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PARP/ATR inhibitor combo shows hints of promise in children with tumors
The small phase 1 trial also identified some molecular signatures in responders that may inform future clinical trials.
The results, presented at the annual meeting of the American Association of Cancer Research, came from a single arm of the European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (ESMART) trial. This trial matches pediatric, adolescent, and young adult cancer patients with treatment regimens based on the molecular profile of their tumors.
In over 220 children to date, the trial has investigated 15 different treatment regimens, most of which are combination therapies.
In adults, PARP) inhibitors have been shown to be effective in tumors with deficiencies in homologous repair, which is a DNA repair mechanism, with notable successes in patients carrying the BRCA1 and BRCA2 mutations. But BRCA1 and BRCA2 mutations are rare in pediatric cancer, and there is a belief that there may be primary resistance to PARP inhibitors in pediatric tumors, according to Susanne Gatz, MD, PhD, who presented the research at the meeting.
Previous research identified alterations in pediatric tumors that are candidates for patient selection. “These tumors have alterations which could potentially cause this resistance effect [against PARP inhibitors] and [also cause] sensitivity to ataxia telangiectasia–mutated Rad3-related inhibitors. This is how this arm [of the ESMART trial] was born,” said Dr. Gatz.
The phase 1 portion of the study included 18 pediatric and young adult patients with relapsed or treatment-refractory tumors. There were eight sarcomas, five central nervous system tumors, four neuroblastomas, and one carcinoma. Each had mutations thought to lead to HR deficiency or replication stress. The study included three dose levels of twice-daily oral olaparib that was given continuously, and ceralasertib, which was given day 1-14 of each 28-day cycle.
Patients underwent a median of 3.5 cycles of treatment. There were dose-limiting adverse events of thrombocytopenia and neutropenia in five patients, two of which occurred at the dose that was recommended for phase 2.
There were some positive clinical signs, including one partial response in a pineoblastoma patient who received treatment for 11 cycles. A neuroblastoma patient had stable disease until cycle 9 of treatment, and then converted to a partial response and is currently in cycle 12. Two other patients remain in treatment at cycle 8 and one is in treatment at cycle 15. None of the patients who experienced clinical benefit had BRCA mutations.
An important goal of the study was to understand molecular signature that might predict response to the drug combination. Although no firm conclusions could be drawn, there were some interesting patterns. In particular, five of the six worst responders had TP53 mutations. “It is striking ... so we need to learn what TP53 in this setting means if it’s mutated, and if it could be a resistance factor,” said Dr. Gatz, an associate clinical professor in pediatric oncology at the Institute of Cancer and Genomic Sciences of the University of Birmingham, during her talk.
Although the study is too small and included too many tumor types to identify tumor-based patterns of response, it did provide some hints as to biomarkers that could inform future studies, according to Julia Glade Bender, MD, who served as a discussant following the presentation and is a pediatric oncologist at Memorial Sloan Kettering Cancer Center, New York.
“The pediatric frequency of the common DNA damage repair biomarkers that have been [identified in] the adult literature – that is to say, BRCA1 and 2 and [ataxia-telangiectasia mutation] – are exceedingly rare in pediatrics,” said Dr. Bender during the session while serving as a discussant. She highlighted the following findings: Loss of the 11q region on chromosome 11 is common among the patients and that region contains three genes involved in the DNA damage response, along with a gene involved in homologous recombination, telomere maintenance, and double strand break repair.
She added that 11q deletion is also found in up to 40% of neuroblastomas, and is associated with poor prognosis, and the patients have multiple segmental chromosomal abnormalities. “That begs the question [of] whether chromosomal instability is another biomarker for pediatric cancer,” said Dr. Bender.
“The research highlights the complexity of pediatric cancers, whose distinct biology could make them more vulnerable to ATR [kinase], [checkpoint kinase 1], and WEE1 pathway inhibition with a PARP inhibitor used to induce replication stress and be the sensitizer. The biomarker profiles are going to be complex, context-dependent, and likely to reflect a constellation of findings that would be signatures or algorithms, rather than single gene alterations. The post hoc iterative analysis of responders and nonresponders is going to be absolutely critical to understanding those biomarkers and the role of DNA damage response inhibitors in pediatrics. Given the rarity of these diagnoses, and then the molecular subclasses, I think collaboration across ages and geography is absolutely critical, and I really congratulate the ESMART consortium for doing just that in Europe,” said Dr. Bender.
The study is limited by its small sample size and the fact that it was not randomized.
The study received funding from French Institut National de Cancer, Imagine for Margo, Fondation ARC, AstraZeneca France, AstraZeneca Global R&D, AstraZeneca UK, Cancer Research UK, Fondation Gustave Roussy, and Little Princess Trust/Children’s Cancer and Leukaemia Group. Dr. Gatz has no relevant financial disclosures. Dr. Bender has done paid consulting for Jazz Pharmaceuticals and has done unpaid work for Bristol-Myers Squibb, Eisai, Springworks Therapeutics, Merck Sharp & Dohme, and Pfizer. She has received research support from Eli Lilly, Loxo-oncology, Eisai, Cellectar, Bayer, Amgen, and Jazz Pharmaceuticals.
From American Association for Cancer Research (AACR) Annual Meeting 2023: Abstract CT019. Presented Tuesday, April 18.
The small phase 1 trial also identified some molecular signatures in responders that may inform future clinical trials.
The results, presented at the annual meeting of the American Association of Cancer Research, came from a single arm of the European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (ESMART) trial. This trial matches pediatric, adolescent, and young adult cancer patients with treatment regimens based on the molecular profile of their tumors.
In over 220 children to date, the trial has investigated 15 different treatment regimens, most of which are combination therapies.
In adults, PARP) inhibitors have been shown to be effective in tumors with deficiencies in homologous repair, which is a DNA repair mechanism, with notable successes in patients carrying the BRCA1 and BRCA2 mutations. But BRCA1 and BRCA2 mutations are rare in pediatric cancer, and there is a belief that there may be primary resistance to PARP inhibitors in pediatric tumors, according to Susanne Gatz, MD, PhD, who presented the research at the meeting.
Previous research identified alterations in pediatric tumors that are candidates for patient selection. “These tumors have alterations which could potentially cause this resistance effect [against PARP inhibitors] and [also cause] sensitivity to ataxia telangiectasia–mutated Rad3-related inhibitors. This is how this arm [of the ESMART trial] was born,” said Dr. Gatz.
The phase 1 portion of the study included 18 pediatric and young adult patients with relapsed or treatment-refractory tumors. There were eight sarcomas, five central nervous system tumors, four neuroblastomas, and one carcinoma. Each had mutations thought to lead to HR deficiency or replication stress. The study included three dose levels of twice-daily oral olaparib that was given continuously, and ceralasertib, which was given day 1-14 of each 28-day cycle.
Patients underwent a median of 3.5 cycles of treatment. There were dose-limiting adverse events of thrombocytopenia and neutropenia in five patients, two of which occurred at the dose that was recommended for phase 2.
There were some positive clinical signs, including one partial response in a pineoblastoma patient who received treatment for 11 cycles. A neuroblastoma patient had stable disease until cycle 9 of treatment, and then converted to a partial response and is currently in cycle 12. Two other patients remain in treatment at cycle 8 and one is in treatment at cycle 15. None of the patients who experienced clinical benefit had BRCA mutations.
An important goal of the study was to understand molecular signature that might predict response to the drug combination. Although no firm conclusions could be drawn, there were some interesting patterns. In particular, five of the six worst responders had TP53 mutations. “It is striking ... so we need to learn what TP53 in this setting means if it’s mutated, and if it could be a resistance factor,” said Dr. Gatz, an associate clinical professor in pediatric oncology at the Institute of Cancer and Genomic Sciences of the University of Birmingham, during her talk.
Although the study is too small and included too many tumor types to identify tumor-based patterns of response, it did provide some hints as to biomarkers that could inform future studies, according to Julia Glade Bender, MD, who served as a discussant following the presentation and is a pediatric oncologist at Memorial Sloan Kettering Cancer Center, New York.
“The pediatric frequency of the common DNA damage repair biomarkers that have been [identified in] the adult literature – that is to say, BRCA1 and 2 and [ataxia-telangiectasia mutation] – are exceedingly rare in pediatrics,” said Dr. Bender during the session while serving as a discussant. She highlighted the following findings: Loss of the 11q region on chromosome 11 is common among the patients and that region contains three genes involved in the DNA damage response, along with a gene involved in homologous recombination, telomere maintenance, and double strand break repair.
She added that 11q deletion is also found in up to 40% of neuroblastomas, and is associated with poor prognosis, and the patients have multiple segmental chromosomal abnormalities. “That begs the question [of] whether chromosomal instability is another biomarker for pediatric cancer,” said Dr. Bender.
“The research highlights the complexity of pediatric cancers, whose distinct biology could make them more vulnerable to ATR [kinase], [checkpoint kinase 1], and WEE1 pathway inhibition with a PARP inhibitor used to induce replication stress and be the sensitizer. The biomarker profiles are going to be complex, context-dependent, and likely to reflect a constellation of findings that would be signatures or algorithms, rather than single gene alterations. The post hoc iterative analysis of responders and nonresponders is going to be absolutely critical to understanding those biomarkers and the role of DNA damage response inhibitors in pediatrics. Given the rarity of these diagnoses, and then the molecular subclasses, I think collaboration across ages and geography is absolutely critical, and I really congratulate the ESMART consortium for doing just that in Europe,” said Dr. Bender.
The study is limited by its small sample size and the fact that it was not randomized.
The study received funding from French Institut National de Cancer, Imagine for Margo, Fondation ARC, AstraZeneca France, AstraZeneca Global R&D, AstraZeneca UK, Cancer Research UK, Fondation Gustave Roussy, and Little Princess Trust/Children’s Cancer and Leukaemia Group. Dr. Gatz has no relevant financial disclosures. Dr. Bender has done paid consulting for Jazz Pharmaceuticals and has done unpaid work for Bristol-Myers Squibb, Eisai, Springworks Therapeutics, Merck Sharp & Dohme, and Pfizer. She has received research support from Eli Lilly, Loxo-oncology, Eisai, Cellectar, Bayer, Amgen, and Jazz Pharmaceuticals.
From American Association for Cancer Research (AACR) Annual Meeting 2023: Abstract CT019. Presented Tuesday, April 18.
The small phase 1 trial also identified some molecular signatures in responders that may inform future clinical trials.
The results, presented at the annual meeting of the American Association of Cancer Research, came from a single arm of the European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (ESMART) trial. This trial matches pediatric, adolescent, and young adult cancer patients with treatment regimens based on the molecular profile of their tumors.
In over 220 children to date, the trial has investigated 15 different treatment regimens, most of which are combination therapies.
In adults, PARP) inhibitors have been shown to be effective in tumors with deficiencies in homologous repair, which is a DNA repair mechanism, with notable successes in patients carrying the BRCA1 and BRCA2 mutations. But BRCA1 and BRCA2 mutations are rare in pediatric cancer, and there is a belief that there may be primary resistance to PARP inhibitors in pediatric tumors, according to Susanne Gatz, MD, PhD, who presented the research at the meeting.
Previous research identified alterations in pediatric tumors that are candidates for patient selection. “These tumors have alterations which could potentially cause this resistance effect [against PARP inhibitors] and [also cause] sensitivity to ataxia telangiectasia–mutated Rad3-related inhibitors. This is how this arm [of the ESMART trial] was born,” said Dr. Gatz.
The phase 1 portion of the study included 18 pediatric and young adult patients with relapsed or treatment-refractory tumors. There were eight sarcomas, five central nervous system tumors, four neuroblastomas, and one carcinoma. Each had mutations thought to lead to HR deficiency or replication stress. The study included three dose levels of twice-daily oral olaparib that was given continuously, and ceralasertib, which was given day 1-14 of each 28-day cycle.
Patients underwent a median of 3.5 cycles of treatment. There were dose-limiting adverse events of thrombocytopenia and neutropenia in five patients, two of which occurred at the dose that was recommended for phase 2.
There were some positive clinical signs, including one partial response in a pineoblastoma patient who received treatment for 11 cycles. A neuroblastoma patient had stable disease until cycle 9 of treatment, and then converted to a partial response and is currently in cycle 12. Two other patients remain in treatment at cycle 8 and one is in treatment at cycle 15. None of the patients who experienced clinical benefit had BRCA mutations.
An important goal of the study was to understand molecular signature that might predict response to the drug combination. Although no firm conclusions could be drawn, there were some interesting patterns. In particular, five of the six worst responders had TP53 mutations. “It is striking ... so we need to learn what TP53 in this setting means if it’s mutated, and if it could be a resistance factor,” said Dr. Gatz, an associate clinical professor in pediatric oncology at the Institute of Cancer and Genomic Sciences of the University of Birmingham, during her talk.
Although the study is too small and included too many tumor types to identify tumor-based patterns of response, it did provide some hints as to biomarkers that could inform future studies, according to Julia Glade Bender, MD, who served as a discussant following the presentation and is a pediatric oncologist at Memorial Sloan Kettering Cancer Center, New York.
“The pediatric frequency of the common DNA damage repair biomarkers that have been [identified in] the adult literature – that is to say, BRCA1 and 2 and [ataxia-telangiectasia mutation] – are exceedingly rare in pediatrics,” said Dr. Bender during the session while serving as a discussant. She highlighted the following findings: Loss of the 11q region on chromosome 11 is common among the patients and that region contains three genes involved in the DNA damage response, along with a gene involved in homologous recombination, telomere maintenance, and double strand break repair.
She added that 11q deletion is also found in up to 40% of neuroblastomas, and is associated with poor prognosis, and the patients have multiple segmental chromosomal abnormalities. “That begs the question [of] whether chromosomal instability is another biomarker for pediatric cancer,” said Dr. Bender.
“The research highlights the complexity of pediatric cancers, whose distinct biology could make them more vulnerable to ATR [kinase], [checkpoint kinase 1], and WEE1 pathway inhibition with a PARP inhibitor used to induce replication stress and be the sensitizer. The biomarker profiles are going to be complex, context-dependent, and likely to reflect a constellation of findings that would be signatures or algorithms, rather than single gene alterations. The post hoc iterative analysis of responders and nonresponders is going to be absolutely critical to understanding those biomarkers and the role of DNA damage response inhibitors in pediatrics. Given the rarity of these diagnoses, and then the molecular subclasses, I think collaboration across ages and geography is absolutely critical, and I really congratulate the ESMART consortium for doing just that in Europe,” said Dr. Bender.
The study is limited by its small sample size and the fact that it was not randomized.
The study received funding from French Institut National de Cancer, Imagine for Margo, Fondation ARC, AstraZeneca France, AstraZeneca Global R&D, AstraZeneca UK, Cancer Research UK, Fondation Gustave Roussy, and Little Princess Trust/Children’s Cancer and Leukaemia Group. Dr. Gatz has no relevant financial disclosures. Dr. Bender has done paid consulting for Jazz Pharmaceuticals and has done unpaid work for Bristol-Myers Squibb, Eisai, Springworks Therapeutics, Merck Sharp & Dohme, and Pfizer. She has received research support from Eli Lilly, Loxo-oncology, Eisai, Cellectar, Bayer, Amgen, and Jazz Pharmaceuticals.
From American Association for Cancer Research (AACR) Annual Meeting 2023: Abstract CT019. Presented Tuesday, April 18.
FROM AACR 2023
Rabies: How to respond to parents’ questions
When most families hear the word rabies, they envision a dog foaming at the mouth and think about receiving multiple painful, often intra-abdominal injections. However, the epidemiology of rabies has changed in the United States. Postexposure prophylaxis (PEP) may not always be indicated and for certain persons preexposure prophylaxis (PrEP) is available and recommended.
Rabies is a Lyssavirus that is transmitted through saliva most often from the bite or scratch of an infected animal. Sometimes it’s via direct contact with mucous membranes. Although rare, cases have been described in which an undiagnosed donor passed the virus via transplant to recipients and four cases of aerosolized transmission were documented in two spelunkers and two laboratory technicians working with the virus. Worldwide it’s estimated that rabies causes 59,000 deaths annually.
Most cases (98%) are secondary to canine rabies. Prior to 1960, dogs were the major reservoir in the United States; however, after introduction of leash laws and animal vaccination in 1947, there was a drastic decline in cases caused by the canine rabies virus variant (CRVV). By 2004, CRVV was eliminated in the United States.
However, the proportion of strains associated with wildlife including raccoons, skunks, foxes, bats, coyotes, and mongoose now account for most of the cases in humans. Wildlife rabies is found in all states except Hawaii. Between 1960 and 2018, 89 cases were acquired in the United States and 62 (70%) were from bat exposure. Dog bites acquired during international travel were the cause of 36 cases.
Once signs and symptoms of disease develop there is no treatment. Regardless of the species variant, rabies virus infection is fatal in over 99% of cases. However, disease can be prevented with prompt initiation of PEP, which includes administration of rabies immune globulin (RIG) and rabies vaccine. Let’s look at a few different scenarios.
1. A delivery person is bitten by your neighbor’s dog while making a delivery. He was told to get rabies vaccine. What should we advise?
Canine rabies has been eliminated in the United States. However, unvaccinated canines can acquire rabies from wildlife. In this situation, you can determine the immunization status of the dog. Contact your local/state health department to assist with enforcement and management. Bites by cats and ferrets should be managed similarly.
Healthy dog:
1. Observe for 10 days.
2. PEP is not indicated unless the animal develops signs/symptoms of rabies. Then euthanize and begin PEP.
Dog appears rabid or suspected to be rabid:
1. Begin PEP.
2. Animal should be euthanized. If immunofluorescent test is negative discontinue PEP.
Dog unavailable:
Contact local/state health department. They are more familiar with rabies surveillance data.
2. Patient relocating to Malaysia for 3-4 years. Rabies PrEP was recommended but the family wants your opinion before receiving the vaccine. What would you advise?
Canine rabies is felt to be the primary cause of rabies outside of the United States. Canines are not routinely vaccinated in many foreign destinations, and the availability of RIG and rabies vaccine is not guaranteed in developing countries. As noted above, dog bites during international travel accounted for 28% of U.S. cases between 1960 and 2018.
In May 2022 recommendations for a modified two-dose PrEP schedule was published that identifies five risk groups and includes specific timing for checking rabies titers. The third rabies dose can now be administered up until year 3 (Morb Mortal Wkly Rep. 2022 May 6;71[18]:619-27). For individuals relocating to countries where CRVV is present, I prefer the traditional three-dose PrEP schedule administered between 21 and 28 days. However, we now have options. If exposure occurs any time after completion of a three-dose PrEP series or within 3 years after completion of a two-dose PrEP series, RIG would not be required. All patients would receive two doses of rabies vaccine (days 0, 3). If exposure occurs after 3 years in a person who received two doses of PrEP who did not have documentation of a protective rabies titer (> 5 IU/mL), treatment will include RIG plus four doses of vaccine (days 0, 3, 7, 14).
For this relocating patient, supporting PrEP would be strongly recommended.
3. A mother tells you she sees bats flying around her home at night and a few have even gotten into the home. This morning she saw one in her child’s room. He was still sleeping. Is there anything she needs to do?
Bats have become the predominant source of rabies in the United States. In addition to the cases noted above, three fatal cases occurred between Sept. 28 and Nov. 10, 2021, after bat exposures in August 2021 (MMWR Morb Mortal Wkly Rep. 2022 Jan 7;71:31-2). All had recognized contact with a bat 3-7 weeks prior to onset of symptoms and died 2-3 weeks after symptom onset. One declined PEP and the other two did not realize the risk for rabies from their exposure or did not notice a scratch or bite. Bites from bats may be small and unnoticed. Exposure to a bat in a closed room while sleeping is considered an exposure. Hawaii is the only state not reporting rabid bats.
PEP is recommended for her child. She should identify potential areas bats may enter the home and seal them in addition to removal of any bat roosts.
