A simple, quick point-of-care urine test for tenofovir adherence, similar to an OTC-pregnancy test, has an accuracy of 99.6% versus laboratory testing, according to a report at the Conference on Retroviruses & Opportunistic Infections.

A few drops of urine yield results in 5 minutes, and tell if patients have been taking tenofovir, a key component of HIV preexposure prophylaxis (PrEP) medications, within the previous 4-7 days. Abbott Rapid Diagnostics is gearing up to market the test widely in the United States, and it won’t be very expensive, according to lead investigator Matthew Spinelli, MD, a clinical fellow and HIV/AIDS researcher at the University of California, San Francisco.

It’s an alternative to the usual approach, measuring tenofovir levels in hair, blood, or urine by liquid chromatography and mass spectrometry. That approach is expensive and requires trained personnel, and the results can take a while. Dr. Spinelli and colleagues saw the need for a quicker, easier way for use in the clinic, since real-time adherence results are most likely to make a difference, he said at the meeting, which was scheduled to be in Boston, but was held online instead this year because of concerns about spreading the COVID-19 virus.

Self-report, meanwhile, is notoriously unreliable. Over 90% of people in two previous PrEP studies said they were taking their medications, but only about a quarter had tenofovir in their plasma.

The investigators identified a tenofovir antibody in urine that could be read by enzyme-linked immunosorbent assay (ELISA), and validated it for adherence accuracy against liquid chromatography and mass spectrometry; they then put the antibody on a test strip to create a lateral flow immunoassay.

After hearing the presentation, moderator Susan Buchbinder, MD, director of HIV prevention research at the San Francisco Department of Public Health, called the work “important” and said it “really has the possibility of opening up a lot of new kinds of studies and new kinds of intervention for both prevention and treatment.”

Dr. Spinelli and colleagues pitted the test strip against their laboratory-based ELISA test using 684 stored urine samples from 324 men and women in disoproxil fumarate/emtricitabine (Truvada) PrEP projects in Africa and the United States.

Overall, the 505 samples that were positive for tenofovir in the lab test were also positive on the urine strip, yielding 100% sensitivity. Of the 179 negative samples on the lab test, 176 were also negative with the strip, yielding a specificity of 98.3%. The results calculated into nearly perfect accuracy.

“We believe that” the urine test strip “is ready for field testing,” and that “point-of-care adherence testing” will be a boon to both PrEP and HIV treatment. A negative test, for instance, would signal the need for immediate counseling, and the patient would still be in the office to hear it. For HIV, high adherence but also high viral load would signal the need for resistance testing, Dr. Spinelli said.

A white-coat effect is possible; people might take their medication when they know they have an upcoming doctor’s appointment. “We will need to evaluate for [that] with additional studies” comparing point-of-care testing with longer-term metrics, such as drug levels in hair, he said.

The study was published to coincide with Dr. Spinelli’s report (J Acquir Immune Defic Syndr. 2020 Mar 10. doi: 10.1097/QAI.0000000000002322).

The funding source wasn’t reported. Dr. Spinelli had no disclosures. Two investigators were Abbott employees.

aotto@mdedge.com

SOURCE: Spinelli MA et al. 2020 CROI abstract 91.

A simple, quick point-of-care urine test for tenofovir adherence, similar to an OTC-pregnancy test, has an accuracy of 99.6% versus laboratory testing, according to a report at the Conference on Retroviruses & Opportunistic Infections.

A few drops of urine yield results in 5 minutes, and tell if patients have been taking tenofovir, a key component of HIV preexposure prophylaxis (PrEP) medications, within the previous 4-7 days. Abbott Rapid Diagnostics is gearing up to market the test widely in the United States, and it won’t be very expensive, according to lead investigator Matthew Spinelli, MD, a clinical fellow and HIV/AIDS researcher at the University of California, San Francisco.

