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Docs reveal perils of giving medical advice to friends and family
Stephen Pribut, DPM, a sports medicine podiatrist based in Washington, has had many friends or family members ask him for medical advice. It’s a scenario every doctor will face at one point or another in their careers, and it’s never an easy one.
Dr. Pribut received a call from a friend about a sore shoulder from swimming, saying that his doctor had dismissed the potential for a rotator cuff injury. “Months later, images revealed it was a rotator cuff tear and he wanted my advice,” says Dr. Pribut.
Not being a shoulder specialist, Dr. Pribut limited his input. “I told him to consider a good physical therapist or a shoulder specialist and gave him some alternative strokes for swimming that hopefully wouldn’t aggravate the injury,” he explains.
But he admits some situations are challenging. “I had a relative asking about a third party with an ankle injury. I advised he hold off on using a balance board until things healed, and to make sure he went to see a specialist. Unfortunately, he went to his general practitioner who likely knows nothing about ankle anatomy,” says Dr. Pribut.
“I finally saw a photo, which revealed swelling higher up on the ankle and no evidence of a hematoma – much lower than we would see in an ankle ligament injury. I would like him to see a sports podiatrist or foot and ankle orthopedist, but now I have to stay calm when the advice isn’t followed,” he says.
When asked, “Do you give medical advice to your friends?” 96% of respondents answered yes.
Yazan Abou-Ismail, MD, assistant professor of medicine in the division of hematology at the University of Utah, Salt Lake City, has often faced questions from friends and family, particularly throughout the COVID-19 pandemic. “How you respond is something all physicians need to analyze carefully,” he says. “I get questions on a regular basis, but this greatly increased with COVID.”
“Sharing general information is okay, and it’s even a requirement that we educate on such topics,” says Dr. Abou-Ismail. “But if someone knows they have COVID, for instance, and wants advice on how to proceed, it’s important to send them to their primary care physician for an evaluation rather than give them instructions on care.”
Dr. Abou-Ismail says that most “curbside consulting” equates to lack of an ethical follow-up. “If you gave medical advice without having assessed them, you’re lacking the medical history, a physical exam, and you should not be giving advice,” he says. “This applies to follow-ups, too.”
Throughout the pandemic, Dr. Abou-Ismail’s requests for advice on COVID even extended to online inquiries, often from strangers. “This is not a place to do a formal assessment,” he reminds. “But there are certain types of advice you can offer appropriately.”
Dr. Abou-Ismail considers safe advice to be simple public health messages that stay far out of specifics. Things like “don’t smoke,” or “eat a healthy diet,” and “get enough sleep,” fall into this safety zone. Even, “What is XYZ disease?” or “How do COVID vaccines work?” are topics he says he answers comfortably.
“But telling someone you need a specific treatment for a condition is inappropriate,” he explains. “This is a general way of practicing medicine – your advice should never venture into the potential of doing harm.”
This approach is exactly in line with legal advice, according to Jeff Caesar Chukwuma, founder and senior partner at Chukwuma Law Group, Miami. “It doesn’t mean that doctors should never give medical advice to friends or family, but if they do, they should make sure to take several precautions to protect both themselves and their family and friends,” he says.
When the request for medical advice from an acquaintance migrates into areas in which a physician is not a specialist, sharing recommendations gets even trickier – and more ethically questionable.
Says Mr. Chukwuma, “Doctors should avoid giving advice in areas outside their area of expertise to lower the possibility of providing erroneous or harmful information,” he says.
How to stay safe when asked for advice
The American Medical Association has weighed in on the topic. In the Code of Medical Ethics Opinion 1.2.1, the AMA states that, “Treating oneself or a member of one’s own family poses several challenges for physicians, including concerns about professional objectivity, patient autonomy, and informed consent.”
What about friends or acquaintances, however?
Even so, some respondents voiced their concerns with the scenario. Responses like, “Due to ethics, I would prefer they go and get first, second, and third opinions,” and “Usually the medical advice is very basic first aid (often mental health first aid), and if it’s anything remotely more complicated, I direct them to the appropriate provider.”
The AMA places advising friends in the same basket as advising and treating family members or oneself. In an article appearing in the AMA Journal of Ethics, Horacio Hojman, MD, of Tufts University School of Medicine, Boston, weighed in: “First and foremost, patients deserve objectivity from their doctors. When a physician is emotionally involved with a patient, that physician’s objectivity can be called into question.”
Why is medical advice so thorny when dealing with friends or relatives?
In some cases, a physician might not ask a friend relevant personal questions about his or her medical history, for instance. Or the friend might not want to share details with the doctor. In either case, the lack of information exchange can lead to improper advice.
The issue of giving medical advice to friends, family, and acquaintances can also wade into legal territory. “Personally or professionally, trust is the decisive factor that puts us at ease with the people we surround ourselves with,” says Mr. Chukwuma. “Nowhere is this truer than in medicine, where we approach doctors with some of the most sensitive matters in our lives and entrust our care to them, especially when the physician in question is a close friend or family member.”
Mr. Chukwuma points out that, while there are few strict legal prohibitions against doctors providing care or advice to family and friends, the AMA’s code of ethics states that such action should be reserved for rare situations, such as emergency settings or isolated settings where there is no other qualified physician available, or for minor, not long-term problems.
This was part of the equation for Dr. Pribut when helping his mother navigate her treatment for breast cancer. “With close relatives, offering advice and help can be very hard,” he says.
“This is to protect both patients and doctors,” says Mr. Chukwuma. “Although seeking advice from a family member or friend who is a doctor may be more convenient for a patient, they run the risk of receiving inadequate care by not going in for a formal medical visit complete with tests, medical examination, and follow-up care.”
Mr. Chukwuma offers guidance on how to share medical advice ethically and legally with family, friends, and acquaintances. “First, as much as possible, speak to general medical facts and knowledge rather than comment directly on the patient’s particular situation,” he says. “In the absence of thorough examination and tests, the doctor’s knowledge of a patient’s condition is limited, therefore, you should take care not to provide seemingly definitive answers on that patient’s unique condition in situations where they can’t rely on data to back up their advice and recommendations.”
The AMA’s Journal of Ethics article shares these tips for staying on the right side of the ethical line when dealing with friends and family members:
- Politely decline.
- Offer other forms of assistance – this might help a friend find the right qualified physician – as Dr. Pribut tends to do. Maybe help in navigating the sometimes-confusing health care system.
- Don’t hesitate in an emergency – the old “is there a doctor on board,” scenario on a plane when someone is in distress is a perfectly acceptable, and recommended, time to step in, even if it is a friend or family member.
Dr. Pribut, a long-time veteran of the tricky medical waters involving friends and family, has this to offer: “Be cautious and always stay in the realm of what you know,” he says. “Always encourage people to seek an opinion from a qualified doctor. Help them find a reputable doctor if that’s useful.”
Mr. Chukwuma adds also that doctors should stand firm when pushed by a friend or family member, especially when offering advice, even if it’s in the form of general education. “The doctor should make it clear to the family member or friend that their advice in no way takes the place of actual treatment or examination by a medical professional and that, if need be, the patient should seek formal medical help from another doctor, ideally one not related to or friends with the patient,” he says.
A version of this article first appeared on Medscape.com.
Stephen Pribut, DPM, a sports medicine podiatrist based in Washington, has had many friends or family members ask him for medical advice. It’s a scenario every doctor will face at one point or another in their careers, and it’s never an easy one.
Dr. Pribut received a call from a friend about a sore shoulder from swimming, saying that his doctor had dismissed the potential for a rotator cuff injury. “Months later, images revealed it was a rotator cuff tear and he wanted my advice,” says Dr. Pribut.
Not being a shoulder specialist, Dr. Pribut limited his input. “I told him to consider a good physical therapist or a shoulder specialist and gave him some alternative strokes for swimming that hopefully wouldn’t aggravate the injury,” he explains.
But he admits some situations are challenging. “I had a relative asking about a third party with an ankle injury. I advised he hold off on using a balance board until things healed, and to make sure he went to see a specialist. Unfortunately, he went to his general practitioner who likely knows nothing about ankle anatomy,” says Dr. Pribut.
“I finally saw a photo, which revealed swelling higher up on the ankle and no evidence of a hematoma – much lower than we would see in an ankle ligament injury. I would like him to see a sports podiatrist or foot and ankle orthopedist, but now I have to stay calm when the advice isn’t followed,” he says.
When asked, “Do you give medical advice to your friends?” 96% of respondents answered yes.
Yazan Abou-Ismail, MD, assistant professor of medicine in the division of hematology at the University of Utah, Salt Lake City, has often faced questions from friends and family, particularly throughout the COVID-19 pandemic. “How you respond is something all physicians need to analyze carefully,” he says. “I get questions on a regular basis, but this greatly increased with COVID.”
“Sharing general information is okay, and it’s even a requirement that we educate on such topics,” says Dr. Abou-Ismail. “But if someone knows they have COVID, for instance, and wants advice on how to proceed, it’s important to send them to their primary care physician for an evaluation rather than give them instructions on care.”
Dr. Abou-Ismail says that most “curbside consulting” equates to lack of an ethical follow-up. “If you gave medical advice without having assessed them, you’re lacking the medical history, a physical exam, and you should not be giving advice,” he says. “This applies to follow-ups, too.”
Throughout the pandemic, Dr. Abou-Ismail’s requests for advice on COVID even extended to online inquiries, often from strangers. “This is not a place to do a formal assessment,” he reminds. “But there are certain types of advice you can offer appropriately.”
Dr. Abou-Ismail considers safe advice to be simple public health messages that stay far out of specifics. Things like “don’t smoke,” or “eat a healthy diet,” and “get enough sleep,” fall into this safety zone. Even, “What is XYZ disease?” or “How do COVID vaccines work?” are topics he says he answers comfortably.
“But telling someone you need a specific treatment for a condition is inappropriate,” he explains. “This is a general way of practicing medicine – your advice should never venture into the potential of doing harm.”
This approach is exactly in line with legal advice, according to Jeff Caesar Chukwuma, founder and senior partner at Chukwuma Law Group, Miami. “It doesn’t mean that doctors should never give medical advice to friends or family, but if they do, they should make sure to take several precautions to protect both themselves and their family and friends,” he says.
When the request for medical advice from an acquaintance migrates into areas in which a physician is not a specialist, sharing recommendations gets even trickier – and more ethically questionable.
Says Mr. Chukwuma, “Doctors should avoid giving advice in areas outside their area of expertise to lower the possibility of providing erroneous or harmful information,” he says.
How to stay safe when asked for advice
The American Medical Association has weighed in on the topic. In the Code of Medical Ethics Opinion 1.2.1, the AMA states that, “Treating oneself or a member of one’s own family poses several challenges for physicians, including concerns about professional objectivity, patient autonomy, and informed consent.”
What about friends or acquaintances, however?
Even so, some respondents voiced their concerns with the scenario. Responses like, “Due to ethics, I would prefer they go and get first, second, and third opinions,” and “Usually the medical advice is very basic first aid (often mental health first aid), and if it’s anything remotely more complicated, I direct them to the appropriate provider.”
The AMA places advising friends in the same basket as advising and treating family members or oneself. In an article appearing in the AMA Journal of Ethics, Horacio Hojman, MD, of Tufts University School of Medicine, Boston, weighed in: “First and foremost, patients deserve objectivity from their doctors. When a physician is emotionally involved with a patient, that physician’s objectivity can be called into question.”
Why is medical advice so thorny when dealing with friends or relatives?
In some cases, a physician might not ask a friend relevant personal questions about his or her medical history, for instance. Or the friend might not want to share details with the doctor. In either case, the lack of information exchange can lead to improper advice.
The issue of giving medical advice to friends, family, and acquaintances can also wade into legal territory. “Personally or professionally, trust is the decisive factor that puts us at ease with the people we surround ourselves with,” says Mr. Chukwuma. “Nowhere is this truer than in medicine, where we approach doctors with some of the most sensitive matters in our lives and entrust our care to them, especially when the physician in question is a close friend or family member.”
Mr. Chukwuma points out that, while there are few strict legal prohibitions against doctors providing care or advice to family and friends, the AMA’s code of ethics states that such action should be reserved for rare situations, such as emergency settings or isolated settings where there is no other qualified physician available, or for minor, not long-term problems.
This was part of the equation for Dr. Pribut when helping his mother navigate her treatment for breast cancer. “With close relatives, offering advice and help can be very hard,” he says.
“This is to protect both patients and doctors,” says Mr. Chukwuma. “Although seeking advice from a family member or friend who is a doctor may be more convenient for a patient, they run the risk of receiving inadequate care by not going in for a formal medical visit complete with tests, medical examination, and follow-up care.”
Mr. Chukwuma offers guidance on how to share medical advice ethically and legally with family, friends, and acquaintances. “First, as much as possible, speak to general medical facts and knowledge rather than comment directly on the patient’s particular situation,” he says. “In the absence of thorough examination and tests, the doctor’s knowledge of a patient’s condition is limited, therefore, you should take care not to provide seemingly definitive answers on that patient’s unique condition in situations where they can’t rely on data to back up their advice and recommendations.”
The AMA’s Journal of Ethics article shares these tips for staying on the right side of the ethical line when dealing with friends and family members:
- Politely decline.
- Offer other forms of assistance – this might help a friend find the right qualified physician – as Dr. Pribut tends to do. Maybe help in navigating the sometimes-confusing health care system.
- Don’t hesitate in an emergency – the old “is there a doctor on board,” scenario on a plane when someone is in distress is a perfectly acceptable, and recommended, time to step in, even if it is a friend or family member.
Dr. Pribut, a long-time veteran of the tricky medical waters involving friends and family, has this to offer: “Be cautious and always stay in the realm of what you know,” he says. “Always encourage people to seek an opinion from a qualified doctor. Help them find a reputable doctor if that’s useful.”
Mr. Chukwuma adds also that doctors should stand firm when pushed by a friend or family member, especially when offering advice, even if it’s in the form of general education. “The doctor should make it clear to the family member or friend that their advice in no way takes the place of actual treatment or examination by a medical professional and that, if need be, the patient should seek formal medical help from another doctor, ideally one not related to or friends with the patient,” he says.
A version of this article first appeared on Medscape.com.
Stephen Pribut, DPM, a sports medicine podiatrist based in Washington, has had many friends or family members ask him for medical advice. It’s a scenario every doctor will face at one point or another in their careers, and it’s never an easy one.
Dr. Pribut received a call from a friend about a sore shoulder from swimming, saying that his doctor had dismissed the potential for a rotator cuff injury. “Months later, images revealed it was a rotator cuff tear and he wanted my advice,” says Dr. Pribut.
Not being a shoulder specialist, Dr. Pribut limited his input. “I told him to consider a good physical therapist or a shoulder specialist and gave him some alternative strokes for swimming that hopefully wouldn’t aggravate the injury,” he explains.
But he admits some situations are challenging. “I had a relative asking about a third party with an ankle injury. I advised he hold off on using a balance board until things healed, and to make sure he went to see a specialist. Unfortunately, he went to his general practitioner who likely knows nothing about ankle anatomy,” says Dr. Pribut.
“I finally saw a photo, which revealed swelling higher up on the ankle and no evidence of a hematoma – much lower than we would see in an ankle ligament injury. I would like him to see a sports podiatrist or foot and ankle orthopedist, but now I have to stay calm when the advice isn’t followed,” he says.
When asked, “Do you give medical advice to your friends?” 96% of respondents answered yes.
Yazan Abou-Ismail, MD, assistant professor of medicine in the division of hematology at the University of Utah, Salt Lake City, has often faced questions from friends and family, particularly throughout the COVID-19 pandemic. “How you respond is something all physicians need to analyze carefully,” he says. “I get questions on a regular basis, but this greatly increased with COVID.”
“Sharing general information is okay, and it’s even a requirement that we educate on such topics,” says Dr. Abou-Ismail. “But if someone knows they have COVID, for instance, and wants advice on how to proceed, it’s important to send them to their primary care physician for an evaluation rather than give them instructions on care.”
Dr. Abou-Ismail says that most “curbside consulting” equates to lack of an ethical follow-up. “If you gave medical advice without having assessed them, you’re lacking the medical history, a physical exam, and you should not be giving advice,” he says. “This applies to follow-ups, too.”
Throughout the pandemic, Dr. Abou-Ismail’s requests for advice on COVID even extended to online inquiries, often from strangers. “This is not a place to do a formal assessment,” he reminds. “But there are certain types of advice you can offer appropriately.”
Dr. Abou-Ismail considers safe advice to be simple public health messages that stay far out of specifics. Things like “don’t smoke,” or “eat a healthy diet,” and “get enough sleep,” fall into this safety zone. Even, “What is XYZ disease?” or “How do COVID vaccines work?” are topics he says he answers comfortably.
“But telling someone you need a specific treatment for a condition is inappropriate,” he explains. “This is a general way of practicing medicine – your advice should never venture into the potential of doing harm.”
This approach is exactly in line with legal advice, according to Jeff Caesar Chukwuma, founder and senior partner at Chukwuma Law Group, Miami. “It doesn’t mean that doctors should never give medical advice to friends or family, but if they do, they should make sure to take several precautions to protect both themselves and their family and friends,” he says.
When the request for medical advice from an acquaintance migrates into areas in which a physician is not a specialist, sharing recommendations gets even trickier – and more ethically questionable.
Says Mr. Chukwuma, “Doctors should avoid giving advice in areas outside their area of expertise to lower the possibility of providing erroneous or harmful information,” he says.
How to stay safe when asked for advice
The American Medical Association has weighed in on the topic. In the Code of Medical Ethics Opinion 1.2.1, the AMA states that, “Treating oneself or a member of one’s own family poses several challenges for physicians, including concerns about professional objectivity, patient autonomy, and informed consent.”
What about friends or acquaintances, however?
Even so, some respondents voiced their concerns with the scenario. Responses like, “Due to ethics, I would prefer they go and get first, second, and third opinions,” and “Usually the medical advice is very basic first aid (often mental health first aid), and if it’s anything remotely more complicated, I direct them to the appropriate provider.”
The AMA places advising friends in the same basket as advising and treating family members or oneself. In an article appearing in the AMA Journal of Ethics, Horacio Hojman, MD, of Tufts University School of Medicine, Boston, weighed in: “First and foremost, patients deserve objectivity from their doctors. When a physician is emotionally involved with a patient, that physician’s objectivity can be called into question.”
Why is medical advice so thorny when dealing with friends or relatives?
In some cases, a physician might not ask a friend relevant personal questions about his or her medical history, for instance. Or the friend might not want to share details with the doctor. In either case, the lack of information exchange can lead to improper advice.
The issue of giving medical advice to friends, family, and acquaintances can also wade into legal territory. “Personally or professionally, trust is the decisive factor that puts us at ease with the people we surround ourselves with,” says Mr. Chukwuma. “Nowhere is this truer than in medicine, where we approach doctors with some of the most sensitive matters in our lives and entrust our care to them, especially when the physician in question is a close friend or family member.”
Mr. Chukwuma points out that, while there are few strict legal prohibitions against doctors providing care or advice to family and friends, the AMA’s code of ethics states that such action should be reserved for rare situations, such as emergency settings or isolated settings where there is no other qualified physician available, or for minor, not long-term problems.