4. A parent realizes a house guest has been feeding raccoons in the backyard. What’s your response?
While bat rabies is the predominant variant associated with disease in the United States, as illustrated in Figure 1, other species of wildlife including raccoons are a major source of rabies. The geographic spread of the raccoon variant of rabies has been limited by oral vaccination via bait. In the situation noted here, the raccoons have returned because food was being offered thus increasing the families chance of a potential rabies exposure. Wildlife including skunks, raccoons, coyotes, foxes, and mongooses are always considered rabid until proven negative by laboratory testing.
You recommend to stop feeding wildlife and never to approach them. Have them contact the local rabies control unit and/or state wildlife services to assist with removal of the raccoons. Depending on the locale, pest control may be required at the owners expense. Inform the family to seek PEP if anyone is bitten or scratched by the raccoons.
As per the Centers for Disease Control and Prevention, about 55,000 residents receive PEP annually with health-associated expenditures including diagnostics, prevention, and control estimated between $245 and $510 million annually. Rabies is one of the most fatal diseases that can be prevented by avoiding contact with wild animals, maintenance of high immunization rates in pets, and keeping people informed of potential sources including bats. One can’t determine if an animal has rabies by looking at it. Rabies remains an urgent disease that we have to remember to address with our patients and their families. For additional information go to www.CDC.gov/rabies.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She has no relevant financial disclosures.
When most families hear the word rabies, they envision a dog foaming at the mouth and think about receiving multiple painful, often intra-abdominal injections. However, the epidemiology of rabies has changed in the United States. Postexposure prophylaxis (PEP) may not always be indicated and for certain persons preexposure prophylaxis (PrEP) is available and recommended.
Rabies is a Lyssavirus that is transmitted through saliva most often from the bite or scratch of an infected animal. Sometimes it’s via direct contact with mucous membranes. Although rare, cases have been described in which an undiagnosed donor passed the virus via transplant to recipients and four cases of aerosolized transmission were documented in two spelunkers and two laboratory technicians working with the virus. Worldwide it’s estimated that rabies causes 59,000 deaths annually.
Most cases (98%) are secondary to canine rabies. Prior to 1960, dogs were the major reservoir in the United States; however, after introduction of leash laws and animal vaccination in 1947, there was a drastic decline in cases caused by the canine rabies virus variant (CRVV). By 2004, CRVV was eliminated in the United States.
However, the proportion of strains associated with wildlife including raccoons, skunks, foxes, bats, coyotes, and mongoose now account for most of the cases in humans. Wildlife rabies is found in all states except Hawaii. Between 1960 and 2018, 89 cases were acquired in the United States and 62 (70%) were from bat exposure. Dog bites acquired during international travel were the cause of 36 cases.
Once signs and symptoms of disease develop there is no treatment. Regardless of the species variant, rabies virus infection is fatal in over 99% of cases. However, disease can be prevented with prompt initiation of PEP, which includes administration of rabies immune globulin (RIG) and rabies vaccine. Let’s look at a few different scenarios.
1. A delivery person is bitten by your neighbor’s dog while making a delivery. He was told to get rabies vaccine. What should we advise?
Canine rabies has been eliminated in the United States. However, unvaccinated canines can acquire rabies from wildlife. In this situation, you can determine the immunization status of the dog. Contact your local/state health department to assist with enforcement and management. Bites by cats and ferrets should be managed similarly.
Healthy dog:
1. Observe for 10 days.
2. PEP is not indicated unless the animal develops signs/symptoms of rabies. Then euthanize and begin PEP.
Dog appears rabid or suspected to be rabid:
1. Begin PEP.
2. Animal should be euthanized. If immunofluorescent test is negative discontinue PEP.
Dog unavailable:
Contact local/state health department. They are more familiar with rabies surveillance data.
2. Patient relocating to Malaysia for 3-4 years. Rabies PrEP was recommended but the family wants your opinion before receiving the vaccine. What would you advise?
Canine rabies is felt to be the primary cause of rabies outside of the United States. Canines are not routinely vaccinated in many foreign destinations, and the availability of RIG and rabies vaccine is not guaranteed in developing countries. As noted above, dog bites during international travel accounted for 28% of U.S. cases between 1960 and 2018.
In May 2022 recommendations for a modified two-dose PrEP schedule was published that identifies five risk groups and includes specific timing for checking rabies titers. The third rabies dose can now be administered up until year 3 (Morb Mortal Wkly Rep. 2022 May 6;71[18]:619-27). For individuals relocating to countries where CRVV is present, I prefer the traditional three-dose PrEP schedule administered between 21 and 28 days. However, we now have options. If exposure occurs any time after completion of a three-dose PrEP series or within 3 years after completion of a two-dose PrEP series, RIG would not be required. All patients would receive two doses of rabies vaccine (days 0, 3). If exposure occurs after 3 years in a person who received two doses of PrEP who did not have documentation of a protective rabies titer (> 5 IU/mL), treatment will include RIG plus four doses of vaccine (days 0, 3, 7, 14).
For this relocating patient, supporting PrEP would be strongly recommended.
3. A mother tells you she sees bats flying around her home at night and a few have even gotten into the home. This morning she saw one in her child’s room. He was still sleeping. Is there anything she needs to do?
Bats have become the predominant source of rabies in the United States. In addition to the cases noted above, three fatal cases occurred between Sept. 28 and Nov. 10, 2021, after bat exposures in August 2021 (MMWR Morb Mortal Wkly Rep. 2022 Jan 7;71:31-2). All had recognized contact with a bat 3-7 weeks prior to onset of symptoms and died 2-3 weeks after symptom onset. One declined PEP and the other two did not realize the risk for rabies from their exposure or did not notice a scratch or bite. Bites from bats may be small and unnoticed. Exposure to a bat in a closed room while sleeping is considered an exposure. Hawaii is the only state not reporting rabid bats.
PEP is recommended for her child. She should identify potential areas bats may enter the home and seal them in addition to removal of any bat roosts.
4. A parent realizes a house guest has been feeding raccoons in the backyard. What’s your response?
While bat rabies is the predominant variant associated with disease in the United States, as illustrated in Figure 1, other species of wildlife including raccoons are a major source of rabies. The geographic spread of the raccoon variant of rabies has been limited by oral vaccination via bait. In the situation noted here, the raccoons have returned because food was being offered thus increasing the families chance of a potential rabies exposure. Wildlife including skunks, raccoons, coyotes, foxes, and mongooses are always considered rabid until proven negative by laboratory testing.
You recommend to stop feeding wildlife and never to approach them. Have them contact the local rabies control unit and/or state wildlife services to assist with removal of the raccoons. Depending on the locale, pest control may be required at the owners expense. Inform the family to seek PEP if anyone is bitten or scratched by the raccoons.
As per the Centers for Disease Control and Prevention, about 55,000 residents receive PEP annually with health-associated expenditures including diagnostics, prevention, and control estimated between $245 and $510 million annually. Rabies is one of the most fatal diseases that can be prevented by avoiding contact with wild animals, maintenance of high immunization rates in pets, and keeping people informed of potential sources including bats. One can’t determine if an animal has rabies by looking at it. Rabies remains an urgent disease that we have to remember to address with our patients and their families. For additional information go to www.CDC.gov/rabies.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She has no relevant financial disclosures.
When most families hear the word rabies, they envision a dog foaming at the mouth and think about receiving multiple painful, often intra-abdominal injections. However, the epidemiology of rabies has changed in the United States. Postexposure prophylaxis (PEP) may not always be indicated and for certain persons preexposure prophylaxis (PrEP) is available and recommended.
Rabies is a Lyssavirus that is transmitted through saliva most often from the bite or scratch of an infected animal. Sometimes it’s via direct contact with mucous membranes. Although rare, cases have been described in which an undiagnosed donor passed the virus via transplant to recipients and four cases of aerosolized transmission were documented in two spelunkers and two laboratory technicians working with the virus. Worldwide it’s estimated that rabies causes 59,000 deaths annually.
Most cases (98%) are secondary to canine rabies. Prior to 1960, dogs were the major reservoir in the United States; however, after introduction of leash laws and animal vaccination in 1947, there was a drastic decline in cases caused by the canine rabies virus variant (CRVV). By 2004, CRVV was eliminated in the United States.
However, the proportion of strains associated with wildlife including raccoons, skunks, foxes, bats, coyotes, and mongoose now account for most of the cases in humans. Wildlife rabies is found in all states except Hawaii. Between 1960 and 2018, 89 cases were acquired in the United States and 62 (70%) were from bat exposure. Dog bites acquired during international travel were the cause of 36 cases.
Once signs and symptoms of disease develop there is no treatment. Regardless of the species variant, rabies virus infection is fatal in over 99% of cases. However, disease can be prevented with prompt initiation of PEP, which includes administration of rabies immune globulin (RIG) and rabies vaccine. Let’s look at a few different scenarios.
1. A delivery person is bitten by your neighbor’s dog while making a delivery. He was told to get rabies vaccine. What should we advise?
Canine rabies has been eliminated in the United States. However, unvaccinated canines can acquire rabies from wildlife. In this situation, you can determine the immunization status of the dog. Contact your local/state health department to assist with enforcement and management. Bites by cats and ferrets should be managed similarly.
Healthy dog:
1. Observe for 10 days.
2. PEP is not indicated unless the animal develops signs/symptoms of rabies. Then euthanize and begin PEP.
Dog appears rabid or suspected to be rabid:
1. Begin PEP.
2. Animal should be euthanized. If immunofluorescent test is negative discontinue PEP.
Dog unavailable:
Contact local/state health department. They are more familiar with rabies surveillance data.
2. Patient relocating to Malaysia for 3-4 years. Rabies PrEP was recommended but the family wants your opinion before receiving the vaccine. What would you advise?
Canine rabies is felt to be the primary cause of rabies outside of the United States. Canines are not routinely vaccinated in many foreign destinations, and the availability of RIG and rabies vaccine is not guaranteed in developing countries. As noted above, dog bites during international travel accounted for 28% of U.S. cases between 1960 and 2018.
In May 2022 recommendations for a modified two-dose PrEP schedule was published that identifies five risk groups and includes specific timing for checking rabies titers. The third rabies dose can now be administered up until year 3 (Morb Mortal Wkly Rep. 2022 May 6;71[18]:619-27). For individuals relocating to countries where CRVV is present, I prefer the traditional three-dose PrEP schedule administered between 21 and 28 days. However, we now have options. If exposure occurs any time after completion of a three-dose PrEP series or within 3 years after completion of a two-dose PrEP series, RIG would not be required. All patients would receive two doses of rabies vaccine (days 0, 3). If exposure occurs after 3 years in a person who received two doses of PrEP who did not have documentation of a protective rabies titer (> 5 IU/mL), treatment will include RIG plus four doses of vaccine (days 0, 3, 7, 14).
For this relocating patient, supporting PrEP would be strongly recommended.
3. A mother tells you she sees bats flying around her home at night and a few have even gotten into the home. This morning she saw one in her child’s room. He was still sleeping. Is there anything she needs to do?
Bats have become the predominant source of rabies in the United States. In addition to the cases noted above, three fatal cases occurred between Sept. 28 and Nov. 10, 2021, after bat exposures in August 2021 (MMWR Morb Mortal Wkly Rep. 2022 Jan 7;71:31-2). All had recognized contact with a bat 3-7 weeks prior to onset of symptoms and died 2-3 weeks after symptom onset. One declined PEP and the other two did not realize the risk for rabies from their exposure or did not notice a scratch or bite. Bites from bats may be small and unnoticed. Exposure to a bat in a closed room while sleeping is considered an exposure. Hawaii is the only state not reporting rabid bats.
PEP is recommended for her child. She should identify potential areas bats may enter the home and seal them in addition to removal of any bat roosts.
4. A parent realizes a house guest has been feeding raccoons in the backyard. What’s your response?
While bat rabies is the predominant variant associated with disease in the United States, as illustrated in Figure 1, other species of wildlife including raccoons are a major source of rabies. The geographic spread of the raccoon variant of rabies has been limited by oral vaccination via bait. In the situation noted here, the raccoons have returned because food was being offered thus increasing the families chance of a potential rabies exposure. Wildlife including skunks, raccoons, coyotes, foxes, and mongooses are always considered rabid until proven negative by laboratory testing.
You recommend to stop feeding wildlife and never to approach them. Have them contact the local rabies control unit and/or state wildlife services to assist with removal of the raccoons. Depending on the locale, pest control may be required at the owners expense. Inform the family to seek PEP if anyone is bitten or scratched by the raccoons.
As per the Centers for Disease Control and Prevention, about 55,000 residents receive PEP annually with health-associated expenditures including diagnostics, prevention, and control estimated between $245 and $510 million annually. Rabies is one of the most fatal diseases that can be prevented by avoiding contact with wild animals, maintenance of high immunization rates in pets, and keeping people informed of potential sources including bats. One can’t determine if an animal has rabies by looking at it. Rabies remains an urgent disease that we have to remember to address with our patients and their families. For additional information go to www.CDC.gov/rabies.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She has no relevant financial disclosures.
Most adults, more than one in three children take dietary supplements: Report
The new figures continue a 15-year trend of small, steady increases in how many people in the United States use the products that can deliver essential nutrients, but their usage includes a risk of getting more nutrients than recommended. In 2007, 48% of adults took supplements, and that figure has reached nearly 59% in this latest count.
The new report looked at whether people took a multivitamin, as well as other more specific supplements. Among children and adolescents aged 19 and under, 23.5% took a multivitamin, while 31.5% of adults reported taking one. The most common specialized supplement that people took was vitamin D.
The report, released by the CDC’s National Center for Health Statistics, compiled survey data from 2017 through 2020 in which 15,548 people reported their household’s usage of dietary supplements. Dietary supplements include vitamins, minerals, herbs, or other botanicals that are taken by mouth in pill, capsule, tablet, or liquid form. The researchers said the vitamin and supplement market is large and growing, totaling $55.7 billion in sales in 2020.
More than one-third of adults (36%) reported taking more than one supplement, and one in four people aged 60 and older said they took four or more.
The data showed demographic trends in who uses dietary supplements. Women and girls were more likely to take supplements than men and boys, although there were similar usage levels for both genders among 1- to 2-year-olds. People with higher education or income levels were more likely to use supplements. Asian people and White people were more likely to take supplements, compared with Hispanic people and Black people.
The authors wrote that monitoring trends in supplement use is important because the products “contribute substantially to nutrient intake as well as increase the risk of excessive intake of certain micronutrients.”
A version of this article originally appeared on WebMD.com.
The new figures continue a 15-year trend of small, steady increases in how many people in the United States use the products that can deliver essential nutrients, but their usage includes a risk of getting more nutrients than recommended. In 2007, 48% of adults took supplements, and that figure has reached nearly 59% in this latest count.
The new report looked at whether people took a multivitamin, as well as other more specific supplements. Among children and adolescents aged 19 and under, 23.5% took a multivitamin, while 31.5% of adults reported taking one. The most common specialized supplement that people took was vitamin D.
The report, released by the CDC’s National Center for Health Statistics, compiled survey data from 2017 through 2020 in which 15,548 people reported their household’s usage of dietary supplements. Dietary supplements include vitamins, minerals, herbs, or other botanicals that are taken by mouth in pill, capsule, tablet, or liquid form. The researchers said the vitamin and supplement market is large and growing, totaling $55.7 billion in sales in 2020.
More than one-third of adults (36%) reported taking more than one supplement, and one in four people aged 60 and older said they took four or more.
The data showed demographic trends in who uses dietary supplements. Women and girls were more likely to take supplements than men and boys, although there were similar usage levels for both genders among 1- to 2-year-olds. People with higher education or income levels were more likely to use supplements. Asian people and White people were more likely to take supplements, compared with Hispanic people and Black people.
The authors wrote that monitoring trends in supplement use is important because the products “contribute substantially to nutrient intake as well as increase the risk of excessive intake of certain micronutrients.”
A version of this article originally appeared on WebMD.com.
The new figures continue a 15-year trend of small, steady increases in how many people in the United States use the products that can deliver essential nutrients, but their usage includes a risk of getting more nutrients than recommended. In 2007, 48% of adults took supplements, and that figure has reached nearly 59% in this latest count.
The new report looked at whether people took a multivitamin, as well as other more specific supplements. Among children and adolescents aged 19 and under, 23.5% took a multivitamin, while 31.5% of adults reported taking one. The most common specialized supplement that people took was vitamin D.
The report, released by the CDC’s National Center for Health Statistics, compiled survey data from 2017 through 2020 in which 15,548 people reported their household’s usage of dietary supplements. Dietary supplements include vitamins, minerals, herbs, or other botanicals that are taken by mouth in pill, capsule, tablet, or liquid form. The researchers said the vitamin and supplement market is large and growing, totaling $55.7 billion in sales in 2020.
More than one-third of adults (36%) reported taking more than one supplement, and one in four people aged 60 and older said they took four or more.
The data showed demographic trends in who uses dietary supplements. Women and girls were more likely to take supplements than men and boys, although there were similar usage levels for both genders among 1- to 2-year-olds. People with higher education or income levels were more likely to use supplements. Asian people and White people were more likely to take supplements, compared with Hispanic people and Black people.
The authors wrote that monitoring trends in supplement use is important because the products “contribute substantially to nutrient intake as well as increase the risk of excessive intake of certain micronutrients.”
A version of this article originally appeared on WebMD.com.
Scattered Red-Brown, Centrally Violaceous, Blanching Papules on an Infant
The Diagnosis: Neonatal-Onset Multisystem Inflammatory Disorder (NOMID)
The punch biopsy demonstrated a predominantly deep but somewhat superficial, periadnexal, neutrophilic and eosinophilic infiltrate (Figure). The eruption resolved 3 days later with supportive treatment, including appropriate wound care. Genetic analysis revealed an autosomal-dominant NLR family pyrin domain containing 3 gene, NLRP3, de novo variant associated with neonatal-onset multisystem inflammatory disorder (NOMID). Additional workup to characterize our patient’s inflammatory profile revealed elevated IL-18, CD3, CD4, S100A12, and S100A8/A9 levels. On day 48 of life, she was started on anakinra, an IL-1 inhibitor, at a dose of 1 mg/kg subcutaneously, which eventually was titrated to 10 mg/kg at hospital discharge. Hearing screenings were within normal limits.
Cryopyrin-associated periodic syndromes (CAPS) consist of 3 rare, IL-1–associated, autoinflammatory disorders, including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and NOMID (also known as chronic infantile neurologic cutaneous and articular syndrome). These conditions result from a sporadic or autosomal-dominant gain-of-function mutations in a single gene, NLRP3, on chromosome 1q44. NLRP3 encodes for cryopyrin, an important component of an IL-1 and IL-18 activating inflammasome.1 The most severe manifestation of CAPS is NOMID, which typically presents at birth as a migratory urticarial eruption, growth failure, myalgia, fever, and abnormal facial features, including frontal bossing, saddle-shaped nose, and protruding eyes.2 The illness also can manifest with hepatosplenomegaly, lymphadenopathy, uveitis, sensorineural hearing loss, cerebral atrophy, and other neurologic manifestations.3 A diagnosis of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome was less likely given that our patient remained afebrile and did not show signs of lipodystrophy and persistent violaceous eyelid swelling. Both FCAS and MWS are less severe forms of CAPS when compared to NOMID. Familial cold autoinflammatory syndrome was less likely given the absence of the typical periodic fever pattern associated with the condition and severity of our patient’s symptoms. Muckle-Wells syndrome typically presents in adolescence with symptoms of FCAS, painful urticarial plaques, and progressive sensorinueral hearing loss. Tumor necrosis factor receptor–associated periodic fever (TRAPS) usually is associated with episodic fevers, abdominal pain, periorbital edema, migratory erythema, and arthralgia.1,3,4
Diagnostic criteria for CAPS include elevated inflammatory markers and serum amyloid, plus at least 2 of the typical CAPS symptoms: urticarial rash, cold-triggered episodes, sensorineural hearing loss, musculoskeletal symptoms, chronic aseptic meningitis, and skeletal abnormalities.4 The sensitivity and specificity of these diagnostic criteria are 84% and 91%, respectively. Additional findings that can be seen but are not part of the diagnostic criteria include intermittent fever, transient joint swelling, bony overgrowths, uveitis, optic disc edema, impaired growth, and hepatosplenomegaly.5 Laboratory findings may reveal leukocytosis, eosinophilia, anemia, and/or thrombocytopenia.3,5
Genetic testing, skin biopsies, ophthalmic examinations, neuroimaging, joint radiography, cerebrospinal fluid tests, and hearing examinations can be performed for confirmation of diagnosis and evaluation of systemic complications.4 A skin biopsy may reveal a neutrophilic infiltrate. Ophthalmic examination can demonstrate uveitis and optic disk edema. Neuroimaging may reveal cerebral atrophy or ventricular dilation. Lastly, joint radiography can be used to evaluate for the presence of premature long bone ossification or osseous overgrowth.4
In summary, NOMID is a multisystemic disorder with cutaneous manifestations. Early recognition of this entity is important given the severe sequelae and available efficacious therapy. Dermatologists should be aware of these manifestations, as dermatologic consultation and a skin biopsy may aid in diagnosis.
