Pediatrics

A 13-year-old boy with ADHD, combined type, presents to his family physician with his parents. His parents called for an appointment outside of his routine follow-up care to discuss what they should do to address their son’s new “aggressive behaviors.” He will throw objects when angry, yell, and slam doors at home when he is told to turn off video games. He used to play soccer but doesn’t anymore. He has maintained very good grades and friends. There is not a concern for substance abuse at this time.He speaks in curt sentences during the appointment, and he has his arms crossed or is looking out of the window the entire time.

His parents share in front on him that he has always been a “difficult child” (their words), but they now are struggling to adjust to his aggressive tendencies as he ages. He is growing bigger and angrier. He will not attend therapy and will not see a consultation psychiatrist in the office. A variety of stimulant trials including Ritalin and amphetamine preparations to manage impulsivity in ADHD were ineffective to curb his aggression, and he doesn’t want to take any medication.

They ask, what do we do? They are not worried for their safety but living like this is eroding their quality of life as a family, and the dynamic seems destined to get worse before it gets better.

They wonder, is there a next medication step to manage his aggression?

A family physician presented the above situation to me in my role as a child and adolescent psychiatrist in the medical home. It led us to a fruitful discussion of aggression and what can be done to help families who are all too often in situations like the above, then in your office looking for immediate solutions. The questions are, what can be done with an aggressive child, even and especially without the child’s buy-in to work on that as a problem?

Markus Wegmann/Thinkstock

Psychoeducation can go a long way in helping families rethink aggression as a symptom of something deeper, either in the environment or a diagnosis, although we all can empathize with the desire to reconcile the above behavior immediately.
 

Characterize the aggression

First, it can be helpful to identify a child’s aggression type. There are two types of aggression, reactive and proactive. We most often see reactive aggression in our clinics, which is aggression as a defensive and impulsive response to something in the environment (often limit-setting, as above). Proactive aggression is premeditated and may appear as aggression for aggression’s sake without the emotional drive behind it.

Secondly, it also can be helpful to know that externalizing and internalizing symptoms can represent different sides of the same coin, with the proverbial “coin” as “emotion” and the associated behaviors (throwing objects, in the above example) as the “signs” that there is a complex difficulty in managing painful emotions. Some children (and adults too!) tend to “externalize” strong emotions as aggression or irritability with others, while others “internalize” them by retreating with internal suffering such as “anxiety and depression.” These styles also can be similar among children and their parents.

With those two points in mind, it’s important to consider the diagnosis, which would guide treatment. It’s generally agreed upon that “reactive aggression” is more likely to be related to underlying untreated ADHD, or a depressive or anxiety disorder. This is much more amenable to treatment than aggression related to oppositional defiant disorder or conduct disorder, which are more defined by proactive forms of aggression.

You can pick up on family dynamics that may inadvertently reinforce the same behaviors they so wish to change. In the above example, the parents have clearly identified their son as “the problem.” You can imagine the difficulty of going to school and being a “problem,” and then coming home and feeling the same way. This negative perception can erode a child’s self-esteem over time, which may appear as disengagement or simply not caring in an appointment. It may become harder and harder to engage the child in psychotherapy or even in taking a medication as their only means of resistance to that painful notion about oneself as the “problem.”

It can be useful to begin appointments with “what is going well?” (in the example above, he “has friends and is maintaining grades”) and “what do you like most about your child?” As we all know, positive reinforcement is more powerful than its counterpart. Also problems in a family often are complex, and may involve many family members needing to change to meet their goals, not just the child.
 

Why you should try behavioral interventions first

Behavioral interventions are the first step always. Parents can do behavioral interventions and change their parenting and family environment through their own behavioral changes – commonly called parent management training. They can assess antecedents of aggression and their own responses, which may contribute or perpetuate a cycle of the aggression – such as giving attention or giving in to fewer limitations to avoid a fight. This small but important point can help protect against a feeling of helplessness that a child will not engage in therapy or skills-building.

In answering the clinician’s question about what to do next, I often feel like the question embedded in this is “what medication is next?” There is a felt pressure to do something “right now” conveyed to a clinician. This drives the impulse to prescribe something immediately – and likely more risky and with less of an evidence base – even before trying the known psychotherapy interventions that have the most evidence to change aggressive tendencies.

In looking deeper into this consultation case, I also found more “food for thought” for one’s thinking about aggression and psychopharmacology in cases like the above: Aggression isn’t an uncomplicated symptom that one can address immediately, and therefore we cannot rely on symptom-specific management to eradicate it. This is similar to prescribing Tylenol to manage a general ache or pain; if the pain persists, we want to know the “whys” of the pain persisting.

Thankfully, there are ways that a parent can better understand behaviors with this philosophy in mind. Applied Behavioral Analysis¹ offers some helpful ideas, not only for children with autism spectrum disorder, but that can be applied to one’s understanding of other’s behavior in general. ABA pays attention to antecedents, perpetuating factors, and consequences as well as their interplay in understanding behaviors. You can encourage a family – rather than wanting to “get rid of a problem behavior” – to try to understand it and come up, with help from a psychotherapist or other professional, with a deeper evaluation of the behavior and a specific, collaborative plan.

Most experts see that ADHD, anxiety disorders, depressive disorders, and unrecognized learning disabilities, in sum, are more common underpinnings than not with aggressive children. This also can be confounded by an environment with parents who have those diagnoses untreated as well. Aggression should raise a red flag in our clinics to consider the above even if a family or child simply says aggression is the one issue, and it’s only the child with the issue.

While there have been attempts to find a “spot treatment” for aggression in a medication, medications not only fail to address the underlying issues many times, but have little evidence that support them and may do more harm long term than good.²

Kids need outlets for “normal aggressive drives.” And puberty, as in the case above, is a time of intense emotions of all varieties. In the example above, you may notice that the child is no longer playing soccer, which was likely serving some protective function in many ways for him and as a positive outlet for aggression. In the same way, you may see that kids who are more sedentary or idle (playing unrestricted video games now instead of sports, ) would benefit from revisiting outlets or finding new ones as a family.
 

Consider medications if the underlying diagnosis merits it

We generally seek to find and treat the underlying diagnosis, if it exists, in the following ways.

If a child has ADHD, as in the case above, you can trial a stimulant or an alpha-adrenergic agent to target impulsivity if that is suspected as the driver of aggression. This may include guanfacine (long-acting Intuniv at night, but I would choose lower dosing such as 0.5 mg to 1 mg at bedtime) to manage ADHD. However, the evidence base that management of ADHD improves aggressive behaviors at all or on their own, is scant. In addition, these medications can represent more harm than good as well, although they are perceived as more innocuous than their antipsychotic counterparts. For example, some patients can begin to have bed-wetting accidents in the evening or become sleepy in classes, which can further erode their sense of self-confidence even if this is clearly attributable to a medication side effect and resolves once the agent is reduced or removed.

In the same way to reorient to diagnosis with children with aggression, you can consider an SSRI for an anxiety disorder or irritable depression. But know that it’s a rare thing for children to say specifically that they are struggling with their emotions, whether they are angry, sad, or nervous and that a deeper dive into this may be warranted. Data by Connor DF et al.³ may indicate anxiety disorders should be highest on one’s differential diagnosis in aggression, followed by consideration for ADHD, which may be a different assumption than one would expect.

Mood stabilizers –lamotrigine (Lamictal), divalproex sodium (Depakote), and lithium – and antipsychotics – aripiprazole (Abilify) and risperidone (Risperdal) – are risky medications and the use of them contradicts the first point, agreed upon by most experts, that diagnosis should drive treatment. One is hardly ever treating a young child for psychosis or bipolar disorder in these circumstances of episodic, reactive aggression. Antipsychotics also carry the notorious risks of metabolic syndrome, among other risks to overall health, which becomes an additive risk over time and potentially into adulthood. I once heard in my child adolescent psychiatry training the haunting phase, “yes, they can ‘work’ quickly but they can work ‘almost too well,’ ” meaning they can sedate or tranquilize an aggressive child when the real goal should be to understand, diagnose, and intervene in ways that see the “big picture” of aggression.

Benzodiazepines generally are avoided in children due to disinhibition and often not even considered, in these circumstances, as they are in adults to manage agitation or aggression, due to this fact.

In many instances in working with families, our role in primary care can be one of illuminating children’s behaviors not just as symptoms to treat, but to understand deeply. This is as true for aggression as it is for anxiety.

Finally, I am reminded of the common question I receive from adult patients in primary care who ask me if anyone has yet made a medication to lose weight that’s safe and effective. Then the counseling commences on our fantasies, from our patients and ourselves, about what medications can do for us and our risks therein.
 

Dr. Pawlowski is an adult, adolescent, and child psychiatrist at the University of Vermont Medical Center and assistant professor of psychiatry at the Larner College of Medicine at UVM in Burlington. Email her at [email protected].
 

References

1. ABA in the Treatment of Aggressive Behavior Disorder and Lack of Impulse Control.

2. Managing Aggression in Children: A Practical Approach, The Carlat Child Psychiatry Report, May 2010, The Explosive Child.

3. Child Psychiatry Hum Dev. 2006 May;37[1]:1-14.

A 13-year-old boy with ADHD, combined type, presents to his family physician with his parents. His parents called for an appointment outside of his routine follow-up care to discuss what they should do to address their son’s new “aggressive behaviors.” He will throw objects when angry, yell, and slam doors at home when he is told to turn off video games. He used to play soccer but doesn’t anymore. He has maintained very good grades and friends. There is not a concern for substance abuse at this time.He speaks in curt sentences during the appointment, and he has his arms crossed or is looking out of the window the entire time.

His parents share in front on him that he has always been a “difficult child” (their words), but they now are struggling to adjust to his aggressive tendencies as he ages. He is growing bigger and angrier. He will not attend therapy and will not see a consultation psychiatrist in the office. A variety of stimulant trials including Ritalin and amphetamine preparations to manage impulsivity in ADHD were ineffective to curb his aggression, and he doesn’t want to take any medication.

They ask, what do we do? They are not worried for their safety but living like this is eroding their quality of life as a family, and the dynamic seems destined to get worse before it gets better.

They wonder, is there a next medication step to manage his aggression?

A family physician presented the above situation to me in my role as a child and adolescent psychiatrist in the medical home. It led us to a fruitful discussion of aggression and what can be done to help families who are all too often in situations like the above, then in your office looking for immediate solutions. The questions are, what can be done with an aggressive child, even and especially without the child’s buy-in to work on that as a problem?

Markus Wegmann/Thinkstock

Psychoeducation can go a long way in helping families rethink aggression as a symptom of something deeper, either in the environment or a diagnosis, although we all can empathize with the desire to reconcile the above behavior immediately.
 

Characterize the aggression

First, it can be helpful to identify a child’s aggression type. There are two types of aggression, reactive and proactive. We most often see reactive aggression in our clinics, which is aggression as a defensive and impulsive response to something in the environment (often limit-setting, as above). Proactive aggression is premeditated and may appear as aggression for aggression’s sake without the emotional drive behind it.

Secondly, it also can be helpful to know that externalizing and internalizing symptoms can represent different sides of the same coin, with the proverbial “coin” as “emotion” and the associated behaviors (throwing objects, in the above example) as the “signs” that there is a complex difficulty in managing painful emotions. Some children (and adults too!) tend to “externalize” strong emotions as aggression or irritability with others, while others “internalize” them by retreating with internal suffering such as “anxiety and depression.” These styles also can be similar among children and their parents.

With those two points in mind, it’s important to consider the diagnosis, which would guide treatment. It’s generally agreed upon that “reactive aggression” is more likely to be related to underlying untreated ADHD, or a depressive or anxiety disorder. This is much more amenable to treatment than aggression related to oppositional defiant disorder or conduct disorder, which are more defined by proactive forms of aggression.

You can pick up on family dynamics that may inadvertently reinforce the same behaviors they so wish to change. In the above example, the parents have clearly identified their son as “the problem.” You can imagine the difficulty of going to school and being a “problem,” and then coming home and feeling the same way. This negative perception can erode a child’s self-esteem over time, which may appear as disengagement or simply not caring in an appointment. It may become harder and harder to engage the child in psychotherapy or even in taking a medication as their only means of resistance to that painful notion about oneself as the “problem.”

It can be useful to begin appointments with “what is going well?” (in the example above, he “has friends and is maintaining grades”) and “what do you like most about your child?” As we all know, positive reinforcement is more powerful than its counterpart. Also problems in a family often are complex, and may involve many family members needing to change to meet their goals, not just the child.
 

Why you should try behavioral interventions first

Behavioral interventions are the first step always. Parents can do behavioral interventions and change their parenting and family environment through their own behavioral changes – commonly called parent management training. They can assess antecedents of aggression and their own responses, which may contribute or perpetuate a cycle of the aggression – such as giving attention or giving in to fewer limitations to avoid a fight. This small but important point can help protect against a feeling of helplessness that a child will not engage in therapy or skills-building.

In answering the clinician’s question about what to do next, I often feel like the question embedded in this is “what medication is next?” There is a felt pressure to do something “right now” conveyed to a clinician. This drives the impulse to prescribe something immediately – and likely more risky and with less of an evidence base – even before trying the known psychotherapy interventions that have the most evidence to change aggressive tendencies.

In looking deeper into this consultation case, I also found more “food for thought” for one’s thinking about aggression and psychopharmacology in cases like the above: Aggression isn’t an uncomplicated symptom that one can address immediately, and therefore we cannot rely on symptom-specific management to eradicate it. This is similar to prescribing Tylenol to manage a general ache or pain; if the pain persists, we want to know the “whys” of the pain persisting.

Thankfully, there are ways that a parent can better understand behaviors with this philosophy in mind. Applied Behavioral Analysis¹ offers some helpful ideas, not only for children with autism spectrum disorder, but that can be applied to one’s understanding of other’s behavior in general. ABA pays attention to antecedents, perpetuating factors, and consequences as well as their interplay in understanding behaviors. You can encourage a family – rather than wanting to “get rid of a problem behavior” – to try to understand it and come up, with help from a psychotherapist or other professional, with a deeper evaluation of the behavior and a specific, collaborative plan.

Most experts see that ADHD, anxiety disorders, depressive disorders, and unrecognized learning disabilities, in sum, are more common underpinnings than not with aggressive children. This also can be confounded by an environment with parents who have those diagnoses untreated as well. Aggression should raise a red flag in our clinics to consider the above even if a family or child simply says aggression is the one issue, and it’s only the child with the issue.

While there have been attempts to find a “spot treatment” for aggression in a medication, medications not only fail to address the underlying issues many times, but have little evidence that support them and may do more harm long term than good.²

Kids need outlets for “normal aggressive drives.” And puberty, as in the case above, is a time of intense emotions of all varieties. In the example above, you may notice that the child is no longer playing soccer, which was likely serving some protective function in many ways for him and as a positive outlet for aggression. In the same way, you may see that kids who are more sedentary or idle (playing unrestricted video games now instead of sports, ) would benefit from revisiting outlets or finding new ones as a family.
 

Consider medications if the underlying diagnosis merits it

We generally seek to find and treat the underlying diagnosis, if it exists, in the following ways.

If a child has ADHD, as in the case above, you can trial a stimulant or an alpha-adrenergic agent to target impulsivity if that is suspected as the driver of aggression. This may include guanfacine (long-acting Intuniv at night, but I would choose lower dosing such as 0.5 mg to 1 mg at bedtime) to manage ADHD. However, the evidence base that management of ADHD improves aggressive behaviors at all or on their own, is scant. In addition, these medications can represent more harm than good as well, although they are perceived as more innocuous than their antipsychotic counterparts. For example, some patients can begin to have bed-wetting accidents in the evening or become sleepy in classes, which can further erode their sense of self-confidence even if this is clearly attributable to a medication side effect and resolves once the agent is reduced or removed.

In the same way to reorient to diagnosis with children with aggression, you can consider an SSRI for an anxiety disorder or irritable depression. But know that it’s a rare thing for children to say specifically that they are struggling with their emotions, whether they are angry, sad, or nervous and that a deeper dive into this may be warranted. Data by Connor DF et al.³ may indicate anxiety disorders should be highest on one’s differential diagnosis in aggression, followed by consideration for ADHD, which may be a different assumption than one would expect.

