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Patch testing in atopic dermatitis: when and how
WAIKOLOA, HAWAII – The according to Jonathan I. Silverberg, MD, PhD.
“What are atopic dermatitis patients allergic to? It’s all coming from their personal care products and the things being used to treat their atopic dermatitis,” Dr. Silverberg said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Dr. Silverberg, of the department of dermatology at Northwestern University, Chicago, coauthored a systematic review and meta-analysis that examined the association between AD and contact sensitization. In their examination of 74 published studies, the investigators found that the likelihood of allergic contact dermatitis was 1.5-fold greater in adults and children with AD than in healthy individuals from the general population (J Am Acad Dermatol. 2017 Jul;77[1]:70-8).
This finding is at odds with an earlier widespread belief that AD patients should not be at increased risk because the immune profile of their primarily Th2-mediated disease would have a suppressant effect on Th1-mediated hypersensitivity.
“Recent data are calling into question old dogmas and reshaping the way we think about this. And this is not just an academic exercise, this is highly clinically relevant,” the dermatologist asserted.
The results of the meta-analysis prompted Dr. Silverberg and colleagues to conduct a retrospective study of more than 500 adults patch tested to an expanded allergen series at Northwestern’s patch test clinic with the purpose of identifying the common offending allergens in patients with AD. The key finding: The patients with AD were significantly more likely to have positive patch test reactions to ingredients in their repetitively used personal care products, topical corticosteroids, and topical antibiotics than the individuals without AD. The probable explanation for this results is that the skin barrier disruption inherent in AD allows for easier passage of weak allergens through the skin (J Am Acad Dermatol. 2018 Dec;79[6]:1028-33.e6).
Lanolin was identified as a particularly common allergen in the AD group. “Lanolin is found in one of the most commonly used moisturizers we recommend to patients: Aquaphor. It’s also found in tons of lip balms and emollients. Pretty much every soft soap out there contains lanolin, and it’s in a variety of other personal care products,” Dr. Silverberg noted.
Other common offenders in the AD population included fragrance mix II, cinnamal, quaternium-15, budesonide, tixocortol, carba mix, neomycin, bacitracin, rubber mix, and chlorhexidine. Relevance was established in more than 90% of the positive reactions.
“You can patch test them directly to their personal care products and make that connection beautifully and see how they’re reacting to them,” he said.
When to patch test atopic dermatitis patients
Dr. Silverberg was a coauthor of multidisciplinary expert consensus guidelines on when to consider patch testing in AD (Dermatitis. 2016 Jul-Aug;27[4]:186-92). “We had to go consensus because we don’t have nearly enough studies to provide true evidence-based recommendations,” he explained.
Because allergic contact dermatitis is a potentially curable comorbid condition in AD patients, it’s important to recognize the scenarios in which patch testing should be considered. These include AD refractory to topical therapy; adolescent- or adult-onset atopic dermatitis; and in AD patients with an atypical or evolving lesional distribution, such as localized dermatitis on the eyelids, head and neck, or hands and feet. Patch testing is also warranted before initiating systemic therapy for AD.
“If you’re about to put a patient on a biologic or phototherapy and step them up to a whole new class of risk of adverse events, that’s an ideal time to think about reversible options,” Dr. Silverberg advised.
Another situation in which he considers patch testing advisable, although this one isn’t covered in the consensus guidelines, is in AD patients with prominent nummular eczema lesions. “Widespread nummular eczema lesions may be a sign of allergic contact dermatitis in atopic dermatitis patients. I’m not saying everyone with nummular lesions is going to have a positive patch test, but it’s definitely a situation you want to think about,” he said.
How to patch test atopic dermatitis patients
Most of the common topical allergens in AD patients are not included in the T.R.U.E. Test. An expanded allergen series, such as the American Contact Dermatitis Society core 80 series, is the better way to go.
Once the dermatologist determines that a patient’s positive patch test reaction is relevant, it’s important to recommend the use of personal care products that are “pretty clean,” Dr. Silverberg said.
“Clean in my opinion is not a matter of ‘It should be all organic and all natural,’ ” he emphasized. “I’m not anti- any of that, but clean means having the fewest ingredients possible and trying to steer clear of those really common allergens that patients are highly likely to have been exposed to and potentially sensitized to over the many years of their tenure of atopic dermatitis.”
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to more than a dozen pharmaceutical companies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – The according to Jonathan I. Silverberg, MD, PhD.
“What are atopic dermatitis patients allergic to? It’s all coming from their personal care products and the things being used to treat their atopic dermatitis,” Dr. Silverberg said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Dr. Silverberg, of the department of dermatology at Northwestern University, Chicago, coauthored a systematic review and meta-analysis that examined the association between AD and contact sensitization. In their examination of 74 published studies, the investigators found that the likelihood of allergic contact dermatitis was 1.5-fold greater in adults and children with AD than in healthy individuals from the general population (J Am Acad Dermatol. 2017 Jul;77[1]:70-8).
This finding is at odds with an earlier widespread belief that AD patients should not be at increased risk because the immune profile of their primarily Th2-mediated disease would have a suppressant effect on Th1-mediated hypersensitivity.
“Recent data are calling into question old dogmas and reshaping the way we think about this. And this is not just an academic exercise, this is highly clinically relevant,” the dermatologist asserted.
The results of the meta-analysis prompted Dr. Silverberg and colleagues to conduct a retrospective study of more than 500 adults patch tested to an expanded allergen series at Northwestern’s patch test clinic with the purpose of identifying the common offending allergens in patients with AD. The key finding: The patients with AD were significantly more likely to have positive patch test reactions to ingredients in their repetitively used personal care products, topical corticosteroids, and topical antibiotics than the individuals without AD. The probable explanation for this results is that the skin barrier disruption inherent in AD allows for easier passage of weak allergens through the skin (J Am Acad Dermatol. 2018 Dec;79[6]:1028-33.e6).
Lanolin was identified as a particularly common allergen in the AD group. “Lanolin is found in one of the most commonly used moisturizers we recommend to patients: Aquaphor. It’s also found in tons of lip balms and emollients. Pretty much every soft soap out there contains lanolin, and it’s in a variety of other personal care products,” Dr. Silverberg noted.
Other common offenders in the AD population included fragrance mix II, cinnamal, quaternium-15, budesonide, tixocortol, carba mix, neomycin, bacitracin, rubber mix, and chlorhexidine. Relevance was established in more than 90% of the positive reactions.
“You can patch test them directly to their personal care products and make that connection beautifully and see how they’re reacting to them,” he said.
When to patch test atopic dermatitis patients
Dr. Silverberg was a coauthor of multidisciplinary expert consensus guidelines on when to consider patch testing in AD (Dermatitis. 2016 Jul-Aug;27[4]:186-92). “We had to go consensus because we don’t have nearly enough studies to provide true evidence-based recommendations,” he explained.
Because allergic contact dermatitis is a potentially curable comorbid condition in AD patients, it’s important to recognize the scenarios in which patch testing should be considered. These include AD refractory to topical therapy; adolescent- or adult-onset atopic dermatitis; and in AD patients with an atypical or evolving lesional distribution, such as localized dermatitis on the eyelids, head and neck, or hands and feet. Patch testing is also warranted before initiating systemic therapy for AD.
“If you’re about to put a patient on a biologic or phototherapy and step them up to a whole new class of risk of adverse events, that’s an ideal time to think about reversible options,” Dr. Silverberg advised.
Another situation in which he considers patch testing advisable, although this one isn’t covered in the consensus guidelines, is in AD patients with prominent nummular eczema lesions. “Widespread nummular eczema lesions may be a sign of allergic contact dermatitis in atopic dermatitis patients. I’m not saying everyone with nummular lesions is going to have a positive patch test, but it’s definitely a situation you want to think about,” he said.
How to patch test atopic dermatitis patients
Most of the common topical allergens in AD patients are not included in the T.R.U.E. Test. An expanded allergen series, such as the American Contact Dermatitis Society core 80 series, is the better way to go.
Once the dermatologist determines that a patient’s positive patch test reaction is relevant, it’s important to recommend the use of personal care products that are “pretty clean,” Dr. Silverberg said.
“Clean in my opinion is not a matter of ‘It should be all organic and all natural,’ ” he emphasized. “I’m not anti- any of that, but clean means having the fewest ingredients possible and trying to steer clear of those really common allergens that patients are highly likely to have been exposed to and potentially sensitized to over the many years of their tenure of atopic dermatitis.”
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to more than a dozen pharmaceutical companies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – The according to Jonathan I. Silverberg, MD, PhD.
“What are atopic dermatitis patients allergic to? It’s all coming from their personal care products and the things being used to treat their atopic dermatitis,” Dr. Silverberg said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Dr. Silverberg, of the department of dermatology at Northwestern University, Chicago, coauthored a systematic review and meta-analysis that examined the association between AD and contact sensitization. In their examination of 74 published studies, the investigators found that the likelihood of allergic contact dermatitis was 1.5-fold greater in adults and children with AD than in healthy individuals from the general population (J Am Acad Dermatol. 2017 Jul;77[1]:70-8).
This finding is at odds with an earlier widespread belief that AD patients should not be at increased risk because the immune profile of their primarily Th2-mediated disease would have a suppressant effect on Th1-mediated hypersensitivity.
“Recent data are calling into question old dogmas and reshaping the way we think about this. And this is not just an academic exercise, this is highly clinically relevant,” the dermatologist asserted.
The results of the meta-analysis prompted Dr. Silverberg and colleagues to conduct a retrospective study of more than 500 adults patch tested to an expanded allergen series at Northwestern’s patch test clinic with the purpose of identifying the common offending allergens in patients with AD. The key finding: The patients with AD were significantly more likely to have positive patch test reactions to ingredients in their repetitively used personal care products, topical corticosteroids, and topical antibiotics than the individuals without AD. The probable explanation for this results is that the skin barrier disruption inherent in AD allows for easier passage of weak allergens through the skin (J Am Acad Dermatol. 2018 Dec;79[6]:1028-33.e6).
Lanolin was identified as a particularly common allergen in the AD group. “Lanolin is found in one of the most commonly used moisturizers we recommend to patients: Aquaphor. It’s also found in tons of lip balms and emollients. Pretty much every soft soap out there contains lanolin, and it’s in a variety of other personal care products,” Dr. Silverberg noted.
Other common offenders in the AD population included fragrance mix II, cinnamal, quaternium-15, budesonide, tixocortol, carba mix, neomycin, bacitracin, rubber mix, and chlorhexidine. Relevance was established in more than 90% of the positive reactions.
“You can patch test them directly to their personal care products and make that connection beautifully and see how they’re reacting to them,” he said.
When to patch test atopic dermatitis patients
Dr. Silverberg was a coauthor of multidisciplinary expert consensus guidelines on when to consider patch testing in AD (Dermatitis. 2016 Jul-Aug;27[4]:186-92). “We had to go consensus because we don’t have nearly enough studies to provide true evidence-based recommendations,” he explained.
Because allergic contact dermatitis is a potentially curable comorbid condition in AD patients, it’s important to recognize the scenarios in which patch testing should be considered. These include AD refractory to topical therapy; adolescent- or adult-onset atopic dermatitis; and in AD patients with an atypical or evolving lesional distribution, such as localized dermatitis on the eyelids, head and neck, or hands and feet. Patch testing is also warranted before initiating systemic therapy for AD.
“If you’re about to put a patient on a biologic or phototherapy and step them up to a whole new class of risk of adverse events, that’s an ideal time to think about reversible options,” Dr. Silverberg advised.
Another situation in which he considers patch testing advisable, although this one isn’t covered in the consensus guidelines, is in AD patients with prominent nummular eczema lesions. “Widespread nummular eczema lesions may be a sign of allergic contact dermatitis in atopic dermatitis patients. I’m not saying everyone with nummular lesions is going to have a positive patch test, but it’s definitely a situation you want to think about,” he said.
How to patch test atopic dermatitis patients
Most of the common topical allergens in AD patients are not included in the T.R.U.E. Test. An expanded allergen series, such as the American Contact Dermatitis Society core 80 series, is the better way to go.
Once the dermatologist determines that a patient’s positive patch test reaction is relevant, it’s important to recommend the use of personal care products that are “pretty clean,” Dr. Silverberg said.
“Clean in my opinion is not a matter of ‘It should be all organic and all natural,’ ” he emphasized. “I’m not anti- any of that, but clean means having the fewest ingredients possible and trying to steer clear of those really common allergens that patients are highly likely to have been exposed to and potentially sensitized to over the many years of their tenure of atopic dermatitis.”
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to more than a dozen pharmaceutical companies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
The art of selecting an MS therapy
DALLAS – , said Mark Freedman, MD, MSc, in a presentation at ACTRIMS Forum 2019, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “Right now, we are probably dealing with more of an imprecise medicine,” said Dr. Freedman.
Information such as a patient’s ability to recover from relapses may indicate MS severity or the likelihood of disease progression, but selecting a therapy remains “an art of medicine,” said Dr. Freedman, professor of neurology at the University of Ottawa, director of the multiple sclerosis research unit at Ottawa Hospital, and senior scientist at the Ottawa Hospital Research Institute.
When prescribing a DMT, neurologists tend to consider three key elements: the disease, the treatment, and patient expectations. “Focus on these three aspects,” Dr. Freedman said.
It is no longer sufficient for neurologists to diagnose MS, hand the patient a drug, and “expect that things are going to go the way you want them to go,” he said.
Immunomodulating, anti–cell trafficking, or cell-depleting therapy?
Genetics, sex, types of relapses, recovery from relapses, response to therapy, MRI burden, and other biomarkers such as oligoclonal bands and neurofilaments may indicate which patients have severe disease and should receive aggressive treatment.
Determining the phase of the disease is a crucial first step “that is going to drive your choice of therapy,” he said.
Dr. Freedman likened the development of progressive MS to approaching the edge of a cliff. If patients appear to be nearing the progressive phase, “then your choice of therapy has to be an aggressive one – one that will hopefully hold them back from falling,” he said. In the earlier phases of MS, on the other hand, “you are looking at a long-term treatment that should probably be safe and still able to contain the disease,” such as an immunomodulator. If a patient is “about to fall off, you may want to go for temporary use of an antitrafficker to control things, and then eventually deplete the cells that are going to be causing the patient to fall off the cliff.”
Prognostic factors
Disease activity over time, and whether the disease is progressing faster or slower than would be expected, may be important prognostic factors. A patient’s sex also may be a factor because women tend to have more attacks and to have their attacks at a younger age, Dr. Freedman said.
The types of relapses and a patient’s ability to recover from them may provide important information. “Some attacks are quite mild. Others tend to build up disease,” Dr. Freedman said. “Some people are better healers than others. We have all seen people who have been quadriplegic in an ICU on a ventilator walk out of the hospital without even a numb toe. And other people who have a little bit of weakness in one leg seem to never be able to recover from that. Exactly what drives repair is still not clear.” Most patients do recover, however, “and the inability to recover early on is a bad omen,” Dr. Freedman said.
When researchers examined the relationship between functional components of the Expanded Disability Status Scale (EDSS) and disability progression, “not surprisingly ... pyramidal and spinal cord and cerebellar [functioning] are more associated with earlier progression” (Neuroepidemiology. 2015;44[1]:16-23).