- Lachmann HJ. Periodic fever syndromes. Best Pract Res Clin Rheumatol. 2017;31:596-609. doi:10.1016/j.berh.2017.12.001
- Hull KM, Shoham N, Jin Chae J, et al. The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations. Curr Opin Rheumatol. 2003;15:61-69. doi:10.1097/00002281-200301000-00011
- Ahmadi N, Brewer CC, Zalewski C, et al. Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations. Otolaryngol Head Neck Surg. 2011;145:295-302. doi:10.1177/0194599811402296
- Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017;76:942-947. doi:10.1136/annrheumdis-2016-209686
- Aksentijevich I, Nowak M, Mallah M, et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrinassociated autoinflammatory diseases. Arthritis Rheum. 2002; 46:3340-3348. doi:10.1002/art.10688
The Diagnosis: Neonatal-Onset Multisystem Inflammatory Disorder (NOMID)
The punch biopsy demonstrated a predominantly deep but somewhat superficial, periadnexal, neutrophilic and eosinophilic infiltrate (Figure). The eruption resolved 3 days later with supportive treatment, including appropriate wound care. Genetic analysis revealed an autosomal-dominant NLR family pyrin domain containing 3 gene, NLRP3, de novo variant associated with neonatal-onset multisystem inflammatory disorder (NOMID). Additional workup to characterize our patient’s inflammatory profile revealed elevated IL-18, CD3, CD4, S100A12, and S100A8/A9 levels. On day 48 of life, she was started on anakinra, an IL-1 inhibitor, at a dose of 1 mg/kg subcutaneously, which eventually was titrated to 10 mg/kg at hospital discharge. Hearing screenings were within normal limits.
Cryopyrin-associated periodic syndromes (CAPS) consist of 3 rare, IL-1–associated, autoinflammatory disorders, including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and NOMID (also known as chronic infantile neurologic cutaneous and articular syndrome). These conditions result from a sporadic or autosomal-dominant gain-of-function mutations in a single gene, NLRP3, on chromosome 1q44. NLRP3 encodes for cryopyrin, an important component of an IL-1 and IL-18 activating inflammasome.1 The most severe manifestation of CAPS is NOMID, which typically presents at birth as a migratory urticarial eruption, growth failure, myalgia, fever, and abnormal facial features, including frontal bossing, saddle-shaped nose, and protruding eyes.2 The illness also can manifest with hepatosplenomegaly, lymphadenopathy, uveitis, sensorineural hearing loss, cerebral atrophy, and other neurologic manifestations.3 A diagnosis of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome was less likely given that our patient remained afebrile and did not show signs of lipodystrophy and persistent violaceous eyelid swelling. Both FCAS and MWS are less severe forms of CAPS when compared to NOMID. Familial cold autoinflammatory syndrome was less likely given the absence of the typical periodic fever pattern associated with the condition and severity of our patient’s symptoms. Muckle-Wells syndrome typically presents in adolescence with symptoms of FCAS, painful urticarial plaques, and progressive sensorinueral hearing loss. Tumor necrosis factor receptor–associated periodic fever (TRAPS) usually is associated with episodic fevers, abdominal pain, periorbital edema, migratory erythema, and arthralgia.1,3,4
Diagnostic criteria for CAPS include elevated inflammatory markers and serum amyloid, plus at least 2 of the typical CAPS symptoms: urticarial rash, cold-triggered episodes, sensorineural hearing loss, musculoskeletal symptoms, chronic aseptic meningitis, and skeletal abnormalities.4 The sensitivity and specificity of these diagnostic criteria are 84% and 91%, respectively. Additional findings that can be seen but are not part of the diagnostic criteria include intermittent fever, transient joint swelling, bony overgrowths, uveitis, optic disc edema, impaired growth, and hepatosplenomegaly.5 Laboratory findings may reveal leukocytosis, eosinophilia, anemia, and/or thrombocytopenia.3,5
Genetic testing, skin biopsies, ophthalmic examinations, neuroimaging, joint radiography, cerebrospinal fluid tests, and hearing examinations can be performed for confirmation of diagnosis and evaluation of systemic complications.4 A skin biopsy may reveal a neutrophilic infiltrate. Ophthalmic examination can demonstrate uveitis and optic disk edema. Neuroimaging may reveal cerebral atrophy or ventricular dilation. Lastly, joint radiography can be used to evaluate for the presence of premature long bone ossification or osseous overgrowth.4
In summary, NOMID is a multisystemic disorder with cutaneous manifestations. Early recognition of this entity is important given the severe sequelae and available efficacious therapy. Dermatologists should be aware of these manifestations, as dermatologic consultation and a skin biopsy may aid in diagnosis.
The Diagnosis: Neonatal-Onset Multisystem Inflammatory Disorder (NOMID)
The punch biopsy demonstrated a predominantly deep but somewhat superficial, periadnexal, neutrophilic and eosinophilic infiltrate (Figure). The eruption resolved 3 days later with supportive treatment, including appropriate wound care. Genetic analysis revealed an autosomal-dominant NLR family pyrin domain containing 3 gene, NLRP3, de novo variant associated with neonatal-onset multisystem inflammatory disorder (NOMID). Additional workup to characterize our patient’s inflammatory profile revealed elevated IL-18, CD3, CD4, S100A12, and S100A8/A9 levels. On day 48 of life, she was started on anakinra, an IL-1 inhibitor, at a dose of 1 mg/kg subcutaneously, which eventually was titrated to 10 mg/kg at hospital discharge. Hearing screenings were within normal limits.
Cryopyrin-associated periodic syndromes (CAPS) consist of 3 rare, IL-1–associated, autoinflammatory disorders, including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and NOMID (also known as chronic infantile neurologic cutaneous and articular syndrome). These conditions result from a sporadic or autosomal-dominant gain-of-function mutations in a single gene, NLRP3, on chromosome 1q44. NLRP3 encodes for cryopyrin, an important component of an IL-1 and IL-18 activating inflammasome.1 The most severe manifestation of CAPS is NOMID, which typically presents at birth as a migratory urticarial eruption, growth failure, myalgia, fever, and abnormal facial features, including frontal bossing, saddle-shaped nose, and protruding eyes.2 The illness also can manifest with hepatosplenomegaly, lymphadenopathy, uveitis, sensorineural hearing loss, cerebral atrophy, and other neurologic manifestations.3 A diagnosis of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome was less likely given that our patient remained afebrile and did not show signs of lipodystrophy and persistent violaceous eyelid swelling. Both FCAS and MWS are less severe forms of CAPS when compared to NOMID. Familial cold autoinflammatory syndrome was less likely given the absence of the typical periodic fever pattern associated with the condition and severity of our patient’s symptoms. Muckle-Wells syndrome typically presents in adolescence with symptoms of FCAS, painful urticarial plaques, and progressive sensorinueral hearing loss. Tumor necrosis factor receptor–associated periodic fever (TRAPS) usually is associated with episodic fevers, abdominal pain, periorbital edema, migratory erythema, and arthralgia.1,3,4
Diagnostic criteria for CAPS include elevated inflammatory markers and serum amyloid, plus at least 2 of the typical CAPS symptoms: urticarial rash, cold-triggered episodes, sensorineural hearing loss, musculoskeletal symptoms, chronic aseptic meningitis, and skeletal abnormalities.4 The sensitivity and specificity of these diagnostic criteria are 84% and 91%, respectively. Additional findings that can be seen but are not part of the diagnostic criteria include intermittent fever, transient joint swelling, bony overgrowths, uveitis, optic disc edema, impaired growth, and hepatosplenomegaly.5 Laboratory findings may reveal leukocytosis, eosinophilia, anemia, and/or thrombocytopenia.3,5
Genetic testing, skin biopsies, ophthalmic examinations, neuroimaging, joint radiography, cerebrospinal fluid tests, and hearing examinations can be performed for confirmation of diagnosis and evaluation of systemic complications.4 A skin biopsy may reveal a neutrophilic infiltrate. Ophthalmic examination can demonstrate uveitis and optic disk edema. Neuroimaging may reveal cerebral atrophy or ventricular dilation. Lastly, joint radiography can be used to evaluate for the presence of premature long bone ossification or osseous overgrowth.4
In summary, NOMID is a multisystemic disorder with cutaneous manifestations. Early recognition of this entity is important given the severe sequelae and available efficacious therapy. Dermatologists should be aware of these manifestations, as dermatologic consultation and a skin biopsy may aid in diagnosis.
- Lachmann HJ. Periodic fever syndromes. Best Pract Res Clin Rheumatol. 2017;31:596-609. doi:10.1016/j.berh.2017.12.001
- Hull KM, Shoham N, Jin Chae J, et al. The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations. Curr Opin Rheumatol. 2003;15:61-69. doi:10.1097/00002281-200301000-00011
- Ahmadi N, Brewer CC, Zalewski C, et al. Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations. Otolaryngol Head Neck Surg. 2011;145:295-302. doi:10.1177/0194599811402296
- Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017;76:942-947. doi:10.1136/annrheumdis-2016-209686
- Aksentijevich I, Nowak M, Mallah M, et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrinassociated autoinflammatory diseases. Arthritis Rheum. 2002; 46:3340-3348. doi:10.1002/art.10688
- Lachmann HJ. Periodic fever syndromes. Best Pract Res Clin Rheumatol. 2017;31:596-609. doi:10.1016/j.berh.2017.12.001
- Hull KM, Shoham N, Jin Chae J, et al. The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations. Curr Opin Rheumatol. 2003;15:61-69. doi:10.1097/00002281-200301000-00011
- Ahmadi N, Brewer CC, Zalewski C, et al. Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations. Otolaryngol Head Neck Surg. 2011;145:295-302. doi:10.1177/0194599811402296
- Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017;76:942-947. doi:10.1136/annrheumdis-2016-209686
- Aksentijevich I, Nowak M, Mallah M, et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrinassociated autoinflammatory diseases. Arthritis Rheum. 2002; 46:3340-3348. doi:10.1002/art.10688
A 2-week-old infant girl was transferred to a specialty pediatric hospital where dermatology was consulted for evaluation of a diffuse eruption triggered by cold that was similar to an eruption present at birth. She was born at 31 weeks and 2 days’ gestation at an outside hospital via caesarean delivery. Early delivery was prompted by superimposed pre-eclampsia with severe hypertension after administration of antenatal steroids. At birth, the infant was cyanotic and apneic and had a documented skin eruption, according to the medical record. She had thrombocytopenia, elevated C-reactive protein, and an elevated temperature without fever. Extensive septic workup, including blood, urine, and cerebrospinal fluid cultures; herpes simplex virus and cytomegalovirus screening; and Toxoplasma polymerase chain reaction were negative. Magnetic resonance imaging of the brain revealed no evidence of intracranial congenital infection. Ampicillinsulbactam was initiated for presumed culture-negative sepsis. On day 2 of hospitalization, she developed conjunctival icterus, hepatomegaly, and jaundice. Direct hyperbilirubinemia; anemia; and elevated triglycerides, ferritin, and ammonia all were present. Coagulation studies were normal. Subsequent workup, including abdominal ultrasonography and hepatobiliary iminodiacetic acid scan, was concerning for biliary atresia. Despite appropriate treatment, her condition did not improve and she was transferred. Repeat abdominal ultrasonography on day 24 of life confirmed hepatomegaly but did not demonstrate other findings of biliary atresia. At the current presentation, physical examination revealed many scattered, redbrown and centrally violaceous, blanching papules measuring a few millimeters involving the trunk, arms, buttocks, and legs. A punch biopsy was obtained.
A 7-month-old male presents with pustules and inflamed papules on the scalp and extremities
The bacterial, fungal, and atypical mycobacterial cultures from the lesions performed at the emergency department were all negative.
Pediatric dermatology was consulted and a punch biopsy of one of the lesions was done. Histopathologic examination showed a mixed perifollicular infiltrate of predominantly eosinophils with some neutrophils and associated microabscesses. Periodic acid Schiff and Fite stains failed to reveal any organisms. CD1 immunostain was negative. Fresh tissue cultures for bacteria, fungi, and atypical mycobacteria were negative.
Given the clinical presentation of chronic recurrent sterile pustules on an infant with associated eosinophilia and the reported histopathologic findings, the patient was diagnosed with eosinophilic pustular folliculitis of infancy (EPFI).
EPFI is a rare and idiopathic cutaneous disorder present in children. About 70% of the cases reported occur in the first 6 month of life and rarely present past 3 years of age. EPF encompasses a group of conditions including the classic adult form, or Ofuji disease. EPF is seen in immunosuppressed patients, mainly HIV positive, and EPF is also seen in infants and children.
In EPFI, males are most commonly affected. The condition presents, as it did in our patient, with recurrent crops of sterile papules and pustules mainly on the scalp, but they can occur in other parts of the body. The lesions go away within a few weeks to months without leaving any scars but it can take months to years to resolve. Histopathologic analysis of the lesions show an eosinophilic infiltrate which can be follicular, perifollicular, or periadnexal with associated flame figures in about 26% of cases.
Aggressive treatment is usually not needed as lesions are self-limited. Lesions can be treated with topical corticosteroids and oral antihistamine medications like cetirizine if symptomatic.
If the lesions start to present during the neonatal period, one may consider in the differential diagnosis, neonatal rashes like transient neonatal pustular melanosis and erythema toxicum neonatorum. Both of these neonatal conditions tend to resolve in the first month of life, compared with EPFI where lesions can come and go for months to years. EPFI lesions can be described as pustules and inflammatory papules, as well as furuncles and vesicles. All of the lesions may be seen in one patient at one time, which will not be typical for transient neonatal pustular melanosis or erythema toxicum. Eosinophils can be seen in erythema toxicum but folliculitis is not present. The inflammatory infiltrate seen in transient neonatal pustular melanosis is polymorphonuclear, not eosinophilic.
Early in the presentation, infectious conditions like staphylococcal or streptococcal folliculitis, cellulitis and furunculosis, tinea capitis, atypical mycobacterial infections, herpes simplex, and parasitic infections like scabies should be considered. In young infants, empiric antibiotic treatment may be started until cultures are finalized. If there is a family history of pruritic papules and pustules, scabies should be considered. A scabies prep can be done to rule out this entity.
Langerhans cell histiocytosis can also present with pustules and papules in early infancy and also has a predilection for the scalp. When this condition is in question, a skin biopsy should be performed which shows a CD1 positive histiocytic infiltrate.
In conclusion, EPFI is a benign rare condition that can present in infants as recurrent pustules and papules, mainly on the scalp, which are self-limited and if symptomatic can be treated with topical corticosteroids and antihistamines.
References
Alonso-Castro L et al. Dermatol Online J. 2012 Oct 15;18(10):6.
Frølunde AS et al. Clin Case Rep. 2021 May 11;9(5):e04167.
Hernández-Martín Á et al. J Am Acad Dermatol. 2013 Jan;68(1):150-5.
The bacterial, fungal, and atypical mycobacterial cultures from the lesions performed at the emergency department were all negative.
Pediatric dermatology was consulted and a punch biopsy of one of the lesions was done. Histopathologic examination showed a mixed perifollicular infiltrate of predominantly eosinophils with some neutrophils and associated microabscesses. Periodic acid Schiff and Fite stains failed to reveal any organisms. CD1 immunostain was negative. Fresh tissue cultures for bacteria, fungi, and atypical mycobacteria were negative.
Given the clinical presentation of chronic recurrent sterile pustules on an infant with associated eosinophilia and the reported histopathologic findings, the patient was diagnosed with eosinophilic pustular folliculitis of infancy (EPFI).
EPFI is a rare and idiopathic cutaneous disorder present in children. About 70% of the cases reported occur in the first 6 month of life and rarely present past 3 years of age. EPF encompasses a group of conditions including the classic adult form, or Ofuji disease. EPF is seen in immunosuppressed patients, mainly HIV positive, and EPF is also seen in infants and children.
In EPFI, males are most commonly affected. The condition presents, as it did in our patient, with recurrent crops of sterile papules and pustules mainly on the scalp, but they can occur in other parts of the body. The lesions go away within a few weeks to months without leaving any scars but it can take months to years to resolve. Histopathologic analysis of the lesions show an eosinophilic infiltrate which can be follicular, perifollicular, or periadnexal with associated flame figures in about 26% of cases.
Aggressive treatment is usually not needed as lesions are self-limited. Lesions can be treated with topical corticosteroids and oral antihistamine medications like cetirizine if symptomatic.
If the lesions start to present during the neonatal period, one may consider in the differential diagnosis, neonatal rashes like transient neonatal pustular melanosis and erythema toxicum neonatorum. Both of these neonatal conditions tend to resolve in the first month of life, compared with EPFI where lesions can come and go for months to years. EPFI lesions can be described as pustules and inflammatory papules, as well as furuncles and vesicles. All of the lesions may be seen in one patient at one time, which will not be typical for transient neonatal pustular melanosis or erythema toxicum. Eosinophils can be seen in erythema toxicum but folliculitis is not present. The inflammatory infiltrate seen in transient neonatal pustular melanosis is polymorphonuclear, not eosinophilic.
Early in the presentation, infectious conditions like staphylococcal or streptococcal folliculitis, cellulitis and furunculosis, tinea capitis, atypical mycobacterial infections, herpes simplex, and parasitic infections like scabies should be considered. In young infants, empiric antibiotic treatment may be started until cultures are finalized. If there is a family history of pruritic papules and pustules, scabies should be considered. A scabies prep can be done to rule out this entity.
Langerhans cell histiocytosis can also present with pustules and papules in early infancy and also has a predilection for the scalp. When this condition is in question, a skin biopsy should be performed which shows a CD1 positive histiocytic infiltrate.
In conclusion, EPFI is a benign rare condition that can present in infants as recurrent pustules and papules, mainly on the scalp, which are self-limited and if symptomatic can be treated with topical corticosteroids and antihistamines.
References
Alonso-Castro L et al. Dermatol Online J. 2012 Oct 15;18(10):6.
Frølunde AS et al. Clin Case Rep. 2021 May 11;9(5):e04167.
Hernández-Martín Á et al. J Am Acad Dermatol. 2013 Jan;68(1):150-5.
The bacterial, fungal, and atypical mycobacterial cultures from the lesions performed at the emergency department were all negative.
Pediatric dermatology was consulted and a punch biopsy of one of the lesions was done. Histopathologic examination showed a mixed perifollicular infiltrate of predominantly eosinophils with some neutrophils and associated microabscesses. Periodic acid Schiff and Fite stains failed to reveal any organisms. CD1 immunostain was negative. Fresh tissue cultures for bacteria, fungi, and atypical mycobacteria were negative.
Given the clinical presentation of chronic recurrent sterile pustules on an infant with associated eosinophilia and the reported histopathologic findings, the patient was diagnosed with eosinophilic pustular folliculitis of infancy (EPFI).