Mood stabilizers –lamotrigine (Lamictal), divalproex sodium (Depakote), and lithium – and antipsychotics – aripiprazole (Abilify) and risperidone (Risperdal) – are risky medications and the use of them contradicts the first point, agreed upon by most experts, that diagnosis should drive treatment. One is hardly ever treating a young child for psychosis or bipolar disorder in these circumstances of episodic, reactive aggression. Antipsychotics also carry the notorious risks of metabolic syndrome, among other risks to overall health, which becomes an additive risk over time and potentially into adulthood. I once heard in my child adolescent psychiatry training the haunting phase, “yes, they can ‘work’ quickly but they can work ‘almost too well,’ ” meaning they can sedate or tranquilize an aggressive child when the real goal should be to understand, diagnose, and intervene in ways that see the “big picture” of aggression.

Benzodiazepines generally are avoided in children due to disinhibition and often not even considered, in these circumstances, as they are in adults to manage agitation or aggression, due to this fact.

In many instances in working with families, our role in primary care can be one of illuminating children’s behaviors not just as symptoms to treat, but to understand deeply. This is as true for aggression as it is for anxiety.

Finally, I am reminded of the common question I receive from adult patients in primary care who ask me if anyone has yet made a medication to lose weight that’s safe and effective. Then the counseling commences on our fantasies, from our patients and ourselves, about what medications can do for us and our risks therein.
 

Dr. Pawlowski is an adult, adolescent, and child psychiatrist at the University of Vermont Medical Center and assistant professor of psychiatry at the Larner College of Medicine at UVM in Burlington. Email her at [email protected].
 

References

1. ABA in the Treatment of Aggressive Behavior Disorder and Lack of Impulse Control.

2. Managing Aggression in Children: A Practical Approach, The Carlat Child Psychiatry Report, May 2010, The Explosive Child.

3. Child Psychiatry Hum Dev. 2006 May;37[1]:1-14.

A 13-year-old boy with ADHD, combined type, presents to his family physician with his parents. His parents called for an appointment outside of his routine follow-up care to discuss what they should do to address their son’s new “aggressive behaviors.” He will throw objects when angry, yell, and slam doors at home when he is told to turn off video games. He used to play soccer but doesn’t anymore. He has maintained very good grades and friends. There is not a concern for substance abuse at this time.He speaks in curt sentences during the appointment, and he has his arms crossed or is looking out of the window the entire time.

His parents share in front on him that he has always been a “difficult child” (their words), but they now are struggling to adjust to his aggressive tendencies as he ages. He is growing bigger and angrier. He will not attend therapy and will not see a consultation psychiatrist in the office. A variety of stimulant trials including Ritalin and amphetamine preparations to manage impulsivity in ADHD were ineffective to curb his aggression, and he doesn’t want to take any medication.

They ask, what do we do? They are not worried for their safety but living like this is eroding their quality of life as a family, and the dynamic seems destined to get worse before it gets better.

They wonder, is there a next medication step to manage his aggression?

A family physician presented the above situation to me in my role as a child and adolescent psychiatrist in the medical home. It led us to a fruitful discussion of aggression and what can be done to help families who are all too often in situations like the above, then in your office looking for immediate solutions. The questions are, what can be done with an aggressive child, even and especially without the child’s buy-in to work on that as a problem?

Markus Wegmann/Thinkstock

Psychoeducation can go a long way in helping families rethink aggression as a symptom of something deeper, either in the environment or a diagnosis, although we all can empathize with the desire to reconcile the above behavior immediately.
 

Characterize the aggression

First, it can be helpful to identify a child’s aggression type. There are two types of aggression, reactive and proactive. We most often see reactive aggression in our clinics, which is aggression as a defensive and impulsive response to something in the environment (often limit-setting, as above). Proactive aggression is premeditated and may appear as aggression for aggression’s sake without the emotional drive behind it.

Secondly, it also can be helpful to know that externalizing and internalizing symptoms can represent different sides of the same coin, with the proverbial “coin” as “emotion” and the associated behaviors (throwing objects, in the above example) as the “signs” that there is a complex difficulty in managing painful emotions. Some children (and adults too!) tend to “externalize” strong emotions as aggression or irritability with others, while others “internalize” them by retreating with internal suffering such as “anxiety and depression.” These styles also can be similar among children and their parents.

With those two points in mind, it’s important to consider the diagnosis, which would guide treatment. It’s generally agreed upon that “reactive aggression” is more likely to be related to underlying untreated ADHD, or a depressive or anxiety disorder. This is much more amenable to treatment than aggression related to oppositional defiant disorder or conduct disorder, which are more defined by proactive forms of aggression.

You can pick up on family dynamics that may inadvertently reinforce the same behaviors they so wish to change. In the above example, the parents have clearly identified their son as “the problem.” You can imagine the difficulty of going to school and being a “problem,” and then coming home and feeling the same way. This negative perception can erode a child’s self-esteem over time, which may appear as disengagement or simply not caring in an appointment. It may become harder and harder to engage the child in psychotherapy or even in taking a medication as their only means of resistance to that painful notion about oneself as the “problem.”

It can be useful to begin appointments with “what is going well?” (in the example above, he “has friends and is maintaining grades”) and “what do you like most about your child?” As we all know, positive reinforcement is more powerful than its counterpart. Also problems in a family often are complex, and may involve many family members needing to change to meet their goals, not just the child.
 

Why you should try behavioral interventions first

Behavioral interventions are the first step always. Parents can do behavioral interventions and change their parenting and family environment through their own behavioral changes – commonly called parent management training. They can assess antecedents of aggression and their own responses, which may contribute or perpetuate a cycle of the aggression – such as giving attention or giving in to fewer limitations to avoid a fight. This small but important point can help protect against a feeling of helplessness that a child will not engage in therapy or skills-building.

In answering the clinician’s question about what to do next, I often feel like the question embedded in this is “what medication is next?” There is a felt pressure to do something “right now” conveyed to a clinician. This drives the impulse to prescribe something immediately – and likely more risky and with less of an evidence base – even before trying the known psychotherapy interventions that have the most evidence to change aggressive tendencies.

In looking deeper into this consultation case, I also found more “food for thought” for one’s thinking about aggression and psychopharmacology in cases like the above: Aggression isn’t an uncomplicated symptom that one can address immediately, and therefore we cannot rely on symptom-specific management to eradicate it. This is similar to prescribing Tylenol to manage a general ache or pain; if the pain persists, we want to know the “whys” of the pain persisting.

Thankfully, there are ways that a parent can better understand behaviors with this philosophy in mind. Applied Behavioral Analysis¹ offers some helpful ideas, not only for children with autism spectrum disorder, but that can be applied to one’s understanding of other’s behavior in general. ABA pays attention to antecedents, perpetuating factors, and consequences as well as their interplay in understanding behaviors. You can encourage a family – rather than wanting to “get rid of a problem behavior” – to try to understand it and come up, with help from a psychotherapist or other professional, with a deeper evaluation of the behavior and a specific, collaborative plan.

Most experts see that ADHD, anxiety disorders, depressive disorders, and unrecognized learning disabilities, in sum, are more common underpinnings than not with aggressive children. This also can be confounded by an environment with parents who have those diagnoses untreated as well. Aggression should raise a red flag in our clinics to consider the above even if a family or child simply says aggression is the one issue, and it’s only the child with the issue.

While there have been attempts to find a “spot treatment” for aggression in a medication, medications not only fail to address the underlying issues many times, but have little evidence that support them and may do more harm long term than good.²

Kids need outlets for “normal aggressive drives.” And puberty, as in the case above, is a time of intense emotions of all varieties. In the example above, you may notice that the child is no longer playing soccer, which was likely serving some protective function in many ways for him and as a positive outlet for aggression. In the same way, you may see that kids who are more sedentary or idle (playing unrestricted video games now instead of sports, ) would benefit from revisiting outlets or finding new ones as a family.
 

Consider medications if the underlying diagnosis merits it

We generally seek to find and treat the underlying diagnosis, if it exists, in the following ways.

If a child has ADHD, as in the case above, you can trial a stimulant or an alpha-adrenergic agent to target impulsivity if that is suspected as the driver of aggression. This may include guanfacine (long-acting Intuniv at night, but I would choose lower dosing such as 0.5 mg to 1 mg at bedtime) to manage ADHD. However, the evidence base that management of ADHD improves aggressive behaviors at all or on their own, is scant. In addition, these medications can represent more harm than good as well, although they are perceived as more innocuous than their antipsychotic counterparts. For example, some patients can begin to have bed-wetting accidents in the evening or become sleepy in classes, which can further erode their sense of self-confidence even if this is clearly attributable to a medication side effect and resolves once the agent is reduced or removed.

In the same way to reorient to diagnosis with children with aggression, you can consider an SSRI for an anxiety disorder or irritable depression. But know that it’s a rare thing for children to say specifically that they are struggling with their emotions, whether they are angry, sad, or nervous and that a deeper dive into this may be warranted. Data by Connor DF et al.³ may indicate anxiety disorders should be highest on one’s differential diagnosis in aggression, followed by consideration for ADHD, which may be a different assumption than one would expect.

Mood stabilizers –lamotrigine (Lamictal), divalproex sodium (Depakote), and lithium – and antipsychotics – aripiprazole (Abilify) and risperidone (Risperdal) – are risky medications and the use of them contradicts the first point, agreed upon by most experts, that diagnosis should drive treatment. One is hardly ever treating a young child for psychosis or bipolar disorder in these circumstances of episodic, reactive aggression. Antipsychotics also carry the notorious risks of metabolic syndrome, among other risks to overall health, which becomes an additive risk over time and potentially into adulthood. I once heard in my child adolescent psychiatry training the haunting phase, “yes, they can ‘work’ quickly but they can work ‘almost too well,’ ” meaning they can sedate or tranquilize an aggressive child when the real goal should be to understand, diagnose, and intervene in ways that see the “big picture” of aggression.

Benzodiazepines generally are avoided in children due to disinhibition and often not even considered, in these circumstances, as they are in adults to manage agitation or aggression, due to this fact.

In many instances in working with families, our role in primary care can be one of illuminating children’s behaviors not just as symptoms to treat, but to understand deeply. This is as true for aggression as it is for anxiety.

Finally, I am reminded of the common question I receive from adult patients in primary care who ask me if anyone has yet made a medication to lose weight that’s safe and effective. Then the counseling commences on our fantasies, from our patients and ourselves, about what medications can do for us and our risks therein.
 

Dr. Pawlowski is an adult, adolescent, and child psychiatrist at the University of Vermont Medical Center and assistant professor of psychiatry at the Larner College of Medicine at UVM in Burlington. Email her at [email protected].
 

References

1. ABA in the Treatment of Aggressive Behavior Disorder and Lack of Impulse Control.

2. Managing Aggression in Children: A Practical Approach, The Carlat Child Psychiatry Report, May 2010, The Explosive Child.

3. Child Psychiatry Hum Dev. 2006 May;37[1]:1-14.

Influenza activity continues to increase, but it has slowed down a bit, according to the Centers for Disease Control and Prevention.

The CDC’s latest report shows that 6.8% of outpatients visiting health care providers had influenza-like illness during the week ending Feb. 8. That’s up from the previous week’s 6.6%, but that rise of 0.2 percentage points is smaller than the 0.6-point rises that occurred each of the 2 weeks before, and that could mean that activity is slowing.

That slowing, however, is not noticeable from this week’s map, which puts 41 states (there were 35 last week) and Puerto Rico in the red at the highest level of activity on the CDC’s 1-10 scale and another three states in the “high” range with levels of 8 or 9, the CDC’s influenza division reported.

That leaves Nevada and Oregon at level 7; Alaska, Florida, and the District of Columbia at level 5; Idaho at level 3, and Delaware with insufficient data (it was at level 5 last week), the CDC said.

The 2019-2020 season’s high activity, fortunately, has not translated into high severity, as overall hospitalization and mortality rates continue to remain at fairly typical levels. Hospitalization rates are elevated among children and young adults, however, and pediatric deaths are now up to 92, the CDC said, which is high for this point in the season.

[email protected]

Influenza activity continues to increase, but it has slowed down a bit, according to the Centers for Disease Control and Prevention.

The CDC’s latest report shows that 6.8% of outpatients visiting health care providers had influenza-like illness during the week ending Feb. 8. That’s up from the previous week’s 6.6%, but that rise of 0.2 percentage points is smaller than the 0.6-point rises that occurred each of the 2 weeks before, and that could mean that activity is slowing.

That slowing, however, is not noticeable from this week’s map, which puts 41 states (there were 35 last week) and Puerto Rico in the red at the highest level of activity on the CDC’s 1-10 scale and another three states in the “high” range with levels of 8 or 9, the CDC’s influenza division reported.

That leaves Nevada and Oregon at level 7; Alaska, Florida, and the District of Columbia at level 5; Idaho at level 3, and Delaware with insufficient data (it was at level 5 last week), the CDC said.

The 2019-2020 season’s high activity, fortunately, has not translated into high severity, as overall hospitalization and mortality rates continue to remain at fairly typical levels. Hospitalization rates are elevated among children and young adults, however, and pediatric deaths are now up to 92, the CDC said, which is high for this point in the season.

[email protected]

Influenza activity continues to increase, but it has slowed down a bit, according to the Centers for Disease Control and Prevention.

The CDC’s latest report shows that 6.8% of outpatients visiting health care providers had influenza-like illness during the week ending Feb. 8. That’s up from the previous week’s 6.6%, but that rise of 0.2 percentage points is smaller than the 0.6-point rises that occurred each of the 2 weeks before, and that could mean that activity is slowing.

That slowing, however, is not noticeable from this week’s map, which puts 41 states (there were 35 last week) and Puerto Rico in the red at the highest level of activity on the CDC’s 1-10 scale and another three states in the “high” range with levels of 8 or 9, the CDC’s influenza division reported.

That leaves Nevada and Oregon at level 7; Alaska, Florida, and the District of Columbia at level 5; Idaho at level 3, and Delaware with insufficient data (it was at level 5 last week), the CDC said.

The 2019-2020 season’s high activity, fortunately, has not translated into high severity, as overall hospitalization and mortality rates continue to remain at fairly typical levels. Hospitalization rates are elevated among children and young adults, however, and pediatric deaths are now up to 92, the CDC said, which is high for this point in the season.

[email protected]

Neonatal transfer was the factor most often associated with unexpected, severe complications at birth, particularly at hospitals that had the highest rates of complications, according to a cross-sectional study published online in JAMA Network Open (2020;3[2]:e1919498).

“Transfers were more likely to be necessary when infants were born in hospitals with lower levels of neonatal care,” Mark A. Clapp, MD, MPH, of Massachusetts General Hospital in Boston, and colleagues wrote. “Thus, if this metric is to be used in its current form, it would appear that accreditors, regulatory bodies, and payers should consider adjusting for or stratifying by a hospital’s level of neonatal care to avoid disincentivizing against appropriate transfers.”

The Joint Commission recently included unexpected complications in term newborns as a marker of quality of obstetric care, but it does not currently recommend any risk adjustment for the metric. The authors aimed to learn which factors regarding patients and hospitals were associated with such complications. Severe, unexpected newborn complications include death, seizure, use of assisted ventilation for at least 6 hours, transfer to another facility, or a 5-minute Apgar score of 3 or less.

“This measure has been proposed to serve as a balancing measure to maternal metrics, such as the rate of nulliparous, term, singleton, vertex-presenting cesarean deliveries,” the authors explained.

This study was supported by a Health Policy Award from the Society for Maternal-Fetal Medicine. The authors reported no relevant financial disclosures.

This story first appeared on Medscape.

Neonatal transfer was the factor most often associated with unexpected, severe complications at birth, particularly at hospitals that had the highest rates of complications, according to a cross-sectional study published online in JAMA Network Open (2020;3[2]:e1919498).

“Transfers were more likely to be necessary when infants were born in hospitals with lower levels of neonatal care,” Mark A. Clapp, MD, MPH, of Massachusetts General Hospital in Boston, and colleagues wrote. “Thus, if this metric is to be used in its current form, it would appear that accreditors, regulatory bodies, and payers should consider adjusting for or stratifying by a hospital’s level of neonatal care to avoid disincentivizing against appropriate transfers.”