It’s an alternative to the usual approach, measuring tenofovir levels in hair, blood, or urine by liquid chromatography and mass spectrometry. That approach is expensive and requires trained personnel, and the results can take a while. Dr. Spinelli and colleagues saw the need for a quicker, easier way for use in the clinic, since real-time adherence results are most likely to make a difference, he said at the meeting, which was scheduled to be in Boston, but was held online instead this year because of concerns about spreading the COVID-19 virus.

Self-report, meanwhile, is notoriously unreliable. Over 90% of people in two previous PrEP studies said they were taking their medications, but only about a quarter had tenofovir in their plasma.

The investigators identified a tenofovir antibody in urine that could be read by enzyme-linked immunosorbent assay (ELISA), and validated it for adherence accuracy against liquid chromatography and mass spectrometry; they then put the antibody on a test strip to create a lateral flow immunoassay.

After hearing the presentation, moderator Susan Buchbinder, MD, director of HIV prevention research at the San Francisco Department of Public Health, called the work “important” and said it “really has the possibility of opening up a lot of new kinds of studies and new kinds of intervention for both prevention and treatment.”

Dr. Spinelli and colleagues pitted the test strip against their laboratory-based ELISA test using 684 stored urine samples from 324 men and women in disoproxil fumarate/emtricitabine (Truvada) PrEP projects in Africa and the United States.

Overall, the 505 samples that were positive for tenofovir in the lab test were also positive on the urine strip, yielding 100% sensitivity. Of the 179 negative samples on the lab test, 176 were also negative with the strip, yielding a specificity of 98.3%. The results calculated into nearly perfect accuracy.

“We believe that” the urine test strip “is ready for field testing,” and that “point-of-care adherence testing” will be a boon to both PrEP and HIV treatment. A negative test, for instance, would signal the need for immediate counseling, and the patient would still be in the office to hear it. For HIV, high adherence but also high viral load would signal the need for resistance testing, Dr. Spinelli said.

A white-coat effect is possible; people might take their medication when they know they have an upcoming doctor’s appointment. “We will need to evaluate for [that] with additional studies” comparing point-of-care testing with longer-term metrics, such as drug levels in hair, he said.

The study was published to coincide with Dr. Spinelli’s report (J Acquir Immune Defic Syndr. 2020 Mar 10. doi: 10.1097/QAI.0000000000002322).

The funding source wasn’t reported. Dr. Spinelli had no disclosures. Two investigators were Abbott employees.

aotto@mdedge.com

SOURCE: Spinelli MA et al. 2020 CROI abstract 91.

A simple, quick point-of-care urine test for tenofovir adherence, similar to an OTC-pregnancy test, has an accuracy of 99.6% versus laboratory testing, according to a report at the Conference on Retroviruses & Opportunistic Infections.

A few drops of urine yield results in 5 minutes, and tell if patients have been taking tenofovir, a key component of HIV preexposure prophylaxis (PrEP) medications, within the previous 4-7 days. Abbott Rapid Diagnostics is gearing up to market the test widely in the United States, and it won’t be very expensive, according to lead investigator Matthew Spinelli, MD, a clinical fellow and HIV/AIDS researcher at the University of California, San Francisco.

It’s an alternative to the usual approach, measuring tenofovir levels in hair, blood, or urine by liquid chromatography and mass spectrometry. That approach is expensive and requires trained personnel, and the results can take a while. Dr. Spinelli and colleagues saw the need for a quicker, easier way for use in the clinic, since real-time adherence results are most likely to make a difference, he said at the meeting, which was scheduled to be in Boston, but was held online instead this year because of concerns about spreading the COVID-19 virus.

Self-report, meanwhile, is notoriously unreliable. Over 90% of people in two previous PrEP studies said they were taking their medications, but only about a quarter had tenofovir in their plasma.

The investigators identified a tenofovir antibody in urine that could be read by enzyme-linked immunosorbent assay (ELISA), and validated it for adherence accuracy against liquid chromatography and mass spectrometry; they then put the antibody on a test strip to create a lateral flow immunoassay.

After hearing the presentation, moderator Susan Buchbinder, MD, director of HIV prevention research at the San Francisco Department of Public Health, called the work “important” and said it “really has the possibility of opening up a lot of new kinds of studies and new kinds of intervention for both prevention and treatment.”

