6.0 mg/L [reference range, 0.08–3.1 mg/L]) also were elevated. A respiratory viral panel was unremarkable. Blood cultures were negative, and an HIV 1/2 assay was nonreactive. A chest radiograph demonstrated clear lung fields. Computed tomography of the abdomen and pelvis showed prominent mesenteric, ileocolic, and retroperitoneal lymph nodes.

The differential diagnoses at this time included acute connective tissue disease, a paraneoplastic phenomenon, cutaneous lymphoma, or an infectious etiology. A punch biopsy of the skin as well as tissue cultures were performed from a lesion on the right arm. Quantitative immunoglobulin (IgA, IgG, IgM) levels were checked, all of which were within reference range. An antinuclear antibody (ANA) assay and rheumatoid factor were normal.

The tissue cultures were negative for bacteria, fungi, and mycobacteria. Microscopic examination of the skin biopsy revealed a moderate perivascular and interstitial infiltrate of predominantly histiocytes and lymphocytes with prominent karyorrhectic debris (nuclear dust) in the upper dermis as well as focal vacuolar interface changes with scattered necrotic keratinocytes in the epidermis (Figure 2). Based on these histopathologic findings, a diagnosis of Kikuchi-Fujimoto disease was considered. To confirm the diagnosis and to rule out the possibility of lymphoma, an excisional biopsy of the cervical lymph node was performed, which showed typical histopathologic features of histiocytic necrotizing lymphadenitis.

Given the patient’s clinical presentation with arthralgia, anorexia, lymphadenitis, and hepatosplenomegaly along with histopathologic findings from both the skin and lymph node biopsies, a diagnosis of Kikuchi-Fujimoto disease was made. The patient was conservatively managed with acetaminophen and was discharged with improvement in his appetite and systemic symptoms.

He was seen for follow-up 3 months later in the outpatient clinic. He denied any recurrence of systemic symptoms but endorsed a recent shedding of hair consistent with telogen effluvium. The rash had substantially improved, though residual asymptomatic erythematous plaques remained on the right forehead and right cheek (Figure 3). He was prescribed triamcinolone acetonide cream 0.1% to apply to the active area twice daily for the following 2 to 3 weeks.

Kikuchi-Fujimoto disease presents with a wide clinical spectrum, classically with benign lymphadenopathy and fever of unknown etiology.^5,6 Lymphadenopathy most often is cervical (55%–99%)⁸ and unilateral,^4,7 but patients can present with polyadenopathy (52%).^7,8 Constitutional signs commonly include fever (35%–76%), weight loss, arthritis (5%–34%), and leukopenia (25%–74%).^4,8,9

Cutaneous findings have been described in up to 40% of cases, of which clinical presentation is variable.⁶ Lesions may include blanchable, erythematous, painful, and/or indurated plaques, nodules, or maculopapules with confluence into patches, urticaria, morbilliform lesions, erythema multiforme, eyelid edema, leukocytoclastic vasculitis, papulopustules, ulcerated gingivae, and mucositis.^6,7,10-13 Patients with skin lesions may be at an increased risk for developing systemic lupus erythematosus (SLE).⁸ Our patient presented with erythematous scaly plaques with a predominance of lesions in photodistributed locations, which clinically mimicked an underlying connective tissue disease process such as SLE.

Infectious agents such as CMV, parvovirus B19, human herpesvirus 6, human herpesvirus 8 and human T-cell lymphotropic virus 1, HIV, Yersinia enterocolitica, and Toxoplasma have all been implicated as possible causes of Kikuchi-Fujimoto disease, but studies have failed to provide convincing causal evidence.^9,14,15 Our patient had positive IgM and IgG for CMV, which may have incited his disease.

Definitive diagnosis of Kikuchi-Fujimoto disease is made by lymph node excisional biopsy, which histologically exhibits a histiocytic cell proliferation with paracortical foci of necrosis and abundant karyorrhectic debris.⁵ Cutaneous histologic findings that support the diagnosis are variable and may include a dermal histiocytic infiltrate, epidermal change with necrotic keratinocytes, non-neutrophilic karyorrhectic debris, basal vacuolar change, papillary dermal edema, a nonspecific superficial and deep perivascular infiltrate, and a patchy infiltration of histiocytes and lymphocytes.^6,13

Clinical and histopathological features of this disease can mimic other diseases, specifically SLE or lymphoma.⁷ An association with SLE has been suspected, though it is not well defined and more frequently is associated with cases from Asia than from Europe (28% and 9%, respectively).⁹ Patients presenting concomitantly with positive ANA, weight loss, arthralgia, and skin lesions are more likely to develop SLE.⁸ Furthermore, the cutaneous histologic finding of interface change suggests a link between the two diseases. As such, recommendations have been made for ANA screenings and follow-up of patients diagnosed with Kikuchi-Fujimoto disease for clinical evidence of autoimmune disease, particularly SLE.⁶ Although our patient did not have a positive ANA, his biopsy did demonstrate interface change, and he should be monitored for possible progression of disease in the future.

Kikuchi-Fujimoto disease differs from lymphoma, as it initially presents with rapid lymph node enlargement as opposed to the gradual enlargement seen in lymphoma. The lymph nodes in Kikuchi-Fujimoto disease often are firm and moveable compared to hard and immobile in lymphoma.³ Excisional lymph node biopsy is necessary for both confirming the diagnosis of Kikuchi-Fujimoto disease and ruling out lymphoma.⁵

Spontaneous resolution usually occurs in 1 to 4 months.^3,6 As such, observation is the most common approach to management. When patients have symptoms that limit activities or cause undue distress such as fevers, joint pains, or abdominal pain, systemic treatment options may be desired. Symptomatic treatment can be managed with a short duration of oral corticosteroids,^10,11 nonsteroidal anti-inflammatory drugs, antimalarials, and/or antipyretics.^8-15 There are no guidelines regarding systemic steroid regimens, and various treatment schedules have been successful. Systemic therapy was considered for our patient for his weight loss and abdominal pain; however, by the time of discharge the patient was tolerating oral intake and his abdominal pain had improved.

To the Editor:

Kikuchi-Fujimoto Disease, also called histiocytic necrotizing lymphadenitis, was described in 1972 by both Kikuchi¹ and Fujimoto et al.² Most cases are reported in Asia, with limited reports in the United States.^3-5 Kikuchi-Fujimoto disease is a rare, self-limiting condition consisting of benign lymphadenopathy and oftentimes fever and systemic symptoms. Lymph node involvement may mimic non-Hodgkin lymphoma or other reactive lymphadenopathy, rendering diagnostic accuracy challenging.⁵ Cutaneous manifestations are reported in only 16% to 40% of patients.^6,7 Herein, we describe the clinical and pathologic features of a case of Kikuchi-Fujimoto disease with cutaneous involvement in an adolescent boy.

A 13-year-old adolescent boy with no notable medical history presented to the pediatric emergency department with cervical lymphadenopathy, weight loss, intermittent fever, and an evolving rash on the face, ears, arms, and thighs of 6 weeks’ duration. The illness began with enlarged lymph nodes and erythematous macules on the face and was diagnosed by his primary care physician as lymphadenitis that was unresponsive to clindamycin. Over the subsequent weeks, the rash worsened, and he developed intermittent fevers, night sweats, abdominal pain, and nausea with a 20-pound weight loss. He presented to the emergency department 3 weeks prior to the current admission and was noted to have elevated cytomegalovirus (CMV) IgM and IgG in addition to lymphopenia and anemia. He was discharged with outpatient follow-up. The rash progressed to involve the face, ears, arms, and thighs. One day prior to the current admission, the patient’s abdominal pain worsened acutely, and he experienced several episodes of emesis. He presented to the pediatric emergency department for further evaluation, and a dermatology consultation was requested at that time.

The patient’s rash was asymptomatic. In addition to the above symptoms, he also noted frequent nosebleeds, gingival bleeding, and diffuse myalgia that was most prominent on the hands and feet; he denied diarrhea, sick contacts, recent travel, or insect bites. His vital signs were normal, and he remained afebrile throughout the hospitalization. Physical examination revealed an ill-appearing patient with sunken eyes and dry lips. He had pink, oval, scaly plaques on the cheeks, ears, and arms (Figure 1). The thighs exhibited folliculocentric erythematous papules. The ocular conjunctivae were clear, but white exudative plaques were noted on the tongue. Tender, bilateral, cervical lymphadenopathy and diffuse abdominal tenderness with guarding and hepatosplenomegaly also were present. The fingers and toes were tender upon palpation.

Laboratory workup at admission revealed the following: low white blood cell count, 2700/μL (reference range, 4500–11,000/μL); low hemoglobin, 9.6 g/dL (reference range, 14.0–17.5 g/dL); elevated aspartate aminotransferase, 91 U/L (reference range, 10–30 U/L); and elevated alanine aminotransferase, 118 U/L (reference range, 10–40 U/L). Lactate dehydrogenase (582 U/L [reference range, 100–200 U/L]), ferritin (1681 ng/mL [reference range, 15–200 ng/mL]), and C-reactive protein (6.0 mg/L [reference range, 0.08–3.1 mg/L]) also were elevated. A respiratory viral panel was unremarkable. Blood cultures were negative, and an HIV 1/2 assay was nonreactive. A chest radiograph demonstrated clear lung fields. Computed tomography of the abdomen and pelvis showed prominent mesenteric, ileocolic, and retroperitoneal lymph nodes.