A study by Lublin et al. found that patients with MS whose attacks left them with residual deficits had more EDSS accumulation over time (Neurology. 2003 Dec 9;61[11]:1528-32.).
Response to immunomodulators
“The inability to control the disease with an immunomodulator is a bad sign,” Dr. Freedman said. He pointed to data from a trial of teriflunomide that included patients who had had suboptimal responses to first-line therapy as well as patients who were treatment naive (Mult Scler. 2018 Apr;24[4]:535-9.). Some of the patients who had received prior MS therapy were randomized to placebo, which “is not something that would happen today,” he said.
“If you just focus on the [patients who received placebo] and look at the rate of attack in patients who had no prior DMT, at least one prior DMT, or two or more prior DMTs, the attack rates are much higher in those individuals who tried and failed first-line therapies,” Dr. Freedman said. These patients also had more EDSS progression. “The majority of people do respond [to first-line treatment], but those who do not you need to worry about a little bit more than those who do respond.”
MRI lesions and brain reserve
MRI activity over time tends to predict disease progression, and lesion location is important. One cohort study found that the likelihood of developing secondary progressive MS was lower among patients who did not develop new spinal cord or brainstem lesions in the first three years of the disease, compared with those who did.
In addition, patients who presented with more lesions were more likely to reach an EDSS score 3 or 6 over 10 years (Brain. 2008 Mar;131[Pt 3]:808-17.).
Brain reserve also may be important. Among 52 treatment-naive Serbian adults with MS, Sumowski et al. found that maximal lifetime brain growth as estimated with intracranial volume was associated with risk of disability progression over 5 years (Neurology. 2016 May 24;86[21]:2006-9.). “Those who had a greater reserve had a much lower risk of disease progression,” Dr. Freedman said. The results suggest that patients with more brain reserve may be better able to sustain damage as the disease progresses and they age, he said.
Comorbidities
In the past, neurologists may have left it up to general practitioners “to sort out the rest of the patient’s health,” Dr. Freedman said. “But we now recognize that having certain comorbidities already puts a higher burden onto the disease. And those patients who have more comorbidities ... are going to do worse. But not only are they going to do worse ... it turns out that patients who have more comorbidities are going to have less of a response to your various therapies.” Vascular comorbidities, in particular, may affect treatment response (Neurology. 2017 Nov 28;89[22]:2222-9.).
If hypertension or diabetes clinics can help control those conditions in patients with MS, “it will help us a lot in getting what we are expecting from the [MS] medications,” Dr. Freedman said.
Adherence, expectations, and symptomatic treatment
Ultimately, selecting an MS therapy is a decision that doctors share with their patients. “You’re going to have a discussion with them,” he said. “You can see what fits their lifestyle.” For example, a world traveler might not be a good candidate for a drug that requires regular monitoring. A patient’s risk averseness also may influence treatment choice.
If you involve patients in the selection process, it may improve medication adherence. In addition, patients need to understand what you aim to accomplish with a DMT, said Dr. Freedman. “That may sound like a trivial thing. But how many times has the patient come in and said, ‘The drug is not working. ... My eye is not better’” when that was not the goal of treatment to begin with. Let patients know that symptomatic treatments may address problems apart from MS DMT. This personalized but imprecise approach to treatment is “probably the best we can do for now,” Dr. Freedman said.
Dr. Freedman has received a research grant from Genzyme and is on the company’s speakers bureau. He has received honoraria and consulting fees from various pharmaceutical companies and serves on companies’ advisory boards.
SOURCE: Freedman MS. ACTRIMS Forum 2019, Session 2.
DALLAS – , said Mark Freedman, MD, MSc, in a presentation at ACTRIMS Forum 2019, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “Right now, we are probably dealing with more of an imprecise medicine,” said Dr. Freedman.
Information such as a patient’s ability to recover from relapses may indicate MS severity or the likelihood of disease progression, but selecting a therapy remains “an art of medicine,” said Dr. Freedman, professor of neurology at the University of Ottawa, director of the multiple sclerosis research unit at Ottawa Hospital, and senior scientist at the Ottawa Hospital Research Institute.
When prescribing a DMT, neurologists tend to consider three key elements: the disease, the treatment, and patient expectations. “Focus on these three aspects,” Dr. Freedman said.
It is no longer sufficient for neurologists to diagnose MS, hand the patient a drug, and “expect that things are going to go the way you want them to go,” he said.
Immunomodulating, anti–cell trafficking, or cell-depleting therapy?
Genetics, sex, types of relapses, recovery from relapses, response to therapy, MRI burden, and other biomarkers such as oligoclonal bands and neurofilaments may indicate which patients have severe disease and should receive aggressive treatment.
Determining the phase of the disease is a crucial first step “that is going to drive your choice of therapy,” he said.
Dr. Freedman likened the development of progressive MS to approaching the edge of a cliff. If patients appear to be nearing the progressive phase, “then your choice of therapy has to be an aggressive one – one that will hopefully hold them back from falling,” he said. In the earlier phases of MS, on the other hand, “you are looking at a long-term treatment that should probably be safe and still able to contain the disease,” such as an immunomodulator. If a patient is “about to fall off, you may want to go for temporary use of an antitrafficker to control things, and then eventually deplete the cells that are going to be causing the patient to fall off the cliff.”
Prognostic factors
Disease activity over time, and whether the disease is progressing faster or slower than would be expected, may be important prognostic factors. A patient’s sex also may be a factor because women tend to have more attacks and to have their attacks at a younger age, Dr. Freedman said.
The types of relapses and a patient’s ability to recover from them may provide important information. “Some attacks are quite mild. Others tend to build up disease,” Dr. Freedman said. “Some people are better healers than others. We have all seen people who have been quadriplegic in an ICU on a ventilator walk out of the hospital without even a numb toe. And other people who have a little bit of weakness in one leg seem to never be able to recover from that. Exactly what drives repair is still not clear.” Most patients do recover, however, “and the inability to recover early on is a bad omen,” Dr. Freedman said.
When researchers examined the relationship between functional components of the Expanded Disability Status Scale (EDSS) and disability progression, “not surprisingly ... pyramidal and spinal cord and cerebellar [functioning] are more associated with earlier progression” (Neuroepidemiology. 2015;44[1]:16-23).
A study by Lublin et al. found that patients with MS whose attacks left them with residual deficits had more EDSS accumulation over time (Neurology. 2003 Dec 9;61[11]:1528-32.).
Response to immunomodulators
“The inability to control the disease with an immunomodulator is a bad sign,” Dr. Freedman said. He pointed to data from a trial of teriflunomide that included patients who had had suboptimal responses to first-line therapy as well as patients who were treatment naive (Mult Scler. 2018 Apr;24[4]:535-9.). Some of the patients who had received prior MS therapy were randomized to placebo, which “is not something that would happen today,” he said.
“If you just focus on the [patients who received placebo] and look at the rate of attack in patients who had no prior DMT, at least one prior DMT, or two or more prior DMTs, the attack rates are much higher in those individuals who tried and failed first-line therapies,” Dr. Freedman said. These patients also had more EDSS progression. “The majority of people do respond [to first-line treatment], but those who do not you need to worry about a little bit more than those who do respond.”
MRI lesions and brain reserve
MRI activity over time tends to predict disease progression, and lesion location is important. One cohort study found that the likelihood of developing secondary progressive MS was lower among patients who did not develop new spinal cord or brainstem lesions in the first three years of the disease, compared with those who did.
In addition, patients who presented with more lesions were more likely to reach an EDSS score 3 or 6 over 10 years (Brain. 2008 Mar;131[Pt 3]:808-17.).
Brain reserve also may be important. Among 52 treatment-naive Serbian adults with MS, Sumowski et al. found that maximal lifetime brain growth as estimated with intracranial volume was associated with risk of disability progression over 5 years (Neurology. 2016 May 24;86[21]:2006-9.). “Those who had a greater reserve had a much lower risk of disease progression,” Dr. Freedman said. The results suggest that patients with more brain reserve may be better able to sustain damage as the disease progresses and they age, he said.
Comorbidities
In the past, neurologists may have left it up to general practitioners “to sort out the rest of the patient’s health,” Dr. Freedman said. “But we now recognize that having certain comorbidities already puts a higher burden onto the disease. And those patients who have more comorbidities ... are going to do worse. But not only are they going to do worse ... it turns out that patients who have more comorbidities are going to have less of a response to your various therapies.” Vascular comorbidities, in particular, may affect treatment response (Neurology. 2017 Nov 28;89[22]:2222-9.).
If hypertension or diabetes clinics can help control those conditions in patients with MS, “it will help us a lot in getting what we are expecting from the [MS] medications,” Dr. Freedman said.
Adherence, expectations, and symptomatic treatment
Ultimately, selecting an MS therapy is a decision that doctors share with their patients. “You’re going to have a discussion with them,” he said. “You can see what fits their lifestyle.” For example, a world traveler might not be a good candidate for a drug that requires regular monitoring. A patient’s risk averseness also may influence treatment choice.
If you involve patients in the selection process, it may improve medication adherence. In addition, patients need to understand what you aim to accomplish with a DMT, said Dr. Freedman. “That may sound like a trivial thing. But how many times has the patient come in and said, ‘The drug is not working. ... My eye is not better’” when that was not the goal of treatment to begin with. Let patients know that symptomatic treatments may address problems apart from MS DMT. This personalized but imprecise approach to treatment is “probably the best we can do for now,” Dr. Freedman said.
Dr. Freedman has received a research grant from Genzyme and is on the company’s speakers bureau. He has received honoraria and consulting fees from various pharmaceutical companies and serves on companies’ advisory boards.
SOURCE: Freedman MS. ACTRIMS Forum 2019, Session 2.
DALLAS – , said Mark Freedman, MD, MSc, in a presentation at ACTRIMS Forum 2019, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “Right now, we are probably dealing with more of an imprecise medicine,” said Dr. Freedman.
Information such as a patient’s ability to recover from relapses may indicate MS severity or the likelihood of disease progression, but selecting a therapy remains “an art of medicine,” said Dr. Freedman, professor of neurology at the University of Ottawa, director of the multiple sclerosis research unit at Ottawa Hospital, and senior scientist at the Ottawa Hospital Research Institute.
When prescribing a DMT, neurologists tend to consider three key elements: the disease, the treatment, and patient expectations. “Focus on these three aspects,” Dr. Freedman said.
It is no longer sufficient for neurologists to diagnose MS, hand the patient a drug, and “expect that things are going to go the way you want them to go,” he said.
Immunomodulating, anti–cell trafficking, or cell-depleting therapy?
Genetics, sex, types of relapses, recovery from relapses, response to therapy, MRI burden, and other biomarkers such as oligoclonal bands and neurofilaments may indicate which patients have severe disease and should receive aggressive treatment.
Determining the phase of the disease is a crucial first step “that is going to drive your choice of therapy,” he said.
Dr. Freedman likened the development of progressive MS to approaching the edge of a cliff. If patients appear to be nearing the progressive phase, “then your choice of therapy has to be an aggressive one – one that will hopefully hold them back from falling,” he said. In the earlier phases of MS, on the other hand, “you are looking at a long-term treatment that should probably be safe and still able to contain the disease,” such as an immunomodulator. If a patient is “about to fall off, you may want to go for temporary use of an antitrafficker to control things, and then eventually deplete the cells that are going to be causing the patient to fall off the cliff.”
Prognostic factors
Disease activity over time, and whether the disease is progressing faster or slower than would be expected, may be important prognostic factors. A patient’s sex also may be a factor because women tend to have more attacks and to have their attacks at a younger age, Dr. Freedman said.
The types of relapses and a patient’s ability to recover from them may provide important information. “Some attacks are quite mild. Others tend to build up disease,” Dr. Freedman said. “Some people are better healers than others. We have all seen people who have been quadriplegic in an ICU on a ventilator walk out of the hospital without even a numb toe. And other people who have a little bit of weakness in one leg seem to never be able to recover from that. Exactly what drives repair is still not clear.” Most patients do recover, however, “and the inability to recover early on is a bad omen,” Dr. Freedman said.
When researchers examined the relationship between functional components of the Expanded Disability Status Scale (EDSS) and disability progression, “not surprisingly ... pyramidal and spinal cord and cerebellar [functioning] are more associated with earlier progression” (Neuroepidemiology. 2015;44[1]:16-23).
A study by Lublin et al. found that patients with MS whose attacks left them with residual deficits had more EDSS accumulation over time (Neurology. 2003 Dec 9;61[11]:1528-32.).
Response to immunomodulators
“The inability to control the disease with an immunomodulator is a bad sign,” Dr. Freedman said. He pointed to data from a trial of teriflunomide that included patients who had had suboptimal responses to first-line therapy as well as patients who were treatment naive (Mult Scler. 2018 Apr;24[4]:535-9.). Some of the patients who had received prior MS therapy were randomized to placebo, which “is not something that would happen today,” he said.
“If you just focus on the [patients who received placebo] and look at the rate of attack in patients who had no prior DMT, at least one prior DMT, or two or more prior DMTs, the attack rates are much higher in those individuals who tried and failed first-line therapies,” Dr. Freedman said. These patients also had more EDSS progression. “The majority of people do respond [to first-line treatment], but those who do not you need to worry about a little bit more than those who do respond.”
MRI lesions and brain reserve
MRI activity over time tends to predict disease progression, and lesion location is important. One cohort study found that the likelihood of developing secondary progressive MS was lower among patients who did not develop new spinal cord or brainstem lesions in the first three years of the disease, compared with those who did.
In addition, patients who presented with more lesions were more likely to reach an EDSS score 3 or 6 over 10 years (Brain. 2008 Mar;131[Pt 3]:808-17.).
Brain reserve also may be important. Among 52 treatment-naive Serbian adults with MS, Sumowski et al. found that maximal lifetime brain growth as estimated with intracranial volume was associated with risk of disability progression over 5 years (Neurology. 2016 May 24;86[21]:2006-9.). “Those who had a greater reserve had a much lower risk of disease progression,” Dr. Freedman said. The results suggest that patients with more brain reserve may be better able to sustain damage as the disease progresses and they age, he said.
Comorbidities
In the past, neurologists may have left it up to general practitioners “to sort out the rest of the patient’s health,” Dr. Freedman said. “But we now recognize that having certain comorbidities already puts a higher burden onto the disease. And those patients who have more comorbidities ... are going to do worse. But not only are they going to do worse ... it turns out that patients who have more comorbidities are going to have less of a response to your various therapies.” Vascular comorbidities, in particular, may affect treatment response (Neurology. 2017 Nov 28;89[22]:2222-9.).
If hypertension or diabetes clinics can help control those conditions in patients with MS, “it will help us a lot in getting what we are expecting from the [MS] medications,” Dr. Freedman said.
Adherence, expectations, and symptomatic treatment
Ultimately, selecting an MS therapy is a decision that doctors share with their patients. “You’re going to have a discussion with them,” he said. “You can see what fits their lifestyle.” For example, a world traveler might not be a good candidate for a drug that requires regular monitoring. A patient’s risk averseness also may influence treatment choice.
If you involve patients in the selection process, it may improve medication adherence. In addition, patients need to understand what you aim to accomplish with a DMT, said Dr. Freedman. “That may sound like a trivial thing. But how many times has the patient come in and said, ‘The drug is not working. ... My eye is not better’” when that was not the goal of treatment to begin with. Let patients know that symptomatic treatments may address problems apart from MS DMT. This personalized but imprecise approach to treatment is “probably the best we can do for now,” Dr. Freedman said.