This was part of the equation for Dr. Pribut when helping his mother navigate her treatment for breast cancer. “With close relatives, offering advice and help can be very hard,” he says.
“This is to protect both patients and doctors,” says Mr. Chukwuma. “Although seeking advice from a family member or friend who is a doctor may be more convenient for a patient, they run the risk of receiving inadequate care by not going in for a formal medical visit complete with tests, medical examination, and follow-up care.”
Mr. Chukwuma offers guidance on how to share medical advice ethically and legally with family, friends, and acquaintances. “First, as much as possible, speak to general medical facts and knowledge rather than comment directly on the patient’s particular situation,” he says. “In the absence of thorough examination and tests, the doctor’s knowledge of a patient’s condition is limited, therefore, you should take care not to provide seemingly definitive answers on that patient’s unique condition in situations where they can’t rely on data to back up their advice and recommendations.”
The AMA’s Journal of Ethics article shares these tips for staying on the right side of the ethical line when dealing with friends and family members:
- Politely decline.
- Offer other forms of assistance – this might help a friend find the right qualified physician – as Dr. Pribut tends to do. Maybe help in navigating the sometimes-confusing health care system.
- Don’t hesitate in an emergency – the old “is there a doctor on board,” scenario on a plane when someone is in distress is a perfectly acceptable, and recommended, time to step in, even if it is a friend or family member.
Dr. Pribut, a long-time veteran of the tricky medical waters involving friends and family, has this to offer: “Be cautious and always stay in the realm of what you know,” he says. “Always encourage people to seek an opinion from a qualified doctor. Help them find a reputable doctor if that’s useful.”
Mr. Chukwuma adds also that doctors should stand firm when pushed by a friend or family member, especially when offering advice, even if it’s in the form of general education. “The doctor should make it clear to the family member or friend that their advice in no way takes the place of actual treatment or examination by a medical professional and that, if need be, the patient should seek formal medical help from another doctor, ideally one not related to or friends with the patient,” he says.
A version of this article first appeared on Medscape.com.
Attacking childhood anxiety in primary care
Multiple media outlets and numerous children’s professional organizations are discussing the child and adolescent mental health crisis. Finally, society at large seems to be taking notice that our kids are not okay, and that they haven’t been okay for a long time.
Over the past 5-7 years, both in my practice in tertiary children’s hospital emergency departments and in primary care pediatrics, I have seen a disturbing decline in kids’ mental well-being. What can a primary care physician do to make a difference? How do we capitalize on these discussions about mental health and illness now that it is rising to a priority status?
The U.S. Preventive Services Task Force recently drafted a statement of recommendations specifically discussing anxiety in children and adolescents. It shows supporting evidence that there is a moderate benefit to screening children 8-18 years old for anxiety. We know from the 2018-2019 National Survey of Children’s Health that almost 8% of children/adolescents ages 3-17 years old have an anxiety disorder. And among those 13-18 years old, the lifetime prevalence rises to nearly 33%, according to National Institutes of Health statistics.
Childhood anxiety unquestionably increases the chances of persistent anxiety or depression in adulthood. I have followed children who had excessive social anxiety from age 3 or 4 who progressed to generalized anxiety disorder as adolescents, usually when no intervention was done or when the family waited for the child to “outgrow” it. The DSM-5 has six separate categories for anxiety disorders in children and adolescents: generalized anxiety disorder, separation anxiety disorder, specific phobias, social phobia, agoraphobia, and panic disorder. Unfortunately, these illnesses cannot be wished away.
Screening, diagnosis, and follow-up
A few simple screening tools can be used to check for anxiety in children and adolescents. These include SCARED (Screen for Child Anxiety Related Emotional Disorders), GAD-7 (Generalized Anxiety Disorder-7), and/or the PHQ-A (Patient Health Questionnaire for Adolescents). Keep in mind that a screening tool is just that – a screen. Diagnostic confirmation and follow-up are appropriate after a positive screen. I like all of these particular screens as they are easy to administer and can be incorporated into a busy practice without extra training to administer. They are also easy for parents and patients to complete prior to a visit or during a visit.
Ideally, after a positive screen, the next step is to consult a child and adolescent psychiatrist (CAP); however, according to statistics from the American Academy of Child and Adolescent Psychiatry (AACAP), there are only 8,300 CAPs in the United States. The reality is that not a single state in the entire country has a “mostly sufficient supply” of CAP’s (defined as ≥ 47 per 100,000 children). In fact, most have a “severe shortage,” defined as 1-17 per 100,000 children
Adding a child/adolescent therapist is also necessary for patients 8 years old and up, but the harsh truth is that it may take up to several months before the child is seen. If a patient is in a rural or other underserved area, it may be even longer.
So, what does this mean for primary care physicians? When you are faced with a positive screening for childhood anxiety, the next step is “tag, you’re it!” Understandably, this is frightening for many physicians who feel unqualified.
Don’t be afraid! Like the old adage says, a journey of a thousand miles begins with a single step. Starting the conversation with patients and families is foremost. Physicians must be first in line to end the stigma surrounding mental illness, and the easiest way to do that is to start the conversation. Remember that anxiety in kids can present as classic fear or worry, but it also can present as irritability, anger outbursts, and attention issues. There have been so many patients referred to me for “being out of control” or “always angry” or “probable ADHD” who turned out to have significant anxiety.
Part of a routine medical evaluation includes obtaining personal, family, and social history; there should be no difference when considering an anxiety disorder. Obtaining information about family history, personality traits, environmental components, early attachment issues, developmental history, parental style, parental conflict, occupants in the home, any adverse childhood events, and history of child maltreatment is crucial. Assessing other risk factors, including socioeconomic status, race, ethnicity, and gender, is key as well. I have seen families literally breathe a sigh of relief when these questions are asked. Parents feel heard and seen. And, equally significant, so does the child/adolescent.
The ‘Big 4’
An in-depth assessment of patient and family lifestyle factors such as nutrition, sleep, physical activity/exercise, and screen time habits is also basic and essential. This kind of evaluation usually cannot be done in the typical 15-minute visit and often will need to be done over several patient visits. I have had numerous conversations with my patients regarding what I call the “Big 4” – simple but not easy concepts and actions. They include nutrition, sleep, exercise, and screen time. Parents will look at me and say, “I can’t believe I never thought of this!” Some of my favorite moments with patients over the years have involved partnering with the patient and family and encouraging them to do the “simple” but not “easy” things.
Nutrition
Does the child have proper nutrition? That is not meant to be an exercise in labeling foods as “good” or “bad” but meant to confirm whether there is a balance of different foods. It’s also a way of exploring whether there are family meals in the home. Family meals have been shown to have a protective factor for children’s social development and emotional regulation.
Sleep
Review the child’s sleep habits, such as difficulty falling/staying asleep, bedtime routine (soothing, relaxing activities vs. the opposite), nightmares, snoring, nighttime cough, etc. The physical sleeping environment is important as well. Is it quiet? Is it a crowded room?
Exercise
Discuss physical activity with the family. Is there time for the child to play outside without a defined goal? So much of a child’s day is structured, in school or with after-school activities, but can the kid simply be a kid? Does the family take walks together? Is it safe to play outside?
Screen time
Reviewing screen time is important for multiple reasons, especially because the more time spent in front of a TV, computer, or video game, the less time there is to be physically active. Numerous experts, including the American Academy of Pediatrics, recommend limits on screen time for children. For adolescents, there appears to be some evidence that excessive screen time contributes to depression/anxiety.
I am not embarrassed to say that with my own kids I felt so strongly about screen time that we did not own any kind of video games or iPad (that was theirs alone), and they spent the summers until they turned 14 building a two-story bamboo fort in our backyard instead of vegging out in front of the TV or computer. It didn’t hurt them a bit; one is an engineer and the other is in nursing school.
It is easy to see that lifestyle factors can come into play with childhood anxiety and are often ignored in the clinical setting. They do not involve technologically advanced techniques or procedures, which are more likely to be reimbursed. They are straightforward – but not easy – concepts, and require active participation from the patient and family. Some of my most exciting moments with families is when they return for follow up and say, “It worked!”
We need to be as comfortable taking care of a child’s mind and spirit as we are taking care of a child’s physical body. Is this easy in a busy office? No. Is this easy in a 15-minute visit? No. Is this easy with poor reimbursement from insurance companies? No. Is it necessary? Unequivocally YES. Start the conversation.
Tag, you’re it!
Dr. Contrucci is an assistant professor of pediatrics, clinical education department, Philadelphia College of Osteopathic Medicine, Georgia Campus, Suwanee. She disclosed no relevant conflict of interest.
A version of this article first appeared on Medscape.com.
Multiple media outlets and numerous children’s professional organizations are discussing the child and adolescent mental health crisis. Finally, society at large seems to be taking notice that our kids are not okay, and that they haven’t been okay for a long time.
Over the past 5-7 years, both in my practice in tertiary children’s hospital emergency departments and in primary care pediatrics, I have seen a disturbing decline in kids’ mental well-being. What can a primary care physician do to make a difference? How do we capitalize on these discussions about mental health and illness now that it is rising to a priority status?
The U.S. Preventive Services Task Force recently drafted a statement of recommendations specifically discussing anxiety in children and adolescents. It shows supporting evidence that there is a moderate benefit to screening children 8-18 years old for anxiety. We know from the 2018-2019 National Survey of Children’s Health that almost 8% of children/adolescents ages 3-17 years old have an anxiety disorder. And among those 13-18 years old, the lifetime prevalence rises to nearly 33%, according to National Institutes of Health statistics.
Childhood anxiety unquestionably increases the chances of persistent anxiety or depression in adulthood. I have followed children who had excessive social anxiety from age 3 or 4 who progressed to generalized anxiety disorder as adolescents, usually when no intervention was done or when the family waited for the child to “outgrow” it. The DSM-5 has six separate categories for anxiety disorders in children and adolescents: generalized anxiety disorder, separation anxiety disorder, specific phobias, social phobia, agoraphobia, and panic disorder. Unfortunately, these illnesses cannot be wished away.
Screening, diagnosis, and follow-up
A few simple screening tools can be used to check for anxiety in children and adolescents. These include SCARED (Screen for Child Anxiety Related Emotional Disorders), GAD-7 (Generalized Anxiety Disorder-7), and/or the PHQ-A (Patient Health Questionnaire for Adolescents). Keep in mind that a screening tool is just that – a screen. Diagnostic confirmation and follow-up are appropriate after a positive screen. I like all of these particular screens as they are easy to administer and can be incorporated into a busy practice without extra training to administer. They are also easy for parents and patients to complete prior to a visit or during a visit.
Ideally, after a positive screen, the next step is to consult a child and adolescent psychiatrist (CAP); however, according to statistics from the American Academy of Child and Adolescent Psychiatry (AACAP), there are only 8,300 CAPs in the United States. The reality is that not a single state in the entire country has a “mostly sufficient supply” of CAP’s (defined as ≥ 47 per 100,000 children). In fact, most have a “severe shortage,” defined as 1-17 per 100,000 children
Adding a child/adolescent therapist is also necessary for patients 8 years old and up, but the harsh truth is that it may take up to several months before the child is seen. If a patient is in a rural or other underserved area, it may be even longer.
So, what does this mean for primary care physicians? When you are faced with a positive screening for childhood anxiety, the next step is “tag, you’re it!” Understandably, this is frightening for many physicians who feel unqualified.
Don’t be afraid! Like the old adage says, a journey of a thousand miles begins with a single step. Starting the conversation with patients and families is foremost. Physicians must be first in line to end the stigma surrounding mental illness, and the easiest way to do that is to start the conversation. Remember that anxiety in kids can present as classic fear or worry, but it also can present as irritability, anger outbursts, and attention issues. There have been so many patients referred to me for “being out of control” or “always angry” or “probable ADHD” who turned out to have significant anxiety.
Part of a routine medical evaluation includes obtaining personal, family, and social history; there should be no difference when considering an anxiety disorder. Obtaining information about family history, personality traits, environmental components, early attachment issues, developmental history, parental style, parental conflict, occupants in the home, any adverse childhood events, and history of child maltreatment is crucial. Assessing other risk factors, including socioeconomic status, race, ethnicity, and gender, is key as well. I have seen families literally breathe a sigh of relief when these questions are asked. Parents feel heard and seen. And, equally significant, so does the child/adolescent.
The ‘Big 4’
An in-depth assessment of patient and family lifestyle factors such as nutrition, sleep, physical activity/exercise, and screen time habits is also basic and essential. This kind of evaluation usually cannot be done in the typical 15-minute visit and often will need to be done over several patient visits. I have had numerous conversations with my patients regarding what I call the “Big 4” – simple but not easy concepts and actions. They include nutrition, sleep, exercise, and screen time. Parents will look at me and say, “I can’t believe I never thought of this!” Some of my favorite moments with patients over the years have involved partnering with the patient and family and encouraging them to do the “simple” but not “easy” things.
Nutrition
Does the child have proper nutrition? That is not meant to be an exercise in labeling foods as “good” or “bad” but meant to confirm whether there is a balance of different foods. It’s also a way of exploring whether there are family meals in the home. Family meals have been shown to have a protective factor for children’s social development and emotional regulation.
Sleep
Review the child’s sleep habits, such as difficulty falling/staying asleep, bedtime routine (soothing, relaxing activities vs. the opposite), nightmares, snoring, nighttime cough, etc. The physical sleeping environment is important as well. Is it quiet? Is it a crowded room?
Exercise
Discuss physical activity with the family. Is there time for the child to play outside without a defined goal? So much of a child’s day is structured, in school or with after-school activities, but can the kid simply be a kid? Does the family take walks together? Is it safe to play outside?
Screen time
Reviewing screen time is important for multiple reasons, especially because the more time spent in front of a TV, computer, or video game, the less time there is to be physically active. Numerous experts, including the American Academy of Pediatrics, recommend limits on screen time for children. For adolescents, there appears to be some evidence that excessive screen time contributes to depression/anxiety.
I am not embarrassed to say that with my own kids I felt so strongly about screen time that we did not own any kind of video games or iPad (that was theirs alone), and they spent the summers until they turned 14 building a two-story bamboo fort in our backyard instead of vegging out in front of the TV or computer. It didn’t hurt them a bit; one is an engineer and the other is in nursing school.
It is easy to see that lifestyle factors can come into play with childhood anxiety and are often ignored in the clinical setting. They do not involve technologically advanced techniques or procedures, which are more likely to be reimbursed. They are straightforward – but not easy – concepts, and require active participation from the patient and family. Some of my most exciting moments with families is when they return for follow up and say, “It worked!”
We need to be as comfortable taking care of a child’s mind and spirit as we are taking care of a child’s physical body. Is this easy in a busy office? No. Is this easy in a 15-minute visit? No. Is this easy with poor reimbursement from insurance companies? No. Is it necessary? Unequivocally YES. Start the conversation.
Tag, you’re it!
Dr. Contrucci is an assistant professor of pediatrics, clinical education department, Philadelphia College of Osteopathic Medicine, Georgia Campus, Suwanee. She disclosed no relevant conflict of interest.
A version of this article first appeared on Medscape.com.
Multiple media outlets and numerous children’s professional organizations are discussing the child and adolescent mental health crisis. Finally, society at large seems to be taking notice that our kids are not okay, and that they haven’t been okay for a long time.
Over the past 5-7 years, both in my practice in tertiary children’s hospital emergency departments and in primary care pediatrics, I have seen a disturbing decline in kids’ mental well-being. What can a primary care physician do to make a difference? How do we capitalize on these discussions about mental health and illness now that it is rising to a priority status?
The U.S. Preventive Services Task Force recently drafted a statement of recommendations specifically discussing anxiety in children and adolescents. It shows supporting evidence that there is a moderate benefit to screening children 8-18 years old for anxiety. We know from the 2018-2019 National Survey of Children’s Health that almost 8% of children/adolescents ages 3-17 years old have an anxiety disorder. And among those 13-18 years old, the lifetime prevalence rises to nearly 33%, according to National Institutes of Health statistics.
Childhood anxiety unquestionably increases the chances of persistent anxiety or depression in adulthood. I have followed children who had excessive social anxiety from age 3 or 4 who progressed to generalized anxiety disorder as adolescents, usually when no intervention was done or when the family waited for the child to “outgrow” it. The DSM-5 has six separate categories for anxiety disorders in children and adolescents: generalized anxiety disorder, separation anxiety disorder, specific phobias, social phobia, agoraphobia, and panic disorder. Unfortunately, these illnesses cannot be wished away.
Screening, diagnosis, and follow-up
A few simple screening tools can be used to check for anxiety in children and adolescents. These include SCARED (Screen for Child Anxiety Related Emotional Disorders), GAD-7 (Generalized Anxiety Disorder-7), and/or the PHQ-A (Patient Health Questionnaire for Adolescents). Keep in mind that a screening tool is just that – a screen. Diagnostic confirmation and follow-up are appropriate after a positive screen. I like all of these particular screens as they are easy to administer and can be incorporated into a busy practice without extra training to administer. They are also easy for parents and patients to complete prior to a visit or during a visit.
Ideally, after a positive screen, the next step is to consult a child and adolescent psychiatrist (CAP); however, according to statistics from the American Academy of Child and Adolescent Psychiatry (AACAP), there are only 8,300 CAPs in the United States. The reality is that not a single state in the entire country has a “mostly sufficient supply” of CAP’s (defined as ≥ 47 per 100,000 children). In fact, most have a “severe shortage,” defined as 1-17 per 100,000 children
Adding a child/adolescent therapist is also necessary for patients 8 years old and up, but the harsh truth is that it may take up to several months before the child is seen. If a patient is in a rural or other underserved area, it may be even longer.
So, what does this mean for primary care physicians? When you are faced with a positive screening for childhood anxiety, the next step is “tag, you’re it!” Understandably, this is frightening for many physicians who feel unqualified.
Don’t be afraid! Like the old adage says, a journey of a thousand miles begins with a single step. Starting the conversation with patients and families is foremost. Physicians must be first in line to end the stigma surrounding mental illness, and the easiest way to do that is to start the conversation. Remember that anxiety in kids can present as classic fear or worry, but it also can present as irritability, anger outbursts, and attention issues. There have been so many patients referred to me for “being out of control” or “always angry” or “probable ADHD” who turned out to have significant anxiety.
Part of a routine medical evaluation includes obtaining personal, family, and social history; there should be no difference when considering an anxiety disorder. Obtaining information about family history, personality traits, environmental components, early attachment issues, developmental history, parental style, parental conflict, occupants in the home, any adverse childhood events, and history of child maltreatment is crucial. Assessing other risk factors, including socioeconomic status, race, ethnicity, and gender, is key as well. I have seen families literally breathe a sigh of relief when these questions are asked. Parents feel heard and seen. And, equally significant, so does the child/adolescent.
The ‘Big 4’
An in-depth assessment of patient and family lifestyle factors such as nutrition, sleep, physical activity/exercise, and screen time habits is also basic and essential. This kind of evaluation usually cannot be done in the typical 15-minute visit and often will need to be done over several patient visits. I have had numerous conversations with my patients regarding what I call the “Big 4” – simple but not easy concepts and actions. They include nutrition, sleep, exercise, and screen time. Parents will look at me and say, “I can’t believe I never thought of this!” Some of my favorite moments with patients over the years have involved partnering with the patient and family and encouraging them to do the “simple” but not “easy” things.