The differential diagnoses at this time included acute connective tissue disease, a paraneoplastic phenomenon, cutaneous lymphoma, or an infectious etiology. A punch biopsy of the skin as well as tissue cultures were performed from a lesion on the right arm. Quantitative immunoglobulin (IgA, IgG, IgM) levels were checked, all of which were within reference range. An antinuclear antibody (ANA) assay and rheumatoid factor were normal.

The tissue cultures were negative for bacteria, fungi, and mycobacteria. Microscopic examination of the skin biopsy revealed a moderate perivascular and interstitial infiltrate of predominantly histiocytes and lymphocytes with prominent karyorrhectic debris (nuclear dust) in the upper dermis as well as focal vacuolar interface changes with scattered necrotic keratinocytes in the epidermis (Figure 2). Based on these histopathologic findings, a diagnosis of Kikuchi-Fujimoto disease was considered. To confirm the diagnosis and to rule out the possibility of lymphoma, an excisional biopsy of the cervical lymph node was performed, which showed typical histopathologic features of histiocytic necrotizing lymphadenitis.

Given the patient’s clinical presentation with arthralgia, anorexia, lymphadenitis, and hepatosplenomegaly along with histopathologic findings from both the skin and lymph node biopsies, a diagnosis of Kikuchi-Fujimoto disease was made. The patient was conservatively managed with acetaminophen and was discharged with improvement in his appetite and systemic symptoms.

He was seen for follow-up 3 months later in the outpatient clinic. He denied any recurrence of systemic symptoms but endorsed a recent shedding of hair consistent with telogen effluvium. The rash had substantially improved, though residual asymptomatic erythematous plaques remained on the right forehead and right cheek (Figure 3). He was prescribed triamcinolone acetonide cream 0.1% to apply to the active area twice daily for the following 2 to 3 weeks.

Kikuchi-Fujimoto disease presents with a wide clinical spectrum, classically with benign lymphadenopathy and fever of unknown etiology.^5,6 Lymphadenopathy most often is cervical (55%–99%)⁸ and unilateral,^4,7 but patients can present with polyadenopathy (52%).^7,8 Constitutional signs commonly include fever (35%–76%), weight loss, arthritis (5%–34%), and leukopenia (25%–74%).^4,8,9

Cutaneous findings have been described in up to 40% of cases, of which clinical presentation is variable.⁶ Lesions may include blanchable, erythematous, painful, and/or indurated plaques, nodules, or maculopapules with confluence into patches, urticaria, morbilliform lesions, erythema multiforme, eyelid edema, leukocytoclastic vasculitis, papulopustules, ulcerated gingivae, and mucositis.^6,7,10-13 Patients with skin lesions may be at an increased risk for developing systemic lupus erythematosus (SLE).⁸ Our patient presented with erythematous scaly plaques with a predominance of lesions in photodistributed locations, which clinically mimicked an underlying connective tissue disease process such as SLE.

Infectious agents such as CMV, parvovirus B19, human herpesvirus 6, human herpesvirus 8 and human T-cell lymphotropic virus 1, HIV, Yersinia enterocolitica, and Toxoplasma have all been implicated as possible causes of Kikuchi-Fujimoto disease, but studies have failed to provide convincing causal evidence.^9,14,15 Our patient had positive IgM and IgG for CMV, which may have incited his disease.

Definitive diagnosis of Kikuchi-Fujimoto disease is made by lymph node excisional biopsy, which histologically exhibits a histiocytic cell proliferation with paracortical foci of necrosis and abundant karyorrhectic debris.⁵ Cutaneous histologic findings that support the diagnosis are variable and may include a dermal histiocytic infiltrate, epidermal change with necrotic keratinocytes, non-neutrophilic karyorrhectic debris, basal vacuolar change, papillary dermal edema, a nonspecific superficial and deep perivascular infiltrate, and a patchy infiltration of histiocytes and lymphocytes.^6,13

Clinical and histopathological features of this disease can mimic other diseases, specifically SLE or lymphoma.⁷ An association with SLE has been suspected, though it is not well defined and more frequently is associated with cases from Asia than from Europe (28% and 9%, respectively).⁹ Patients presenting concomitantly with positive ANA, weight loss, arthralgia, and skin lesions are more likely to develop SLE.⁸ Furthermore, the cutaneous histologic finding of interface change suggests a link between the two diseases. As such, recommendations have been made for ANA screenings and follow-up of patients diagnosed with Kikuchi-Fujimoto disease for clinical evidence of autoimmune disease, particularly SLE.⁶ Although our patient did not have a positive ANA, his biopsy did demonstrate interface change, and he should be monitored for possible progression of disease in the future.

Kikuchi-Fujimoto disease differs from lymphoma, as it initially presents with rapid lymph node enlargement as opposed to the gradual enlargement seen in lymphoma. The lymph nodes in Kikuchi-Fujimoto disease often are firm and moveable compared to hard and immobile in lymphoma.³ Excisional lymph node biopsy is necessary for both confirming the diagnosis of Kikuchi-Fujimoto disease and ruling out lymphoma.⁵

Spontaneous resolution usually occurs in 1 to 4 months.^3,6 As such, observation is the most common approach to management. When patients have symptoms that limit activities or cause undue distress such as fevers, joint pains, or abdominal pain, systemic treatment options may be desired. Symptomatic treatment can be managed with a short duration of oral corticosteroids,^10,11 nonsteroidal anti-inflammatory drugs, antimalarials, and/or antipyretics.^8-15 There are no guidelines regarding systemic steroid regimens, and various treatment schedules have been successful. Systemic therapy was considered for our patient for his weight loss and abdominal pain; however, by the time of discharge the patient was tolerating oral intake and his abdominal pain had improved.

A handheld vision screening device to test for amblyopia and strabismus has been found to have a sensitivity of 100%, a specificity of 85%, and a median acquisition time of 28 seconds, according to a study published in the Journal of American Association for Pediatric Ophthalmology and Strabismus.

The prospective study involved 300 children recruited from two Kaiser Permanente Southern California pediatric clinics. The patients, aged 24-72 months, were first screened by trained research staff for amblyopia and strabismus using the device, called the Pediatric Vision Scanner (PVS). They were subsequently screened by a pediatric ophthalmologist who was masked to the previous screening results and who then performed a comprehensive eye examination.

With the gold-standard ophthalmologist examination, six children (2%) were identified as having amblyopia and/or strabismus. Using the PVS, all six children with amblyopia and/or strabismus were identified, yielding 100% sensitivity. PVS findings were normal for 45 children (15%), yielding a specificity rate of 85%. The positive predictive value was 26.0% (95% confidence interval, 12.4%-32.4%), and the negative predictive value was 100% (95% CI, 97.1%-100%).

The findings suggest that the device could be used to screen for amblyopia, according to Shaival S. Shah, MD, the study’s first author, who is a pediatric ophthalmologist and regional section lead of pediatric ophthalmology, Southern California Permanente Medical Group.

“A strength of this device is that it is user friendly and easy to use and very quick, which is essential when working with young children,” said Dr. Shah in an interview. He noted that the device could be used for children as young as 2 years.

Dr. Shah pointed out that the children were recruited from a pediatrician’s office and reflect more of a “real-world setting” than had they been recruited from a pediatric ophthalmology clinic.

Dr. Shah added that, with a negative predictive value of 100%, the device is highly reliable at informing the clinician that amblyopia is not present. “It did have a positive predictive value of 26%, which needs to be considered when deciding one’s vision screening strategy,” he said.

A limitation of the study is that there was no head-to-head comparison with another screening device, noted Dr. Shah. “While it may have been more useful to include another vision screening device to have a head-to-head comparison, we did not do this to limit complexity and cost.”

Michael J. Wan, MD, FRCSC, pediatric ophthalmologist, Sick Kids Hospital, Toronto, and assistant professor at the University of Toronto, told this news organization that the device has multiple strengths, including quick acquisition time and excellent detection rate of amblyopia and strabismus in children as young as 2 years.

“It is highly reliable at informing the clinician that amblyopia is not present,” said Dr. Wan, who was not involved in the study. “The PVS uses an elegant mechanism to test for amblyopia directly (as opposed to other screening devices, which only detect risk factors). This study demonstrates the impressive diagnostic accuracy of this approach. With a study population of 300 children, the PVS had a sensitivity of 100% and specificity of 85% (over 90% in cooperative children). This means that the PVS would detect essentially all cases of amblyopia and strabismus while minimizing the number of unnecessary referrals and examinations.”

He added that, although the study included children as young as 2 years, only 2.5% of the children were unable to complete the PVS test. “Detecting amblyopia in children at an age when treatment is still effective has been a longstanding goal in pediatric ophthalmology,” said Dr. Wan, who described the technology as user friendly. “Based on this study, the search for an accurate and practical pediatric vision screening device appears to be over.”

Dr. Wan said it would be useful to replicate this study with a different population to confirm the findings.