The Joint Commission recently included unexpected complications in term newborns as a marker of quality of obstetric care, but it does not currently recommend any risk adjustment for the metric. The authors aimed to learn which factors regarding patients and hospitals were associated with such complications. Severe, unexpected newborn complications include death, seizure, use of assisted ventilation for at least 6 hours, transfer to another facility, or a 5-minute Apgar score of 3 or less.

“This measure has been proposed to serve as a balancing measure to maternal metrics, such as the rate of nulliparous, term, singleton, vertex-presenting cesarean deliveries,” the authors explained.

This study was supported by a Health Policy Award from the Society for Maternal-Fetal Medicine. The authors reported no relevant financial disclosures.

This story first appeared on Medscape.

Neonatal transfer was the factor most often associated with unexpected, severe complications at birth, particularly at hospitals that had the highest rates of complications, according to a cross-sectional study published online in JAMA Network Open (2020;3[2]:e1919498).

“Transfers were more likely to be necessary when infants were born in hospitals with lower levels of neonatal care,” Mark A. Clapp, MD, MPH, of Massachusetts General Hospital in Boston, and colleagues wrote. “Thus, if this metric is to be used in its current form, it would appear that accreditors, regulatory bodies, and payers should consider adjusting for or stratifying by a hospital’s level of neonatal care to avoid disincentivizing against appropriate transfers.”

The Joint Commission recently included unexpected complications in term newborns as a marker of quality of obstetric care, but it does not currently recommend any risk adjustment for the metric. The authors aimed to learn which factors regarding patients and hospitals were associated with such complications. Severe, unexpected newborn complications include death, seizure, use of assisted ventilation for at least 6 hours, transfer to another facility, or a 5-minute Apgar score of 3 or less.

“This measure has been proposed to serve as a balancing measure to maternal metrics, such as the rate of nulliparous, term, singleton, vertex-presenting cesarean deliveries,” the authors explained.

This study was supported by a Health Policy Award from the Society for Maternal-Fetal Medicine. The authors reported no relevant financial disclosures.

This story first appeared on Medscape.

The Diagnosis: Capillary Malformation-Arteriovenous Malformation Syndrome 

Capillary malformation-arteriovenous malformation (CM-AVM) was suspected, and a sample of the patient's blood was sent for a diagnostic genetic workup. DNA sequencing evaluated the following 5 genes that have been implicated in telangiectasia or AVM disorders: ACVRL1 (activin A receptorlike type 1), ENG (endoglin), GDF2 (growth differentiation factor 2), RASA1 (RAS p21 protein activator 1), and SMAD4 (SMAD family member 4). The patient was found to be heterozygous for a known pathogenic splice-site mutation in the RASA1 gene, consistent with a diagnosis of CM-AVM. 

Capillary malformation-arteriovenous malformation presents with multiple small cutaneous CMs and associated arteriovenous fistulas as well as high-flow AVMs located in the soft tissues, bones, or central nervous system (CNS). Occasionally, the cutaneous CMs are surrounded by a blanched halo.¹ Because of the potential for CNS involvement in CM-AVM, our patient was further evaluated with spine and brain magnetic resonance imaging (MRI). The brain MRI revealed 2 right occipital pole and fusiform gyral AVMs (Figure). No vascular abnormalities were found in the spine. The patient was referred to interventional neuroradiology to assess the feasibility of ablation to reduce the risk for complications, including intracranial hemorrhage.

Compared to other well-established congenital vascular disorders, CM-AVM has only recently been described in the literature. It was first reported by Eerola and colleagues² in 2003. They studied several families with CMs and identified heterozygous inactivating RASA1 mutations in 6 families manifesting atypical CMs that were multiple small, round to oval, and pinkish red.² 

It has been estimated that RASA1 mutations contribute to 68% of CM-AVM cases. Another gene--EPHB4 (EPH receptor B4)--has been implicated in patients with RASA1-negative disease. Two separate subtypes for patients with CM-AVM have been described: (1) CM-AVM type 1 for patients with RASA1 mutations, and (2) CM-AVM type 2 for those with EPHB4 mutations.³  

Both CM-AVM types are characterized by small multifocal CMs and an increased risk for CNS fast-flow vascular malformations.⁴ It has been suggested that there are morphologic differences between the cutaneous manifestations of the 2 types. For example, one group stated Bier spots are more frequently observed in CM-AVM type 2. This same group suggested telangiectases seen primarily on the lips but also in the perioral region and on the upper thorax were seen in CM-AVM type 2 but not in CM-AVM type 1.4 In our patient, it is plausible that the pinpoint red macules on the lips and oral mucosa could be confused for telangiectases (quiz image [bottom]). At this time, we do not feel that there is sufficient evidence to clinically distinguish between CM-AVM types 1 and 2.  

Central nervous system involvement seems to be more common in patients with CM-AVM type 1 (10%) than those with CM-AVM type 2 (3%).^1,4 Of the 2 CM-AVM type 2 patients found to have intracranial AVMs in one study, both were found to have vein of Galen aneurysmal malformations (VGAMs).⁴ The study examining CNS involvement in CM-AVM type 1 did not comment on the percentage of VGAMs seen in all patients.¹ However, in the retrospective component of the study, the authors reported that in 161 patients with CM-AVM type 1, 24 AVMs were observed, 6 of which were intracranial. Half of these intracranial AVMs were at the vein of Galen, demonstrating that VGAMs are seen in both types of CM-AVM.¹ Further study is necessary to better characterize potential phenotypic differences between the 2 forms of CM-AVM.  

Overall, the annual risk for hemorrhage associated with brain AVMs is approximately 2% per year.⁵ Because the morbidity and mortality of undiagnosed CNS malformations is high, it is recommended that patients with both types of CM-AVM undergo spine and brain MRI evaluation. If CNS malformations are identified, patients should be referred to interventional neuroradiology to assess the feasibility of ablation.  

It is unclear if patients who initially screen negative for AVMs will go on to develop these fast-flow lesions later. We have noted that new CMs develop over time in our patients. Therefore, it does not seem far-fetched to hypothesize that AVMs of CNS are similarly dynamic. Ultimately, we recommend ongoing screening for brain and spinal AVMs at regular intervals, determined by discussions of risks and benefits between the treating team and patient/family.  

It is important to distinguish CM-AVM from hereditary hemorrhagic telangiectasia (HHT), as the distinction affects patient management. Unlike the AVMs found in HHT, AVMs in CM-AVM seldom are found in the lungs or liver.¹ Thus, asymptomatic patients with HHT, but not CM-AVM, often are screened for pulmonary AVMs. 

The diagnosis of HHT is based on the following 4 findings: spontaneous and recurrent epistaxis; multiple mucocutaneous telangiectasia at characteristic sites, including the lips, oral cavity, fingers, and nose; visceral involvement, such as gastrointestinal, pulmonary, cerebral, or hepatic AVMs; and a first-degree relative with the disorder. Three of the criteria are required for diagnosis. 

Notably, the lesions seen in HHT and CM-AVM are morphologically different. Our patient did have 1-mm red macules on the lower lip that had clinical features overlapping with telangiectases, but other cutaneous findings including the presence of red macules and small patches, some with blanched halos, were clearly characteristic of CMs, not telangiectases.⁶ Furthermore, our patient did not have a personal history of epistaxis or a family history of any affected first-degree relatives. Finally, individuals with HHT tend to develop symptoms later in life compared to patients with CM-AVM, starting with epistaxis at 12 years of age.⁶ 

Patients with Henoch-Schönlein purpura also present in childhood but typically demonstrate palpable purpura and acute abdominal pain. Patients with Klippel-Trenaunay syndrome present with CM and venous malformation but also typically display limb overgrowth. Most patients with Klippel-Trenaunay syndrome are born with a port-wine stain.  

Diffuse neonatal hemangiomatosis is characterized by multiple progressive, rapidly growing cutaneous hemangiomas associated with widespread visceral hemangiomas in the liver, lungs, gastrointestinal tract, brain, and meninges. Our patient's macules were much more slowly progressive.  

The Diagnosis: Capillary Malformation-Arteriovenous Malformation Syndrome 

Capillary malformation-arteriovenous malformation (CM-AVM) was suspected, and a sample of the patient's blood was sent for a diagnostic genetic workup. DNA sequencing evaluated the following 5 genes that have been implicated in telangiectasia or AVM disorders: ACVRL1 (activin A receptorlike type 1), ENG (endoglin), GDF2 (growth differentiation factor 2), RASA1 (RAS p21 protein activator 1), and SMAD4 (SMAD family member 4). The patient was found to be heterozygous for a known pathogenic splice-site mutation in the RASA1 gene, consistent with a diagnosis of CM-AVM. 

Capillary malformation-arteriovenous malformation presents with multiple small cutaneous CMs and associated arteriovenous fistulas as well as high-flow AVMs located in the soft tissues, bones, or central nervous system (CNS). Occasionally, the cutaneous CMs are surrounded by a blanched halo.¹ Because of the potential for CNS involvement in CM-AVM, our patient was further evaluated with spine and brain magnetic resonance imaging (MRI). The brain MRI revealed 2 right occipital pole and fusiform gyral AVMs (Figure). No vascular abnormalities were found in the spine. The patient was referred to interventional neuroradiology to assess the feasibility of ablation to reduce the risk for complications, including intracranial hemorrhage.

Compared to other well-established congenital vascular disorders, CM-AVM has only recently been described in the literature. It was first reported by Eerola and colleagues² in 2003. They studied several families with CMs and identified heterozygous inactivating RASA1 mutations in 6 families manifesting atypical CMs that were multiple small, round to oval, and pinkish red.² 

It has been estimated that RASA1 mutations contribute to 68% of CM-AVM cases. Another gene--EPHB4 (EPH receptor B4)--has been implicated in patients with RASA1-negative disease. Two separate subtypes for patients with CM-AVM have been described: (1) CM-AVM type 1 for patients with RASA1 mutations, and (2) CM-AVM type 2 for those with EPHB4 mutations.³  

Both CM-AVM types are characterized by small multifocal CMs and an increased risk for CNS fast-flow vascular malformations.⁴ It has been suggested that there are morphologic differences between the cutaneous manifestations of the 2 types. For example, one group stated Bier spots are more frequently observed in CM-AVM type 2. This same group suggested telangiectases seen primarily on the lips but also in the perioral region and on the upper thorax were seen in CM-AVM type 2 but not in CM-AVM type 1.4 In our patient, it is plausible that the pinpoint red macules on the lips and oral mucosa could be confused for telangiectases (quiz image [bottom]). At this time, we do not feel that there is sufficient evidence to clinically distinguish between CM-AVM types 1 and 2.  

Central nervous system involvement seems to be more common in patients with CM-AVM type 1 (10%) than those with CM-AVM type 2 (3%).^1,4 Of the 2 CM-AVM type 2 patients found to have intracranial AVMs in one study, both were found to have vein of Galen aneurysmal malformations (VGAMs).⁴ The study examining CNS involvement in CM-AVM type 1 did not comment on the percentage of VGAMs seen in all patients.¹ However, in the retrospective component of the study, the authors reported that in 161 patients with CM-AVM type 1, 24 AVMs were observed, 6 of which were intracranial. Half of these intracranial AVMs were at the vein of Galen, demonstrating that VGAMs are seen in both types of CM-AVM.¹ Further study is necessary to better characterize potential phenotypic differences between the 2 forms of CM-AVM.  

Overall, the annual risk for hemorrhage associated with brain AVMs is approximately 2% per year.⁵ Because the morbidity and mortality of undiagnosed CNS malformations is high, it is recommended that patients with both types of CM-AVM undergo spine and brain MRI evaluation. If CNS malformations are identified, patients should be referred to interventional neuroradiology to assess the feasibility of ablation.  

It is unclear if patients who initially screen negative for AVMs will go on to develop these fast-flow lesions later. We have noted that new CMs develop over time in our patients. Therefore, it does not seem far-fetched to hypothesize that AVMs of CNS are similarly dynamic. Ultimately, we recommend ongoing screening for brain and spinal AVMs at regular intervals, determined by discussions of risks and benefits between the treating team and patient/family.  

It is important to distinguish CM-AVM from hereditary hemorrhagic telangiectasia (HHT), as the distinction affects patient management. Unlike the AVMs found in HHT, AVMs in CM-AVM seldom are found in the lungs or liver.¹ Thus, asymptomatic patients with HHT, but not CM-AVM, often are screened for pulmonary AVMs. 

The diagnosis of HHT is based on the following 4 findings: spontaneous and recurrent epistaxis; multiple mucocutaneous telangiectasia at characteristic sites, including the lips, oral cavity, fingers, and nose; visceral involvement, such as gastrointestinal, pulmonary, cerebral, or hepatic AVMs; and a first-degree relative with the disorder. Three of the criteria are required for diagnosis. 

Notably, the lesions seen in HHT and CM-AVM are morphologically different. Our patient did have 1-mm red macules on the lower lip that had clinical features overlapping with telangiectases, but other cutaneous findings including the presence of red macules and small patches, some with blanched halos, were clearly characteristic of CMs, not telangiectases.⁶ Furthermore, our patient did not have a personal history of epistaxis or a family history of any affected first-degree relatives. Finally, individuals with HHT tend to develop symptoms later in life compared to patients with CM-AVM, starting with epistaxis at 12 years of age.⁶ 

Patients with Henoch-Schönlein purpura also present in childhood but typically demonstrate palpable purpura and acute abdominal pain. Patients with Klippel-Trenaunay syndrome present with CM and venous malformation but also typically display limb overgrowth. Most patients with Klippel-Trenaunay syndrome are born with a port-wine stain.  

Diffuse neonatal hemangiomatosis is characterized by multiple progressive, rapidly growing cutaneous hemangiomas associated with widespread visceral hemangiomas in the liver, lungs, gastrointestinal tract, brain, and meninges. Our patient's macules were much more slowly progressive.  

The Diagnosis: Capillary Malformation-Arteriovenous Malformation Syndrome 

Capillary malformation-arteriovenous malformation (CM-AVM) was suspected, and a sample of the patient's blood was sent for a diagnostic genetic workup. DNA sequencing evaluated the following 5 genes that have been implicated in telangiectasia or AVM disorders: ACVRL1 (activin A receptorlike type 1), ENG (endoglin), GDF2 (growth differentiation factor 2), RASA1 (RAS p21 protein activator 1), and SMAD4 (SMAD family member 4). The patient was found to be heterozygous for a known pathogenic splice-site mutation in the RASA1 gene, consistent with a diagnosis of CM-AVM. 

Capillary malformation-arteriovenous malformation presents with multiple small cutaneous CMs and associated arteriovenous fistulas as well as high-flow AVMs located in the soft tissues, bones, or central nervous system (CNS). Occasionally, the cutaneous CMs are surrounded by a blanched halo.¹ Because of the potential for CNS involvement in CM-AVM, our patient was further evaluated with spine and brain magnetic resonance imaging (MRI). The brain MRI revealed 2 right occipital pole and fusiform gyral AVMs (Figure). No vascular abnormalities were found in the spine. The patient was referred to interventional neuroradiology to assess the feasibility of ablation to reduce the risk for complications, including intracranial hemorrhage.

Compared to other well-established congenital vascular disorders, CM-AVM has only recently been described in the literature. It was first reported by Eerola and colleagues² in 2003. They studied several families with CMs and identified heterozygous inactivating RASA1 mutations in 6 families manifesting atypical CMs that were multiple small, round to oval, and pinkish red.² 

It has been estimated that RASA1 mutations contribute to 68% of CM-AVM cases. Another gene--EPHB4 (EPH receptor B4)--has been implicated in patients with RASA1-negative disease. Two separate subtypes for patients with CM-AVM have been described: (1) CM-AVM type 1 for patients with RASA1 mutations, and (2) CM-AVM type 2 for those with EPHB4 mutations.³  

Both CM-AVM types are characterized by small multifocal CMs and an increased risk for CNS fast-flow vascular malformations.⁴ It has been suggested that there are morphologic differences between the cutaneous manifestations of the 2 types. For example, one group stated Bier spots are more frequently observed in CM-AVM type 2. This same group suggested telangiectases seen primarily on the lips but also in the perioral region and on the upper thorax were seen in CM-AVM type 2 but not in CM-AVM type 1.4 In our patient, it is plausible that the pinpoint red macules on the lips and oral mucosa could be confused for telangiectases (quiz image [bottom]). At this time, we do not feel that there is sufficient evidence to clinically distinguish between CM-AVM types 1 and 2.  

