Summer camps need help managing childhood anaphylaxis

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Fri, 01/18/2019 - 16:39

 

– Summer camp personnel need a refresher course on the recognition, treatment, and prevention of allergic reactions in children, according to an online survey of camps in almost 40 U.S. states and Canadian provinces.

There’s a lot of data about how schools handle allergies but almost nothing about summer camps. To fill the gap, the investigators sent surveys across North America to 158 camp directors, 141 camp medical personnel – mostly registered nurses – and 198 camp staffers. Most of the camps were traditional rural affairs where children stay for several weeks, but there were also suburban and city day camps.

M. Alexander Otto/Frontline Medical News
Dr. John Lee
“Parents have questions, but we really didn’t have any data” about what happens at camp, senior investigator John Lee, MD, director of the food allergy program at Boston Children’s Hospital, reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The results weren’t good. About a third of directors and staff, and almost 20% of medical personnel, said they had no education on food allergies. Less than 40% had a good understanding of the different ways that anaphylaxis can present. Less than 80% of camp directors and medical personnel and less than 50% of staff knew the right sequence for anaphylaxis treatment – epinephrine first, followed by a 911 call, and then a call to parents. Many respondents didn’t know the correct injection site for epinephrine.

They also were confused about hand sanitizers versus soap and water. Many mistakenly thought that sanitizers were as good as washing for removing allergens. “Their knowledge about how to clean tables and clean hands of food allergens was limited,” said lead investigator Margaret T. Redmond, MD, an allergist at Nationwide Children’s Hospital in Columbus, Ohio.

Dr. Margaret T. Redmond
Meanwhile, less than half of camp directors said they required a food allergy action plan, and about 20% of camps didn’t have epinephrine on site. About a third let children go on day trips without their autoinjectors. About a fifth of camps said it would take more than 10 minutes for an anaphylactic child to get an epinephrine shot.

It all points to the need for education. “We were surprised at the poor recognition of anaphylactic symptoms. We are trying to identify the weaknesses in camps for targeted interventions. We know from the school data that, with education, people can change,” Dr. Redmond said.

During the 2016 summer session, 51 camps agreed to report epinephrine. Most were rural, with an average of 150 campers per day staying a median of 51 days. There were 12 epinephrine shots over that time, about half for peanut reactions and the rest for bee, wasp, and fire ant stings. None of the children died.

“Families that have kids with food allergies should reach out to camps about their policies and make sure they have epinephrine available at all times and that they have food allergy action plans” that staff know about, Dr. Redmond said.

The work was funded by Mylan and kaleo, both makers of epinephrine autoinjectors. Dr. Lee and Dr. Redmond had no relevant financial disclosures.

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– Summer camp personnel need a refresher course on the recognition, treatment, and prevention of allergic reactions in children, according to an online survey of camps in almost 40 U.S. states and Canadian provinces.

There’s a lot of data about how schools handle allergies but almost nothing about summer camps. To fill the gap, the investigators sent surveys across North America to 158 camp directors, 141 camp medical personnel – mostly registered nurses – and 198 camp staffers. Most of the camps were traditional rural affairs where children stay for several weeks, but there were also suburban and city day camps.

M. Alexander Otto/Frontline Medical News
Dr. John Lee
“Parents have questions, but we really didn’t have any data” about what happens at camp, senior investigator John Lee, MD, director of the food allergy program at Boston Children’s Hospital, reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The results weren’t good. About a third of directors and staff, and almost 20% of medical personnel, said they had no education on food allergies. Less than 40% had a good understanding of the different ways that anaphylaxis can present. Less than 80% of camp directors and medical personnel and less than 50% of staff knew the right sequence for anaphylaxis treatment – epinephrine first, followed by a 911 call, and then a call to parents. Many respondents didn’t know the correct injection site for epinephrine.

They also were confused about hand sanitizers versus soap and water. Many mistakenly thought that sanitizers were as good as washing for removing allergens. “Their knowledge about how to clean tables and clean hands of food allergens was limited,” said lead investigator Margaret T. Redmond, MD, an allergist at Nationwide Children’s Hospital in Columbus, Ohio.

Dr. Margaret T. Redmond
Meanwhile, less than half of camp directors said they required a food allergy action plan, and about 20% of camps didn’t have epinephrine on site. About a third let children go on day trips without their autoinjectors. About a fifth of camps said it would take more than 10 minutes for an anaphylactic child to get an epinephrine shot.

It all points to the need for education. “We were surprised at the poor recognition of anaphylactic symptoms. We are trying to identify the weaknesses in camps for targeted interventions. We know from the school data that, with education, people can change,” Dr. Redmond said.

During the 2016 summer session, 51 camps agreed to report epinephrine. Most were rural, with an average of 150 campers per day staying a median of 51 days. There were 12 epinephrine shots over that time, about half for peanut reactions and the rest for bee, wasp, and fire ant stings. None of the children died.

“Families that have kids with food allergies should reach out to camps about their policies and make sure they have epinephrine available at all times and that they have food allergy action plans” that staff know about, Dr. Redmond said.

The work was funded by Mylan and kaleo, both makers of epinephrine autoinjectors. Dr. Lee and Dr. Redmond had no relevant financial disclosures.

 

– Summer camp personnel need a refresher course on the recognition, treatment, and prevention of allergic reactions in children, according to an online survey of camps in almost 40 U.S. states and Canadian provinces.

There’s a lot of data about how schools handle allergies but almost nothing about summer camps. To fill the gap, the investigators sent surveys across North America to 158 camp directors, 141 camp medical personnel – mostly registered nurses – and 198 camp staffers. Most of the camps were traditional rural affairs where children stay for several weeks, but there were also suburban and city day camps.

M. Alexander Otto/Frontline Medical News
Dr. John Lee
“Parents have questions, but we really didn’t have any data” about what happens at camp, senior investigator John Lee, MD, director of the food allergy program at Boston Children’s Hospital, reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The results weren’t good. About a third of directors and staff, and almost 20% of medical personnel, said they had no education on food allergies. Less than 40% had a good understanding of the different ways that anaphylaxis can present. Less than 80% of camp directors and medical personnel and less than 50% of staff knew the right sequence for anaphylaxis treatment – epinephrine first, followed by a 911 call, and then a call to parents. Many respondents didn’t know the correct injection site for epinephrine.

They also were confused about hand sanitizers versus soap and water. Many mistakenly thought that sanitizers were as good as washing for removing allergens. “Their knowledge about how to clean tables and clean hands of food allergens was limited,” said lead investigator Margaret T. Redmond, MD, an allergist at Nationwide Children’s Hospital in Columbus, Ohio.

Dr. Margaret T. Redmond
Meanwhile, less than half of camp directors said they required a food allergy action plan, and about 20% of camps didn’t have epinephrine on site. About a third let children go on day trips without their autoinjectors. About a fifth of camps said it would take more than 10 minutes for an anaphylactic child to get an epinephrine shot.

It all points to the need for education. “We were surprised at the poor recognition of anaphylactic symptoms. We are trying to identify the weaknesses in camps for targeted interventions. We know from the school data that, with education, people can change,” Dr. Redmond said.

During the 2016 summer session, 51 camps agreed to report epinephrine. Most were rural, with an average of 150 campers per day staying a median of 51 days. There were 12 epinephrine shots over that time, about half for peanut reactions and the rest for bee, wasp, and fire ant stings. None of the children died.

“Families that have kids with food allergies should reach out to camps about their policies and make sure they have epinephrine available at all times and that they have food allergy action plans” that staff know about, Dr. Redmond said.

The work was funded by Mylan and kaleo, both makers of epinephrine autoinjectors. Dr. Lee and Dr. Redmond had no relevant financial disclosures.

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Key clinical point: Summer camp personnel need a refresher course on how to recognize, treat, and prevent allergic reactions in children.

Major finding: About a third of directors and camp staff and almost 20% of medical personnel (mostly registered nurses) said they had no previous education on food allergies.

Data source: An online survey of camps in almost 40 U.S. states and Canadian provinces, including almost 500 personnel.

Disclosures: The work was funded by Mylan and kaleo, both makers of epinephrine autoinjectors. Dr. Lee and Dr. Redmond had no relevant financial disclosures.

USPSTF: No recommendation on screening for celiac disease

Low threshold for screening considered “reasonable”
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Changed
Fri, 05/05/2017 - 11:07

 

The current evidence is insufficient for the U.S. Preventive Services Task Force to recommend either for or against routine screening of asymptomatic people for celiac disease, according to a Recommendation Statement published online March 28 in JAMA.

 
Body

 

Even though the current evidence on the effectiveness of screening for celiac disease is scarce or absent, it remains reasonable for clinicians to have a low threshold for testing patients, especially in high-risk populations such as those with an affected family member or a related autoimmune disorder.

This is because most celiac disease is unrecognized, and patients can present with diverse symptoms rather than the classic triad of abdominal pain, diarrhea, and weight loss.

Dr. Joseph A. Murray
As less-invasive testing becomes available and gluten-free diets become more accessible to patients, reducing the burden of diagnosis and treatment, the medical research community must come forward with the data to determine who should be screened and treated and when and how they should be screened.

Rok Seon Choung, MD, and Joseph A. Murray, MD , are in the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn. Dr. Murray reported ties to Alvine Pharmaceuticals, Alba Therapeutics, Celimmune, BioLineRx, and numerous others. Dr. Choung and Dr. Murray made these remarks in an editorial accompanying the USPSTF reports (JAMA. 2017 Mar 28;317:1221-3).

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Even though the current evidence on the effectiveness of screening for celiac disease is scarce or absent, it remains reasonable for clinicians to have a low threshold for testing patients, especially in high-risk populations such as those with an affected family member or a related autoimmune disorder.

This is because most celiac disease is unrecognized, and patients can present with diverse symptoms rather than the classic triad of abdominal pain, diarrhea, and weight loss.

Dr. Joseph A. Murray
As less-invasive testing becomes available and gluten-free diets become more accessible to patients, reducing the burden of diagnosis and treatment, the medical research community must come forward with the data to determine who should be screened and treated and when and how they should be screened.

Rok Seon Choung, MD, and Joseph A. Murray, MD , are in the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn. Dr. Murray reported ties to Alvine Pharmaceuticals, Alba Therapeutics, Celimmune, BioLineRx, and numerous others. Dr. Choung and Dr. Murray made these remarks in an editorial accompanying the USPSTF reports (JAMA. 2017 Mar 28;317:1221-3).

Body

 

Even though the current evidence on the effectiveness of screening for celiac disease is scarce or absent, it remains reasonable for clinicians to have a low threshold for testing patients, especially in high-risk populations such as those with an affected family member or a related autoimmune disorder.

This is because most celiac disease is unrecognized, and patients can present with diverse symptoms rather than the classic triad of abdominal pain, diarrhea, and weight loss.

Dr. Joseph A. Murray
As less-invasive testing becomes available and gluten-free diets become more accessible to patients, reducing the burden of diagnosis and treatment, the medical research community must come forward with the data to determine who should be screened and treated and when and how they should be screened.

Rok Seon Choung, MD, and Joseph A. Murray, MD , are in the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn. Dr. Murray reported ties to Alvine Pharmaceuticals, Alba Therapeutics, Celimmune, BioLineRx, and numerous others. Dr. Choung and Dr. Murray made these remarks in an editorial accompanying the USPSTF reports (JAMA. 2017 Mar 28;317:1221-3).

Title
Low threshold for screening considered “reasonable”
Low threshold for screening considered “reasonable”

 

The current evidence is insufficient for the U.S. Preventive Services Task Force to recommend either for or against routine screening of asymptomatic people for celiac disease, according to a Recommendation Statement published online March 28 in JAMA.

 

 

The current evidence is insufficient for the U.S. Preventive Services Task Force to recommend either for or against routine screening of asymptomatic people for celiac disease, according to a Recommendation Statement published online March 28 in JAMA.

 
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FROM JAMA

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Key clinical point: The current evidence is insufficient for the USPSTF to recommend either for or against routine screening of asymptomatic people for celiac disease.

Major finding: Only 4 studies out of the 3,036 that were examined addressed the question of screening adequately.

Data source: An assessment of the benefits and harms of screening based on a review of four studies.