Dr. Shah and Dr. Wan disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A handheld vision screening device to test for amblyopia and strabismus has been found to have a sensitivity of 100%, a specificity of 85%, and a median acquisition time of 28 seconds, according to a study published in the Journal of American Association for Pediatric Ophthalmology and Strabismus.

The prospective study involved 300 children recruited from two Kaiser Permanente Southern California pediatric clinics. The patients, aged 24-72 months, were first screened by trained research staff for amblyopia and strabismus using the device, called the Pediatric Vision Scanner (PVS). They were subsequently screened by a pediatric ophthalmologist who was masked to the previous screening results and who then performed a comprehensive eye examination.

With the gold-standard ophthalmologist examination, six children (2%) were identified as having amblyopia and/or strabismus. Using the PVS, all six children with amblyopia and/or strabismus were identified, yielding 100% sensitivity. PVS findings were normal for 45 children (15%), yielding a specificity rate of 85%. The positive predictive value was 26.0% (95% confidence interval, 12.4%-32.4%), and the negative predictive value was 100% (95% CI, 97.1%-100%).

The findings suggest that the device could be used to screen for amblyopia, according to Shaival S. Shah, MD, the study’s first author, who is a pediatric ophthalmologist and regional section lead of pediatric ophthalmology, Southern California Permanente Medical Group.

“A strength of this device is that it is user friendly and easy to use and very quick, which is essential when working with young children,” said Dr. Shah in an interview. He noted that the device could be used for children as young as 2 years.

Dr. Shah pointed out that the children were recruited from a pediatrician’s office and reflect more of a “real-world setting” than had they been recruited from a pediatric ophthalmology clinic.

Dr. Shah added that, with a negative predictive value of 100%, the device is highly reliable at informing the clinician that amblyopia is not present. “It did have a positive predictive value of 26%, which needs to be considered when deciding one’s vision screening strategy,” he said.

A limitation of the study is that there was no head-to-head comparison with another screening device, noted Dr. Shah. “While it may have been more useful to include another vision screening device to have a head-to-head comparison, we did not do this to limit complexity and cost.”

Michael J. Wan, MD, FRCSC, pediatric ophthalmologist, Sick Kids Hospital, Toronto, and assistant professor at the University of Toronto, told this news organization that the device has multiple strengths, including quick acquisition time and excellent detection rate of amblyopia and strabismus in children as young as 2 years.

“It is highly reliable at informing the clinician that amblyopia is not present,” said Dr. Wan, who was not involved in the study. “The PVS uses an elegant mechanism to test for amblyopia directly (as opposed to other screening devices, which only detect risk factors). This study demonstrates the impressive diagnostic accuracy of this approach. With a study population of 300 children, the PVS had a sensitivity of 100% and specificity of 85% (over 90% in cooperative children). This means that the PVS would detect essentially all cases of amblyopia and strabismus while minimizing the number of unnecessary referrals and examinations.”

He added that, although the study included children as young as 2 years, only 2.5% of the children were unable to complete the PVS test. “Detecting amblyopia in children at an age when treatment is still effective has been a longstanding goal in pediatric ophthalmology,” said Dr. Wan, who described the technology as user friendly. “Based on this study, the search for an accurate and practical pediatric vision screening device appears to be over.”

Dr. Wan said it would be useful to replicate this study with a different population to confirm the findings.

Dr. Shah and Dr. Wan disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A handheld vision screening device to test for amblyopia and strabismus has been found to have a sensitivity of 100%, a specificity of 85%, and a median acquisition time of 28 seconds, according to a study published in the Journal of American Association for Pediatric Ophthalmology and Strabismus.

The prospective study involved 300 children recruited from two Kaiser Permanente Southern California pediatric clinics. The patients, aged 24-72 months, were first screened by trained research staff for amblyopia and strabismus using the device, called the Pediatric Vision Scanner (PVS). They were subsequently screened by a pediatric ophthalmologist who was masked to the previous screening results and who then performed a comprehensive eye examination.

With the gold-standard ophthalmologist examination, six children (2%) were identified as having amblyopia and/or strabismus. Using the PVS, all six children with amblyopia and/or strabismus were identified, yielding 100% sensitivity. PVS findings were normal for 45 children (15%), yielding a specificity rate of 85%. The positive predictive value was 26.0% (95% confidence interval, 12.4%-32.4%), and the negative predictive value was 100% (95% CI, 97.1%-100%).

The findings suggest that the device could be used to screen for amblyopia, according to Shaival S. Shah, MD, the study’s first author, who is a pediatric ophthalmologist and regional section lead of pediatric ophthalmology, Southern California Permanente Medical Group.

“A strength of this device is that it is user friendly and easy to use and very quick, which is essential when working with young children,” said Dr. Shah in an interview. He noted that the device could be used for children as young as 2 years.

Dr. Shah pointed out that the children were recruited from a pediatrician’s office and reflect more of a “real-world setting” than had they been recruited from a pediatric ophthalmology clinic.

Dr. Shah added that, with a negative predictive value of 100%, the device is highly reliable at informing the clinician that amblyopia is not present. “It did have a positive predictive value of 26%, which needs to be considered when deciding one’s vision screening strategy,” he said.

A limitation of the study is that there was no head-to-head comparison with another screening device, noted Dr. Shah. “While it may have been more useful to include another vision screening device to have a head-to-head comparison, we did not do this to limit complexity and cost.”

Michael J. Wan, MD, FRCSC, pediatric ophthalmologist, Sick Kids Hospital, Toronto, and assistant professor at the University of Toronto, told this news organization that the device has multiple strengths, including quick acquisition time and excellent detection rate of amblyopia and strabismus in children as young as 2 years.

“It is highly reliable at informing the clinician that amblyopia is not present,” said Dr. Wan, who was not involved in the study. “The PVS uses an elegant mechanism to test for amblyopia directly (as opposed to other screening devices, which only detect risk factors). This study demonstrates the impressive diagnostic accuracy of this approach. With a study population of 300 children, the PVS had a sensitivity of 100% and specificity of 85% (over 90% in cooperative children). This means that the PVS would detect essentially all cases of amblyopia and strabismus while minimizing the number of unnecessary referrals and examinations.”

He added that, although the study included children as young as 2 years, only 2.5% of the children were unable to complete the PVS test. “Detecting amblyopia in children at an age when treatment is still effective has been a longstanding goal in pediatric ophthalmology,” said Dr. Wan, who described the technology as user friendly. “Based on this study, the search for an accurate and practical pediatric vision screening device appears to be over.”

Dr. Wan said it would be useful to replicate this study with a different population to confirm the findings.

Dr. Shah and Dr. Wan disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The continuing decline in COVID-19 incidence suggests the latest surge has peaked as new cases in children dropped for the 4th consecutive week, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Preliminary data from the Centers for Disease Control and Prevention, however, show an uptick in new cases in late September, largely among younger children, that may indicate otherwise. Those data have a potential 2-week reporting delay, the CDC said on its COVID Data Tracker, so the most recent points on the graph (see above) could still go up.

The AAP and the CHA said that 173,000 new cases were reported for the week of Sept. 24-30, down 16% from the week before and 31% from the peak in early September. Those new cases made up almost 27% of all cases for the week, and the nearly 5.9 million child cases that have been reported since the start of the pandemic represent 16.2% of cases among Americans of all ages, the two groups said in their weekly COVID-19 report.

The CDC data on new cases by age group suggest that younger children have borne a heavier burden in the summer surge of COVID than they did last winter. The rate of new cases was not as high for 16- and 17-year-olds in the summer, but the other age groups all reached higher peaks than in the winter, including the 12- to 15-year-olds, who have been getting vaccinated since May, according to the COVID Data Tracker.

With vaccination approval getting closer for children under age 12 years, initiation in those already eligible continues to slide. Those aged 12-15 made up just 6.9% of new vaccinations during the 2 weeks from Sept. 21 to Oct. 4, and that figure has been dropping since July 13-26, when it was 14.1%. Vaccine initiation among 16- and 17-year-olds over that time has dropped by almost half, from 5.4% to 2.9%, the CDC data show.

All the vaccinations so far add up to this: Almost 55% of those aged 12-15 have gotten at least one dose of COVID vaccine, as have over 62% of those aged 16-17, and 52% of the older group is fully vaccinated, as is 44% of the younger group. Altogether, 10.8 million children were fully vaccinated as of Oct. 4, including those under 12 who may be participating in clinical trials or had a birth date entered incorrectly, the CDC said.

[email protected]

The continuing decline in COVID-19 incidence suggests the latest surge has peaked as new cases in children dropped for the 4th consecutive week, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Preliminary data from the Centers for Disease Control and Prevention, however, show an uptick in new cases in late September, largely among younger children, that may indicate otherwise. Those data have a potential 2-week reporting delay, the CDC said on its COVID Data Tracker, so the most recent points on the graph (see above) could still go up.

The AAP and the CHA said that 173,000 new cases were reported for the week of Sept. 24-30, down 16% from the week before and 31% from the peak in early September. Those new cases made up almost 27% of all cases for the week, and the nearly 5.9 million child cases that have been reported since the start of the pandemic represent 16.2% of cases among Americans of all ages, the two groups said in their weekly COVID-19 report.