Central nervous system involvement seems to be more common in patients with CM-AVM type 1 (10%) than those with CM-AVM type 2 (3%).^1,4 Of the 2 CM-AVM type 2 patients found to have intracranial AVMs in one study, both were found to have vein of Galen aneurysmal malformations (VGAMs).⁴ The study examining CNS involvement in CM-AVM type 1 did not comment on the percentage of VGAMs seen in all patients.¹ However, in the retrospective component of the study, the authors reported that in 161 patients with CM-AVM type 1, 24 AVMs were observed, 6 of which were intracranial. Half of these intracranial AVMs were at the vein of Galen, demonstrating that VGAMs are seen in both types of CM-AVM.¹ Further study is necessary to better characterize potential phenotypic differences between the 2 forms of CM-AVM.  

Overall, the annual risk for hemorrhage associated with brain AVMs is approximately 2% per year.⁵ Because the morbidity and mortality of undiagnosed CNS malformations is high, it is recommended that patients with both types of CM-AVM undergo spine and brain MRI evaluation. If CNS malformations are identified, patients should be referred to interventional neuroradiology to assess the feasibility of ablation.  

It is unclear if patients who initially screen negative for AVMs will go on to develop these fast-flow lesions later. We have noted that new CMs develop over time in our patients. Therefore, it does not seem far-fetched to hypothesize that AVMs of CNS are similarly dynamic. Ultimately, we recommend ongoing screening for brain and spinal AVMs at regular intervals, determined by discussions of risks and benefits between the treating team and patient/family.  

It is important to distinguish CM-AVM from hereditary hemorrhagic telangiectasia (HHT), as the distinction affects patient management. Unlike the AVMs found in HHT, AVMs in CM-AVM seldom are found in the lungs or liver.¹ Thus, asymptomatic patients with HHT, but not CM-AVM, often are screened for pulmonary AVMs. 

The diagnosis of HHT is based on the following 4 findings: spontaneous and recurrent epistaxis; multiple mucocutaneous telangiectasia at characteristic sites, including the lips, oral cavity, fingers, and nose; visceral involvement, such as gastrointestinal, pulmonary, cerebral, or hepatic AVMs; and a first-degree relative with the disorder. Three of the criteria are required for diagnosis. 

Notably, the lesions seen in HHT and CM-AVM are morphologically different. Our patient did have 1-mm red macules on the lower lip that had clinical features overlapping with telangiectases, but other cutaneous findings including the presence of red macules and small patches, some with blanched halos, were clearly characteristic of CMs, not telangiectases.⁶ Furthermore, our patient did not have a personal history of epistaxis or a family history of any affected first-degree relatives. Finally, individuals with HHT tend to develop symptoms later in life compared to patients with CM-AVM, starting with epistaxis at 12 years of age.⁶ 

Patients with Henoch-Schönlein purpura also present in childhood but typically demonstrate palpable purpura and acute abdominal pain. Patients with Klippel-Trenaunay syndrome present with CM and venous malformation but also typically display limb overgrowth. Most patients with Klippel-Trenaunay syndrome are born with a port-wine stain.  

Diffuse neonatal hemangiomatosis is characterized by multiple progressive, rapidly growing cutaneous hemangiomas associated with widespread visceral hemangiomas in the liver, lungs, gastrointestinal tract, brain, and meninges. Our patient's macules were much more slowly progressive.  

The American Academy of Neurology (AAN) has issued a new guideline for the treatment of sleep problems in children and teenagers with autism spectrum disorders (ASD). The guideline was published online ahead of print Feb. 12 in Neurology.

“While up to 40% of children and teens in the general population will have sleep problems at some point during their childhood, such problems usually lessen with age,” lead author Ashura Williams Buckley, MD, director of the Sleep and Neurodevelopment Service at the National Institute of Mental Health in Bethesda, Md., said in a press release. “For children and teens with autism, sleep problems are more common and more likely to persist, resulting in poor health and poor quality of life. Some sleep problems may be directly related to autism, but others are not. Regardless, autism symptoms may make sleep problems worse.”
 

Few evidence-based treatments are available

Dr. Williams Buckley and colleagues developed the current guideline to evaluate which pharmacologic, behavioral, and complementary and alternative medicine (CAM) interventions improve bedtime resistance, sleep onset latency, sleep continuity, total sleep time, and daytime behavior in children and adolescents with ASD. The panel evaluated 900 abstracts of articles that had been included in systematic reviews, as well as 1,087 additional abstracts. One hundred thirty-nine articles were potentially relevant, 12 met criteria for data extraction, and eight were rated class III or higher and were included in the panel’s review.

The authors observed what they called a dearth of evidence-based treatments for sleep dysregulation in ASD. Evidence indicates that melatonin, with or without cognitive–behavioral therapy (CBT), improves several sleep outcomes, compared with placebo. “Evidence for other interventions is largely lacking,” wrote Dr. Williams Buckley and colleagues. They observed a lack of long-term safety data for melatonin in children, which they considered concerning, because melatonin affects the hypothalamic–gonadal axis and can potentially influence pubertal development.
 

Screening for comorbid conditions and concomitant medications

The guideline recommends that clinicians assess children with ASD and sleep disturbances for coexisting conditions and concomitant medications that could be contributing to these sleep disturbances. They should ensure that children receive appropriate treatment for coexisting conditions and adjust or discontinue potentially problematic medications appropriately, according to the guideline.

Furthermore, clinicians should counsel parents or guardians about behavioral strategies as a first-line treatment for improving sleep function. These strategies could be administered alone or with pharmacologic or neutraceutical approaches as needed, according to the authors. Suggested behavioral approaches include unmodified extinction (i.e., imposing a bedtime and ignoring a child’s protests), graduated extinction (i.e., ignoring protests for a specified period before responding), positive routines (i.e., establishing pre-bedtime calming rituals), and bedtime fading (i.e., putting a child to bed close to the time he or she begins to fall asleep).

If a child’s contributing coexisting conditions and medications have been addressed and behavioral strategies have not been helpful, clinicians should offer melatonin, according to the guideline. Because over-the-counter formulations contain variable concentrations of melatonin, clinicians should write a prescription for it or recommend high-purity pharmaceutical grade melatonin. The initial dose should be 1-3 mg/day at 60-30 minutes before bedtime. The dose can be titrated to 10 mg/day. Clinicians also should counsel children and their parents about potential adverse events of melatonin and the lack of long-term safety data, according to the guideline.

In addition, clinicians should advise children and parents that no evidence supports the routine use of weighted blankets or specialized mattress technology for improving sleep. Parents who ask about weighted blankets should be told that the reviewed trial reported no serious adverse events with this intervention, and that blankets could be a reasonable nonpharmacologic approach for some patients, according to the guideline.
 

Optimal outcome measures are undefined

Dr. Williams Buckley and colleagues also suggested areas for future research. Investigators have not yet defined optimal outcome measures (e.g., questionnaires, polysomnography, and actigraphy) that balance tolerability and accuracy, they wrote. Clinically important differences for most measures also have yet to be determined. Researchers should investigate whether long-term adverse events are associated with chronic melatonin use and study patients with ASD and comorbid mood disorders, wrote the authors. “Research tying the underlying neurobiology in early-life sleep disruption to behavior might help clinicians and researchers understand which treatments might work for which people with ASD,” they concluded.

The AAN supported the development of the guideline. Dr. Williams Buckley had no conflicts of interest. Six authors had conflicts of interest that the AAN deemed not significant enough to prevent their participation in the development of the guideline.

[email protected]

SOURCE: Williams Buckley A et al. Neurology. 2020;94:393-405. doi: 10.1212/WNL0000000000009033.

The American Academy of Neurology (AAN) has issued a new guideline for the treatment of sleep problems in children and teenagers with autism spectrum disorders (ASD). The guideline was published online ahead of print Feb. 12 in Neurology.

“While up to 40% of children and teens in the general population will have sleep problems at some point during their childhood, such problems usually lessen with age,” lead author Ashura Williams Buckley, MD, director of the Sleep and Neurodevelopment Service at the National Institute of Mental Health in Bethesda, Md., said in a press release. “For children and teens with autism, sleep problems are more common and more likely to persist, resulting in poor health and poor quality of life. Some sleep problems may be directly related to autism, but others are not. Regardless, autism symptoms may make sleep problems worse.”
 

Few evidence-based treatments are available

Dr. Williams Buckley and colleagues developed the current guideline to evaluate which pharmacologic, behavioral, and complementary and alternative medicine (CAM) interventions improve bedtime resistance, sleep onset latency, sleep continuity, total sleep time, and daytime behavior in children and adolescents with ASD. The panel evaluated 900 abstracts of articles that had been included in systematic reviews, as well as 1,087 additional abstracts. One hundred thirty-nine articles were potentially relevant, 12 met criteria for data extraction, and eight were rated class III or higher and were included in the panel’s review.

The authors observed what they called a dearth of evidence-based treatments for sleep dysregulation in ASD. Evidence indicates that melatonin, with or without cognitive–behavioral therapy (CBT), improves several sleep outcomes, compared with placebo. “Evidence for other interventions is largely lacking,” wrote Dr. Williams Buckley and colleagues. They observed a lack of long-term safety data for melatonin in children, which they considered concerning, because melatonin affects the hypothalamic–gonadal axis and can potentially influence pubertal development.
 

Screening for comorbid conditions and concomitant medications

The guideline recommends that clinicians assess children with ASD and sleep disturbances for coexisting conditions and concomitant medications that could be contributing to these sleep disturbances. They should ensure that children receive appropriate treatment for coexisting conditions and adjust or discontinue potentially problematic medications appropriately, according to the guideline.

Furthermore, clinicians should counsel parents or guardians about behavioral strategies as a first-line treatment for improving sleep function. These strategies could be administered alone or with pharmacologic or neutraceutical approaches as needed, according to the authors. Suggested behavioral approaches include unmodified extinction (i.e., imposing a bedtime and ignoring a child’s protests), graduated extinction (i.e., ignoring protests for a specified period before responding), positive routines (i.e., establishing pre-bedtime calming rituals), and bedtime fading (i.e., putting a child to bed close to the time he or she begins to fall asleep).

If a child’s contributing coexisting conditions and medications have been addressed and behavioral strategies have not been helpful, clinicians should offer melatonin, according to the guideline. Because over-the-counter formulations contain variable concentrations of melatonin, clinicians should write a prescription for it or recommend high-purity pharmaceutical grade melatonin. The initial dose should be 1-3 mg/day at 60-30 minutes before bedtime. The dose can be titrated to 10 mg/day. Clinicians also should counsel children and their parents about potential adverse events of melatonin and the lack of long-term safety data, according to the guideline.

In addition, clinicians should advise children and parents that no evidence supports the routine use of weighted blankets or specialized mattress technology for improving sleep. Parents who ask about weighted blankets should be told that the reviewed trial reported no serious adverse events with this intervention, and that blankets could be a reasonable nonpharmacologic approach for some patients, according to the guideline.
 

Optimal outcome measures are undefined

Dr. Williams Buckley and colleagues also suggested areas for future research. Investigators have not yet defined optimal outcome measures (e.g., questionnaires, polysomnography, and actigraphy) that balance tolerability and accuracy, they wrote. Clinically important differences for most measures also have yet to be determined. Researchers should investigate whether long-term adverse events are associated with chronic melatonin use and study patients with ASD and comorbid mood disorders, wrote the authors. “Research tying the underlying neurobiology in early-life sleep disruption to behavior might help clinicians and researchers understand which treatments might work for which people with ASD,” they concluded.

The AAN supported the development of the guideline. Dr. Williams Buckley had no conflicts of interest. Six authors had conflicts of interest that the AAN deemed not significant enough to prevent their participation in the development of the guideline.

[email protected]

SOURCE: Williams Buckley A et al. Neurology. 2020;94:393-405. doi: 10.1212/WNL0000000000009033.

The American Academy of Neurology (AAN) has issued a new guideline for the treatment of sleep problems in children and teenagers with autism spectrum disorders (ASD). The guideline was published online ahead of print Feb. 12 in Neurology.

“While up to 40% of children and teens in the general population will have sleep problems at some point during their childhood, such problems usually lessen with age,” lead author Ashura Williams Buckley, MD, director of the Sleep and Neurodevelopment Service at the National Institute of Mental Health in Bethesda, Md., said in a press release. “For children and teens with autism, sleep problems are more common and more likely to persist, resulting in poor health and poor quality of life. Some sleep problems may be directly related to autism, but others are not. Regardless, autism symptoms may make sleep problems worse.”
 

Few evidence-based treatments are available

Dr. Williams Buckley and colleagues developed the current guideline to evaluate which pharmacologic, behavioral, and complementary and alternative medicine (CAM) interventions improve bedtime resistance, sleep onset latency, sleep continuity, total sleep time, and daytime behavior in children and adolescents with ASD. The panel evaluated 900 abstracts of articles that had been included in systematic reviews, as well as 1,087 additional abstracts. One hundred thirty-nine articles were potentially relevant, 12 met criteria for data extraction, and eight were rated class III or higher and were included in the panel’s review.

The authors observed what they called a dearth of evidence-based treatments for sleep dysregulation in ASD. Evidence indicates that melatonin, with or without cognitive–behavioral therapy (CBT), improves several sleep outcomes, compared with placebo. “Evidence for other interventions is largely lacking,” wrote Dr. Williams Buckley and colleagues. They observed a lack of long-term safety data for melatonin in children, which they considered concerning, because melatonin affects the hypothalamic–gonadal axis and can potentially influence pubertal development.
 

Screening for comorbid conditions and concomitant medications

The guideline recommends that clinicians assess children with ASD and sleep disturbances for coexisting conditions and concomitant medications that could be contributing to these sleep disturbances. They should ensure that children receive appropriate treatment for coexisting conditions and adjust or discontinue potentially problematic medications appropriately, according to the guideline.

Furthermore, clinicians should counsel parents or guardians about behavioral strategies as a first-line treatment for improving sleep function. These strategies could be administered alone or with pharmacologic or neutraceutical approaches as needed, according to the authors. Suggested behavioral approaches include unmodified extinction (i.e., imposing a bedtime and ignoring a child’s protests), graduated extinction (i.e., ignoring protests for a specified period before responding), positive routines (i.e., establishing pre-bedtime calming rituals), and bedtime fading (i.e., putting a child to bed close to the time he or she begins to fall asleep).

If a child’s contributing coexisting conditions and medications have been addressed and behavioral strategies have not been helpful, clinicians should offer melatonin, according to the guideline. Because over-the-counter formulations contain variable concentrations of melatonin, clinicians should write a prescription for it or recommend high-purity pharmaceutical grade melatonin. The initial dose should be 1-3 mg/day at 60-30 minutes before bedtime. The dose can be titrated to 10 mg/day. Clinicians also should counsel children and their parents about potential adverse events of melatonin and the lack of long-term safety data, according to the guideline.

In addition, clinicians should advise children and parents that no evidence supports the routine use of weighted blankets or specialized mattress technology for improving sleep. Parents who ask about weighted blankets should be told that the reviewed trial reported no serious adverse events with this intervention, and that blankets could be a reasonable nonpharmacologic approach for some patients, according to the guideline.
 

Optimal outcome measures are undefined

Dr. Williams Buckley and colleagues also suggested areas for future research. Investigators have not yet defined optimal outcome measures (e.g., questionnaires, polysomnography, and actigraphy) that balance tolerability and accuracy, they wrote. Clinically important differences for most measures also have yet to be determined. Researchers should investigate whether long-term adverse events are associated with chronic melatonin use and study patients with ASD and comorbid mood disorders, wrote the authors. “Research tying the underlying neurobiology in early-life sleep disruption to behavior might help clinicians and researchers understand which treatments might work for which people with ASD,” they concluded.

The AAN supported the development of the guideline. Dr. Williams Buckley had no conflicts of interest. Six authors had conflicts of interest that the AAN deemed not significant enough to prevent their participation in the development of the guideline.

[email protected]

SOURCE: Williams Buckley A et al. Neurology. 2020;94:393-405. doi: 10.1212/WNL0000000000009033.

LONDON – Revised classification criteria for epidermolysis bullosa (EB) demonstrate how far researchers and clinicians have come in understanding this debilitating group of genetic skin diseases, but also how far there is still to go towards improving the management of those affected.