Dr. Freedman has received a research grant from Genzyme and is on the company’s speakers bureau. He has received honoraria and consulting fees from various pharmaceutical companies and serves on companies’ advisory boards.
SOURCE: Freedman MS. ACTRIMS Forum 2019, Session 2.
EXPERT ANALYSIS FROM ACTRIMS
Most pregnancy-related deaths are preventable
according to the Centers for Disease Control and Prevention.
Deaths from pregnancy-related complications can occur “up to a year after delivery,” the CDC emphasized in a report released May 7. Indeed, 31% of pregnancy-related deaths happen during pregnancy, 36% happen at delivery or in the week after, and 33% happen 1 week to 1 year post partum. Yet detailed data from 13 state maternal mortality review committees (MMRCs) showed that 60% of such deaths are preventable.
There were 17 pregnancy-related deaths per 100,000 live births during 2011-2015, based on another data source: 3,410 pregnancy-related deaths (an average of 682 deaths per year) in the CDC’s Pregnancy Mortality Surveillance System. That pregnancy-related mortality ratio varied by race/ethnicity, Emily E. Peterson, MD, and the other CDC investigators reported in Morbidity and Mortality Weekly Report: Hispanic (11 deaths per 100,000), white (13), Asian/Pacific Islander (14), American Indian/Alaska Native (33), and black (43).
One aspect of the disparity was addressed by Wanda Barfield, MD, MPH, director of the CDC’s division of reproductive health and assistant surgeon general in the U.S. Public Health Service. “Recent studies have shown that racial and ethnic minority women deliver at different and lower-quality hospitals than white women and that these hospitals disproportionately care for black women at delivery,” she said at a CDC telebriefing.
Analysis of the timing of 2,990 deaths from the Pregnancy Mortality Surveillance System showed that almost a third (31.3%) occurred during pregnancy and 16.9% occurred on the day of delivery. Dr. Peterson and her CDC associates noted that more than half of pregnancy-related deaths, however, took place later: 1-6 days post partum (18.6%), 7-42 days (21.4%), and 43-365 days (11.7%).
The data on preventability were collected by the state MMRCs and included 232 deaths that occurred during 2013-2017. The MMRCs considered deaths preventable if they could be “averted by one or more reasonable changes to patient, community, provider, health facility, and/or system factors.”
“Our new analysis underscores the need for access to quality services, risk awareness, and early diagnosis, but it also highlights opportunities for preventing future pregnancy-related deaths,” Dr. Barfield said. “By identifying and promptly responding to warning signs not just during pregnancy, but even up to a year after delivery, we can save lives.”
according to the Centers for Disease Control and Prevention.
Deaths from pregnancy-related complications can occur “up to a year after delivery,” the CDC emphasized in a report released May 7. Indeed, 31% of pregnancy-related deaths happen during pregnancy, 36% happen at delivery or in the week after, and 33% happen 1 week to 1 year post partum. Yet detailed data from 13 state maternal mortality review committees (MMRCs) showed that 60% of such deaths are preventable.
There were 17 pregnancy-related deaths per 100,000 live births during 2011-2015, based on another data source: 3,410 pregnancy-related deaths (an average of 682 deaths per year) in the CDC’s Pregnancy Mortality Surveillance System. That pregnancy-related mortality ratio varied by race/ethnicity, Emily E. Peterson, MD, and the other CDC investigators reported in Morbidity and Mortality Weekly Report: Hispanic (11 deaths per 100,000), white (13), Asian/Pacific Islander (14), American Indian/Alaska Native (33), and black (43).
One aspect of the disparity was addressed by Wanda Barfield, MD, MPH, director of the CDC’s division of reproductive health and assistant surgeon general in the U.S. Public Health Service. “Recent studies have shown that racial and ethnic minority women deliver at different and lower-quality hospitals than white women and that these hospitals disproportionately care for black women at delivery,” she said at a CDC telebriefing.
Analysis of the timing of 2,990 deaths from the Pregnancy Mortality Surveillance System showed that almost a third (31.3%) occurred during pregnancy and 16.9% occurred on the day of delivery. Dr. Peterson and her CDC associates noted that more than half of pregnancy-related deaths, however, took place later: 1-6 days post partum (18.6%), 7-42 days (21.4%), and 43-365 days (11.7%).
The data on preventability were collected by the state MMRCs and included 232 deaths that occurred during 2013-2017. The MMRCs considered deaths preventable if they could be “averted by one or more reasonable changes to patient, community, provider, health facility, and/or system factors.”
“Our new analysis underscores the need for access to quality services, risk awareness, and early diagnosis, but it also highlights opportunities for preventing future pregnancy-related deaths,” Dr. Barfield said. “By identifying and promptly responding to warning signs not just during pregnancy, but even up to a year after delivery, we can save lives.”
according to the Centers for Disease Control and Prevention.
Deaths from pregnancy-related complications can occur “up to a year after delivery,” the CDC emphasized in a report released May 7. Indeed, 31% of pregnancy-related deaths happen during pregnancy, 36% happen at delivery or in the week after, and 33% happen 1 week to 1 year post partum. Yet detailed data from 13 state maternal mortality review committees (MMRCs) showed that 60% of such deaths are preventable.
There were 17 pregnancy-related deaths per 100,000 live births during 2011-2015, based on another data source: 3,410 pregnancy-related deaths (an average of 682 deaths per year) in the CDC’s Pregnancy Mortality Surveillance System. That pregnancy-related mortality ratio varied by race/ethnicity, Emily E. Peterson, MD, and the other CDC investigators reported in Morbidity and Mortality Weekly Report: Hispanic (11 deaths per 100,000), white (13), Asian/Pacific Islander (14), American Indian/Alaska Native (33), and black (43).
One aspect of the disparity was addressed by Wanda Barfield, MD, MPH, director of the CDC’s division of reproductive health and assistant surgeon general in the U.S. Public Health Service. “Recent studies have shown that racial and ethnic minority women deliver at different and lower-quality hospitals than white women and that these hospitals disproportionately care for black women at delivery,” she said at a CDC telebriefing.
Analysis of the timing of 2,990 deaths from the Pregnancy Mortality Surveillance System showed that almost a third (31.3%) occurred during pregnancy and 16.9% occurred on the day of delivery. Dr. Peterson and her CDC associates noted that more than half of pregnancy-related deaths, however, took place later: 1-6 days post partum (18.6%), 7-42 days (21.4%), and 43-365 days (11.7%).
The data on preventability were collected by the state MMRCs and included 232 deaths that occurred during 2013-2017. The MMRCs considered deaths preventable if they could be “averted by one or more reasonable changes to patient, community, provider, health facility, and/or system factors.”
“Our new analysis underscores the need for access to quality services, risk awareness, and early diagnosis, but it also highlights opportunities for preventing future pregnancy-related deaths,” Dr. Barfield said. “By identifying and promptly responding to warning signs not just during pregnancy, but even up to a year after delivery, we can save lives.”
PCV13 vaccine reduces frequency of otitis media visits
The mean number of office visits for otitis media in children younger than 5 years dropped significantly after the introduction of the 13-valent pneumococcal conjugate vaccine, according to findings published in the International Journal of Pediatric Otorhinolaryngology.
Previous studies have shown that more than half of children with otitis media (OM) have serotypes included in the PCV7 vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F), wrote Xiaofeng Zhou, MD, of Pfizer, New York, and colleagues.
To assess the impact of PCV13, with the additional serotypes 1, 3, 5, 6A, 7F, and 19A, the researchers analyzed data from the U.S. National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for three time periods: pre-PCV7 (1997-1999), after the introduction of PCV7 (2001-2009), and after the introduction of PCV13 (2011-2013).
Between the pre-PCV7 and PCV13 time periods, the researchers found significant reductions in the mean rates of OM visits of 48% and 41% among children younger than 2 years and younger than 5 years, respectively; reductions were 24% and 22%, respectively, when comparing PCV13 and PCV7. Ambulatory care visits for skin rash and trauma were not significantly different among the study periods.
Comparing the PCV7 and PCV13 time periods, the mean number of OM visits per 100 children declined from 84 to 64 per 100 children younger than 2 years, 41 to 34 per 100 children between ages 2 and 5 years, and from 59 to 46 per 100 children younger than 5 years.
The study findings were limited by several factors including the use of an ecologic study design, which was chosen to help reduce selection bias, but that did not show evidence of the field effectiveness of the PCV13 vaccine. Another limitation was the potential misclassification of patients with OM given clinician variability in diagnostic criteria, the researchers noted.
“Our results in this study, while not providing direct evidence of causality, nonetheless suggest a significant and positive impact of the PCV13 vaccination program on otitis media for children less than 5 years of age in the U.S., with further reductions in OM visits observed in PCV13 period following a decade of PCV7 use,” Dr. Zhou and associates said.
The investigators are employed by Pfizer, which funded the study.
SOURCE: Zhou X et al. Int J Pediatr Otorhinolaryngol. 2019 Apr. 119:96-102.
The mean number of office visits for otitis media in children younger than 5 years dropped significantly after the introduction of the 13-valent pneumococcal conjugate vaccine, according to findings published in the International Journal of Pediatric Otorhinolaryngology.
Previous studies have shown that more than half of children with otitis media (OM) have serotypes included in the PCV7 vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F), wrote Xiaofeng Zhou, MD, of Pfizer, New York, and colleagues.
To assess the impact of PCV13, with the additional serotypes 1, 3, 5, 6A, 7F, and 19A, the researchers analyzed data from the U.S. National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for three time periods: pre-PCV7 (1997-1999), after the introduction of PCV7 (2001-2009), and after the introduction of PCV13 (2011-2013).
Between the pre-PCV7 and PCV13 time periods, the researchers found significant reductions in the mean rates of OM visits of 48% and 41% among children younger than 2 years and younger than 5 years, respectively; reductions were 24% and 22%, respectively, when comparing PCV13 and PCV7. Ambulatory care visits for skin rash and trauma were not significantly different among the study periods.
Comparing the PCV7 and PCV13 time periods, the mean number of OM visits per 100 children declined from 84 to 64 per 100 children younger than 2 years, 41 to 34 per 100 children between ages 2 and 5 years, and from 59 to 46 per 100 children younger than 5 years.
The study findings were limited by several factors including the use of an ecologic study design, which was chosen to help reduce selection bias, but that did not show evidence of the field effectiveness of the PCV13 vaccine. Another limitation was the potential misclassification of patients with OM given clinician variability in diagnostic criteria, the researchers noted.
“Our results in this study, while not providing direct evidence of causality, nonetheless suggest a significant and positive impact of the PCV13 vaccination program on otitis media for children less than 5 years of age in the U.S., with further reductions in OM visits observed in PCV13 period following a decade of PCV7 use,” Dr. Zhou and associates said.
The investigators are employed by Pfizer, which funded the study.
SOURCE: Zhou X et al. Int J Pediatr Otorhinolaryngol. 2019 Apr. 119:96-102.
The mean number of office visits for otitis media in children younger than 5 years dropped significantly after the introduction of the 13-valent pneumococcal conjugate vaccine, according to findings published in the International Journal of Pediatric Otorhinolaryngology.
Previous studies have shown that more than half of children with otitis media (OM) have serotypes included in the PCV7 vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F), wrote Xiaofeng Zhou, MD, of Pfizer, New York, and colleagues.
To assess the impact of PCV13, with the additional serotypes 1, 3, 5, 6A, 7F, and 19A, the researchers analyzed data from the U.S. National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for three time periods: pre-PCV7 (1997-1999), after the introduction of PCV7 (2001-2009), and after the introduction of PCV13 (2011-2013).
Between the pre-PCV7 and PCV13 time periods, the researchers found significant reductions in the mean rates of OM visits of 48% and 41% among children younger than 2 years and younger than 5 years, respectively; reductions were 24% and 22%, respectively, when comparing PCV13 and PCV7. Ambulatory care visits for skin rash and trauma were not significantly different among the study periods.
Comparing the PCV7 and PCV13 time periods, the mean number of OM visits per 100 children declined from 84 to 64 per 100 children younger than 2 years, 41 to 34 per 100 children between ages 2 and 5 years, and from 59 to 46 per 100 children younger than 5 years.
The study findings were limited by several factors including the use of an ecologic study design, which was chosen to help reduce selection bias, but that did not show evidence of the field effectiveness of the PCV13 vaccine. Another limitation was the potential misclassification of patients with OM given clinician variability in diagnostic criteria, the researchers noted.
“Our results in this study, while not providing direct evidence of causality, nonetheless suggest a significant and positive impact of the PCV13 vaccination program on otitis media for children less than 5 years of age in the U.S., with further reductions in OM visits observed in PCV13 period following a decade of PCV7 use,” Dr. Zhou and associates said.
The investigators are employed by Pfizer, which funded the study.
SOURCE: Zhou X et al. Int J Pediatr Otorhinolaryngol. 2019 Apr. 119:96-102.
FROM THE INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY
Coalescing Papules on Bilateral Mastectomy Scars
The Diagnosis: Scar Sarcoidosis
Although scars on both breasts were involved, the decision was made to biopsy the right breast because the patient reported more pain on the left breast. Biopsy showed noncaseating granulomas consistent with scar sarcoidosis (Figure). Additional screening tests were performed to evaluate for any systemic involvement of sarcoidosis, including a complete blood cell count, comprehensive metabolic panel, angiotensin-converting enzyme level, tuberculosis serology screening, electrocardiogram, chest radiograph, and pulmonary function tests. She also was referred to rheumatology and ophthalmology for consultation. The results of all screenings were within reference range, and no sign of systemic sarcoidosis was found. She was treated with hydrocortisone ointment 2.5% for several weeks without notable improvement. She elected not to pursue any additional treatment and to monitor the symptoms with close follow-up only. One year after the initial visit, the skin lesions spontaneously and notably improved.
Sarcoidosis is a systemic granulomatous disorder of unknown etiology that most commonly affects the lungs. It also can involve the lymph nodes, liver, spleen, bones, gastrointestinal tract, eyes, and skin. Cutaneous sarcoidosis has been documented in the literature since the late 1800s and occurs in up to one-third of sarcoid patients.1 Cutaneous lesions developing within a preexisting scar is a well-known variant, occurring in 29% of patients with cutaneous sarcoidosis in one clinical study (N=818).2 There have been many reports describing scar sarcoidosis, with its development at prior sites of surgery, trauma, acne, or venipuncture.3 Other case reports have described variants of scar sarcoidosis developing at sites of hyaluronic acid injection, laser surgery, ritual scarification, tattoos, and desensitization injections, as well as prior herpes zoster infections.4-9
Cutaneous sarcoidosis has a wide range of clinical presentations. Lesions can be described as specific or nonspecific. Specific lesions demonstrate the typical sarcoid granuloma on histology and more often are seen in chronic disease, while nonspecific lesions more often are seen in acute disease.3,10 Scar sarcoidosis is an example of a specific lesion in which old scars become infiltrated with noncaseating granulomas. The granulomas typically are in the superficial dermis but may involve the full thickness of the dermis, extending into the subcutaneous tissue.11 The cause of granulomas developing in scars is unknown. Prior contamination of the scar with foreign material, possibly at the time of the trauma, is a possible underlying cause.12
Typical scar sarcoidosis presents as swollen, erythematous, indurated lesions with a purple-red hue that may become brown.3,12 Tenderness or pruritus also may be present.13 Interestingly, our patient's scar sarcoidosis presented with a yellow hue at both mastectomy sites.