EPFI is a rare and idiopathic cutaneous disorder present in children. About 70% of the cases reported occur in the first 6 month of life and rarely present past 3 years of age. EPF encompasses a group of conditions including the classic adult form, or Ofuji disease. EPF is seen in immunosuppressed patients, mainly HIV positive, and EPF is also seen in infants and children.
In EPFI, males are most commonly affected. The condition presents, as it did in our patient, with recurrent crops of sterile papules and pustules mainly on the scalp, but they can occur in other parts of the body. The lesions go away within a few weeks to months without leaving any scars but it can take months to years to resolve. Histopathologic analysis of the lesions show an eosinophilic infiltrate which can be follicular, perifollicular, or periadnexal with associated flame figures in about 26% of cases.
Aggressive treatment is usually not needed as lesions are self-limited. Lesions can be treated with topical corticosteroids and oral antihistamine medications like cetirizine if symptomatic.
If the lesions start to present during the neonatal period, one may consider in the differential diagnosis, neonatal rashes like transient neonatal pustular melanosis and erythema toxicum neonatorum. Both of these neonatal conditions tend to resolve in the first month of life, compared with EPFI where lesions can come and go for months to years. EPFI lesions can be described as pustules and inflammatory papules, as well as furuncles and vesicles. All of the lesions may be seen in one patient at one time, which will not be typical for transient neonatal pustular melanosis or erythema toxicum. Eosinophils can be seen in erythema toxicum but folliculitis is not present. The inflammatory infiltrate seen in transient neonatal pustular melanosis is polymorphonuclear, not eosinophilic.
Early in the presentation, infectious conditions like staphylococcal or streptococcal folliculitis, cellulitis and furunculosis, tinea capitis, atypical mycobacterial infections, herpes simplex, and parasitic infections like scabies should be considered. In young infants, empiric antibiotic treatment may be started until cultures are finalized. If there is a family history of pruritic papules and pustules, scabies should be considered. A scabies prep can be done to rule out this entity.
Langerhans cell histiocytosis can also present with pustules and papules in early infancy and also has a predilection for the scalp. When this condition is in question, a skin biopsy should be performed which shows a CD1 positive histiocytic infiltrate.
In conclusion, EPFI is a benign rare condition that can present in infants as recurrent pustules and papules, mainly on the scalp, which are self-limited and if symptomatic can be treated with topical corticosteroids and antihistamines.
References
Alonso-Castro L et al. Dermatol Online J. 2012 Oct 15;18(10):6.
Frølunde AS et al. Clin Case Rep. 2021 May 11;9(5):e04167.
Hernández-Martín Á et al. J Am Acad Dermatol. 2013 Jan;68(1):150-5.
A 7-month-old male is brought to the emergency department for evaluation of pustules and inflamed papules on the scalp and extremities for several weeks of duration. The parents report the lesions started about a month prior and he has already been treated with cephalexin, clindamycin, and sulfamethoxazole without any improvement. Cultures sent prior by the child's pediatrician did not reveal any fungus or bacteria. The parents report a low-grade fever for about 3 days.
He was born via natural vaginal delivery with no instrumentation or external monitoring. Mom had prenatal care. Besides the skin lesions, the baby has been healthy and growing well. He has no history of eczema or severe infections. He has not been hospitalized before.
On physical examination the baby was not febrile. On the scalp and forehead, he had diffusely distributed pustules, erythematous papules, and nodules. He also presented with scattered, fine, small, crusted 1-2-mm pink papules on the trunk and extremities. He had no adenopathy or hepatosplenomegaly.
At the emergency department, samples from one of the pustules were sent for bacterial, fungal, and atypical mycobacteria cultures. Laboratory test showed a normal blood count with associated eosinophilia (2.8 x 109 L), and normal liver and kidney function. A head ultrasound showed three ill-defined hypoechoic foci within the scalp.
The patient was admitted for treatment with broad-spectrum antibiotics and dermatology was consulted.
Perinatal HIV nearly eradicated in U.S.
, with less than 1 baby for every 100,000 live births having the virus, a new study released by researchers at the Centers for Disease Control and Prevention finds.
The report marks significant progress on the U.S. government’s goal to eradicate perinatal HIV, an immune-weakening and potentially deadly virus that is passed from mother to baby during pregnancy. Just 32 children in the country were diagnosed in 2019, compared with twice as many in 2010, according to the CDC.
Mothers who are HIV positive can prevent transmission of the infection by receiving antiretroviral therapy, according to Monica Gandhi, MD, MPH, a professor of medicine at University of California, San Francisco’s division of HIV, infectious disease and global medicine.
Dr. Gandhi said she could recall only one case of perinatal HIV in the San Francisco area over the last decade.
“This country has been really aggressive about counseling women who are pregnant and getting mothers in care,” Dr. Gandhi said.
The treatment method was discovered more than 30 years ago. Prior to the therapy and ensuing awareness campaigns to prevent transmission, mothers with HIV would typically pass the virus to their child in utero, during delivery, or while breastfeeding.
“There should be zero children born with HIV, given that we’ve had these drugs for so long,” Dr. Ghandi said.
Disparities persist
But challenges remain in some communities, where babies born to Black mothers are disproportionately affected by the disease, the new study found. “Racial and ethnic differences in perinatal HIV diagnoses persisted through the 10-year period,” the report’s authors concluded. “The highest rates of perinatal HIV diagnoses were seen among infants born to Black women.”
Although rates of perinatal HIV declined for babies born to Black mothers over the decade-long study, the diagnosis rate was above the goal of elimination at 3.1 for every 100,000 live births, according to the data.
Meanwhile, transmission rates hovered around 1%-2% for Latinx and Hispanic women and mothers who identified as “other races,” including Native American.
Despite the availability of medication, expectant mothers may face several hurdles to getting the daily treatment they need to prevent transmission to their fetus, according to Jennifer Jao, MD, MPH, a physician of infectious diseases at Lurie Children’s Hospital of Chicago.
They might have trouble securing health insurance or finding transportation to doctor’s appointments, or face other problems like lacking secure housing or food – all factors that prevent them from prioritizing the care.
“All of those things play into the mix,” Dr. Jao said. “We see over and over again that closing the gap means you’ve got to reach the women who are pregnant and who don’t have resources.”
Progress in ‘danger’
Experts said they’re not sure what the impact of the COVID-19 pandemic, accompanied by a recent uptick in sexually transmitted diseases, will be on rates of perinatal HIV. Some women were unable to access prenatal health care during the pandemic because they couldn’t access public transportation or childcare, the U.S. Government Accountability Office said in 2022.
Globally, a decline in rates of HIV and AIDS rates has slowed, prompting the World Health Organization to warn last year that progress on the disease is in danger. Researchers only included HIV rates in the United States through 2019, so the data are outdated, Dr. Gandhi noted.
“All of this put together means we don’t know where we are with perinatal transmission over the last 3 years,” she said.
In an accompanying editorial, coauthors Nahida Chakhtoura, MD, MsGH, and Bill Kapogiannis, MD, both with the National Institutes of Health, urge health care professionals to take an active role in eliminating these racial and ethnic disparities in an effort to – as the title of their editorial proclaims – achieve a “road to zero perinatal HIV transmission” in the United States.
“The more proactive we are in identifying and promptly addressing systematic deficiencies that exacerbate health inequities in cutting-edge research innovations and optimal clinical service provision,” they write, “the less reactive we will need to be when new transmissible infections appear at our doorstep.”
A version of this article first appeared on Medscape.com.
, with less than 1 baby for every 100,000 live births having the virus, a new study released by researchers at the Centers for Disease Control and Prevention finds.
The report marks significant progress on the U.S. government’s goal to eradicate perinatal HIV, an immune-weakening and potentially deadly virus that is passed from mother to baby during pregnancy. Just 32 children in the country were diagnosed in 2019, compared with twice as many in 2010, according to the CDC.
Mothers who are HIV positive can prevent transmission of the infection by receiving antiretroviral therapy, according to Monica Gandhi, MD, MPH, a professor of medicine at University of California, San Francisco’s division of HIV, infectious disease and global medicine.
Dr. Gandhi said she could recall only one case of perinatal HIV in the San Francisco area over the last decade.
“This country has been really aggressive about counseling women who are pregnant and getting mothers in care,” Dr. Gandhi said.
The treatment method was discovered more than 30 years ago. Prior to the therapy and ensuing awareness campaigns to prevent transmission, mothers with HIV would typically pass the virus to their child in utero, during delivery, or while breastfeeding.
“There should be zero children born with HIV, given that we’ve had these drugs for so long,” Dr. Ghandi said.
Disparities persist
But challenges remain in some communities, where babies born to Black mothers are disproportionately affected by the disease, the new study found. “Racial and ethnic differences in perinatal HIV diagnoses persisted through the 10-year period,” the report’s authors concluded. “The highest rates of perinatal HIV diagnoses were seen among infants born to Black women.”
Although rates of perinatal HIV declined for babies born to Black mothers over the decade-long study, the diagnosis rate was above the goal of elimination at 3.1 for every 100,000 live births, according to the data.
Meanwhile, transmission rates hovered around 1%-2% for Latinx and Hispanic women and mothers who identified as “other races,” including Native American.
Despite the availability of medication, expectant mothers may face several hurdles to getting the daily treatment they need to prevent transmission to their fetus, according to Jennifer Jao, MD, MPH, a physician of infectious diseases at Lurie Children’s Hospital of Chicago.
They might have trouble securing health insurance or finding transportation to doctor’s appointments, or face other problems like lacking secure housing or food – all factors that prevent them from prioritizing the care.
“All of those things play into the mix,” Dr. Jao said. “We see over and over again that closing the gap means you’ve got to reach the women who are pregnant and who don’t have resources.”
Progress in ‘danger’
Experts said they’re not sure what the impact of the COVID-19 pandemic, accompanied by a recent uptick in sexually transmitted diseases, will be on rates of perinatal HIV. Some women were unable to access prenatal health care during the pandemic because they couldn’t access public transportation or childcare, the U.S. Government Accountability Office said in 2022.
Globally, a decline in rates of HIV and AIDS rates has slowed, prompting the World Health Organization to warn last year that progress on the disease is in danger. Researchers only included HIV rates in the United States through 2019, so the data are outdated, Dr. Gandhi noted.
“All of this put together means we don’t know where we are with perinatal transmission over the last 3 years,” she said.
In an accompanying editorial, coauthors Nahida Chakhtoura, MD, MsGH, and Bill Kapogiannis, MD, both with the National Institutes of Health, urge health care professionals to take an active role in eliminating these racial and ethnic disparities in an effort to – as the title of their editorial proclaims – achieve a “road to zero perinatal HIV transmission” in the United States.
“The more proactive we are in identifying and promptly addressing systematic deficiencies that exacerbate health inequities in cutting-edge research innovations and optimal clinical service provision,” they write, “the less reactive we will need to be when new transmissible infections appear at our doorstep.”
A version of this article first appeared on Medscape.com.
, with less than 1 baby for every 100,000 live births having the virus, a new study released by researchers at the Centers for Disease Control and Prevention finds.
The report marks significant progress on the U.S. government’s goal to eradicate perinatal HIV, an immune-weakening and potentially deadly virus that is passed from mother to baby during pregnancy. Just 32 children in the country were diagnosed in 2019, compared with twice as many in 2010, according to the CDC.
Mothers who are HIV positive can prevent transmission of the infection by receiving antiretroviral therapy, according to Monica Gandhi, MD, MPH, a professor of medicine at University of California, San Francisco’s division of HIV, infectious disease and global medicine.
Dr. Gandhi said she could recall only one case of perinatal HIV in the San Francisco area over the last decade.
“This country has been really aggressive about counseling women who are pregnant and getting mothers in care,” Dr. Gandhi said.
The treatment method was discovered more than 30 years ago. Prior to the therapy and ensuing awareness campaigns to prevent transmission, mothers with HIV would typically pass the virus to their child in utero, during delivery, or while breastfeeding.
“There should be zero children born with HIV, given that we’ve had these drugs for so long,” Dr. Ghandi said.
Disparities persist
But challenges remain in some communities, where babies born to Black mothers are disproportionately affected by the disease, the new study found. “Racial and ethnic differences in perinatal HIV diagnoses persisted through the 10-year period,” the report’s authors concluded. “The highest rates of perinatal HIV diagnoses were seen among infants born to Black women.”
Although rates of perinatal HIV declined for babies born to Black mothers over the decade-long study, the diagnosis rate was above the goal of elimination at 3.1 for every 100,000 live births, according to the data.
Meanwhile, transmission rates hovered around 1%-2% for Latinx and Hispanic women and mothers who identified as “other races,” including Native American.
Despite the availability of medication, expectant mothers may face several hurdles to getting the daily treatment they need to prevent transmission to their fetus, according to Jennifer Jao, MD, MPH, a physician of infectious diseases at Lurie Children’s Hospital of Chicago.
They might have trouble securing health insurance or finding transportation to doctor’s appointments, or face other problems like lacking secure housing or food – all factors that prevent them from prioritizing the care.
“All of those things play into the mix,” Dr. Jao said. “We see over and over again that closing the gap means you’ve got to reach the women who are pregnant and who don’t have resources.”
Progress in ‘danger’
Experts said they’re not sure what the impact of the COVID-19 pandemic, accompanied by a recent uptick in sexually transmitted diseases, will be on rates of perinatal HIV. Some women were unable to access prenatal health care during the pandemic because they couldn’t access public transportation or childcare, the U.S. Government Accountability Office said in 2022.
Globally, a decline in rates of HIV and AIDS rates has slowed, prompting the World Health Organization to warn last year that progress on the disease is in danger. Researchers only included HIV rates in the United States through 2019, so the data are outdated, Dr. Gandhi noted.
“All of this put together means we don’t know where we are with perinatal transmission over the last 3 years,” she said.
In an accompanying editorial, coauthors Nahida Chakhtoura, MD, MsGH, and Bill Kapogiannis, MD, both with the National Institutes of Health, urge health care professionals to take an active role in eliminating these racial and ethnic disparities in an effort to – as the title of their editorial proclaims – achieve a “road to zero perinatal HIV transmission” in the United States.
“The more proactive we are in identifying and promptly addressing systematic deficiencies that exacerbate health inequities in cutting-edge research innovations and optimal clinical service provision,” they write, “the less reactive we will need to be when new transmissible infections appear at our doorstep.”
A version of this article first appeared on Medscape.com.
Progress, gaps as pediatricians expand mental health roles
but a review of electronic health records highlights areas for improvement in delivering the care.
The findings were published online in Pediatrics.
The researchers, led by Talia R. Lester, MD, with the division of developmental behavioral pediatrics in the quantitative science unit at Stanford (Calif.) University, identified 1,685 patients aged 6-18 years who had at least one visit with a diagnosis of anxiety and/or depression in a large primary care network in northern California and who were prescribed an SSRI by a network primary care pediatrician (PCP). The team randomly chose 110 patients and reviewed charts from the visit when the SSRI was first prescribed (medication visit); the immediately previous visit; and immediately subsequent visit.
Encouraging signs
The chart reviews showed some encouraging signs. For example, when pediatricians prescribe an SSRI, 82% are appropriately documenting rationales for starting the medication at the medication visit. However, they are not monitoring medication side effects systematically, according to the report. Of 69 patients with a visit after the medication visit, fewer than half (48%) had documentation of monitoring for side effects.
Three areas for improvement
The researchers identified three main shortfall areas and suggested improvements.
PCPs often referred patients for unspecified therapy at the medication visit; however, they rarely prescribed evidence-based therapies such as cognitive-behavioral therapy (CBT) (4% of patients). The authors suggested embedding a summary of evidence-based treatment into order sets.
Secondly, PCPs are not often using screening tools. The data show only 26% of patients had a documented depression- or anxiety-specific screening tool result at the medication visit. The authors recommend making the screening tools accessible through the EHR to increase use.
The researchers also found many patients didn’t have a follow-up visit after SSRI medication was prescribed. Even when they did, the range was so wide between the medication visit and the follow-up (7-365 days) that it’s clear pediatricians are taking inconsistent approaches to scheduling follow-up.
Half are seeing only their primary care pediatrician
About half of children and adolescents prescribed an SSRI by a pediatrician for mental health reasons were seeing only their primary care pediatrician, the data showed.
Eric M. Butter, PhD, chief of psychology at Nationwide Children’s Hospital and Ohio State University, Columbus, pointed out in an accompanying editorial that some of the news in pediatricians’ expanded role is particularly encouraging.
Pediatricians, he noted, are making medication decisions consistent with decisions a subspecialist would make.
Of cases in which a subspecialist became involved after a pediatrician initiated medication, subspecialists changed the medication for only two patients, which “is encouraging because it validates pediatricians’ decisions,” Dr. Butter said.
It’s important for pediatricians to understand key evidence-based programs that can work in combination with medications to achieve better results, Dr. Butter said. For example, CBT can help with depression “and break the cycle of avoidance that worsens symptoms of anxiety.”
He highlighted Interpersonal Therapy for Adolescents, a 12-session treatment that “can also address depression by improving patients’ personal relationships.”
“No primary care pediatrician will have the training or time to implement the many treatments that are available,” Dr. Butter wrote. “However, pediatricians can work to understand the key features of the evidence-based treatments referenced by Lester et al.”
Most concerning statistics
Dr. Butter said the most concerning shortcoming in the pediatricians’ health care delivery was lack of referral for evidence-based psychological treatments and low rates for referral to access supports from schools through programs such as the education 504 plan and Individualized Education Plans.
Dr. Lester’s team found that pediatricians recommended that patients receive support from such programs in only 8% of cases.
“The children’s mental health crisis requires all child-serving health care providers to do more. Improved care for anxiety and depression in pediatric primary care is needed and does not have to be overly burdensome to pediatricians,” Dr. Butter wrote.
The authors and Dr. Butter declared no relevant financial relationships.
but a review of electronic health records highlights areas for improvement in delivering the care.
The findings were published online in Pediatrics.
The researchers, led by Talia R. Lester, MD, with the division of developmental behavioral pediatrics in the quantitative science unit at Stanford (Calif.) University, identified 1,685 patients aged 6-18 years who had at least one visit with a diagnosis of anxiety and/or depression in a large primary care network in northern California and who were prescribed an SSRI by a network primary care pediatrician (PCP). The team randomly chose 110 patients and reviewed charts from the visit when the SSRI was first prescribed (medication visit); the immediately previous visit; and immediately subsequent visit.
Encouraging signs
The chart reviews showed some encouraging signs. For example, when pediatricians prescribe an SSRI, 82% are appropriately documenting rationales for starting the medication at the medication visit. However, they are not monitoring medication side effects systematically, according to the report. Of 69 patients with a visit after the medication visit, fewer than half (48%) had documentation of monitoring for side effects.
Three areas for improvement
The researchers identified three main shortfall areas and suggested improvements.
PCPs often referred patients for unspecified therapy at the medication visit; however, they rarely prescribed evidence-based therapies such as cognitive-behavioral therapy (CBT) (4% of patients). The authors suggested embedding a summary of evidence-based treatment into order sets.
Secondly, PCPs are not often using screening tools. The data show only 26% of patients had a documented depression- or anxiety-specific screening tool result at the medication visit. The authors recommend making the screening tools accessible through the EHR to increase use.
The researchers also found many patients didn’t have a follow-up visit after SSRI medication was prescribed. Even when they did, the range was so wide between the medication visit and the follow-up (7-365 days) that it’s clear pediatricians are taking inconsistent approaches to scheduling follow-up.
Half are seeing only their primary care pediatrician
About half of children and adolescents prescribed an SSRI by a pediatrician for mental health reasons were seeing only their primary care pediatrician, the data showed.
Eric M. Butter, PhD, chief of psychology at Nationwide Children’s Hospital and Ohio State University, Columbus, pointed out in an accompanying editorial that some of the news in pediatricians’ expanded role is particularly encouraging.
Pediatricians, he noted, are making medication decisions consistent with decisions a subspecialist would make.