Sara Freeman/MDedge News

Previous criteria issued in 2014 represented “important progress” and “built on the achievements of several generations of physicians and researchers who described the phenotypes, the level of skin cleavage, developed and characterized antibodies, and discovered EB-associated genes,” Cristina Has, MD, said at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

Dr. Has, a senior dermatologist and professor of experimental dermatology at the University of Freiburg (Germany), observed that prior criteria had “introduced genetic and molecular data in a so-called onion-skin classification of EB, and removed most of the eponyms,” which had been maintained in the latest update.

“What is new, and probably the most important change, is making the distinction between classical EB and other disorders with skin fragility,” she said, noting that the revised classification criteria for EB included minor changes to the nomenclature of EB. Six new EB subtypes and genes have also been added, and there are new sections on genotype/phenotype correlations, disease modifying factors, and the natural history of EB. Furthermore, supporting information included a concise description of clinical and genetic features of all EB types and subtypes.

The updated criteria are the result of an expert meeting held in April 2019 and have been accepted for publication. The expert panel that developed the criteria think that the revised classification criteria will be “useful and, we hope, inspiring and motivating for the young generation of dermatologists, pediatricians, and for the researchers who work in this field,” Dr. Has said.

“The term EB has been used in the last years for many new disorders, and this is the reason why we thought we have to somehow control this, and to make the distinction between classical epidermolysis bullosa due to defects at the dermal junction and other disorders with skin fragility where the anomalies occur within other layers of the epidermis or in the dermis,” Dr. Has explained.

There are still 4 main types of classical EB: EB simplex (EBS), dystrophic EB (DEB), junctional EB, and Kindler EB, but there are now 34 subtypes, slightly fewer than before. The updated criteria distinguish between the types and subtypes according to the level of skin cleavage, the inheritance pattern, the mutated gene, and the targeted protein, Dr. Has said.

As for peeling disorders, these have been classified as being erosive or hyperkeratotic, or as affecting the connective tissue with skin blistering. Similar to classical EB, these disorders are associated with fragility of the skin and mucosa and share some pathogenetic mechanisms. Moreover, as “the suffering of the patient is similar,” Dr. Has said, “we’d like to consider them under the umbrella of EB.” Most of the disorders she listed were inherited via an autosomal recessive mechanism, with intraepidermal disorders inherited via an autosomal dominant mechanism. New genes are being identified the time, she added, so these groupings will no doubt be subject to future revisions.

Minor changes to nomenclature were made to avoid confusion among clinicians and those living with the condition. As such, Kindler EB replaces Kindler syndrome, names of some subtypes were simplified, and a new “self-improving” type of DEB was introduced to replace the term “transient dermolysis of the newborn.” Altogether, there are now 11 subtypes of DEB. A distinction was also made between syndromic and nonsyndromic EB. “We all know that EB can be a systemic disorder with secondary manifestations within different organs,” Dr. Has told conference attendees. Anemia and failure to thrive can be associated, but it still remains a nonsyndromic disorder, she said. By contrast, “syndromic EB is due to genetic defects, which are also expressed in other organs than the skin or mucosal membranes, and lead to primary extracutaneous manifestations, such as cardiomyopathy, nephropathy, and so on.”

There are fewer subtypes of EBS and “we think they are better defined,” Dr. Has stated. “EB simplex is the most heterogenous EB type, clinically and genetically, and includes several syndromic disorders,” and the new classification criteria should be useful in helping categorize individuals with EBS and thus help target their management.

One of the six new subtypes of EB included in the revised classification criteria is “syndromic EBS with cardiomyopathy” caused by the KLH24 mutation. This gene was discovered in 2016 and more than 40 cases have so far been identified, 50% of which have been sporadic de novo mutations.

Other new EB subtypes are:

• “EBS with localized nephropathy” caused by a mutation in the CD151 gene.
• An autosomal recessive EBS linked to the KRT5 gene.
• A new phenotype that manifests with oral mucosal blisters linked to the DSG3 gene. (Although only a single case has been reported to date, it was felt worthy of inclusion.)
• Another linked to DSG3 that leads to skin fragility and hypertrichosis.
• A new dystrophic EB subtype linked to mutations in the PLOD3 gene.

In an interview, Dr. Has reiterated the importance of keeping classification criteria updated in line with current research findings. She emphasized that there were many types of EB and how important it was to refine how these were classified based on the underlying genetics.

“We brought much more genetic data into the paper, because we are in the era of personalized medicine,” she said. “There are specific therapies for mutations and for different subtypes and that’s why we think that, step by step, we have to bring in more and more data into the classification.”

There are many people with EBS, she observed, and while these individuals may not have such a dramatic clinical presentation as those with recessive DEB, for example, the effect of the condition on their daily lives is no less. “These people are active, they have jobs, they have to work, and they have pain, they have blister,” Dr. Has said.

While the criteria are intended only for classification of EB, they might help in practice. Dr. Has gave an anecdotal example of a woman that has been misdiagnosed as having a type of DEB with a high risk of squamous cell carcinoma but in fact had a different form of EB with no risk of developing SCC. “That’s why criteria are important,” she said.

Dr. Has had no conflicts of interest to disclose.
 

LONDON – Revised classification criteria for epidermolysis bullosa (EB) demonstrate how far researchers and clinicians have come in understanding this debilitating group of genetic skin diseases, but also how far there is still to go towards improving the management of those affected.

Sara Freeman/MDedge News

Previous criteria issued in 2014 represented “important progress” and “built on the achievements of several generations of physicians and researchers who described the phenotypes, the level of skin cleavage, developed and characterized antibodies, and discovered EB-associated genes,” Cristina Has, MD, said at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

Dr. Has, a senior dermatologist and professor of experimental dermatology at the University of Freiburg (Germany), observed that prior criteria had “introduced genetic and molecular data in a so-called onion-skin classification of EB, and removed most of the eponyms,” which had been maintained in the latest update.

“What is new, and probably the most important change, is making the distinction between classical EB and other disorders with skin fragility,” she said, noting that the revised classification criteria for EB included minor changes to the nomenclature of EB. Six new EB subtypes and genes have also been added, and there are new sections on genotype/phenotype correlations, disease modifying factors, and the natural history of EB. Furthermore, supporting information included a concise description of clinical and genetic features of all EB types and subtypes.

The updated criteria are the result of an expert meeting held in April 2019 and have been accepted for publication. The expert panel that developed the criteria think that the revised classification criteria will be “useful and, we hope, inspiring and motivating for the young generation of dermatologists, pediatricians, and for the researchers who work in this field,” Dr. Has said.

“The term EB has been used in the last years for many new disorders, and this is the reason why we thought we have to somehow control this, and to make the distinction between classical epidermolysis bullosa due to defects at the dermal junction and other disorders with skin fragility where the anomalies occur within other layers of the epidermis or in the dermis,” Dr. Has explained.

There are still 4 main types of classical EB: EB simplex (EBS), dystrophic EB (DEB), junctional EB, and Kindler EB, but there are now 34 subtypes, slightly fewer than before. The updated criteria distinguish between the types and subtypes according to the level of skin cleavage, the inheritance pattern, the mutated gene, and the targeted protein, Dr. Has said.

As for peeling disorders, these have been classified as being erosive or hyperkeratotic, or as affecting the connective tissue with skin blistering. Similar to classical EB, these disorders are associated with fragility of the skin and mucosa and share some pathogenetic mechanisms. Moreover, as “the suffering of the patient is similar,” Dr. Has said, “we’d like to consider them under the umbrella of EB.” Most of the disorders she listed were inherited via an autosomal recessive mechanism, with intraepidermal disorders inherited via an autosomal dominant mechanism. New genes are being identified the time, she added, so these groupings will no doubt be subject to future revisions.

Minor changes to nomenclature were made to avoid confusion among clinicians and those living with the condition. As such, Kindler EB replaces Kindler syndrome, names of some subtypes were simplified, and a new “self-improving” type of DEB was introduced to replace the term “transient dermolysis of the newborn.” Altogether, there are now 11 subtypes of DEB. A distinction was also made between syndromic and nonsyndromic EB. “We all know that EB can be a systemic disorder with secondary manifestations within different organs,” Dr. Has told conference attendees. Anemia and failure to thrive can be associated, but it still remains a nonsyndromic disorder, she said. By contrast, “syndromic EB is due to genetic defects, which are also expressed in other organs than the skin or mucosal membranes, and lead to primary extracutaneous manifestations, such as cardiomyopathy, nephropathy, and so on.”

There are fewer subtypes of EBS and “we think they are better defined,” Dr. Has stated. “EB simplex is the most heterogenous EB type, clinically and genetically, and includes several syndromic disorders,” and the new classification criteria should be useful in helping categorize individuals with EBS and thus help target their management.

One of the six new subtypes of EB included in the revised classification criteria is “syndromic EBS with cardiomyopathy” caused by the KLH24 mutation. This gene was discovered in 2016 and more than 40 cases have so far been identified, 50% of which have been sporadic de novo mutations.

Other new EB subtypes are:

• “EBS with localized nephropathy” caused by a mutation in the CD151 gene.
• An autosomal recessive EBS linked to the KRT5 gene.
• A new phenotype that manifests with oral mucosal blisters linked to the DSG3 gene. (Although only a single case has been reported to date, it was felt worthy of inclusion.)
• Another linked to DSG3 that leads to skin fragility and hypertrichosis.
• A new dystrophic EB subtype linked to mutations in the PLOD3 gene.

In an interview, Dr. Has reiterated the importance of keeping classification criteria updated in line with current research findings. She emphasized that there were many types of EB and how important it was to refine how these were classified based on the underlying genetics.

“We brought much more genetic data into the paper, because we are in the era of personalized medicine,” she said. “There are specific therapies for mutations and for different subtypes and that’s why we think that, step by step, we have to bring in more and more data into the classification.”

There are many people with EBS, she observed, and while these individuals may not have such a dramatic clinical presentation as those with recessive DEB, for example, the effect of the condition on their daily lives is no less. “These people are active, they have jobs, they have to work, and they have pain, they have blister,” Dr. Has said.

While the criteria are intended only for classification of EB, they might help in practice. Dr. Has gave an anecdotal example of a woman that has been misdiagnosed as having a type of DEB with a high risk of squamous cell carcinoma but in fact had a different form of EB with no risk of developing SCC. “That’s why criteria are important,” she said.

Dr. Has had no conflicts of interest to disclose.
 

LONDON – Revised classification criteria for epidermolysis bullosa (EB) demonstrate how far researchers and clinicians have come in understanding this debilitating group of genetic skin diseases, but also how far there is still to go towards improving the management of those affected.

Sara Freeman/MDedge News

Previous criteria issued in 2014 represented “important progress” and “built on the achievements of several generations of physicians and researchers who described the phenotypes, the level of skin cleavage, developed and characterized antibodies, and discovered EB-associated genes,” Cristina Has, MD, said at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

Dr. Has, a senior dermatologist and professor of experimental dermatology at the University of Freiburg (Germany), observed that prior criteria had “introduced genetic and molecular data in a so-called onion-skin classification of EB, and removed most of the eponyms,” which had been maintained in the latest update.

“What is new, and probably the most important change, is making the distinction between classical EB and other disorders with skin fragility,” she said, noting that the revised classification criteria for EB included minor changes to the nomenclature of EB. Six new EB subtypes and genes have also been added, and there are new sections on genotype/phenotype correlations, disease modifying factors, and the natural history of EB. Furthermore, supporting information included a concise description of clinical and genetic features of all EB types and subtypes.

The updated criteria are the result of an expert meeting held in April 2019 and have been accepted for publication. The expert panel that developed the criteria think that the revised classification criteria will be “useful and, we hope, inspiring and motivating for the young generation of dermatologists, pediatricians, and for the researchers who work in this field,” Dr. Has said.

“The term EB has been used in the last years for many new disorders, and this is the reason why we thought we have to somehow control this, and to make the distinction between classical epidermolysis bullosa due to defects at the dermal junction and other disorders with skin fragility where the anomalies occur within other layers of the epidermis or in the dermis,” Dr. Has explained.

There are still 4 main types of classical EB: EB simplex (EBS), dystrophic EB (DEB), junctional EB, and Kindler EB, but there are now 34 subtypes, slightly fewer than before. The updated criteria distinguish between the types and subtypes according to the level of skin cleavage, the inheritance pattern, the mutated gene, and the targeted protein, Dr. Has said.

As for peeling disorders, these have been classified as being erosive or hyperkeratotic, or as affecting the connective tissue with skin blistering. Similar to classical EB, these disorders are associated with fragility of the skin and mucosa and share some pathogenetic mechanisms. Moreover, as “the suffering of the patient is similar,” Dr. Has said, “we’d like to consider them under the umbrella of EB.” Most of the disorders she listed were inherited via an autosomal recessive mechanism, with intraepidermal disorders inherited via an autosomal dominant mechanism. New genes are being identified the time, she added, so these groupings will no doubt be subject to future revisions.

Minor changes to nomenclature were made to avoid confusion among clinicians and those living with the condition. As such, Kindler EB replaces Kindler syndrome, names of some subtypes were simplified, and a new “self-improving” type of DEB was introduced to replace the term “transient dermolysis of the newborn.” Altogether, there are now 11 subtypes of DEB. A distinction was also made between syndromic and nonsyndromic EB. “We all know that EB can be a systemic disorder with secondary manifestations within different organs,” Dr. Has told conference attendees. Anemia and failure to thrive can be associated, but it still remains a nonsyndromic disorder, she said. By contrast, “syndromic EB is due to genetic defects, which are also expressed in other organs than the skin or mucosal membranes, and lead to primary extracutaneous manifestations, such as cardiomyopathy, nephropathy, and so on.”

There are fewer subtypes of EBS and “we think they are better defined,” Dr. Has stated. “EB simplex is the most heterogenous EB type, clinically and genetically, and includes several syndromic disorders,” and the new classification criteria should be useful in helping categorize individuals with EBS and thus help target their management.

One of the six new subtypes of EB included in the revised classification criteria is “syndromic EBS with cardiomyopathy” caused by the KLH24 mutation. This gene was discovered in 2016 and more than 40 cases have so far been identified, 50% of which have been sporadic de novo mutations.

Other new EB subtypes are:

• “EBS with localized nephropathy” caused by a mutation in the CD151 gene.
• An autosomal recessive EBS linked to the KRT5 gene.
• A new phenotype that manifests with oral mucosal blisters linked to the DSG3 gene. (Although only a single case has been reported to date, it was felt worthy of inclusion.)
• Another linked to DSG3 that leads to skin fragility and hypertrichosis.
• A new dystrophic EB subtype linked to mutations in the PLOD3 gene.

In an interview, Dr. Has reiterated the importance of keeping classification criteria updated in line with current research findings. She emphasized that there were many types of EB and how important it was to refine how these were classified based on the underlying genetics.

“We brought much more genetic data into the paper, because we are in the era of personalized medicine,” she said. “There are specific therapies for mutations and for different subtypes and that’s why we think that, step by step, we have to bring in more and more data into the classification.”

There are many people with EBS, she observed, and while these individuals may not have such a dramatic clinical presentation as those with recessive DEB, for example, the effect of the condition on their daily lives is no less. “These people are active, they have jobs, they have to work, and they have pain, they have blister,” Dr. Has said.

While the criteria are intended only for classification of EB, they might help in practice. Dr. Has gave an anecdotal example of a woman that has been misdiagnosed as having a type of DEB with a high risk of squamous cell carcinoma but in fact had a different form of EB with no risk of developing SCC. “That’s why criteria are important,” she said.

Dr. Has had no conflicts of interest to disclose.
 

NEW ORLEANS – Weight-based harassment and bias is extremely prevalent throughout society and in doctors’ own offices, so be aware of ways to address it and support your patients regardless of weight.

Rebecca Puhl, PhD, a deputy director of the Rudd Center for Food Policy and Obesity at the University of Connecticut, Hartford, said that weight-based discrimination can occur whatever a person’s size or body shape, but it’s most often targeted at youth who are overweight or obese.

These children and teens commonly face teasing, harassment, cyberbullying, physical aggression, and social bullying from peers, coaches, teachers, and even parents, Dr. Puhl told attendees at the annual meeting of the American Academy of Pediatrics.