Diagnosing scar sarcoidosis can be challenging. Patients are diagnosed with sarcoidosis when a compatible clinical or radiologic picture is present along with histologic evidence of a noncaseating granuloma and other potential causes are excluded.11 The differential includes an infectious etiology, other types of granulomatous dermatitis, hypertrophic scar, keloid, or foreign body granuloma.
Scar sarcoidosis can be isolated in occurrence. It also can precede or occur concomitantly or during a relapse of systemic sarcoidosis.10 Most commonly, patients with scar sarcoidosis also have systemic manifestations of sarcoidosis, and changing scars may be an indicator of disease exacerbation or relapse.10 For patients who only demonstrate specific skin lesions of cutaneous sarcoidosis, approximately 30% develop systemic involvement later in life.3 For this reason, close monitoring and regular follow-up are necessary.
Treatment of scar sarcoidosis is dependent on the extent of the disease and presence of systemic sarcoidosis. Topical and systemic corticosteroids, hydroxychloroquine, chloroquine phosphate, and methotrexate all have been shown to be helpful in treating cutaneous sarcoidosis.3 For scar sarcoidosis that is limited to only the scar site, as seen in our case, monitoring and close follow-up is acceptable. Topical steroids can be prescribed for symptomatic relief. Scar sarcoidosis can resolve slowly and spontaneously over time.10 Our patient notably improved 1 year after the initial presentation without treatment.
Scar sarcoidosis is a well-documented variant of cutaneous sarcoidosis that can have important implications for diagnosing systemic sarcoidosis. Although there are typical lesions that represent scar sarcoidosis, it is important to have a high degree of suspicion with any changing scar. Once diagnosed through biopsy, a thorough investigation for systemic signs of sarcoidosis needs to be performed to guide treatment.
- Bolognia JL, Jorizzo JL, Shaffer JV, eds. Dermatology. 3rd ed. Vol 2. Philadelphia, PA: Elsevier/Saunders; 2012.
- Neville E, Walker AN, James DG. Prognostic factors predicting the outcome of sarcoidosis: an analysis of 818 patients. Q J Med. 1983;52:525-533.
- Mañá J, Marcoval J, Graells J, et al. Cutaneous involvement in sarcoidosis: relationship to systemic disease. Arch Dermatol. 1997;133:882-888.
- Dal Sacco D, Cozzani E, Parodi A, et al. Scar sarcoidosis after hyaluronic acid injection. Int J Dermatol. 2005;44:411-412.
- Kormeili T, Neel V, Moy RL. Cutaneous sarcoidosis at sites of previous laser surgery. Cutis. 2004;73:53-55.
- Nayar M. Sarcoidosis on ritual scarification. Int J Dermatol. 1993;32:116-118.
- James WD, Elston DM, Berger TG, et al. Andrews' Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, PA: Elsevier/Saunders; 2011.
- Healsmith MF, Hutchinson PE. The development of scar sarcoidosis at the site of desensitization injections. Clin Exp Dermatol. 1992;17:369-370.
- Singal A, Vij A, Pandhi D. Post herpes-zoster scar sarcoidosis with pulmonary involvement. Indian Dermatol Online J. 2014;5:77-79.
- Chudomirova K, Velichkova L, Anavi B, et al. Recurrent sarcoidosis in skin scars accompanying systemic sarcoidosis. J Eur Acad Dermatol Venereol. 2003;17:360-361.
- Selim A, Ehrsam E, Atassi MB, et al. Scar sarcoidosis: a case report and brief review. Cutis. 2006;78:418-422.
- Singal A, Thami GP, Goraya JS. Scar sarcoidosis in childhood: case report and review of the literature. Clin Exp Dermatol. 2005;30:244-246.
- Marchell RM, Judson MA. Chronic cutaneous lesions of sarcoidosis. Clin Dermatol. 2007;25:295-302.
The Diagnosis: Scar Sarcoidosis
Although scars on both breasts were involved, the decision was made to biopsy the right breast because the patient reported more pain on the left breast. Biopsy showed noncaseating granulomas consistent with scar sarcoidosis (Figure). Additional screening tests were performed to evaluate for any systemic involvement of sarcoidosis, including a complete blood cell count, comprehensive metabolic panel, angiotensin-converting enzyme level, tuberculosis serology screening, electrocardiogram, chest radiograph, and pulmonary function tests. She also was referred to rheumatology and ophthalmology for consultation. The results of all screenings were within reference range, and no sign of systemic sarcoidosis was found. She was treated with hydrocortisone ointment 2.5% for several weeks without notable improvement. She elected not to pursue any additional treatment and to monitor the symptoms with close follow-up only. One year after the initial visit, the skin lesions spontaneously and notably improved.
Sarcoidosis is a systemic granulomatous disorder of unknown etiology that most commonly affects the lungs. It also can involve the lymph nodes, liver, spleen, bones, gastrointestinal tract, eyes, and skin. Cutaneous sarcoidosis has been documented in the literature since the late 1800s and occurs in up to one-third of sarcoid patients.1 Cutaneous lesions developing within a preexisting scar is a well-known variant, occurring in 29% of patients with cutaneous sarcoidosis in one clinical study (N=818).2 There have been many reports describing scar sarcoidosis, with its development at prior sites of surgery, trauma, acne, or venipuncture.3 Other case reports have described variants of scar sarcoidosis developing at sites of hyaluronic acid injection, laser surgery, ritual scarification, tattoos, and desensitization injections, as well as prior herpes zoster infections.4-9
Cutaneous sarcoidosis has a wide range of clinical presentations. Lesions can be described as specific or nonspecific. Specific lesions demonstrate the typical sarcoid granuloma on histology and more often are seen in chronic disease, while nonspecific lesions more often are seen in acute disease.3,10 Scar sarcoidosis is an example of a specific lesion in which old scars become infiltrated with noncaseating granulomas. The granulomas typically are in the superficial dermis but may involve the full thickness of the dermis, extending into the subcutaneous tissue.11 The cause of granulomas developing in scars is unknown. Prior contamination of the scar with foreign material, possibly at the time of the trauma, is a possible underlying cause.12
Typical scar sarcoidosis presents as swollen, erythematous, indurated lesions with a purple-red hue that may become brown.3,12 Tenderness or pruritus also may be present.13 Interestingly, our patient's scar sarcoidosis presented with a yellow hue at both mastectomy sites.
Diagnosing scar sarcoidosis can be challenging. Patients are diagnosed with sarcoidosis when a compatible clinical or radiologic picture is present along with histologic evidence of a noncaseating granuloma and other potential causes are excluded.11 The differential includes an infectious etiology, other types of granulomatous dermatitis, hypertrophic scar, keloid, or foreign body granuloma.
Scar sarcoidosis can be isolated in occurrence. It also can precede or occur concomitantly or during a relapse of systemic sarcoidosis.10 Most commonly, patients with scar sarcoidosis also have systemic manifestations of sarcoidosis, and changing scars may be an indicator of disease exacerbation or relapse.10 For patients who only demonstrate specific skin lesions of cutaneous sarcoidosis, approximately 30% develop systemic involvement later in life.3 For this reason, close monitoring and regular follow-up are necessary.
Treatment of scar sarcoidosis is dependent on the extent of the disease and presence of systemic sarcoidosis. Topical and systemic corticosteroids, hydroxychloroquine, chloroquine phosphate, and methotrexate all have been shown to be helpful in treating cutaneous sarcoidosis.3 For scar sarcoidosis that is limited to only the scar site, as seen in our case, monitoring and close follow-up is acceptable. Topical steroids can be prescribed for symptomatic relief. Scar sarcoidosis can resolve slowly and spontaneously over time.10 Our patient notably improved 1 year after the initial presentation without treatment.
Scar sarcoidosis is a well-documented variant of cutaneous sarcoidosis that can have important implications for diagnosing systemic sarcoidosis. Although there are typical lesions that represent scar sarcoidosis, it is important to have a high degree of suspicion with any changing scar. Once diagnosed through biopsy, a thorough investigation for systemic signs of sarcoidosis needs to be performed to guide treatment.
The Diagnosis: Scar Sarcoidosis
Although scars on both breasts were involved, the decision was made to biopsy the right breast because the patient reported more pain on the left breast. Biopsy showed noncaseating granulomas consistent with scar sarcoidosis (Figure). Additional screening tests were performed to evaluate for any systemic involvement of sarcoidosis, including a complete blood cell count, comprehensive metabolic panel, angiotensin-converting enzyme level, tuberculosis serology screening, electrocardiogram, chest radiograph, and pulmonary function tests. She also was referred to rheumatology and ophthalmology for consultation. The results of all screenings were within reference range, and no sign of systemic sarcoidosis was found. She was treated with hydrocortisone ointment 2.5% for several weeks without notable improvement. She elected not to pursue any additional treatment and to monitor the symptoms with close follow-up only. One year after the initial visit, the skin lesions spontaneously and notably improved.
Sarcoidosis is a systemic granulomatous disorder of unknown etiology that most commonly affects the lungs. It also can involve the lymph nodes, liver, spleen, bones, gastrointestinal tract, eyes, and skin. Cutaneous sarcoidosis has been documented in the literature since the late 1800s and occurs in up to one-third of sarcoid patients.1 Cutaneous lesions developing within a preexisting scar is a well-known variant, occurring in 29% of patients with cutaneous sarcoidosis in one clinical study (N=818).2 There have been many reports describing scar sarcoidosis, with its development at prior sites of surgery, trauma, acne, or venipuncture.3 Other case reports have described variants of scar sarcoidosis developing at sites of hyaluronic acid injection, laser surgery, ritual scarification, tattoos, and desensitization injections, as well as prior herpes zoster infections.4-9
Cutaneous sarcoidosis has a wide range of clinical presentations. Lesions can be described as specific or nonspecific. Specific lesions demonstrate the typical sarcoid granuloma on histology and more often are seen in chronic disease, while nonspecific lesions more often are seen in acute disease.3,10 Scar sarcoidosis is an example of a specific lesion in which old scars become infiltrated with noncaseating granulomas. The granulomas typically are in the superficial dermis but may involve the full thickness of the dermis, extending into the subcutaneous tissue.11 The cause of granulomas developing in scars is unknown. Prior contamination of the scar with foreign material, possibly at the time of the trauma, is a possible underlying cause.12
Typical scar sarcoidosis presents as swollen, erythematous, indurated lesions with a purple-red hue that may become brown.3,12 Tenderness or pruritus also may be present.13 Interestingly, our patient's scar sarcoidosis presented with a yellow hue at both mastectomy sites.
Diagnosing scar sarcoidosis can be challenging. Patients are diagnosed with sarcoidosis when a compatible clinical or radiologic picture is present along with histologic evidence of a noncaseating granuloma and other potential causes are excluded.11 The differential includes an infectious etiology, other types of granulomatous dermatitis, hypertrophic scar, keloid, or foreign body granuloma.
Scar sarcoidosis can be isolated in occurrence. It also can precede or occur concomitantly or during a relapse of systemic sarcoidosis.10 Most commonly, patients with scar sarcoidosis also have systemic manifestations of sarcoidosis, and changing scars may be an indicator of disease exacerbation or relapse.10 For patients who only demonstrate specific skin lesions of cutaneous sarcoidosis, approximately 30% develop systemic involvement later in life.3 For this reason, close monitoring and regular follow-up are necessary.
Treatment of scar sarcoidosis is dependent on the extent of the disease and presence of systemic sarcoidosis. Topical and systemic corticosteroids, hydroxychloroquine, chloroquine phosphate, and methotrexate all have been shown to be helpful in treating cutaneous sarcoidosis.3 For scar sarcoidosis that is limited to only the scar site, as seen in our case, monitoring and close follow-up is acceptable. Topical steroids can be prescribed for symptomatic relief. Scar sarcoidosis can resolve slowly and spontaneously over time.10 Our patient notably improved 1 year after the initial presentation without treatment.
Scar sarcoidosis is a well-documented variant of cutaneous sarcoidosis that can have important implications for diagnosing systemic sarcoidosis. Although there are typical lesions that represent scar sarcoidosis, it is important to have a high degree of suspicion with any changing scar. Once diagnosed through biopsy, a thorough investigation for systemic signs of sarcoidosis needs to be performed to guide treatment.
- Bolognia JL, Jorizzo JL, Shaffer JV, eds. Dermatology. 3rd ed. Vol 2. Philadelphia, PA: Elsevier/Saunders; 2012.
- Neville E, Walker AN, James DG. Prognostic factors predicting the outcome of sarcoidosis: an analysis of 818 patients. Q J Med. 1983;52:525-533.
- Mañá J, Marcoval J, Graells J, et al. Cutaneous involvement in sarcoidosis: relationship to systemic disease. Arch Dermatol. 1997;133:882-888.
- Dal Sacco D, Cozzani E, Parodi A, et al. Scar sarcoidosis after hyaluronic acid injection. Int J Dermatol. 2005;44:411-412.
- Kormeili T, Neel V, Moy RL. Cutaneous sarcoidosis at sites of previous laser surgery. Cutis. 2004;73:53-55.
- Nayar M. Sarcoidosis on ritual scarification. Int J Dermatol. 1993;32:116-118.
- James WD, Elston DM, Berger TG, et al. Andrews' Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, PA: Elsevier/Saunders; 2011.
- Healsmith MF, Hutchinson PE. The development of scar sarcoidosis at the site of desensitization injections. Clin Exp Dermatol. 1992;17:369-370.
- Singal A, Vij A, Pandhi D. Post herpes-zoster scar sarcoidosis with pulmonary involvement. Indian Dermatol Online J. 2014;5:77-79.
- Chudomirova K, Velichkova L, Anavi B, et al. Recurrent sarcoidosis in skin scars accompanying systemic sarcoidosis. J Eur Acad Dermatol Venereol. 2003;17:360-361.
- Selim A, Ehrsam E, Atassi MB, et al. Scar sarcoidosis: a case report and brief review. Cutis. 2006;78:418-422.
- Singal A, Thami GP, Goraya JS. Scar sarcoidosis in childhood: case report and review of the literature. Clin Exp Dermatol. 2005;30:244-246.
- Marchell RM, Judson MA. Chronic cutaneous lesions of sarcoidosis. Clin Dermatol. 2007;25:295-302.
- Bolognia JL, Jorizzo JL, Shaffer JV, eds. Dermatology. 3rd ed. Vol 2. Philadelphia, PA: Elsevier/Saunders; 2012.
- Neville E, Walker AN, James DG. Prognostic factors predicting the outcome of sarcoidosis: an analysis of 818 patients. Q J Med. 1983;52:525-533.
- Mañá J, Marcoval J, Graells J, et al. Cutaneous involvement in sarcoidosis: relationship to systemic disease. Arch Dermatol. 1997;133:882-888.
- Dal Sacco D, Cozzani E, Parodi A, et al. Scar sarcoidosis after hyaluronic acid injection. Int J Dermatol. 2005;44:411-412.
- Kormeili T, Neel V, Moy RL. Cutaneous sarcoidosis at sites of previous laser surgery. Cutis. 2004;73:53-55.