The CDC data on new cases by age group suggest that younger children have borne a heavier burden in the summer surge of COVID than they did last winter. The rate of new cases was not as high for 16- and 17-year-olds in the summer, but the other age groups all reached higher peaks than in the winter, including the 12- to 15-year-olds, who have been getting vaccinated since May, according to the COVID Data Tracker.

With vaccination approval getting closer for children under age 12 years, initiation in those already eligible continues to slide. Those aged 12-15 made up just 6.9% of new vaccinations during the 2 weeks from Sept. 21 to Oct. 4, and that figure has been dropping since July 13-26, when it was 14.1%. Vaccine initiation among 16- and 17-year-olds over that time has dropped by almost half, from 5.4% to 2.9%, the CDC data show.

All the vaccinations so far add up to this: Almost 55% of those aged 12-15 have gotten at least one dose of COVID vaccine, as have over 62% of those aged 16-17, and 52% of the older group is fully vaccinated, as is 44% of the younger group. Altogether, 10.8 million children were fully vaccinated as of Oct. 4, including those under 12 who may be participating in clinical trials or had a birth date entered incorrectly, the CDC said.

[email protected]

The continuing decline in COVID-19 incidence suggests the latest surge has peaked as new cases in children dropped for the 4th consecutive week, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Preliminary data from the Centers for Disease Control and Prevention, however, show an uptick in new cases in late September, largely among younger children, that may indicate otherwise. Those data have a potential 2-week reporting delay, the CDC said on its COVID Data Tracker, so the most recent points on the graph (see above) could still go up.

The AAP and the CHA said that 173,000 new cases were reported for the week of Sept. 24-30, down 16% from the week before and 31% from the peak in early September. Those new cases made up almost 27% of all cases for the week, and the nearly 5.9 million child cases that have been reported since the start of the pandemic represent 16.2% of cases among Americans of all ages, the two groups said in their weekly COVID-19 report.

The CDC data on new cases by age group suggest that younger children have borne a heavier burden in the summer surge of COVID than they did last winter. The rate of new cases was not as high for 16- and 17-year-olds in the summer, but the other age groups all reached higher peaks than in the winter, including the 12- to 15-year-olds, who have been getting vaccinated since May, according to the COVID Data Tracker.

With vaccination approval getting closer for children under age 12 years, initiation in those already eligible continues to slide. Those aged 12-15 made up just 6.9% of new vaccinations during the 2 weeks from Sept. 21 to Oct. 4, and that figure has been dropping since July 13-26, when it was 14.1%. Vaccine initiation among 16- and 17-year-olds over that time has dropped by almost half, from 5.4% to 2.9%, the CDC data show.

All the vaccinations so far add up to this: Almost 55% of those aged 12-15 have gotten at least one dose of COVID vaccine, as have over 62% of those aged 16-17, and 52% of the older group is fully vaccinated, as is 44% of the younger group. Altogether, 10.8 million children were fully vaccinated as of Oct. 4, including those under 12 who may be participating in clinical trials or had a birth date entered incorrectly, the CDC said.

[email protected]

Irish dermatologists are reporting two more cases of a rare skin ulcer known as reactive infectious mucocutaneous eruption (RIME) in teenage males who were infected with COVID-19. A similar case in an adolescent, also with ulcers affecting the mouth and penis, was reported earlier in 2021 in the United States.

“Our cases show that a swab for COVID-19 can be added to the list of investigations for mucosal and cutaneous rashes in children and probably adults,” said dermatologist Stephanie Bowe, MD, of South Infirmary-Victoria University Hospital in Cork, Ireland, in an interview. “Our patients seemed to improve with IV steroids, but there is not enough data to recommend them to all patients or for use in the different cutaneous presentations associated with COVID-19.”

The new case reports were presented at the 2021 meeting of the World Congress of Pediatric Dermatology and published in Pediatric Dermatology.

Researchers have noted that skin disorders linked to COVID-19 infection are different than those in adults. In children, the conditions include morbilliform rash, pernio-like acral lesions, urticaria, macular erythema, vesicular eruption, papulosquamous eruption, and retiform purpura. “The pathogenesis of each is not fully understood but likely related to the inflammatory response to COVID-19 and the various pathways within the body, which become activated,” Dr. Bowe said.

The first patient, a 17-year-old boy, presented at clinic 6 days after he’d been confirmed to be infected with COVID-19 and 8 days after developing fever and cough. “He had a 2-day history of conjunctivitis and ulceration of his oral mucosa, erythematous circumferential erosions of the glans penis with no other cutaneous findings,” the authors write in the report.

The boy “was distressed and embarrassed about his genital ulceration and also found eating very painful due to his oral ulceration,” Dr. Bowe said.

The second patient, a 14-year-old boy, was hospitalized 7 days after a positive COVID-19 test and 9 days after developing cough and fever. “He had a 5-day history of ulceration of the oral mucosa with mild conjunctivitis,” the authors wrote. “Ulceration of the glans penis developed on day 2 of admission.”

The 14-year-old was sicker than the 17-year-old boy, Dr. Bowe said. “He was unable to tolerate an oral diet for several days and had exquisite pain and vomiting with his coughing fits.”

This patient had a history of recurrent herpes labialis, but it’s unclear whether herpes simplex virus (HSV) played a role in the COVID-19–related case. “There is a possibility that the patient was more susceptible to viral cutaneous reactions during COVID-19 infection, but we didn’t have any definite history of HSV infection at the time of mucositis,” Dr. Bowe said. “We also didn’t have any swabs positive for HSV even though several were done at the time.”

Both patients received IV steroids – hydrocortisone at 100 mg 3 times daily for 3 days. This treatment was used “because of deterioration in symptoms and COVID-19 infection,” Dr. Bowe said. “IV steroids were used for respiratory symptoms of COVID-19, so we felt these cutaneous symptoms may have also been caused by an inflammatory response and might benefit from steroids. There was very little literature about this specific situation, though.”

She added that intravenous steroids wouldn’t be appropriate for most pediatric patients, and noted that “their use is controversial in the literature for erythema multiforme and RIME.”

In addition, the patients received betamethasone valerate 0.1% ointment once daily, hydrocortisone 2.5 mg buccal tablets 4 times daily, analgesia with acetaminophen and ibuprofen, and intravenous hydration. The first patient also received prednisolone 1% eye drops, while the second patient was given lidocaine hydrochloride mouthwash and total parenteral nutrition for 5 days.

The patients were discharged after 4 and 14 days, respectively.

Dermatologists in Massachusetts reported a similar case earlier in 2021 in a 17-year-old boy who was positive for COVID-19 and presented with “shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities.”

The patient received betamethasone valerate 0.1% ointment for the lips and penis, intraoral dexamethasone solution, viscous lidocaine, acetaminophen, and ibuprofen. He also received oral prednisone at approximately 1 mg/kg daily for 4 consecutive days after worsening oral pain. A recurrence of oral pain 3 months later was resolved with a higher and longer treatment with oral prednisone.

Dermatologists have also reported cases of erythema multiforme lesions of the mucosa in adults with COVID-19. One case was reported in Iran, and the other in France.

The authors report no study funding and disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Irish dermatologists are reporting two more cases of a rare skin ulcer known as reactive infectious mucocutaneous eruption (RIME) in teenage males who were infected with COVID-19. A similar case in an adolescent, also with ulcers affecting the mouth and penis, was reported earlier in 2021 in the United States.

“Our cases show that a swab for COVID-19 can be added to the list of investigations for mucosal and cutaneous rashes in children and probably adults,” said dermatologist Stephanie Bowe, MD, of South Infirmary-Victoria University Hospital in Cork, Ireland, in an interview. “Our patients seemed to improve with IV steroids, but there is not enough data to recommend them to all patients or for use in the different cutaneous presentations associated with COVID-19.”

The new case reports were presented at the 2021 meeting of the World Congress of Pediatric Dermatology and published in Pediatric Dermatology.

Researchers have noted that skin disorders linked to COVID-19 infection are different than those in adults. In children, the conditions include morbilliform rash, pernio-like acral lesions, urticaria, macular erythema, vesicular eruption, papulosquamous eruption, and retiform purpura. “The pathogenesis of each is not fully understood but likely related to the inflammatory response to COVID-19 and the various pathways within the body, which become activated,” Dr. Bowe said.

The first patient, a 17-year-old boy, presented at clinic 6 days after he’d been confirmed to be infected with COVID-19 and 8 days after developing fever and cough. “He had a 2-day history of conjunctivitis and ulceration of his oral mucosa, erythematous circumferential erosions of the glans penis with no other cutaneous findings,” the authors write in the report.

The boy “was distressed and embarrassed about his genital ulceration and also found eating very painful due to his oral ulceration,” Dr. Bowe said.

The second patient, a 14-year-old boy, was hospitalized 7 days after a positive COVID-19 test and 9 days after developing cough and fever. “He had a 5-day history of ulceration of the oral mucosa with mild conjunctivitis,” the authors wrote. “Ulceration of the glans penis developed on day 2 of admission.”

The 14-year-old was sicker than the 17-year-old boy, Dr. Bowe said. “He was unable to tolerate an oral diet for several days and had exquisite pain and vomiting with his coughing fits.”