Disclosures: The USPSTF’s work is supported by the U.S. Agency for Healthcare Research and Quality. The authors’ financial disclosures are available at www.uspreventiveservicestaskforce.org.

Clotting Protein May Not Improve Hemorrhagic Stroke Outcomes

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Changed
Mon, 01/07/2019 - 10:28
The spot sign, which is visible on routine imaging, may be a good predictor of continued bleeding.

HOUSTON—Acute hemostatic treatment with a clotting protein does not improve short- or long-term outcomes in patients with intracerebral hemorrhage (ICH), according to research presented at the International Stroke Conference 2017.

David Gladstone, MD, PhD
When patients who displayed a high-risk imaging marker suggestive of active bleeding were given recombinant activated blood coagulation factor VII (rFVII), it did not significantly reduce 24-hour hemorrhage volume or improve 90-day stroke outcomes, relative to placebo, said David Gladstone, MD, PhD, Director of the Sunnybrook Regional Stroke Prevention Clinic and Rapid Transient Ischemic Attack Clinic in Toronto.

This is not the first time rFVII has been investigated as an acute treatment for ICH, said Dr. Gladstone. In the large phase III FAST trial, rFVII reduced the growth of hematoma, but did not improve survival or functional outcome in an unselected population.

No medical interventions are available for patients with ICH, and investigators hope to identify a narrower patient population with active bleeding that might be more responsive to rFVII. This goal prompted the initiation of the SPOTLIGHT and STOP-IT studies, said Dr. Gladstone. The former study was Canadian, and the latter American.

Spot Sign Imaging Biomarker

For both studies, researchers stratified patients using the spot sign, a relatively new imaging biomarker thought to reflect active bleeding in the ICH hematoma. The hyperintense signal can easily be seen on cerebral angiography.

“It shows up like a flashlight as a bright spot in the margin of the hematoma,” Dr. Gladstone said. “When we see this, we know this patient has a possible active bleed that is likely to expand and get worse. They are at highest risk for ICH expansion and should be the best candidates for hemostatic therapy.”

Spot-positive patients were randomized to placebo or to a single IV bolus of 80 µg/kg of rFVII given in the emergency department within 6.5 hours of stroke onset. Spot-negative patients were enrolled in a prospective observational cohort, which provided data to support the sign’s use as a predictor of outcome.

Exclusion criteria included brainstem ICH; ICH with secondary cause (eg, tumor or trauma); additional treatments such as plasma or prothrombin; acute coronary ischemia; history of other strokes, angioplasty, or stenting; past thrombotic events; a Glasgow Coma Scale score less than 8; or a modified Rankin Scale (mRS) score more than 2.

These criteria, plus the relative infrequency of ICH events, compared with other cerebrovascular events, made recruitment difficult. After six years, the trials together enrolled 69 spot-positive and 72 spot-negative patients. Both studies were stopped because of the low numbers and insufficient funds.

The studies’ primary efficacy end point was 24-hour ICH volume. Secondary outcomes were 24-hour total ICH plus intraventricular hemorrhage volumes, 90-day mRS of 5 to 6, and comparisons between the spot-negative and spot-positive groups. The primary safety outcome was acute myocardial infarction, ischemic stroke, or pulmonary embolism within four days of treatment.

Results by Spot Status

Patients’ mean age was 70, although spot-positive patients were older than spot-negative patients (71 vs 61). Spot-positive patients were also less likely to have a Glasgow Coma Scale score of 15 to 16 (56% vs 66%). The mean NIH Stroke Scale score was 16 in the spot-positive group and 10 in the spot-negative group. Intraventricular hemorrhage was also more common in the spot-positive group (44% vs 18%).

After researchers adjusted for baseline ICH volume and onset-to-needle time, rFVII exerted no significant effect on either 24-hour ICH volume or 24-hour total volume. In the treated group, median ICH volume increased from 16 mL at baseline to 22 mL by 24 hours. In the placebo group, it increased from 20 mL at baseline to 29 mL at 24 hours.

In the treated group, the median total volume (ICH plus intraventricular hemorrhage) increased from 24 mL at baseline to 26 mL at 24 hours. In the placebo group, it increased from 25 mL at baseline to 31 mL at 24 hours. Researchers did not observe a significant difference between groups in the number of patients who had a volume increase of more than 6 mL or more than 33% (41% vs 43%).

A Predictor of Continued Bleeding

Spot-negative patients had lower baseline and 24-hour total hematoma volumes. In the spot-negative group, total volumes increased from a median of 13 mL at baseline to 14 mL at 24 hours. Significantly fewer spot-negative patients than spot-positive patients had hematoma growth of more than 6 mL or 33% (11% vs 43%).

The spot sign was a good predictor of continued bleeding. In all spot-positive patients, median ICH volume expanded by a median of 9 mL over 24 hours (ie, from 20 mL to 29 mL), compared with a median ICH expansion of 1 mL over 24 hours (ie, from 12 mL to 13 mL) for spot-negative patients.

There were no significant differences in 90-day mRS scores between the treated and placebo groups. One-fifth of each group had a score of 1–2, and one-fifth died. The proportion of patients with mRS scores of 3 to 5 also was similar between the groups.

Despite similar scores, the spot-negative patients had significantly better outcomes. Approximately 38% had an mRS of 0–1 at 90 days. Six percent of this group died.

In addition, treatment time intervals were prolonged in these studies, compared with those that have been achieved with antithrombotic therapy in ischemic stroke. Time from stroke onset to the emergency department was similar in both spot-positive groups taking rFVII and spot-positive controls (64 min and 66 min). Onset-to-CT time was significantly longer in the rFVII patients than in controls (89 min vs 83 min). Door-to-needle time was also longer in the rFVII patients than in controls (104 min vs 87 min), as was onset-to-needle time (195 min vs 161 min).

Thirty-seven percent of spot-positive patients receiving rFVII were treated in less than three hours. This proportion was significantly lower than the 65% that were treated that quickly in the spot-positive placebo group. No significant adverse events were related to rFVII.

 

 

Future Directions

“The spot sign predicted final ICH volume, but the magnitude of ICH expansion was small: less than we expected,” Dr. Gladstone said. “The median absolute ICH volume increase overall was only 2.5 mm, which is surprisingly small for this group of patients. And I do believe that treatment was administered too late, after most of the ICH expansion had already happened.”

Nonetheless, “there is much to learn here,” he said. “The biggest issue is that treatment was just too little, too late. We need to be catching these patients at a much earlier phase to make a difference, and that is probably the largest reason we did not see a difference.

“The spot sign “was a statistically significant predictor of final ICH volumes,” Dr. Gladstone said. It is easy to recognize on an imaging study that is routinely acquired for stroke patients.

“We are also beginning to understand that there are many different types of spot signs associated with different kinds of bleeding at different times,” he said. “We need to understand this variation further, and this should allow us to characterize the patients who are likely to be big bleeders.”

Michelle G. Sullivan

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The spot sign, which is visible on routine imaging, may be a good predictor of continued bleeding.
The spot sign, which is visible on routine imaging, may be a good predictor of continued bleeding.

HOUSTON—Acute hemostatic treatment with a clotting protein does not improve short- or long-term outcomes in patients with intracerebral hemorrhage (ICH), according to research presented at the International Stroke Conference 2017.

David Gladstone, MD, PhD
When patients who displayed a high-risk imaging marker suggestive of active bleeding were given recombinant activated blood coagulation factor VII (rFVII), it did not significantly reduce 24-hour hemorrhage volume or improve 90-day stroke outcomes, relative to placebo, said David Gladstone, MD, PhD, Director of the Sunnybrook Regional Stroke Prevention Clinic and Rapid Transient Ischemic Attack Clinic in Toronto.

This is not the first time rFVII has been investigated as an acute treatment for ICH, said Dr. Gladstone. In the large phase III FAST trial, rFVII reduced the growth of hematoma, but did not improve survival or functional outcome in an unselected population.

No medical interventions are available for patients with ICH, and investigators hope to identify a narrower patient population with active bleeding that might be more responsive to rFVII. This goal prompted the initiation of the SPOTLIGHT and STOP-IT studies, said Dr. Gladstone. The former study was Canadian, and the latter American.

Spot Sign Imaging Biomarker

For both studies, researchers stratified patients using the spot sign, a relatively new imaging biomarker thought to reflect active bleeding in the ICH hematoma. The hyperintense signal can easily be seen on cerebral angiography.

“It shows up like a flashlight as a bright spot in the margin of the hematoma,” Dr. Gladstone said. “When we see this, we know this patient has a possible active bleed that is likely to expand and get worse. They are at highest risk for ICH expansion and should be the best candidates for hemostatic therapy.”

Spot-positive patients were randomized to placebo or to a single IV bolus of 80 µg/kg of rFVII given in the emergency department within 6.5 hours of stroke onset. Spot-negative patients were enrolled in a prospective observational cohort, which provided data to support the sign’s use as a predictor of outcome.

Exclusion criteria included brainstem ICH; ICH with secondary cause (eg, tumor or trauma); additional treatments such as plasma or prothrombin; acute coronary ischemia; history of other strokes, angioplasty, or stenting; past thrombotic events; a Glasgow Coma Scale score less than 8; or a modified Rankin Scale (mRS) score more than 2.

These criteria, plus the relative infrequency of ICH events, compared with other cerebrovascular events, made recruitment difficult. After six years, the trials together enrolled 69 spot-positive and 72 spot-negative patients. Both studies were stopped because of the low numbers and insufficient funds.

The studies’ primary efficacy end point was 24-hour ICH volume. Secondary outcomes were 24-hour total ICH plus intraventricular hemorrhage volumes, 90-day mRS of 5 to 6, and comparisons between the spot-negative and spot-positive groups. The primary safety outcome was acute myocardial infarction, ischemic stroke, or pulmonary embolism within four days of treatment.

Results by Spot Status

Patients’ mean age was 70, although spot-positive patients were older than spot-negative patients (71 vs 61). Spot-positive patients were also less likely to have a Glasgow Coma Scale score of 15 to 16 (56% vs 66%). The mean NIH Stroke Scale score was 16 in the spot-positive group and 10 in the spot-negative group. Intraventricular hemorrhage was also more common in the spot-positive group (44% vs 18%).

After researchers adjusted for baseline ICH volume and onset-to-needle time, rFVII exerted no significant effect on either 24-hour ICH volume or 24-hour total volume. In the treated group, median ICH volume increased from 16 mL at baseline to 22 mL by 24 hours. In the placebo group, it increased from 20 mL at baseline to 29 mL at 24 hours.

In the treated group, the median total volume (ICH plus intraventricular hemorrhage) increased from 24 mL at baseline to 26 mL at 24 hours. In the placebo group, it increased from 25 mL at baseline to 31 mL at 24 hours. Researchers did not observe a significant difference between groups in the number of patients who had a volume increase of more than 6 mL or more than 33% (41% vs 43%).

A Predictor of Continued Bleeding

Spot-negative patients had lower baseline and 24-hour total hematoma volumes. In the spot-negative group, total volumes increased from a median of 13 mL at baseline to 14 mL at 24 hours. Significantly fewer spot-negative patients than spot-positive patients had hematoma growth of more than 6 mL or 33% (11% vs 43%).

The spot sign was a good predictor of continued bleeding. In all spot-positive patients, median ICH volume expanded by a median of 9 mL over 24 hours (ie, from 20 mL to 29 mL), compared with a median ICH expansion of 1 mL over 24 hours (ie, from 12 mL to 13 mL) for spot-negative patients.

There were no significant differences in 90-day mRS scores between the treated and placebo groups. One-fifth of each group had a score of 1–2, and one-fifth died. The proportion of patients with mRS scores of 3 to 5 also was similar between the groups.

Despite similar scores, the spot-negative patients had significantly better outcomes. Approximately 38% had an mRS of 0–1 at 90 days. Six percent of this group died.

In addition, treatment time intervals were prolonged in these studies, compared with those that have been achieved with antithrombotic therapy in ischemic stroke. Time from stroke onset to the emergency department was similar in both spot-positive groups taking rFVII and spot-positive controls (64 min and 66 min). Onset-to-CT time was significantly longer in the rFVII patients than in controls (89 min vs 83 min). Door-to-needle time was also longer in the rFVII patients than in controls (104 min vs 87 min), as was onset-to-needle time (195 min vs 161 min).