Common beliefs about overweight people – that they have little self discipline or poor eating and activity habits – only perpetuate stereotypes, she said. Common stereotypes are that people with obesity are noncompliant, lazy, sloppy, unsuccessful, unintelligent, dishonest, and awkward.

And health professionals of every type have been found to harbor these biases. In one study of more than 4,000 first-year medical students, well over half the respondents revealed explicit (74%) and implicit (67%) weight bias (Obesity. 2014 Apr;22[4]:1201-8). The study also found that explicit weight bias was stronger than explicit bias against blacks, Hispanics, LGBTQ people, and poor people.
 

Know the effects of weight stigma

Far from a minor issue, the discrimination that begins in childhood against those who are overweight can have a long-lasting impact on their future prospects and mental health. Being overweight is overwhelmingly cited as the most common reason for bullying (Pediatr Obes. 2016 Aug;11[4]:241-50). Dr. Puhl described to attendees how weight bias shifts throughout a lifetime, beginning as early as preschool. In childhood, the stereotypes about being overweight worsen, and the teasing and bullying increase. By adolescence, this treatment affects teens’ psychological, social, and physical well-being. It then translates in adulthood into reduced opportunities in employment and education, and poorer access and treatment in health care.

The mental distress caused by weight bullying often takes the form of depression, anxiety, and substance use, Dr. Puhl said, and children’s academic success can be hampered by bullying about their weight. One study found a higher risk of poor grades and school avoidance with each additional teasing incident (J Youth Adolesc. 2012 Jan;41[1]:27-40).

Weight stigma also can contribute to more weight gain, obesity, and lower physical activity levels. Maladaptive eating behaviors can result from weight stigmatization as well: binge eating, emotional eating, increased consumption in general, and other eating disorders. Severe binge eating is 80% more likely among teens who are bullied about their weight, Dr. Puhl said, and the risk increases with increased frequency and types of bullying.

Children who are teased about their weight often become less willing to engage in physical activity, she noted. They may skip gym class, feel less competent about physical activity, and end up enjoying sports participation less.

Further, sexual- and gender-minority youth report high rates of weight-related teasing from friends and family regardless of their body mass index (BMI) percentile, Dr. Puhl emphasized. Researchers have found bullying about weight in this population linked to dieting, difficulty sleeping, high stress levels, binge drinking, smoking, and marijuana use.
 

Know how to combat weight bias

Dr. Puhl described strategies for reducing weight bias based on clinical practice recommendations in the American Academy of Pediatrics’ policy statement entitled “Stigma Experienced by Children and Adolescents With Obesity” (Pediatrics. 2017 Dec;140[6]:e20173034).

Be aware. Consider how personal assumptions and attitudes about weight can affect your body language, tone of voice, facial expression, gestures, eye contact (or lack thereof), and spatial distance from the patient.

Recognizing the biological, genetic, and environmental causes of obesity can reduce stigma and improve understanding of the complexity of obesity etiology. It’s also important that you help parents understand this complexity and the negative impact of weight stigma.

Consider language and word choice. “Carefully consider language that might unintentionally communicate bias, blame, or negative judgment,” Dr. Puhl told attendees. “Use language that is supportive and empowering.”

Terms such as “unhealthy weight” and “high BMI” are less stigmatizing than “fat” and “morbidly obese” to parents, she said, and research has found nearly a quarter of parents would avoid future doctor appointments if their child’s doctor used stigmatizing terms to discuss weight (Pediatrics. 2011 Oct;128[4]:e786-93).

Teens themselves may have diverse preferences for the language used. Start by asking: “Could we talk about your weight today?” and then follow up by directly asking, “what words would you feel most comfortable with as we talk about your weight?”

Person-first language – such as “person with obesity” instead of “obese person” also is important to reducing stigma, she said.

It’s normal for you to feel uneasy about bringing up weight with patients, so Dr. Puhl recommended you practice dialogue out loud.

“Acknowledge your strengths,” she said. “You already have the skills and experience of engaging in difficult conversations with patients and families on a range of other health issues,” so apply that in this context as well.

Screen for negative experiences that could indicate weight-based bullying. These could include teasing and bullying, low self-esteem, poor school performance, depression, and anxiety.

“Remember that weight-based victimization can occur at diverse body sizes, not just in youth with obesity,” Dr. Puhl said. If you discover your patient is experiencing weight-related bullying, determine whether they have a support system in place and whether a mental health referral is appropriate. Provide or refer for behavior change counseling with motivational interviewing and patient-centered, empathic approaches. Parents should be aware of the issue and should contact the child’s teachers and school administration to help address it.

But before you do that, keep in mind that it’s not just peers doing the bullying. According to a study of teens with obesity enrolled in a national weight-loss camp, 37% of teen participants in 2012 said that their parents bully them (Pediatrics. 2013 Jan;131[1]:e1-9).

You should assess whether family interactions or the parents’ own history with weight is involved. If parents make disparaging comments about their child’s weight, “use this as an opportunity to model appropriate language and educate parents about weight bias,” Dr. Puhl said.

It’s also important to realize that parents themselves often are frustrated, so critical comments about their language or approach can backfire, she warned. Instead, help parents understand how to create a home setting that encourages healthy food choices, praises children for healthy decision making, and models positive health behaviors. It is key for them to focus on improving their children’s health behaviors rather than focusing on weight.

And before you contact the school, remember teachers also are common perpetrators of weight stigma, Dr. Puhl noted. She gave as an example a study in which investigators assessed 133 teachers’ perceptions of middle or high school students’ abilities based on photos that had been digitally altered to show each girl both as average weight or as overweight. Each photo was associated with an essay specifically chosen because it was neither particularly good nor bad (Brit J Educ Psychol. 2019 Oct 26. doi: 10.1111/bjep.12322). The teachers judged the essays believed to be submitted by overweight girls to be “similar in structural quality,” but they gave the overweight girls lower grades than the average-weight girls. They also indicated that they considered the overweight girls “put forth more effort, needed more remedial assistance, and had lower overall grades in school.” The teachers also rated other teachers’ weight bias to be at a low level, and their own weight bias to be “significantly lower” than the others.

Assess your clinical environment. Be aware of your clinical environment and whether it meets the needs of youth with diverse body sizes. That includes having a range of sturdy armless seating options and adequately sized doorways, hallways, and restrooms. You also should have beds, wheelchairs, and exam tables with adequate weight capacity. Also check that you have supplies, such as robes or blood pressure cuffs, on hand for a variety of body sizes.

NEW ORLEANS – Weight-based harassment and bias is extremely prevalent throughout society and in doctors’ own offices, so be aware of ways to address it and support your patients regardless of weight.

Rebecca Puhl, PhD, a deputy director of the Rudd Center for Food Policy and Obesity at the University of Connecticut, Hartford, said that weight-based discrimination can occur whatever a person’s size or body shape, but it’s most often targeted at youth who are overweight or obese.

These children and teens commonly face teasing, harassment, cyberbullying, physical aggression, and social bullying from peers, coaches, teachers, and even parents, Dr. Puhl told attendees at the annual meeting of the American Academy of Pediatrics.

Common beliefs about overweight people – that they have little self discipline or poor eating and activity habits – only perpetuate stereotypes, she said. Common stereotypes are that people with obesity are noncompliant, lazy, sloppy, unsuccessful, unintelligent, dishonest, and awkward.

And health professionals of every type have been found to harbor these biases. In one study of more than 4,000 first-year medical students, well over half the respondents revealed explicit (74%) and implicit (67%) weight bias (Obesity. 2014 Apr;22[4]:1201-8). The study also found that explicit weight bias was stronger than explicit bias against blacks, Hispanics, LGBTQ people, and poor people.
 

Know the effects of weight stigma

Far from a minor issue, the discrimination that begins in childhood against those who are overweight can have a long-lasting impact on their future prospects and mental health. Being overweight is overwhelmingly cited as the most common reason for bullying (Pediatr Obes. 2016 Aug;11[4]:241-50). Dr. Puhl described to attendees how weight bias shifts throughout a lifetime, beginning as early as preschool. In childhood, the stereotypes about being overweight worsen, and the teasing and bullying increase. By adolescence, this treatment affects teens’ psychological, social, and physical well-being. It then translates in adulthood into reduced opportunities in employment and education, and poorer access and treatment in health care.

The mental distress caused by weight bullying often takes the form of depression, anxiety, and substance use, Dr. Puhl said, and children’s academic success can be hampered by bullying about their weight. One study found a higher risk of poor grades and school avoidance with each additional teasing incident (J Youth Adolesc. 2012 Jan;41[1]:27-40).

Weight stigma also can contribute to more weight gain, obesity, and lower physical activity levels. Maladaptive eating behaviors can result from weight stigmatization as well: binge eating, emotional eating, increased consumption in general, and other eating disorders. Severe binge eating is 80% more likely among teens who are bullied about their weight, Dr. Puhl said, and the risk increases with increased frequency and types of bullying.

Children who are teased about their weight often become less willing to engage in physical activity, she noted. They may skip gym class, feel less competent about physical activity, and end up enjoying sports participation less.

Further, sexual- and gender-minority youth report high rates of weight-related teasing from friends and family regardless of their body mass index (BMI) percentile, Dr. Puhl emphasized. Researchers have found bullying about weight in this population linked to dieting, difficulty sleeping, high stress levels, binge drinking, smoking, and marijuana use.
 

Know how to combat weight bias

Dr. Puhl described strategies for reducing weight bias based on clinical practice recommendations in the American Academy of Pediatrics’ policy statement entitled “Stigma Experienced by Children and Adolescents With Obesity” (Pediatrics. 2017 Dec;140[6]:e20173034).

Be aware. Consider how personal assumptions and attitudes about weight can affect your body language, tone of voice, facial expression, gestures, eye contact (or lack thereof), and spatial distance from the patient.

Recognizing the biological, genetic, and environmental causes of obesity can reduce stigma and improve understanding of the complexity of obesity etiology. It’s also important that you help parents understand this complexity and the negative impact of weight stigma.

Consider language and word choice. “Carefully consider language that might unintentionally communicate bias, blame, or negative judgment,” Dr. Puhl told attendees. “Use language that is supportive and empowering.”

Terms such as “unhealthy weight” and “high BMI” are less stigmatizing than “fat” and “morbidly obese” to parents, she said, and research has found nearly a quarter of parents would avoid future doctor appointments if their child’s doctor used stigmatizing terms to discuss weight (Pediatrics. 2011 Oct;128[4]:e786-93).

Teens themselves may have diverse preferences for the language used. Start by asking: “Could we talk about your weight today?” and then follow up by directly asking, “what words would you feel most comfortable with as we talk about your weight?”

Person-first language – such as “person with obesity” instead of “obese person” also is important to reducing stigma, she said.

It’s normal for you to feel uneasy about bringing up weight with patients, so Dr. Puhl recommended you practice dialogue out loud.

“Acknowledge your strengths,” she said. “You already have the skills and experience of engaging in difficult conversations with patients and families on a range of other health issues,” so apply that in this context as well.

Screen for negative experiences that could indicate weight-based bullying. These could include teasing and bullying, low self-esteem, poor school performance, depression, and anxiety.

“Remember that weight-based victimization can occur at diverse body sizes, not just in youth with obesity,” Dr. Puhl said. If you discover your patient is experiencing weight-related bullying, determine whether they have a support system in place and whether a mental health referral is appropriate. Provide or refer for behavior change counseling with motivational interviewing and patient-centered, empathic approaches. Parents should be aware of the issue and should contact the child’s teachers and school administration to help address it.

But before you do that, keep in mind that it’s not just peers doing the bullying. According to a study of teens with obesity enrolled in a national weight-loss camp, 37% of teen participants in 2012 said that their parents bully them (Pediatrics. 2013 Jan;131[1]:e1-9).

You should assess whether family interactions or the parents’ own history with weight is involved. If parents make disparaging comments about their child’s weight, “use this as an opportunity to model appropriate language and educate parents about weight bias,” Dr. Puhl said.

It’s also important to realize that parents themselves often are frustrated, so critical comments about their language or approach can backfire, she warned. Instead, help parents understand how to create a home setting that encourages healthy food choices, praises children for healthy decision making, and models positive health behaviors. It is key for them to focus on improving their children’s health behaviors rather than focusing on weight.

And before you contact the school, remember teachers also are common perpetrators of weight stigma, Dr. Puhl noted. She gave as an example a study in which investigators assessed 133 teachers’ perceptions of middle or high school students’ abilities based on photos that had been digitally altered to show each girl both as average weight or as overweight. Each photo was associated with an essay specifically chosen because it was neither particularly good nor bad (Brit J Educ Psychol. 2019 Oct 26. doi: 10.1111/bjep.12322). The teachers judged the essays believed to be submitted by overweight girls to be “similar in structural quality,” but they gave the overweight girls lower grades than the average-weight girls. They also indicated that they considered the overweight girls “put forth more effort, needed more remedial assistance, and had lower overall grades in school.” The teachers also rated other teachers’ weight bias to be at a low level, and their own weight bias to be “significantly lower” than the others.

Assess your clinical environment. Be aware of your clinical environment and whether it meets the needs of youth with diverse body sizes. That includes having a range of sturdy armless seating options and adequately sized doorways, hallways, and restrooms. You also should have beds, wheelchairs, and exam tables with adequate weight capacity. Also check that you have supplies, such as robes or blood pressure cuffs, on hand for a variety of body sizes.

NEW ORLEANS – Weight-based harassment and bias is extremely prevalent throughout society and in doctors’ own offices, so be aware of ways to address it and support your patients regardless of weight.

Rebecca Puhl, PhD, a deputy director of the Rudd Center for Food Policy and Obesity at the University of Connecticut, Hartford, said that weight-based discrimination can occur whatever a person’s size or body shape, but it’s most often targeted at youth who are overweight or obese.

These children and teens commonly face teasing, harassment, cyberbullying, physical aggression, and social bullying from peers, coaches, teachers, and even parents, Dr. Puhl told attendees at the annual meeting of the American Academy of Pediatrics.

Common beliefs about overweight people – that they have little self discipline or poor eating and activity habits – only perpetuate stereotypes, she said. Common stereotypes are that people with obesity are noncompliant, lazy, sloppy, unsuccessful, unintelligent, dishonest, and awkward.

And health professionals of every type have been found to harbor these biases. In one study of more than 4,000 first-year medical students, well over half the respondents revealed explicit (74%) and implicit (67%) weight bias (Obesity. 2014 Apr;22[4]:1201-8). The study also found that explicit weight bias was stronger than explicit bias against blacks, Hispanics, LGBTQ people, and poor people.
 

Know the effects of weight stigma

Far from a minor issue, the discrimination that begins in childhood against those who are overweight can have a long-lasting impact on their future prospects and mental health. Being overweight is overwhelmingly cited as the most common reason for bullying (Pediatr Obes. 2016 Aug;11[4]:241-50). Dr. Puhl described to attendees how weight bias shifts throughout a lifetime, beginning as early as preschool. In childhood, the stereotypes about being overweight worsen, and the teasing and bullying increase. By adolescence, this treatment affects teens’ psychological, social, and physical well-being. It then translates in adulthood into reduced opportunities in employment and education, and poorer access and treatment in health care.

The mental distress caused by weight bullying often takes the form of depression, anxiety, and substance use, Dr. Puhl said, and children’s academic success can be hampered by bullying about their weight. One study found a higher risk of poor grades and school avoidance with each additional teasing incident (J Youth Adolesc. 2012 Jan;41[1]:27-40).

Weight stigma also can contribute to more weight gain, obesity, and lower physical activity levels. Maladaptive eating behaviors can result from weight stigmatization as well: binge eating, emotional eating, increased consumption in general, and other eating disorders. Severe binge eating is 80% more likely among teens who are bullied about their weight, Dr. Puhl said, and the risk increases with increased frequency and types of bullying.

Children who are teased about their weight often become less willing to engage in physical activity, she noted. They may skip gym class, feel less competent about physical activity, and end up enjoying sports participation less.

Further, sexual- and gender-minority youth report high rates of weight-related teasing from friends and family regardless of their body mass index (BMI) percentile, Dr. Puhl emphasized. Researchers have found bullying about weight in this population linked to dieting, difficulty sleeping, high stress levels, binge drinking, smoking, and marijuana use.
 