Nutrition
Does the child have proper nutrition? That is not meant to be an exercise in labeling foods as “good” or “bad” but meant to confirm whether there is a balance of different foods. It’s also a way of exploring whether there are family meals in the home. Family meals have been shown to have a protective factor for children’s social development and emotional regulation.
Sleep
Review the child’s sleep habits, such as difficulty falling/staying asleep, bedtime routine (soothing, relaxing activities vs. the opposite), nightmares, snoring, nighttime cough, etc. The physical sleeping environment is important as well. Is it quiet? Is it a crowded room?
Exercise
Discuss physical activity with the family. Is there time for the child to play outside without a defined goal? So much of a child’s day is structured, in school or with after-school activities, but can the kid simply be a kid? Does the family take walks together? Is it safe to play outside?
Screen time
Reviewing screen time is important for multiple reasons, especially because the more time spent in front of a TV, computer, or video game, the less time there is to be physically active. Numerous experts, including the American Academy of Pediatrics, recommend limits on screen time for children. For adolescents, there appears to be some evidence that excessive screen time contributes to depression/anxiety.
I am not embarrassed to say that with my own kids I felt so strongly about screen time that we did not own any kind of video games or iPad (that was theirs alone), and they spent the summers until they turned 14 building a two-story bamboo fort in our backyard instead of vegging out in front of the TV or computer. It didn’t hurt them a bit; one is an engineer and the other is in nursing school.
It is easy to see that lifestyle factors can come into play with childhood anxiety and are often ignored in the clinical setting. They do not involve technologically advanced techniques or procedures, which are more likely to be reimbursed. They are straightforward – but not easy – concepts, and require active participation from the patient and family. Some of my most exciting moments with families is when they return for follow up and say, “It worked!”
We need to be as comfortable taking care of a child’s mind and spirit as we are taking care of a child’s physical body. Is this easy in a busy office? No. Is this easy in a 15-minute visit? No. Is this easy with poor reimbursement from insurance companies? No. Is it necessary? Unequivocally YES. Start the conversation.
Tag, you’re it!
Dr. Contrucci is an assistant professor of pediatrics, clinical education department, Philadelphia College of Osteopathic Medicine, Georgia Campus, Suwanee. She disclosed no relevant conflict of interest.
A version of this article first appeared on Medscape.com.
Transgender youth on hormone therapy risk substantial bone loss
, and this is true regardless of gender assignment at birth.
The problem worsens as the time during which these patients receive sex steroid hormones increases. So far, the “bone mineral density effects of these therapies are understudied,” warned Natalie Nokoff, MD, who presented a cross-sectional study at the annual meeting of the Endocrine Society.
The study of bone density is part of a larger body of research being conducted by Dr. Nokoff and her co-investigators on the long-term health effects of gender-affirming therapy in children and adolescents. In one of several recent studies, transgender youths taking gonadotropin-releasing hormone (GnRH) agonists, which effectively block puberty, were shown to be at greater risk of adverse changes in body composition and markers of cardiometabolic health than youths who were not taking them.
“We need more information on the optimal length of treatment with puberty-delaying medications before either discontinuation or introduction of gender-affirming hormones,” said Dr. Nokoff, an assistant professor of pediatrics and endocrinology at the University of Colorado School of Medicine, Aurora.
In this study, 56 transgender youth underwent total body dual-energy x-ray absorptiometry (DEXA). The patients ranged in age from 10 years to almost 20 years. Just over half (53%) were assigned female sex at birth.
The mean Z scores, signifying deviation from age-matched norms, were lower regardless of current use or past use of GnRH agonists in both transgender males or transgender females, relative to age-matched norms.
Asked to comment, Michele A. O’Connell, MBBCh, department of endocrinology and diabetes, Royal Children’s Hospital, Victoria, Australia, said the risk of bone loss is real.
“Monitoring of bone health is recommended for all transgender-diverse adolescents treated with gonadotropin-releasing hormone agonists,” said Dr. O’Connell. He referred to multiple guidelines, including those issued by the World Professional Association of Transgender Health in 2012 and those from the Endocrine Society that were issued in 2017.
Inverse correlation between duration of GnRH agonist therapy and Z scores
In Dr. Nokoff’s study, for transgender males, the BMD Z score was reduced 0.2 relative to male norms and by 0.4 relative to female norms. For transgender females, the scores were reduced by 0.4 relative to male norms and by 0.2 relative to female norms.
Among transgender males who were taking testosterone and who had previously been exposed to GnRH agonists, the Z score was significantly lower than those taking testosterone alone (P = .004). There were no differences in Z score for transgender females taking estradiol alone relative to estradiol with current or past use of GnRH agonists.
There was a significant inverse correlation for duration of GnRH agonist therapy and Z scores for transgender females relative to male norms (P = .005) or female norms (P = .029). However, Z scores were unrelated to length of time receiving testosterone or estradiol therapy or to sex steroid concentrations.
The number of children and adolescents taking puberty-delaying or gender-affirming therapies is increasing. Although reliable data are limited, the exploration of gender identify appears to have become more common with the growing social acceptance of gender dysphoria. That term refers to a sense of unease among individuals who feel that their biological sex does not match their gender identity, according to Dr. Nokoff.
“It is now estimated that 2% of youths identify as transgender,” she said.
Findings from studies investigating the relationship between gender-affirming therapy and bone loss among adults have not been consistent. In a single-center study that followed 543 transgender men and 711 transgender women who had undergone DEXA scanning at baseline prior to starting hormone therapy, there did not appear to be any substantial negative effects on lumbar bone density over time (J Bone Min Res. 2018 Dec;34:447-54).
For adolescents, there is growing evidence of the risk of bone loss in relation to gender-affirming therapy, but there is limited agreement on clinical risks and how they can be avoided. Relevant variables include genetics and diet, as well as the types, doses, and length of time receiving gender-affirming therapy.
Monitor bone in transgender youth; Use vitamin D and weight-bearing exercise
Dr. O’Connell is the first author of a recent summary of the pharmacologic management of trans and gender-diverse adolescents. That summary covered multiple topics in addition to risk of bone loss, including the impact on growth, cognition, and mental health (J Clin Endocrinol Metab. 2022 Jan;107:241-257).
Overall, she believes that bone health should be monitored for children receiving puberty-delaying or gender-affirming therapies but agrees with Dr. Nokoff that the clinical impact remains poorly defined.
“Long-term follow-up studies will be required to assess the impact, if any, on functional outcomes such as fracture risk,” she reported. Still, she encouraged use of standard ways of improving bone health, including adequate vitamin D intake and weight-bearing exercise.
Dr. Nokoff and Dr. O’Connell have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, and this is true regardless of gender assignment at birth.
The problem worsens as the time during which these patients receive sex steroid hormones increases. So far, the “bone mineral density effects of these therapies are understudied,” warned Natalie Nokoff, MD, who presented a cross-sectional study at the annual meeting of the Endocrine Society.
The study of bone density is part of a larger body of research being conducted by Dr. Nokoff and her co-investigators on the long-term health effects of gender-affirming therapy in children and adolescents. In one of several recent studies, transgender youths taking gonadotropin-releasing hormone (GnRH) agonists, which effectively block puberty, were shown to be at greater risk of adverse changes in body composition and markers of cardiometabolic health than youths who were not taking them.
“We need more information on the optimal length of treatment with puberty-delaying medications before either discontinuation or introduction of gender-affirming hormones,” said Dr. Nokoff, an assistant professor of pediatrics and endocrinology at the University of Colorado School of Medicine, Aurora.
In this study, 56 transgender youth underwent total body dual-energy x-ray absorptiometry (DEXA). The patients ranged in age from 10 years to almost 20 years. Just over half (53%) were assigned female sex at birth.
The mean Z scores, signifying deviation from age-matched norms, were lower regardless of current use or past use of GnRH agonists in both transgender males or transgender females, relative to age-matched norms.
Asked to comment, Michele A. O’Connell, MBBCh, department of endocrinology and diabetes, Royal Children’s Hospital, Victoria, Australia, said the risk of bone loss is real.
“Monitoring of bone health is recommended for all transgender-diverse adolescents treated with gonadotropin-releasing hormone agonists,” said Dr. O’Connell. He referred to multiple guidelines, including those issued by the World Professional Association of Transgender Health in 2012 and those from the Endocrine Society that were issued in 2017.
Inverse correlation between duration of GnRH agonist therapy and Z scores
In Dr. Nokoff’s study, for transgender males, the BMD Z score was reduced 0.2 relative to male norms and by 0.4 relative to female norms. For transgender females, the scores were reduced by 0.4 relative to male norms and by 0.2 relative to female norms.
Among transgender males who were taking testosterone and who had previously been exposed to GnRH agonists, the Z score was significantly lower than those taking testosterone alone (P = .004). There were no differences in Z score for transgender females taking estradiol alone relative to estradiol with current or past use of GnRH agonists.
There was a significant inverse correlation for duration of GnRH agonist therapy and Z scores for transgender females relative to male norms (P = .005) or female norms (P = .029). However, Z scores were unrelated to length of time receiving testosterone or estradiol therapy or to sex steroid concentrations.
The number of children and adolescents taking puberty-delaying or gender-affirming therapies is increasing. Although reliable data are limited, the exploration of gender identify appears to have become more common with the growing social acceptance of gender dysphoria. That term refers to a sense of unease among individuals who feel that their biological sex does not match their gender identity, according to Dr. Nokoff.
“It is now estimated that 2% of youths identify as transgender,” she said.
Findings from studies investigating the relationship between gender-affirming therapy and bone loss among adults have not been consistent. In a single-center study that followed 543 transgender men and 711 transgender women who had undergone DEXA scanning at baseline prior to starting hormone therapy, there did not appear to be any substantial negative effects on lumbar bone density over time (J Bone Min Res. 2018 Dec;34:447-54).
For adolescents, there is growing evidence of the risk of bone loss in relation to gender-affirming therapy, but there is limited agreement on clinical risks and how they can be avoided. Relevant variables include genetics and diet, as well as the types, doses, and length of time receiving gender-affirming therapy.
Monitor bone in transgender youth; Use vitamin D and weight-bearing exercise
Dr. O’Connell is the first author of a recent summary of the pharmacologic management of trans and gender-diverse adolescents. That summary covered multiple topics in addition to risk of bone loss, including the impact on growth, cognition, and mental health (J Clin Endocrinol Metab. 2022 Jan;107:241-257).
Overall, she believes that bone health should be monitored for children receiving puberty-delaying or gender-affirming therapies but agrees with Dr. Nokoff that the clinical impact remains poorly defined.
“Long-term follow-up studies will be required to assess the impact, if any, on functional outcomes such as fracture risk,” she reported. Still, she encouraged use of standard ways of improving bone health, including adequate vitamin D intake and weight-bearing exercise.
Dr. Nokoff and Dr. O’Connell have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, and this is true regardless of gender assignment at birth.
The problem worsens as the time during which these patients receive sex steroid hormones increases. So far, the “bone mineral density effects of these therapies are understudied,” warned Natalie Nokoff, MD, who presented a cross-sectional study at the annual meeting of the Endocrine Society.
The study of bone density is part of a larger body of research being conducted by Dr. Nokoff and her co-investigators on the long-term health effects of gender-affirming therapy in children and adolescents. In one of several recent studies, transgender youths taking gonadotropin-releasing hormone (GnRH) agonists, which effectively block puberty, were shown to be at greater risk of adverse changes in body composition and markers of cardiometabolic health than youths who were not taking them.
“We need more information on the optimal length of treatment with puberty-delaying medications before either discontinuation or introduction of gender-affirming hormones,” said Dr. Nokoff, an assistant professor of pediatrics and endocrinology at the University of Colorado School of Medicine, Aurora.
In this study, 56 transgender youth underwent total body dual-energy x-ray absorptiometry (DEXA). The patients ranged in age from 10 years to almost 20 years. Just over half (53%) were assigned female sex at birth.
The mean Z scores, signifying deviation from age-matched norms, were lower regardless of current use or past use of GnRH agonists in both transgender males or transgender females, relative to age-matched norms.
Asked to comment, Michele A. O’Connell, MBBCh, department of endocrinology and diabetes, Royal Children’s Hospital, Victoria, Australia, said the risk of bone loss is real.
“Monitoring of bone health is recommended for all transgender-diverse adolescents treated with gonadotropin-releasing hormone agonists,” said Dr. O’Connell. He referred to multiple guidelines, including those issued by the World Professional Association of Transgender Health in 2012 and those from the Endocrine Society that were issued in 2017.
Inverse correlation between duration of GnRH agonist therapy and Z scores
In Dr. Nokoff’s study, for transgender males, the BMD Z score was reduced 0.2 relative to male norms and by 0.4 relative to female norms. For transgender females, the scores were reduced by 0.4 relative to male norms and by 0.2 relative to female norms.
Among transgender males who were taking testosterone and who had previously been exposed to GnRH agonists, the Z score was significantly lower than those taking testosterone alone (P = .004). There were no differences in Z score for transgender females taking estradiol alone relative to estradiol with current or past use of GnRH agonists.
There was a significant inverse correlation for duration of GnRH agonist therapy and Z scores for transgender females relative to male norms (P = .005) or female norms (P = .029). However, Z scores were unrelated to length of time receiving testosterone or estradiol therapy or to sex steroid concentrations.
The number of children and adolescents taking puberty-delaying or gender-affirming therapies is increasing. Although reliable data are limited, the exploration of gender identify appears to have become more common with the growing social acceptance of gender dysphoria. That term refers to a sense of unease among individuals who feel that their biological sex does not match their gender identity, according to Dr. Nokoff.
“It is now estimated that 2% of youths identify as transgender,” she said.
Findings from studies investigating the relationship between gender-affirming therapy and bone loss among adults have not been consistent. In a single-center study that followed 543 transgender men and 711 transgender women who had undergone DEXA scanning at baseline prior to starting hormone therapy, there did not appear to be any substantial negative effects on lumbar bone density over time (J Bone Min Res. 2018 Dec;34:447-54).
For adolescents, there is growing evidence of the risk of bone loss in relation to gender-affirming therapy, but there is limited agreement on clinical risks and how they can be avoided. Relevant variables include genetics and diet, as well as the types, doses, and length of time receiving gender-affirming therapy.
Monitor bone in transgender youth; Use vitamin D and weight-bearing exercise
Dr. O’Connell is the first author of a recent summary of the pharmacologic management of trans and gender-diverse adolescents. That summary covered multiple topics in addition to risk of bone loss, including the impact on growth, cognition, and mental health (J Clin Endocrinol Metab. 2022 Jan;107:241-257).
Overall, she believes that bone health should be monitored for children receiving puberty-delaying or gender-affirming therapies but agrees with Dr. Nokoff that the clinical impact remains poorly defined.
“Long-term follow-up studies will be required to assess the impact, if any, on functional outcomes such as fracture risk,” she reported. Still, she encouraged use of standard ways of improving bone health, including adequate vitamin D intake and weight-bearing exercise.
Dr. Nokoff and Dr. O’Connell have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ENDO 2022
Early childhood allergies linked with ADHD and ASD
, according to a large retrospective study.
“Our study provides strong evidence for the association between allergic disorders in early childhood and the development of ADHD,” Shay Nemet, MD, of the Kaplan Medical Center, Rehovot, Israel, and colleagues write in Pediatric Allergy and Immunology. “The risk of those children to develop ASD was less significant.”
The researchers analyzed data from 117,022 consecutive children diagnosed with at least one allergic disorder – asthma, conjunctivitis, rhinitis, and drug, food, or skin allergy – and 116,968 children without allergies in the Clalit Health Services pediatric database. The children had been treated from 2000 to 2018; the mean follow-up period was 11 years.
The children who were diagnosed with one or more allergies (mean age, 4.5 years) were significantly more likely to develop ADHD (odds ratio, 2.45; 95% confidence interval, 2.39-2.51), ASD (OR, 1.17; 95% CI, 1.08-1.27), or both ADHD and ASD (OR, 1.56; 95% CI, 1.35-1.79) than were the control children who did not have allergies.
Children diagnosed with rhinitis (OR, 3.96; 95% CI, 3.80-4.12) and conjunctivitis (OR, 3.63; 95% CI, 3.53-3.74) were the most likely to develop ADHD.
Allergy correlation with ADHD and ASD
Cy B. Nadler, PhD, a clinical psychologist and the director of Autism Services at Children’s Mercy Kansas City, Missouri, told this news organization that children and adults with neurodevelopmental differences are also more likely to have other health problems.
“Clinicians practicing in subspecialties such as allergy and immunology may have opportunities to help psychologists identify developmental and behavioral concerns early in childhood,” he added.
“Studies like this can’t be accomplished without large health care databases, but this approach has drawbacks, too,” Dr. Nadler said in an email. “Without more information about these patients’ co-occurring medical and behavioral conditions, we are almost certainly missing important contributors to the observed associations.”
Dr. Nadler, who was not involved in the study, noted that in the multivariable analysis that controlled for age at study entry, gender, and number of annual visits, the link between allergy and ASD diagnosis was not significant.
“It is important to remember not to interpret these study results as causal,” he added.
Desha M. Jordan, MD, FAAP, an assistant professor of pediatrics at UPMC Children’s Hospital of Pittsburgh, called the study “an interesting new area that has been speculated about for some time” and “one of the first I have seen with statistically significant correlations found between ADHD, ASD, and allergic conditions.”
More questions for future studies
Health care providers need to understand the potential sequelae of allergic conditions so that they can manage their patients appropriately, she advised.
Although symptoms and diagnoses were confirmed for all patients, the study’s retrospective design and the possibility of recall bias were limitations, said Dr. Jordan in an email. She also was not involved in the study.
“For example, the family of a child diagnosed with ADHD or ASD may have been more mindful of anything out of the norm in that child’s past, while the family of a child without these conditions may not have recalled allergic symptoms as important,” she explained.
Another question that arises is whether some patients were treated and managed well while others were not and whether this disparity in care affected the development or severity of ADHD or ASD, she added.
“Is a patient with a well-controlled allergic condition less likely to develop ADHD or ASD than a patient with an uncontrolled allergic condition? Does a well-controlled patient ever return to the same probability of getting ADHD or ASD as a nonallergic patient?”
“While this study expands our understanding of these conditions and their interrelationships, it also brings up many additional questions and opens a new segment of research,” Dr. Jordan said. “More studies in this area are necessary to confirm the findings of this paper.”
The study was partially funded by the Israel Ambulatory Pediatric Association. The authors, Dr. Nadler, and Dr. Jordan report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to a large retrospective study.
“Our study provides strong evidence for the association between allergic disorders in early childhood and the development of ADHD,” Shay Nemet, MD, of the Kaplan Medical Center, Rehovot, Israel, and colleagues write in Pediatric Allergy and Immunology. “The risk of those children to develop ASD was less significant.”
The researchers analyzed data from 117,022 consecutive children diagnosed with at least one allergic disorder – asthma, conjunctivitis, rhinitis, and drug, food, or skin allergy – and 116,968 children without allergies in the Clalit Health Services pediatric database. The children had been treated from 2000 to 2018; the mean follow-up period was 11 years.