Thirty-seven percent of spot-positive patients receiving rFVII were treated in less than three hours. This proportion was significantly lower than the 65% that were treated that quickly in the spot-positive placebo group. No significant adverse events were related to rFVII.

 

 

Future Directions

“The spot sign predicted final ICH volume, but the magnitude of ICH expansion was small: less than we expected,” Dr. Gladstone said. “The median absolute ICH volume increase overall was only 2.5 mm, which is surprisingly small for this group of patients. And I do believe that treatment was administered too late, after most of the ICH expansion had already happened.”

Nonetheless, “there is much to learn here,” he said. “The biggest issue is that treatment was just too little, too late. We need to be catching these patients at a much earlier phase to make a difference, and that is probably the largest reason we did not see a difference.

“The spot sign “was a statistically significant predictor of final ICH volumes,” Dr. Gladstone said. It is easy to recognize on an imaging study that is routinely acquired for stroke patients.

“We are also beginning to understand that there are many different types of spot signs associated with different kinds of bleeding at different times,” he said. “We need to understand this variation further, and this should allow us to characterize the patients who are likely to be big bleeders.”

Michelle G. Sullivan

HOUSTON—Acute hemostatic treatment with a clotting protein does not improve short- or long-term outcomes in patients with intracerebral hemorrhage (ICH), according to research presented at the International Stroke Conference 2017.

David Gladstone, MD, PhD
When patients who displayed a high-risk imaging marker suggestive of active bleeding were given recombinant activated blood coagulation factor VII (rFVII), it did not significantly reduce 24-hour hemorrhage volume or improve 90-day stroke outcomes, relative to placebo, said David Gladstone, MD, PhD, Director of the Sunnybrook Regional Stroke Prevention Clinic and Rapid Transient Ischemic Attack Clinic in Toronto.

This is not the first time rFVII has been investigated as an acute treatment for ICH, said Dr. Gladstone. In the large phase III FAST trial, rFVII reduced the growth of hematoma, but did not improve survival or functional outcome in an unselected population.

No medical interventions are available for patients with ICH, and investigators hope to identify a narrower patient population with active bleeding that might be more responsive to rFVII. This goal prompted the initiation of the SPOTLIGHT and STOP-IT studies, said Dr. Gladstone. The former study was Canadian, and the latter American.

Spot Sign Imaging Biomarker

For both studies, researchers stratified patients using the spot sign, a relatively new imaging biomarker thought to reflect active bleeding in the ICH hematoma. The hyperintense signal can easily be seen on cerebral angiography.

“It shows up like a flashlight as a bright spot in the margin of the hematoma,” Dr. Gladstone said. “When we see this, we know this patient has a possible active bleed that is likely to expand and get worse. They are at highest risk for ICH expansion and should be the best candidates for hemostatic therapy.”

Spot-positive patients were randomized to placebo or to a single IV bolus of 80 µg/kg of rFVII given in the emergency department within 6.5 hours of stroke onset. Spot-negative patients were enrolled in a prospective observational cohort, which provided data to support the sign’s use as a predictor of outcome.

Exclusion criteria included brainstem ICH; ICH with secondary cause (eg, tumor or trauma); additional treatments such as plasma or prothrombin; acute coronary ischemia; history of other strokes, angioplasty, or stenting; past thrombotic events; a Glasgow Coma Scale score less than 8; or a modified Rankin Scale (mRS) score more than 2.

These criteria, plus the relative infrequency of ICH events, compared with other cerebrovascular events, made recruitment difficult. After six years, the trials together enrolled 69 spot-positive and 72 spot-negative patients. Both studies were stopped because of the low numbers and insufficient funds.

The studies’ primary efficacy end point was 24-hour ICH volume. Secondary outcomes were 24-hour total ICH plus intraventricular hemorrhage volumes, 90-day mRS of 5 to 6, and comparisons between the spot-negative and spot-positive groups. The primary safety outcome was acute myocardial infarction, ischemic stroke, or pulmonary embolism within four days of treatment.

Results by Spot Status

Patients’ mean age was 70, although spot-positive patients were older than spot-negative patients (71 vs 61). Spot-positive patients were also less likely to have a Glasgow Coma Scale score of 15 to 16 (56% vs 66%). The mean NIH Stroke Scale score was 16 in the spot-positive group and 10 in the spot-negative group. Intraventricular hemorrhage was also more common in the spot-positive group (44% vs 18%).

After researchers adjusted for baseline ICH volume and onset-to-needle time, rFVII exerted no significant effect on either 24-hour ICH volume or 24-hour total volume. In the treated group, median ICH volume increased from 16 mL at baseline to 22 mL by 24 hours. In the placebo group, it increased from 20 mL at baseline to 29 mL at 24 hours.

In the treated group, the median total volume (ICH plus intraventricular hemorrhage) increased from 24 mL at baseline to 26 mL at 24 hours. In the placebo group, it increased from 25 mL at baseline to 31 mL at 24 hours. Researchers did not observe a significant difference between groups in the number of patients who had a volume increase of more than 6 mL or more than 33% (41% vs 43%).

A Predictor of Continued Bleeding

Spot-negative patients had lower baseline and 24-hour total hematoma volumes. In the spot-negative group, total volumes increased from a median of 13 mL at baseline to 14 mL at 24 hours. Significantly fewer spot-negative patients than spot-positive patients had hematoma growth of more than 6 mL or 33% (11% vs 43%).

The spot sign was a good predictor of continued bleeding. In all spot-positive patients, median ICH volume expanded by a median of 9 mL over 24 hours (ie, from 20 mL to 29 mL), compared with a median ICH expansion of 1 mL over 24 hours (ie, from 12 mL to 13 mL) for spot-negative patients.

There were no significant differences in 90-day mRS scores between the treated and placebo groups. One-fifth of each group had a score of 1–2, and one-fifth died. The proportion of patients with mRS scores of 3 to 5 also was similar between the groups.

Despite similar scores, the spot-negative patients had significantly better outcomes. Approximately 38% had an mRS of 0–1 at 90 days. Six percent of this group died.

In addition, treatment time intervals were prolonged in these studies, compared with those that have been achieved with antithrombotic therapy in ischemic stroke. Time from stroke onset to the emergency department was similar in both spot-positive groups taking rFVII and spot-positive controls (64 min and 66 min). Onset-to-CT time was significantly longer in the rFVII patients than in controls (89 min vs 83 min). Door-to-needle time was also longer in the rFVII patients than in controls (104 min vs 87 min), as was onset-to-needle time (195 min vs 161 min).

Thirty-seven percent of spot-positive patients receiving rFVII were treated in less than three hours. This proportion was significantly lower than the 65% that were treated that quickly in the spot-positive placebo group. No significant adverse events were related to rFVII.

 

 

Future Directions

“The spot sign predicted final ICH volume, but the magnitude of ICH expansion was small: less than we expected,” Dr. Gladstone said. “The median absolute ICH volume increase overall was only 2.5 mm, which is surprisingly small for this group of patients. And I do believe that treatment was administered too late, after most of the ICH expansion had already happened.”

Nonetheless, “there is much to learn here,” he said. “The biggest issue is that treatment was just too little, too late. We need to be catching these patients at a much earlier phase to make a difference, and that is probably the largest reason we did not see a difference.

“The spot sign “was a statistically significant predictor of final ICH volumes,” Dr. Gladstone said. It is easy to recognize on an imaging study that is routinely acquired for stroke patients.

“We are also beginning to understand that there are many different types of spot signs associated with different kinds of bleeding at different times,” he said. “We need to understand this variation further, and this should allow us to characterize the patients who are likely to be big bleeders.”

Michelle G. Sullivan

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PPI-responsive eosinophilic esophagitis may be misnomer

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PHILADELPHIA – Eosinophilic esophagitis (EoE) responsive to a proton pump inhibitor (PPI) has been characterized as PPI-responsive esophageal eosinophilia (PPI-REE), but there is no compelling evidence that it is a distinct EoE subgroup, according to an expert who updated current thinking about this disease at Digestive Diseases: New Advances.

Dr. Stuart Spechler
The substantial response in EoE patients to PPI therapy, which is nearly 50% in some studies, has been a source of confusion. PPIs reduce gastric acid, but EoE is not an acid-related disease, according to Dr. Spechler. The picture is now becoming clearer with new evidence that PPIs do more. Dr. Spechler reviewed evidence that PPIs inhibit inflammatory cells, exert antioxidant properties, and decrease the inflammatory cytokine signaling that drives eosinophil activation and adhesion.

Although it is true that only a subset of EoE patients respond to PPIs, few therapies are effective for all patients in any disease Dr. Spechler observed. As an example, he noted that ulcerative colitis patients who respond to sulfasalazine are not subclassified as sulfasalazine-responsive ulcerative colitis.

“I do think the term PPI-REE should be retired, although I acknowledge that not everyone in this field is ready to agree,” Dr. Spechler said at the meeting, held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.

The confusion regarding PPI responsiveness in EoE has been driven by the fact that acid control has been widely regarded as the only pertinent mechanism of action from PPIs. Although coexisting gastroesophageal reflux disease could explain symptom relief in some patients with EoE, no evidence of excess acid is found in many responders. Detailed evaluations of the PPI-REE subgroup relative to EOE overall emphasize this point, according to Dr. Spechler.

“Studies have shown that the clinical, endoscopic, histologic, and gene expression features of these two disorders are identical,” he reported.

The lack of distinction is now easier to understand with a growing body of evidence that PPIs have acid-independent effects relevant to benefit in EoE, according to Dr. Spechler. Tracing the advances in understanding the pathogenesis in EoE since it was first described in 1978, Dr. Spechler explained that EoE is now understood to be an antigen-driven expression of food allergy related to up-regulation of the Th2 helper adaptive response. After briefly reviewing several potential anti-inflammatory effects of PPIs, Dr. Spechler focused on evidence that PPIs inhibit the adhesion molecule eotaxin-3.

Specifically, when squamous cells from EoE patients are exposed to the cytokine interleukin-4 (IL-4), “production of eotaxin-3 is increased dramatically but you can block that cytokine Th2 stimulation with [the PPI] omeprazole,” said Dr. Spechler, citing published work by Edaire Cheng, MD, a researcher with whom he has collaborated at the University of Texas Southwestern Medical School, Dallas. This is a potentially important observation, because up-regulation of eotaxin-3 is considered a critical molecular event for the activation of eosinophils and their migration.

The relative importance of this specific mechanism for explaining the benefits of PPIs in EoE requires additional confirmation, but Dr. Spechler indicated that there is strong evidence of acid-independent effects from PPIs. In fact, in outlining an algorithm for treatment of EoE, he listed a trial of PPIs as a reasonable first choice.

“In my opinion, the major reason that we created an arbitrary distinction is this persistent notion that acid inhibition is the only possible therapeutic effect of PPIs,” Dr. Spechler reported. “I hope I have convinced you otherwise.”

In his brief update of EoE treatment in 2017, Dr. Spechler identified a trial of PPIs as first line “simply because they work.” However PPIs have been rendered even more attractive by the evidence of a plausible mechanism of action in EoE. Conversely, he cautioned that steroids are “just a band-aid” because “they cover up the allergy but the allergy remains.” Ultimately, while PPIs are a reasonable first-line therapy to control symptoms, Dr. Spechler suggested that elimination diets are ultimately the best strategy for treating the underlying cause of EoE.

Dr. Spechler reported a financial relationship with Ironwood Pharmaceuticals.

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PHILADELPHIA – Eosinophilic esophagitis (EoE) responsive to a proton pump inhibitor (PPI) has been characterized as PPI-responsive esophageal eosinophilia (PPI-REE), but there is no compelling evidence that it is a distinct EoE subgroup, according to an expert who updated current thinking about this disease at Digestive Diseases: New Advances.