Of cases in which a subspecialist became involved after a pediatrician initiated medication, subspecialists changed the medication for only two patients, which “is encouraging because it validates pediatricians’ decisions,” Dr. Butter said.
It’s important for pediatricians to understand key evidence-based programs that can work in combination with medications to achieve better results, Dr. Butter said. For example, CBT can help with depression “and break the cycle of avoidance that worsens symptoms of anxiety.”
He highlighted Interpersonal Therapy for Adolescents, a 12-session treatment that “can also address depression by improving patients’ personal relationships.”
“No primary care pediatrician will have the training or time to implement the many treatments that are available,” Dr. Butter wrote. “However, pediatricians can work to understand the key features of the evidence-based treatments referenced by Lester et al.”
Most concerning statistics
Dr. Butter said the most concerning shortcoming in the pediatricians’ health care delivery was lack of referral for evidence-based psychological treatments and low rates for referral to access supports from schools through programs such as the education 504 plan and Individualized Education Plans.
Dr. Lester’s team found that pediatricians recommended that patients receive support from such programs in only 8% of cases.
“The children’s mental health crisis requires all child-serving health care providers to do more. Improved care for anxiety and depression in pediatric primary care is needed and does not have to be overly burdensome to pediatricians,” Dr. Butter wrote.
The authors and Dr. Butter declared no relevant financial relationships.
but a review of electronic health records highlights areas for improvement in delivering the care.
The findings were published online in Pediatrics.
The researchers, led by Talia R. Lester, MD, with the division of developmental behavioral pediatrics in the quantitative science unit at Stanford (Calif.) University, identified 1,685 patients aged 6-18 years who had at least one visit with a diagnosis of anxiety and/or depression in a large primary care network in northern California and who were prescribed an SSRI by a network primary care pediatrician (PCP). The team randomly chose 110 patients and reviewed charts from the visit when the SSRI was first prescribed (medication visit); the immediately previous visit; and immediately subsequent visit.
Encouraging signs
The chart reviews showed some encouraging signs. For example, when pediatricians prescribe an SSRI, 82% are appropriately documenting rationales for starting the medication at the medication visit. However, they are not monitoring medication side effects systematically, according to the report. Of 69 patients with a visit after the medication visit, fewer than half (48%) had documentation of monitoring for side effects.
Three areas for improvement
The researchers identified three main shortfall areas and suggested improvements.
PCPs often referred patients for unspecified therapy at the medication visit; however, they rarely prescribed evidence-based therapies such as cognitive-behavioral therapy (CBT) (4% of patients). The authors suggested embedding a summary of evidence-based treatment into order sets.
Secondly, PCPs are not often using screening tools. The data show only 26% of patients had a documented depression- or anxiety-specific screening tool result at the medication visit. The authors recommend making the screening tools accessible through the EHR to increase use.
The researchers also found many patients didn’t have a follow-up visit after SSRI medication was prescribed. Even when they did, the range was so wide between the medication visit and the follow-up (7-365 days) that it’s clear pediatricians are taking inconsistent approaches to scheduling follow-up.
Half are seeing only their primary care pediatrician
About half of children and adolescents prescribed an SSRI by a pediatrician for mental health reasons were seeing only their primary care pediatrician, the data showed.
Eric M. Butter, PhD, chief of psychology at Nationwide Children’s Hospital and Ohio State University, Columbus, pointed out in an accompanying editorial that some of the news in pediatricians’ expanded role is particularly encouraging.
Pediatricians, he noted, are making medication decisions consistent with decisions a subspecialist would make.
Of cases in which a subspecialist became involved after a pediatrician initiated medication, subspecialists changed the medication for only two patients, which “is encouraging because it validates pediatricians’ decisions,” Dr. Butter said.
It’s important for pediatricians to understand key evidence-based programs that can work in combination with medications to achieve better results, Dr. Butter said. For example, CBT can help with depression “and break the cycle of avoidance that worsens symptoms of anxiety.”
He highlighted Interpersonal Therapy for Adolescents, a 12-session treatment that “can also address depression by improving patients’ personal relationships.”
“No primary care pediatrician will have the training or time to implement the many treatments that are available,” Dr. Butter wrote. “However, pediatricians can work to understand the key features of the evidence-based treatments referenced by Lester et al.”
Most concerning statistics
Dr. Butter said the most concerning shortcoming in the pediatricians’ health care delivery was lack of referral for evidence-based psychological treatments and low rates for referral to access supports from schools through programs such as the education 504 plan and Individualized Education Plans.
Dr. Lester’s team found that pediatricians recommended that patients receive support from such programs in only 8% of cases.
“The children’s mental health crisis requires all child-serving health care providers to do more. Improved care for anxiety and depression in pediatric primary care is needed and does not have to be overly burdensome to pediatricians,” Dr. Butter wrote.
The authors and Dr. Butter declared no relevant financial relationships.
FROM PEDIATRICS
What will vaping lead to? Emerging research shows damage, and addiction
Jake Warn calls vaping “a toxic artificial love.”
Jake, of Winslow, Maine, was 16 years old when he began vaping. Unlike cigarettes, vaping can be odorless, and its smoke leaves no trace, which allowed him and his friends to use the devices in school bathrooms without fear of being caught.
He would use an entire cartridge containing the vape liquid, the equivalent of smoking one pack of tobacco cigarettes, within 1 school day. By the fall semester of his first year in college, Jake said his use had increased even more.
“It got pricey, so that’s when I really started to notice” the extent of his dependency, he said recently.
Vaping rates among teenagers in Maine doubled from 15.3% to 28.7% between 2017 and 2019, while Jake was in high school. In 2021, 11% of high schoolers across the nation said they regularly smoked e-cigarettes, and an estimated 28% have ever tried the devices, according to the Centers for Disease Control and Prevention.
The Food and Drug Administration classifies e-cigarettes as a tobacco product because many contain nicotine, which comes from tobacco. Like Jake, the habit is likely to carry into adulthood for many who start in their teenage years, experts say.
Electronic nicotine delivery systems (ENDS) such as vapes have been touted by their manufacturers and by some in the medical field as a healthier alternative to cigarettes and as a method to help smokers give up the habit.
But, that’s not how Jake – who had never used combustible cigarettes – picked up vaping, or how he sold the idea to his mother.
“It’s all organic and natural flavoring, it’s just flavored water,” Mary Lou Warn recalled her son saying to her. She researched the health effects of vaping but didn’t find much online. “I knew they were dangerous because you don’t put anything in your lungs that isn’t fresh air.”
A determined athlete in high school, Jake found that his asthma worsened as he transitioned to college, especially when he ran a track meet or during a soccer game.
Mrs. Warn noticed changes off the field, too.
“He was coughing constantly, he wasn’t sleeping well, he wasn’t eating well,” she said. “I knew the addiction was taking over.”
Vaping irritated Jake’s throat, and he would get nosebleeds that he couldn’t stop, she added.
Since Mrs. Warn first looked into the effects of e-cigarettes on respiratory health back in 2017, many studies have been conducted of the short-term health outcomes for first-time smokers who never used combustible tobacco products. Studies suggest that vaping may worsen bronchitis and asthma, raise blood pressure, interfere with brain development in young users, suppress the immune system, and increase the risk of developing a chronic lung disease (Am J Prev Med. 2020 Feb;58[2]:182-90). Studies of mice and cell cultures have found that the vapor or extracts from vapes damage the chemical structure of DNA.
Still, the limited number of long-term human studies has made it hard to know what the health outcomes of e-cigarette users will be in the future. Conclusive studies linking commercial cigarette use to deaths from heart disease and cancer didn’t emerge until the mid-1950s, decades after manufacturers began mass production and marketing in the early 20th century.
Years could pass before researchers gain a clearer understanding of the health implications of long-term e-cigarette use, according to Nigar Nargis, PhD, senior scientific director of tobacco control research at the American Cancer Society.
“There hasn’t been any such study to establish the direct link from ENDS to cancer, but it is understood that it [vaping] may promote the development of cancer and lung damage and inflammation,” Dr. Nargis said.
For decades, advocates built awareness of the harms of tobacco use, which led to a sharp decline in tobacco-related illnesses such as lung cancer. But Hilary Schneider, Maine’s director of government relations for the ACS Cancer Action Network, said she fears the uptick in the use of vapes – especially among those who never smoked or those who use both combustible cigarettes and e-cigarettes – may reverse declines in the rates of smoking-relating diseases.
Multiple studies suggest that inhaling chemicals found in e-cigarettes – including nicotine-carrying aerosols – can damage arteries and inflame and injure the lungs.
Vapes “basically have created a pediatric tobacco-use epidemic,” Ms. Schneider said. “What we’re seeing is unprecedented tobacco use rates, higher rates than we’ve seen in decades.”
One reason many young people start vaping is the attraction to flavors, which range from classic menthol to fruits and sweets. A handful of states have enacted bans or restrictions on the sale of flavored vapes.
“It’s new, and it’s just been marketed in a way that we’re really fighting the false narrative put out there by makers of these products that are trying to make them appealing to kids,” said Rachel Boykan, MD, clinical professor of pediatrics and attending physician at Stony Brook (N.Y.) Children’s Hospital.
The flavor Red Bull, in particular, hooked Jake. And though he wasn’t aware of it at the time, nicotine packed into the pods may have kept him from quitting: The average nicotine concentration in e-cigarettes more than doubled from 2013 to 2018, according to a study by the Truth Initiative and the CDC.
The immediate risks of nicotine on the developing brain are well documented. Studies suggest that nicotine – which is found in ENDS products – may affect adolescents’ ability to learn, remember, and maintain attention.
But many adolescents and young adults who use e-cigarettes say that vaping helps alleviate anxiety and keep them attentive, which adds to the complexity of their dependency, according to Dr. Boykan.
Nicotine “actually interrupts neural circuits, that it can be associated with more anxiety, depression, attention to learning, and susceptibility to other addictive substances,” she said. “That is enough to make it very scary.”
Jake also said a social environment in which so many of his friends vaped also made it difficult for him to quit.
“You’re hanging out with your friends at night, and all of them are using it, and you’re trying not to,” he said.
Jake eventually took a semester off from college for an unrelated surgery. He moved home, away from his vaping classmates. He eventually transferred to a different college and lived at home, where no one vaped and where he wasn’t allowed to smoke in the house, he said.
“He came home and we took him to a doctor, and they didn’t know quite how to handle kids and addiction to e-cigarettes,” Mrs. Warn said.
Not fully understanding the long-term health implications of e-cigarette use has precluded many clinicians from offering clear messaging on the risk of vaping to current and potential users.
“It’s taken pediatricians time to ask the right questions and recognize nicotine addiction” from vaping, said Dr. Boykan, who serves as chair of the Section on Nicotine and Tobacco Prevention and Treatment of the American Academy of Pediatrics. “It’s just hit us so fast.”
But once pediatricians do identify a nicotine dependency, it can be difficult to treat, Dr. Boykan said. Many pediatricians now recognize that e-cigarette addiction may occur in children as early as middle school.
“We don’t have a lot of evidence-based treatments for kids to recommend,” Dr. Boykan said.
Will vaping be a ‘phase?’
Aware of his vaping dependency and the possible risks to his long-term health, Jake, now 23, said he’s lessened his use, compared with his college days, but still struggles to kick the habit for good.
“I’d like to not be able to use all the time, not to feel the urge,” Jake said. “But I think over time it’ll just kind of phase out.”
But his mother said quitting may not be that simple.
“This will be a lifelong journey,” she said. “When I think of who he is, addiction is something he will always have. It’s a part of him now.”
Dr. Boykan, Ms. Schneider, and Dr. Nardis reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Jake Warn calls vaping “a toxic artificial love.”
Jake, of Winslow, Maine, was 16 years old when he began vaping. Unlike cigarettes, vaping can be odorless, and its smoke leaves no trace, which allowed him and his friends to use the devices in school bathrooms without fear of being caught.
He would use an entire cartridge containing the vape liquid, the equivalent of smoking one pack of tobacco cigarettes, within 1 school day. By the fall semester of his first year in college, Jake said his use had increased even more.
“It got pricey, so that’s when I really started to notice” the extent of his dependency, he said recently.
Vaping rates among teenagers in Maine doubled from 15.3% to 28.7% between 2017 and 2019, while Jake was in high school. In 2021, 11% of high schoolers across the nation said they regularly smoked e-cigarettes, and an estimated 28% have ever tried the devices, according to the Centers for Disease Control and Prevention.
The Food and Drug Administration classifies e-cigarettes as a tobacco product because many contain nicotine, which comes from tobacco. Like Jake, the habit is likely to carry into adulthood for many who start in their teenage years, experts say.
Electronic nicotine delivery systems (ENDS) such as vapes have been touted by their manufacturers and by some in the medical field as a healthier alternative to cigarettes and as a method to help smokers give up the habit.
But, that’s not how Jake – who had never used combustible cigarettes – picked up vaping, or how he sold the idea to his mother.
“It’s all organic and natural flavoring, it’s just flavored water,” Mary Lou Warn recalled her son saying to her. She researched the health effects of vaping but didn’t find much online. “I knew they were dangerous because you don’t put anything in your lungs that isn’t fresh air.”
A determined athlete in high school, Jake found that his asthma worsened as he transitioned to college, especially when he ran a track meet or during a soccer game.
Mrs. Warn noticed changes off the field, too.
“He was coughing constantly, he wasn’t sleeping well, he wasn’t eating well,” she said. “I knew the addiction was taking over.”
Vaping irritated Jake’s throat, and he would get nosebleeds that he couldn’t stop, she added.
Since Mrs. Warn first looked into the effects of e-cigarettes on respiratory health back in 2017, many studies have been conducted of the short-term health outcomes for first-time smokers who never used combustible tobacco products. Studies suggest that vaping may worsen bronchitis and asthma, raise blood pressure, interfere with brain development in young users, suppress the immune system, and increase the risk of developing a chronic lung disease (Am J Prev Med. 2020 Feb;58[2]:182-90). Studies of mice and cell cultures have found that the vapor or extracts from vapes damage the chemical structure of DNA.
Still, the limited number of long-term human studies has made it hard to know what the health outcomes of e-cigarette users will be in the future. Conclusive studies linking commercial cigarette use to deaths from heart disease and cancer didn’t emerge until the mid-1950s, decades after manufacturers began mass production and marketing in the early 20th century.
Years could pass before researchers gain a clearer understanding of the health implications of long-term e-cigarette use, according to Nigar Nargis, PhD, senior scientific director of tobacco control research at the American Cancer Society.
“There hasn’t been any such study to establish the direct link from ENDS to cancer, but it is understood that it [vaping] may promote the development of cancer and lung damage and inflammation,” Dr. Nargis said.
For decades, advocates built awareness of the harms of tobacco use, which led to a sharp decline in tobacco-related illnesses such as lung cancer. But Hilary Schneider, Maine’s director of government relations for the ACS Cancer Action Network, said she fears the uptick in the use of vapes – especially among those who never smoked or those who use both combustible cigarettes and e-cigarettes – may reverse declines in the rates of smoking-relating diseases.
Multiple studies suggest that inhaling chemicals found in e-cigarettes – including nicotine-carrying aerosols – can damage arteries and inflame and injure the lungs.
Vapes “basically have created a pediatric tobacco-use epidemic,” Ms. Schneider said. “What we’re seeing is unprecedented tobacco use rates, higher rates than we’ve seen in decades.”
One reason many young people start vaping is the attraction to flavors, which range from classic menthol to fruits and sweets. A handful of states have enacted bans or restrictions on the sale of flavored vapes.
“It’s new, and it’s just been marketed in a way that we’re really fighting the false narrative put out there by makers of these products that are trying to make them appealing to kids,” said Rachel Boykan, MD, clinical professor of pediatrics and attending physician at Stony Brook (N.Y.) Children’s Hospital.
The flavor Red Bull, in particular, hooked Jake. And though he wasn’t aware of it at the time, nicotine packed into the pods may have kept him from quitting: The average nicotine concentration in e-cigarettes more than doubled from 2013 to 2018, according to a study by the Truth Initiative and the CDC.
The immediate risks of nicotine on the developing brain are well documented. Studies suggest that nicotine – which is found in ENDS products – may affect adolescents’ ability to learn, remember, and maintain attention.
But many adolescents and young adults who use e-cigarettes say that vaping helps alleviate anxiety and keep them attentive, which adds to the complexity of their dependency, according to Dr. Boykan.
Nicotine “actually interrupts neural circuits, that it can be associated with more anxiety, depression, attention to learning, and susceptibility to other addictive substances,” she said. “That is enough to make it very scary.”
Jake also said a social environment in which so many of his friends vaped also made it difficult for him to quit.
“You’re hanging out with your friends at night, and all of them are using it, and you’re trying not to,” he said.
Jake eventually took a semester off from college for an unrelated surgery. He moved home, away from his vaping classmates. He eventually transferred to a different college and lived at home, where no one vaped and where he wasn’t allowed to smoke in the house, he said.
“He came home and we took him to a doctor, and they didn’t know quite how to handle kids and addiction to e-cigarettes,” Mrs. Warn said.
Not fully understanding the long-term health implications of e-cigarette use has precluded many clinicians from offering clear messaging on the risk of vaping to current and potential users.
“It’s taken pediatricians time to ask the right questions and recognize nicotine addiction” from vaping, said Dr. Boykan, who serves as chair of the Section on Nicotine and Tobacco Prevention and Treatment of the American Academy of Pediatrics. “It’s just hit us so fast.”
But once pediatricians do identify a nicotine dependency, it can be difficult to treat, Dr. Boykan said. Many pediatricians now recognize that e-cigarette addiction may occur in children as early as middle school.
“We don’t have a lot of evidence-based treatments for kids to recommend,” Dr. Boykan said.
Will vaping be a ‘phase?’
Aware of his vaping dependency and the possible risks to his long-term health, Jake, now 23, said he’s lessened his use, compared with his college days, but still struggles to kick the habit for good.
“I’d like to not be able to use all the time, not to feel the urge,” Jake said. “But I think over time it’ll just kind of phase out.”
But his mother said quitting may not be that simple.
“This will be a lifelong journey,” she said. “When I think of who he is, addiction is something he will always have. It’s a part of him now.”
Dr. Boykan, Ms. Schneider, and Dr. Nardis reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Jake Warn calls vaping “a toxic artificial love.”
Jake, of Winslow, Maine, was 16 years old when he began vaping. Unlike cigarettes, vaping can be odorless, and its smoke leaves no trace, which allowed him and his friends to use the devices in school bathrooms without fear of being caught.
He would use an entire cartridge containing the vape liquid, the equivalent of smoking one pack of tobacco cigarettes, within 1 school day. By the fall semester of his first year in college, Jake said his use had increased even more.
“It got pricey, so that’s when I really started to notice” the extent of his dependency, he said recently.
Vaping rates among teenagers in Maine doubled from 15.3% to 28.7% between 2017 and 2019, while Jake was in high school. In 2021, 11% of high schoolers across the nation said they regularly smoked e-cigarettes, and an estimated 28% have ever tried the devices, according to the Centers for Disease Control and Prevention.
The Food and Drug Administration classifies e-cigarettes as a tobacco product because many contain nicotine, which comes from tobacco. Like Jake, the habit is likely to carry into adulthood for many who start in their teenage years, experts say.
Electronic nicotine delivery systems (ENDS) such as vapes have been touted by their manufacturers and by some in the medical field as a healthier alternative to cigarettes and as a method to help smokers give up the habit.
But, that’s not how Jake – who had never used combustible cigarettes – picked up vaping, or how he sold the idea to his mother.
“It’s all organic and natural flavoring, it’s just flavored water,” Mary Lou Warn recalled her son saying to her. She researched the health effects of vaping but didn’t find much online. “I knew they were dangerous because you don’t put anything in your lungs that isn’t fresh air.”
A determined athlete in high school, Jake found that his asthma worsened as he transitioned to college, especially when he ran a track meet or during a soccer game.