The children who were diagnosed with one or more allergies (mean age, 4.5 years) were significantly more likely to develop ADHD (odds ratio, 2.45; 95% confidence interval, 2.39-2.51), ASD (OR, 1.17; 95% CI, 1.08-1.27), or both ADHD and ASD (OR, 1.56; 95% CI, 1.35-1.79) than were the control children who did not have allergies.
Children diagnosed with rhinitis (OR, 3.96; 95% CI, 3.80-4.12) and conjunctivitis (OR, 3.63; 95% CI, 3.53-3.74) were the most likely to develop ADHD.
Allergy correlation with ADHD and ASD
Cy B. Nadler, PhD, a clinical psychologist and the director of Autism Services at Children’s Mercy Kansas City, Missouri, told this news organization that children and adults with neurodevelopmental differences are also more likely to have other health problems.
“Clinicians practicing in subspecialties such as allergy and immunology may have opportunities to help psychologists identify developmental and behavioral concerns early in childhood,” he added.
“Studies like this can’t be accomplished without large health care databases, but this approach has drawbacks, too,” Dr. Nadler said in an email. “Without more information about these patients’ co-occurring medical and behavioral conditions, we are almost certainly missing important contributors to the observed associations.”
Dr. Nadler, who was not involved in the study, noted that in the multivariable analysis that controlled for age at study entry, gender, and number of annual visits, the link between allergy and ASD diagnosis was not significant.
“It is important to remember not to interpret these study results as causal,” he added.
Desha M. Jordan, MD, FAAP, an assistant professor of pediatrics at UPMC Children’s Hospital of Pittsburgh, called the study “an interesting new area that has been speculated about for some time” and “one of the first I have seen with statistically significant correlations found between ADHD, ASD, and allergic conditions.”
More questions for future studies
Health care providers need to understand the potential sequelae of allergic conditions so that they can manage their patients appropriately, she advised.
Although symptoms and diagnoses were confirmed for all patients, the study’s retrospective design and the possibility of recall bias were limitations, said Dr. Jordan in an email. She also was not involved in the study.
“For example, the family of a child diagnosed with ADHD or ASD may have been more mindful of anything out of the norm in that child’s past, while the family of a child without these conditions may not have recalled allergic symptoms as important,” she explained.
Another question that arises is whether some patients were treated and managed well while others were not and whether this disparity in care affected the development or severity of ADHD or ASD, she added.
“Is a patient with a well-controlled allergic condition less likely to develop ADHD or ASD than a patient with an uncontrolled allergic condition? Does a well-controlled patient ever return to the same probability of getting ADHD or ASD as a nonallergic patient?”
“While this study expands our understanding of these conditions and their interrelationships, it also brings up many additional questions and opens a new segment of research,” Dr. Jordan said. “More studies in this area are necessary to confirm the findings of this paper.”
The study was partially funded by the Israel Ambulatory Pediatric Association. The authors, Dr. Nadler, and Dr. Jordan report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to a large retrospective study.
“Our study provides strong evidence for the association between allergic disorders in early childhood and the development of ADHD,” Shay Nemet, MD, of the Kaplan Medical Center, Rehovot, Israel, and colleagues write in Pediatric Allergy and Immunology. “The risk of those children to develop ASD was less significant.”
The researchers analyzed data from 117,022 consecutive children diagnosed with at least one allergic disorder – asthma, conjunctivitis, rhinitis, and drug, food, or skin allergy – and 116,968 children without allergies in the Clalit Health Services pediatric database. The children had been treated from 2000 to 2018; the mean follow-up period was 11 years.
The children who were diagnosed with one or more allergies (mean age, 4.5 years) were significantly more likely to develop ADHD (odds ratio, 2.45; 95% confidence interval, 2.39-2.51), ASD (OR, 1.17; 95% CI, 1.08-1.27), or both ADHD and ASD (OR, 1.56; 95% CI, 1.35-1.79) than were the control children who did not have allergies.
Children diagnosed with rhinitis (OR, 3.96; 95% CI, 3.80-4.12) and conjunctivitis (OR, 3.63; 95% CI, 3.53-3.74) were the most likely to develop ADHD.
Allergy correlation with ADHD and ASD
Cy B. Nadler, PhD, a clinical psychologist and the director of Autism Services at Children’s Mercy Kansas City, Missouri, told this news organization that children and adults with neurodevelopmental differences are also more likely to have other health problems.
“Clinicians practicing in subspecialties such as allergy and immunology may have opportunities to help psychologists identify developmental and behavioral concerns early in childhood,” he added.
“Studies like this can’t be accomplished without large health care databases, but this approach has drawbacks, too,” Dr. Nadler said in an email. “Without more information about these patients’ co-occurring medical and behavioral conditions, we are almost certainly missing important contributors to the observed associations.”
Dr. Nadler, who was not involved in the study, noted that in the multivariable analysis that controlled for age at study entry, gender, and number of annual visits, the link between allergy and ASD diagnosis was not significant.
“It is important to remember not to interpret these study results as causal,” he added.
Desha M. Jordan, MD, FAAP, an assistant professor of pediatrics at UPMC Children’s Hospital of Pittsburgh, called the study “an interesting new area that has been speculated about for some time” and “one of the first I have seen with statistically significant correlations found between ADHD, ASD, and allergic conditions.”
More questions for future studies
Health care providers need to understand the potential sequelae of allergic conditions so that they can manage their patients appropriately, she advised.
Although symptoms and diagnoses were confirmed for all patients, the study’s retrospective design and the possibility of recall bias were limitations, said Dr. Jordan in an email. She also was not involved in the study.
“For example, the family of a child diagnosed with ADHD or ASD may have been more mindful of anything out of the norm in that child’s past, while the family of a child without these conditions may not have recalled allergic symptoms as important,” she explained.
Another question that arises is whether some patients were treated and managed well while others were not and whether this disparity in care affected the development or severity of ADHD or ASD, she added.
“Is a patient with a well-controlled allergic condition less likely to develop ADHD or ASD than a patient with an uncontrolled allergic condition? Does a well-controlled patient ever return to the same probability of getting ADHD or ASD as a nonallergic patient?”
“While this study expands our understanding of these conditions and their interrelationships, it also brings up many additional questions and opens a new segment of research,” Dr. Jordan said. “More studies in this area are necessary to confirm the findings of this paper.”
The study was partially funded by the Israel Ambulatory Pediatric Association. The authors, Dr. Nadler, and Dr. Jordan report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM PEDIATRIC ALLERGY AND IMMUNOLOGY
U.S. allows pharmacists to prescribe Paxlovid directly
The Food and Drug Administration revised the drug’s emergency use authorization on July 6, letting state-licensed pharmacists screen patients and determine if they are eligible for Paxlovid, according to The Associated Press.
Previously, only doctors could prescribe the antiviral drug, the AP reported. With some limits, pharmacists can now prescribe the medication for patients who face high risks for severe COVID-19.
“The FDA recognizes the important role pharmacists have played and continue to play in combating this pandemic,” Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a statement.
“Since Paxlovid must be taken within 5 days after symptoms begin, authorizing state-licensed pharmacists to prescribe Paxlovid could expand access to timely treatment for some patients who are eligible to receive this drug for the treatment of COVID-19,” she said.
Tom Kraus, the vice president of government relations at the American Society of Health-System Pharmacists, said in a statement that the organization was “pleased to see the FDA remove this barrier to patients’ access to this critical treatment.”
“Pharmacists have played a vital role in our pandemic response efforts and are well-positioned to help patients, particularly those in rural and underserved communities, benefit from this medication,” he said.
But some doctor’s groups questioned the FDA’s move. Jack Resneck Jr., MD, the president of the American Medical Association, said in a statement that prescribing Paxlovid “requires knowledge of a patient’s medical history, as well as clinical monitoring for side effects and follow-up care to determine whether a patient is improving” – requirements that are “far beyond a pharmacist’s scope and training.”
“In the fight against a virus that has killed more than a million people in the United States and is still extremely present and transmissible, patients will get the best, most comprehensive care from physician-led teams – teams that include pharmacists. But, whenever possible, prescribing decisions should be made by a physician with knowledge of a patient’s medical history and the ability to follow up. To ensure the best possible care for COVID-19 patients, we urge people who test positive to discuss treatment options with their physician, if they have one,” he said.
After testing positive for COVID-19, patients should first consider seeking care from their regular health care provider or locating a Test-to-Treat site in their area, the FDA said. Although the latest update allows pharmacists to prescribe Paxlovid, community pharmacies that don’t yet take part in the Test-to-Treat program can decide if they will offer the prescription service to patients.
Paxlovid is authorized to treat mild to moderate COVID-19 in adults and in kids ages 12 and older who weigh at least 88 pounds. Patients who report a positive at-home test are eligible for Paxlovid under the FDA authorization.
If patients want to seek a prescription directly from a pharmacist, they should bring electronic or printed health records from the past year, including their most recent reports of blood work, so the pharmacist can review for kidney or liver problems. Pharmacists can also get this information from the patient’s health care provider.
In addition, patients should bring a list of all medications they are taking, including over-the-counter medications, so the pharmacist can screen for drugs that can have serious interactions with Paxlovid.
Under the limits in the updated FDA authorization, pharmacists should refer patients for more screening if Paxlovid isn’t a good option or if there’s not enough information to find out how well their kidneys or liver works, as well as potential drug interactions.
Paxlovid is intended for people with COVID-19 who face the highest risks for serious disease, the AP reported, including older adults and those with health conditions such as heart disease, obesity, cancer, or diabetes. It isn’t recommended for people with severe kidney or liver problems. A course of treatment requires three pills twice a day for 5 days.
A version of this article first appeared on WebMD.com.
The Food and Drug Administration revised the drug’s emergency use authorization on July 6, letting state-licensed pharmacists screen patients and determine if they are eligible for Paxlovid, according to The Associated Press.
Previously, only doctors could prescribe the antiviral drug, the AP reported. With some limits, pharmacists can now prescribe the medication for patients who face high risks for severe COVID-19.
“The FDA recognizes the important role pharmacists have played and continue to play in combating this pandemic,” Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a statement.
“Since Paxlovid must be taken within 5 days after symptoms begin, authorizing state-licensed pharmacists to prescribe Paxlovid could expand access to timely treatment for some patients who are eligible to receive this drug for the treatment of COVID-19,” she said.
Tom Kraus, the vice president of government relations at the American Society of Health-System Pharmacists, said in a statement that the organization was “pleased to see the FDA remove this barrier to patients’ access to this critical treatment.”
“Pharmacists have played a vital role in our pandemic response efforts and are well-positioned to help patients, particularly those in rural and underserved communities, benefit from this medication,” he said.
But some doctor’s groups questioned the FDA’s move. Jack Resneck Jr., MD, the president of the American Medical Association, said in a statement that prescribing Paxlovid “requires knowledge of a patient’s medical history, as well as clinical monitoring for side effects and follow-up care to determine whether a patient is improving” – requirements that are “far beyond a pharmacist’s scope and training.”
“In the fight against a virus that has killed more than a million people in the United States and is still extremely present and transmissible, patients will get the best, most comprehensive care from physician-led teams – teams that include pharmacists. But, whenever possible, prescribing decisions should be made by a physician with knowledge of a patient’s medical history and the ability to follow up. To ensure the best possible care for COVID-19 patients, we urge people who test positive to discuss treatment options with their physician, if they have one,” he said.
After testing positive for COVID-19, patients should first consider seeking care from their regular health care provider or locating a Test-to-Treat site in their area, the FDA said. Although the latest update allows pharmacists to prescribe Paxlovid, community pharmacies that don’t yet take part in the Test-to-Treat program can decide if they will offer the prescription service to patients.
Paxlovid is authorized to treat mild to moderate COVID-19 in adults and in kids ages 12 and older who weigh at least 88 pounds. Patients who report a positive at-home test are eligible for Paxlovid under the FDA authorization.
If patients want to seek a prescription directly from a pharmacist, they should bring electronic or printed health records from the past year, including their most recent reports of blood work, so the pharmacist can review for kidney or liver problems. Pharmacists can also get this information from the patient’s health care provider.
In addition, patients should bring a list of all medications they are taking, including over-the-counter medications, so the pharmacist can screen for drugs that can have serious interactions with Paxlovid.
Under the limits in the updated FDA authorization, pharmacists should refer patients for more screening if Paxlovid isn’t a good option or if there’s not enough information to find out how well their kidneys or liver works, as well as potential drug interactions.
Paxlovid is intended for people with COVID-19 who face the highest risks for serious disease, the AP reported, including older adults and those with health conditions such as heart disease, obesity, cancer, or diabetes. It isn’t recommended for people with severe kidney or liver problems. A course of treatment requires three pills twice a day for 5 days.
A version of this article first appeared on WebMD.com.
The Food and Drug Administration revised the drug’s emergency use authorization on July 6, letting state-licensed pharmacists screen patients and determine if they are eligible for Paxlovid, according to The Associated Press.
Previously, only doctors could prescribe the antiviral drug, the AP reported. With some limits, pharmacists can now prescribe the medication for patients who face high risks for severe COVID-19.
“The FDA recognizes the important role pharmacists have played and continue to play in combating this pandemic,” Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a statement.
“Since Paxlovid must be taken within 5 days after symptoms begin, authorizing state-licensed pharmacists to prescribe Paxlovid could expand access to timely treatment for some patients who are eligible to receive this drug for the treatment of COVID-19,” she said.
Tom Kraus, the vice president of government relations at the American Society of Health-System Pharmacists, said in a statement that the organization was “pleased to see the FDA remove this barrier to patients’ access to this critical treatment.”
“Pharmacists have played a vital role in our pandemic response efforts and are well-positioned to help patients, particularly those in rural and underserved communities, benefit from this medication,” he said.
But some doctor’s groups questioned the FDA’s move. Jack Resneck Jr., MD, the president of the American Medical Association, said in a statement that prescribing Paxlovid “requires knowledge of a patient’s medical history, as well as clinical monitoring for side effects and follow-up care to determine whether a patient is improving” – requirements that are “far beyond a pharmacist’s scope and training.”
“In the fight against a virus that has killed more than a million people in the United States and is still extremely present and transmissible, patients will get the best, most comprehensive care from physician-led teams – teams that include pharmacists. But, whenever possible, prescribing decisions should be made by a physician with knowledge of a patient’s medical history and the ability to follow up. To ensure the best possible care for COVID-19 patients, we urge people who test positive to discuss treatment options with their physician, if they have one,” he said.
After testing positive for COVID-19, patients should first consider seeking care from their regular health care provider or locating a Test-to-Treat site in their area, the FDA said. Although the latest update allows pharmacists to prescribe Paxlovid, community pharmacies that don’t yet take part in the Test-to-Treat program can decide if they will offer the prescription service to patients.
Paxlovid is authorized to treat mild to moderate COVID-19 in adults and in kids ages 12 and older who weigh at least 88 pounds. Patients who report a positive at-home test are eligible for Paxlovid under the FDA authorization.
If patients want to seek a prescription directly from a pharmacist, they should bring electronic or printed health records from the past year, including their most recent reports of blood work, so the pharmacist can review for kidney or liver problems. Pharmacists can also get this information from the patient’s health care provider.
In addition, patients should bring a list of all medications they are taking, including over-the-counter medications, so the pharmacist can screen for drugs that can have serious interactions with Paxlovid.
Under the limits in the updated FDA authorization, pharmacists should refer patients for more screening if Paxlovid isn’t a good option or if there’s not enough information to find out how well their kidneys or liver works, as well as potential drug interactions.
Paxlovid is intended for people with COVID-19 who face the highest risks for serious disease, the AP reported, including older adults and those with health conditions such as heart disease, obesity, cancer, or diabetes. It isn’t recommended for people with severe kidney or liver problems. A course of treatment requires three pills twice a day for 5 days.
A version of this article first appeared on WebMD.com.
WHO tracking new Omicron subvariant in India
The subvariant, a sublineage of BA.2 being called BA.2.75, has been reported in eight countries and hasn’t yet been declared a variant of concern.
“There’s been an emergence of a ‘could be’ subvariant. It’s been not yet officially called, but some people are referring to it as BA.2.75,” Soumya Swaminathan, MD, the WHO’s chief scientist, said in a video posted on Twitter.
The subvariant appears to have mutations similar to other contagious strains, she said, though there are a limited number of sequences available to analyze. How transmissible and severe it is, and how well it can evade our immunity, aren’t yet known.
“We have to wait and see, and of course, we are tracking it,” Dr. Swaminathan said.
The WHO committee responsible for analyzing global coronavirus data will label the subvariant officially and release more information as the situation warrants it, she said.
Public health experts around the world are also talking about the subvariant, which has been nicknamed Centaurus. BA.2.75 was first found in India in May and is now competing with BA.5, which has become dominant in the United States.
BA.2.75 has eight mutations beyond those seen in BA.5, which “could make immune escape worse than what we’re seeing now,” Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief at Medscape, wrote in a Twitter post.
Individually, the extra mutations aren’t too concerning, “but all appearing together at once is another matter,” Tom Peacock, PhD, a virologist at Imperial College London, wrote in a Twitter post.
The “apparent rapid growth and wide geographical spread” are “worth keeping a close eye on,” he said.
BA.2.75 has been found in a handful of cases in the United States, Australia, Canada, Germany, Japan, New Zealand, and the United Kingdom. In India, the sequence accounts for about 23% of recent samples.
“It is really too early to know if BA.2.75 will take over relative to BA.2 or even relative to BA.5,” Ulrich Elling, PhD, a researcher at Australia’s Institute of Molecular Biotechnology, wrote in a Twitter post.
“Just to emphasize it again: While the distribution across Indian regions as well as internationally and the very rapid appearance makes it likely we are dealing with a variant spreading fast and spread widely already, the absolute data points are few,” he said.
Globally, coronavirus cases have increased nearly 30% during the past 2 weeks, the WHO said July 6. Four out of six of the WHO subregions reported an increase in the last week, with BA.4 and BA.5 driving waves in the United States and Europe.
A version of this article first appeared on WebMD.com.
The subvariant, a sublineage of BA.2 being called BA.2.75, has been reported in eight countries and hasn’t yet been declared a variant of concern.
“There’s been an emergence of a ‘could be’ subvariant. It’s been not yet officially called, but some people are referring to it as BA.2.75,” Soumya Swaminathan, MD, the WHO’s chief scientist, said in a video posted on Twitter.
The subvariant appears to have mutations similar to other contagious strains, she said, though there are a limited number of sequences available to analyze. How transmissible and severe it is, and how well it can evade our immunity, aren’t yet known.
“We have to wait and see, and of course, we are tracking it,” Dr. Swaminathan said.
The WHO committee responsible for analyzing global coronavirus data will label the subvariant officially and release more information as the situation warrants it, she said.
Public health experts around the world are also talking about the subvariant, which has been nicknamed Centaurus. BA.2.75 was first found in India in May and is now competing with BA.5, which has become dominant in the United States.
BA.2.75 has eight mutations beyond those seen in BA.5, which “could make immune escape worse than what we’re seeing now,” Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief at Medscape, wrote in a Twitter post.
Individually, the extra mutations aren’t too concerning, “but all appearing together at once is another matter,” Tom Peacock, PhD, a virologist at Imperial College London, wrote in a Twitter post.