Dr. Stuart Spechler
The substantial response in EoE patients to PPI therapy, which is nearly 50% in some studies, has been a source of confusion. PPIs reduce gastric acid, but EoE is not an acid-related disease, according to Dr. Spechler. The picture is now becoming clearer with new evidence that PPIs do more. Dr. Spechler reviewed evidence that PPIs inhibit inflammatory cells, exert antioxidant properties, and decrease the inflammatory cytokine signaling that drives eosinophil activation and adhesion.

Although it is true that only a subset of EoE patients respond to PPIs, few therapies are effective for all patients in any disease Dr. Spechler observed. As an example, he noted that ulcerative colitis patients who respond to sulfasalazine are not subclassified as sulfasalazine-responsive ulcerative colitis.

“I do think the term PPI-REE should be retired, although I acknowledge that not everyone in this field is ready to agree,” Dr. Spechler said at the meeting, held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.

The confusion regarding PPI responsiveness in EoE has been driven by the fact that acid control has been widely regarded as the only pertinent mechanism of action from PPIs. Although coexisting gastroesophageal reflux disease could explain symptom relief in some patients with EoE, no evidence of excess acid is found in many responders. Detailed evaluations of the PPI-REE subgroup relative to EOE overall emphasize this point, according to Dr. Spechler.

“Studies have shown that the clinical, endoscopic, histologic, and gene expression features of these two disorders are identical,” he reported.

The lack of distinction is now easier to understand with a growing body of evidence that PPIs have acid-independent effects relevant to benefit in EoE, according to Dr. Spechler. Tracing the advances in understanding the pathogenesis in EoE since it was first described in 1978, Dr. Spechler explained that EoE is now understood to be an antigen-driven expression of food allergy related to up-regulation of the Th2 helper adaptive response. After briefly reviewing several potential anti-inflammatory effects of PPIs, Dr. Spechler focused on evidence that PPIs inhibit the adhesion molecule eotaxin-3.

Specifically, when squamous cells from EoE patients are exposed to the cytokine interleukin-4 (IL-4), “production of eotaxin-3 is increased dramatically but you can block that cytokine Th2 stimulation with [the PPI] omeprazole,” said Dr. Spechler, citing published work by Edaire Cheng, MD, a researcher with whom he has collaborated at the University of Texas Southwestern Medical School, Dallas. This is a potentially important observation, because up-regulation of eotaxin-3 is considered a critical molecular event for the activation of eosinophils and their migration.

The relative importance of this specific mechanism for explaining the benefits of PPIs in EoE requires additional confirmation, but Dr. Spechler indicated that there is strong evidence of acid-independent effects from PPIs. In fact, in outlining an algorithm for treatment of EoE, he listed a trial of PPIs as a reasonable first choice.

“In my opinion, the major reason that we created an arbitrary distinction is this persistent notion that acid inhibition is the only possible therapeutic effect of PPIs,” Dr. Spechler reported. “I hope I have convinced you otherwise.”

In his brief update of EoE treatment in 2017, Dr. Spechler identified a trial of PPIs as first line “simply because they work.” However PPIs have been rendered even more attractive by the evidence of a plausible mechanism of action in EoE. Conversely, he cautioned that steroids are “just a band-aid” because “they cover up the allergy but the allergy remains.” Ultimately, while PPIs are a reasonable first-line therapy to control symptoms, Dr. Spechler suggested that elimination diets are ultimately the best strategy for treating the underlying cause of EoE.

Dr. Spechler reported a financial relationship with Ironwood Pharmaceuticals.

 

PHILADELPHIA – Eosinophilic esophagitis (EoE) responsive to a proton pump inhibitor (PPI) has been characterized as PPI-responsive esophageal eosinophilia (PPI-REE), but there is no compelling evidence that it is a distinct EoE subgroup, according to an expert who updated current thinking about this disease at Digestive Diseases: New Advances.

Dr. Stuart Spechler
The substantial response in EoE patients to PPI therapy, which is nearly 50% in some studies, has been a source of confusion. PPIs reduce gastric acid, but EoE is not an acid-related disease, according to Dr. Spechler. The picture is now becoming clearer with new evidence that PPIs do more. Dr. Spechler reviewed evidence that PPIs inhibit inflammatory cells, exert antioxidant properties, and decrease the inflammatory cytokine signaling that drives eosinophil activation and adhesion.

Although it is true that only a subset of EoE patients respond to PPIs, few therapies are effective for all patients in any disease Dr. Spechler observed. As an example, he noted that ulcerative colitis patients who respond to sulfasalazine are not subclassified as sulfasalazine-responsive ulcerative colitis.

“I do think the term PPI-REE should be retired, although I acknowledge that not everyone in this field is ready to agree,” Dr. Spechler said at the meeting, held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.

The confusion regarding PPI responsiveness in EoE has been driven by the fact that acid control has been widely regarded as the only pertinent mechanism of action from PPIs. Although coexisting gastroesophageal reflux disease could explain symptom relief in some patients with EoE, no evidence of excess acid is found in many responders. Detailed evaluations of the PPI-REE subgroup relative to EOE overall emphasize this point, according to Dr. Spechler.

“Studies have shown that the clinical, endoscopic, histologic, and gene expression features of these two disorders are identical,” he reported.

The lack of distinction is now easier to understand with a growing body of evidence that PPIs have acid-independent effects relevant to benefit in EoE, according to Dr. Spechler. Tracing the advances in understanding the pathogenesis in EoE since it was first described in 1978, Dr. Spechler explained that EoE is now understood to be an antigen-driven expression of food allergy related to up-regulation of the Th2 helper adaptive response. After briefly reviewing several potential anti-inflammatory effects of PPIs, Dr. Spechler focused on evidence that PPIs inhibit the adhesion molecule eotaxin-3.

Specifically, when squamous cells from EoE patients are exposed to the cytokine interleukin-4 (IL-4), “production of eotaxin-3 is increased dramatically but you can block that cytokine Th2 stimulation with [the PPI] omeprazole,” said Dr. Spechler, citing published work by Edaire Cheng, MD, a researcher with whom he has collaborated at the University of Texas Southwestern Medical School, Dallas. This is a potentially important observation, because up-regulation of eotaxin-3 is considered a critical molecular event for the activation of eosinophils and their migration.

The relative importance of this specific mechanism for explaining the benefits of PPIs in EoE requires additional confirmation, but Dr. Spechler indicated that there is strong evidence of acid-independent effects from PPIs. In fact, in outlining an algorithm for treatment of EoE, he listed a trial of PPIs as a reasonable first choice.

“In my opinion, the major reason that we created an arbitrary distinction is this persistent notion that acid inhibition is the only possible therapeutic effect of PPIs,” Dr. Spechler reported. “I hope I have convinced you otherwise.”

In his brief update of EoE treatment in 2017, Dr. Spechler identified a trial of PPIs as first line “simply because they work.” However PPIs have been rendered even more attractive by the evidence of a plausible mechanism of action in EoE. Conversely, he cautioned that steroids are “just a band-aid” because “they cover up the allergy but the allergy remains.” Ultimately, while PPIs are a reasonable first-line therapy to control symptoms, Dr. Spechler suggested that elimination diets are ultimately the best strategy for treating the underlying cause of EoE.

Dr. Spechler reported a financial relationship with Ironwood Pharmaceuticals.

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EXPERT ANALYSIS FROM DIGESTIVE DISEASES: NEW ADVANCES

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Second-Generation Hydrogel Coils May Improve Treatment of Aneurysms

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Compared with platinum coils, hydrogel coils decrease the likelihood of aneurysm recurrence.

HOUSTON—Compared with standard platinum coils, second-generation hydrogel coils decrease the likelihood of adverse outcomes in the endovascular treatment of medium-sized intracranial aneurysms, according to research presented at the International Stroke Conference 2017. Hydrogel coils provide greater packing density and are associated with decreased risks of aneurysm recurrence and retreatment, compared with standard coils, according to the researchers.

Approximately 85% of subarachnoid hemorrhages result from ruptured intracranial aneurysms, which can be detected with CT angiography. A randomized controlled trial published in 2002 demonstrated that endovascular coiling was superior to neurosurgical clipping in the treatment of ruptured aneurysms. A drawback of coiling, however, is that it entails a relatively high rate of aneurysm recurrence. A novel approach adds a soft hydrogel filament into platinum coils. The hydrogel, once in contact with liquid, increases in volume, resulting in a greater fill of the underlying aneurysm.

Christian A. Taschner, MD, PhD
Christian A. Taschner, MD, PhD, Senior Physician in Neuroradiology at University Hospital Freiburg in Germany, and colleagues conducted a prospective randomized trial to evaluate whether treatment of intracranial aneurysms with second-generation hydrogel coils would improve outcomes, compared with treatment with standard platinum coils. The study was conducted at 15 centers in France and seven centers in Germany, and the investigators used a web-based tool to randomize patients to treatment with hydrogel coils or treatment with standard platinum coils. Treatment was open label, and a blinded end point evaluation occurred at 18 months of follow-up. The study’s primary end point was a composite that included major aneurysm recurrence at 18 months, any retreatment within 18 months, morbidity that prevented angiographic follow-up, and death during follow-up.

Between October 2009 and February 2014, Prof. Taschner and colleagues randomized 513 participants, and 29 patients were excluded from the analysis. The analysis included 243 patients treated with hydrogel coils and 241 patients treated with platinum coils. Of this population, 208 participants (43%) were treated for ruptured aneurysms.

Mean packing density was significantly higher in patients treated with hydrogel coils (39%), compared with patients treated with platinum coils (31%). At 18 months, the major recurrence rate was 12% in patients receiving hydrogel coils and 18% in patients receiving platinum coils. The retreatment rate at 18 months was 3% in patients receiving hydrogel coils and 6% in patients receiving platinum coils. The researchers found no difference in modified Rankin Scale score or mortality rate between groups.

In total, 45 patients in the hydrogel coil group and 66 controls had an adverse composite primary outcome. The hydrogel coils thus reduced the proportion of adverse composite primary outcomes, compared with platinum coils, by 8.4%, said Prof. Taschner.

Erik Greb

Suggested Reading

Gaba RC, Ansari SA, Roy SS, et al. Embolization of intracranial aneurysms with hydrogel-coated coils versus inert platinum coils: effects on packing density, coil length and quantity, procedure performance, cost, length of hospital stay, and durability of therapy. Stroke. 2006;37(6):1443-1450.

Molyneux AJ, Kerr RS, Yu LM, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005;366(9488):809-817.

White PM, Lewis SC, Gholkar A, et al. Hydrogel-coated coils versus bare platinum coils for the endovascular treatment of intracranial aneurysms (HELPS): a randomised controlled trial. Lancet. 2011;377(9778):1655-1662.

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Compared with platinum coils, hydrogel coils decrease the likelihood of aneurysm recurrence.
Compared with platinum coils, hydrogel coils decrease the likelihood of aneurysm recurrence.

HOUSTON—Compared with standard platinum coils, second-generation hydrogel coils decrease the likelihood of adverse outcomes in the endovascular treatment of medium-sized intracranial aneurysms, according to research presented at the International Stroke Conference 2017. Hydrogel coils provide greater packing density and are associated with decreased risks of aneurysm recurrence and retreatment, compared with standard coils, according to the researchers.

Approximately 85% of subarachnoid hemorrhages result from ruptured intracranial aneurysms, which can be detected with CT angiography. A randomized controlled trial published in 2002 demonstrated that endovascular coiling was superior to neurosurgical clipping in the treatment of ruptured aneurysms. A drawback of coiling, however, is that it entails a relatively high rate of aneurysm recurrence. A novel approach adds a soft hydrogel filament into platinum coils. The hydrogel, once in contact with liquid, increases in volume, resulting in a greater fill of the underlying aneurysm.

Christian A. Taschner, MD, PhD
Christian A. Taschner, MD, PhD, Senior Physician in Neuroradiology at University Hospital Freiburg in Germany, and colleagues conducted a prospective randomized trial to evaluate whether treatment of intracranial aneurysms with second-generation hydrogel coils would improve outcomes, compared with treatment with standard platinum coils. The study was conducted at 15 centers in France and seven centers in Germany, and the investigators used a web-based tool to randomize patients to treatment with hydrogel coils or treatment with standard platinum coils. Treatment was open label, and a blinded end point evaluation occurred at 18 months of follow-up. The study’s primary end point was a composite that included major aneurysm recurrence at 18 months, any retreatment within 18 months, morbidity that prevented angiographic follow-up, and death during follow-up.