Dr. Spinelli and colleagues pitted the test strip against their laboratory-based ELISA test using 684 stored urine samples from 324 men and women in disoproxil fumarate/emtricitabine (Truvada) PrEP projects in Africa and the United States.

Overall, the 505 samples that were positive for tenofovir in the lab test were also positive on the urine strip, yielding 100% sensitivity. Of the 179 negative samples on the lab test, 176 were also negative with the strip, yielding a specificity of 98.3%. The results calculated into nearly perfect accuracy.

“We believe that” the urine test strip “is ready for field testing,” and that “point-of-care adherence testing” will be a boon to both PrEP and HIV treatment. A negative test, for instance, would signal the need for immediate counseling, and the patient would still be in the office to hear it. For HIV, high adherence but also high viral load would signal the need for resistance testing, Dr. Spinelli said.

A white-coat effect is possible; people might take their medication when they know they have an upcoming doctor’s appointment. “We will need to evaluate for [that] with additional studies” comparing point-of-care testing with longer-term metrics, such as drug levels in hair, he said.

The study was published to coincide with Dr. Spinelli’s report (J Acquir Immune Defic Syndr. 2020 Mar 10. doi: 10.1097/QAI.0000000000002322).

The funding source wasn’t reported. Dr. Spinelli had no disclosures. Two investigators were Abbott employees.

aotto@mdedge.com

SOURCE: Spinelli MA et al. 2020 CROI abstract 91.

Khadija Hafidh, MD, was already booked on a 14-hour, direct flight from Dubai to Los Angeles, when the American College of Physicians (ACP) announced it was canceling its internal medicine meeting scheduled for April.

Canceling her hotel reservation was not a problem, and she was assured a refund for the conference fee, but her airline ticket was another matter, said Dr. Hafidh, an internist and diabetologist with the Dubai Health Authority.

“The airline I booked my ticket with is willing to waive the change fees, but will deduct a cancellation fee if I choose not to take the trip,” Dr. Hafidh said in an interview. “The cancellation fees is $300. A bit steep I must admit.”

Dr. Hafidh now faces a dilemma: Lose the $300 and cancel, or change her flight dates to June for the American Diabetes Association meeting in Chicago.

“But then again, we aren’t sure if that meeting will take place,” Dr. Hafidh said. “A few weeks ago I thought this whole thing was just a storm in a tea cup. However when it was declared a pandemic yesterday, it brought about another dimension.”

More than 25 medical meetings and conferences across the globe have been canceled or postponed because of COVID-19 concerns. The sudden cancellations have caused reservation woes and travel headaches for thousands of physicians who planned to attend the meetings. Some societies are considering the idea of virtual conferences, while other associations have scrapped their meetings until next year.

For physicians facing a canceled conference, the most likely question is, what now? Read on for tips and suggestions.
 

Reservation refunds vary

Refunds on airfare because of conference cancellations differ, depending on the airline and where you were traveling. Some airlines, such as United Airlines, have waived all change fees for tickets issued March 3, 2020, through March 31, 2020, and passengers can change their dates for up to 12 months after the ticket was issued.

Full refunds often depend on whether your ticket was nonrefundable when purchased. Many airlines, such as Delta, are providing full refunds if the airline canceled your flight. JetBlue is waiving all change and cancellation fees for customers scheduled to travel March 10, 2020, through April 30, 2020.

Las Vegas–based dermatologist H.L. Greenberg, MD, was satisfied with the credit he received from Southwest Airlines after the American Academy of Dermatology (AAD) canceled its Denver meeting. He and his staff were looking forward to the gathering, but he noted that the meeting would likely have been limited, even if it had take place as scheduled.

“I am disappointed that I won’t be able to meet with colleagues and industry to explore what the latest advances and interests are in dermatology,” he said. “Because many academic institutions were forbidding their faculty from traveling, the content of the meeting was going to be severely diminished. It’s just a rough time for everyone.”