- Nayar M. Sarcoidosis on ritual scarification. Int J Dermatol. 1993;32:116-118.
- James WD, Elston DM, Berger TG, et al. Andrews' Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, PA: Elsevier/Saunders; 2011.
- Healsmith MF, Hutchinson PE. The development of scar sarcoidosis at the site of desensitization injections. Clin Exp Dermatol. 1992;17:369-370.
- Singal A, Vij A, Pandhi D. Post herpes-zoster scar sarcoidosis with pulmonary involvement. Indian Dermatol Online J. 2014;5:77-79.
- Chudomirova K, Velichkova L, Anavi B, et al. Recurrent sarcoidosis in skin scars accompanying systemic sarcoidosis. J Eur Acad Dermatol Venereol. 2003;17:360-361.
- Selim A, Ehrsam E, Atassi MB, et al. Scar sarcoidosis: a case report and brief review. Cutis. 2006;78:418-422.
- Singal A, Thami GP, Goraya JS. Scar sarcoidosis in childhood: case report and review of the literature. Clin Exp Dermatol. 2005;30:244-246.
- Marchell RM, Judson MA. Chronic cutaneous lesions of sarcoidosis. Clin Dermatol. 2007;25:295-302.
A 57-year-old woman with triple-negative ductal breast cancer presented with a mildly pruritic rash on bilateral mastectomy scars of 3 to 4 months' duration. More than a year prior to presentation, she was diagnosed with breast cancer and treated with a bilateral mastectomy and chemotherapy. On physical examination, faintly yellow, slightly indurated, coalescing papules with red rims were present on the bilateral mastectomy scars, with the scar on the left side appearing worse than the right. She previously had not sought treatment.
Patients describe significant impact of epilepsy on their lives
PHILADELPHIA – said Jacqueline French, MD, a professor at the Comprehensive Epilepsy Center at New York University.
“This underscores the need to consider these experiences, and potentially the stage of disease, when developing patient-reported outcome measures,” she said at the annual meeting of the American Academy of Neurology.
To describe the patient’s experience of living with epilepsy, including the occurrence of disease-related signs and symptoms and impact on daily life at different disease stages, Dr. French conducted qualitative, semistructured interviews with adults with focal epilepsy at the following stages: early (1 year or less since diagnosis), middle (1-5 years since diagnosis), and late (more than 5 years since diagnosis). The patients had varying seizure frequency and treatment experiences. They were asked to describe the symptoms and functional impact they had experienced related to epilepsy, and then to rate the degree to which each symptom and impact “bothered” them, using a disturbance rating scale from 0 (not at all) to 10 (extremely).
A total of 62 patients who were aged 18-60 years (mean age, 37 years; 73% female) were interviewed. In all, 19 of the patients had early-stage disease, 17 had middle-stage, and 26 had late-stage disease. Symptoms reported with the highest frequency and highest average disturbance (AD) ratings across all cohorts included twitching/tremors (80% of patients; AD, 5.3), confusion (78%; AD, 7.8), difficulty talking (75%; AD, 8.1), impaired/loss of consciousness (70%; AD, 6.8), stiffening (65%; AD, 5.4), déjà vu (62%; AD, 5.1), difficulty remembering (60%; AD, 8.5), and dizziness/light-headedness (58%; AD, 6.4).
The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (74%; AD, 7.1), limited ability to work and/or go to school (61%; AD, 6.7), limitations on leisure and social activities (58%; AD, 6.3), and memory loss (47%; AD, 8.4).
Dr French noted that, although disease experiences were similar among the cohorts, some heterogeneity across patient subgroups was observed.
Eisai sponsored the study.
PHILADELPHIA – said Jacqueline French, MD, a professor at the Comprehensive Epilepsy Center at New York University.
“This underscores the need to consider these experiences, and potentially the stage of disease, when developing patient-reported outcome measures,” she said at the annual meeting of the American Academy of Neurology.
To describe the patient’s experience of living with epilepsy, including the occurrence of disease-related signs and symptoms and impact on daily life at different disease stages, Dr. French conducted qualitative, semistructured interviews with adults with focal epilepsy at the following stages: early (1 year or less since diagnosis), middle (1-5 years since diagnosis), and late (more than 5 years since diagnosis). The patients had varying seizure frequency and treatment experiences. They were asked to describe the symptoms and functional impact they had experienced related to epilepsy, and then to rate the degree to which each symptom and impact “bothered” them, using a disturbance rating scale from 0 (not at all) to 10 (extremely).
A total of 62 patients who were aged 18-60 years (mean age, 37 years; 73% female) were interviewed. In all, 19 of the patients had early-stage disease, 17 had middle-stage, and 26 had late-stage disease. Symptoms reported with the highest frequency and highest average disturbance (AD) ratings across all cohorts included twitching/tremors (80% of patients; AD, 5.3), confusion (78%; AD, 7.8), difficulty talking (75%; AD, 8.1), impaired/loss of consciousness (70%; AD, 6.8), stiffening (65%; AD, 5.4), déjà vu (62%; AD, 5.1), difficulty remembering (60%; AD, 8.5), and dizziness/light-headedness (58%; AD, 6.4).
The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (74%; AD, 7.1), limited ability to work and/or go to school (61%; AD, 6.7), limitations on leisure and social activities (58%; AD, 6.3), and memory loss (47%; AD, 8.4).
Dr French noted that, although disease experiences were similar among the cohorts, some heterogeneity across patient subgroups was observed.
Eisai sponsored the study.
PHILADELPHIA – said Jacqueline French, MD, a professor at the Comprehensive Epilepsy Center at New York University.
“This underscores the need to consider these experiences, and potentially the stage of disease, when developing patient-reported outcome measures,” she said at the annual meeting of the American Academy of Neurology.
To describe the patient’s experience of living with epilepsy, including the occurrence of disease-related signs and symptoms and impact on daily life at different disease stages, Dr. French conducted qualitative, semistructured interviews with adults with focal epilepsy at the following stages: early (1 year or less since diagnosis), middle (1-5 years since diagnosis), and late (more than 5 years since diagnosis). The patients had varying seizure frequency and treatment experiences. They were asked to describe the symptoms and functional impact they had experienced related to epilepsy, and then to rate the degree to which each symptom and impact “bothered” them, using a disturbance rating scale from 0 (not at all) to 10 (extremely).
A total of 62 patients who were aged 18-60 years (mean age, 37 years; 73% female) were interviewed. In all, 19 of the patients had early-stage disease, 17 had middle-stage, and 26 had late-stage disease. Symptoms reported with the highest frequency and highest average disturbance (AD) ratings across all cohorts included twitching/tremors (80% of patients; AD, 5.3), confusion (78%; AD, 7.8), difficulty talking (75%; AD, 8.1), impaired/loss of consciousness (70%; AD, 6.8), stiffening (65%; AD, 5.4), déjà vu (62%; AD, 5.1), difficulty remembering (60%; AD, 8.5), and dizziness/light-headedness (58%; AD, 6.4).
The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (74%; AD, 7.1), limited ability to work and/or go to school (61%; AD, 6.7), limitations on leisure and social activities (58%; AD, 6.3), and memory loss (47%; AD, 8.4).
Dr French noted that, although disease experiences were similar among the cohorts, some heterogeneity across patient subgroups was observed.
Eisai sponsored the study.
REPORTING FROM AAN 2019
Key clinical point: Adults with focal epilepsy report a range of high-disturbance symptoms and impacts on daily life.
Major finding: The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (reported by 74% of respondents), limited ability to work and/or go to school (61%), limitations on leisure and social activities (58%), and memory loss (47%).
Study details: Qualitative, semistructured interviews with 62 adults with focal epilepsy at different stages of illness: early, middle, and late.
Disclosures: Eisai sponsored the study.
Physical activity slows cognitive decline in patients with Parkinson’s disease
PHILADELPHIA – according to Sneha Mantri, MD, of Duke University in Durham, N.C., and colleagues, who presented the results of their study at the annual meeting of the American Academy of Neurology.
Physical activity is an important component of the management of Parkinson’s disease and is shown to mitigate cognitive decline among patients with moderate disease, said Dr. Mantri and colleagues. “Exercise levels in de novo and early disease may influence risk of future cognitive decline; early disease also presents an opportunity for early intervention and possible disease modification,” Dr. Mantri said.
Physical activity levels in early disease are known to be low, but the effects of activity on cognition are currently unclear. To assess the relationship between physical activity and cognition, Dr. Mantri and colleagues examined patients with Parkinson’s disease who were enrolled in the prospective Parkinson’s Progression Markers Initiative (PPMI) cohort. At annual study visits, participants completed the Physical Activity Scale for the Elderly (PASE), a validated self-reported questionnaire assessing household, leisure, and work activities over the previous 7 days. The researchers used a linear mixed-effects model to compare rates of change in the Montreal Cognitive Assessment (MoCA) according to PASE scores; covariates included age, sex, Unified Parkinson’s Disease Rating Scale (UPDRS) part III score, and baseline MoCA.
A total of 379 patients completed at least one PASE questionnaire over the course of the study. PASE scores in this cohort have been previously described (Mantri S et al. J Park Dis. 2018;8[1]:107-11). Although overall rates of cognitive decline are known to be modest in this early cohort, PASE over time has a significant effect on MoCA during follow-up (P = 0.02) which suggest that higher levels of activity throughout disease are associated with better cognitive performance.
Dr. Mantri had nothing to disclose. Among her coauthors, Dr. Tropea received personal compensation from Genzyme and Medtronics and research support from Sanofi. Dr. Morley had nothing to disclose.
SOURCE: Mantri S et al. AAN 2019, Abstract P2.8-021.
PHILADELPHIA – according to Sneha Mantri, MD, of Duke University in Durham, N.C., and colleagues, who presented the results of their study at the annual meeting of the American Academy of Neurology.
Physical activity is an important component of the management of Parkinson’s disease and is shown to mitigate cognitive decline among patients with moderate disease, said Dr. Mantri and colleagues. “Exercise levels in de novo and early disease may influence risk of future cognitive decline; early disease also presents an opportunity for early intervention and possible disease modification,” Dr. Mantri said.
Physical activity levels in early disease are known to be low, but the effects of activity on cognition are currently unclear. To assess the relationship between physical activity and cognition, Dr. Mantri and colleagues examined patients with Parkinson’s disease who were enrolled in the prospective Parkinson’s Progression Markers Initiative (PPMI) cohort. At annual study visits, participants completed the Physical Activity Scale for the Elderly (PASE), a validated self-reported questionnaire assessing household, leisure, and work activities over the previous 7 days. The researchers used a linear mixed-effects model to compare rates of change in the Montreal Cognitive Assessment (MoCA) according to PASE scores; covariates included age, sex, Unified Parkinson’s Disease Rating Scale (UPDRS) part III score, and baseline MoCA.
A total of 379 patients completed at least one PASE questionnaire over the course of the study. PASE scores in this cohort have been previously described (Mantri S et al. J Park Dis. 2018;8[1]:107-11). Although overall rates of cognitive decline are known to be modest in this early cohort, PASE over time has a significant effect on MoCA during follow-up (P = 0.02) which suggest that higher levels of activity throughout disease are associated with better cognitive performance.
Dr. Mantri had nothing to disclose. Among her coauthors, Dr. Tropea received personal compensation from Genzyme and Medtronics and research support from Sanofi. Dr. Morley had nothing to disclose.
SOURCE: Mantri S et al. AAN 2019, Abstract P2.8-021.
PHILADELPHIA – according to Sneha Mantri, MD, of Duke University in Durham, N.C., and colleagues, who presented the results of their study at the annual meeting of the American Academy of Neurology.
Physical activity is an important component of the management of Parkinson’s disease and is shown to mitigate cognitive decline among patients with moderate disease, said Dr. Mantri and colleagues. “Exercise levels in de novo and early disease may influence risk of future cognitive decline; early disease also presents an opportunity for early intervention and possible disease modification,” Dr. Mantri said.
Physical activity levels in early disease are known to be low, but the effects of activity on cognition are currently unclear. To assess the relationship between physical activity and cognition, Dr. Mantri and colleagues examined patients with Parkinson’s disease who were enrolled in the prospective Parkinson’s Progression Markers Initiative (PPMI) cohort. At annual study visits, participants completed the Physical Activity Scale for the Elderly (PASE), a validated self-reported questionnaire assessing household, leisure, and work activities over the previous 7 days. The researchers used a linear mixed-effects model to compare rates of change in the Montreal Cognitive Assessment (MoCA) according to PASE scores; covariates included age, sex, Unified Parkinson’s Disease Rating Scale (UPDRS) part III score, and baseline MoCA.
A total of 379 patients completed at least one PASE questionnaire over the course of the study. PASE scores in this cohort have been previously described (Mantri S et al. J Park Dis. 2018;8[1]:107-11). Although overall rates of cognitive decline are known to be modest in this early cohort, PASE over time has a significant effect on MoCA during follow-up (P = 0.02) which suggest that higher levels of activity throughout disease are associated with better cognitive performance.
Dr. Mantri had nothing to disclose. Among her coauthors, Dr. Tropea received personal compensation from Genzyme and Medtronics and research support from Sanofi. Dr. Morley had nothing to disclose.
SOURCE: Mantri S et al. AAN 2019, Abstract P2.8-021.
REPORTING FROM AAN 2019
Key clinical point: Physical activity is associated with slower cognitive decline in patients with de novo Parkinson’s disease.
Major finding: Higher scores on the Physical Activity Scale for the Elderly over time had a significant effect on cognitive function.
Study details: A prospective study of 379 patients enrolled in the Parkinson’s Progression Markers Initiative.
Disclosures: Dr. Mantri had no relevant financial disclosures. Among her coauthors, Dr. Tropea received personal compensation from Genzyme and Medtronics and research support from Sanofi. Dr. Morley had nothing to disclose.
Source: Mantri S et al. AAN 2019, Abstract P2.8-021.
Methylenetetrahydrofolate Reductase Screening in Treatment-Resistant Depression
Therapeutic response to antidepressant drugs is often partial. Multiple trials of medications may be prescribed before a patient achieves remission of symptoms. Further, no universally accepted definition for treatment-resistant depression (TRD) has been established. The most commonly proposed definition (and the definition used in this article) is the failure to achieve remission with 2 or more adequate antidepressant treatments.1
About 20% to 30% of patients with depression are treatment resistant. The overall Canada-wide prevalence of TRD in primary care was 21.7%.2 In the US, about 15.7 million adults have had at least 1 major depressive episode in the past year, and 10% to 15% of major depressive disorder (MDD) cases can be classified as treatment resistant.3,4 In a retrospective, longitudinal cohort analysis in a Medicaid population, 25.9% of pharmacologically treated adults with MDD met criteria for TRD.5 Similarly, TRD in this review was defined as starting a third treatment regimen after 2 adequate regimens of antidepressants.
Why is this important? Treatment resistance is often associated with high rates of disability and comorbidity. Given the significant prevalence and impact of TRD, research into better understanding and treating these patients is paramount. Pharmacogenetics has been proposed for tailoring therapy and theoretically circumventing treatment resistance to achieve better outcomes.