This patient had a history of recurrent herpes labialis, but it’s unclear whether herpes simplex virus (HSV) played a role in the COVID-19–related case. “There is a possibility that the patient was more susceptible to viral cutaneous reactions during COVID-19 infection, but we didn’t have any definite history of HSV infection at the time of mucositis,” Dr. Bowe said. “We also didn’t have any swabs positive for HSV even though several were done at the time.”

Both patients received IV steroids – hydrocortisone at 100 mg 3 times daily for 3 days. This treatment was used “because of deterioration in symptoms and COVID-19 infection,” Dr. Bowe said. “IV steroids were used for respiratory symptoms of COVID-19, so we felt these cutaneous symptoms may have also been caused by an inflammatory response and might benefit from steroids. There was very little literature about this specific situation, though.”

She added that intravenous steroids wouldn’t be appropriate for most pediatric patients, and noted that “their use is controversial in the literature for erythema multiforme and RIME.”

In addition, the patients received betamethasone valerate 0.1% ointment once daily, hydrocortisone 2.5 mg buccal tablets 4 times daily, analgesia with acetaminophen and ibuprofen, and intravenous hydration. The first patient also received prednisolone 1% eye drops, while the second patient was given lidocaine hydrochloride mouthwash and total parenteral nutrition for 5 days.

The patients were discharged after 4 and 14 days, respectively.

Dermatologists in Massachusetts reported a similar case earlier in 2021 in a 17-year-old boy who was positive for COVID-19 and presented with “shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities.”

The patient received betamethasone valerate 0.1% ointment for the lips and penis, intraoral dexamethasone solution, viscous lidocaine, acetaminophen, and ibuprofen. He also received oral prednisone at approximately 1 mg/kg daily for 4 consecutive days after worsening oral pain. A recurrence of oral pain 3 months later was resolved with a higher and longer treatment with oral prednisone.

Dermatologists have also reported cases of erythema multiforme lesions of the mucosa in adults with COVID-19. One case was reported in Iran, and the other in France.

The authors report no study funding and disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Irish dermatologists are reporting two more cases of a rare skin ulcer known as reactive infectious mucocutaneous eruption (RIME) in teenage males who were infected with COVID-19. A similar case in an adolescent, also with ulcers affecting the mouth and penis, was reported earlier in 2021 in the United States.

“Our cases show that a swab for COVID-19 can be added to the list of investigations for mucosal and cutaneous rashes in children and probably adults,” said dermatologist Stephanie Bowe, MD, of South Infirmary-Victoria University Hospital in Cork, Ireland, in an interview. “Our patients seemed to improve with IV steroids, but there is not enough data to recommend them to all patients or for use in the different cutaneous presentations associated with COVID-19.”

The new case reports were presented at the 2021 meeting of the World Congress of Pediatric Dermatology and published in Pediatric Dermatology.

Researchers have noted that skin disorders linked to COVID-19 infection are different than those in adults. In children, the conditions include morbilliform rash, pernio-like acral lesions, urticaria, macular erythema, vesicular eruption, papulosquamous eruption, and retiform purpura. “The pathogenesis of each is not fully understood but likely related to the inflammatory response to COVID-19 and the various pathways within the body, which become activated,” Dr. Bowe said.

The first patient, a 17-year-old boy, presented at clinic 6 days after he’d been confirmed to be infected with COVID-19 and 8 days after developing fever and cough. “He had a 2-day history of conjunctivitis and ulceration of his oral mucosa, erythematous circumferential erosions of the glans penis with no other cutaneous findings,” the authors write in the report.

The boy “was distressed and embarrassed about his genital ulceration and also found eating very painful due to his oral ulceration,” Dr. Bowe said.

The second patient, a 14-year-old boy, was hospitalized 7 days after a positive COVID-19 test and 9 days after developing cough and fever. “He had a 5-day history of ulceration of the oral mucosa with mild conjunctivitis,” the authors wrote. “Ulceration of the glans penis developed on day 2 of admission.”

The 14-year-old was sicker than the 17-year-old boy, Dr. Bowe said. “He was unable to tolerate an oral diet for several days and had exquisite pain and vomiting with his coughing fits.”

This patient had a history of recurrent herpes labialis, but it’s unclear whether herpes simplex virus (HSV) played a role in the COVID-19–related case. “There is a possibility that the patient was more susceptible to viral cutaneous reactions during COVID-19 infection, but we didn’t have any definite history of HSV infection at the time of mucositis,” Dr. Bowe said. “We also didn’t have any swabs positive for HSV even though several were done at the time.”

Both patients received IV steroids – hydrocortisone at 100 mg 3 times daily for 3 days. This treatment was used “because of deterioration in symptoms and COVID-19 infection,” Dr. Bowe said. “IV steroids were used for respiratory symptoms of COVID-19, so we felt these cutaneous symptoms may have also been caused by an inflammatory response and might benefit from steroids. There was very little literature about this specific situation, though.”

She added that intravenous steroids wouldn’t be appropriate for most pediatric patients, and noted that “their use is controversial in the literature for erythema multiforme and RIME.”

In addition, the patients received betamethasone valerate 0.1% ointment once daily, hydrocortisone 2.5 mg buccal tablets 4 times daily, analgesia with acetaminophen and ibuprofen, and intravenous hydration. The first patient also received prednisolone 1% eye drops, while the second patient was given lidocaine hydrochloride mouthwash and total parenteral nutrition for 5 days.

The patients were discharged after 4 and 14 days, respectively.

Dermatologists in Massachusetts reported a similar case earlier in 2021 in a 17-year-old boy who was positive for COVID-19 and presented with “shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities.”

The patient received betamethasone valerate 0.1% ointment for the lips and penis, intraoral dexamethasone solution, viscous lidocaine, acetaminophen, and ibuprofen. He also received oral prednisone at approximately 1 mg/kg daily for 4 consecutive days after worsening oral pain. A recurrence of oral pain 3 months later was resolved with a higher and longer treatment with oral prednisone.

Dermatologists have also reported cases of erythema multiforme lesions of the mucosa in adults with COVID-19. One case was reported in Iran, and the other in France.

The authors report no study funding and disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Serious adverse events remained rare and skin remained largely clear in adolescents treated with dupilumab for moderate to severe atopic dermatitis (AD) for up to 52 weeks in a phase 3, open-label extension trial, researchers reported.

At 1 year, 86% of 50 remaining patients with weights under 60 kg (132 lb) had achieved 75% improvement on the Eczema Area and Severity Index (EASI-75, and 77% of 51 remaining patients with weights over 60 kg reached that level of clearance. Only 5 (1.7%) of 294 patients had serious treatment-emergent adverse events (TEAEs).

The findings back up a perception that patients can stay on dupilumab for some time instead of having to switch from one biologic to another after a few years, study coauthor Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, said in an interview. He added that the drug’s long-term safety profile is “very reassuring.”

The industry-funded findings of the study were released in a poster at the 2021 meeting of the World Congress of Pediatric Dermatology.

The FDA approved dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, for treating AD in adults in 2017; it is now approved for treating patients ages 6 years and older with moderate to severe atopic dermatitis whose disease is not adequately controlled with topicals.

The new study tracked patients who received at least 300 mg dupilumab subcutaneously every 4 weeks. The dose could be increased if needed to improve clinical response to once every 2 weeks (200 mg if baseline weight was <60 kg; 300 mg if ≥60 kg).

At 52 weeks, 37% of 52 patients with weights under 60 kg reached an Investigator Global Assessment (IGA) of 0/1, a level that had been fairly steady since week 16 (n = 146). Among 51 heavier patients, 49% reached an IGA of 0/1 at 52 weeks; this percentage grew steadily since baseline.

The mean percentage change in EASI was –87% in the lower-weight group (n = 50) at 52 weeks and –80.1% in the larger-weight group (n = 51). The majority of the reduction in EASI occurred in the first 4 weeks of treatment.

At 52 weeks, the mean Children’s Dermatology Life Quality Index level, which judges the effect of AD on life, was judged as “small” (low) in 71 patients. At baseline, the mean level among 189 patients was “moderate.” The levels dipped below “moderate” at week 4 and never rose above “small” after that.

“Treatment-emergent adverse events reported in ≥5% of patients were nasopharyngitis (21.1%), AD (19.4%), upper respiratory tract infection (12.4%), headache (9.4%), and oropharyngeal pain (5.7%),” the investigators wrote in the poster. They add that 6.7% of patients experienced injection-site reactions, and 8.7% of patients experienced treatment-emergent “narrow conjunctivitis,” which includes conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, and atopic keratoconjunctivitis.

Dr. Simpson noted that cases of conjunctivitis fell over time. It’s not clear why this adverse effect appears, he said.

He said that the findings reflect his own experience in clinic. Many of his adolescent patients took part in early dupilumab trials, he said, and dozens have been taking the drug for more than 5 years. “They just seem to get better and better,” he said.

University of Minnesota, Minneapolis, dermatologist Sheilagh Maguiness, MD, who wasn’t involved with the study, said in an interview that dupilumab remains “the safest, most effective and evidence-based therapy we had for children with moderate to severe atopic dermatitis.”

The new study’s findings are “very reassuring,” she said, and similar to those in a 2021 report that tracked long-term use of the drug in children aged 6-11.