Meanwhile, Asa Radix, MD, PhD, a New York–based internist, received a full refund for his Amtrak ticket to Boston when the Conference on Retroviruses and Opportunistic Infections (CROI) scheduled for early March was converted to a virtual meeting. Dr. Radix, senior director of research and education at the Callen-Lorde Community Health Center in New York, left another meeting in Brazil early to get to the Boston conference, he said.

“I was packed, but really that was a minor inconvenience,” he said in an interview. “I appreciate that they prioritized health concerns and changed to a virtual meeting. I received full refunds, no issues whatsoever. [It was] really great since I had no travel insurance.”

Check with your individual airline or train line for information about ticket refunds and credits. Many airlines are currently making special accommodations because of COVID-19. If your flight was covered by trip insurance, also called travel assistance, you are generally protected against unforeseen financial losses such as cancellations. The U.S. Department of Transportation provides this general online resource about airline refunds.
 

Hotel refunds probable

Most meeting organizations who have made the decision to cancel or postpone a conference also have canceled block hotel reservations reserved for the meeting. Medical associations are not directly refunding the hotel costs, but the majority of hotels are refunding reservations with no questions asked. Physicians interviewed for this story all reported no trouble getting refunds for their hotel reservations. However, attendees who did not book a hotel in official housing blocks should contact the hotel directly to cancel.

What about registration fees?

In response to COVID-19 cancellations, most conference leaders are refunding registration fees in full for both attendees and exhibitors. The refund may not be automatic, some associations such as ACP and the American College of Obstetricians and Gynecologists state it may take up to 45 days for the funds to be credited, depending on the payment used.

If the conference you planned to attend was postponed, the registration fee may be assigned to the new meeting dates and the money may not be refunded. Registration fees for the Minimally Invasive Surgery Symposium, for example, delayed until an unconfirmed date, and for the European Association of Urology (EAU) meeting, postponed until July, will be automatically credited to the rescheduled meeting, according to the websites. If attendees cannot attend the rescheduled EAU meeting, the association will not provide a refund and the registration will not apply to the 2021 meeting, according to its website. However, the group is providing registrants with a free access code for the EAU20 Resource Centre, which contains websites of sessions and scientific content.

A number of physicians have expressed disappointment with the EAU’s postponement on social media. On Twitter, some doctors wrote that the rescheduled dates were bad timing, while others lamented the refund refusal.

The EAU said it regrets that some delegates will experience financial losses, but that the organization has already experienced a significant outlay that cannot be recovered including venue, logistics, travel, and accommodation costs.  

"We are doing what we can to absorb costs, but we need to be realistic about what is affordable; should the organization have to refund all or even most registrations, it would significantly jeopardize the viability of the organization," the EAU said in a statement.  "These are difficult times, not only for the EAU, but on a global scale. Where there are specific cases of hardship or very extenuating financial circumstances, we will be willing to review individual cases. So far, we believe that we have done what we can do to meet the conflicting demands presented by the postponement of the congress, but this is a situation which changes from day to day, and we need to continuously evaluate what might be the best course of action." * 

Contact your medical association directly for details on postponements.
 

What if I’m a presenter?

In an attempt to save the hard work and time that planners and presenters have invested into now-canceled meetings, some conferences are moving to a digital format. The Conference on Retroviruses and Opportunistic Infections (CROI) was the first to convert its in-person conference to a virtual meeting, held from March 8 to 11, 2020. At-home attendees logged onto CROI’s digital platform to hear plenaries, oral abstracts, themed discussion sessions, and symposia.

Dr. Radix was one of many CROI speakers who changed his presentation on HIV prevalence among transgender men to a virtual format.

“We were provided with detailed instructions from CROI about how to do this,” said Dr. Radix, who tweeted about the experience. “For my presentation, I used the video option in PowerPoint; it seemed the most straightforward and didn’t require buying additional software. It was fairly easy to follow the instructions to create the video but it was disappointing to present to an empty room.”

Matthew Spinelli, MD, an HIV researcher with the University of California, San Francisco, who also presented virtually, said it was remarkable that CROI leaders were able to put together the virtual program in such a short time. He delivered his presentation on the accuracy of a real-time urine tenofovir test using PowerPoint and a podcast microphone.