Methylenetetrahydrofolate reductase (MTHFR) is a gene that encodes an enzyme similarly called MTHFR. The enzyme converts 5,10-MTHF to 5-MTHF. 5-MTHF then donates a methyl group in the conversion of homocysteine to methionine. Decreased or absent expression of MTHFR leads to decreased levels of 5-MTHF, which then leads to high levels of homocysteine. This results in suboptimal production of monoamines, including serotonin, dopamine, and norepinephrine as well as subsequent abnormalities in neural and vascular pathways.6
Screening for MTHFR polymorphisms has been proposed in past years due to weak associations with conditions such as cardiac disease, poor pregnancy outcomes, and colorectal cancer.7 Recently, an increasing number of studies suggest screening for MTHFR polymorphisms in patients with depression. This proposal is based on demonstrated links between abnormal folate metabolism and high levels of homocysteine and an increased risk for MDD and reduced antidepressant effectiveness.
In a meta-analysis by Wu and colleagues of 26 published studies, including 4,992 depression cases and 17,082 controls, MTHFR C677T polymorphism was associated with an increased risk of depression especially in Asian populations. This relationship was not observed in the elderly.8 A more recent article reviewing 6 small studies from 2005 to 2016 suggested that the MTHFR A1298C polymorphism (via abnormal homocysteine metabolism and folate cycles) may play a role in identifying those at risk of developing MDD particularly women in white populations.9
As the proposed mechanism of treatment resistance associated with the MTHFR polymorphisms seems to be related to folate metabolism, L-methylfolate supplementation has been recommended. In a 60-day randomized trial of a selective serotonin reuptake inhibitor (SSRI) and L-methylfolate vs SSRI and placebo, patients prescribed an SSRI with L-methylfolate had a greater response rate (reduction of baseline symptoms by at least 50%) that was statistically significant (P = .04) vs patients taking the placebo.10
In primary care and specialty settings, screening patients with TRD for MTHFR polymorphisms has been proposed. LabCorp (Burlington, NC) and Quest Diagnostics (Secaucus, NJ) have a DNA assay that detects C677T and A1298C mutations in the MTHFR gene, using whole blood samples; however, the cost is high. In the DC/Maryland/Virginia region, test cost varies from $390 if the patient requests it from the lab to $325 if requested through an institution that has an account with LabCorp. Although there are little data regarding false positive and false negative rates, 1 source suggested an analytic sensitivity and specificity of 99% for the tests.11
Once obtained, positive screening results may assist in directing next steps in terms of adjunctive or next-line therapies. Given the high price of the test and positive responses with L-methylfolate supplementation thus far, the question remains: Why not supplement patients with TRD with folate and forego screening? For these 2 reasons: The treatment dosage in the studies referenced is 15 mg of L-methylfolate. This dosage is often unavailable over-the-counter and can cost as much as $75 for 90 capsules. Additionally, the high dosage of methylfolate may increase the risk of colon cancer in certain subpopulations, such as those with precancerous lesions.12Although the current data seem promising, further research is needed to explore the benefits of folate supplementation in larger study samples and perhaps other targeted treatment options for patients with TRD with MTHFR gene polymorphisms.
1. McIntyre RS, Filteau MJ, Martin L, et al. Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord. 2014;156:1-7.
2. Rizvi SJ, Grima E, Tan M, et al. Treatment-resistant depression in primary care across Canada. Can J Psychiatry. 2014;59(7):349-357.
3. Stahl SM. Novel therapeutics for depression: L-methylfolate as a trimonoamine modulator and antidepressant-augmenting agent. CNS Spectr. 2007;12(10):739-744.
4. Little A. Treatment-resistant depression. Am Fam Physician. 2009;80(2):167-172.
5. Olfson M, Amos TB, Benson C, McRae J, Marcus SC. Prospective service use and health care costs of Medicaid beneficiaries with treatment resistant depression. J Manag Care Spec Pharm. 2018;24(3):226-236.
6. Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry. 2000;69(2):228-232.
7. Long S, Goldblatt J. MTHFR genetic testing: controversy and clinical implications. Aust Fam Physician. 2016;45(4):237-240.
8. Wu YL, Ding XX, Sun YH, et al. Association between MTHFR C677T polymorphism and depression: an updated meta-analysis of 26 studies. Prog Neuropsychopharmacol Biol Psychiatry. 2013;46:78-85.
9. Cho K, Amin ZM, An J, Rambaran KA, Johnson TB, Alzghari SK. Methylenetetrahydrogolate reductase A1298C polymorphism and major depressive disorder. Cureus. 2017;9(10):e1734.
10. Papakostas GI, Shelton RC, Zajecka JM, et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double blind, parallel-sequential trials. Am J Psychiatry. 2012;169(12):1267-1274.
11. Hickey SE, Curry CJ, Toriello HV. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013;15(2):153-156.
12. Baggott JE, Oster RA, Tamura T. Meta-analysis of cancer risk in folic acid supplementation trials. Cancer Epidemiol. 2012;36(1):78-81.
Therapeutic response to antidepressant drugs is often partial. Multiple trials of medications may be prescribed before a patient achieves remission of symptoms. Further, no universally accepted definition for treatment-resistant depression (TRD) has been established. The most commonly proposed definition (and the definition used in this article) is the failure to achieve remission with 2 or more adequate antidepressant treatments.1
About 20% to 30% of patients with depression are treatment resistant. The overall Canada-wide prevalence of TRD in primary care was 21.7%.2 In the US, about 15.7 million adults have had at least 1 major depressive episode in the past year, and 10% to 15% of major depressive disorder (MDD) cases can be classified as treatment resistant.3,4 In a retrospective, longitudinal cohort analysis in a Medicaid population, 25.9% of pharmacologically treated adults with MDD met criteria for TRD.5 Similarly, TRD in this review was defined as starting a third treatment regimen after 2 adequate regimens of antidepressants.
Why is this important? Treatment resistance is often associated with high rates of disability and comorbidity. Given the significant prevalence and impact of TRD, research into better understanding and treating these patients is paramount. Pharmacogenetics has been proposed for tailoring therapy and theoretically circumventing treatment resistance to achieve better outcomes.
Methylenetetrahydrofolate reductase (MTHFR) is a gene that encodes an enzyme similarly called MTHFR. The enzyme converts 5,10-MTHF to 5-MTHF. 5-MTHF then donates a methyl group in the conversion of homocysteine to methionine. Decreased or absent expression of MTHFR leads to decreased levels of 5-MTHF, which then leads to high levels of homocysteine. This results in suboptimal production of monoamines, including serotonin, dopamine, and norepinephrine as well as subsequent abnormalities in neural and vascular pathways.6
Screening for MTHFR polymorphisms has been proposed in past years due to weak associations with conditions such as cardiac disease, poor pregnancy outcomes, and colorectal cancer.7 Recently, an increasing number of studies suggest screening for MTHFR polymorphisms in patients with depression. This proposal is based on demonstrated links between abnormal folate metabolism and high levels of homocysteine and an increased risk for MDD and reduced antidepressant effectiveness.
In a meta-analysis by Wu and colleagues of 26 published studies, including 4,992 depression cases and 17,082 controls, MTHFR C677T polymorphism was associated with an increased risk of depression especially in Asian populations. This relationship was not observed in the elderly.8 A more recent article reviewing 6 small studies from 2005 to 2016 suggested that the MTHFR A1298C polymorphism (via abnormal homocysteine metabolism and folate cycles) may play a role in identifying those at risk of developing MDD particularly women in white populations.9
As the proposed mechanism of treatment resistance associated with the MTHFR polymorphisms seems to be related to folate metabolism, L-methylfolate supplementation has been recommended. In a 60-day randomized trial of a selective serotonin reuptake inhibitor (SSRI) and L-methylfolate vs SSRI and placebo, patients prescribed an SSRI with L-methylfolate had a greater response rate (reduction of baseline symptoms by at least 50%) that was statistically significant (P = .04) vs patients taking the placebo.10
In primary care and specialty settings, screening patients with TRD for MTHFR polymorphisms has been proposed. LabCorp (Burlington, NC) and Quest Diagnostics (Secaucus, NJ) have a DNA assay that detects C677T and A1298C mutations in the MTHFR gene, using whole blood samples; however, the cost is high. In the DC/Maryland/Virginia region, test cost varies from $390 if the patient requests it from the lab to $325 if requested through an institution that has an account with LabCorp. Although there are little data regarding false positive and false negative rates, 1 source suggested an analytic sensitivity and specificity of 99% for the tests.11
Once obtained, positive screening results may assist in directing next steps in terms of adjunctive or next-line therapies. Given the high price of the test and positive responses with L-methylfolate supplementation thus far, the question remains: Why not supplement patients with TRD with folate and forego screening? For these 2 reasons: The treatment dosage in the studies referenced is 15 mg of L-methylfolate. This dosage is often unavailable over-the-counter and can cost as much as $75 for 90 capsules. Additionally, the high dosage of methylfolate may increase the risk of colon cancer in certain subpopulations, such as those with precancerous lesions.12Although the current data seem promising, further research is needed to explore the benefits of folate supplementation in larger study samples and perhaps other targeted treatment options for patients with TRD with MTHFR gene polymorphisms.
Therapeutic response to antidepressant drugs is often partial. Multiple trials of medications may be prescribed before a patient achieves remission of symptoms. Further, no universally accepted definition for treatment-resistant depression (TRD) has been established. The most commonly proposed definition (and the definition used in this article) is the failure to achieve remission with 2 or more adequate antidepressant treatments.1
About 20% to 30% of patients with depression are treatment resistant. The overall Canada-wide prevalence of TRD in primary care was 21.7%.2 In the US, about 15.7 million adults have had at least 1 major depressive episode in the past year, and 10% to 15% of major depressive disorder (MDD) cases can be classified as treatment resistant.3,4 In a retrospective, longitudinal cohort analysis in a Medicaid population, 25.9% of pharmacologically treated adults with MDD met criteria for TRD.5 Similarly, TRD in this review was defined as starting a third treatment regimen after 2 adequate regimens of antidepressants.
Why is this important? Treatment resistance is often associated with high rates of disability and comorbidity. Given the significant prevalence and impact of TRD, research into better understanding and treating these patients is paramount. Pharmacogenetics has been proposed for tailoring therapy and theoretically circumventing treatment resistance to achieve better outcomes.
Methylenetetrahydrofolate reductase (MTHFR) is a gene that encodes an enzyme similarly called MTHFR. The enzyme converts 5,10-MTHF to 5-MTHF. 5-MTHF then donates a methyl group in the conversion of homocysteine to methionine. Decreased or absent expression of MTHFR leads to decreased levels of 5-MTHF, which then leads to high levels of homocysteine. This results in suboptimal production of monoamines, including serotonin, dopamine, and norepinephrine as well as subsequent abnormalities in neural and vascular pathways.6
Screening for MTHFR polymorphisms has been proposed in past years due to weak associations with conditions such as cardiac disease, poor pregnancy outcomes, and colorectal cancer.7 Recently, an increasing number of studies suggest screening for MTHFR polymorphisms in patients with depression. This proposal is based on demonstrated links between abnormal folate metabolism and high levels of homocysteine and an increased risk for MDD and reduced antidepressant effectiveness.
In a meta-analysis by Wu and colleagues of 26 published studies, including 4,992 depression cases and 17,082 controls, MTHFR C677T polymorphism was associated with an increased risk of depression especially in Asian populations. This relationship was not observed in the elderly.8 A more recent article reviewing 6 small studies from 2005 to 2016 suggested that the MTHFR A1298C polymorphism (via abnormal homocysteine metabolism and folate cycles) may play a role in identifying those at risk of developing MDD particularly women in white populations.9
As the proposed mechanism of treatment resistance associated with the MTHFR polymorphisms seems to be related to folate metabolism, L-methylfolate supplementation has been recommended. In a 60-day randomized trial of a selective serotonin reuptake inhibitor (SSRI) and L-methylfolate vs SSRI and placebo, patients prescribed an SSRI with L-methylfolate had a greater response rate (reduction of baseline symptoms by at least 50%) that was statistically significant (P = .04) vs patients taking the placebo.10
In primary care and specialty settings, screening patients with TRD for MTHFR polymorphisms has been proposed. LabCorp (Burlington, NC) and Quest Diagnostics (Secaucus, NJ) have a DNA assay that detects C677T and A1298C mutations in the MTHFR gene, using whole blood samples; however, the cost is high. In the DC/Maryland/Virginia region, test cost varies from $390 if the patient requests it from the lab to $325 if requested through an institution that has an account with LabCorp. Although there are little data regarding false positive and false negative rates, 1 source suggested an analytic sensitivity and specificity of 99% for the tests.11
Once obtained, positive screening results may assist in directing next steps in terms of adjunctive or next-line therapies. Given the high price of the test and positive responses with L-methylfolate supplementation thus far, the question remains: Why not supplement patients with TRD with folate and forego screening? For these 2 reasons: The treatment dosage in the studies referenced is 15 mg of L-methylfolate. This dosage is often unavailable over-the-counter and can cost as much as $75 for 90 capsules. Additionally, the high dosage of methylfolate may increase the risk of colon cancer in certain subpopulations, such as those with precancerous lesions.12Although the current data seem promising, further research is needed to explore the benefits of folate supplementation in larger study samples and perhaps other targeted treatment options for patients with TRD with MTHFR gene polymorphisms.
1. McIntyre RS, Filteau MJ, Martin L, et al. Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord. 2014;156:1-7.
2. Rizvi SJ, Grima E, Tan M, et al. Treatment-resistant depression in primary care across Canada. Can J Psychiatry. 2014;59(7):349-357.
3. Stahl SM. Novel therapeutics for depression: L-methylfolate as a trimonoamine modulator and antidepressant-augmenting agent. CNS Spectr. 2007;12(10):739-744.
4. Little A. Treatment-resistant depression. Am Fam Physician. 2009;80(2):167-172.
5. Olfson M, Amos TB, Benson C, McRae J, Marcus SC. Prospective service use and health care costs of Medicaid beneficiaries with treatment resistant depression. J Manag Care Spec Pharm. 2018;24(3):226-236.
6. Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry. 2000;69(2):228-232.
7. Long S, Goldblatt J. MTHFR genetic testing: controversy and clinical implications. Aust Fam Physician. 2016;45(4):237-240.
8. Wu YL, Ding XX, Sun YH, et al. Association between MTHFR C677T polymorphism and depression: an updated meta-analysis of 26 studies. Prog Neuropsychopharmacol Biol Psychiatry. 2013;46:78-85.
9. Cho K, Amin ZM, An J, Rambaran KA, Johnson TB, Alzghari SK. Methylenetetrahydrogolate reductase A1298C polymorphism and major depressive disorder. Cureus. 2017;9(10):e1734.
10. Papakostas GI, Shelton RC, Zajecka JM, et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double blind, parallel-sequential trials. Am J Psychiatry. 2012;169(12):1267-1274.
11. Hickey SE, Curry CJ, Toriello HV. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013;15(2):153-156.
12. Baggott JE, Oster RA, Tamura T. Meta-analysis of cancer risk in folic acid supplementation trials. Cancer Epidemiol. 2012;36(1):78-81.
1. McIntyre RS, Filteau MJ, Martin L, et al. Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord. 2014;156:1-7.
2. Rizvi SJ, Grima E, Tan M, et al. Treatment-resistant depression in primary care across Canada. Can J Psychiatry. 2014;59(7):349-357.