Mrs. Warn noticed changes off the field, too.
“He was coughing constantly, he wasn’t sleeping well, he wasn’t eating well,” she said. “I knew the addiction was taking over.”
Vaping irritated Jake’s throat, and he would get nosebleeds that he couldn’t stop, she added.
Since Mrs. Warn first looked into the effects of e-cigarettes on respiratory health back in 2017, many studies have been conducted of the short-term health outcomes for first-time smokers who never used combustible tobacco products. Studies suggest that vaping may worsen bronchitis and asthma, raise blood pressure, interfere with brain development in young users, suppress the immune system, and increase the risk of developing a chronic lung disease (Am J Prev Med. 2020 Feb;58[2]:182-90). Studies of mice and cell cultures have found that the vapor or extracts from vapes damage the chemical structure of DNA.
Still, the limited number of long-term human studies has made it hard to know what the health outcomes of e-cigarette users will be in the future. Conclusive studies linking commercial cigarette use to deaths from heart disease and cancer didn’t emerge until the mid-1950s, decades after manufacturers began mass production and marketing in the early 20th century.
Years could pass before researchers gain a clearer understanding of the health implications of long-term e-cigarette use, according to Nigar Nargis, PhD, senior scientific director of tobacco control research at the American Cancer Society.
“There hasn’t been any such study to establish the direct link from ENDS to cancer, but it is understood that it [vaping] may promote the development of cancer and lung damage and inflammation,” Dr. Nargis said.
For decades, advocates built awareness of the harms of tobacco use, which led to a sharp decline in tobacco-related illnesses such as lung cancer. But Hilary Schneider, Maine’s director of government relations for the ACS Cancer Action Network, said she fears the uptick in the use of vapes – especially among those who never smoked or those who use both combustible cigarettes and e-cigarettes – may reverse declines in the rates of smoking-relating diseases.
Multiple studies suggest that inhaling chemicals found in e-cigarettes – including nicotine-carrying aerosols – can damage arteries and inflame and injure the lungs.
Vapes “basically have created a pediatric tobacco-use epidemic,” Ms. Schneider said. “What we’re seeing is unprecedented tobacco use rates, higher rates than we’ve seen in decades.”
One reason many young people start vaping is the attraction to flavors, which range from classic menthol to fruits and sweets. A handful of states have enacted bans or restrictions on the sale of flavored vapes.
“It’s new, and it’s just been marketed in a way that we’re really fighting the false narrative put out there by makers of these products that are trying to make them appealing to kids,” said Rachel Boykan, MD, clinical professor of pediatrics and attending physician at Stony Brook (N.Y.) Children’s Hospital.
The flavor Red Bull, in particular, hooked Jake. And though he wasn’t aware of it at the time, nicotine packed into the pods may have kept him from quitting: The average nicotine concentration in e-cigarettes more than doubled from 2013 to 2018, according to a study by the Truth Initiative and the CDC.
The immediate risks of nicotine on the developing brain are well documented. Studies suggest that nicotine – which is found in ENDS products – may affect adolescents’ ability to learn, remember, and maintain attention.
But many adolescents and young adults who use e-cigarettes say that vaping helps alleviate anxiety and keep them attentive, which adds to the complexity of their dependency, according to Dr. Boykan.
Nicotine “actually interrupts neural circuits, that it can be associated with more anxiety, depression, attention to learning, and susceptibility to other addictive substances,” she said. “That is enough to make it very scary.”
Jake also said a social environment in which so many of his friends vaped also made it difficult for him to quit.
“You’re hanging out with your friends at night, and all of them are using it, and you’re trying not to,” he said.
Jake eventually took a semester off from college for an unrelated surgery. He moved home, away from his vaping classmates. He eventually transferred to a different college and lived at home, where no one vaped and where he wasn’t allowed to smoke in the house, he said.
“He came home and we took him to a doctor, and they didn’t know quite how to handle kids and addiction to e-cigarettes,” Mrs. Warn said.
Not fully understanding the long-term health implications of e-cigarette use has precluded many clinicians from offering clear messaging on the risk of vaping to current and potential users.
“It’s taken pediatricians time to ask the right questions and recognize nicotine addiction” from vaping, said Dr. Boykan, who serves as chair of the Section on Nicotine and Tobacco Prevention and Treatment of the American Academy of Pediatrics. “It’s just hit us so fast.”
But once pediatricians do identify a nicotine dependency, it can be difficult to treat, Dr. Boykan said. Many pediatricians now recognize that e-cigarette addiction may occur in children as early as middle school.
“We don’t have a lot of evidence-based treatments for kids to recommend,” Dr. Boykan said.
Will vaping be a ‘phase?’
Aware of his vaping dependency and the possible risks to his long-term health, Jake, now 23, said he’s lessened his use, compared with his college days, but still struggles to kick the habit for good.
“I’d like to not be able to use all the time, not to feel the urge,” Jake said. “But I think over time it’ll just kind of phase out.”
But his mother said quitting may not be that simple.
“This will be a lifelong journey,” she said. “When I think of who he is, addiction is something he will always have. It’s a part of him now.”
Dr. Boykan, Ms. Schneider, and Dr. Nardis reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Teen girls are in crisis: A call to action resulting from 2021 CDC data
Case: “Where’s my mommy?”
A 13-year-old girl “D” appeared lifeless in her hospital bed, swallowed by tubes, gauze, and crisp white sheets. She seemed fragile next to the giant machines beeping all around her, as they churned and groaned to keep her alive. She was in the pediatric intensive care unit, a place she had only seen once or twice on TV. Her sleeping mother lay next to her in an uncomfortable-looking recliner chair, curled up in a ball. She abruptly woke up when I walked into the room, doing her best to wipe away 5 days’ worth of worry and sadness from her exhausted face. She saw “Child Psychiatrist” written on my hospital badge, desperately searching my face for answers or a sign of hope.
Her daughter – a straight-A middle school student who loved Taylor Swift and soccer – had overdosed on Tylenol after discovering that she did not make the cheerleading team. I reported that her daughter’s liver enzymes were finally trending down and that she would likely not require a liver transplant. She would survive. As tears welled up in this mother’s eyes, I heard a faint whisper from across the room. “Where’s my mommy?” D was awake and frantically searching the room for her mother, someone who could soothe her in this living nightmare. As the two embraced, I felt tears well up in my eyes as I couldn’t help but think of my own 3-year-old daughter at home. How could I protect her from the sadness and despair that this little girl was feeling? How can we collectively protect every little girl from wanting to end their life?
CDC data: Teen girls need help now
The latest biennial Centers for Disease Control and Prevention Youth Risk Behavior Survey, administered in the fall of 2021, resulted in alarming data showing that mental health has worsened for all adolescents, but especially for girls. The survey was administered to more than 17,000 students in 152 public and private schools throughout the United States, showing that “America’s teen girls are engulfed in a growing wave of sadness, violence, and trauma.”1 In particular, rates of sadness, suicidal ideation, suicide attempts, and mental health crisis ED visits among girls are the highest reported in a decade. Nearly 60% of girls felt persistent sadness or hopelessness during the past year, double the rate of boys. More than 25% of girls made a suicide plan; this percentage increased 60% over the past 10 years. Alarmingly, ED visits for suicide attempts for girls increased more than 50% in the past 2 years alone.
Even before the COVID-19 pandemic, experts were sounding the alarm on the growing rates of anxiety and depression in U.S. youth. The pandemic-driven isolation, lack of social connection, and missing of major milestones did not help the situation and only deepened the cracks in a faulty mental health care system. Further, civil unrest and social upheaval in the United States felt – and continues to feel – chaotic and unpredictable. For teens, the current cultural climate represents their not-too-distant future as adults, causing worry and anxiety.
In addition to securing their futures through performance in school and extracurricular activities, teenagers are forming their identities. Establishing a personal identity is a difficult task for all teens, though teenage girls face uniquely difficult challenges in our current society. In particular, teenage girls are expected to conform their behaviors to fit societal expectations that may clash with their desires and self-conceptualization. This conflict is further complicated by heightened beauty standards, online hate and competition, academic pressure, and self-doubt. CDC data show that girls experience sexual harassment and cyberbullying at roughly twice the rate of their male counterparts. Girls also experience higher levels of sexual violence and bullying. Alarmingly, 14% of girls reported being forced to have sex at some point in their lives. The sad truth is that, for every 10 teenage girls you know, at least one of them, and probably more, has likely been raped.
A call to action for providers
As providers, what can we do about these alarming statistics? It’s easy to become overwhelmed by data on a national level. However, regardless of our current clinical practice situation, we cannot lose sight of the humanity behind these numbers. Five extra minutes of truly listening to our patients, normalizing conversations about mental health, and looking for mental health warning signs (that is, increased isolation, declining function in school, maladaptive coping skills such as self-injurious behavior or substance use) can mean the difference between life and death.
As pediatric providers, formally screening for suicide risk is critical. Specifically, the American Academy of Pediatrics recommends that all youth aged 12 years or older be screened for suicide risk.2 In addition to asking families to reduce access to lethal means, it is important to utilize suicide-specific screeners to prevent suicide attempts and deaths in the pediatric community. Pediatric providers must feel prepared to counsel patients and families on suicide prevention and, if this skill set is underdeveloped, appropriate referrals and support must be provided.
At the same time, it is important to note the larger context. This national tragedy has been long-standing and further accelerated by the social isolation and stress of the pandemic. Madigan and colleagues recently showed that the lack of a social outlet resulting from COVID-19 caused an increase in screen time among all children.3 As a result, many teen girls turned to social media to recreate these social connections online.4 This dependence on social media for validation has contributed to increased rates of depression by intensifying unrealistic body standards, comparisons, and competition among peers.5 However, recent pediatric partnership programs have improved mental health access, reduced ED visits, and increased primary care physician’s comfort with managing mental health concerns.6 These programs are called Child Psychiatry Access Programs (CPAPs) and utilize a collaborative care model through which primary care clinicians consult with child and adolescent psychiatrists. CPAPs, while not the entire solution, offer a major step in the right direction toward tackling this mental health crisis in a sustainable, collaborative, and effective way.
As students return to in-person learning, connectedness at school is a powerful protective factor against depression and anxiety. We must infuse resources and support into our schools and teachers, as they stand on the front lines for our children. Specifically, bolstering schools with school counselors and appropriate mental health support staff will help rescue teachers from burnout while also explicitly identifying mental health care as a priority. Finally, modeling positive behavior for families and identifying safe adults at school can help at-risk youth feel more connected. To achieve meaningful improvement in children’s mental health, it is crucial to collaboratively remodel broken systems to ensure that all children are supported early, effectively, and equitably.
Dr. Richards is assistant clinical professor in the department of psychiatry and biobehavioral sciences, program director of the child and adolescent psychiatry fellowship, and associate medical director of the perinatal program at the UCLA Semel Institute for Neuroscience and Human Behavior in Los Angeles.
References
1. Centers for Disease Control and Prevention. YRBSS Data Summary & Trends. 2023 Feb 13. https://www.cdc.gov/healthyyouth/data/yrbs/yrbs_data_summary_and_trends.htm
2. American Academy of Pediatrics. Screening for Suicide Risk in Clinical Practice. 2023 Feb 22. https://www.aap.org/en/patient-care/blueprint-for-youth-suicide-prevention/strategies-for-clinical-settings-for-youth-suicide-prevention/screening-for-suicide-risk-in-clinical-practice/
3. Madigan S et al. JAMA Pediatr. 2022;176(12):1188-98. doi: 10.1001/JAMAPEDIATRICS.2022.4116
4. Pew Research Center. Teens, Social Media and Technology 2022. 2022 Aug 10. https://www.pewresearch.org/internet/2022/08/10/teens-social-media-and-technology-2022/
5. Hunt MG et al. J Social Clin Psychology. 2018;37(10):751-68. doi: 10.1521/JSCP.2018.37.10.751
6. Godoy L et al. J Pediatr Health Care. 2022 Dec 16. doi: 10.1016/j.pedhc.2022.11.009.
Case: “Where’s my mommy?”
A 13-year-old girl “D” appeared lifeless in her hospital bed, swallowed by tubes, gauze, and crisp white sheets. She seemed fragile next to the giant machines beeping all around her, as they churned and groaned to keep her alive. She was in the pediatric intensive care unit, a place she had only seen once or twice on TV. Her sleeping mother lay next to her in an uncomfortable-looking recliner chair, curled up in a ball. She abruptly woke up when I walked into the room, doing her best to wipe away 5 days’ worth of worry and sadness from her exhausted face. She saw “Child Psychiatrist” written on my hospital badge, desperately searching my face for answers or a sign of hope.
Her daughter – a straight-A middle school student who loved Taylor Swift and soccer – had overdosed on Tylenol after discovering that she did not make the cheerleading team. I reported that her daughter’s liver enzymes were finally trending down and that she would likely not require a liver transplant. She would survive. As tears welled up in this mother’s eyes, I heard a faint whisper from across the room. “Where’s my mommy?” D was awake and frantically searching the room for her mother, someone who could soothe her in this living nightmare. As the two embraced, I felt tears well up in my eyes as I couldn’t help but think of my own 3-year-old daughter at home. How could I protect her from the sadness and despair that this little girl was feeling? How can we collectively protect every little girl from wanting to end their life?
CDC data: Teen girls need help now
The latest biennial Centers for Disease Control and Prevention Youth Risk Behavior Survey, administered in the fall of 2021, resulted in alarming data showing that mental health has worsened for all adolescents, but especially for girls. The survey was administered to more than 17,000 students in 152 public and private schools throughout the United States, showing that “America’s teen girls are engulfed in a growing wave of sadness, violence, and trauma.”1 In particular, rates of sadness, suicidal ideation, suicide attempts, and mental health crisis ED visits among girls are the highest reported in a decade. Nearly 60% of girls felt persistent sadness or hopelessness during the past year, double the rate of boys. More than 25% of girls made a suicide plan; this percentage increased 60% over the past 10 years. Alarmingly, ED visits for suicide attempts for girls increased more than 50% in the past 2 years alone.
Even before the COVID-19 pandemic, experts were sounding the alarm on the growing rates of anxiety and depression in U.S. youth. The pandemic-driven isolation, lack of social connection, and missing of major milestones did not help the situation and only deepened the cracks in a faulty mental health care system. Further, civil unrest and social upheaval in the United States felt – and continues to feel – chaotic and unpredictable. For teens, the current cultural climate represents their not-too-distant future as adults, causing worry and anxiety.
In addition to securing their futures through performance in school and extracurricular activities, teenagers are forming their identities. Establishing a personal identity is a difficult task for all teens, though teenage girls face uniquely difficult challenges in our current society. In particular, teenage girls are expected to conform their behaviors to fit societal expectations that may clash with their desires and self-conceptualization. This conflict is further complicated by heightened beauty standards, online hate and competition, academic pressure, and self-doubt. CDC data show that girls experience sexual harassment and cyberbullying at roughly twice the rate of their male counterparts. Girls also experience higher levels of sexual violence and bullying. Alarmingly, 14% of girls reported being forced to have sex at some point in their lives. The sad truth is that, for every 10 teenage girls you know, at least one of them, and probably more, has likely been raped.
A call to action for providers
As providers, what can we do about these alarming statistics? It’s easy to become overwhelmed by data on a national level. However, regardless of our current clinical practice situation, we cannot lose sight of the humanity behind these numbers. Five extra minutes of truly listening to our patients, normalizing conversations about mental health, and looking for mental health warning signs (that is, increased isolation, declining function in school, maladaptive coping skills such as self-injurious behavior or substance use) can mean the difference between life and death.
As pediatric providers, formally screening for suicide risk is critical. Specifically, the American Academy of Pediatrics recommends that all youth aged 12 years or older be screened for suicide risk.2 In addition to asking families to reduce access to lethal means, it is important to utilize suicide-specific screeners to prevent suicide attempts and deaths in the pediatric community. Pediatric providers must feel prepared to counsel patients and families on suicide prevention and, if this skill set is underdeveloped, appropriate referrals and support must be provided.
At the same time, it is important to note the larger context. This national tragedy has been long-standing and further accelerated by the social isolation and stress of the pandemic. Madigan and colleagues recently showed that the lack of a social outlet resulting from COVID-19 caused an increase in screen time among all children.3 As a result, many teen girls turned to social media to recreate these social connections online.4 This dependence on social media for validation has contributed to increased rates of depression by intensifying unrealistic body standards, comparisons, and competition among peers.5 However, recent pediatric partnership programs have improved mental health access, reduced ED visits, and increased primary care physician’s comfort with managing mental health concerns.6 These programs are called Child Psychiatry Access Programs (CPAPs) and utilize a collaborative care model through which primary care clinicians consult with child and adolescent psychiatrists. CPAPs, while not the entire solution, offer a major step in the right direction toward tackling this mental health crisis in a sustainable, collaborative, and effective way.
As students return to in-person learning, connectedness at school is a powerful protective factor against depression and anxiety. We must infuse resources and support into our schools and teachers, as they stand on the front lines for our children. Specifically, bolstering schools with school counselors and appropriate mental health support staff will help rescue teachers from burnout while also explicitly identifying mental health care as a priority. Finally, modeling positive behavior for families and identifying safe adults at school can help at-risk youth feel more connected. To achieve meaningful improvement in children’s mental health, it is crucial to collaboratively remodel broken systems to ensure that all children are supported early, effectively, and equitably.
Dr. Richards is assistant clinical professor in the department of psychiatry and biobehavioral sciences, program director of the child and adolescent psychiatry fellowship, and associate medical director of the perinatal program at the UCLA Semel Institute for Neuroscience and Human Behavior in Los Angeles.
References
1. Centers for Disease Control and Prevention. YRBSS Data Summary & Trends. 2023 Feb 13. https://www.cdc.gov/healthyyouth/data/yrbs/yrbs_data_summary_and_trends.htm
2. American Academy of Pediatrics. Screening for Suicide Risk in Clinical Practice. 2023 Feb 22. https://www.aap.org/en/patient-care/blueprint-for-youth-suicide-prevention/strategies-for-clinical-settings-for-youth-suicide-prevention/screening-for-suicide-risk-in-clinical-practice/
3. Madigan S et al. JAMA Pediatr. 2022;176(12):1188-98. doi: 10.1001/JAMAPEDIATRICS.2022.4116
4. Pew Research Center. Teens, Social Media and Technology 2022. 2022 Aug 10. https://www.pewresearch.org/internet/2022/08/10/teens-social-media-and-technology-2022/
5. Hunt MG et al. J Social Clin Psychology. 2018;37(10):751-68. doi: 10.1521/JSCP.2018.37.10.751
6. Godoy L et al. J Pediatr Health Care. 2022 Dec 16. doi: 10.1016/j.pedhc.2022.11.009.
Case: “Where’s my mommy?”
A 13-year-old girl “D” appeared lifeless in her hospital bed, swallowed by tubes, gauze, and crisp white sheets. She seemed fragile next to the giant machines beeping all around her, as they churned and groaned to keep her alive. She was in the pediatric intensive care unit, a place she had only seen once or twice on TV. Her sleeping mother lay next to her in an uncomfortable-looking recliner chair, curled up in a ball. She abruptly woke up when I walked into the room, doing her best to wipe away 5 days’ worth of worry and sadness from her exhausted face. She saw “Child Psychiatrist” written on my hospital badge, desperately searching my face for answers or a sign of hope.
Her daughter – a straight-A middle school student who loved Taylor Swift and soccer – had overdosed on Tylenol after discovering that she did not make the cheerleading team. I reported that her daughter’s liver enzymes were finally trending down and that she would likely not require a liver transplant. She would survive. As tears welled up in this mother’s eyes, I heard a faint whisper from across the room. “Where’s my mommy?” D was awake and frantically searching the room for her mother, someone who could soothe her in this living nightmare. As the two embraced, I felt tears well up in my eyes as I couldn’t help but think of my own 3-year-old daughter at home. How could I protect her from the sadness and despair that this little girl was feeling? How can we collectively protect every little girl from wanting to end their life?