“It seemed to work pretty well,” he said in an interview. “It’s not the same as being there in person, there’s a lot of networking and chance conversations that happen when you’re all in the same place, but it was the right decision to cancel. If I have to be at home or at work doing social distancing, this was the best possible way of doing it.”

Following in CROI’s footsteps, the National Kidney Foundation’s spring conference has moved to a live virtual conference. The 2020 Healthcare Information and Management Systems Society (HIMSS) global health conference also will move to a digital format. Other societies are considering similar virtual options. Check with your meeting website for more details on digital options and attendee access.

agallegos@mdedge.com

*The article was updated on 03/16/2020.

Khadija Hafidh, MD, was already booked on a 14-hour, direct flight from Dubai to Los Angeles, when the American College of Physicians (ACP) announced it was canceling its internal medicine meeting scheduled for April.

Canceling her hotel reservation was not a problem, and she was assured a refund for the conference fee, but her airline ticket was another matter, said Dr. Hafidh, an internist and diabetologist with the Dubai Health Authority.

“The airline I booked my ticket with is willing to waive the change fees, but will deduct a cancellation fee if I choose not to take the trip,” Dr. Hafidh said in an interview. “The cancellation fees is $300. A bit steep I must admit.”

Dr. Hafidh now faces a dilemma: Lose the $300 and cancel, or change her flight dates to June for the American Diabetes Association meeting in Chicago.

“But then again, we aren’t sure if that meeting will take place,” Dr. Hafidh said. “A few weeks ago I thought this whole thing was just a storm in a tea cup. However when it was declared a pandemic yesterday, it brought about another dimension.”

More than 25 medical meetings and conferences across the globe have been canceled or postponed because of COVID-19 concerns. The sudden cancellations have caused reservation woes and travel headaches for thousands of physicians who planned to attend the meetings. Some societies are considering the idea of virtual conferences, while other associations have scrapped their meetings until next year.

For physicians facing a canceled conference, the most likely question is, what now? Read on for tips and suggestions.
 

Reservation refunds vary

Refunds on airfare because of conference cancellations differ, depending on the airline and where you were traveling. Some airlines, such as United Airlines, have waived all change fees for tickets issued March 3, 2020, through March 31, 2020, and passengers can change their dates for up to 12 months after the ticket was issued.

Full refunds often depend on whether your ticket was nonrefundable when purchased. Many airlines, such as Delta, are providing full refunds if the airline canceled your flight. JetBlue is waiving all change and cancellation fees for customers scheduled to travel March 10, 2020, through April 30, 2020.

Las Vegas–based dermatologist H.L. Greenberg, MD, was satisfied with the credit he received from Southwest Airlines after the American Academy of Dermatology (AAD) canceled its Denver meeting. He and his staff were looking forward to the gathering, but he noted that the meeting would likely have been limited, even if it had take place as scheduled.

“I am disappointed that I won’t be able to meet with colleagues and industry to explore what the latest advances and interests are in dermatology,” he said. “Because many academic institutions were forbidding their faculty from traveling, the content of the meeting was going to be severely diminished. It’s just a rough time for everyone.”

Meanwhile, Asa Radix, MD, PhD, a New York–based internist, received a full refund for his Amtrak ticket to Boston when the Conference on Retroviruses and Opportunistic Infections (CROI) scheduled for early March was converted to a virtual meeting. Dr. Radix, senior director of research and education at the Callen-Lorde Community Health Center in New York, left another meeting in Brazil early to get to the Boston conference, he said.

“I was packed, but really that was a minor inconvenience,” he said in an interview. “I appreciate that they prioritized health concerns and changed to a virtual meeting. I received full refunds, no issues whatsoever. [It was] really great since I had no travel insurance.”

Check with your individual airline or train line for information about ticket refunds and credits. Many airlines are currently making special accommodations because of COVID-19. If your flight was covered by trip insurance, also called travel assistance, you are generally protected against unforeseen financial losses such as cancellations. The U.S. Department of Transportation provides this general online resource about airline refunds.
 