Like Dr. Simpson, Dr. Maguiness said many pediatric patients at her clinic have stayed on the drug for more than 5 years. They still have “sustained improvement in skin disease and in their quality of life as well”

There are, however, still questions about dupilumab treatment. “For children who have responded well, when could we consider dose reduction or discontinuation? I have done this successfully just a handful of times, but I would love to see data about what percentage of pediatric patients experience rebound disease after coming off the drug and after what duration of treatment,” she said. “Another mystery that will be very interesting to unravel is the question as to whether or not early treatment with dupilumab may attenuate other atopic diseases.”

Dr. Maguiness added that “another issue specific to pediatric use of dupilumab is the recommendation surrounding vaccinations. This is an issue that should be studied in terms of antibody response and safety surrounding vaccinations, particularly as we are eagerly awaiting a pediatric FDA approval for the COVID-19 vaccine in children.”

She also urged colleagues to push back against insurers who resist paying for dupilumab. “Whether prescribing this medication on or off label, insurance companies are often requiring patients to try and fail other traditional immunosuppressive medications such as methotrexate, cyclosporine, or to pursue phototherapy,” she said. “Oftentimes, these are not practical or even safe options for children for a multitude of reasons. Don’t be shy about advocating for your patients by second- or even third-level appeals to try and gain approval for children who are in need of treatment.”

The study was funded by Sanofi Genzyme and Regeneron Pharmaceuticals. The study authors reported various disclosures. Dr. Simpson reported investigator and consultant fee relationships from various pharmaceutical companies. Dr. Maguiness was an investigator for one of the initial pediatric dupilumab trials.

A version of this article first appeared on Medscape.com.

Serious adverse events remained rare and skin remained largely clear in adolescents treated with dupilumab for moderate to severe atopic dermatitis (AD) for up to 52 weeks in a phase 3, open-label extension trial, researchers reported.

At 1 year, 86% of 50 remaining patients with weights under 60 kg (132 lb) had achieved 75% improvement on the Eczema Area and Severity Index (EASI-75, and 77% of 51 remaining patients with weights over 60 kg reached that level of clearance. Only 5 (1.7%) of 294 patients had serious treatment-emergent adverse events (TEAEs).

The findings back up a perception that patients can stay on dupilumab for some time instead of having to switch from one biologic to another after a few years, study coauthor Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, said in an interview. He added that the drug’s long-term safety profile is “very reassuring.”

The industry-funded findings of the study were released in a poster at the 2021 meeting of the World Congress of Pediatric Dermatology.

The FDA approved dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, for treating AD in adults in 2017; it is now approved for treating patients ages 6 years and older with moderate to severe atopic dermatitis whose disease is not adequately controlled with topicals.

The new study tracked patients who received at least 300 mg dupilumab subcutaneously every 4 weeks. The dose could be increased if needed to improve clinical response to once every 2 weeks (200 mg if baseline weight was <60 kg; 300 mg if ≥60 kg).

At 52 weeks, 37% of 52 patients with weights under 60 kg reached an Investigator Global Assessment (IGA) of 0/1, a level that had been fairly steady since week 16 (n = 146). Among 51 heavier patients, 49% reached an IGA of 0/1 at 52 weeks; this percentage grew steadily since baseline.

The mean percentage change in EASI was –87% in the lower-weight group (n = 50) at 52 weeks and –80.1% in the larger-weight group (n = 51). The majority of the reduction in EASI occurred in the first 4 weeks of treatment.

At 52 weeks, the mean Children’s Dermatology Life Quality Index level, which judges the effect of AD on life, was judged as “small” (low) in 71 patients. At baseline, the mean level among 189 patients was “moderate.” The levels dipped below “moderate” at week 4 and never rose above “small” after that.

“Treatment-emergent adverse events reported in ≥5% of patients were nasopharyngitis (21.1%), AD (19.4%), upper respiratory tract infection (12.4%), headache (9.4%), and oropharyngeal pain (5.7%),” the investigators wrote in the poster. They add that 6.7% of patients experienced injection-site reactions, and 8.7% of patients experienced treatment-emergent “narrow conjunctivitis,” which includes conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, and atopic keratoconjunctivitis.

Dr. Simpson noted that cases of conjunctivitis fell over time. It’s not clear why this adverse effect appears, he said.

He said that the findings reflect his own experience in clinic. Many of his adolescent patients took part in early dupilumab trials, he said, and dozens have been taking the drug for more than 5 years. “They just seem to get better and better,” he said.

University of Minnesota, Minneapolis, dermatologist Sheilagh Maguiness, MD, who wasn’t involved with the study, said in an interview that dupilumab remains “the safest, most effective and evidence-based therapy we had for children with moderate to severe atopic dermatitis.”

The new study’s findings are “very reassuring,” she said, and similar to those in a 2021 report that tracked long-term use of the drug in children aged 6-11.

Like Dr. Simpson, Dr. Maguiness said many pediatric patients at her clinic have stayed on the drug for more than 5 years. They still have “sustained improvement in skin disease and in their quality of life as well”

There are, however, still questions about dupilumab treatment. “For children who have responded well, when could we consider dose reduction or discontinuation? I have done this successfully just a handful of times, but I would love to see data about what percentage of pediatric patients experience rebound disease after coming off the drug and after what duration of treatment,” she said. “Another mystery that will be very interesting to unravel is the question as to whether or not early treatment with dupilumab may attenuate other atopic diseases.”

Dr. Maguiness added that “another issue specific to pediatric use of dupilumab is the recommendation surrounding vaccinations. This is an issue that should be studied in terms of antibody response and safety surrounding vaccinations, particularly as we are eagerly awaiting a pediatric FDA approval for the COVID-19 vaccine in children.”

She also urged colleagues to push back against insurers who resist paying for dupilumab. “Whether prescribing this medication on or off label, insurance companies are often requiring patients to try and fail other traditional immunosuppressive medications such as methotrexate, cyclosporine, or to pursue phototherapy,” she said. “Oftentimes, these are not practical or even safe options for children for a multitude of reasons. Don’t be shy about advocating for your patients by second- or even third-level appeals to try and gain approval for children who are in need of treatment.”

The study was funded by Sanofi Genzyme and Regeneron Pharmaceuticals. The study authors reported various disclosures. Dr. Simpson reported investigator and consultant fee relationships from various pharmaceutical companies. Dr. Maguiness was an investigator for one of the initial pediatric dupilumab trials.

A version of this article first appeared on Medscape.com.

Serious adverse events remained rare and skin remained largely clear in adolescents treated with dupilumab for moderate to severe atopic dermatitis (AD) for up to 52 weeks in a phase 3, open-label extension trial, researchers reported.

At 1 year, 86% of 50 remaining patients with weights under 60 kg (132 lb) had achieved 75% improvement on the Eczema Area and Severity Index (EASI-75, and 77% of 51 remaining patients with weights over 60 kg reached that level of clearance. Only 5 (1.7%) of 294 patients had serious treatment-emergent adverse events (TEAEs).

The findings back up a perception that patients can stay on dupilumab for some time instead of having to switch from one biologic to another after a few years, study coauthor Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, said in an interview. He added that the drug’s long-term safety profile is “very reassuring.”

The industry-funded findings of the study were released in a poster at the 2021 meeting of the World Congress of Pediatric Dermatology.

The FDA approved dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, for treating AD in adults in 2017; it is now approved for treating patients ages 6 years and older with moderate to severe atopic dermatitis whose disease is not adequately controlled with topicals.

The new study tracked patients who received at least 300 mg dupilumab subcutaneously every 4 weeks. The dose could be increased if needed to improve clinical response to once every 2 weeks (200 mg if baseline weight was <60 kg; 300 mg if ≥60 kg).

At 52 weeks, 37% of 52 patients with weights under 60 kg reached an Investigator Global Assessment (IGA) of 0/1, a level that had been fairly steady since week 16 (n = 146). Among 51 heavier patients, 49% reached an IGA of 0/1 at 52 weeks; this percentage grew steadily since baseline.

The mean percentage change in EASI was –87% in the lower-weight group (n = 50) at 52 weeks and –80.1% in the larger-weight group (n = 51). The majority of the reduction in EASI occurred in the first 4 weeks of treatment.

At 52 weeks, the mean Children’s Dermatology Life Quality Index level, which judges the effect of AD on life, was judged as “small” (low) in 71 patients. At baseline, the mean level among 189 patients was “moderate.” The levels dipped below “moderate” at week 4 and never rose above “small” after that.

“Treatment-emergent adverse events reported in ≥5% of patients were nasopharyngitis (21.1%), AD (19.4%), upper respiratory tract infection (12.4%), headache (9.4%), and oropharyngeal pain (5.7%),” the investigators wrote in the poster. They add that 6.7% of patients experienced injection-site reactions, and 8.7% of patients experienced treatment-emergent “narrow conjunctivitis,” which includes conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, and atopic keratoconjunctivitis.

Dr. Simpson noted that cases of conjunctivitis fell over time. It’s not clear why this adverse effect appears, he said.

He said that the findings reflect his own experience in clinic. Many of his adolescent patients took part in early dupilumab trials, he said, and dozens have been taking the drug for more than 5 years. “They just seem to get better and better,” he said.