Between October 2009 and February 2014, Prof. Taschner and colleagues randomized 513 participants, and 29 patients were excluded from the analysis. The analysis included 243 patients treated with hydrogel coils and 241 patients treated with platinum coils. Of this population, 208 participants (43%) were treated for ruptured aneurysms.

Mean packing density was significantly higher in patients treated with hydrogel coils (39%), compared with patients treated with platinum coils (31%). At 18 months, the major recurrence rate was 12% in patients receiving hydrogel coils and 18% in patients receiving platinum coils. The retreatment rate at 18 months was 3% in patients receiving hydrogel coils and 6% in patients receiving platinum coils. The researchers found no difference in modified Rankin Scale score or mortality rate between groups.

In total, 45 patients in the hydrogel coil group and 66 controls had an adverse composite primary outcome. The hydrogel coils thus reduced the proportion of adverse composite primary outcomes, compared with platinum coils, by 8.4%, said Prof. Taschner.

Erik Greb

Suggested Reading

Gaba RC, Ansari SA, Roy SS, et al. Embolization of intracranial aneurysms with hydrogel-coated coils versus inert platinum coils: effects on packing density, coil length and quantity, procedure performance, cost, length of hospital stay, and durability of therapy. Stroke. 2006;37(6):1443-1450.

Molyneux AJ, Kerr RS, Yu LM, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005;366(9488):809-817.

White PM, Lewis SC, Gholkar A, et al. Hydrogel-coated coils versus bare platinum coils for the endovascular treatment of intracranial aneurysms (HELPS): a randomised controlled trial. Lancet. 2011;377(9778):1655-1662.

HOUSTON—Compared with standard platinum coils, second-generation hydrogel coils decrease the likelihood of adverse outcomes in the endovascular treatment of medium-sized intracranial aneurysms, according to research presented at the International Stroke Conference 2017. Hydrogel coils provide greater packing density and are associated with decreased risks of aneurysm recurrence and retreatment, compared with standard coils, according to the researchers.

Approximately 85% of subarachnoid hemorrhages result from ruptured intracranial aneurysms, which can be detected with CT angiography. A randomized controlled trial published in 2002 demonstrated that endovascular coiling was superior to neurosurgical clipping in the treatment of ruptured aneurysms. A drawback of coiling, however, is that it entails a relatively high rate of aneurysm recurrence. A novel approach adds a soft hydrogel filament into platinum coils. The hydrogel, once in contact with liquid, increases in volume, resulting in a greater fill of the underlying aneurysm.

Christian A. Taschner, MD, PhD
Christian A. Taschner, MD, PhD, Senior Physician in Neuroradiology at University Hospital Freiburg in Germany, and colleagues conducted a prospective randomized trial to evaluate whether treatment of intracranial aneurysms with second-generation hydrogel coils would improve outcomes, compared with treatment with standard platinum coils. The study was conducted at 15 centers in France and seven centers in Germany, and the investigators used a web-based tool to randomize patients to treatment with hydrogel coils or treatment with standard platinum coils. Treatment was open label, and a blinded end point evaluation occurred at 18 months of follow-up. The study’s primary end point was a composite that included major aneurysm recurrence at 18 months, any retreatment within 18 months, morbidity that prevented angiographic follow-up, and death during follow-up.

Between October 2009 and February 2014, Prof. Taschner and colleagues randomized 513 participants, and 29 patients were excluded from the analysis. The analysis included 243 patients treated with hydrogel coils and 241 patients treated with platinum coils. Of this population, 208 participants (43%) were treated for ruptured aneurysms.

Mean packing density was significantly higher in patients treated with hydrogel coils (39%), compared with patients treated with platinum coils (31%). At 18 months, the major recurrence rate was 12% in patients receiving hydrogel coils and 18% in patients receiving platinum coils. The retreatment rate at 18 months was 3% in patients receiving hydrogel coils and 6% in patients receiving platinum coils. The researchers found no difference in modified Rankin Scale score or mortality rate between groups.

In total, 45 patients in the hydrogel coil group and 66 controls had an adverse composite primary outcome. The hydrogel coils thus reduced the proportion of adverse composite primary outcomes, compared with platinum coils, by 8.4%, said Prof. Taschner.

Erik Greb

Suggested Reading

Gaba RC, Ansari SA, Roy SS, et al. Embolization of intracranial aneurysms with hydrogel-coated coils versus inert platinum coils: effects on packing density, coil length and quantity, procedure performance, cost, length of hospital stay, and durability of therapy. Stroke. 2006;37(6):1443-1450.

Molyneux AJ, Kerr RS, Yu LM, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005;366(9488):809-817.

White PM, Lewis SC, Gholkar A, et al. Hydrogel-coated coils versus bare platinum coils for the endovascular treatment of intracranial aneurysms (HELPS): a randomised controlled trial. Lancet. 2011;377(9778):1655-1662.

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Make the Diagnosis - April 2017

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Trichomycosis axillaris

Trichomycosis axillaris (TA) is a bacterial infection of the genus Corynebacterium that affects hairs in the axilla. Predisposing factors include poor local hygiene, hyperhidrosis, obesity, and warm, humid climates. Gram-positive diphtheroids, classically Corynebacterium tenuis, mix with sweat on hair shafts and subsequently produce a cementing material. In the majority of cases, bacterial infection causes keratin damage to the hair shaft with sparing of the cortex. However, recent cases have reported significant invasion of the hair cortex by bacterial structures.

A presents as malodorous, diaphoretic armpits without other apparent symptoms. Bacterial metabolism of testosterone in the apocrine sweat results in production of compounds that yield an acidic odor. Physical examination reveals small amounts of brown-to-yellow concretions adhered to the central part of the hair shaft. Rarely, red or black nodules can also be found. These concretions give a thickened and beaded appearance to the affected hairs.

TA is often a clinical diagnosis. Histopathology reveals a discontinuous thick-layer coating of bacterial structures adhered to the hair shafts. Periodic acid–Schiff, gram, and Grocott silver stains are all positive. Examination of hairs with 20% hydrogen peroxide solution can provide a microscopic diagnosis. Wood lamp examination produces a weak, yellow fluorescence, and potassium hydroxide test demonstrates yellowish material of minimal translucency surrounding the hair cortex.

Complete resolution can be achieved by shaving off all the axillary hairs. It is imperative to maintain good hygiene and keep the area dry and clean. To prevent recurrence, topical benzoyl peroxide or topical antibiotics such as erythromycin and clindamycin can be applied. If axillary hyperhidrosis is concurrently present, aluminum chloride hexahydrate solution can decrease sweating and reduce the risk of bacterial regrowth. Injections of botulinum toxin can be used to treat the hyperhidrosis as well. 

This patient responded well to topical erythromycin lotion.

This case and photo are courtesy of Jessica Cervantes, University of Miami Miller School of Medicine, and Dr. Bilu Martin.

Donna Bilu Martin, MD, is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/edermatologynews. To submit a case for possible publication, send an email to [email protected].

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Trichomycosis axillaris

Trichomycosis axillaris (TA) is a bacterial infection of the genus Corynebacterium that affects hairs in the axilla. Predisposing factors include poor local hygiene, hyperhidrosis, obesity, and warm, humid climates. Gram-positive diphtheroids, classically Corynebacterium tenuis, mix with sweat on hair shafts and subsequently produce a cementing material. In the majority of cases, bacterial infection causes keratin damage to the hair shaft with sparing of the cortex. However, recent cases have reported significant invasion of the hair cortex by bacterial structures.

A presents as malodorous, diaphoretic armpits without other apparent symptoms. Bacterial metabolism of testosterone in the apocrine sweat results in production of compounds that yield an acidic odor. Physical examination reveals small amounts of brown-to-yellow concretions adhered to the central part of the hair shaft. Rarely, red or black nodules can also be found. These concretions give a thickened and beaded appearance to the affected hairs.

TA is often a clinical diagnosis. Histopathology reveals a discontinuous thick-layer coating of bacterial structures adhered to the hair shafts. Periodic acid–Schiff, gram, and Grocott silver stains are all positive. Examination of hairs with 20% hydrogen peroxide solution can provide a microscopic diagnosis. Wood lamp examination produces a weak, yellow fluorescence, and potassium hydroxide test demonstrates yellowish material of minimal translucency surrounding the hair cortex.

Complete resolution can be achieved by shaving off all the axillary hairs. It is imperative to maintain good hygiene and keep the area dry and clean. To prevent recurrence, topical benzoyl peroxide or topical antibiotics such as erythromycin and clindamycin can be applied. If axillary hyperhidrosis is concurrently present, aluminum chloride hexahydrate solution can decrease sweating and reduce the risk of bacterial regrowth. Injections of botulinum toxin can be used to treat the hyperhidrosis as well. 

This patient responded well to topical erythromycin lotion.

This case and photo are courtesy of Jessica Cervantes, University of Miami Miller School of Medicine, and Dr. Bilu Martin.

Donna Bilu Martin, MD, is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/edermatologynews. To submit a case for possible publication, send an email to [email protected].

Trichomycosis axillaris

Trichomycosis axillaris (TA) is a bacterial infection of the genus Corynebacterium that affects hairs in the axilla. Predisposing factors include poor local hygiene, hyperhidrosis, obesity, and warm, humid climates. Gram-positive diphtheroids, classically Corynebacterium tenuis, mix with sweat on hair shafts and subsequently produce a cementing material. In the majority of cases, bacterial infection causes keratin damage to the hair shaft with sparing of the cortex. However, recent cases have reported significant invasion of the hair cortex by bacterial structures.

A presents as malodorous, diaphoretic armpits without other apparent symptoms. Bacterial metabolism of testosterone in the apocrine sweat results in production of compounds that yield an acidic odor. Physical examination reveals small amounts of brown-to-yellow concretions adhered to the central part of the hair shaft. Rarely, red or black nodules can also be found. These concretions give a thickened and beaded appearance to the affected hairs.

TA is often a clinical diagnosis. Histopathology reveals a discontinuous thick-layer coating of bacterial structures adhered to the hair shafts. Periodic acid–Schiff, gram, and Grocott silver stains are all positive. Examination of hairs with 20% hydrogen peroxide solution can provide a microscopic diagnosis. Wood lamp examination produces a weak, yellow fluorescence, and potassium hydroxide test demonstrates yellowish material of minimal translucency surrounding the hair cortex.

Complete resolution can be achieved by shaving off all the axillary hairs. It is imperative to maintain good hygiene and keep the area dry and clean. To prevent recurrence, topical benzoyl peroxide or topical antibiotics such as erythromycin and clindamycin can be applied. If axillary hyperhidrosis is concurrently present, aluminum chloride hexahydrate solution can decrease sweating and reduce the risk of bacterial regrowth. Injections of botulinum toxin can be used to treat the hyperhidrosis as well. 

This patient responded well to topical erythromycin lotion.

This case and photo are courtesy of Jessica Cervantes, University of Miami Miller School of Medicine, and Dr. Bilu Martin.

Donna Bilu Martin, MD, is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/edermatologynews. To submit a case for possible publication, send an email to [email protected].

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This case and photo are courtesy of Jessica Cervantes, University of Miami Miller School of Medicine, and Dr. Bilu Martin.

 

A 35-year-old male with no significant past medical history presented with the chief complaint of occasional malodorous “crust in his underarms.” He used no prior treatments, and he did report axillary hyperhidrosis.

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Sublingual Apomorphine Film May Induce On State in Patients With Parkinson’s Disease

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In a dose-titration study, the median dose required to turn patients to fully on was 20 mg, and patients assessed time to onset as between five and 12 minutes.

MIAMI—Among patients with Parkinson’s disease with well-defined morning off episodes, 83% achieved an on-medication state within 45 minutes of treatment with sublingual apomorphine film, according to research presented at the First Pan American Parkinson’s Disease and Movement Disorders Congress. Investigators presented preliminary results from an open-label dose titration phase of a phase III trial.