Hotel refunds probable

Most meeting organizations who have made the decision to cancel or postpone a conference also have canceled block hotel reservations reserved for the meeting. Medical associations are not directly refunding the hotel costs, but the majority of hotels are refunding reservations with no questions asked. Physicians interviewed for this story all reported no trouble getting refunds for their hotel reservations. However, attendees who did not book a hotel in official housing blocks should contact the hotel directly to cancel.

What about registration fees?

In response to COVID-19 cancellations, most conference leaders are refunding registration fees in full for both attendees and exhibitors. The refund may not be automatic, some associations such as ACP and the American College of Obstetricians and Gynecologists state it may take up to 45 days for the funds to be credited, depending on the payment used.

If the conference you planned to attend was postponed, the registration fee may be assigned to the new meeting dates and the money may not be refunded. Registration fees for the Minimally Invasive Surgery Symposium, for example, delayed until an unconfirmed date, and for the European Association of Urology (EAU) meeting, postponed until July, will be automatically credited to the rescheduled meeting, according to the websites. If attendees cannot attend the rescheduled EAU meeting, the association will not provide a refund and the registration will not apply to the 2021 meeting, according to its website. However, the group is providing registrants with a free access code for the EAU20 Resource Centre, which contains websites of sessions and scientific content.

A number of physicians have expressed disappointment with the EAU’s postponement on social media. On Twitter, some doctors wrote that the rescheduled dates were bad timing, while others lamented the refund refusal.

The EAU said it regrets that some delegates will experience financial losses, but that the organization has already experienced a significant outlay that cannot be recovered including venue, logistics, travel, and accommodation costs.  

"We are doing what we can to absorb costs, but we need to be realistic about what is affordable; should the organization have to refund all or even most registrations, it would significantly jeopardize the viability of the organization," the EAU said in a statement.  "These are difficult times, not only for the EAU, but on a global scale. Where there are specific cases of hardship or very extenuating financial circumstances, we will be willing to review individual cases. So far, we believe that we have done what we can do to meet the conflicting demands presented by the postponement of the congress, but this is a situation which changes from day to day, and we need to continuously evaluate what might be the best course of action." * 

Contact your medical association directly for details on postponements.
 

What if I’m a presenter?

In an attempt to save the hard work and time that planners and presenters have invested into now-canceled meetings, some conferences are moving to a digital format. The Conference on Retroviruses and Opportunistic Infections (CROI) was the first to convert its in-person conference to a virtual meeting, held from March 8 to 11, 2020. At-home attendees logged onto CROI’s digital platform to hear plenaries, oral abstracts, themed discussion sessions, and symposia.

Dr. Radix was one of many CROI speakers who changed his presentation on HIV prevalence among transgender men to a virtual format.

“We were provided with detailed instructions from CROI about how to do this,” said Dr. Radix, who tweeted about the experience. “For my presentation, I used the video option in PowerPoint; it seemed the most straightforward and didn’t require buying additional software. It was fairly easy to follow the instructions to create the video but it was disappointing to present to an empty room.”

Matthew Spinelli, MD, an HIV researcher with the University of California, San Francisco, who also presented virtually, said it was remarkable that CROI leaders were able to put together the virtual program in such a short time. He delivered his presentation on the accuracy of a real-time urine tenofovir test using PowerPoint and a podcast microphone.

“It seemed to work pretty well,” he said in an interview. “It’s not the same as being there in person, there’s a lot of networking and chance conversations that happen when you’re all in the same place, but it was the right decision to cancel. If I have to be at home or at work doing social distancing, this was the best possible way of doing it.”

Following in CROI’s footsteps, the National Kidney Foundation’s spring conference has moved to a live virtual conference. The 2020 Healthcare Information and Management Systems Society (HIMSS) global health conference also will move to a digital format. Other societies are considering similar virtual options. Check with your meeting website for more details on digital options and attendee access.

agallegos@mdedge.com

*The article was updated on 03/16/2020.