University of Minnesota, Minneapolis, dermatologist Sheilagh Maguiness, MD, who wasn’t involved with the study, said in an interview that dupilumab remains “the safest, most effective and evidence-based therapy we had for children with moderate to severe atopic dermatitis.”

The new study’s findings are “very reassuring,” she said, and similar to those in a 2021 report that tracked long-term use of the drug in children aged 6-11.

Like Dr. Simpson, Dr. Maguiness said many pediatric patients at her clinic have stayed on the drug for more than 5 years. They still have “sustained improvement in skin disease and in their quality of life as well”

There are, however, still questions about dupilumab treatment. “For children who have responded well, when could we consider dose reduction or discontinuation? I have done this successfully just a handful of times, but I would love to see data about what percentage of pediatric patients experience rebound disease after coming off the drug and after what duration of treatment,” she said. “Another mystery that will be very interesting to unravel is the question as to whether or not early treatment with dupilumab may attenuate other atopic diseases.”

Dr. Maguiness added that “another issue specific to pediatric use of dupilumab is the recommendation surrounding vaccinations. This is an issue that should be studied in terms of antibody response and safety surrounding vaccinations, particularly as we are eagerly awaiting a pediatric FDA approval for the COVID-19 vaccine in children.”

She also urged colleagues to push back against insurers who resist paying for dupilumab. “Whether prescribing this medication on or off label, insurance companies are often requiring patients to try and fail other traditional immunosuppressive medications such as methotrexate, cyclosporine, or to pursue phototherapy,” she said. “Oftentimes, these are not practical or even safe options for children for a multitude of reasons. Don’t be shy about advocating for your patients by second- or even third-level appeals to try and gain approval for children who are in need of treatment.”

The study was funded by Sanofi Genzyme and Regeneron Pharmaceuticals. The study authors reported various disclosures. Dr. Simpson reported investigator and consultant fee relationships from various pharmaceutical companies. Dr. Maguiness was an investigator for one of the initial pediatric dupilumab trials.

A version of this article first appeared on Medscape.com.

Lead poisoning remains a significant threat to the health of young children in the United States, based on data from blood tests of more than 1 million children.

Any level of lead is potentially harmful, although blood lead levels have decreased over the past several decades in part because of the elimination of lead from many consumer products, as well as from gas, paint, and plumbing fixtures, wrote Marissa Hauptman, MD, of Boston Children’s Hospital and colleagues.

However, “numerous environmental sources of legacy lead still exist,” and children living in poverty and in older housing in particular remain at increased risk for lead exposure, they noted.

In a study published in JAMA Pediatrics, the researchers analyzed deidentified results from blood lead tests performed at a single clinical laboratory for 1,141,441 children younger than 6 years between Oct. 1, 2018, and Feb. 29, 2020. The mean age of the children was 2.3 years; approximately half were boys.

Overall, 50.5% of the children tested (576,092 children) had detectable blood lead levels (BLLs), defined as 1.0 mcg/dL or higher, and 1.9% (21,172 children) had elevated BLLs, defined as 5.0 mcg/dL or higher.

In multivariate analysis, both detectable BLLs and elevated BLLs were significantly more common among children with public insurance (adjusted odds ratios, 2.01 and 1.08, respectively).

Children in the highest vs. lowest quintile of pre-1950s housing had significantly greater odds of both detectable and elevated BLLs (aOR, 1.65 and aOR, 3.06); those in the highest vs. lowest quintiles of poverty showed similarly increased risk of detectable and elevated BLLs (aOR, 1.89 and aOR, 1.99, respectively; P < .001 for all).

When the data were broken out by ZIP code, children in predominantly Black non-Hispanic and non-Latino neighborhoods were more likely than those living in other ZIP codes to have detectable BLLs (aOR, 1.13), but less likely to have elevated BLLs (aOR, 0.83). States with the highest overall proportions of children with detectable BLLs were Nebraska (83%), Missouri (82%), and Michigan (78%).

The study findings were limited by several factors, especially the potential for selection bias because of the use of a single reference laboratory (Quest Diagnostics), that does not perform all lead testing in the United States, the researchers noted. Other limitations included variability in testing at the state level, and the use of ZIP code–level data to estimate race, ethnicity, housing, and poverty, they said.

However, the results suggest that lead exposure remains a problem in young children, with significant disparities at the individual and community level, and national efforts must focus on further reductions of lead exposure in areas of highest risk, they concluded.
 

Step up lead elimination efforts

“The removal of lead from gasoline and new paint produced a precipitous decrease in blood lead levels from a population mean of 17 mcg/dL (all ages) in 1976 to 4 mcg/dL in the early 1990s to less than 2 mcg/dL today,” wrote Philip J. Landrigan, MD, of Boston College and David Bellinger, PhD, of Harvard University, Boston, in an accompanying editorial. However, “The findings from this study underscore the urgent need to eliminate all sources of lead exposure from U.S. children’s environments,” and highlight the persistent disparities in children’s lead exposure, they said.

The authors emphasized the need to remove existing lead paint from U.S. homes, as not only the paint itself, but the dust that enters the environment as the pain wears over time, continue to account for most detectable and elevated BLLs in children. A comprehensive lead paint removal effort would be an investment that would protect children now and would protect future generations, they emphasized. They proposed “creating a lead paint removal workforce through federally supported partnerships between city governments and major unions,” that would not only protect children from disease and disability, but could potentially provide jobs and vocational programs that would have a significant impact on communities.
 

Elevated lead levels may be underreported

In fact, the situation of children’s lead exposure in the United States may be more severe than indicated by the study findings, given the variation in testing at the state and local levels, said Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn.

“There are no available lead test kits in our offices, so I do worry that many elevated lead levels will be missed,” she said.

“The recent case of elevated lead levels in drinking water in Flint, Michigan, was largely detected through pediatric clinic screening and showed that elevated lead levels may remain a major issue in some communities,” said Tim Joos, MD, a clinician in combined internal medicine/pediatrics in Seattle, Wash., in an interview.

“It is important to highlight to what extent baseline and point-source lead contamination still exists, monitor progress towards lowering levels, and identify communities at high risk,” Dr. Joos emphasized. “The exact prevalence of elevated lead levels among the general pediatric populations is hard to estimate from this study because of the methodology, which looked at demographic characteristics of the subset of the pediatric population that had venous samples sent to Quest Lab,” he noted.

“As the authors pointed out, it is hard to know what biases went into deciding whether to screen or not, and whether these were confirmatory tests for elevated point of care testing done earlier in the clinic,” said Dr. Joos. “Nonetheless, it does point to the role of poverty and pre-1950s housing in elevated blood lead levels,” he added. “The study also highlights that, as the CDC considers lowering the level for what is considered an ‘elevated blood lead level’ from 5.0 to perhaps 3.5 mcg/dL, we still have a lot more work to do,” he said.

The study was funded by Quest Diagnostics and the company provided salaries to several coauthors during the study. Dr. Hauptmann disclosed support from the National Institutes of Health/National Institute of Environmental Health Sciences during the current study and support from the Agency for Toxic Substances and Disease Registry and the U.S. Environmental Protection Agency unrelated to the current study. Dr. Landrigan had no financial conflicts to disclose. Dr. Bellinger disclosed fees from attorneys for testimony in cases unrelated to the editorial. Dr. Kinsella had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News. Dr. Joos had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Lead poisoning remains a significant threat to the health of young children in the United States, based on data from blood tests of more than 1 million children.

Any level of lead is potentially harmful, although blood lead levels have decreased over the past several decades in part because of the elimination of lead from many consumer products, as well as from gas, paint, and plumbing fixtures, wrote Marissa Hauptman, MD, of Boston Children’s Hospital and colleagues.

However, “numerous environmental sources of legacy lead still exist,” and children living in poverty and in older housing in particular remain at increased risk for lead exposure, they noted.

In a study published in JAMA Pediatrics, the researchers analyzed deidentified results from blood lead tests performed at a single clinical laboratory for 1,141,441 children younger than 6 years between Oct. 1, 2018, and Feb. 29, 2020. The mean age of the children was 2.3 years; approximately half were boys.

Overall, 50.5% of the children tested (576,092 children) had detectable blood lead levels (BLLs), defined as 1.0 mcg/dL or higher, and 1.9% (21,172 children) had elevated BLLs, defined as 5.0 mcg/dL or higher.

In multivariate analysis, both detectable BLLs and elevated BLLs were significantly more common among children with public insurance (adjusted odds ratios, 2.01 and 1.08, respectively).

Children in the highest vs. lowest quintile of pre-1950s housing had significantly greater odds of both detectable and elevated BLLs (aOR, 1.65 and aOR, 3.06); those in the highest vs. lowest quintiles of poverty showed similarly increased risk of detectable and elevated BLLs (aOR, 1.89 and aOR, 1.99, respectively; P < .001 for all).

When the data were broken out by ZIP code, children in predominantly Black non-Hispanic and non-Latino neighborhoods were more likely than those living in other ZIP codes to have detectable BLLs (aOR, 1.13), but less likely to have elevated BLLs (aOR, 0.83). States with the highest overall proportions of children with detectable BLLs were Nebraska (83%), Missouri (82%), and Michigan (78%).