The sublingual apomorphine film, known as APL-130277, is being developed by Marlborough, Massachusetts-based Sunovion Pharmaceuticals. Apomorphine injected subcutaneously is approved for the acute, intermittent treatment of off episodes, but it is not widely used, possibly because of its parenteral administration, researchers have said. The dissolvable film consists of an apomorphine drug layer and a second layer that is designed to neutralize acid generation and enhance drug permeability. The film appeared to be effective in a phase II open-label study.

Robert A. Hauser, MD
To determine the dose of APL-130277 required by patients to turn from off to fully on in the phase III trial, Robert A. Hauser, MD, Professor of Neurology, Molecular Pharmacology, and Physiology and Director of the Parkinson’s Disease and Movement Disorders Center at the University of South Florida in Tampa, and colleagues conducted a dose-titration phase before randomizing patients to a 12-week, double-blind, placebo-controlled maintenance treatment phase.

Daily Off Episodes

Participants were older than 18, had idiopathic Parkinson’s disease, and had a modified Hoehn and Yahr stage between 1 and 3 on medication. Participants were responsive to levodopa and had more than two hours of off time per day. Patients were receiving stable doses of levodopa–carbidopa. Investigators excluded patients with psychosis, dementia, or impulse control disorders; mouth cankers or sores; or prior treatment of Parkinson’s disease with a neurosurgical procedure, continuous subcutaneous apomorphine infusion, or levodopa–carbidopa enteral suspension. They also excluded patients who received subcutaneous apomorphine within seven days before screening or were taking 5-HT3 antagonists, dopamine antagonists (other than quetiapine or clozapine), or dopamine-depleting agents.

Three days prior to the dose-titration phase, patients initiated treatment with trimethobenzamide or domperidone, which may reduce nausea and vomiting that can occur during the initiation of apomorphine therapy. Patients arrived at a clinic in an off state, having not taken their regular morning levodopa dose or other adjunctive medication later than midnight, and received 10 mg of APL-130277. Investigators assessed patients using the Unified Parkinson’s Disease Rating Scale Part III prior to dosing and 15, 30, 45, 60, and 90 minutes after dosing. Patients who responded with a fully on response (ie, patients and investigators agreed that medication was benefiting mobility, stiffness, and slowness such that patients had adequate motor function to perform their normal daily activities) were considered to have completed the dose- titration phase and could proceed to randomization for the maintenance treatment phase. Patients who responded to a dose could try the next highest dose at a subsequent titration visit to assess the potential for an improved response at the higher dose. Doses increased by 5-mg increments up to 35 mg.

Of 76 patients who entered the dose-titration phase, 63 (83%) turned fully on with treatment. Among patients who turned fully on, 24 (38%) did so within 15 minutes, and 49 (78%) did so within 30 minutes. The median dose turning patients to fully on was 20 mg. Patients who turned fully on assessed time to onset as between five and 12 minutes.

Safety Data

In a presentation of preliminary safety data from the dose-titration phase, Stuart Isaacson, MD, Director of the Parkinson’s Disease and Movement Disorders Center of Boca Raton in Florida, and colleagues reported that five of the 76 patients who entered the dose-titration phase discontinued the trial due to adverse events—two due to nausea, one due to somnolence, one due to headache, and one due to presyncope. Another two patients withdrew consent, and nine patients who did not turn on at the 35-mg dose were discontinued from the trial. Other reported adverse events included dizziness, yawning, vomiting, and symptomatic hypotension. Most adverse events were considered mild. “In this preliminary analysis, APL-130277 was well tolerated in patients in the dose-titration phase,” Dr. Isaacson and colleagues concluded.

Jake Remaly

Suggested Reading

Hauser RA, Olanow CW, Dzyngel B, et al. Sublingual apomorphine (APL-130277) for the acute conversion of OFF to ON in Parkinson’s disease. Mov Disord. 2016;31(9):1366-1372.

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In a dose-titration study, the median dose required to turn patients to fully on was 20 mg, and patients assessed time to onset as between five and 12 minutes.
In a dose-titration study, the median dose required to turn patients to fully on was 20 mg, and patients assessed time to onset as between five and 12 minutes.

MIAMI—Among patients with Parkinson’s disease with well-defined morning off episodes, 83% achieved an on-medication state within 45 minutes of treatment with sublingual apomorphine film, according to research presented at the First Pan American Parkinson’s Disease and Movement Disorders Congress. Investigators presented preliminary results from an open-label dose titration phase of a phase III trial.

The sublingual apomorphine film, known as APL-130277, is being developed by Marlborough, Massachusetts-based Sunovion Pharmaceuticals. Apomorphine injected subcutaneously is approved for the acute, intermittent treatment of off episodes, but it is not widely used, possibly because of its parenteral administration, researchers have said. The dissolvable film consists of an apomorphine drug layer and a second layer that is designed to neutralize acid generation and enhance drug permeability. The film appeared to be effective in a phase II open-label study.

Robert A. Hauser, MD
To determine the dose of APL-130277 required by patients to turn from off to fully on in the phase III trial, Robert A. Hauser, MD, Professor of Neurology, Molecular Pharmacology, and Physiology and Director of the Parkinson’s Disease and Movement Disorders Center at the University of South Florida in Tampa, and colleagues conducted a dose-titration phase before randomizing patients to a 12-week, double-blind, placebo-controlled maintenance treatment phase.

Daily Off Episodes

Participants were older than 18, had idiopathic Parkinson’s disease, and had a modified Hoehn and Yahr stage between 1 and 3 on medication. Participants were responsive to levodopa and had more than two hours of off time per day. Patients were receiving stable doses of levodopa–carbidopa. Investigators excluded patients with psychosis, dementia, or impulse control disorders; mouth cankers or sores; or prior treatment of Parkinson’s disease with a neurosurgical procedure, continuous subcutaneous apomorphine infusion, or levodopa–carbidopa enteral suspension. They also excluded patients who received subcutaneous apomorphine within seven days before screening or were taking 5-HT3 antagonists, dopamine antagonists (other than quetiapine or clozapine), or dopamine-depleting agents.

Three days prior to the dose-titration phase, patients initiated treatment with trimethobenzamide or domperidone, which may reduce nausea and vomiting that can occur during the initiation of apomorphine therapy. Patients arrived at a clinic in an off state, having not taken their regular morning levodopa dose or other adjunctive medication later than midnight, and received 10 mg of APL-130277. Investigators assessed patients using the Unified Parkinson’s Disease Rating Scale Part III prior to dosing and 15, 30, 45, 60, and 90 minutes after dosing. Patients who responded with a fully on response (ie, patients and investigators agreed that medication was benefiting mobility, stiffness, and slowness such that patients had adequate motor function to perform their normal daily activities) were considered to have completed the dose- titration phase and could proceed to randomization for the maintenance treatment phase. Patients who responded to a dose could try the next highest dose at a subsequent titration visit to assess the potential for an improved response at the higher dose. Doses increased by 5-mg increments up to 35 mg.

Of 76 patients who entered the dose-titration phase, 63 (83%) turned fully on with treatment. Among patients who turned fully on, 24 (38%) did so within 15 minutes, and 49 (78%) did so within 30 minutes. The median dose turning patients to fully on was 20 mg. Patients who turned fully on assessed time to onset as between five and 12 minutes.

Safety Data

In a presentation of preliminary safety data from the dose-titration phase, Stuart Isaacson, MD, Director of the Parkinson’s Disease and Movement Disorders Center of Boca Raton in Florida, and colleagues reported that five of the 76 patients who entered the dose-titration phase discontinued the trial due to adverse events—two due to nausea, one due to somnolence, one due to headache, and one due to presyncope. Another two patients withdrew consent, and nine patients who did not turn on at the 35-mg dose were discontinued from the trial. Other reported adverse events included dizziness, yawning, vomiting, and symptomatic hypotension. Most adverse events were considered mild. “In this preliminary analysis, APL-130277 was well tolerated in patients in the dose-titration phase,” Dr. Isaacson and colleagues concluded.

Jake Remaly

Suggested Reading

Hauser RA, Olanow CW, Dzyngel B, et al. Sublingual apomorphine (APL-130277) for the acute conversion of OFF to ON in Parkinson’s disease. Mov Disord. 2016;31(9):1366-1372.

MIAMI—Among patients with Parkinson’s disease with well-defined morning off episodes, 83% achieved an on-medication state within 45 minutes of treatment with sublingual apomorphine film, according to research presented at the First Pan American Parkinson’s Disease and Movement Disorders Congress. Investigators presented preliminary results from an open-label dose titration phase of a phase III trial.

The sublingual apomorphine film, known as APL-130277, is being developed by Marlborough, Massachusetts-based Sunovion Pharmaceuticals. Apomorphine injected subcutaneously is approved for the acute, intermittent treatment of off episodes, but it is not widely used, possibly because of its parenteral administration, researchers have said. The dissolvable film consists of an apomorphine drug layer and a second layer that is designed to neutralize acid generation and enhance drug permeability. The film appeared to be effective in a phase II open-label study.

Robert A. Hauser, MD
To determine the dose of APL-130277 required by patients to turn from off to fully on in the phase III trial, Robert A. Hauser, MD, Professor of Neurology, Molecular Pharmacology, and Physiology and Director of the Parkinson’s Disease and Movement Disorders Center at the University of South Florida in Tampa, and colleagues conducted a dose-titration phase before randomizing patients to a 12-week, double-blind, placebo-controlled maintenance treatment phase.

Daily Off Episodes

Participants were older than 18, had idiopathic Parkinson’s disease, and had a modified Hoehn and Yahr stage between 1 and 3 on medication. Participants were responsive to levodopa and had more than two hours of off time per day. Patients were receiving stable doses of levodopa–carbidopa. Investigators excluded patients with psychosis, dementia, or impulse control disorders; mouth cankers or sores; or prior treatment of Parkinson’s disease with a neurosurgical procedure, continuous subcutaneous apomorphine infusion, or levodopa–carbidopa enteral suspension. They also excluded patients who received subcutaneous apomorphine within seven days before screening or were taking 5-HT3 antagonists, dopamine antagonists (other than quetiapine or clozapine), or dopamine-depleting agents.

Three days prior to the dose-titration phase, patients initiated treatment with trimethobenzamide or domperidone, which may reduce nausea and vomiting that can occur during the initiation of apomorphine therapy. Patients arrived at a clinic in an off state, having not taken their regular morning levodopa dose or other adjunctive medication later than midnight, and received 10 mg of APL-130277. Investigators assessed patients using the Unified Parkinson’s Disease Rating Scale Part III prior to dosing and 15, 30, 45, 60, and 90 minutes after dosing. Patients who responded with a fully on response (ie, patients and investigators agreed that medication was benefiting mobility, stiffness, and slowness such that patients had adequate motor function to perform their normal daily activities) were considered to have completed the dose- titration phase and could proceed to randomization for the maintenance treatment phase. Patients who responded to a dose could try the next highest dose at a subsequent titration visit to assess the potential for an improved response at the higher dose. Doses increased by 5-mg increments up to 35 mg.

Of 76 patients who entered the dose-titration phase, 63 (83%) turned fully on with treatment. Among patients who turned fully on, 24 (38%) did so within 15 minutes, and 49 (78%) did so within 30 minutes. The median dose turning patients to fully on was 20 mg. Patients who turned fully on assessed time to onset as between five and 12 minutes.

Safety Data

In a presentation of preliminary safety data from the dose-titration phase, Stuart Isaacson, MD, Director of the Parkinson’s Disease and Movement Disorders Center of Boca Raton in Florida, and colleagues reported that five of the 76 patients who entered the dose-titration phase discontinued the trial due to adverse events—two due to nausea, one due to somnolence, one due to headache, and one due to presyncope. Another two patients withdrew consent, and nine patients who did not turn on at the 35-mg dose were discontinued from the trial. Other reported adverse events included dizziness, yawning, vomiting, and symptomatic hypotension. Most adverse events were considered mild. “In this preliminary analysis, APL-130277 was well tolerated in patients in the dose-titration phase,” Dr. Isaacson and colleagues concluded.

Jake Remaly

Suggested Reading

Hauser RA, Olanow CW, Dzyngel B, et al. Sublingual apomorphine (APL-130277) for the acute conversion of OFF to ON in Parkinson’s disease. Mov Disord. 2016;31(9):1366-1372.