The “apparent rapid growth and wide geographical spread” are “worth keeping a close eye on,” he said.
BA.2.75 has been found in a handful of cases in the United States, Australia, Canada, Germany, Japan, New Zealand, and the United Kingdom. In India, the sequence accounts for about 23% of recent samples.
“It is really too early to know if BA.2.75 will take over relative to BA.2 or even relative to BA.5,” Ulrich Elling, PhD, a researcher at Australia’s Institute of Molecular Biotechnology, wrote in a Twitter post.
“Just to emphasize it again: While the distribution across Indian regions as well as internationally and the very rapid appearance makes it likely we are dealing with a variant spreading fast and spread widely already, the absolute data points are few,” he said.
Globally, coronavirus cases have increased nearly 30% during the past 2 weeks, the WHO said July 6. Four out of six of the WHO subregions reported an increase in the last week, with BA.4 and BA.5 driving waves in the United States and Europe.
A version of this article first appeared on WebMD.com.
The subvariant, a sublineage of BA.2 being called BA.2.75, has been reported in eight countries and hasn’t yet been declared a variant of concern.
“There’s been an emergence of a ‘could be’ subvariant. It’s been not yet officially called, but some people are referring to it as BA.2.75,” Soumya Swaminathan, MD, the WHO’s chief scientist, said in a video posted on Twitter.
The subvariant appears to have mutations similar to other contagious strains, she said, though there are a limited number of sequences available to analyze. How transmissible and severe it is, and how well it can evade our immunity, aren’t yet known.
“We have to wait and see, and of course, we are tracking it,” Dr. Swaminathan said.
The WHO committee responsible for analyzing global coronavirus data will label the subvariant officially and release more information as the situation warrants it, she said.
Public health experts around the world are also talking about the subvariant, which has been nicknamed Centaurus. BA.2.75 was first found in India in May and is now competing with BA.5, which has become dominant in the United States.
BA.2.75 has eight mutations beyond those seen in BA.5, which “could make immune escape worse than what we’re seeing now,” Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief at Medscape, wrote in a Twitter post.
Individually, the extra mutations aren’t too concerning, “but all appearing together at once is another matter,” Tom Peacock, PhD, a virologist at Imperial College London, wrote in a Twitter post.
The “apparent rapid growth and wide geographical spread” are “worth keeping a close eye on,” he said.
BA.2.75 has been found in a handful of cases in the United States, Australia, Canada, Germany, Japan, New Zealand, and the United Kingdom. In India, the sequence accounts for about 23% of recent samples.
“It is really too early to know if BA.2.75 will take over relative to BA.2 or even relative to BA.5,” Ulrich Elling, PhD, a researcher at Australia’s Institute of Molecular Biotechnology, wrote in a Twitter post.
“Just to emphasize it again: While the distribution across Indian regions as well as internationally and the very rapid appearance makes it likely we are dealing with a variant spreading fast and spread widely already, the absolute data points are few,” he said.
Globally, coronavirus cases have increased nearly 30% during the past 2 weeks, the WHO said July 6. Four out of six of the WHO subregions reported an increase in the last week, with BA.4 and BA.5 driving waves in the United States and Europe.
A version of this article first appeared on WebMD.com.
Study explores gender differences in pediatric melanoma
INDIANAPOLIS – .
In addition, male gender was independently associated with increased mortality, but age was not.
Those are key findings from a retrospective cohort analysis of nearly 5,000 records from the National Cancer Database.
“There are multiple studies from primarily adult populations showing females with melanoma have a different presentation and better outcomes than males,” co-first author Rebecca M. Thiede, MD, a dermatologist at the University of Arizona, Tucson, said in an interview with this news organization in advance of the annual meeting of the Society for Pediatric Dermatology, where the abstract was presented during a poster session. “However, because melanoma is so rare in younger patients, little is known about gender differences in presentation and survival in pediatric and adolescent patients. To our knowledge, this is one of the largest studies to date in this population, and the first to explore gender differences in detail in pediatric and adolescent patients with melanoma.”
Working with co-first author Sabrina Dahak, a fourth-year medical student at the University of Arizona, Phoenix, Dr. Thiede and colleagues retrospectively analyzed the National Cancer Database to identify biopsy-confirmed invasive primary cutaneous melanoma cases diagnosed in patients 0-21 years of age between 2004 and 2018. The search yielded 4,645 cases, and the researchers used American Academy of Pediatrics definitions to categorize the patients by age, from infancy (birth to 2 years), to childhood (3-10 years), early adolescence (11-14 years), middle adolescence (15-17 years), and late adolescence (18-21 years). They used the Kaplan Meier analysis to determine overall survival and multivariate Cox regression to determine independent survival predictors.
Of the 4,645 pediatric melanoma cases, 63.4% were in females and 36.6% were in males, a difference that was significant (P < .001). Dr. Thiede and colleagues also observed a significant relationship between primary site and gender (P < .001). Primary sites included the trunk (34.3% of females vs. 32.9% of males, respectively), head and neck (16.4% vs. 30.9%), upper extremities (19.5% vs. 16%), lower extremities (27.9% vs. 16.5%), and “unspecified” (1.9% vs. 3.7%).
Females had higher rates of superficial spreading melanoma while males were affected by nodular melanoma more often. For example, the median Breslow depth was higher for males (1.05 mm; interquartile range [IQR] 0.50-2.31) than for females (0.80 mm; IQR, 0.40-1.67; P < .001).
Although females accounted for a higher percentage of cases than males overall, from birth to 17 years, a higher percentage of males than females were found to have later stage of melanoma at time of diagnosis: Females were more likely to be diagnosed with stage I disease (67.8%) than were males (53.6%), and males were more likely than were females to be diagnosed with stages II (15.9% vs. 12.3%), III (27.1% vs. 18.3%), and IV disease (3.3% vs. 1.6%; P < .001 for all).
In other findings, the 5- and 10-year overall survival rates were higher for females (95.9% and 93.9%, respectively) than for males (92.0% vs. 86.7%, respectively; P < .001). However, by age group, overall survival rates were similar between females and males among infants, children, and those in early adolescence – but not for those in middle adolescence (96.7% vs. 91.9%; P < .001) or late adolescence (95.7% vs. 90.4%; P < .001).
When the researchers adjusted for confounding variables, male gender was independently associated with an increased risk of death (adjusted hazard ratio 1.37; P < .001), but age was not.
“It was particularly surprising to see that even at such a young age, there is a significant difference in overall survival between males and females, where females have better outcomes than males,” Dr. Thiede said. “When examining pediatric and adolescent patients, it is essential to maintain cutaneous melanoma on the differential,” she advised. “It is important for clinicians to perform a thorough exam at annual visits particularly for those at high risk for melanoma to catch this rare but potentially devastating diagnosis.”
She acknowledged certain limitations of the study, including its reliance on one database, “as comparing multiple databases would strengthen the conclusions,” she said. “There was some missing data present in our dataset, and a large percentage of the histologic subtypes were unspecified, both of which are common issues with cancer registries. An additional limitation is related to the low death rates in adolescent and pediatric patients, which may impact the analysis related to survival and independent predictors of survival.”
Asked to comment on the study results, Carrie C. Coughlin, MD, who directs the section of pediatric dermatology Washington University/St. Louis Children’s Hospital, said that the finding that males were more likely to present with stage II or higher disease compared with females “could be related to their finding that females had more superficial spreading melanomas, whereas males had more nodular melanoma.” Those differences “could influence how providers evaluate melanocytic lesions in children,” she added.
Dr. Coughlin, who directs the pediatric dermatology fellowship at Washington University/St. Louis Children’s Hospital, said it was “interesting” that the authors found no association between older age and an increased risk of death. “It would be helpful to have more data about melanoma subtype, including information about Spitz or Spitzoid melanomas,” she said. “Also, knowing the distribution of melanoma across the age categories could provide more insight into their data.”
Ms. Dahak received an award from the National Cancer Institute to fund travel for presentation of this study at the SPD meeting. No other financial conflicts were reported by the researchers. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance (PeDRA) and the International Immunosuppression and Transplant Skin Cancer Collaborative.
INDIANAPOLIS – .
In addition, male gender was independently associated with increased mortality, but age was not.
Those are key findings from a retrospective cohort analysis of nearly 5,000 records from the National Cancer Database.
“There are multiple studies from primarily adult populations showing females with melanoma have a different presentation and better outcomes than males,” co-first author Rebecca M. Thiede, MD, a dermatologist at the University of Arizona, Tucson, said in an interview with this news organization in advance of the annual meeting of the Society for Pediatric Dermatology, where the abstract was presented during a poster session. “However, because melanoma is so rare in younger patients, little is known about gender differences in presentation and survival in pediatric and adolescent patients. To our knowledge, this is one of the largest studies to date in this population, and the first to explore gender differences in detail in pediatric and adolescent patients with melanoma.”
Working with co-first author Sabrina Dahak, a fourth-year medical student at the University of Arizona, Phoenix, Dr. Thiede and colleagues retrospectively analyzed the National Cancer Database to identify biopsy-confirmed invasive primary cutaneous melanoma cases diagnosed in patients 0-21 years of age between 2004 and 2018. The search yielded 4,645 cases, and the researchers used American Academy of Pediatrics definitions to categorize the patients by age, from infancy (birth to 2 years), to childhood (3-10 years), early adolescence (11-14 years), middle adolescence (15-17 years), and late adolescence (18-21 years). They used the Kaplan Meier analysis to determine overall survival and multivariate Cox regression to determine independent survival predictors.
Of the 4,645 pediatric melanoma cases, 63.4% were in females and 36.6% were in males, a difference that was significant (P < .001). Dr. Thiede and colleagues also observed a significant relationship between primary site and gender (P < .001). Primary sites included the trunk (34.3% of females vs. 32.9% of males, respectively), head and neck (16.4% vs. 30.9%), upper extremities (19.5% vs. 16%), lower extremities (27.9% vs. 16.5%), and “unspecified” (1.9% vs. 3.7%).
Females had higher rates of superficial spreading melanoma while males were affected by nodular melanoma more often. For example, the median Breslow depth was higher for males (1.05 mm; interquartile range [IQR] 0.50-2.31) than for females (0.80 mm; IQR, 0.40-1.67; P < .001).
Although females accounted for a higher percentage of cases than males overall, from birth to 17 years, a higher percentage of males than females were found to have later stage of melanoma at time of diagnosis: Females were more likely to be diagnosed with stage I disease (67.8%) than were males (53.6%), and males were more likely than were females to be diagnosed with stages II (15.9% vs. 12.3%), III (27.1% vs. 18.3%), and IV disease (3.3% vs. 1.6%; P < .001 for all).
In other findings, the 5- and 10-year overall survival rates were higher for females (95.9% and 93.9%, respectively) than for males (92.0% vs. 86.7%, respectively; P < .001). However, by age group, overall survival rates were similar between females and males among infants, children, and those in early adolescence – but not for those in middle adolescence (96.7% vs. 91.9%; P < .001) or late adolescence (95.7% vs. 90.4%; P < .001).
When the researchers adjusted for confounding variables, male gender was independently associated with an increased risk of death (adjusted hazard ratio 1.37; P < .001), but age was not.
“It was particularly surprising to see that even at such a young age, there is a significant difference in overall survival between males and females, where females have better outcomes than males,” Dr. Thiede said. “When examining pediatric and adolescent patients, it is essential to maintain cutaneous melanoma on the differential,” she advised. “It is important for clinicians to perform a thorough exam at annual visits particularly for those at high risk for melanoma to catch this rare but potentially devastating diagnosis.”
She acknowledged certain limitations of the study, including its reliance on one database, “as comparing multiple databases would strengthen the conclusions,” she said. “There was some missing data present in our dataset, and a large percentage of the histologic subtypes were unspecified, both of which are common issues with cancer registries. An additional limitation is related to the low death rates in adolescent and pediatric patients, which may impact the analysis related to survival and independent predictors of survival.”
Asked to comment on the study results, Carrie C. Coughlin, MD, who directs the section of pediatric dermatology Washington University/St. Louis Children’s Hospital, said that the finding that males were more likely to present with stage II or higher disease compared with females “could be related to their finding that females had more superficial spreading melanomas, whereas males had more nodular melanoma.” Those differences “could influence how providers evaluate melanocytic lesions in children,” she added.
Dr. Coughlin, who directs the pediatric dermatology fellowship at Washington University/St. Louis Children’s Hospital, said it was “interesting” that the authors found no association between older age and an increased risk of death. “It would be helpful to have more data about melanoma subtype, including information about Spitz or Spitzoid melanomas,” she said. “Also, knowing the distribution of melanoma across the age categories could provide more insight into their data.”
Ms. Dahak received an award from the National Cancer Institute to fund travel for presentation of this study at the SPD meeting. No other financial conflicts were reported by the researchers. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance (PeDRA) and the International Immunosuppression and Transplant Skin Cancer Collaborative.
INDIANAPOLIS – .
In addition, male gender was independently associated with increased mortality, but age was not.
Those are key findings from a retrospective cohort analysis of nearly 5,000 records from the National Cancer Database.
“There are multiple studies from primarily adult populations showing females with melanoma have a different presentation and better outcomes than males,” co-first author Rebecca M. Thiede, MD, a dermatologist at the University of Arizona, Tucson, said in an interview with this news organization in advance of the annual meeting of the Society for Pediatric Dermatology, where the abstract was presented during a poster session. “However, because melanoma is so rare in younger patients, little is known about gender differences in presentation and survival in pediatric and adolescent patients. To our knowledge, this is one of the largest studies to date in this population, and the first to explore gender differences in detail in pediatric and adolescent patients with melanoma.”
Working with co-first author Sabrina Dahak, a fourth-year medical student at the University of Arizona, Phoenix, Dr. Thiede and colleagues retrospectively analyzed the National Cancer Database to identify biopsy-confirmed invasive primary cutaneous melanoma cases diagnosed in patients 0-21 years of age between 2004 and 2018. The search yielded 4,645 cases, and the researchers used American Academy of Pediatrics definitions to categorize the patients by age, from infancy (birth to 2 years), to childhood (3-10 years), early adolescence (11-14 years), middle adolescence (15-17 years), and late adolescence (18-21 years). They used the Kaplan Meier analysis to determine overall survival and multivariate Cox regression to determine independent survival predictors.
Of the 4,645 pediatric melanoma cases, 63.4% were in females and 36.6% were in males, a difference that was significant (P < .001). Dr. Thiede and colleagues also observed a significant relationship between primary site and gender (P < .001). Primary sites included the trunk (34.3% of females vs. 32.9% of males, respectively), head and neck (16.4% vs. 30.9%), upper extremities (19.5% vs. 16%), lower extremities (27.9% vs. 16.5%), and “unspecified” (1.9% vs. 3.7%).
Females had higher rates of superficial spreading melanoma while males were affected by nodular melanoma more often. For example, the median Breslow depth was higher for males (1.05 mm; interquartile range [IQR] 0.50-2.31) than for females (0.80 mm; IQR, 0.40-1.67; P < .001).
Although females accounted for a higher percentage of cases than males overall, from birth to 17 years, a higher percentage of males than females were found to have later stage of melanoma at time of diagnosis: Females were more likely to be diagnosed with stage I disease (67.8%) than were males (53.6%), and males were more likely than were females to be diagnosed with stages II (15.9% vs. 12.3%), III (27.1% vs. 18.3%), and IV disease (3.3% vs. 1.6%; P < .001 for all).
In other findings, the 5- and 10-year overall survival rates were higher for females (95.9% and 93.9%, respectively) than for males (92.0% vs. 86.7%, respectively; P < .001). However, by age group, overall survival rates were similar between females and males among infants, children, and those in early adolescence – but not for those in middle adolescence (96.7% vs. 91.9%; P < .001) or late adolescence (95.7% vs. 90.4%; P < .001).
When the researchers adjusted for confounding variables, male gender was independently associated with an increased risk of death (adjusted hazard ratio 1.37; P < .001), but age was not.
“It was particularly surprising to see that even at such a young age, there is a significant difference in overall survival between males and females, where females have better outcomes than males,” Dr. Thiede said. “When examining pediatric and adolescent patients, it is essential to maintain cutaneous melanoma on the differential,” she advised. “It is important for clinicians to perform a thorough exam at annual visits particularly for those at high risk for melanoma to catch this rare but potentially devastating diagnosis.”
She acknowledged certain limitations of the study, including its reliance on one database, “as comparing multiple databases would strengthen the conclusions,” she said. “There was some missing data present in our dataset, and a large percentage of the histologic subtypes were unspecified, both of which are common issues with cancer registries. An additional limitation is related to the low death rates in adolescent and pediatric patients, which may impact the analysis related to survival and independent predictors of survival.”
Asked to comment on the study results, Carrie C. Coughlin, MD, who directs the section of pediatric dermatology Washington University/St. Louis Children’s Hospital, said that the finding that males were more likely to present with stage II or higher disease compared with females “could be related to their finding that females had more superficial spreading melanomas, whereas males had more nodular melanoma.” Those differences “could influence how providers evaluate melanocytic lesions in children,” she added.
Dr. Coughlin, who directs the pediatric dermatology fellowship at Washington University/St. Louis Children’s Hospital, said it was “interesting” that the authors found no association between older age and an increased risk of death. “It would be helpful to have more data about melanoma subtype, including information about Spitz or Spitzoid melanomas,” she said. “Also, knowing the distribution of melanoma across the age categories could provide more insight into their data.”
Ms. Dahak received an award from the National Cancer Institute to fund travel for presentation of this study at the SPD meeting. No other financial conflicts were reported by the researchers. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance (PeDRA) and the International Immunosuppression and Transplant Skin Cancer Collaborative.
AT SPD 2022
Ruxolitinib found to benefit adolescents with vitiligo up to one year
INDIANAPOLIS – and a higher proportion responded at week 52, results from a pooled analysis of phase 3 data showed.
Currently, there is no treatment approved by the Food and Drug Administration to repigment patients with vitiligo, but the cream formulation of the Janus kinase inhibitor ruxolitinib was shown to be effective and have a favorable safety profile in patients aged 12 years and up in the phase 3 clinical trials, TRuE-V1 and TruE-V2. “We know that about half of patients will develop vitiligo by the age of 20, so there is a significant need to have treatments available for the pediatric population,” lead study author David Rosmarin, MD, told this news organization in advance of the annual meeting of the Society for Pediatric Dermatology.
In September 2021, topical ruxolitinib (Opzelura) was approved by the FDA for treating atopic dermatitis in nonimmunocompromised patients aged 12 years and older. The manufacturer, Incyte, has submitted an application for approval to the agency for treating vitiligo in patients ages 12 years and older based on 24-week results; the FDA is expected to make a decision by July 18.