The study findings were limited by several factors, especially the potential for selection bias because of the use of a single reference laboratory (Quest Diagnostics), that does not perform all lead testing in the United States, the researchers noted. Other limitations included variability in testing at the state level, and the use of ZIP code–level data to estimate race, ethnicity, housing, and poverty, they said.

However, the results suggest that lead exposure remains a problem in young children, with significant disparities at the individual and community level, and national efforts must focus on further reductions of lead exposure in areas of highest risk, they concluded.
 

Step up lead elimination efforts

“The removal of lead from gasoline and new paint produced a precipitous decrease in blood lead levels from a population mean of 17 mcg/dL (all ages) in 1976 to 4 mcg/dL in the early 1990s to less than 2 mcg/dL today,” wrote Philip J. Landrigan, MD, of Boston College and David Bellinger, PhD, of Harvard University, Boston, in an accompanying editorial. However, “The findings from this study underscore the urgent need to eliminate all sources of lead exposure from U.S. children’s environments,” and highlight the persistent disparities in children’s lead exposure, they said.

The authors emphasized the need to remove existing lead paint from U.S. homes, as not only the paint itself, but the dust that enters the environment as the pain wears over time, continue to account for most detectable and elevated BLLs in children. A comprehensive lead paint removal effort would be an investment that would protect children now and would protect future generations, they emphasized. They proposed “creating a lead paint removal workforce through federally supported partnerships between city governments and major unions,” that would not only protect children from disease and disability, but could potentially provide jobs and vocational programs that would have a significant impact on communities.
 

Elevated lead levels may be underreported

In fact, the situation of children’s lead exposure in the United States may be more severe than indicated by the study findings, given the variation in testing at the state and local levels, said Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn.

“There are no available lead test kits in our offices, so I do worry that many elevated lead levels will be missed,” she said.

“The recent case of elevated lead levels in drinking water in Flint, Michigan, was largely detected through pediatric clinic screening and showed that elevated lead levels may remain a major issue in some communities,” said Tim Joos, MD, a clinician in combined internal medicine/pediatrics in Seattle, Wash., in an interview.

“It is important to highlight to what extent baseline and point-source lead contamination still exists, monitor progress towards lowering levels, and identify communities at high risk,” Dr. Joos emphasized. “The exact prevalence of elevated lead levels among the general pediatric populations is hard to estimate from this study because of the methodology, which looked at demographic characteristics of the subset of the pediatric population that had venous samples sent to Quest Lab,” he noted.

“As the authors pointed out, it is hard to know what biases went into deciding whether to screen or not, and whether these were confirmatory tests for elevated point of care testing done earlier in the clinic,” said Dr. Joos. “Nonetheless, it does point to the role of poverty and pre-1950s housing in elevated blood lead levels,” he added. “The study also highlights that, as the CDC considers lowering the level for what is considered an ‘elevated blood lead level’ from 5.0 to perhaps 3.5 mcg/dL, we still have a lot more work to do,” he said.

The study was funded by Quest Diagnostics and the company provided salaries to several coauthors during the study. Dr. Hauptmann disclosed support from the National Institutes of Health/National Institute of Environmental Health Sciences during the current study and support from the Agency for Toxic Substances and Disease Registry and the U.S. Environmental Protection Agency unrelated to the current study. Dr. Landrigan had no financial conflicts to disclose. Dr. Bellinger disclosed fees from attorneys for testimony in cases unrelated to the editorial. Dr. Kinsella had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News. Dr. Joos had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Lead poisoning remains a significant threat to the health of young children in the United States, based on data from blood tests of more than 1 million children.

Any level of lead is potentially harmful, although blood lead levels have decreased over the past several decades in part because of the elimination of lead from many consumer products, as well as from gas, paint, and plumbing fixtures, wrote Marissa Hauptman, MD, of Boston Children’s Hospital and colleagues.

However, “numerous environmental sources of legacy lead still exist,” and children living in poverty and in older housing in particular remain at increased risk for lead exposure, they noted.

In a study published in JAMA Pediatrics, the researchers analyzed deidentified results from blood lead tests performed at a single clinical laboratory for 1,141,441 children younger than 6 years between Oct. 1, 2018, and Feb. 29, 2020. The mean age of the children was 2.3 years; approximately half were boys.

Overall, 50.5% of the children tested (576,092 children) had detectable blood lead levels (BLLs), defined as 1.0 mcg/dL or higher, and 1.9% (21,172 children) had elevated BLLs, defined as 5.0 mcg/dL or higher.

In multivariate analysis, both detectable BLLs and elevated BLLs were significantly more common among children with public insurance (adjusted odds ratios, 2.01 and 1.08, respectively).

Children in the highest vs. lowest quintile of pre-1950s housing had significantly greater odds of both detectable and elevated BLLs (aOR, 1.65 and aOR, 3.06); those in the highest vs. lowest quintiles of poverty showed similarly increased risk of detectable and elevated BLLs (aOR, 1.89 and aOR, 1.99, respectively; P < .001 for all).

When the data were broken out by ZIP code, children in predominantly Black non-Hispanic and non-Latino neighborhoods were more likely than those living in other ZIP codes to have detectable BLLs (aOR, 1.13), but less likely to have elevated BLLs (aOR, 0.83). States with the highest overall proportions of children with detectable BLLs were Nebraska (83%), Missouri (82%), and Michigan (78%).

The study findings were limited by several factors, especially the potential for selection bias because of the use of a single reference laboratory (Quest Diagnostics), that does not perform all lead testing in the United States, the researchers noted. Other limitations included variability in testing at the state level, and the use of ZIP code–level data to estimate race, ethnicity, housing, and poverty, they said.

However, the results suggest that lead exposure remains a problem in young children, with significant disparities at the individual and community level, and national efforts must focus on further reductions of lead exposure in areas of highest risk, they concluded.
 

Step up lead elimination efforts

“The removal of lead from gasoline and new paint produced a precipitous decrease in blood lead levels from a population mean of 17 mcg/dL (all ages) in 1976 to 4 mcg/dL in the early 1990s to less than 2 mcg/dL today,” wrote Philip J. Landrigan, MD, of Boston College and David Bellinger, PhD, of Harvard University, Boston, in an accompanying editorial. However, “The findings from this study underscore the urgent need to eliminate all sources of lead exposure from U.S. children’s environments,” and highlight the persistent disparities in children’s lead exposure, they said.

The authors emphasized the need to remove existing lead paint from U.S. homes, as not only the paint itself, but the dust that enters the environment as the pain wears over time, continue to account for most detectable and elevated BLLs in children. A comprehensive lead paint removal effort would be an investment that would protect children now and would protect future generations, they emphasized. They proposed “creating a lead paint removal workforce through federally supported partnerships between city governments and major unions,” that would not only protect children from disease and disability, but could potentially provide jobs and vocational programs that would have a significant impact on communities.
 

Elevated lead levels may be underreported

In fact, the situation of children’s lead exposure in the United States may be more severe than indicated by the study findings, given the variation in testing at the state and local levels, said Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn.

“There are no available lead test kits in our offices, so I do worry that many elevated lead levels will be missed,” she said.

“The recent case of elevated lead levels in drinking water in Flint, Michigan, was largely detected through pediatric clinic screening and showed that elevated lead levels may remain a major issue in some communities,” said Tim Joos, MD, a clinician in combined internal medicine/pediatrics in Seattle, Wash., in an interview.

“It is important to highlight to what extent baseline and point-source lead contamination still exists, monitor progress towards lowering levels, and identify communities at high risk,” Dr. Joos emphasized. “The exact prevalence of elevated lead levels among the general pediatric populations is hard to estimate from this study because of the methodology, which looked at demographic characteristics of the subset of the pediatric population that had venous samples sent to Quest Lab,” he noted.

“As the authors pointed out, it is hard to know what biases went into deciding whether to screen or not, and whether these were confirmatory tests for elevated point of care testing done earlier in the clinic,” said Dr. Joos. “Nonetheless, it does point to the role of poverty and pre-1950s housing in elevated blood lead levels,” he added. “The study also highlights that, as the CDC considers lowering the level for what is considered an ‘elevated blood lead level’ from 5.0 to perhaps 3.5 mcg/dL, we still have a lot more work to do,” he said.

The study was funded by Quest Diagnostics and the company provided salaries to several coauthors during the study. Dr. Hauptmann disclosed support from the National Institutes of Health/National Institute of Environmental Health Sciences during the current study and support from the Agency for Toxic Substances and Disease Registry and the U.S. Environmental Protection Agency unrelated to the current study. Dr. Landrigan had no financial conflicts to disclose. Dr. Bellinger disclosed fees from attorneys for testimony in cases unrelated to the editorial. Dr. Kinsella had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News. Dr. Joos had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.

David Schairer, MD

JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
 

What is on the differential?

Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.

Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.

Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.

Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.

Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
 

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Kleinman is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Kleinman have no relevant financial disclosures.

References

Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.

Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).

Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.

Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.

Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.

David Schairer, MD

JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
 

What is on the differential?

Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.

Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.

Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.

Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.

Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
 

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Kleinman is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Kleinman have no relevant financial disclosures.

References

Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.

Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).

Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.

Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.

Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.

David Schairer, MD

JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
 

What is on the differential?

Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.

Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.

Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.

Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.

Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
 

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Kleinman is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Kleinman have no relevant financial disclosures.

References

Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.

Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).

Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.

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