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Down syndrome in adolescents

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Teen years, no doubt, come with expected challenges. For teens with Down syndrome (DS), the challenges are exponentially greater. Although DS is associated with mental retardation, the vast majority of people with DS have only mild to moderate intellectual disability. Still, this can lead to a great deal of internal stress for the adolescent and anxiety and stress for the parents.

Many issues must be considered for the adolescent with DS. Annual surveillance changes as the child ages and the need for intervention do as well. For example, 50% of children with DS are born with congenital heart defect. During infancy, it is important to do echocardiograms to identify and follow specific lesions. Approximately 57% of adolescents with DS will develop mitral valve prolapse and 10% will develop aortic regurgitation.1 Therefore, close evaluation should be done, listening for new onset murmurs, clicks, and unexplained fatigue, and, if these are identified, an echocardiogram should be repeated.
 

Dr. Francine Pearce
Obesity rates in people with DS are far greater than in the general population. Mental impairment, decreased physical activity, and endocrine pathology all contribute to this issue. Body mass index evaluation, healthy eating, and participation in developmentally appropriate activity should be encouraged. Surveillance for rapid changes in weight, skin, and menstrual cycle warrant evaluation of thyroid level, which should be done annually, regardless.2 Persons with DS are at a 16%-20% risk of thyroid disease and a 1.4%-10% increased risk of type 2 diabetes.1 They are also at increased risk for autoimmune diseases.

Dysmorphic features such as midfacial hypoplasia, tonsillar hypertrophy, and narrow ear canals also lead to issues that develop in the adolescent years. Chronic otitis, conductive hearing loss because of chronic middle-ear effusion or impacted cerumen, and enlarged tonsils can result in obstructive sleep apnea. As individuals gain weight, these issues are further affected, and a sleep study may be required. Annual hearing screens are recommended.1

George Doyle/Thinkstock
Teenage girl with down syndrome working on a laptop
Accommodative esotropia, myopia, strabismus, and blepharitis are common ophthalmologic conditions associated with DS1, as is the rarer keratoconus, or anterior bulging of the cornea. Therefore, close observation for vision impairment is imperative.

Musculoskeletal disorders such as ligamentous laxity and atlantoaxial instability can also present with complications in the adolescent years. Pes planus is a very common finding that can further lead to hip and knee pain. Obesity also further adds to its occurrence (14%-67%).3 

Now, the most pressing and, likely, most overlooked issue is the issue of sexuality. We spend a great deal of time educating teens without DS about the risks of unprotected sex and exposures to STIs, but many assume that these issues do not affect teens with DS. Secondary sexual characteristics develop in the same manner and at the same age that they do in children without DS. Therefore, it is a safe assumption that sexual curiosity and arousal do as well. Given that there can be varying levels of mental impairment, the approach to sex education needs to be developmentally appropriate. Normalizing the feelings and having discussions on appropriate and inappropriate expression are important.

As with all teens, acceptance and inclusion are of utmost importance. Physical and learning disabilities set them apart despite shared sexual and emotional development. This can lead to anxiety, depression, and behavior issues. Understanding that these are real issues for the adolescent with DS is important when providing the appropriate resources and support.

Management of the menstrual cycle can add new challenges for both the adolescent and the parent and, thus, should be investigated during health maintenance visits. Amenorrhea can result from introduction of hormonal therapy and should be considered. Sexual abuse also is increased in this age group, so close supervision and awareness of this issue are important.

Assisting parents of children with DS through the teen years is imperative. Making them aware of local support groups and national organizations for children with disabilities will help them navigate these years. The American Academy of Pediatrics has guidelines for health maintenance for DS.2

 

Dr. Pearce is a pediatrician in Frankfort, Ill. She reported no relevant financial disclosures. Email her at [email protected]

References

1. J Pediatr Health Care. 2006 May-Jun;20(3):198-205.

2. Pediatrics. 2011. doi: 10.1542/peds.2011-1605.

3. Clin Obes. 2015;5(2):52-9.

 

Correction, 7/26/17: An earlier version of this article misstated a recommendation about radiologic evaluation of the cervical spine in asymptomatic children

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Teen years, no doubt, come with expected challenges. For teens with Down syndrome (DS), the challenges are exponentially greater. Although DS is associated with mental retardation, the vast majority of people with DS have only mild to moderate intellectual disability. Still, this can lead to a great deal of internal stress for the adolescent and anxiety and stress for the parents.

Many issues must be considered for the adolescent with DS. Annual surveillance changes as the child ages and the need for intervention do as well. For example, 50% of children with DS are born with congenital heart defect. During infancy, it is important to do echocardiograms to identify and follow specific lesions. Approximately 57% of adolescents with DS will develop mitral valve prolapse and 10% will develop aortic regurgitation.1 Therefore, close evaluation should be done, listening for new onset murmurs, clicks, and unexplained fatigue, and, if these are identified, an echocardiogram should be repeated.
 

Dr. Francine Pearce
Obesity rates in people with DS are far greater than in the general population. Mental impairment, decreased physical activity, and endocrine pathology all contribute to this issue. Body mass index evaluation, healthy eating, and participation in developmentally appropriate activity should be encouraged. Surveillance for rapid changes in weight, skin, and menstrual cycle warrant evaluation of thyroid level, which should be done annually, regardless.2 Persons with DS are at a 16%-20% risk of thyroid disease and a 1.4%-10% increased risk of type 2 diabetes.1 They are also at increased risk for autoimmune diseases.

Dysmorphic features such as midfacial hypoplasia, tonsillar hypertrophy, and narrow ear canals also lead to issues that develop in the adolescent years. Chronic otitis, conductive hearing loss because of chronic middle-ear effusion or impacted cerumen, and enlarged tonsils can result in obstructive sleep apnea. As individuals gain weight, these issues are further affected, and a sleep study may be required. Annual hearing screens are recommended.1

George Doyle/Thinkstock
Teenage girl with down syndrome working on a laptop
Accommodative esotropia, myopia, strabismus, and blepharitis are common ophthalmologic conditions associated with DS1, as is the rarer keratoconus, or anterior bulging of the cornea. Therefore, close observation for vision impairment is imperative.

Musculoskeletal disorders such as ligamentous laxity and atlantoaxial instability can also present with complications in the adolescent years. Pes planus is a very common finding that can further lead to hip and knee pain. Obesity also further adds to its occurrence (14%-67%).3 

Now, the most pressing and, likely, most overlooked issue is the issue of sexuality. We spend a great deal of time educating teens without DS about the risks of unprotected sex and exposures to STIs, but many assume that these issues do not affect teens with DS. Secondary sexual characteristics develop in the same manner and at the same age that they do in children without DS. Therefore, it is a safe assumption that sexual curiosity and arousal do as well. Given that there can be varying levels of mental impairment, the approach to sex education needs to be developmentally appropriate. Normalizing the feelings and having discussions on appropriate and inappropriate expression are important.

As with all teens, acceptance and inclusion are of utmost importance. Physical and learning disabilities set them apart despite shared sexual and emotional development. This can lead to anxiety, depression, and behavior issues. Understanding that these are real issues for the adolescent with DS is important when providing the appropriate resources and support.

Management of the menstrual cycle can add new challenges for both the adolescent and the parent and, thus, should be investigated during health maintenance visits. Amenorrhea can result from introduction of hormonal therapy and should be considered. Sexual abuse also is increased in this age group, so close supervision and awareness of this issue are important.

Assisting parents of children with DS through the teen years is imperative. Making them aware of local support groups and national organizations for children with disabilities will help them navigate these years. The American Academy of Pediatrics has guidelines for health maintenance for DS.2

 

Dr. Pearce is a pediatrician in Frankfort, Ill. She reported no relevant financial disclosures. Email her at [email protected]

References

1. J Pediatr Health Care. 2006 May-Jun;20(3):198-205.

2. Pediatrics. 2011. doi: 10.1542/peds.2011-1605.

3. Clin Obes. 2015;5(2):52-9.

 

Correction, 7/26/17: An earlier version of this article misstated a recommendation about radiologic evaluation of the cervical spine in asymptomatic children

 

Teen years, no doubt, come with expected challenges. For teens with Down syndrome (DS), the challenges are exponentially greater. Although DS is associated with mental retardation, the vast majority of people with DS have only mild to moderate intellectual disability. Still, this can lead to a great deal of internal stress for the adolescent and anxiety and stress for the parents.

Many issues must be considered for the adolescent with DS. Annual surveillance changes as the child ages and the need for intervention do as well. For example, 50% of children with DS are born with congenital heart defect. During infancy, it is important to do echocardiograms to identify and follow specific lesions. Approximately 57% of adolescents with DS will develop mitral valve prolapse and 10% will develop aortic regurgitation.1 Therefore, close evaluation should be done, listening for new onset murmurs, clicks, and unexplained fatigue, and, if these are identified, an echocardiogram should be repeated.
 

Dr. Francine Pearce
Obesity rates in people with DS are far greater than in the general population. Mental impairment, decreased physical activity, and endocrine pathology all contribute to this issue. Body mass index evaluation, healthy eating, and participation in developmentally appropriate activity should be encouraged. Surveillance for rapid changes in weight, skin, and menstrual cycle warrant evaluation of thyroid level, which should be done annually, regardless.2 Persons with DS are at a 16%-20% risk of thyroid disease and a 1.4%-10% increased risk of type 2 diabetes.1 They are also at increased risk for autoimmune diseases.

Dysmorphic features such as midfacial hypoplasia, tonsillar hypertrophy, and narrow ear canals also lead to issues that develop in the adolescent years. Chronic otitis, conductive hearing loss because of chronic middle-ear effusion or impacted cerumen, and enlarged tonsils can result in obstructive sleep apnea. As individuals gain weight, these issues are further affected, and a sleep study may be required. Annual hearing screens are recommended.1

George Doyle/Thinkstock
Teenage girl with down syndrome working on a laptop
Accommodative esotropia, myopia, strabismus, and blepharitis are common ophthalmologic conditions associated with DS1, as is the rarer keratoconus, or anterior bulging of the cornea. Therefore, close observation for vision impairment is imperative.

Musculoskeletal disorders such as ligamentous laxity and atlantoaxial instability can also present with complications in the adolescent years. Pes planus is a very common finding that can further lead to hip and knee pain. Obesity also further adds to its occurrence (14%-67%).3 

Now, the most pressing and, likely, most overlooked issue is the issue of sexuality. We spend a great deal of time educating teens without DS about the risks of unprotected sex and exposures to STIs, but many assume that these issues do not affect teens with DS. Secondary sexual characteristics develop in the same manner and at the same age that they do in children without DS. Therefore, it is a safe assumption that sexual curiosity and arousal do as well. Given that there can be varying levels of mental impairment, the approach to sex education needs to be developmentally appropriate. Normalizing the feelings and having discussions on appropriate and inappropriate expression are important.

As with all teens, acceptance and inclusion are of utmost importance. Physical and learning disabilities set them apart despite shared sexual and emotional development. This can lead to anxiety, depression, and behavior issues. Understanding that these are real issues for the adolescent with DS is important when providing the appropriate resources and support.

Management of the menstrual cycle can add new challenges for both the adolescent and the parent and, thus, should be investigated during health maintenance visits. Amenorrhea can result from introduction of hormonal therapy and should be considered. Sexual abuse also is increased in this age group, so close supervision and awareness of this issue are important.

Assisting parents of children with DS through the teen years is imperative. Making them aware of local support groups and national organizations for children with disabilities will help them navigate these years. The American Academy of Pediatrics has guidelines for health maintenance for DS.2

 

Dr. Pearce is a pediatrician in Frankfort, Ill. She reported no relevant financial disclosures. Email her at [email protected]

References

1. J Pediatr Health Care. 2006 May-Jun;20(3):198-205.

2. Pediatrics. 2011. doi: 10.1542/peds.2011-1605.

3. Clin Obes. 2015;5(2):52-9.

 

Correction, 7/26/17: An earlier version of this article misstated a recommendation about radiologic evaluation of the cervical spine in asymptomatic children

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The many faces of formaldehyde contact allergy

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ATLANTA – Formaldehyde has various clinical presentations and variable thresholds to trigger allergic contact dermatitis, so it requires a high index of suspicion, according to Salma de la Feld, MD.