For the current study, presented during a poster session at the meeting, Dr. Rosmarin, of the department of dermatology at Tufts Medical Center, Boston, and colleagues pooled efficacy and safety data for adolescent patients aged 12-17 years from the TRuE-V studies, which enrolled patients 12 years of age and older diagnosed with nonsegmental vitiligo with depigmentation covering up to 10% of total body surface area (BSA), including facial and total Vitiligo Area Scoring Index (F-VASI/T-VASI) scores of ≥ 0.5/≥ 3. Investigators randomized patients 2:1 to twice-daily 1.5% ruxolitinib cream or vehicle for 24 weeks, after which all patients could apply 1.5% ruxolitinib cream through week 52. Efficacy endpoints included the proportions of patients who achieved at least 75%, 50%, and 90% improvement from baseline in F-VASI scores (F-VASI75, F-VASI50, F-VASI90); the proportion of patients who achieved at least a 50% improvement from baseline in T-VASI (T-VASI50); the proportion of patients who achieved a Vitiligo Noticeability Scale (VNS) rating of 4 or 5; and percentage change from baseline in facial BSA (F-BSA). Safety and tolerability were also assessed.
For the pooled analysis, Dr. Rosmarin and colleagues reported results on 72 adolescents: 55 who received ruxolitinib cream and 17 who received vehicle. At week 24, 32.1% of adolescents treated with ruxolitinib cream achieved F-VASI75, compared with none of those in the vehicle group. Further, response rates at week 52 for patients who applied ruxolitinib cream from day 1 were as follows: F-VASI75, 48.0%; F-VASI50, 70.0%; F-VASI90, 24.0%; T-VASI50, 60.0%; VNS score of 4/5, 56.0%; and F-BSA mean percentage change from baseline, –41.9%.
Efficacy at week 52 among crossover patients (after 28 weeks of ruxolitinib cream) was consistent with week 24 data in patients who applied ruxolitinib cream from day 1.
“As we know that repigmentation takes time, about half of the patients achieved the F-VASI75 at the 52-week endpoint,” said Dr. Rosmarin, who is also vice-chair for research and education at Tufts Medical Center, Boston. “Particularly remarkable is that 60% of adolescents achieved a T-VASI50 [50% or more repigmentation of the whole body at the year mark] and over half the patients described their vitiligo as a lot less noticeable or no longer noticeable at the year mark.”
In terms of safety, treatment-related adverse events occurred in 12.9% of patients treated with ruxolitinib (no information was available on the specific events). Serious adverse events occurred in 1.4% of patients; none were considered related to treatment.
“Overall, these results are quite impressive,” Dr. Rosmarin said. “While it can be very challenging to repigment patients with vitiligo, ruxolitinib cream provides an effective option which can help many of my patients.” He acknowledged certain limitations of the analysis, including the fact that the TRuE-V studies were conducted during the COVID-19 pandemic, “which may have contributed to patients being lost to follow-up. Also, the majority of the patients had skin phototypes 1-3.”
Carrie C. Coughlin, MD, who was asked to comment on the study, said that patients with vitiligo need treatment options that are well-studied and covered by insurance. “This study is a great step forward in developing medications for this underserved patient population,” said Dr. Coughlin, who directs the section of pediatric dermatology at Washington University/St. Louis Children’s Hospital.
However, she continued, “the authors mention approximately 13% of patients had a treatment-related adverse reaction, but the abstract does not delineate these reactions.” In addition, the study was limited to children who had less than or equal to 10% body surface area involvement of vitiligo, she noted, adding that “more work is needed to learn about safety of application to larger surface areas.”
Going forward, “it will be important to learn the durability of response,” said Dr. Coughlin, who is also assistant professor of dermatology at Washington University in St. Louis. “Does the vitiligo return if patients stop applying the ruxolitinib cream?”
Dr. Rosmarin disclosed that he has received honoraria as a consultant for Incyte, AbbVie, Abcuro, AltruBio, Arena, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Janssen, Kyowa Kirin, Lilly, Novartis, Pfizer, Regeneron, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, and VielaBio. He has also received research support from Incyte, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Dermira, Galderma, Janssen, Lilly, Merck, Novartis, Pfizer, and Regeneron; and has served as a paid speaker for Incyte, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Incyte, Janssen, Lilly, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance and the International Immunosuppression and Transplant Skin Cancer Collaborative.
INDIANAPOLIS – and a higher proportion responded at week 52, results from a pooled analysis of phase 3 data showed.
Currently, there is no treatment approved by the Food and Drug Administration to repigment patients with vitiligo, but the cream formulation of the Janus kinase inhibitor ruxolitinib was shown to be effective and have a favorable safety profile in patients aged 12 years and up in the phase 3 clinical trials, TRuE-V1 and TruE-V2. “We know that about half of patients will develop vitiligo by the age of 20, so there is a significant need to have treatments available for the pediatric population,” lead study author David Rosmarin, MD, told this news organization in advance of the annual meeting of the Society for Pediatric Dermatology.
In September 2021, topical ruxolitinib (Opzelura) was approved by the FDA for treating atopic dermatitis in nonimmunocompromised patients aged 12 years and older. The manufacturer, Incyte, has submitted an application for approval to the agency for treating vitiligo in patients ages 12 years and older based on 24-week results; the FDA is expected to make a decision by July 18.
For the current study, presented during a poster session at the meeting, Dr. Rosmarin, of the department of dermatology at Tufts Medical Center, Boston, and colleagues pooled efficacy and safety data for adolescent patients aged 12-17 years from the TRuE-V studies, which enrolled patients 12 years of age and older diagnosed with nonsegmental vitiligo with depigmentation covering up to 10% of total body surface area (BSA), including facial and total Vitiligo Area Scoring Index (F-VASI/T-VASI) scores of ≥ 0.5/≥ 3. Investigators randomized patients 2:1 to twice-daily 1.5% ruxolitinib cream or vehicle for 24 weeks, after which all patients could apply 1.5% ruxolitinib cream through week 52. Efficacy endpoints included the proportions of patients who achieved at least 75%, 50%, and 90% improvement from baseline in F-VASI scores (F-VASI75, F-VASI50, F-VASI90); the proportion of patients who achieved at least a 50% improvement from baseline in T-VASI (T-VASI50); the proportion of patients who achieved a Vitiligo Noticeability Scale (VNS) rating of 4 or 5; and percentage change from baseline in facial BSA (F-BSA). Safety and tolerability were also assessed.
For the pooled analysis, Dr. Rosmarin and colleagues reported results on 72 adolescents: 55 who received ruxolitinib cream and 17 who received vehicle. At week 24, 32.1% of adolescents treated with ruxolitinib cream achieved F-VASI75, compared with none of those in the vehicle group. Further, response rates at week 52 for patients who applied ruxolitinib cream from day 1 were as follows: F-VASI75, 48.0%; F-VASI50, 70.0%; F-VASI90, 24.0%; T-VASI50, 60.0%; VNS score of 4/5, 56.0%; and F-BSA mean percentage change from baseline, –41.9%.
Efficacy at week 52 among crossover patients (after 28 weeks of ruxolitinib cream) was consistent with week 24 data in patients who applied ruxolitinib cream from day 1.
“As we know that repigmentation takes time, about half of the patients achieved the F-VASI75 at the 52-week endpoint,” said Dr. Rosmarin, who is also vice-chair for research and education at Tufts Medical Center, Boston. “Particularly remarkable is that 60% of adolescents achieved a T-VASI50 [50% or more repigmentation of the whole body at the year mark] and over half the patients described their vitiligo as a lot less noticeable or no longer noticeable at the year mark.”
In terms of safety, treatment-related adverse events occurred in 12.9% of patients treated with ruxolitinib (no information was available on the specific events). Serious adverse events occurred in 1.4% of patients; none were considered related to treatment.
“Overall, these results are quite impressive,” Dr. Rosmarin said. “While it can be very challenging to repigment patients with vitiligo, ruxolitinib cream provides an effective option which can help many of my patients.” He acknowledged certain limitations of the analysis, including the fact that the TRuE-V studies were conducted during the COVID-19 pandemic, “which may have contributed to patients being lost to follow-up. Also, the majority of the patients had skin phototypes 1-3.”
Carrie C. Coughlin, MD, who was asked to comment on the study, said that patients with vitiligo need treatment options that are well-studied and covered by insurance. “This study is a great step forward in developing medications for this underserved patient population,” said Dr. Coughlin, who directs the section of pediatric dermatology at Washington University/St. Louis Children’s Hospital.
However, she continued, “the authors mention approximately 13% of patients had a treatment-related adverse reaction, but the abstract does not delineate these reactions.” In addition, the study was limited to children who had less than or equal to 10% body surface area involvement of vitiligo, she noted, adding that “more work is needed to learn about safety of application to larger surface areas.”
Going forward, “it will be important to learn the durability of response,” said Dr. Coughlin, who is also assistant professor of dermatology at Washington University in St. Louis. “Does the vitiligo return if patients stop applying the ruxolitinib cream?”
Dr. Rosmarin disclosed that he has received honoraria as a consultant for Incyte, AbbVie, Abcuro, AltruBio, Arena, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Janssen, Kyowa Kirin, Lilly, Novartis, Pfizer, Regeneron, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, and VielaBio. He has also received research support from Incyte, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Dermira, Galderma, Janssen, Lilly, Merck, Novartis, Pfizer, and Regeneron; and has served as a paid speaker for Incyte, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Incyte, Janssen, Lilly, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance and the International Immunosuppression and Transplant Skin Cancer Collaborative.
INDIANAPOLIS – and a higher proportion responded at week 52, results from a pooled analysis of phase 3 data showed.
Currently, there is no treatment approved by the Food and Drug Administration to repigment patients with vitiligo, but the cream formulation of the Janus kinase inhibitor ruxolitinib was shown to be effective and have a favorable safety profile in patients aged 12 years and up in the phase 3 clinical trials, TRuE-V1 and TruE-V2. “We know that about half of patients will develop vitiligo by the age of 20, so there is a significant need to have treatments available for the pediatric population,” lead study author David Rosmarin, MD, told this news organization in advance of the annual meeting of the Society for Pediatric Dermatology.
In September 2021, topical ruxolitinib (Opzelura) was approved by the FDA for treating atopic dermatitis in nonimmunocompromised patients aged 12 years and older. The manufacturer, Incyte, has submitted an application for approval to the agency for treating vitiligo in patients ages 12 years and older based on 24-week results; the FDA is expected to make a decision by July 18.
For the current study, presented during a poster session at the meeting, Dr. Rosmarin, of the department of dermatology at Tufts Medical Center, Boston, and colleagues pooled efficacy and safety data for adolescent patients aged 12-17 years from the TRuE-V studies, which enrolled patients 12 years of age and older diagnosed with nonsegmental vitiligo with depigmentation covering up to 10% of total body surface area (BSA), including facial and total Vitiligo Area Scoring Index (F-VASI/T-VASI) scores of ≥ 0.5/≥ 3. Investigators randomized patients 2:1 to twice-daily 1.5% ruxolitinib cream or vehicle for 24 weeks, after which all patients could apply 1.5% ruxolitinib cream through week 52. Efficacy endpoints included the proportions of patients who achieved at least 75%, 50%, and 90% improvement from baseline in F-VASI scores (F-VASI75, F-VASI50, F-VASI90); the proportion of patients who achieved at least a 50% improvement from baseline in T-VASI (T-VASI50); the proportion of patients who achieved a Vitiligo Noticeability Scale (VNS) rating of 4 or 5; and percentage change from baseline in facial BSA (F-BSA). Safety and tolerability were also assessed.
For the pooled analysis, Dr. Rosmarin and colleagues reported results on 72 adolescents: 55 who received ruxolitinib cream and 17 who received vehicle. At week 24, 32.1% of adolescents treated with ruxolitinib cream achieved F-VASI75, compared with none of those in the vehicle group. Further, response rates at week 52 for patients who applied ruxolitinib cream from day 1 were as follows: F-VASI75, 48.0%; F-VASI50, 70.0%; F-VASI90, 24.0%; T-VASI50, 60.0%; VNS score of 4/5, 56.0%; and F-BSA mean percentage change from baseline, –41.9%.
Efficacy at week 52 among crossover patients (after 28 weeks of ruxolitinib cream) was consistent with week 24 data in patients who applied ruxolitinib cream from day 1.
“As we know that repigmentation takes time, about half of the patients achieved the F-VASI75 at the 52-week endpoint,” said Dr. Rosmarin, who is also vice-chair for research and education at Tufts Medical Center, Boston. “Particularly remarkable is that 60% of adolescents achieved a T-VASI50 [50% or more repigmentation of the whole body at the year mark] and over half the patients described their vitiligo as a lot less noticeable or no longer noticeable at the year mark.”
In terms of safety, treatment-related adverse events occurred in 12.9% of patients treated with ruxolitinib (no information was available on the specific events). Serious adverse events occurred in 1.4% of patients; none were considered related to treatment.
“Overall, these results are quite impressive,” Dr. Rosmarin said. “While it can be very challenging to repigment patients with vitiligo, ruxolitinib cream provides an effective option which can help many of my patients.” He acknowledged certain limitations of the analysis, including the fact that the TRuE-V studies were conducted during the COVID-19 pandemic, “which may have contributed to patients being lost to follow-up. Also, the majority of the patients had skin phototypes 1-3.”
Carrie C. Coughlin, MD, who was asked to comment on the study, said that patients with vitiligo need treatment options that are well-studied and covered by insurance. “This study is a great step forward in developing medications for this underserved patient population,” said Dr. Coughlin, who directs the section of pediatric dermatology at Washington University/St. Louis Children’s Hospital.
However, she continued, “the authors mention approximately 13% of patients had a treatment-related adverse reaction, but the abstract does not delineate these reactions.” In addition, the study was limited to children who had less than or equal to 10% body surface area involvement of vitiligo, she noted, adding that “more work is needed to learn about safety of application to larger surface areas.”
Going forward, “it will be important to learn the durability of response,” said Dr. Coughlin, who is also assistant professor of dermatology at Washington University in St. Louis. “Does the vitiligo return if patients stop applying the ruxolitinib cream?”
Dr. Rosmarin disclosed that he has received honoraria as a consultant for Incyte, AbbVie, Abcuro, AltruBio, Arena, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Janssen, Kyowa Kirin, Lilly, Novartis, Pfizer, Regeneron, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, and VielaBio. He has also received research support from Incyte, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Dermira, Galderma, Janssen, Lilly, Merck, Novartis, Pfizer, and Regeneron; and has served as a paid speaker for Incyte, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Incyte, Janssen, Lilly, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance and the International Immunosuppression and Transplant Skin Cancer Collaborative.
AT SPD 2022
To vaccinate 6-month- to 5-year-olds against SARS-CoV-2 or not to vaccinate
A family’s decision to vaccinate their child is best made jointly with a trusted medical provider who knows the child and family. The American Academy of Pediatrics created a toolkit with resources for answering questions about the recently authorized SARS-CoV-2 mRNA vaccines (Pfizer and Moderna) for 6-month- to 5-year-olds with science-backed vaccine facts, including links to other useful AAP information websites, talking points, graphics, and videos.1
SARS-CoV-2 seasonality
SARS-CoV-2 is now endemic, not a once-a-year seasonal virus. Seasons (aka surges) will occur whenever a new variant arises (twice yearly since 2020, Omicron BA.4/BA.5 currently), or when enough vaccine holdouts, newborns, and/or those with waning of prior immunity (vaccine or infection induced) accrue.
Emergency use authorization submission data for mRNA vaccine responses in young children2,3
Moderna in 6-month- through 5-year-olds. Two 25-mcg doses given 4-8 weeks apart produced 37.8% (95% confidence interval, 20.9%-51.1%) protection against symptomatic Omicron SARS-CoV-2 infections through 3 months of follow-up. Immunobridging analysis of antibody responses compared to 18- to 25-year-olds (100-mcg doses) showed the children’s responses were noninferior. Thus, the committee inferred that vaccine effectiveness in children should be similar to that in 18- to 25-year-olds. Fever, irritability, or local reaction/pain occurred in two-thirds after the second dose. Grade 3 reactions were noted in less than 5%.
Pfizer in 6-month- through 4-year-olds. Three 3-mcg doses, two doses 3-8 weeks apart and the third dose at least 8 weeks later (median 16 weeks), produced 80.3% (95% CI, 13.9%-96.7%) protection against symptomatic COVID-19 during the 6 weeks after the third dose. Local and systemic reactions occurred in 63.8%; less than 5% had grade 3 reactions (fever in about 3%, irritability in 1.3%, fatigue in 0.8%) mostly after second dose.
Neither duration of follow-up is very long. The Moderna data tell me that a third primary dose would have been better but restarting the trial to evaluate third doses would have delayed Moderna’s EUA another 4-6 months. The three-dose Pfizer data look better but may not have been as good with another 6 weeks of follow-up.
Additional post-EUA data will be collected. Boosters will be needed when immunity from both vaccines wanes (one estimate is about 6 months after the primary series). The Advisory Committee on Immunization Practices noted in their deliberations that vaccine-induced antibody responses are higher and cross-neutralize variants (even Omicron) better than infection-induced immunity.4
Are there downsides to the vaccines? Naysayers question vaccinating children less than 5 years old with reasons containing enough “truth” that they catch people’s attention, for example, “young children don’t get very sick with COVID-19,” “most have been infected already,” “RNA for the spike protein stays in the body for months,” or “myocarditis.” Naysayers can quote references in reputable journals but seem to spin selected data out of context or quote unconfirmed data from the Vaccine Adverse Event Reporting System.
Reasons to vaccinate
- While children have milder disease than adults, mid-June 2022 surveillance indicated 50 hospitalizations and 1 pediatric death each day from SARS-CoV-2.5
- Vaccinating young children endows a foundation of vaccine-induced SARS-CoV-2 immunity that is superior to infection-induced immunity.4
- Long-term effects of large numbers of SARS-CoV-2 particles that enter every organ of a developing child have not been determined.
- Viral loads are lowered by prior vaccine; fewer viral replications lessen chances for newer variants to arise.
- Transmission is less in breakthrough infections than infections in the unvaccinated.
- Thirty percent of 5- to 11-year-olds hospitalized for SARS-CoV-2 had no underlying conditions;6 hospitalization rates in newborn to 4-year-olds have been the highest in the Omicron surge.7
- No myocarditis or pericarditis episodes have been detected in 6-month- to 11-year-old trials.
- The AAP and ACIP recommend the mRNA vaccines.
My thoughts are that SARS-CoV-2 vaccine is just another “routine” childhood vaccine that prepares children for healthier futures, pandemic or not, and the vaccines are as safe as other routine vaccines.
And like other pediatric vaccines, it should be no surprise that boosters will be needed, even if no newer variants than Omicron BA.4/BA.5 arise. But we know newer variants will arise and, similar to influenza vaccine, new formulations, perhaps with multiple SARS-CoV-2 strain antigens, will be needed every year or so. Everyone will get SARS-CoV-2 multiple times in their lives no matter how careful they are. So isn’t it good medical practice to establish early the best available foundation for maintaining lifelong SARS-CoV-2 immunity?
To me it is like pertussis. Most pertussis-infected children are sick enough to be hospitalized; very few die. They are miserable with illnesses that take weeks to months to subside. The worst disease usually occurs in unvaccinated young children or those with underlying conditions. Reactogenicity was reduced with acellular vaccine but resulted in less immunogenicity, so we give boosters at intervals that best match waning immunity. Circulating strains can be different than the vaccine strain, so protection against infection is 80%. Finally, even the safest vaccine may very rarely have sequelae. That is why The National Vaccine Injury Compensation Program was created. Yet the benefit-to-harm ratio for children and society favors universal pertussis vaccine use. And we vaccinate even those who have had pertussis because even infection-based immunity is incomplete and protection wanes. If arguments similar to those by SARS-CoV-2 vaccine naysayers were applied to acellular pertussis vaccine, it seems they would argue against pertussis vaccine for young children.