Know how to combat weight bias

Dr. Puhl described strategies for reducing weight bias based on clinical practice recommendations in the American Academy of Pediatrics’ policy statement entitled “Stigma Experienced by Children and Adolescents With Obesity” (Pediatrics. 2017 Dec;140[6]:e20173034).

Be aware. Consider how personal assumptions and attitudes about weight can affect your body language, tone of voice, facial expression, gestures, eye contact (or lack thereof), and spatial distance from the patient.

Recognizing the biological, genetic, and environmental causes of obesity can reduce stigma and improve understanding of the complexity of obesity etiology. It’s also important that you help parents understand this complexity and the negative impact of weight stigma.

Consider language and word choice. “Carefully consider language that might unintentionally communicate bias, blame, or negative judgment,” Dr. Puhl told attendees. “Use language that is supportive and empowering.”

Terms such as “unhealthy weight” and “high BMI” are less stigmatizing than “fat” and “morbidly obese” to parents, she said, and research has found nearly a quarter of parents would avoid future doctor appointments if their child’s doctor used stigmatizing terms to discuss weight (Pediatrics. 2011 Oct;128[4]:e786-93).

Teens themselves may have diverse preferences for the language used. Start by asking: “Could we talk about your weight today?” and then follow up by directly asking, “what words would you feel most comfortable with as we talk about your weight?”

Person-first language – such as “person with obesity” instead of “obese person” also is important to reducing stigma, she said.

It’s normal for you to feel uneasy about bringing up weight with patients, so Dr. Puhl recommended you practice dialogue out loud.

“Acknowledge your strengths,” she said. “You already have the skills and experience of engaging in difficult conversations with patients and families on a range of other health issues,” so apply that in this context as well.

Screen for negative experiences that could indicate weight-based bullying. These could include teasing and bullying, low self-esteem, poor school performance, depression, and anxiety.

“Remember that weight-based victimization can occur at diverse body sizes, not just in youth with obesity,” Dr. Puhl said. If you discover your patient is experiencing weight-related bullying, determine whether they have a support system in place and whether a mental health referral is appropriate. Provide or refer for behavior change counseling with motivational interviewing and patient-centered, empathic approaches. Parents should be aware of the issue and should contact the child’s teachers and school administration to help address it.

But before you do that, keep in mind that it’s not just peers doing the bullying. According to a study of teens with obesity enrolled in a national weight-loss camp, 37% of teen participants in 2012 said that their parents bully them (Pediatrics. 2013 Jan;131[1]:e1-9).

You should assess whether family interactions or the parents’ own history with weight is involved. If parents make disparaging comments about their child’s weight, “use this as an opportunity to model appropriate language and educate parents about weight bias,” Dr. Puhl said.

It’s also important to realize that parents themselves often are frustrated, so critical comments about their language or approach can backfire, she warned. Instead, help parents understand how to create a home setting that encourages healthy food choices, praises children for healthy decision making, and models positive health behaviors. It is key for them to focus on improving their children’s health behaviors rather than focusing on weight.

And before you contact the school, remember teachers also are common perpetrators of weight stigma, Dr. Puhl noted. She gave as an example a study in which investigators assessed 133 teachers’ perceptions of middle or high school students’ abilities based on photos that had been digitally altered to show each girl both as average weight or as overweight. Each photo was associated with an essay specifically chosen because it was neither particularly good nor bad (Brit J Educ Psychol. 2019 Oct 26. doi: 10.1111/bjep.12322). The teachers judged the essays believed to be submitted by overweight girls to be “similar in structural quality,” but they gave the overweight girls lower grades than the average-weight girls. They also indicated that they considered the overweight girls “put forth more effort, needed more remedial assistance, and had lower overall grades in school.” The teachers also rated other teachers’ weight bias to be at a low level, and their own weight bias to be “significantly lower” than the others.

Assess your clinical environment. Be aware of your clinical environment and whether it meets the needs of youth with diverse body sizes. That includes having a range of sturdy armless seating options and adequately sized doorways, hallways, and restrooms. You also should have beds, wheelchairs, and exam tables with adequate weight capacity. Also check that you have supplies, such as robes or blood pressure cuffs, on hand for a variety of body sizes.

Confirmatory genetic testing may be useful in the diagnosis of hemoglobinopathies for newborns with an abnormal hemoglobin (Hb) pattern, according to a recent study.

The findings suggest further research is needed to evaluate whether genetic testing programs for newborns could have diagnostic value in the clinical setting.

“We studied a consecutive cohort of newborns with an ‘FSA’ pattern (a suspected diagnosis of HbSbeta⁺) on the initial newborn screening test,” explained Lisa M. Shook of the University of Cincinnati and colleagues. The results were published in the International Journal of Neonatal Screening.

The retrospective study included a total of 1,151 newborns with an abnormal Hb pattern, 31 of which had an FSA pattern. The newborns were screened for hemoglobinopathies from 2015 to 2018. The findings of the initial newborn screening test (a suspected diagnosis of HbSbeta⁺) were compared with the diagnosis established using both protein-based and genetic confirmatory testing. Protein-based testing cannot accurately detect several hemoglobinopathies in newborns, especially when beta-thalassemia mutations are involved, according to the authors.

“During this study period, genetic testing was not universally applied in advance; it was used based on clinical suspicion,” the researchers wrote.

Among newborns with an FSA pattern, the mean gestational age was 38.7 weeks. In total, 17 newborns received genetic testing, and 30 had protein-based confirmatory testing.

“In this consecutive cohort of 31 newborns with a suspected diagnosis of HbSbeta⁺ based on initial newborn screening (an FSA pattern), none actually had HbSbeta⁺. All had the sickle cell trait (HbAS), instead; that is, we found that an initial FSA pattern was much more likely to indicate a final diagnosis of HbAS than HbSbeta⁺,” the authors wrote.

This meant that two-thirds of these newborns had a correct diagnosis of HbAS established at 2-4 weeks of age by protein-based confirmatory testing (and confirmed by genetic testing in a subset), but that the remaining one-third still had an incorrect, suspected diagnosis of HbSbeta⁺. This could lead to unnecessary treatment and testing of infants and incorrect, disease-focused counseling of parents and family members, according to the authors.

Two key limitations of the study were the small sample size and retrospective design.

“Based on this experience in which genetic testing was not universally applied, we now perform simultaneous protein-based and genetic testing as our standard clinical practice,” they concluded.

The study was funded by the National Institutes of Health and the Ohio Department of Health. The authors reported having no conflicts of interest.

SOURCE: Shook LM et al. Int J Neonatal Screen. 2020 Jan 31. doi: 10.3390/ijns6010007

Confirmatory genetic testing may be useful in the diagnosis of hemoglobinopathies for newborns with an abnormal hemoglobin (Hb) pattern, according to a recent study.

The findings suggest further research is needed to evaluate whether genetic testing programs for newborns could have diagnostic value in the clinical setting.

“We studied a consecutive cohort of newborns with an ‘FSA’ pattern (a suspected diagnosis of HbSbeta⁺) on the initial newborn screening test,” explained Lisa M. Shook of the University of Cincinnati and colleagues. The results were published in the International Journal of Neonatal Screening.

The retrospective study included a total of 1,151 newborns with an abnormal Hb pattern, 31 of which had an FSA pattern. The newborns were screened for hemoglobinopathies from 2015 to 2018. The findings of the initial newborn screening test (a suspected diagnosis of HbSbeta⁺) were compared with the diagnosis established using both protein-based and genetic confirmatory testing. Protein-based testing cannot accurately detect several hemoglobinopathies in newborns, especially when beta-thalassemia mutations are involved, according to the authors.

“During this study period, genetic testing was not universally applied in advance; it was used based on clinical suspicion,” the researchers wrote.

Among newborns with an FSA pattern, the mean gestational age was 38.7 weeks. In total, 17 newborns received genetic testing, and 30 had protein-based confirmatory testing.

“In this consecutive cohort of 31 newborns with a suspected diagnosis of HbSbeta⁺ based on initial newborn screening (an FSA pattern), none actually had HbSbeta⁺. All had the sickle cell trait (HbAS), instead; that is, we found that an initial FSA pattern was much more likely to indicate a final diagnosis of HbAS than HbSbeta⁺,” the authors wrote.

This meant that two-thirds of these newborns had a correct diagnosis of HbAS established at 2-4 weeks of age by protein-based confirmatory testing (and confirmed by genetic testing in a subset), but that the remaining one-third still had an incorrect, suspected diagnosis of HbSbeta⁺. This could lead to unnecessary treatment and testing of infants and incorrect, disease-focused counseling of parents and family members, according to the authors.

Two key limitations of the study were the small sample size and retrospective design.

“Based on this experience in which genetic testing was not universally applied, we now perform simultaneous protein-based and genetic testing as our standard clinical practice,” they concluded.

The study was funded by the National Institutes of Health and the Ohio Department of Health. The authors reported having no conflicts of interest.

SOURCE: Shook LM et al. Int J Neonatal Screen. 2020 Jan 31. doi: 10.3390/ijns6010007

Confirmatory genetic testing may be useful in the diagnosis of hemoglobinopathies for newborns with an abnormal hemoglobin (Hb) pattern, according to a recent study.

The findings suggest further research is needed to evaluate whether genetic testing programs for newborns could have diagnostic value in the clinical setting.

“We studied a consecutive cohort of newborns with an ‘FSA’ pattern (a suspected diagnosis of HbSbeta⁺) on the initial newborn screening test,” explained Lisa M. Shook of the University of Cincinnati and colleagues. The results were published in the International Journal of Neonatal Screening.

The retrospective study included a total of 1,151 newborns with an abnormal Hb pattern, 31 of which had an FSA pattern. The newborns were screened for hemoglobinopathies from 2015 to 2018. The findings of the initial newborn screening test (a suspected diagnosis of HbSbeta⁺) were compared with the diagnosis established using both protein-based and genetic confirmatory testing. Protein-based testing cannot accurately detect several hemoglobinopathies in newborns, especially when beta-thalassemia mutations are involved, according to the authors.

“During this study period, genetic testing was not universally applied in advance; it was used based on clinical suspicion,” the researchers wrote.

Among newborns with an FSA pattern, the mean gestational age was 38.7 weeks. In total, 17 newborns received genetic testing, and 30 had protein-based confirmatory testing.

“In this consecutive cohort of 31 newborns with a suspected diagnosis of HbSbeta⁺ based on initial newborn screening (an FSA pattern), none actually had HbSbeta⁺. All had the sickle cell trait (HbAS), instead; that is, we found that an initial FSA pattern was much more likely to indicate a final diagnosis of HbAS than HbSbeta⁺,” the authors wrote.

This meant that two-thirds of these newborns had a correct diagnosis of HbAS established at 2-4 weeks of age by protein-based confirmatory testing (and confirmed by genetic testing in a subset), but that the remaining one-third still had an incorrect, suspected diagnosis of HbSbeta⁺. This could lead to unnecessary treatment and testing of infants and incorrect, disease-focused counseling of parents and family members, according to the authors.

Two key limitations of the study were the small sample size and retrospective design.

“Based on this experience in which genetic testing was not universally applied, we now perform simultaneous protein-based and genetic testing as our standard clinical practice,” they concluded.

The study was funded by the National Institutes of Health and the Ohio Department of Health. The authors reported having no conflicts of interest.

SOURCE: Shook LM et al. Int J Neonatal Screen. 2020 Jan 31. doi: 10.3390/ijns6010007

LONDON – Low-dose calcipotriol ointment eased pruritus in people with recessive dystrophic epidermolysis bullosa (RDEB), in a small, placebo-controlled, phase 2 study.

Sara Freeman/MDedge News

More importantly, use of the ointment promoted wound healing in those with the severe skin-blistering condition. Indeed, compared with placebo, a greater reduction in wound size was observed after 2 weeks when the ointment was applied (a mean reduction of 65.5% vs. 88.4%; P less than .006). However, at 1 month, no significant differences were seen in the size of the wounds between the two treatment arms.

“Calcipotriol is a vitamin D analog and it is well known that vitamin D is a very critical factor for skin homeostasis and proper wound healing,” Christina Guttmann-Gruber, PhD, said at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA). Dr. Guttmann-Gruber, a group lead researcher for EB House Austria, which is based at the Salzburg (Austria) University Clinic for Dermatology, noted that vitamin D also helps with tissue repair and immune modulation, and enhances local antimicrobial activity.

During an oral poster presentation at the meeting, Dr. Guttmann-Gruber explained that in previous in vitro studies, it was found that low concentrations (100 nmol) of calcipotriol inhibited proliferation of RDEB tumor cells (Sci Rep. 2018 Sep 7;8:13430). Calcipotriol (also known as calcipotriene) also was found to improve the expression of antimicrobial peptides and promote wound closure. “Therefore, we thought that applying calcipotriol at the site of injury, on chronic wounds prone to superinfection where it is needed, might be beneficial for our patients.”

She and her associates designed a two-arm, randomized, double-blind crossover study to assess the effects of an existing calcipotriol-containing ointment on wound healing in patients with RDEB. The ointment used in the study is approved for treating psoriasis but was adapted by the in-house pharmacy team to reduce the concentration of calcipotriol to about 0.05 mcg/g, or around 121 nmol. The reason for the reduction was that, at higher doses, keratinocyte proliferation was reduced, which would be detrimental in RDEB patients.

Nine patients were included in the study and were randomized to either apply 1 g of the active or placebo ointment to each of two designated wounds, of at least 6 cm² in size, every day for 4 weeks. A 2-month washout period then followed before the groups switched to use the other ointment for 1 month. Six out of the nine patients completed both treatment phases. The reasons for the patients not completing both intervention phases were not related to the drug.

Calcipotriol treatment resulted in a significant and steady reduction in itch over the entire course of treatment, which was not seen among those on placebo, Dr. Guttmann-Gruber observed. The reduction in itch was “striking,” but only while the treatment was being used, she said. Results for pain were less clear, with a significant reduction in pain after 2 weeks seen only in the placebo group, while both treatments reduced pain to the same degree by 1 month.

No serious adverse events were observed at any time point and topical use of the low-dose calcipotriol did not significantly change serum levels of calcium or vitamin D in the two patients in which this was studied, Dr. Guttmann-Gruber said.

“This is an approved drug; it’s used in psoriasis, but at a very high concentration. We were able to use it off label and make a diluted version,” she observed. “Any pharmacy can do it.” Although it was applied topically, it could be done by applying it to the dressing rather directly onto the wounded skin, she said.

Data on the skin microbiome response to treatment were also collected but were not available to analyze in time for presentation, but it appeared that there was improvement with the low-dose calcipotriol treatment, Dr. Guttmann-Gruber said. “When the wounds are healing, the microbial flora is improving.”

The next step will probably be to plan a multicenter trial of this treatment, Dr. Guttmann-Gruber said in an interview. The questions is whether such a trial would get the financial backing it needed, but if an orphan drug designation could be obtained for calcipotriol for EB, then it would be possible to conduct such a trial.

The study was funded by DEBRA Austria. The presenting author, Dr. Guttmann-Gruber, had no conflicts of interest to disclose.

SOURCE: Guttmann-Gruber C et al. EB World Congress 2020. Poster 34.

LONDON – Low-dose calcipotriol ointment eased pruritus in people with recessive dystrophic epidermolysis bullosa (RDEB), in a small, placebo-controlled, phase 2 study.

Sara Freeman/MDedge News

More importantly, use of the ointment promoted wound healing in those with the severe skin-blistering condition. Indeed, compared with placebo, a greater reduction in wound size was observed after 2 weeks when the ointment was applied (a mean reduction of 65.5% vs. 88.4%; P less than .006). However, at 1 month, no significant differences were seen in the size of the wounds between the two treatment arms.

“Calcipotriol is a vitamin D analog and it is well known that vitamin D is a very critical factor for skin homeostasis and proper wound healing,” Christina Guttmann-Gruber, PhD, said at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA). Dr. Guttmann-Gruber, a group lead researcher for EB House Austria, which is based at the Salzburg (Austria) University Clinic for Dermatology, noted that vitamin D also helps with tissue repair and immune modulation, and enhances local antimicrobial activity.

During an oral poster presentation at the meeting, Dr. Guttmann-Gruber explained that in previous in vitro studies, it was found that low concentrations (100 nmol) of calcipotriol inhibited proliferation of RDEB tumor cells (Sci Rep. 2018 Sep 7;8:13430). Calcipotriol (also known as calcipotriene) also was found to improve the expression of antimicrobial peptides and promote wound closure. “Therefore, we thought that applying calcipotriol at the site of injury, on chronic wounds prone to superinfection where it is needed, might be beneficial for our patients.”