3. Stahl SM. Novel therapeutics for depression: L-methylfolate as a trimonoamine modulator and antidepressant-augmenting agent. CNS Spectr. 2007;12(10):739-744.
4. Little A. Treatment-resistant depression. Am Fam Physician. 2009;80(2):167-172.
5. Olfson M, Amos TB, Benson C, McRae J, Marcus SC. Prospective service use and health care costs of Medicaid beneficiaries with treatment resistant depression. J Manag Care Spec Pharm. 2018;24(3):226-236.
6. Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry. 2000;69(2):228-232.
7. Long S, Goldblatt J. MTHFR genetic testing: controversy and clinical implications. Aust Fam Physician. 2016;45(4):237-240.
8. Wu YL, Ding XX, Sun YH, et al. Association between MTHFR C677T polymorphism and depression: an updated meta-analysis of 26 studies. Prog Neuropsychopharmacol Biol Psychiatry. 2013;46:78-85.
9. Cho K, Amin ZM, An J, Rambaran KA, Johnson TB, Alzghari SK. Methylenetetrahydrogolate reductase A1298C polymorphism and major depressive disorder. Cureus. 2017;9(10):e1734.
10. Papakostas GI, Shelton RC, Zajecka JM, et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double blind, parallel-sequential trials. Am J Psychiatry. 2012;169(12):1267-1274.
11. Hickey SE, Curry CJ, Toriello HV. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013;15(2):153-156.
12. Baggott JE, Oster RA, Tamura T. Meta-analysis of cancer risk in folic acid supplementation trials. Cancer Epidemiol. 2012;36(1):78-81.
Can Medicine Bring Good Out of War?
The title of this essay is more often posed as “Is War Good for Medicine?”2 The career VA physician in me, and the daughter and granddaughter of combat veterans, finds this question historically accurate, but ethically problematic. So I have rewritten the question to one that enables us to examine the historic relationship of medical advances and war from a more ethically justifiable posture. I am by no means ascribing to authors of other publications with this title anything but the highest motives of education and edification.
Yet the more I read and thought about the question(s), I realized that the moral assumptions underlying and supporting each concept are significantly different. What led me to that realization was a story my father told me when I was young which in my youthful ignorance I either dismissed or ignored. I now see that the narrative captured a profound truth about how war is not good especially for those who must wage it, but good may come from it for those who now live in peace.
My father was one of the founders of military pediatrics. Surprisingly, pediatricians were valuable members of the military medical forces because of their knowledge of infectious diseases.3 My father had gone in to the then new specialty of pediatrics because in the 1930s, infectious diseases were the primary cause of death in children. Before antibiotics, children would often die of common infections. Service as a combat medical officer in World War II stationed in the European Theater, my father had experience with and access to penicillin. After returning from the war to work in an Army hospital, he and his staff went into the acute pediatric ward and gave the drug to several very sick children, many of whom were likely to die. The next morning on rounds, they noted that many of the children were feeling much better, some even bouncing on their beds.
Perhaps either his telling or my remembering of these events is partly apocryphal, but the reality is that those lethal microbes had no idea what had hit them. Before human physicians overused the new drugs and nature struck back with antibiotic resistance, penicillin seemed miraculous.
Most likely, in 1945 those children would never have been prescribed penicillin, much less survived, if not for the unprecedented and war-driven consortium of industry and government that mass-produced penicillin to treat the troops with infections. Without a doubt then, from the sacrifice and devastation of World War II came the benefits and boons of the antibiotic era—one of the greatest discoveries in medical science.4
Penicillin is but one of legions of scientific discoveries that emerged during wartime. Many of these dramatic improvements, especially those in surgical techniques and emergency medicine, quickly entered the civilian sector. The French surgeon Amboise Paré, for example, revived an old Roman Army practice of using ligatures or tourniquets to stop excessive blood loss, now a staple of emergency responders in disasters. The ambulance services that transported wounded troops to the hospital began on the battlefields of the Civil War.5
These impressive contributions are the direct result of military medicine intended to preserve fighting strength. There are also indirect, although just as revolutionary, efforts of DoD and VA scientists and health care professionals to minimize disability and prevent progression especially of service-connected injuries and illnesses. Among the most groundbreaking is the VA’s 3D-printed artificial lung. I have to admit at first I thought that it was futuristic, but quickly I learned that it was a realistic possibility for the coming decades.6 VA researchers hope the lung will offer a treatment option for patients with chronic obstructive pulmonary disease (COPD), a lung condition more prevalent in veterans than in the civilian population.7 One contributing factor to the increased risk of COPD among former military is the higher rate of smoking among both active duty and veterans than that in the civilian population.8 And the last chain in the link of causation is that smoking is more common in those service members who have posttraumatic stress disorder.9
However, there also is a very dark side to the link between wartime research and medicine—most infamously the Nazi hypothermia experiments conducted at concentration camps. The proposed publication aroused a decades long ethical controversy regarding whether the data should be published, much less used, in research and practice even if it could save the lives of present or future warriors. In 1990, Marcia Angel, MD, then editor-in-chief of the prestigious New England Journal of Medicine, published the information with an accompanying ethical justification. “Finally, refusal to publish the unethical work serves notice to society at large that even scientists do not consider science the primary measure of a civilization. Knowledge, although important, may be less important to a decent society than the way it is obtained.”10 Ethicist Stephen Post writing on behalf of Holocaust victims strenuously disagreed with the decision to publish the research, “Because the Nazi experiments on human beings were so appallingly unethical, it follows, prima facie, that the use of the records is unethical.”11
This debate is key to the distinction between the 2 questions posed at the beginning of this column. Few who have been on a battlefield or who have cared for those who were can suggest or defend that wars should be fought as a catalyst for scientific research or an impetus to medical advancement. Such an instrumentalist view justifies the end of healing with the means of death, which is an intrinsic contradiction that would eventually corrode the integrity of the medical and scientific professions. Conversely, the second question challenges all of us in federal practice to assume a mantle of obligation to take the interventions that enabled combat medicine to save soldiers and apply them to improve the health and save the lives of veterans and civilians alike. It summons scientists laboring in the hundreds of DoD and VA laboratories to use the unparalleled funding and infrastructure of the institutions to develop promising therapeutics to treat the psychological toll and physical cost of war. And finally it charges the citizens whose family and friends have and will serve in uniform to enlist in a political process that enables military medicine and science to achieve the greatest good-health in peace.
1. Remarque EM. All Quiet on the Western Front. New York, NY: Fawcett Books; 1929:228.
2. Connell C. Is war good for medicine: war’s medical legacy? http://sm.stanford.edu/archive/stanmed/2007summer/main.html. Published 2007. Accessed April 18, 2019.
3. Burnett MW, Callahan CW. American pediatricians at war; a legacy of service. Pediatrics. 2012;129(suppl 1):S33-S49.
4. Ligon BL. Penicillin: its discovery and early development. Semin Pediatr Infect Dis. 2004;15(1):52-57.
5. Samuel L. 6 medical innovations that moved from the battlefield to mainstream medicine. https://www.scientificamercan.com/article/6-medical-innovations-that-moved-from-the-battlefield-to-mainstream-medicine. Published November 11, 2017. Accessed April 18, 2019.
6. Richman M. Breathing easier. https://www.research.va.gov/currents/0818-Researchers-strive-to-make-3D-printed-artificial-lung-to-help-Vets-with-respiratory-disease.cfm. Published August 1, 2018. Accessed April 18, 2019.
7. Murphy DE, Chaudry Z, Almoosa KF, Panos RJ. High prevalence of chronic obstructive pulmonary disease among veterans in the urban Midwest. Mill Med. 2011;176(5):552-560.
8. Thompson WH, St-Hilaire C. Prevalence of chronic obstructive pulmonary disease and tobacco use in veterans at Boise Veterans Affairs Medical Center. Respir Care. 2010;55(5):555-560.
9. Cook J, Jakupcak M, Rosenheck R, Fontana A, McFall M. Influence of PTSD symptom clusters on smoking status among help-seeking Iraq and Afghanistan veterans. Nicotine Tob Res. 2009;11(10):1189-1195.
10. Angell M. The Nazi hypothermia experiments and unethical research today. N Eng J Med 1990;322(20):1462-1464.
11. Post SG. The echo of Nuremberg: Nazi data and ethics. J Med Ethics. 1991;17(1):42-44.
The title of this essay is more often posed as “Is War Good for Medicine?”2 The career VA physician in me, and the daughter and granddaughter of combat veterans, finds this question historically accurate, but ethically problematic. So I have rewritten the question to one that enables us to examine the historic relationship of medical advances and war from a more ethically justifiable posture. I am by no means ascribing to authors of other publications with this title anything but the highest motives of education and edification.
Yet the more I read and thought about the question(s), I realized that the moral assumptions underlying and supporting each concept are significantly different. What led me to that realization was a story my father told me when I was young which in my youthful ignorance I either dismissed or ignored. I now see that the narrative captured a profound truth about how war is not good especially for those who must wage it, but good may come from it for those who now live in peace.
My father was one of the founders of military pediatrics. Surprisingly, pediatricians were valuable members of the military medical forces because of their knowledge of infectious diseases.3 My father had gone in to the then new specialty of pediatrics because in the 1930s, infectious diseases were the primary cause of death in children. Before antibiotics, children would often die of common infections. Service as a combat medical officer in World War II stationed in the European Theater, my father had experience with and access to penicillin. After returning from the war to work in an Army hospital, he and his staff went into the acute pediatric ward and gave the drug to several very sick children, many of whom were likely to die. The next morning on rounds, they noted that many of the children were feeling much better, some even bouncing on their beds.
Perhaps either his telling or my remembering of these events is partly apocryphal, but the reality is that those lethal microbes had no idea what had hit them. Before human physicians overused the new drugs and nature struck back with antibiotic resistance, penicillin seemed miraculous.
Most likely, in 1945 those children would never have been prescribed penicillin, much less survived, if not for the unprecedented and war-driven consortium of industry and government that mass-produced penicillin to treat the troops with infections. Without a doubt then, from the sacrifice and devastation of World War II came the benefits and boons of the antibiotic era—one of the greatest discoveries in medical science.4
Penicillin is but one of legions of scientific discoveries that emerged during wartime. Many of these dramatic improvements, especially those in surgical techniques and emergency medicine, quickly entered the civilian sector. The French surgeon Amboise Paré, for example, revived an old Roman Army practice of using ligatures or tourniquets to stop excessive blood loss, now a staple of emergency responders in disasters. The ambulance services that transported wounded troops to the hospital began on the battlefields of the Civil War.5
These impressive contributions are the direct result of military medicine intended to preserve fighting strength. There are also indirect, although just as revolutionary, efforts of DoD and VA scientists and health care professionals to minimize disability and prevent progression especially of service-connected injuries and illnesses. Among the most groundbreaking is the VA’s 3D-printed artificial lung. I have to admit at first I thought that it was futuristic, but quickly I learned that it was a realistic possibility for the coming decades.6 VA researchers hope the lung will offer a treatment option for patients with chronic obstructive pulmonary disease (COPD), a lung condition more prevalent in veterans than in the civilian population.7 One contributing factor to the increased risk of COPD among former military is the higher rate of smoking among both active duty and veterans than that in the civilian population.8 And the last chain in the link of causation is that smoking is more common in those service members who have posttraumatic stress disorder.9
However, there also is a very dark side to the link between wartime research and medicine—most infamously the Nazi hypothermia experiments conducted at concentration camps. The proposed publication aroused a decades long ethical controversy regarding whether the data should be published, much less used, in research and practice even if it could save the lives of present or future warriors. In 1990, Marcia Angel, MD, then editor-in-chief of the prestigious New England Journal of Medicine, published the information with an accompanying ethical justification. “Finally, refusal to publish the unethical work serves notice to society at large that even scientists do not consider science the primary measure of a civilization. Knowledge, although important, may be less important to a decent society than the way it is obtained.”10 Ethicist Stephen Post writing on behalf of Holocaust victims strenuously disagreed with the decision to publish the research, “Because the Nazi experiments on human beings were so appallingly unethical, it follows, prima facie, that the use of the records is unethical.”11
This debate is key to the distinction between the 2 questions posed at the beginning of this column. Few who have been on a battlefield or who have cared for those who were can suggest or defend that wars should be fought as a catalyst for scientific research or an impetus to medical advancement. Such an instrumentalist view justifies the end of healing with the means of death, which is an intrinsic contradiction that would eventually corrode the integrity of the medical and scientific professions. Conversely, the second question challenges all of us in federal practice to assume a mantle of obligation to take the interventions that enabled combat medicine to save soldiers and apply them to improve the health and save the lives of veterans and civilians alike. It summons scientists laboring in the hundreds of DoD and VA laboratories to use the unparalleled funding and infrastructure of the institutions to develop promising therapeutics to treat the psychological toll and physical cost of war. And finally it charges the citizens whose family and friends have and will serve in uniform to enlist in a political process that enables military medicine and science to achieve the greatest good-health in peace.
The title of this essay is more often posed as “Is War Good for Medicine?”2 The career VA physician in me, and the daughter and granddaughter of combat veterans, finds this question historically accurate, but ethically problematic. So I have rewritten the question to one that enables us to examine the historic relationship of medical advances and war from a more ethically justifiable posture. I am by no means ascribing to authors of other publications with this title anything but the highest motives of education and edification.
Yet the more I read and thought about the question(s), I realized that the moral assumptions underlying and supporting each concept are significantly different. What led me to that realization was a story my father told me when I was young which in my youthful ignorance I either dismissed or ignored. I now see that the narrative captured a profound truth about how war is not good especially for those who must wage it, but good may come from it for those who now live in peace.
My father was one of the founders of military pediatrics. Surprisingly, pediatricians were valuable members of the military medical forces because of their knowledge of infectious diseases.3 My father had gone in to the then new specialty of pediatrics because in the 1930s, infectious diseases were the primary cause of death in children. Before antibiotics, children would often die of common infections. Service as a combat medical officer in World War II stationed in the European Theater, my father had experience with and access to penicillin. After returning from the war to work in an Army hospital, he and his staff went into the acute pediatric ward and gave the drug to several very sick children, many of whom were likely to die. The next morning on rounds, they noted that many of the children were feeling much better, some even bouncing on their beds.
Perhaps either his telling or my remembering of these events is partly apocryphal, but the reality is that those lethal microbes had no idea what had hit them. Before human physicians overused the new drugs and nature struck back with antibiotic resistance, penicillin seemed miraculous.