Another major issue has been “safety concerns” about the vaccines’ small amount of mRNA for the spike protein encased in microscopic lipid bubbles injected in the arm or leg. This mRNA is picked up by human cells, and in the cytoplasm (not the nucleus where our DNA resides) produces a limited supply of spike protein that is then picked up by antigen-presenting cells for short-lived distribution (days to 2 weeks at most) to regional lymph nodes where immune-memory processes are jump-started. Contrast that to even asymptomatic SARS-CoV-2 infection where multibillions of virus particles are produced for up to 14 days with access to every bodily organ that contains ACE-2 receptors (they all do). Each virus particle hijacks a human cell producing thousands of mRNA for spike protein (and multiple other SARS-CoV-2 proteins), eventually releasing multibillions of lipid fragments from the ruptured cell. Comparing the amount of these components in the mRNA vaccines to those from infection is like comparing a campfire to the many-thousand-acre wildfire. So, if one is worried about the effects of spike protein and lipid fragments, the limited localized amounts in mRNA vaccines should make one much less concerned than the enormous amounts circulating throughout the body as a result of a SARS-CoV-2 infection.
My take is that children 6-months to 5-years-old deserve SARS-CoV-2–induced vaccine protection and we can and should strongly recommend it as medical providers and child advocates.
*Dr. Harrison is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. Email him at pdnews@mdedge.com.
References
1. AAP. 2022 Jun 21. As COVID-19 vaccines become available for children ages 6 months to 4 years, AAP urges families to reach out to pediatricians to ask questions and access vaccine. www.aap.org.
2. CDC. Grading of recommendations, assessment, development, and evaluation (GRADE): Moderna COVID-19 vaccine for children aged 6 months–5 years. www.cdc.gov.
3. CDC. ACIP evidence to recommendations for use of Moderna COVID-19 vaccine in children ages 6 months–5 years and Pfizer-BioNTech COVID-19 vaccine in children ages 6 months–4 years under an emergency use authorization. www.cdc.gov.
4. Tang J et al. Nat Commun. 2022;13:2979.
5. Children and COVID-19: State Data Report. 2022 Jun 30. www.aap.org.
6. Shi DS et al. MMWR Morb Mortal Wkly Rep. 2022;71:574-81.
7. Marks KJ et al. MMWR Morb Mortal Wkly Rep. 2022;71:429-36.
Other good resources for families are https://getvaccineanswers.org/ or www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-in-babies-and-children/art-20484405.
*This story was updated on July 19, 2022.
A family’s decision to vaccinate their child is best made jointly with a trusted medical provider who knows the child and family. The American Academy of Pediatrics created a toolkit with resources for answering questions about the recently authorized SARS-CoV-2 mRNA vaccines (Pfizer and Moderna) for 6-month- to 5-year-olds with science-backed vaccine facts, including links to other useful AAP information websites, talking points, graphics, and videos.1
SARS-CoV-2 seasonality
SARS-CoV-2 is now endemic, not a once-a-year seasonal virus. Seasons (aka surges) will occur whenever a new variant arises (twice yearly since 2020, Omicron BA.4/BA.5 currently), or when enough vaccine holdouts, newborns, and/or those with waning of prior immunity (vaccine or infection induced) accrue.
Emergency use authorization submission data for mRNA vaccine responses in young children2,3
Moderna in 6-month- through 5-year-olds. Two 25-mcg doses given 4-8 weeks apart produced 37.8% (95% confidence interval, 20.9%-51.1%) protection against symptomatic Omicron SARS-CoV-2 infections through 3 months of follow-up. Immunobridging analysis of antibody responses compared to 18- to 25-year-olds (100-mcg doses) showed the children’s responses were noninferior. Thus, the committee inferred that vaccine effectiveness in children should be similar to that in 18- to 25-year-olds. Fever, irritability, or local reaction/pain occurred in two-thirds after the second dose. Grade 3 reactions were noted in less than 5%.
Pfizer in 6-month- through 4-year-olds. Three 3-mcg doses, two doses 3-8 weeks apart and the third dose at least 8 weeks later (median 16 weeks), produced 80.3% (95% CI, 13.9%-96.7%) protection against symptomatic COVID-19 during the 6 weeks after the third dose. Local and systemic reactions occurred in 63.8%; less than 5% had grade 3 reactions (fever in about 3%, irritability in 1.3%, fatigue in 0.8%) mostly after second dose.
Neither duration of follow-up is very long. The Moderna data tell me that a third primary dose would have been better but restarting the trial to evaluate third doses would have delayed Moderna’s EUA another 4-6 months. The three-dose Pfizer data look better but may not have been as good with another 6 weeks of follow-up.
Additional post-EUA data will be collected. Boosters will be needed when immunity from both vaccines wanes (one estimate is about 6 months after the primary series). The Advisory Committee on Immunization Practices noted in their deliberations that vaccine-induced antibody responses are higher and cross-neutralize variants (even Omicron) better than infection-induced immunity.4
Are there downsides to the vaccines? Naysayers question vaccinating children less than 5 years old with reasons containing enough “truth” that they catch people’s attention, for example, “young children don’t get very sick with COVID-19,” “most have been infected already,” “RNA for the spike protein stays in the body for months,” or “myocarditis.” Naysayers can quote references in reputable journals but seem to spin selected data out of context or quote unconfirmed data from the Vaccine Adverse Event Reporting System.
Reasons to vaccinate
- While children have milder disease than adults, mid-June 2022 surveillance indicated 50 hospitalizations and 1 pediatric death each day from SARS-CoV-2.5
- Vaccinating young children endows a foundation of vaccine-induced SARS-CoV-2 immunity that is superior to infection-induced immunity.4
- Long-term effects of large numbers of SARS-CoV-2 particles that enter every organ of a developing child have not been determined.
- Viral loads are lowered by prior vaccine; fewer viral replications lessen chances for newer variants to arise.
- Transmission is less in breakthrough infections than infections in the unvaccinated.
- Thirty percent of 5- to 11-year-olds hospitalized for SARS-CoV-2 had no underlying conditions;6 hospitalization rates in newborn to 4-year-olds have been the highest in the Omicron surge.7
- No myocarditis or pericarditis episodes have been detected in 6-month- to 11-year-old trials.
- The AAP and ACIP recommend the mRNA vaccines.
My thoughts are that SARS-CoV-2 vaccine is just another “routine” childhood vaccine that prepares children for healthier futures, pandemic or not, and the vaccines are as safe as other routine vaccines.
And like other pediatric vaccines, it should be no surprise that boosters will be needed, even if no newer variants than Omicron BA.4/BA.5 arise. But we know newer variants will arise and, similar to influenza vaccine, new formulations, perhaps with multiple SARS-CoV-2 strain antigens, will be needed every year or so. Everyone will get SARS-CoV-2 multiple times in their lives no matter how careful they are. So isn’t it good medical practice to establish early the best available foundation for maintaining lifelong SARS-CoV-2 immunity?
To me it is like pertussis. Most pertussis-infected children are sick enough to be hospitalized; very few die. They are miserable with illnesses that take weeks to months to subside. The worst disease usually occurs in unvaccinated young children or those with underlying conditions. Reactogenicity was reduced with acellular vaccine but resulted in less immunogenicity, so we give boosters at intervals that best match waning immunity. Circulating strains can be different than the vaccine strain, so protection against infection is 80%. Finally, even the safest vaccine may very rarely have sequelae. That is why The National Vaccine Injury Compensation Program was created. Yet the benefit-to-harm ratio for children and society favors universal pertussis vaccine use. And we vaccinate even those who have had pertussis because even infection-based immunity is incomplete and protection wanes. If arguments similar to those by SARS-CoV-2 vaccine naysayers were applied to acellular pertussis vaccine, it seems they would argue against pertussis vaccine for young children.
Another major issue has been “safety concerns” about the vaccines’ small amount of mRNA for the spike protein encased in microscopic lipid bubbles injected in the arm or leg. This mRNA is picked up by human cells, and in the cytoplasm (not the nucleus where our DNA resides) produces a limited supply of spike protein that is then picked up by antigen-presenting cells for short-lived distribution (days to 2 weeks at most) to regional lymph nodes where immune-memory processes are jump-started. Contrast that to even asymptomatic SARS-CoV-2 infection where multibillions of virus particles are produced for up to 14 days with access to every bodily organ that contains ACE-2 receptors (they all do). Each virus particle hijacks a human cell producing thousands of mRNA for spike protein (and multiple other SARS-CoV-2 proteins), eventually releasing multibillions of lipid fragments from the ruptured cell. Comparing the amount of these components in the mRNA vaccines to those from infection is like comparing a campfire to the many-thousand-acre wildfire. So, if one is worried about the effects of spike protein and lipid fragments, the limited localized amounts in mRNA vaccines should make one much less concerned than the enormous amounts circulating throughout the body as a result of a SARS-CoV-2 infection.
My take is that children 6-months to 5-years-old deserve SARS-CoV-2–induced vaccine protection and we can and should strongly recommend it as medical providers and child advocates.
*Dr. Harrison is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. Email him at pdnews@mdedge.com.
References
1. AAP. 2022 Jun 21. As COVID-19 vaccines become available for children ages 6 months to 4 years, AAP urges families to reach out to pediatricians to ask questions and access vaccine. www.aap.org.
2. CDC. Grading of recommendations, assessment, development, and evaluation (GRADE): Moderna COVID-19 vaccine for children aged 6 months–5 years. www.cdc.gov.
3. CDC. ACIP evidence to recommendations for use of Moderna COVID-19 vaccine in children ages 6 months–5 years and Pfizer-BioNTech COVID-19 vaccine in children ages 6 months–4 years under an emergency use authorization. www.cdc.gov.
4. Tang J et al. Nat Commun. 2022;13:2979.
5. Children and COVID-19: State Data Report. 2022 Jun 30. www.aap.org.
6. Shi DS et al. MMWR Morb Mortal Wkly Rep. 2022;71:574-81.
7. Marks KJ et al. MMWR Morb Mortal Wkly Rep. 2022;71:429-36.
Other good resources for families are https://getvaccineanswers.org/ or www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-in-babies-and-children/art-20484405.
*This story was updated on July 19, 2022.
A family’s decision to vaccinate their child is best made jointly with a trusted medical provider who knows the child and family. The American Academy of Pediatrics created a toolkit with resources for answering questions about the recently authorized SARS-CoV-2 mRNA vaccines (Pfizer and Moderna) for 6-month- to 5-year-olds with science-backed vaccine facts, including links to other useful AAP information websites, talking points, graphics, and videos.1
SARS-CoV-2 seasonality
SARS-CoV-2 is now endemic, not a once-a-year seasonal virus. Seasons (aka surges) will occur whenever a new variant arises (twice yearly since 2020, Omicron BA.4/BA.5 currently), or when enough vaccine holdouts, newborns, and/or those with waning of prior immunity (vaccine or infection induced) accrue.
Emergency use authorization submission data for mRNA vaccine responses in young children2,3
Moderna in 6-month- through 5-year-olds. Two 25-mcg doses given 4-8 weeks apart produced 37.8% (95% confidence interval, 20.9%-51.1%) protection against symptomatic Omicron SARS-CoV-2 infections through 3 months of follow-up. Immunobridging analysis of antibody responses compared to 18- to 25-year-olds (100-mcg doses) showed the children’s responses were noninferior. Thus, the committee inferred that vaccine effectiveness in children should be similar to that in 18- to 25-year-olds. Fever, irritability, or local reaction/pain occurred in two-thirds after the second dose. Grade 3 reactions were noted in less than 5%.
Pfizer in 6-month- through 4-year-olds. Three 3-mcg doses, two doses 3-8 weeks apart and the third dose at least 8 weeks later (median 16 weeks), produced 80.3% (95% CI, 13.9%-96.7%) protection against symptomatic COVID-19 during the 6 weeks after the third dose. Local and systemic reactions occurred in 63.8%; less than 5% had grade 3 reactions (fever in about 3%, irritability in 1.3%, fatigue in 0.8%) mostly after second dose.
Neither duration of follow-up is very long. The Moderna data tell me that a third primary dose would have been better but restarting the trial to evaluate third doses would have delayed Moderna’s EUA another 4-6 months. The three-dose Pfizer data look better but may not have been as good with another 6 weeks of follow-up.
Additional post-EUA data will be collected. Boosters will be needed when immunity from both vaccines wanes (one estimate is about 6 months after the primary series). The Advisory Committee on Immunization Practices noted in their deliberations that vaccine-induced antibody responses are higher and cross-neutralize variants (even Omicron) better than infection-induced immunity.4
Are there downsides to the vaccines? Naysayers question vaccinating children less than 5 years old with reasons containing enough “truth” that they catch people’s attention, for example, “young children don’t get very sick with COVID-19,” “most have been infected already,” “RNA for the spike protein stays in the body for months,” or “myocarditis.” Naysayers can quote references in reputable journals but seem to spin selected data out of context or quote unconfirmed data from the Vaccine Adverse Event Reporting System.
Reasons to vaccinate
- While children have milder disease than adults, mid-June 2022 surveillance indicated 50 hospitalizations and 1 pediatric death each day from SARS-CoV-2.5
- Vaccinating young children endows a foundation of vaccine-induced SARS-CoV-2 immunity that is superior to infection-induced immunity.4
- Long-term effects of large numbers of SARS-CoV-2 particles that enter every organ of a developing child have not been determined.
- Viral loads are lowered by prior vaccine; fewer viral replications lessen chances for newer variants to arise.
- Transmission is less in breakthrough infections than infections in the unvaccinated.
- Thirty percent of 5- to 11-year-olds hospitalized for SARS-CoV-2 had no underlying conditions;6 hospitalization rates in newborn to 4-year-olds have been the highest in the Omicron surge.7
- No myocarditis or pericarditis episodes have been detected in 6-month- to 11-year-old trials.
- The AAP and ACIP recommend the mRNA vaccines.
My thoughts are that SARS-CoV-2 vaccine is just another “routine” childhood vaccine that prepares children for healthier futures, pandemic or not, and the vaccines are as safe as other routine vaccines.
And like other pediatric vaccines, it should be no surprise that boosters will be needed, even if no newer variants than Omicron BA.4/BA.5 arise. But we know newer variants will arise and, similar to influenza vaccine, new formulations, perhaps with multiple SARS-CoV-2 strain antigens, will be needed every year or so. Everyone will get SARS-CoV-2 multiple times in their lives no matter how careful they are. So isn’t it good medical practice to establish early the best available foundation for maintaining lifelong SARS-CoV-2 immunity?
To me it is like pertussis. Most pertussis-infected children are sick enough to be hospitalized; very few die. They are miserable with illnesses that take weeks to months to subside. The worst disease usually occurs in unvaccinated young children or those with underlying conditions. Reactogenicity was reduced with acellular vaccine but resulted in less immunogenicity, so we give boosters at intervals that best match waning immunity. Circulating strains can be different than the vaccine strain, so protection against infection is 80%. Finally, even the safest vaccine may very rarely have sequelae. That is why The National Vaccine Injury Compensation Program was created. Yet the benefit-to-harm ratio for children and society favors universal pertussis vaccine use. And we vaccinate even those who have had pertussis because even infection-based immunity is incomplete and protection wanes. If arguments similar to those by SARS-CoV-2 vaccine naysayers were applied to acellular pertussis vaccine, it seems they would argue against pertussis vaccine for young children.
Another major issue has been “safety concerns” about the vaccines’ small amount of mRNA for the spike protein encased in microscopic lipid bubbles injected in the arm or leg. This mRNA is picked up by human cells, and in the cytoplasm (not the nucleus where our DNA resides) produces a limited supply of spike protein that is then picked up by antigen-presenting cells for short-lived distribution (days to 2 weeks at most) to regional lymph nodes where immune-memory processes are jump-started. Contrast that to even asymptomatic SARS-CoV-2 infection where multibillions of virus particles are produced for up to 14 days with access to every bodily organ that contains ACE-2 receptors (they all do). Each virus particle hijacks a human cell producing thousands of mRNA for spike protein (and multiple other SARS-CoV-2 proteins), eventually releasing multibillions of lipid fragments from the ruptured cell. Comparing the amount of these components in the mRNA vaccines to those from infection is like comparing a campfire to the many-thousand-acre wildfire. So, if one is worried about the effects of spike protein and lipid fragments, the limited localized amounts in mRNA vaccines should make one much less concerned than the enormous amounts circulating throughout the body as a result of a SARS-CoV-2 infection.
My take is that children 6-months to 5-years-old deserve SARS-CoV-2–induced vaccine protection and we can and should strongly recommend it as medical providers and child advocates.
*Dr. Harrison is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. Email him at pdnews@mdedge.com.
References
1. AAP. 2022 Jun 21. As COVID-19 vaccines become available for children ages 6 months to 4 years, AAP urges families to reach out to pediatricians to ask questions and access vaccine. www.aap.org.
2. CDC. Grading of recommendations, assessment, development, and evaluation (GRADE): Moderna COVID-19 vaccine for children aged 6 months–5 years. www.cdc.gov.
3. CDC. ACIP evidence to recommendations for use of Moderna COVID-19 vaccine in children ages 6 months–5 years and Pfizer-BioNTech COVID-19 vaccine in children ages 6 months–4 years under an emergency use authorization. www.cdc.gov.
4. Tang J et al. Nat Commun. 2022;13:2979.
5. Children and COVID-19: State Data Report. 2022 Jun 30. www.aap.org.
6. Shi DS et al. MMWR Morb Mortal Wkly Rep. 2022;71:574-81.
7. Marks KJ et al. MMWR Morb Mortal Wkly Rep. 2022;71:429-36.
Other good resources for families are https://getvaccineanswers.org/ or www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-in-babies-and-children/art-20484405.
*This story was updated on July 19, 2022.
Precocious puberty – how early is too soon?
A 6-year-old girl presents with breast development. Her medical history is unremarkable. The parents are of average height, and the mother reports her thelarche was age 11 years. The girl is at the 97th percentile for her height and 90th percentile for her weight. She has Tanner stage 3 breast development and Tanner stage 2 pubic hair development. She has grown slightly more than 3 inches over the past year. How should she be evaluated and managed (N Engl J Med. 2008;358:2366-77)?
The premature onset of puberty, i.e., precocious puberty (PP), can be an emotionally traumatic event for the child and parents. Over the past century, improvements in public health and nutrition, and, more recently, increased obesity, have been associated with earlier puberty and the dominant factor has been attributed to genetics (Curr Opin Endocrinol Diabetes Obes. 2018;25[1]:49-54). This month’s article will focus on understanding what is considered “early” puberty, evaluating for causes, and managing precocious puberty.
More commonly seen in girls than boys, PP is defined as the onset of secondary sexual characteristics before age 7.5 years in Black and Hispanic girls, and prior to 8 years in White girls, which is 2-2.5 standard deviations below the average age of pubertal onset in healthy children (J Pediatr Adolesc Gynecol. 2019;32:455-9). As a comparison, PP is diagnosed with onset before age 9 years in boys. For White compared with Black girls, the average timing of thelarche is age 10 vs. 9.5 years, peak growth velocity is age 11.5, menarche is age 12.5 vs. 12, while completion of puberty is near age 14.5 vs. 13.5, respectively (J Pediatr. 1985;107:317). Fortunately, most girls with PP have common variants rather than serious pathology.