She and her associates designed a two-arm, randomized, double-blind crossover study to assess the effects of an existing calcipotriol-containing ointment on wound healing in patients with RDEB. The ointment used in the study is approved for treating psoriasis but was adapted by the in-house pharmacy team to reduce the concentration of calcipotriol to about 0.05 mcg/g, or around 121 nmol. The reason for the reduction was that, at higher doses, keratinocyte proliferation was reduced, which would be detrimental in RDEB patients.

Nine patients were included in the study and were randomized to either apply 1 g of the active or placebo ointment to each of two designated wounds, of at least 6 cm² in size, every day for 4 weeks. A 2-month washout period then followed before the groups switched to use the other ointment for 1 month. Six out of the nine patients completed both treatment phases. The reasons for the patients not completing both intervention phases were not related to the drug.

Calcipotriol treatment resulted in a significant and steady reduction in itch over the entire course of treatment, which was not seen among those on placebo, Dr. Guttmann-Gruber observed. The reduction in itch was “striking,” but only while the treatment was being used, she said. Results for pain were less clear, with a significant reduction in pain after 2 weeks seen only in the placebo group, while both treatments reduced pain to the same degree by 1 month.

No serious adverse events were observed at any time point and topical use of the low-dose calcipotriol did not significantly change serum levels of calcium or vitamin D in the two patients in which this was studied, Dr. Guttmann-Gruber said.

“This is an approved drug; it’s used in psoriasis, but at a very high concentration. We were able to use it off label and make a diluted version,” she observed. “Any pharmacy can do it.” Although it was applied topically, it could be done by applying it to the dressing rather directly onto the wounded skin, she said.

Data on the skin microbiome response to treatment were also collected but were not available to analyze in time for presentation, but it appeared that there was improvement with the low-dose calcipotriol treatment, Dr. Guttmann-Gruber said. “When the wounds are healing, the microbial flora is improving.”

The next step will probably be to plan a multicenter trial of this treatment, Dr. Guttmann-Gruber said in an interview. The questions is whether such a trial would get the financial backing it needed, but if an orphan drug designation could be obtained for calcipotriol for EB, then it would be possible to conduct such a trial.

The study was funded by DEBRA Austria. The presenting author, Dr. Guttmann-Gruber, had no conflicts of interest to disclose.

SOURCE: Guttmann-Gruber C et al. EB World Congress 2020. Poster 34.

LONDON – Low-dose calcipotriol ointment eased pruritus in people with recessive dystrophic epidermolysis bullosa (RDEB), in a small, placebo-controlled, phase 2 study.

Sara Freeman/MDedge News

More importantly, use of the ointment promoted wound healing in those with the severe skin-blistering condition. Indeed, compared with placebo, a greater reduction in wound size was observed after 2 weeks when the ointment was applied (a mean reduction of 65.5% vs. 88.4%; P less than .006). However, at 1 month, no significant differences were seen in the size of the wounds between the two treatment arms.

“Calcipotriol is a vitamin D analog and it is well known that vitamin D is a very critical factor for skin homeostasis and proper wound healing,” Christina Guttmann-Gruber, PhD, said at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA). Dr. Guttmann-Gruber, a group lead researcher for EB House Austria, which is based at the Salzburg (Austria) University Clinic for Dermatology, noted that vitamin D also helps with tissue repair and immune modulation, and enhances local antimicrobial activity.

During an oral poster presentation at the meeting, Dr. Guttmann-Gruber explained that in previous in vitro studies, it was found that low concentrations (100 nmol) of calcipotriol inhibited proliferation of RDEB tumor cells (Sci Rep. 2018 Sep 7;8:13430). Calcipotriol (also known as calcipotriene) also was found to improve the expression of antimicrobial peptides and promote wound closure. “Therefore, we thought that applying calcipotriol at the site of injury, on chronic wounds prone to superinfection where it is needed, might be beneficial for our patients.”

She and her associates designed a two-arm, randomized, double-blind crossover study to assess the effects of an existing calcipotriol-containing ointment on wound healing in patients with RDEB. The ointment used in the study is approved for treating psoriasis but was adapted by the in-house pharmacy team to reduce the concentration of calcipotriol to about 0.05 mcg/g, or around 121 nmol. The reason for the reduction was that, at higher doses, keratinocyte proliferation was reduced, which would be detrimental in RDEB patients.

Nine patients were included in the study and were randomized to either apply 1 g of the active or placebo ointment to each of two designated wounds, of at least 6 cm² in size, every day for 4 weeks. A 2-month washout period then followed before the groups switched to use the other ointment for 1 month. Six out of the nine patients completed both treatment phases. The reasons for the patients not completing both intervention phases were not related to the drug.

Calcipotriol treatment resulted in a significant and steady reduction in itch over the entire course of treatment, which was not seen among those on placebo, Dr. Guttmann-Gruber observed. The reduction in itch was “striking,” but only while the treatment was being used, she said. Results for pain were less clear, with a significant reduction in pain after 2 weeks seen only in the placebo group, while both treatments reduced pain to the same degree by 1 month.

No serious adverse events were observed at any time point and topical use of the low-dose calcipotriol did not significantly change serum levels of calcium or vitamin D in the two patients in which this was studied, Dr. Guttmann-Gruber said.

“This is an approved drug; it’s used in psoriasis, but at a very high concentration. We were able to use it off label and make a diluted version,” she observed. “Any pharmacy can do it.” Although it was applied topically, it could be done by applying it to the dressing rather directly onto the wounded skin, she said.

Data on the skin microbiome response to treatment were also collected but were not available to analyze in time for presentation, but it appeared that there was improvement with the low-dose calcipotriol treatment, Dr. Guttmann-Gruber said. “When the wounds are healing, the microbial flora is improving.”

The next step will probably be to plan a multicenter trial of this treatment, Dr. Guttmann-Gruber said in an interview. The questions is whether such a trial would get the financial backing it needed, but if an orphan drug designation could be obtained for calcipotriol for EB, then it would be possible to conduct such a trial.

The study was funded by DEBRA Austria. The presenting author, Dr. Guttmann-Gruber, had no conflicts of interest to disclose.

SOURCE: Guttmann-Gruber C et al. EB World Congress 2020. Poster 34.

A network meta-analysis of migraine treatments in children found little evidence that prophylactic medicines work in this population.

Marta Ortiz/iStock/Getty Images Plus

Clinicians hoped that medications used in adults – such as antidepressants, antiepileptics, antihypertensive agents, calcium channel blockers, and food supplements – would find similar success in children. Unfortunately, researchers found only short-term signs of efficacy over placebo, with no benefit lasting more than 6 months.

The study, conducted by a team led by Cosima Locher, PhD, of Boston Children’s Hospital, included 23 double-blind, randomized, controlled trials with a total of 2,217 patients; the mean age was 11 years. They compared 12 pharmacologic agents with each other or with placebo in the study, published online in JAMA Pediatrics.

In a main efficacy analysis that included 19 studies, only two treatments outperformed placebo: propranolol (standardized mean difference, 0.60; 95% confidence interval, 0.03-1.17) and topiramate (SMD, 0.59; 95% CI, 0.03-1.15). There were no statistically significant between-treatment differences.

The results had an overall low to moderate certainty.

When propranolol was compared to placebo, the 95% prediction interval (–0.62 to 1.82) was wider than the significant confidence interval (0.03-1.17), and comprised both beneficial and detrimental effects. A similar result was found with topiramate, with a prediction interval of –0.62 to 1.80 extending into nonsignificant effects (95% CI, 0.03-1.15). In both cases, significant effects were found only when the prediction interval was 70%.

In a long-term analysis (greater than 6 months), no treatment outperformed placebo.

The treatments generally were acceptable. The researchers found no significant difference in tolerability between any of the treatments and each other or placebo. Safety data analyzed from 13 trials revealed no significant differences between treatments and placebo.

“Because specific effects of drugs are associated with the size of the placebo effect, the lack of drug efficacy in our NMA [network meta-analysis] could be owing to a comparatively high placebo effect in children. In fact, there is indirect evidence [from other studies] that the placebo effect is more pronounced in children and adolescents than in adults,” Dr. Locher and associates said. They suggested that studies were needed to quantify the placebo effect in pediatric migraine, and if it was large, to develop innovative therapies making use of this.

The findings should lead to some changes in practice, Boris Zernikow, MD, PhD, of Children’s and Adolescents’ Hospital Datteln (Germany) wrote in an accompanying editorial.

Pharmacological prophylactic treatment of childhood migraine should be an exception rather than the rule, and nonpharmacologic approaches should be emphasized, particularly because the placebo effect is magnified in children, he said.

Many who suffer migraines in childhood will continue to be affected in adulthood, so pediatric intervention is a good opportunity to instill effective strategies. These include: using abortive medication early in an attack and using antimigraine medications for only that specific type of headache; engaging in physical activity to reduce migraine attacks; getting sufficient sleep; and learning relaxation and other psychological approaches to counter migraines.

Dr. Zernikow had no relevant financial disclosures. One study author received grants from Amgen and other support from Grunenthal and Akelos. The study received funding from the Sara Page Mayo Endowment for Pediatric Pain Research, Education, and Treatment; the Swiss National Science Foundation; the Schweizer-Arau-Foundation; and the Theophrastus Foundation.

SOURCES: Locher C et al. JAMA Pediatrics. 2020 Feb 10. doi: 10.1001/jamapediatrics.2019.5856; Zernikow B. JAMA Pediatrics. 2020 Feb 10. doi: 10.1001/jamapediatrics.2019.5907.

A network meta-analysis of migraine treatments in children found little evidence that prophylactic medicines work in this population.

Marta Ortiz/iStock/Getty Images Plus

Clinicians hoped that medications used in adults – such as antidepressants, antiepileptics, antihypertensive agents, calcium channel blockers, and food supplements – would find similar success in children. Unfortunately, researchers found only short-term signs of efficacy over placebo, with no benefit lasting more than 6 months.

The study, conducted by a team led by Cosima Locher, PhD, of Boston Children’s Hospital, included 23 double-blind, randomized, controlled trials with a total of 2,217 patients; the mean age was 11 years. They compared 12 pharmacologic agents with each other or with placebo in the study, published online in JAMA Pediatrics.

In a main efficacy analysis that included 19 studies, only two treatments outperformed placebo: propranolol (standardized mean difference, 0.60; 95% confidence interval, 0.03-1.17) and topiramate (SMD, 0.59; 95% CI, 0.03-1.15). There were no statistically significant between-treatment differences.

The results had an overall low to moderate certainty.

When propranolol was compared to placebo, the 95% prediction interval (–0.62 to 1.82) was wider than the significant confidence interval (0.03-1.17), and comprised both beneficial and detrimental effects. A similar result was found with topiramate, with a prediction interval of –0.62 to 1.80 extending into nonsignificant effects (95% CI, 0.03-1.15). In both cases, significant effects were found only when the prediction interval was 70%.

In a long-term analysis (greater than 6 months), no treatment outperformed placebo.

The treatments generally were acceptable. The researchers found no significant difference in tolerability between any of the treatments and each other or placebo. Safety data analyzed from 13 trials revealed no significant differences between treatments and placebo.

“Because specific effects of drugs are associated with the size of the placebo effect, the lack of drug efficacy in our NMA [network meta-analysis] could be owing to a comparatively high placebo effect in children. In fact, there is indirect evidence [from other studies] that the placebo effect is more pronounced in children and adolescents than in adults,” Dr. Locher and associates said. They suggested that studies were needed to quantify the placebo effect in pediatric migraine, and if it was large, to develop innovative therapies making use of this.

The findings should lead to some changes in practice, Boris Zernikow, MD, PhD, of Children’s and Adolescents’ Hospital Datteln (Germany) wrote in an accompanying editorial.

Pharmacological prophylactic treatment of childhood migraine should be an exception rather than the rule, and nonpharmacologic approaches should be emphasized, particularly because the placebo effect is magnified in children, he said.

Many who suffer migraines in childhood will continue to be affected in adulthood, so pediatric intervention is a good opportunity to instill effective strategies. These include: using abortive medication early in an attack and using antimigraine medications for only that specific type of headache; engaging in physical activity to reduce migraine attacks; getting sufficient sleep; and learning relaxation and other psychological approaches to counter migraines.

Dr. Zernikow had no relevant financial disclosures. One study author received grants from Amgen and other support from Grunenthal and Akelos. The study received funding from the Sara Page Mayo Endowment for Pediatric Pain Research, Education, and Treatment; the Swiss National Science Foundation; the Schweizer-Arau-Foundation; and the Theophrastus Foundation.

SOURCES: Locher C et al. JAMA Pediatrics. 2020 Feb 10. doi: 10.1001/jamapediatrics.2019.5856; Zernikow B. JAMA Pediatrics. 2020 Feb 10. doi: 10.1001/jamapediatrics.2019.5907.

A network meta-analysis of migraine treatments in children found little evidence that prophylactic medicines work in this population.

Marta Ortiz/iStock/Getty Images Plus

Clinicians hoped that medications used in adults – such as antidepressants, antiepileptics, antihypertensive agents, calcium channel blockers, and food supplements – would find similar success in children. Unfortunately, researchers found only short-term signs of efficacy over placebo, with no benefit lasting more than 6 months.

The study, conducted by a team led by Cosima Locher, PhD, of Boston Children’s Hospital, included 23 double-blind, randomized, controlled trials with a total of 2,217 patients; the mean age was 11 years. They compared 12 pharmacologic agents with each other or with placebo in the study, published online in JAMA Pediatrics.

In a main efficacy analysis that included 19 studies, only two treatments outperformed placebo: propranolol (standardized mean difference, 0.60; 95% confidence interval, 0.03-1.17) and topiramate (SMD, 0.59; 95% CI, 0.03-1.15). There were no statistically significant between-treatment differences.

The results had an overall low to moderate certainty.

When propranolol was compared to placebo, the 95% prediction interval (–0.62 to 1.82) was wider than the significant confidence interval (0.03-1.17), and comprised both beneficial and detrimental effects. A similar result was found with topiramate, with a prediction interval of –0.62 to 1.80 extending into nonsignificant effects (95% CI, 0.03-1.15). In both cases, significant effects were found only when the prediction interval was 70%.

In a long-term analysis (greater than 6 months), no treatment outperformed placebo.

The treatments generally were acceptable. The researchers found no significant difference in tolerability between any of the treatments and each other or placebo. Safety data analyzed from 13 trials revealed no significant differences between treatments and placebo.

“Because specific effects of drugs are associated with the size of the placebo effect, the lack of drug efficacy in our NMA [network meta-analysis] could be owing to a comparatively high placebo effect in children. In fact, there is indirect evidence [from other studies] that the placebo effect is more pronounced in children and adolescents than in adults,” Dr. Locher and associates said. They suggested that studies were needed to quantify the placebo effect in pediatric migraine, and if it was large, to develop innovative therapies making use of this.

The findings should lead to some changes in practice, Boris Zernikow, MD, PhD, of Children’s and Adolescents’ Hospital Datteln (Germany) wrote in an accompanying editorial.

Pharmacological prophylactic treatment of childhood migraine should be an exception rather than the rule, and nonpharmacologic approaches should be emphasized, particularly because the placebo effect is magnified in children, he said.

Many who suffer migraines in childhood will continue to be affected in adulthood, so pediatric intervention is a good opportunity to instill effective strategies. These include: using abortive medication early in an attack and using antimigraine medications for only that specific type of headache; engaging in physical activity to reduce migraine attacks; getting sufficient sleep; and learning relaxation and other psychological approaches to counter migraines.

Dr. Zernikow had no relevant financial disclosures. One study author received grants from Amgen and other support from Grunenthal and Akelos. The study received funding from the Sara Page Mayo Endowment for Pediatric Pain Research, Education, and Treatment; the Swiss National Science Foundation; the Schweizer-Arau-Foundation; and the Theophrastus Foundation.

SOURCES: Locher C et al. JAMA Pediatrics. 2020 Feb 10. doi: 10.1001/jamapediatrics.2019.5856; Zernikow B. JAMA Pediatrics. 2020 Feb 10. doi: 10.1001/jamapediatrics.2019.5907.