Most likely, in 1945 those children would never have been prescribed penicillin, much less survived, if not for the unprecedented and war-driven consortium of industry and government that mass-produced penicillin to treat the troops with infections. Without a doubt then, from the sacrifice and devastation of World War II came the benefits and boons of the antibiotic era—one of the greatest discoveries in medical science.4
Penicillin is but one of legions of scientific discoveries that emerged during wartime. Many of these dramatic improvements, especially those in surgical techniques and emergency medicine, quickly entered the civilian sector. The French surgeon Amboise Paré, for example, revived an old Roman Army practice of using ligatures or tourniquets to stop excessive blood loss, now a staple of emergency responders in disasters. The ambulance services that transported wounded troops to the hospital began on the battlefields of the Civil War.5
These impressive contributions are the direct result of military medicine intended to preserve fighting strength. There are also indirect, although just as revolutionary, efforts of DoD and VA scientists and health care professionals to minimize disability and prevent progression especially of service-connected injuries and illnesses. Among the most groundbreaking is the VA’s 3D-printed artificial lung. I have to admit at first I thought that it was futuristic, but quickly I learned that it was a realistic possibility for the coming decades.6 VA researchers hope the lung will offer a treatment option for patients with chronic obstructive pulmonary disease (COPD), a lung condition more prevalent in veterans than in the civilian population.7 One contributing factor to the increased risk of COPD among former military is the higher rate of smoking among both active duty and veterans than that in the civilian population.8 And the last chain in the link of causation is that smoking is more common in those service members who have posttraumatic stress disorder.9
However, there also is a very dark side to the link between wartime research and medicine—most infamously the Nazi hypothermia experiments conducted at concentration camps. The proposed publication aroused a decades long ethical controversy regarding whether the data should be published, much less used, in research and practice even if it could save the lives of present or future warriors. In 1990, Marcia Angel, MD, then editor-in-chief of the prestigious New England Journal of Medicine, published the information with an accompanying ethical justification. “Finally, refusal to publish the unethical work serves notice to society at large that even scientists do not consider science the primary measure of a civilization. Knowledge, although important, may be less important to a decent society than the way it is obtained.”10 Ethicist Stephen Post writing on behalf of Holocaust victims strenuously disagreed with the decision to publish the research, “Because the Nazi experiments on human beings were so appallingly unethical, it follows, prima facie, that the use of the records is unethical.”11
This debate is key to the distinction between the 2 questions posed at the beginning of this column. Few who have been on a battlefield or who have cared for those who were can suggest or defend that wars should be fought as a catalyst for scientific research or an impetus to medical advancement. Such an instrumentalist view justifies the end of healing with the means of death, which is an intrinsic contradiction that would eventually corrode the integrity of the medical and scientific professions. Conversely, the second question challenges all of us in federal practice to assume a mantle of obligation to take the interventions that enabled combat medicine to save soldiers and apply them to improve the health and save the lives of veterans and civilians alike. It summons scientists laboring in the hundreds of DoD and VA laboratories to use the unparalleled funding and infrastructure of the institutions to develop promising therapeutics to treat the psychological toll and physical cost of war. And finally it charges the citizens whose family and friends have and will serve in uniform to enlist in a political process that enables military medicine and science to achieve the greatest good-health in peace.
1. Remarque EM. All Quiet on the Western Front. New York, NY: Fawcett Books; 1929:228.
2. Connell C. Is war good for medicine: war’s medical legacy? http://sm.stanford.edu/archive/stanmed/2007summer/main.html. Published 2007. Accessed April 18, 2019.
3. Burnett MW, Callahan CW. American pediatricians at war; a legacy of service. Pediatrics. 2012;129(suppl 1):S33-S49.
4. Ligon BL. Penicillin: its discovery and early development. Semin Pediatr Infect Dis. 2004;15(1):52-57.
5. Samuel L. 6 medical innovations that moved from the battlefield to mainstream medicine. https://www.scientificamercan.com/article/6-medical-innovations-that-moved-from-the-battlefield-to-mainstream-medicine. Published November 11, 2017. Accessed April 18, 2019.
6. Richman M. Breathing easier. https://www.research.va.gov/currents/0818-Researchers-strive-to-make-3D-printed-artificial-lung-to-help-Vets-with-respiratory-disease.cfm. Published August 1, 2018. Accessed April 18, 2019.
7. Murphy DE, Chaudry Z, Almoosa KF, Panos RJ. High prevalence of chronic obstructive pulmonary disease among veterans in the urban Midwest. Mill Med. 2011;176(5):552-560.
8. Thompson WH, St-Hilaire C. Prevalence of chronic obstructive pulmonary disease and tobacco use in veterans at Boise Veterans Affairs Medical Center. Respir Care. 2010;55(5):555-560.
9. Cook J, Jakupcak M, Rosenheck R, Fontana A, McFall M. Influence of PTSD symptom clusters on smoking status among help-seeking Iraq and Afghanistan veterans. Nicotine Tob Res. 2009;11(10):1189-1195.
10. Angell M. The Nazi hypothermia experiments and unethical research today. N Eng J Med 1990;322(20):1462-1464.
11. Post SG. The echo of Nuremberg: Nazi data and ethics. J Med Ethics. 1991;17(1):42-44.
1. Remarque EM. All Quiet on the Western Front. New York, NY: Fawcett Books; 1929:228.
2. Connell C. Is war good for medicine: war’s medical legacy? http://sm.stanford.edu/archive/stanmed/2007summer/main.html. Published 2007. Accessed April 18, 2019.
3. Burnett MW, Callahan CW. American pediatricians at war; a legacy of service. Pediatrics. 2012;129(suppl 1):S33-S49.
4. Ligon BL. Penicillin: its discovery and early development. Semin Pediatr Infect Dis. 2004;15(1):52-57.
5. Samuel L. 6 medical innovations that moved from the battlefield to mainstream medicine. https://www.scientificamercan.com/article/6-medical-innovations-that-moved-from-the-battlefield-to-mainstream-medicine. Published November 11, 2017. Accessed April 18, 2019.
6. Richman M. Breathing easier. https://www.research.va.gov/currents/0818-Researchers-strive-to-make-3D-printed-artificial-lung-to-help-Vets-with-respiratory-disease.cfm. Published August 1, 2018. Accessed April 18, 2019.
7. Murphy DE, Chaudry Z, Almoosa KF, Panos RJ. High prevalence of chronic obstructive pulmonary disease among veterans in the urban Midwest. Mill Med. 2011;176(5):552-560.
8. Thompson WH, St-Hilaire C. Prevalence of chronic obstructive pulmonary disease and tobacco use in veterans at Boise Veterans Affairs Medical Center. Respir Care. 2010;55(5):555-560.
9. Cook J, Jakupcak M, Rosenheck R, Fontana A, McFall M. Influence of PTSD symptom clusters on smoking status among help-seeking Iraq and Afghanistan veterans. Nicotine Tob Res. 2009;11(10):1189-1195.
10. Angell M. The Nazi hypothermia experiments and unethical research today. N Eng J Med 1990;322(20):1462-1464.
11. Post SG. The echo of Nuremberg: Nazi data and ethics. J Med Ethics. 1991;17(1):42-44.
Universal adolescent anxiety screening is feasible in primary care
BALTIMORE – according to a new study.
The findings suggest that implementing a universal anxiety screening for teen patients is feasible and improves detection of patients with anxiety.
“Our providers were able to act on these positive screens and are able to catch a really serious entry-level condition that may have otherwise been missed,” presenter Sarah Malik, MD, a resident at Penn State Children’s Hospital, told attendees at the Pediatric Academic Societies annual meeting. “Hopefully, this will make a really meaningful difference in these kids’ lives, which is, of course, what we all want.”
An estimated 32% of U.S. teens have anxiety, according to the National Institute of Mental Health, and “8.3% of adolescents with anxiety have severe impairment defined by DSM4 criteria,” according to the study’s background information. Yet neither the American Academy of Pediatrics nor the U.S. Preventive Services Task Force has issued recommendations regarding screening for anxiety in teens.
“For this reason, we developed a study in which we implemented and measured the effect of a universal anxiety screening program in the pediatric primary care setting,” Dr Malik said.
The screening intervention took place in a single Penn State Health Children’s Hospital primary care practice in Hershey, Pa., that typically received 37,000 visits a year from 12,500 patients. The practice has 19 attending physicians, 4 nurse practitioners, and 21 residents.
Providers asked patients aged 11-18 years to fill out a nine-question Generalized Anxiety Disorder subscale of the Screen for Child Anxiety Related Disorders (SCARED) during their well-child visits from April 2017 to March 2018. Two-thirds of the patients had private insurance, 80% were white and 8% were black; 10% were Hispanic.
Providers had access to the screening results after nurses transcribed them into electronic medical records. The researchers used EMRs to determine how many patients completed a SCARED at their well-child visit and how many screened positive for anxiety, defined as a score of at least 9/18.
Then the providers compared the prevalence of anxiety 1 year after implementing the routine screening with the prevalence of teens with an ICD-10 anxiety diagnosis within the 36 months before the screening was implemented. The practice’s prevalence of adolescent anxiety was 13.3% 1 year after implementing universal anxiety screening, compared with 9.6% in the previous 3 years (P less than .0001).
Among 2,276 well-child visits for adolescents during the study period, 80% completed a SCARED. Of those who completed the screening, 17% screened positive. The physicians identified 70% of those patients with positive screens (214/306) as having anxiety, and 82% of those patients (n = 176) were diagnosed with anxiety.
About half of those diagnosed with anxiety (n = 93) received one or more interventions: 77 received referrals for counseling, 15 received psychiatric referrals, and 20 were prescribed new anxiety medication.
“We did find that a universal screening program for anxiety is very useful to implement in the primary care setting, and it’s also really effective at identifying adolescents with anxiety symptoms,” Dr. Malik said.
The study’s generalizability is limited by its implementation at a single academic center with integrated behavioral health, and the use of the SCARED, a portion of the GAD scale, is not considered a standard of care.
The researchers used no external funding, and they had no disclosures.
BALTIMORE – according to a new study.
The findings suggest that implementing a universal anxiety screening for teen patients is feasible and improves detection of patients with anxiety.
“Our providers were able to act on these positive screens and are able to catch a really serious entry-level condition that may have otherwise been missed,” presenter Sarah Malik, MD, a resident at Penn State Children’s Hospital, told attendees at the Pediatric Academic Societies annual meeting. “Hopefully, this will make a really meaningful difference in these kids’ lives, which is, of course, what we all want.”
An estimated 32% of U.S. teens have anxiety, according to the National Institute of Mental Health, and “8.3% of adolescents with anxiety have severe impairment defined by DSM4 criteria,” according to the study’s background information. Yet neither the American Academy of Pediatrics nor the U.S. Preventive Services Task Force has issued recommendations regarding screening for anxiety in teens.
“For this reason, we developed a study in which we implemented and measured the effect of a universal anxiety screening program in the pediatric primary care setting,” Dr Malik said.
The screening intervention took place in a single Penn State Health Children’s Hospital primary care practice in Hershey, Pa., that typically received 37,000 visits a year from 12,500 patients. The practice has 19 attending physicians, 4 nurse practitioners, and 21 residents.
Providers asked patients aged 11-18 years to fill out a nine-question Generalized Anxiety Disorder subscale of the Screen for Child Anxiety Related Disorders (SCARED) during their well-child visits from April 2017 to March 2018. Two-thirds of the patients had private insurance, 80% were white and 8% were black; 10% were Hispanic.
Providers had access to the screening results after nurses transcribed them into electronic medical records. The researchers used EMRs to determine how many patients completed a SCARED at their well-child visit and how many screened positive for anxiety, defined as a score of at least 9/18.
Then the providers compared the prevalence of anxiety 1 year after implementing the routine screening with the prevalence of teens with an ICD-10 anxiety diagnosis within the 36 months before the screening was implemented. The practice’s prevalence of adolescent anxiety was 13.3% 1 year after implementing universal anxiety screening, compared with 9.6% in the previous 3 years (P less than .0001).
Among 2,276 well-child visits for adolescents during the study period, 80% completed a SCARED. Of those who completed the screening, 17% screened positive. The physicians identified 70% of those patients with positive screens (214/306) as having anxiety, and 82% of those patients (n = 176) were diagnosed with anxiety.
About half of those diagnosed with anxiety (n = 93) received one or more interventions: 77 received referrals for counseling, 15 received psychiatric referrals, and 20 were prescribed new anxiety medication.
“We did find that a universal screening program for anxiety is very useful to implement in the primary care setting, and it’s also really effective at identifying adolescents with anxiety symptoms,” Dr. Malik said.
The study’s generalizability is limited by its implementation at a single academic center with integrated behavioral health, and the use of the SCARED, a portion of the GAD scale, is not considered a standard of care.
The researchers used no external funding, and they had no disclosures.
BALTIMORE – according to a new study.
The findings suggest that implementing a universal anxiety screening for teen patients is feasible and improves detection of patients with anxiety.
“Our providers were able to act on these positive screens and are able to catch a really serious entry-level condition that may have otherwise been missed,” presenter Sarah Malik, MD, a resident at Penn State Children’s Hospital, told attendees at the Pediatric Academic Societies annual meeting. “Hopefully, this will make a really meaningful difference in these kids’ lives, which is, of course, what we all want.”
An estimated 32% of U.S. teens have anxiety, according to the National Institute of Mental Health, and “8.3% of adolescents with anxiety have severe impairment defined by DSM4 criteria,” according to the study’s background information. Yet neither the American Academy of Pediatrics nor the U.S. Preventive Services Task Force has issued recommendations regarding screening for anxiety in teens.
“For this reason, we developed a study in which we implemented and measured the effect of a universal anxiety screening program in the pediatric primary care setting,” Dr Malik said.
The screening intervention took place in a single Penn State Health Children’s Hospital primary care practice in Hershey, Pa., that typically received 37,000 visits a year from 12,500 patients. The practice has 19 attending physicians, 4 nurse practitioners, and 21 residents.
Providers asked patients aged 11-18 years to fill out a nine-question Generalized Anxiety Disorder subscale of the Screen for Child Anxiety Related Disorders (SCARED) during their well-child visits from April 2017 to March 2018. Two-thirds of the patients had private insurance, 80% were white and 8% were black; 10% were Hispanic.
Providers had access to the screening results after nurses transcribed them into electronic medical records. The researchers used EMRs to determine how many patients completed a SCARED at their well-child visit and how many screened positive for anxiety, defined as a score of at least 9/18.
Then the providers compared the prevalence of anxiety 1 year after implementing the routine screening with the prevalence of teens with an ICD-10 anxiety diagnosis within the 36 months before the screening was implemented. The practice’s prevalence of adolescent anxiety was 13.3% 1 year after implementing universal anxiety screening, compared with 9.6% in the previous 3 years (P less than .0001).
Among 2,276 well-child visits for adolescents during the study period, 80% completed a SCARED. Of those who completed the screening, 17% screened positive. The physicians identified 70% of those patients with positive screens (214/306) as having anxiety, and 82% of those patients (n = 176) were diagnosed with anxiety.
About half of those diagnosed with anxiety (n = 93) received one or more interventions: 77 received referrals for counseling, 15 received psychiatric referrals, and 20 were prescribed new anxiety medication.
“We did find that a universal screening program for anxiety is very useful to implement in the primary care setting, and it’s also really effective at identifying adolescents with anxiety symptoms,” Dr. Malik said.
The study’s generalizability is limited by its implementation at a single academic center with integrated behavioral health, and the use of the SCARED, a portion of the GAD scale, is not considered a standard of care.
The researchers used no external funding, and they had no disclosures.
REPORTING FROM PAS 2019
Key clinical point: Universal anxiety screening for adolescents is feasible and effective in pediatric primary care.
Major finding: Adolescent anxiety diagnoses increased from 9.6% to 13.3% 1 year after university screening (P less than .0001).
Study details: The findings are based on assessment of a universal anxiety screening program implemented at a single academic pediatric primary care practice, involving 2,276 well visits between April 2017 and March 2018 for patients aged 11-18 years.
Disclosures: The researchers used no external funding, and they had no disclosures.