Classification: Central (CPP) vs. peripheral (PPP)
CPP is gonadotropin dependent, meaning the hypothalamic-pituitary-ovarian axis (HPO) is prematurely activated resulting in the normal progression of puberty.
PPP is gonadotropin independent, caused by sex steroid secretion from any source – ovaries, adrenal gland, exogenous or ectopic production, e.g., germ-cell tumor. This results in a disordered progression of pubertal milestones.
Whereas CPP is typically isosexual development, i.e., consistent with the child’s gender, PPP can be isosexual or contrasexual, e.g., virilization of girls. A third classification is “benign or nonprogressive pubertal variants” manifesting as isolated premature thelarche or adrenarche.
Causes (see table)
CPP. Idiopathic causes account for 80%-90% of presentations in girls and 25%-80% in boys. Remarkably, international and domestic adoption, as well as a family history of PP increases the likelihood of CPP in girls. Other etiologies include CNS lesions, e.g., hamartomas, which are the most common cause of PP in young children. MRI with contrast has been the traditional mode of diagnosis for CNS tumors, yet the yield is dubious in girls above age 6. Genetic causes are found in only a small percentage of PP cases. Rarely, CPP can result from gonadotropin-secreting tumors because of elevated luteinizing hormone levels.
PPP. As a result of sex steroid secretion, peripheral causes of PPP include ovarian cysts and ovarian tumors that increase circulating estradiol, such as granulosa cell tumors, which would cause isosexual PPP and Sertoli-Leydig cell tumors that secrete testosterone, which can result in contrasexual PPP. Mild congenital adrenal hyperplasia can result in PPP with virilization (contrasexual) and markedly advanced bone age.
McCune-Albright syndrome is rare and presents with the classic triad of PPP, skin pigmentation called café-au-lait, and fibrous dysplasia of bone. The pathophysiology of McCune-Albright syndrome is autoactivation of the G-protein leading to activation of ovarian tissue that results in formation of large ovarian cysts and extreme elevations in serum estradiol as well as the potential production of other hormones, e.g., thyrotoxicosis, excess growth hormone (acromegaly), and Cushing syndrome.
Premature thelarche. Premature thelarche typically occurs in girls between the ages of 1 and 3 years and is limited to breast enlargement. While no cause has been determined, the plausible explanations include partial activation of the HPO axis, endocrine-disrupting chemicals (EDCs), or a genetic origin. A small percentage of these girls progress to CPP.
EDCs have been considered as potential influencers of early puberty, but no consensus has been established. (Examples of EDCs in the environment include air, soil, or water supply along with food sources, personal care products, and manufactured products that can affect the endocrine system.)
Premature adenarche. Premature adrenarche presents with adult body odor and/or body hair (pubic and/or axillary) in girls who have an elevated body mass index, most commonly at the ages of 6-7 years. The presumed mechanism is normal maturation of the adrenal gland with resultant elevation of circulating androgens. Bone age may be mildly accelerated and DHEAS is prematurely elevated for age. These girls appear to be at increased risk for polycystic ovary syndrome.
Evaluation
The initial step in the evaluation of PP is to determine whether the cause is CPP or PPP; the latter includes distinguishing isosexual from contrasexual development. A thorough history (growth, headaches, behavior or visual change, seizures, abdominal pain), physical exam, including Tanner staging, and bone age is required. However, with isolated premature thelarche or adrenarche, a bone age may not be necessary, as initial close clinical observation for pubertal progression is likely sufficient.
For CPP, the diagnosis is based on serum LH, whether random levels or elevations follow GnRH stimulation. Puberty milestones progress normally although adrenarche is not consistently apparent. For girls younger than age 6, a brain MRI is recommended but not in asymptomatic older girls with CPP. LH and FSH along with estradiol or testosterone, the latter especially in boys, are the first line of serum testing. Serum TSH is recommended for suspicion of primary hypothyroidism. In girls with premature adrenarche, a bone age, testosterone, DHEAS, and 17-OHP to rule out adrenal hyperplasia should be obtained. Pelvic ultrasound may be a useful adjunct to assess uterine volume and/or ovarian cysts/tumors.
Rapidity of onset can also lead the evaluation since a normal growth chart and skeletal maturation suggests a benign pubertal variant whereas a more rapid rate can signal CPP or PPP. Of note, health care providers should ensure prescription, over-the-counter oral or topical sources of hormones, and EDCs are ruled out.
Consequences
An association between childhood sexual abuse and earlier pubertal onset has been cited. These girls may be at increased risk for psychosocial difficulties, menstrual and fertility problems, and even reproductive cancers because of prolonged exposure to sex hormones (J Adolesc Health. 2016;60[1]:65-71).
Treatment
The mainstay of CPP treatment is maximizing adult height, typically through the use of a GnRH agonist for HPO suppression from pituitary downregulation. For girls above age 8 years, attempts at improving adult height have not shown a benefit.
In girls with PPP, treatment is directed at the prevailing pathology. Interestingly, early PPP can activate the HPO axis thereby converting to “secondary” CPP. In PPP, McCune-Albright syndrome treatment targets reducing circulating estrogens through letrozole or tamoxifen as well as addressing other autoactivated hormone production. Ovarian and adrenal tumors, albeit rare, can cause PP; therefore, surgical excision is the goal of treatment.
PP should be approached with equal concerns about the physical and emotional effects while including the family to help them understand the pathophysiology and psychosocial risks.
Dr. Mark P. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
A 6-year-old girl presents with breast development. Her medical history is unremarkable. The parents are of average height, and the mother reports her thelarche was age 11 years. The girl is at the 97th percentile for her height and 90th percentile for her weight. She has Tanner stage 3 breast development and Tanner stage 2 pubic hair development. She has grown slightly more than 3 inches over the past year. How should she be evaluated and managed (N Engl J Med. 2008;358:2366-77)?
The premature onset of puberty, i.e., precocious puberty (PP), can be an emotionally traumatic event for the child and parents. Over the past century, improvements in public health and nutrition, and, more recently, increased obesity, have been associated with earlier puberty and the dominant factor has been attributed to genetics (Curr Opin Endocrinol Diabetes Obes. 2018;25[1]:49-54). This month’s article will focus on understanding what is considered “early” puberty, evaluating for causes, and managing precocious puberty.
More commonly seen in girls than boys, PP is defined as the onset of secondary sexual characteristics before age 7.5 years in Black and Hispanic girls, and prior to 8 years in White girls, which is 2-2.5 standard deviations below the average age of pubertal onset in healthy children (J Pediatr Adolesc Gynecol. 2019;32:455-9). As a comparison, PP is diagnosed with onset before age 9 years in boys. For White compared with Black girls, the average timing of thelarche is age 10 vs. 9.5 years, peak growth velocity is age 11.5, menarche is age 12.5 vs. 12, while completion of puberty is near age 14.5 vs. 13.5, respectively (J Pediatr. 1985;107:317). Fortunately, most girls with PP have common variants rather than serious pathology.
Classification: Central (CPP) vs. peripheral (PPP)
CPP is gonadotropin dependent, meaning the hypothalamic-pituitary-ovarian axis (HPO) is prematurely activated resulting in the normal progression of puberty.
PPP is gonadotropin independent, caused by sex steroid secretion from any source – ovaries, adrenal gland, exogenous or ectopic production, e.g., germ-cell tumor. This results in a disordered progression of pubertal milestones.
Whereas CPP is typically isosexual development, i.e., consistent with the child’s gender, PPP can be isosexual or contrasexual, e.g., virilization of girls. A third classification is “benign or nonprogressive pubertal variants” manifesting as isolated premature thelarche or adrenarche.
Causes (see table)
CPP. Idiopathic causes account for 80%-90% of presentations in girls and 25%-80% in boys. Remarkably, international and domestic adoption, as well as a family history of PP increases the likelihood of CPP in girls. Other etiologies include CNS lesions, e.g., hamartomas, which are the most common cause of PP in young children. MRI with contrast has been the traditional mode of diagnosis for CNS tumors, yet the yield is dubious in girls above age 6. Genetic causes are found in only a small percentage of PP cases. Rarely, CPP can result from gonadotropin-secreting tumors because of elevated luteinizing hormone levels.
PPP. As a result of sex steroid secretion, peripheral causes of PPP include ovarian cysts and ovarian tumors that increase circulating estradiol, such as granulosa cell tumors, which would cause isosexual PPP and Sertoli-Leydig cell tumors that secrete testosterone, which can result in contrasexual PPP. Mild congenital adrenal hyperplasia can result in PPP with virilization (contrasexual) and markedly advanced bone age.
McCune-Albright syndrome is rare and presents with the classic triad of PPP, skin pigmentation called café-au-lait, and fibrous dysplasia of bone. The pathophysiology of McCune-Albright syndrome is autoactivation of the G-protein leading to activation of ovarian tissue that results in formation of large ovarian cysts and extreme elevations in serum estradiol as well as the potential production of other hormones, e.g., thyrotoxicosis, excess growth hormone (acromegaly), and Cushing syndrome.
Premature thelarche. Premature thelarche typically occurs in girls between the ages of 1 and 3 years and is limited to breast enlargement. While no cause has been determined, the plausible explanations include partial activation of the HPO axis, endocrine-disrupting chemicals (EDCs), or a genetic origin. A small percentage of these girls progress to CPP.
EDCs have been considered as potential influencers of early puberty, but no consensus has been established. (Examples of EDCs in the environment include air, soil, or water supply along with food sources, personal care products, and manufactured products that can affect the endocrine system.)
Premature adenarche. Premature adrenarche presents with adult body odor and/or body hair (pubic and/or axillary) in girls who have an elevated body mass index, most commonly at the ages of 6-7 years. The presumed mechanism is normal maturation of the adrenal gland with resultant elevation of circulating androgens. Bone age may be mildly accelerated and DHEAS is prematurely elevated for age. These girls appear to be at increased risk for polycystic ovary syndrome.
Evaluation
The initial step in the evaluation of PP is to determine whether the cause is CPP or PPP; the latter includes distinguishing isosexual from contrasexual development. A thorough history (growth, headaches, behavior or visual change, seizures, abdominal pain), physical exam, including Tanner staging, and bone age is required. However, with isolated premature thelarche or adrenarche, a bone age may not be necessary, as initial close clinical observation for pubertal progression is likely sufficient.
For CPP, the diagnosis is based on serum LH, whether random levels or elevations follow GnRH stimulation. Puberty milestones progress normally although adrenarche is not consistently apparent. For girls younger than age 6, a brain MRI is recommended but not in asymptomatic older girls with CPP. LH and FSH along with estradiol or testosterone, the latter especially in boys, are the first line of serum testing. Serum TSH is recommended for suspicion of primary hypothyroidism. In girls with premature adrenarche, a bone age, testosterone, DHEAS, and 17-OHP to rule out adrenal hyperplasia should be obtained. Pelvic ultrasound may be a useful adjunct to assess uterine volume and/or ovarian cysts/tumors.
Rapidity of onset can also lead the evaluation since a normal growth chart and skeletal maturation suggests a benign pubertal variant whereas a more rapid rate can signal CPP or PPP. Of note, health care providers should ensure prescription, over-the-counter oral or topical sources of hormones, and EDCs are ruled out.
Consequences
An association between childhood sexual abuse and earlier pubertal onset has been cited. These girls may be at increased risk for psychosocial difficulties, menstrual and fertility problems, and even reproductive cancers because of prolonged exposure to sex hormones (J Adolesc Health. 2016;60[1]:65-71).
Treatment
The mainstay of CPP treatment is maximizing adult height, typically through the use of a GnRH agonist for HPO suppression from pituitary downregulation. For girls above age 8 years, attempts at improving adult height have not shown a benefit.
In girls with PPP, treatment is directed at the prevailing pathology. Interestingly, early PPP can activate the HPO axis thereby converting to “secondary” CPP. In PPP, McCune-Albright syndrome treatment targets reducing circulating estrogens through letrozole or tamoxifen as well as addressing other autoactivated hormone production. Ovarian and adrenal tumors, albeit rare, can cause PP; therefore, surgical excision is the goal of treatment.
PP should be approached with equal concerns about the physical and emotional effects while including the family to help them understand the pathophysiology and psychosocial risks.
Dr. Mark P. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
A 6-year-old girl presents with breast development. Her medical history is unremarkable. The parents are of average height, and the mother reports her thelarche was age 11 years. The girl is at the 97th percentile for her height and 90th percentile for her weight. She has Tanner stage 3 breast development and Tanner stage 2 pubic hair development. She has grown slightly more than 3 inches over the past year. How should she be evaluated and managed (N Engl J Med. 2008;358:2366-77)?
The premature onset of puberty, i.e., precocious puberty (PP), can be an emotionally traumatic event for the child and parents. Over the past century, improvements in public health and nutrition, and, more recently, increased obesity, have been associated with earlier puberty and the dominant factor has been attributed to genetics (Curr Opin Endocrinol Diabetes Obes. 2018;25[1]:49-54). This month’s article will focus on understanding what is considered “early” puberty, evaluating for causes, and managing precocious puberty.
More commonly seen in girls than boys, PP is defined as the onset of secondary sexual characteristics before age 7.5 years in Black and Hispanic girls, and prior to 8 years in White girls, which is 2-2.5 standard deviations below the average age of pubertal onset in healthy children (J Pediatr Adolesc Gynecol. 2019;32:455-9). As a comparison, PP is diagnosed with onset before age 9 years in boys. For White compared with Black girls, the average timing of thelarche is age 10 vs. 9.5 years, peak growth velocity is age 11.5, menarche is age 12.5 vs. 12, while completion of puberty is near age 14.5 vs. 13.5, respectively (J Pediatr. 1985;107:317). Fortunately, most girls with PP have common variants rather than serious pathology.
Classification: Central (CPP) vs. peripheral (PPP)
CPP is gonadotropin dependent, meaning the hypothalamic-pituitary-ovarian axis (HPO) is prematurely activated resulting in the normal progression of puberty.
PPP is gonadotropin independent, caused by sex steroid secretion from any source – ovaries, adrenal gland, exogenous or ectopic production, e.g., germ-cell tumor. This results in a disordered progression of pubertal milestones.
Whereas CPP is typically isosexual development, i.e., consistent with the child’s gender, PPP can be isosexual or contrasexual, e.g., virilization of girls. A third classification is “benign or nonprogressive pubertal variants” manifesting as isolated premature thelarche or adrenarche.
Causes (see table)
CPP. Idiopathic causes account for 80%-90% of presentations in girls and 25%-80% in boys. Remarkably, international and domestic adoption, as well as a family history of PP increases the likelihood of CPP in girls. Other etiologies include CNS lesions, e.g., hamartomas, which are the most common cause of PP in young children. MRI with contrast has been the traditional mode of diagnosis for CNS tumors, yet the yield is dubious in girls above age 6. Genetic causes are found in only a small percentage of PP cases. Rarely, CPP can result from gonadotropin-secreting tumors because of elevated luteinizing hormone levels.
PPP. As a result of sex steroid secretion, peripheral causes of PPP include ovarian cysts and ovarian tumors that increase circulating estradiol, such as granulosa cell tumors, which would cause isosexual PPP and Sertoli-Leydig cell tumors that secrete testosterone, which can result in contrasexual PPP. Mild congenital adrenal hyperplasia can result in PPP with virilization (contrasexual) and markedly advanced bone age.
McCune-Albright syndrome is rare and presents with the classic triad of PPP, skin pigmentation called café-au-lait, and fibrous dysplasia of bone. The pathophysiology of McCune-Albright syndrome is autoactivation of the G-protein leading to activation of ovarian tissue that results in formation of large ovarian cysts and extreme elevations in serum estradiol as well as the potential production of other hormones, e.g., thyrotoxicosis, excess growth hormone (acromegaly), and Cushing syndrome.
Premature thelarche. Premature thelarche typically occurs in girls between the ages of 1 and 3 years and is limited to breast enlargement. While no cause has been determined, the plausible explanations include partial activation of the HPO axis, endocrine-disrupting chemicals (EDCs), or a genetic origin. A small percentage of these girls progress to CPP.
EDCs have been considered as potential influencers of early puberty, but no consensus has been established. (Examples of EDCs in the environment include air, soil, or water supply along with food sources, personal care products, and manufactured products that can affect the endocrine system.)
Premature adenarche. Premature adrenarche presents with adult body odor and/or body hair (pubic and/or axillary) in girls who have an elevated body mass index, most commonly at the ages of 6-7 years. The presumed mechanism is normal maturation of the adrenal gland with resultant elevation of circulating androgens. Bone age may be mildly accelerated and DHEAS is prematurely elevated for age. These girls appear to be at increased risk for polycystic ovary syndrome.
Evaluation
The initial step in the evaluation of PP is to determine whether the cause is CPP or PPP; the latter includes distinguishing isosexual from contrasexual development. A thorough history (growth, headaches, behavior or visual change, seizures, abdominal pain), physical exam, including Tanner staging, and bone age is required. However, with isolated premature thelarche or adrenarche, a bone age may not be necessary, as initial close clinical observation for pubertal progression is likely sufficient.
For CPP, the diagnosis is based on serum LH, whether random levels or elevations follow GnRH stimulation. Puberty milestones progress normally although adrenarche is not consistently apparent. For girls younger than age 6, a brain MRI is recommended but not in asymptomatic older girls with CPP. LH and FSH along with estradiol or testosterone, the latter especially in boys, are the first line of serum testing. Serum TSH is recommended for suspicion of primary hypothyroidism. In girls with premature adrenarche, a bone age, testosterone, DHEAS, and 17-OHP to rule out adrenal hyperplasia should be obtained. Pelvic ultrasound may be a useful adjunct to assess uterine volume and/or ovarian cysts/tumors.
Rapidity of onset can also lead the evaluation since a normal growth chart and skeletal maturation suggests a benign pubertal variant whereas a more rapid rate can signal CPP or PPP. Of note, health care providers should ensure prescription, over-the-counter oral or topical sources of hormones, and EDCs are ruled out.
Consequences
An association between childhood sexual abuse and earlier pubertal onset has been cited. These girls may be at increased risk for psychosocial difficulties, menstrual and fertility problems, and even reproductive cancers because of prolonged exposure to sex hormones (J Adolesc Health. 2016;60[1]:65-71).
Treatment
The mainstay of CPP treatment is maximizing adult height, typically through the use of a GnRH agonist for HPO suppression from pituitary downregulation. For girls above age 8 years, attempts at improving adult height have not shown a benefit.
In girls with PPP, treatment is directed at the prevailing pathology. Interestingly, early PPP can activate the HPO axis thereby converting to “secondary” CPP. In PPP, McCune-Albright syndrome treatment targets reducing circulating estrogens through letrozole or tamoxifen as well as addressing other autoactivated hormone production. Ovarian and adrenal tumors, albeit rare, can cause PP; therefore, surgical excision is the goal of treatment.
PP should be approached with equal concerns about the physical and emotional effects while including the family to help them understand the pathophysiology and psychosocial risks.
Dr. Mark P. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