CDC data: Teen girls need help now
The latest biennial Centers for Disease Control and Prevention Youth Risk Behavior Survey, administered in the fall of 2021, resulted in alarming data showing that mental health has worsened for all adolescents, but especially for girls. The survey was administered to more than 17,000 students in 152 public and private schools throughout the United States, showing that “America’s teen girls are engulfed in a growing wave of sadness, violence, and trauma.”1 In particular, rates of sadness, suicidal ideation, suicide attempts, and mental health crisis ED visits among girls are the highest reported in a decade. Nearly 60% of girls felt persistent sadness or hopelessness during the past year, double the rate of boys. More than 25% of girls made a suicide plan; this percentage increased 60% over the past 10 years. Alarmingly, ED visits for suicide attempts for girls increased more than 50% in the past 2 years alone.
Even before the COVID-19 pandemic, experts were sounding the alarm on the growing rates of anxiety and depression in U.S. youth. The pandemic-driven isolation, lack of social connection, and missing of major milestones did not help the situation and only deepened the cracks in a faulty mental health care system. Further, civil unrest and social upheaval in the United States felt – and continues to feel – chaotic and unpredictable. For teens, the current cultural climate represents their not-too-distant future as adults, causing worry and anxiety.
In addition to securing their futures through performance in school and extracurricular activities, teenagers are forming their identities. Establishing a personal identity is a difficult task for all teens, though teenage girls face uniquely difficult challenges in our current society. In particular, teenage girls are expected to conform their behaviors to fit societal expectations that may clash with their desires and self-conceptualization. This conflict is further complicated by heightened beauty standards, online hate and competition, academic pressure, and self-doubt. CDC data show that girls experience sexual harassment and cyberbullying at roughly twice the rate of their male counterparts. Girls also experience higher levels of sexual violence and bullying. Alarmingly, 14% of girls reported being forced to have sex at some point in their lives. The sad truth is that, for every 10 teenage girls you know, at least one of them, and probably more, has likely been raped.
A call to action for providers
As providers, what can we do about these alarming statistics? It’s easy to become overwhelmed by data on a national level. However, regardless of our current clinical practice situation, we cannot lose sight of the humanity behind these numbers. Five extra minutes of truly listening to our patients, normalizing conversations about mental health, and looking for mental health warning signs (that is, increased isolation, declining function in school, maladaptive coping skills such as self-injurious behavior or substance use) can mean the difference between life and death.
As pediatric providers, formally screening for suicide risk is critical. Specifically, the American Academy of Pediatrics recommends that all youth aged 12 years or older be screened for suicide risk.2 In addition to asking families to reduce access to lethal means, it is important to utilize suicide-specific screeners to prevent suicide attempts and deaths in the pediatric community. Pediatric providers must feel prepared to counsel patients and families on suicide prevention and, if this skill set is underdeveloped, appropriate referrals and support must be provided.
At the same time, it is important to note the larger context. This national tragedy has been long-standing and further accelerated by the social isolation and stress of the pandemic. Madigan and colleagues recently showed that the lack of a social outlet resulting from COVID-19 caused an increase in screen time among all children.3 As a result, many teen girls turned to social media to recreate these social connections online.4 This dependence on social media for validation has contributed to increased rates of depression by intensifying unrealistic body standards, comparisons, and competition among peers.5 However, recent pediatric partnership programs have improved mental health access, reduced ED visits, and increased primary care physician’s comfort with managing mental health concerns.6 These programs are called Child Psychiatry Access Programs (CPAPs) and utilize a collaborative care model through which primary care clinicians consult with child and adolescent psychiatrists. CPAPs, while not the entire solution, offer a major step in the right direction toward tackling this mental health crisis in a sustainable, collaborative, and effective way.
As students return to in-person learning, connectedness at school is a powerful protective factor against depression and anxiety. We must infuse resources and support into our schools and teachers, as they stand on the front lines for our children. Specifically, bolstering schools with school counselors and appropriate mental health support staff will help rescue teachers from burnout while also explicitly identifying mental health care as a priority. Finally, modeling positive behavior for families and identifying safe adults at school can help at-risk youth feel more connected. To achieve meaningful improvement in children’s mental health, it is crucial to collaboratively remodel broken systems to ensure that all children are supported early, effectively, and equitably.
Dr. Richards is assistant clinical professor in the department of psychiatry and biobehavioral sciences, program director of the child and adolescent psychiatry fellowship, and associate medical director of the perinatal program at the UCLA Semel Institute for Neuroscience and Human Behavior in Los Angeles.
References
1. Centers for Disease Control and Prevention. YRBSS Data Summary & Trends. 2023 Feb 13. https://www.cdc.gov/healthyyouth/data/yrbs/yrbs_data_summary_and_trends.htm
2. American Academy of Pediatrics. Screening for Suicide Risk in Clinical Practice. 2023 Feb 22. https://www.aap.org/en/patient-care/blueprint-for-youth-suicide-prevention/strategies-for-clinical-settings-for-youth-suicide-prevention/screening-for-suicide-risk-in-clinical-practice/
3. Madigan S et al. JAMA Pediatr. 2022;176(12):1188-98. doi: 10.1001/JAMAPEDIATRICS.2022.4116
4. Pew Research Center. Teens, Social Media and Technology 2022. 2022 Aug 10. https://www.pewresearch.org/internet/2022/08/10/teens-social-media-and-technology-2022/
5. Hunt MG et al. J Social Clin Psychology. 2018;37(10):751-68. doi: 10.1521/JSCP.2018.37.10.751
6. Godoy L et al. J Pediatr Health Care. 2022 Dec 16. doi: 10.1016/j.pedhc.2022.11.009.
Answers sought for mental health challenges in pediatric rheumatology patients
NEW ORLEANS – Pediatric patients with rheumatologic diseases experience a particularly high prevalence of psychological distress and depression and anxiety symptoms, according to research presented at the Pediatric Rheumatology Symposium. Although this finding is not necessarily surprising, the extent to which depression and psychological distress impacts these young patients’ quality of life has led to greater research and innovation in seeking ways to identify, address, and treat depression and anxiety in children and adolescents with diseases such as juvenile idiopathic arthritis (JIA) or systemic lupus erythematosus (SLE).
Accordingly, other studies presented at the conference examined more efficient ways to screen adolescent patients for depression and assessed programs designed to improve symptoms. In fact, the American College of Rheumatology award for the top Quality, Health Services, and Education Research abstract at this year’s symposium went to Lauren Harper, MD, a pediatric rheumatology fellow at Nationwide Children’s Hospital, Columbus, whose research examined the effects of automating depression screening during check-in for adolescent patients with SLE. Her findings revealed that automation of screening increased detection of depression and suicidality, thereby increasing interventions and ultimately resulting in a reduction in depression prevalence.
“The key clinical takeaway is that mental health screening is really important – it affects our patients in so many different ways – and it’s very doable in your rheumatology clinic,” Dr. Harper said in an interview. “It’s also important because they’re coming to us very frequently, but they don’t see their PCP [primary care provider] very often, so we can’t leave screening to the PCPs.”
Two other studies assessed the effectiveness of a 6-week cognitive-behavioral intervention for youth called Treatment and Education Approach for Childhood-Onset Lupus (TEACH). One study found that remote delivery of TEACH resulted in improved mood symptoms and reduced fatigue, and another found the program particularly effective in improving mood for patients deemed “high risk” because of greater depression and fatigue symptoms.
The impact of growing mental health problems has been enormous both in the pediatric rheumatology population and society at large, Daria Sosna, MSc, a research coordinator at the University of Calgary (Alta.), said in an interview as she visited the research posters related to psychological stress and depression.
“We need to do something,” said Ms. Sosna, whose department is currently applying for funding to develop a research project to improve mental health outcomes in adolescents with lupus. “This population, specifically, has higher numbers than anyone else does because they have chronic illness” – and those issues need to be addressed.
High psychological stress levels
The study looking at psychological stress in pediatric rheumatology patients, led by Natalie Rosenwasser, MD, of Seattle Children’s Hospital, relied on cross-sectional data from patients enrolled in two Childhood Arthritis and Rheumatology Research Alliance sites, one in Utah and one in Seattle. The average age of the 71 patients who completed the surveys was 13, and the researchers reported the findings in two separate age groups: those aged 13-17, who completed the surveys themselves, and those aged 8-12, whose parents completed the surveys. Nearly all the patients (94.4%) had JIA, but one had lupus and three had juvenile dermatomyositis.
The participants completed the Patient-Reported Outcomes Measurement Information System (PROMIS) for psychological stress, physical stress, and depressive symptoms. They also filled out the National Institutes of Health–Toolbox Perceived Stress survey, the 9-item Patient Health Questionnaire (PHQ-9), the Screen for Child Anxiety Related Disorders (SCARED), a visual analog scale for COVID-related distress, and a questionnaire asking about how receptive they were to mental health screening. The researchers determined that a score 1 standard deviation above the mean on the PROMIS and NIH-Toolbox assessments qualified as a high level of psychological stress.
“There are data that suggest that psychological stress can be a precursor to depression and anxiety, which raises the concern that not every patient who’s experiencing mental health symptoms is going to be picked up on traditional measures that meet that clinical threshold, but they may really need interventions to protect their mental health,” presenter Erin Treemarcki, DO, an assistant professor of pediatric rheumatology at the University of Utah, Salt Lake City, said in an interview. “Not every patient may necessarily need referral to a mental health specialist, but there are still potential interventions that we can do in the clinical setting to address mental health, which in turn can improve outcomes, including medication compliance and knowing how patients are feeling.”
More than one-third of the patients (39%) reported a high level of psychological stress, and 43% had elevated physical stress. Broken down by age, 26% of the teens and 15% of the younger patients reported high levels of perceived stress. The PROMIS only identified increased depressive symptoms in 26% of the participants, whereas more than half (54%) had a positive PHQ-9 depression screen. Furthermore, half the patients had SCARED scores (50%) that likely indicated anxiety disorder. Only 6% of patients reported severe stress specifically related to the pandemic, but most reported mild distress from the pandemic.
“Psychological stress was highly correlated with physical stress, perceived stress, depressive symptoms [PROMIS and PHQ-9], and anxiety,” the authors reported (P < .05). The authors next plan to expand their assessment to a third CARRA site and then explore the interaction between psychological distress and sociodemographic factors.
“There’s such an increase in mental health disorders right now, and we’re overwhelmed in general,” Ms. Sosna said in an interview. “There have to be interventions that approach this. We can use pharmacological approaches, we can use CBT, we can use a lot of these things that are very well established, and they’re absolutely fantastic, but we don’t necessarily have the resources or capabilities to do that all the time.”
Benefits of automated depression screening
To reduce the likelihood of depression screenings falling through the cracks during visits, Dr. Harper’s study assessed the impact of automating screens in an adolescent population. In her presentation, she noted previous research finding that nearly half of youth with lupus (47%) had depression, compared with 24% of adults with lupus. Pediatric patients have nearly three times the odds of depression and more than five times the odds of suicidal ideation, she told attendees. These mood disorders are correlated with greater physical disability, higher cardiovascular risk, more disease activity, higher risk of premature death, and decreased educational attainment, medication compliance, and quality of life.
Despite recommendations for depression screening from the U.S. Preventive Services Task Force and the American Academy of Pediatrics, only 2% of pediatric rheumatology patients are routinely screened for depression with a validated instrument, and only 7% of those with depressive symptoms are screened, according to a 2016 study that Dr. Harper cited. Yet the same study found that nearly all pediatric rheumatologists (95%) supported routine depression screening every 6-12 months. Hence her team’s decision to test whether automating screening improved their screening rates.
Their population included lupus patients aged 12 and older seen at Nationwide Children’s Hospital between 2014 and 2022. Initially, patients completed the PHQ-9 on paper, which was then transcribed into the electronic health record. The process became automated and administered on an iPad at every visit in 2022. Positive screens – those endorsing suicidality or with a score of at least 10 – caused an alert to pop up for clinicians during their workflow so that they would talk to the mental health team about the patient’s needs.
A total of 149 patients completed 529 screenings during the study’s 8 years. Only 1 patient completed a PHQ-9 in 2014, which increased to just 17 patients in 2017. Automation resulted in 225 screens (P < .01). Subsequently, positive screens increased from 0% in 2014 to 25%-30% in 2018-2021, but then fell to 12% in 2022 (P < .01). The median PHQ-9 score was 3; overall scores decreased as screening increased.
The overall incidence of positive screens during the study period was 20% and prevalence was 38%, the authors reported. Of the 10 automated alerts triggered by positive screens, 90% resulted in a meeting with a psychologist or social worker, and 90% completed a suicide risk assessment. The intrusive alert for clinicians requires them to acknowledge the alert, agreeing to initiate a risk assessment, before they can enter data into the patient’s chart.
The study findings reveal “that you can successfully screen a high-risk population using an automated, seamless process, and you can alert providers without too much disruption to their typical clinic flow,” Dr. Harper told attendees. “And all of these processes have led to sustainability for routine depression screening in our lupus clinic.”
Dr. Harper’s team next plans to expand the automated screenings to populations with other diseases, to add an automated screening for anxiety, and to explore how PHQ-9 scores correlate with disease activity.
Treating patients’ mental health
Another two other abstracts at the symposium looked at another option, the 6-week cognitive-behavioral TEACH program. Deborah Levy, MD, MS, an associate professor of pediatrics at the University of Toronto and the clinical director of rheumatology at The Hospital for Sick Children, and colleagues assessed the program’s success when delivered remotely to adolescent patients with lupus. Pilot testing with TEACH had already shown improvements in fatigue and mood, Dr. Levy told attendees, but barriers to in-person delivery limited its utility even before the pandemic, so this study aimed to determine a remote version’s feasibility and effects, compared with treatment as usual.
The randomized, controlled trial, led by Natoshia Cunningham, PhD, from Michigan State University, Grand Rapids, included 57 participants, aged 12-22, from seven U.S. and Canadian rheumatology sites. All had been diagnosed with childhood-onset SLE by age 18 and had elevated symptoms in fatigue, pain, or depression. A PROMIS Fatigue T score of 60 or greater indicated elevated fatigue scores, whereas a high pain score was at least a 3/10 on a visual analog scale, and a high depression T score was at least a 60 but not higher than 80 on the Children’s Depression Inventory–2 or the Beck Depression Inventory–II (depending on the patient’s age).
Patients with other chronic medical conditions, developmental delays, or untreated major psychiatric illness were excluded from the study, as were patients who were receiving overlapping treatment, such as cognitive-behavioral therapy for pain or mood. Thirty patients were randomly assigned to receive treatment as usual while 27 patients were assigned to participate in the remote TEACH program.
Nearly all the patients (94%) were female, but they were racially diverse, with 42% White, 28% Asian, 19% Black, 19% Hispanic, and 4% multiracial. The patients were an average 16 years old and had been diagnosed for a median 5 years. Three of the intervention’s six modules involved the caregivers or, for older patients, their partners if desired. The communication strategies taught in the program were also tailored to patients’ ages.
“All of these strategies are educational, cognitive, behavioral, mindfulness strategies that target fatigue [and] pain, and they also developed web content for participants to use on their own,” Dr. Levy told attendees.
The researchers had complete postassessment data from 88% of participants, but they also reported some of the statements made during qualitative interviews about the program’s feasibility.
“I think it makes people more aware of themselves to become a better version of themselves, whether that’s in their normal life or in handling a lupus kind of life,” one participant said about the program’s benefits. Another appreciated the “alternative ways of thinking,” including “being more mindful of my thoughts and how those kind of aggravate my stress.”
The quantitative findings revealed a statistically significant reduction in depressive symptoms and fatigue for TEACH participants, compared with treatment as usual. Mood scores fell by an average 13.7 points in the TEACH group, compared with a drop of 2.4 points in the treatment as usual group (P < .001). Scores for fatigue fell 9.16 points in the TEACH group and 2.93 in the control group (P = .003). No statistically significant difference showed up in pain scores between the groups, although pain, medication adherence, and disease activity did improve slightly more in the TEACH group.
In addition to the significant improvements in mood and fatigue, therefore, “completion of TEACH may be associated with improved medication adherence and disease activity versus treatment as usual,” Dr. Levy said.
A much smaller study authored by some of the same researchers also assessed TEACH’s impact not in remote form but in terms of its value specifically for adolescent patients with SLE and elevated depression and fatigue scores. Comparison of 6 high-risk patients with 10 low-risk patients who underwent TEACH suggested that the program was especially effective for improving depression in high-risk patients since these patients had a statistically significantly greater improvement in mood. Fatigue, pain, anxiety, quality of life, and disease activity scores did not statistically differ between the groups.
Authors of the automated depression screening study reported no disclosures or outside funding. The study assessing psychological distress was funded by a CARRA–Arthritis Foundation grant, and the authors reported no disclosures. The remote TEACH study was funded by a CARRA–Arthritis Foundation grant, and all but one author reported no disclosures. One author had disclosures with Janssen, Roche, and Sobi. The high-risk TEACH study was also funded by a CARRA grant, and the authors had no disclosures.
NEW ORLEANS – Pediatric patients with rheumatologic diseases experience a particularly high prevalence of psychological distress and depression and anxiety symptoms, according to research presented at the Pediatric Rheumatology Symposium. Although this finding is not necessarily surprising, the extent to which depression and psychological distress impacts these young patients’ quality of life has led to greater research and innovation in seeking ways to identify, address, and treat depression and anxiety in children and adolescents with diseases such as juvenile idiopathic arthritis (JIA) or systemic lupus erythematosus (SLE).
Accordingly, other studies presented at the conference examined more efficient ways to screen adolescent patients for depression and assessed programs designed to improve symptoms. In fact, the American College of Rheumatology award for the top Quality, Health Services, and Education Research abstract at this year’s symposium went to Lauren Harper, MD, a pediatric rheumatology fellow at Nationwide Children’s Hospital, Columbus, whose research examined the effects of automating depression screening during check-in for adolescent patients with SLE. Her findings revealed that automation of screening increased detection of depression and suicidality, thereby increasing interventions and ultimately resulting in a reduction in depression prevalence.
“The key clinical takeaway is that mental health screening is really important – it affects our patients in so many different ways – and it’s very doable in your rheumatology clinic,” Dr. Harper said in an interview. “It’s also important because they’re coming to us very frequently, but they don’t see their PCP [primary care provider] very often, so we can’t leave screening to the PCPs.”
Two other studies assessed the effectiveness of a 6-week cognitive-behavioral intervention for youth called Treatment and Education Approach for Childhood-Onset Lupus (TEACH). One study found that remote delivery of TEACH resulted in improved mood symptoms and reduced fatigue, and another found the program particularly effective in improving mood for patients deemed “high risk” because of greater depression and fatigue symptoms.
The impact of growing mental health problems has been enormous both in the pediatric rheumatology population and society at large, Daria Sosna, MSc, a research coordinator at the University of Calgary (Alta.), said in an interview as she visited the research posters related to psychological stress and depression.
“We need to do something,” said Ms. Sosna, whose department is currently applying for funding to develop a research project to improve mental health outcomes in adolescents with lupus. “This population, specifically, has higher numbers than anyone else does because they have chronic illness” – and those issues need to be addressed.
High psychological stress levels
The study looking at psychological stress in pediatric rheumatology patients, led by Natalie Rosenwasser, MD, of Seattle Children’s Hospital, relied on cross-sectional data from patients enrolled in two Childhood Arthritis and Rheumatology Research Alliance sites, one in Utah and one in Seattle. The average age of the 71 patients who completed the surveys was 13, and the researchers reported the findings in two separate age groups: those aged 13-17, who completed the surveys themselves, and those aged 8-12, whose parents completed the surveys. Nearly all the patients (94.4%) had JIA, but one had lupus and three had juvenile dermatomyositis.