It may present as irritant contact dermatitis, allergic contact dermatitis (especially to the hands and face), airborne allergic contact dermatitis, or systemic allergic contact dermatitis (to aspartame).

Doug Brunk/Frontline Medical News
Dr. Salma de la Feld*
In 2015 the American Contact Dermatitis Society named formaldehyde, an antimicrobial preservative, the Allergen of the Year, and it currently ranks as the ninth most common allergen. Part of that stems from the fact that formaldehyde can be released from several different chemicals, Dr. de la Feld said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

From most-releasing to least-releasing, these chemicals include quaternium-15, diazolidinyl urea, DMDM hydantoin, imidazolidinyl urea, and bronopol. Exposure can come from personal care products, prescription topical steroids and acne creams, Brazilian hair keratin, cigarettes, and textiles made of blended fabrics, as well as occupations such as a leather handler, surgical nurse, pathology lab worker, and hairdresser.

“Patients can be allergic to either the formaldehyde that [a product] releases or the non–formaldehyde component or both,” said Dr. de la Feld, who is a dermatologist at Emory University, Atlanta.

Recent studies suggest that the formaldehyde allergen should be tested at 2% instead of at 1%. “You do get a few more irritant reactions [with this approach], but you’re also going to catch more people who have a true positive reaction,” she said. “If you see a borderline papule with a little pink, that might be an irritant. You want to test for the formaldehyde releasers. When you do have a positive reaction, you want to have a high index of suspicion. Patients have to be strict in what personal care products they’re using. Some people might be able to tolerate a low concentration of formaldehyde in some products and that magic number differs between patients.”

From a treatment standpoint, Dr. de la Feld advises patients to avoid all formaldehyde releasers and to wear 100% fabrics in an effort to steer clear of textile exposure. “I like to have people be really strict [in their avoidance] when they’re first starting out,” she said. “They don’t like it, but I’ll say, ‘You’re so itchy. Let’s start really strict to get you clear and better.’ Once they’re better and there’s that one moisturizing cream that they really love, then [you] can do a repeat open application test. If nothing happens, it’s probably safe. If [they] start getting red and itchy there, [they] should probably throw away that moisturizer.”

Fragrance

Fragrance, which was named Allergen of the Year in 2007, is another common contact allergen. An estimated 4%-11% of the worldwide population is allergic to fragrance mix, while 1.6%-10.8% is allergic to balsam of Peru. T.R.U.E. tests for the allergen often yield false-negative results. Clinicians who fail to test for fragrance mix 2 will miss about one-third of fragrance allergic contact dermatitis diagnoses. “If the distribution is scattered, you want to be suspicious for fragrance allergy,” Dr. de la Feld said. “Sometimes patients get exposed inadvertently by their significant other or by a family member who is spraying a fragrant product.” Treatment is avoidance. “You want to tell patients to look for products labeled as fragrance free,” she said. “ ‘Unscented’ does not count. When patients tell you that they’re not using any perfume, you want to ask them if they’ve put any on their clothes.”

Systemic contact dermatitis

Dr. de la Feld finished her presentation by discussing systemic contact dermatitis, which she defined as a rash from systemic exposure to an allergen in someone who was previously sensitized. Alternative names for the condition include endogenous contact eczema, systemically-induced contact dermatitis, and internal-external contact-type hypersensitivity. She acknowledged that not all dermatologists believe systemic contact dermatitis to be a true clinical condition, but she does.

“It’s most classically and commonly reported with nickel and balsam of Peru and more slowly with some other allergens,” she said. “It can have multiple clinical presentations, and it’s not always widespread.” The three most common presentations are dyshidrotic hand eczema, sites of prior contact dermatitis (from contact or patch test), and anogenital and/or flexural areas (Baboon syndrome). There are other reports of systemic contact dermatitis presenting as disseminated patchy dermatitis, generalized erythroderma, cheilitis, and lichen planus of the lip.

Dr. de la Feld reported having no relevant financial disclosures.

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ATLANTA – Formaldehyde has various clinical presentations and variable thresholds to trigger allergic contact dermatitis, so it requires a high index of suspicion, according to Salma de la Feld, MD.

It may present as irritant contact dermatitis, allergic contact dermatitis (especially to the hands and face), airborne allergic contact dermatitis, or systemic allergic contact dermatitis (to aspartame).

Doug Brunk/Frontline Medical News
Dr. Salma de la Feld*
In 2015 the American Contact Dermatitis Society named formaldehyde, an antimicrobial preservative, the Allergen of the Year, and it currently ranks as the ninth most common allergen. Part of that stems from the fact that formaldehyde can be released from several different chemicals, Dr. de la Feld said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

From most-releasing to least-releasing, these chemicals include quaternium-15, diazolidinyl urea, DMDM hydantoin, imidazolidinyl urea, and bronopol. Exposure can come from personal care products, prescription topical steroids and acne creams, Brazilian hair keratin, cigarettes, and textiles made of blended fabrics, as well as occupations such as a leather handler, surgical nurse, pathology lab worker, and hairdresser.

“Patients can be allergic to either the formaldehyde that [a product] releases or the non–formaldehyde component or both,” said Dr. de la Feld, who is a dermatologist at Emory University, Atlanta.

Recent studies suggest that the formaldehyde allergen should be tested at 2% instead of at 1%. “You do get a few more irritant reactions [with this approach], but you’re also going to catch more people who have a true positive reaction,” she said. “If you see a borderline papule with a little pink, that might be an irritant. You want to test for the formaldehyde releasers. When you do have a positive reaction, you want to have a high index of suspicion. Patients have to be strict in what personal care products they’re using. Some people might be able to tolerate a low concentration of formaldehyde in some products and that magic number differs between patients.”

From a treatment standpoint, Dr. de la Feld advises patients to avoid all formaldehyde releasers and to wear 100% fabrics in an effort to steer clear of textile exposure. “I like to have people be really strict [in their avoidance] when they’re first starting out,” she said. “They don’t like it, but I’ll say, ‘You’re so itchy. Let’s start really strict to get you clear and better.’ Once they’re better and there’s that one moisturizing cream that they really love, then [you] can do a repeat open application test. If nothing happens, it’s probably safe. If [they] start getting red and itchy there, [they] should probably throw away that moisturizer.”

Fragrance

Fragrance, which was named Allergen of the Year in 2007, is another common contact allergen. An estimated 4%-11% of the worldwide population is allergic to fragrance mix, while 1.6%-10.8% is allergic to balsam of Peru. T.R.U.E. tests for the allergen often yield false-negative results. Clinicians who fail to test for fragrance mix 2 will miss about one-third of fragrance allergic contact dermatitis diagnoses. “If the distribution is scattered, you want to be suspicious for fragrance allergy,” Dr. de la Feld said. “Sometimes patients get exposed inadvertently by their significant other or by a family member who is spraying a fragrant product.” Treatment is avoidance. “You want to tell patients to look for products labeled as fragrance free,” she said. “ ‘Unscented’ does not count. When patients tell you that they’re not using any perfume, you want to ask them if they’ve put any on their clothes.”

Systemic contact dermatitis

Dr. de la Feld finished her presentation by discussing systemic contact dermatitis, which she defined as a rash from systemic exposure to an allergen in someone who was previously sensitized. Alternative names for the condition include endogenous contact eczema, systemically-induced contact dermatitis, and internal-external contact-type hypersensitivity. She acknowledged that not all dermatologists believe systemic contact dermatitis to be a true clinical condition, but she does.

“It’s most classically and commonly reported with nickel and balsam of Peru and more slowly with some other allergens,” she said. “It can have multiple clinical presentations, and it’s not always widespread.” The three most common presentations are dyshidrotic hand eczema, sites of prior contact dermatitis (from contact or patch test), and anogenital and/or flexural areas (Baboon syndrome). There are other reports of systemic contact dermatitis presenting as disseminated patchy dermatitis, generalized erythroderma, cheilitis, and lichen planus of the lip.

Dr. de la Feld reported having no relevant financial disclosures.

 

ATLANTA – Formaldehyde has various clinical presentations and variable thresholds to trigger allergic contact dermatitis, so it requires a high index of suspicion, according to Salma de la Feld, MD.

It may present as irritant contact dermatitis, allergic contact dermatitis (especially to the hands and face), airborne allergic contact dermatitis, or systemic allergic contact dermatitis (to aspartame).

Doug Brunk/Frontline Medical News
Dr. Salma de la Feld*
In 2015 the American Contact Dermatitis Society named formaldehyde, an antimicrobial preservative, the Allergen of the Year, and it currently ranks as the ninth most common allergen. Part of that stems from the fact that formaldehyde can be released from several different chemicals, Dr. de la Feld said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

From most-releasing to least-releasing, these chemicals include quaternium-15, diazolidinyl urea, DMDM hydantoin, imidazolidinyl urea, and bronopol. Exposure can come from personal care products, prescription topical steroids and acne creams, Brazilian hair keratin, cigarettes, and textiles made of blended fabrics, as well as occupations such as a leather handler, surgical nurse, pathology lab worker, and hairdresser.

“Patients can be allergic to either the formaldehyde that [a product] releases or the non–formaldehyde component or both,” said Dr. de la Feld, who is a dermatologist at Emory University, Atlanta.

Recent studies suggest that the formaldehyde allergen should be tested at 2% instead of at 1%. “You do get a few more irritant reactions [with this approach], but you’re also going to catch more people who have a true positive reaction,” she said. “If you see a borderline papule with a little pink, that might be an irritant. You want to test for the formaldehyde releasers. When you do have a positive reaction, you want to have a high index of suspicion. Patients have to be strict in what personal care products they’re using. Some people might be able to tolerate a low concentration of formaldehyde in some products and that magic number differs between patients.”

From a treatment standpoint, Dr. de la Feld advises patients to avoid all formaldehyde releasers and to wear 100% fabrics in an effort to steer clear of textile exposure. “I like to have people be really strict [in their avoidance] when they’re first starting out,” she said. “They don’t like it, but I’ll say, ‘You’re so itchy. Let’s start really strict to get you clear and better.’ Once they’re better and there’s that one moisturizing cream that they really love, then [you] can do a repeat open application test. If nothing happens, it’s probably safe. If [they] start getting red and itchy there, [they] should probably throw away that moisturizer.”

Fragrance

Fragrance, which was named Allergen of the Year in 2007, is another common contact allergen. An estimated 4%-11% of the worldwide population is allergic to fragrance mix, while 1.6%-10.8% is allergic to balsam of Peru. T.R.U.E. tests for the allergen often yield false-negative results. Clinicians who fail to test for fragrance mix 2 will miss about one-third of fragrance allergic contact dermatitis diagnoses. “If the distribution is scattered, you want to be suspicious for fragrance allergy,” Dr. de la Feld said. “Sometimes patients get exposed inadvertently by their significant other or by a family member who is spraying a fragrant product.” Treatment is avoidance. “You want to tell patients to look for products labeled as fragrance free,” she said. “ ‘Unscented’ does not count. When patients tell you that they’re not using any perfume, you want to ask them if they’ve put any on their clothes.”

Systemic contact dermatitis

Dr. de la Feld finished her presentation by discussing systemic contact dermatitis, which she defined as a rash from systemic exposure to an allergen in someone who was previously sensitized. Alternative names for the condition include endogenous contact eczema, systemically-induced contact dermatitis, and internal-external contact-type hypersensitivity. She acknowledged that not all dermatologists believe systemic contact dermatitis to be a true clinical condition, but she does.

“It’s most classically and commonly reported with nickel and balsam of Peru and more slowly with some other allergens,” she said. “It can have multiple clinical presentations, and it’s not always widespread.” The three most common presentations are dyshidrotic hand eczema, sites of prior contact dermatitis (from contact or patch test), and anogenital and/or flexural areas (Baboon syndrome). There are other reports of systemic contact dermatitis presenting as disseminated patchy dermatitis, generalized erythroderma, cheilitis, and lichen planus of the lip.

Dr. de la Feld reported having no relevant financial disclosures.

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EXPERT ANALYSIS AT THE 2017 AAAAI ANNUAL MEETING

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