The participants completed the Patient-Reported Outcomes Measurement Information System (PROMIS) for psychological stress, physical stress, and depressive symptoms. They also filled out the National Institutes of Health–Toolbox Perceived Stress survey, the 9-item Patient Health Questionnaire (PHQ-9), the Screen for Child Anxiety Related Disorders (SCARED), a visual analog scale for COVID-related distress, and a questionnaire asking about how receptive they were to mental health screening. The researchers determined that a score 1 standard deviation above the mean on the PROMIS and NIH-Toolbox assessments qualified as a high level of psychological stress.
“There are data that suggest that psychological stress can be a precursor to depression and anxiety, which raises the concern that not every patient who’s experiencing mental health symptoms is going to be picked up on traditional measures that meet that clinical threshold, but they may really need interventions to protect their mental health,” presenter Erin Treemarcki, DO, an assistant professor of pediatric rheumatology at the University of Utah, Salt Lake City, said in an interview. “Not every patient may necessarily need referral to a mental health specialist, but there are still potential interventions that we can do in the clinical setting to address mental health, which in turn can improve outcomes, including medication compliance and knowing how patients are feeling.”
More than one-third of the patients (39%) reported a high level of psychological stress, and 43% had elevated physical stress. Broken down by age, 26% of the teens and 15% of the younger patients reported high levels of perceived stress. The PROMIS only identified increased depressive symptoms in 26% of the participants, whereas more than half (54%) had a positive PHQ-9 depression screen. Furthermore, half the patients had SCARED scores (50%) that likely indicated anxiety disorder. Only 6% of patients reported severe stress specifically related to the pandemic, but most reported mild distress from the pandemic.
“Psychological stress was highly correlated with physical stress, perceived stress, depressive symptoms [PROMIS and PHQ-9], and anxiety,” the authors reported (P < .05). The authors next plan to expand their assessment to a third CARRA site and then explore the interaction between psychological distress and sociodemographic factors.
“There’s such an increase in mental health disorders right now, and we’re overwhelmed in general,” Ms. Sosna said in an interview. “There have to be interventions that approach this. We can use pharmacological approaches, we can use CBT, we can use a lot of these things that are very well established, and they’re absolutely fantastic, but we don’t necessarily have the resources or capabilities to do that all the time.”
Benefits of automated depression screening
To reduce the likelihood of depression screenings falling through the cracks during visits, Dr. Harper’s study assessed the impact of automating screens in an adolescent population. In her presentation, she noted previous research finding that nearly half of youth with lupus (47%) had depression, compared with 24% of adults with lupus. Pediatric patients have nearly three times the odds of depression and more than five times the odds of suicidal ideation, she told attendees. These mood disorders are correlated with greater physical disability, higher cardiovascular risk, more disease activity, higher risk of premature death, and decreased educational attainment, medication compliance, and quality of life.
Despite recommendations for depression screening from the U.S. Preventive Services Task Force and the American Academy of Pediatrics, only 2% of pediatric rheumatology patients are routinely screened for depression with a validated instrument, and only 7% of those with depressive symptoms are screened, according to a 2016 study that Dr. Harper cited. Yet the same study found that nearly all pediatric rheumatologists (95%) supported routine depression screening every 6-12 months. Hence her team’s decision to test whether automating screening improved their screening rates.
Their population included lupus patients aged 12 and older seen at Nationwide Children’s Hospital between 2014 and 2022. Initially, patients completed the PHQ-9 on paper, which was then transcribed into the electronic health record. The process became automated and administered on an iPad at every visit in 2022. Positive screens – those endorsing suicidality or with a score of at least 10 – caused an alert to pop up for clinicians during their workflow so that they would talk to the mental health team about the patient’s needs.
A total of 149 patients completed 529 screenings during the study’s 8 years. Only 1 patient completed a PHQ-9 in 2014, which increased to just 17 patients in 2017. Automation resulted in 225 screens (P < .01). Subsequently, positive screens increased from 0% in 2014 to 25%-30% in 2018-2021, but then fell to 12% in 2022 (P < .01). The median PHQ-9 score was 3; overall scores decreased as screening increased.
The overall incidence of positive screens during the study period was 20% and prevalence was 38%, the authors reported. Of the 10 automated alerts triggered by positive screens, 90% resulted in a meeting with a psychologist or social worker, and 90% completed a suicide risk assessment. The intrusive alert for clinicians requires them to acknowledge the alert, agreeing to initiate a risk assessment, before they can enter data into the patient’s chart.
The study findings reveal “that you can successfully screen a high-risk population using an automated, seamless process, and you can alert providers without too much disruption to their typical clinic flow,” Dr. Harper told attendees. “And all of these processes have led to sustainability for routine depression screening in our lupus clinic.”
Dr. Harper’s team next plans to expand the automated screenings to populations with other diseases, to add an automated screening for anxiety, and to explore how PHQ-9 scores correlate with disease activity.
Treating patients’ mental health
Another two other abstracts at the symposium looked at another option, the 6-week cognitive-behavioral TEACH program. Deborah Levy, MD, MS, an associate professor of pediatrics at the University of Toronto and the clinical director of rheumatology at The Hospital for Sick Children, and colleagues assessed the program’s success when delivered remotely to adolescent patients with lupus. Pilot testing with TEACH had already shown improvements in fatigue and mood, Dr. Levy told attendees, but barriers to in-person delivery limited its utility even before the pandemic, so this study aimed to determine a remote version’s feasibility and effects, compared with treatment as usual.
The randomized, controlled trial, led by Natoshia Cunningham, PhD, from Michigan State University, Grand Rapids, included 57 participants, aged 12-22, from seven U.S. and Canadian rheumatology sites. All had been diagnosed with childhood-onset SLE by age 18 and had elevated symptoms in fatigue, pain, or depression. A PROMIS Fatigue T score of 60 or greater indicated elevated fatigue scores, whereas a high pain score was at least a 3/10 on a visual analog scale, and a high depression T score was at least a 60 but not higher than 80 on the Children’s Depression Inventory–2 or the Beck Depression Inventory–II (depending on the patient’s age).
Patients with other chronic medical conditions, developmental delays, or untreated major psychiatric illness were excluded from the study, as were patients who were receiving overlapping treatment, such as cognitive-behavioral therapy for pain or mood. Thirty patients were randomly assigned to receive treatment as usual while 27 patients were assigned to participate in the remote TEACH program.
Nearly all the patients (94%) were female, but they were racially diverse, with 42% White, 28% Asian, 19% Black, 19% Hispanic, and 4% multiracial. The patients were an average 16 years old and had been diagnosed for a median 5 years. Three of the intervention’s six modules involved the caregivers or, for older patients, their partners if desired. The communication strategies taught in the program were also tailored to patients’ ages.
“All of these strategies are educational, cognitive, behavioral, mindfulness strategies that target fatigue [and] pain, and they also developed web content for participants to use on their own,” Dr. Levy told attendees.
The researchers had complete postassessment data from 88% of participants, but they also reported some of the statements made during qualitative interviews about the program’s feasibility.
“I think it makes people more aware of themselves to become a better version of themselves, whether that’s in their normal life or in handling a lupus kind of life,” one participant said about the program’s benefits. Another appreciated the “alternative ways of thinking,” including “being more mindful of my thoughts and how those kind of aggravate my stress.”
The quantitative findings revealed a statistically significant reduction in depressive symptoms and fatigue for TEACH participants, compared with treatment as usual. Mood scores fell by an average 13.7 points in the TEACH group, compared with a drop of 2.4 points in the treatment as usual group (P < .001). Scores for fatigue fell 9.16 points in the TEACH group and 2.93 in the control group (P = .003). No statistically significant difference showed up in pain scores between the groups, although pain, medication adherence, and disease activity did improve slightly more in the TEACH group.
In addition to the significant improvements in mood and fatigue, therefore, “completion of TEACH may be associated with improved medication adherence and disease activity versus treatment as usual,” Dr. Levy said.
A much smaller study authored by some of the same researchers also assessed TEACH’s impact not in remote form but in terms of its value specifically for adolescent patients with SLE and elevated depression and fatigue scores. Comparison of 6 high-risk patients with 10 low-risk patients who underwent TEACH suggested that the program was especially effective for improving depression in high-risk patients since these patients had a statistically significantly greater improvement in mood. Fatigue, pain, anxiety, quality of life, and disease activity scores did not statistically differ between the groups.
Authors of the automated depression screening study reported no disclosures or outside funding. The study assessing psychological distress was funded by a CARRA–Arthritis Foundation grant, and the authors reported no disclosures. The remote TEACH study was funded by a CARRA–Arthritis Foundation grant, and all but one author reported no disclosures. One author had disclosures with Janssen, Roche, and Sobi. The high-risk TEACH study was also funded by a CARRA grant, and the authors had no disclosures.
NEW ORLEANS – Pediatric patients with rheumatologic diseases experience a particularly high prevalence of psychological distress and depression and anxiety symptoms, according to research presented at the Pediatric Rheumatology Symposium. Although this finding is not necessarily surprising, the extent to which depression and psychological distress impacts these young patients’ quality of life has led to greater research and innovation in seeking ways to identify, address, and treat depression and anxiety in children and adolescents with diseases such as juvenile idiopathic arthritis (JIA) or systemic lupus erythematosus (SLE).
Accordingly, other studies presented at the conference examined more efficient ways to screen adolescent patients for depression and assessed programs designed to improve symptoms. In fact, the American College of Rheumatology award for the top Quality, Health Services, and Education Research abstract at this year’s symposium went to Lauren Harper, MD, a pediatric rheumatology fellow at Nationwide Children’s Hospital, Columbus, whose research examined the effects of automating depression screening during check-in for adolescent patients with SLE. Her findings revealed that automation of screening increased detection of depression and suicidality, thereby increasing interventions and ultimately resulting in a reduction in depression prevalence.
“The key clinical takeaway is that mental health screening is really important – it affects our patients in so many different ways – and it’s very doable in your rheumatology clinic,” Dr. Harper said in an interview. “It’s also important because they’re coming to us very frequently, but they don’t see their PCP [primary care provider] very often, so we can’t leave screening to the PCPs.”
Two other studies assessed the effectiveness of a 6-week cognitive-behavioral intervention for youth called Treatment and Education Approach for Childhood-Onset Lupus (TEACH). One study found that remote delivery of TEACH resulted in improved mood symptoms and reduced fatigue, and another found the program particularly effective in improving mood for patients deemed “high risk” because of greater depression and fatigue symptoms.
The impact of growing mental health problems has been enormous both in the pediatric rheumatology population and society at large, Daria Sosna, MSc, a research coordinator at the University of Calgary (Alta.), said in an interview as she visited the research posters related to psychological stress and depression.
“We need to do something,” said Ms. Sosna, whose department is currently applying for funding to develop a research project to improve mental health outcomes in adolescents with lupus. “This population, specifically, has higher numbers than anyone else does because they have chronic illness” – and those issues need to be addressed.
High psychological stress levels
The study looking at psychological stress in pediatric rheumatology patients, led by Natalie Rosenwasser, MD, of Seattle Children’s Hospital, relied on cross-sectional data from patients enrolled in two Childhood Arthritis and Rheumatology Research Alliance sites, one in Utah and one in Seattle. The average age of the 71 patients who completed the surveys was 13, and the researchers reported the findings in two separate age groups: those aged 13-17, who completed the surveys themselves, and those aged 8-12, whose parents completed the surveys. Nearly all the patients (94.4%) had JIA, but one had lupus and three had juvenile dermatomyositis.
The participants completed the Patient-Reported Outcomes Measurement Information System (PROMIS) for psychological stress, physical stress, and depressive symptoms. They also filled out the National Institutes of Health–Toolbox Perceived Stress survey, the 9-item Patient Health Questionnaire (PHQ-9), the Screen for Child Anxiety Related Disorders (SCARED), a visual analog scale for COVID-related distress, and a questionnaire asking about how receptive they were to mental health screening. The researchers determined that a score 1 standard deviation above the mean on the PROMIS and NIH-Toolbox assessments qualified as a high level of psychological stress.
“There are data that suggest that psychological stress can be a precursor to depression and anxiety, which raises the concern that not every patient who’s experiencing mental health symptoms is going to be picked up on traditional measures that meet that clinical threshold, but they may really need interventions to protect their mental health,” presenter Erin Treemarcki, DO, an assistant professor of pediatric rheumatology at the University of Utah, Salt Lake City, said in an interview. “Not every patient may necessarily need referral to a mental health specialist, but there are still potential interventions that we can do in the clinical setting to address mental health, which in turn can improve outcomes, including medication compliance and knowing how patients are feeling.”
More than one-third of the patients (39%) reported a high level of psychological stress, and 43% had elevated physical stress. Broken down by age, 26% of the teens and 15% of the younger patients reported high levels of perceived stress. The PROMIS only identified increased depressive symptoms in 26% of the participants, whereas more than half (54%) had a positive PHQ-9 depression screen. Furthermore, half the patients had SCARED scores (50%) that likely indicated anxiety disorder. Only 6% of patients reported severe stress specifically related to the pandemic, but most reported mild distress from the pandemic.
“Psychological stress was highly correlated with physical stress, perceived stress, depressive symptoms [PROMIS and PHQ-9], and anxiety,” the authors reported (P < .05). The authors next plan to expand their assessment to a third CARRA site and then explore the interaction between psychological distress and sociodemographic factors.
“There’s such an increase in mental health disorders right now, and we’re overwhelmed in general,” Ms. Sosna said in an interview. “There have to be interventions that approach this. We can use pharmacological approaches, we can use CBT, we can use a lot of these things that are very well established, and they’re absolutely fantastic, but we don’t necessarily have the resources or capabilities to do that all the time.”
Benefits of automated depression screening
To reduce the likelihood of depression screenings falling through the cracks during visits, Dr. Harper’s study assessed the impact of automating screens in an adolescent population. In her presentation, she noted previous research finding that nearly half of youth with lupus (47%) had depression, compared with 24% of adults with lupus. Pediatric patients have nearly three times the odds of depression and more than five times the odds of suicidal ideation, she told attendees. These mood disorders are correlated with greater physical disability, higher cardiovascular risk, more disease activity, higher risk of premature death, and decreased educational attainment, medication compliance, and quality of life.
Despite recommendations for depression screening from the U.S. Preventive Services Task Force and the American Academy of Pediatrics, only 2% of pediatric rheumatology patients are routinely screened for depression with a validated instrument, and only 7% of those with depressive symptoms are screened, according to a 2016 study that Dr. Harper cited. Yet the same study found that nearly all pediatric rheumatologists (95%) supported routine depression screening every 6-12 months. Hence her team’s decision to test whether automating screening improved their screening rates.
Their population included lupus patients aged 12 and older seen at Nationwide Children’s Hospital between 2014 and 2022. Initially, patients completed the PHQ-9 on paper, which was then transcribed into the electronic health record. The process became automated and administered on an iPad at every visit in 2022. Positive screens – those endorsing suicidality or with a score of at least 10 – caused an alert to pop up for clinicians during their workflow so that they would talk to the mental health team about the patient’s needs.
A total of 149 patients completed 529 screenings during the study’s 8 years. Only 1 patient completed a PHQ-9 in 2014, which increased to just 17 patients in 2017. Automation resulted in 225 screens (P < .01). Subsequently, positive screens increased from 0% in 2014 to 25%-30% in 2018-2021, but then fell to 12% in 2022 (P < .01). The median PHQ-9 score was 3; overall scores decreased as screening increased.
The overall incidence of positive screens during the study period was 20% and prevalence was 38%, the authors reported. Of the 10 automated alerts triggered by positive screens, 90% resulted in a meeting with a psychologist or social worker, and 90% completed a suicide risk assessment. The intrusive alert for clinicians requires them to acknowledge the alert, agreeing to initiate a risk assessment, before they can enter data into the patient’s chart.
The study findings reveal “that you can successfully screen a high-risk population using an automated, seamless process, and you can alert providers without too much disruption to their typical clinic flow,” Dr. Harper told attendees. “And all of these processes have led to sustainability for routine depression screening in our lupus clinic.”
Dr. Harper’s team next plans to expand the automated screenings to populations with other diseases, to add an automated screening for anxiety, and to explore how PHQ-9 scores correlate with disease activity.
Treating patients’ mental health
Another two other abstracts at the symposium looked at another option, the 6-week cognitive-behavioral TEACH program. Deborah Levy, MD, MS, an associate professor of pediatrics at the University of Toronto and the clinical director of rheumatology at The Hospital for Sick Children, and colleagues assessed the program’s success when delivered remotely to adolescent patients with lupus. Pilot testing with TEACH had already shown improvements in fatigue and mood, Dr. Levy told attendees, but barriers to in-person delivery limited its utility even before the pandemic, so this study aimed to determine a remote version’s feasibility and effects, compared with treatment as usual.
The randomized, controlled trial, led by Natoshia Cunningham, PhD, from Michigan State University, Grand Rapids, included 57 participants, aged 12-22, from seven U.S. and Canadian rheumatology sites. All had been diagnosed with childhood-onset SLE by age 18 and had elevated symptoms in fatigue, pain, or depression. A PROMIS Fatigue T score of 60 or greater indicated elevated fatigue scores, whereas a high pain score was at least a 3/10 on a visual analog scale, and a high depression T score was at least a 60 but not higher than 80 on the Children’s Depression Inventory–2 or the Beck Depression Inventory–II (depending on the patient’s age).
Patients with other chronic medical conditions, developmental delays, or untreated major psychiatric illness were excluded from the study, as were patients who were receiving overlapping treatment, such as cognitive-behavioral therapy for pain or mood. Thirty patients were randomly assigned to receive treatment as usual while 27 patients were assigned to participate in the remote TEACH program.
Nearly all the patients (94%) were female, but they were racially diverse, with 42% White, 28% Asian, 19% Black, 19% Hispanic, and 4% multiracial. The patients were an average 16 years old and had been diagnosed for a median 5 years. Three of the intervention’s six modules involved the caregivers or, for older patients, their partners if desired. The communication strategies taught in the program were also tailored to patients’ ages.
“All of these strategies are educational, cognitive, behavioral, mindfulness strategies that target fatigue [and] pain, and they also developed web content for participants to use on their own,” Dr. Levy told attendees.
The researchers had complete postassessment data from 88% of participants, but they also reported some of the statements made during qualitative interviews about the program’s feasibility.
“I think it makes people more aware of themselves to become a better version of themselves, whether that’s in their normal life or in handling a lupus kind of life,” one participant said about the program’s benefits. Another appreciated the “alternative ways of thinking,” including “being more mindful of my thoughts and how those kind of aggravate my stress.”
The quantitative findings revealed a statistically significant reduction in depressive symptoms and fatigue for TEACH participants, compared with treatment as usual. Mood scores fell by an average 13.7 points in the TEACH group, compared with a drop of 2.4 points in the treatment as usual group (P < .001). Scores for fatigue fell 9.16 points in the TEACH group and 2.93 in the control group (P = .003). No statistically significant difference showed up in pain scores between the groups, although pain, medication adherence, and disease activity did improve slightly more in the TEACH group.
In addition to the significant improvements in mood and fatigue, therefore, “completion of TEACH may be associated with improved medication adherence and disease activity versus treatment as usual,” Dr. Levy said.
A much smaller study authored by some of the same researchers also assessed TEACH’s impact not in remote form but in terms of its value specifically for adolescent patients with SLE and elevated depression and fatigue scores. Comparison of 6 high-risk patients with 10 low-risk patients who underwent TEACH suggested that the program was especially effective for improving depression in high-risk patients since these patients had a statistically significantly greater improvement in mood. Fatigue, pain, anxiety, quality of life, and disease activity scores did not statistically differ between the groups.
Authors of the automated depression screening study reported no disclosures or outside funding. The study assessing psychological distress was funded by a CARRA–Arthritis Foundation grant, and the authors reported no disclosures. The remote TEACH study was funded by a CARRA–Arthritis Foundation grant, and all but one author reported no disclosures. One author had disclosures with Janssen, Roche, and Sobi. The high-risk TEACH study was also funded by a CARRA grant, and the authors had no disclosures.
AT PRSYM 2023