Khadija Hafidh, MD, was already booked on a 14-hour, direct flight from Dubai to Los Angeles, when the American College of Physicians (ACP) announced it was canceling its internal medicine meeting scheduled for April.

Canceling her hotel reservation was not a problem, and she was assured a refund for the conference fee, but her airline ticket was another matter, said Dr. Hafidh, an internist and diabetologist with the Dubai Health Authority.

“The airline I booked my ticket with is willing to waive the change fees, but will deduct a cancellation fee if I choose not to take the trip,” Dr. Hafidh said in an interview. “The cancellation fees is $300. A bit steep I must admit.”

Dr. Hafidh now faces a dilemma: Lose the $300 and cancel, or change her flight dates to June for the American Diabetes Association meeting in Chicago.

“But then again, we aren’t sure if that meeting will take place,” Dr. Hafidh said. “A few weeks ago I thought this whole thing was just a storm in a tea cup. However when it was declared a pandemic yesterday, it brought about another dimension.”

More than 25 medical meetings and conferences across the globe have been canceled or postponed because of COVID-19 concerns. The sudden cancellations have caused reservation woes and travel headaches for thousands of physicians who planned to attend the meetings. Some societies are considering the idea of virtual conferences, while other associations have scrapped their meetings until next year.

For physicians facing a canceled conference, the most likely question is, what now? Read on for tips and suggestions.
 

Reservation refunds vary

Refunds on airfare because of conference cancellations differ, depending on the airline and where you were traveling. Some airlines, such as United Airlines, have waived all change fees for tickets issued March 3, 2020, through March 31, 2020, and passengers can change their dates for up to 12 months after the ticket was issued.

Full refunds often depend on whether your ticket was nonrefundable when purchased. Many airlines, such as Delta, are providing full refunds if the airline canceled your flight. JetBlue is waiving all change and cancellation fees for customers scheduled to travel March 10, 2020, through April 30, 2020.

Las Vegas–based dermatologist H.L. Greenberg, MD, was satisfied with the credit he received from Southwest Airlines after the American Academy of Dermatology (AAD) canceled its Denver meeting. He and his staff were looking forward to the gathering, but he noted that the meeting would likely have been limited, even if it had take place as scheduled.

“I am disappointed that I won’t be able to meet with colleagues and industry to explore what the latest advances and interests are in dermatology,” he said. “Because many academic institutions were forbidding their faculty from traveling, the content of the meeting was going to be severely diminished. It’s just a rough time for everyone.”

Meanwhile, Asa Radix, MD, PhD, a New York–based internist, received a full refund for his Amtrak ticket to Boston when the Conference on Retroviruses and Opportunistic Infections (CROI) scheduled for early March was converted to a virtual meeting. Dr. Radix, senior director of research and education at the Callen-Lorde Community Health Center in New York, left another meeting in Brazil early to get to the Boston conference, he said.

“I was packed, but really that was a minor inconvenience,” he said in an interview. “I appreciate that they prioritized health concerns and changed to a virtual meeting. I received full refunds, no issues whatsoever. [It was] really great since I had no travel insurance.”

Check with your individual airline or train line for information about ticket refunds and credits. Many airlines are currently making special accommodations because of COVID-19. If your flight was covered by trip insurance, also called travel assistance, you are generally protected against unforeseen financial losses such as cancellations. The U.S. Department of Transportation provides this general online resource about airline refunds.
 

Hotel refunds probable

Most meeting organizations who have made the decision to cancel or postpone a conference also have canceled block hotel reservations reserved for the meeting. Medical associations are not directly refunding the hotel costs, but the majority of hotels are refunding reservations with no questions asked. Physicians interviewed for this story all reported no trouble getting refunds for their hotel reservations. However, attendees who did not book a hotel in official housing blocks should contact the hotel directly to cancel.

What about registration fees?

In response to COVID-19 cancellations, most conference leaders are refunding registration fees in full for both attendees and exhibitors. The refund may not be automatic, some associations such as ACP and the American College of Obstetricians and Gynecologists state it may take up to 45 days for the funds to be credited, depending on the payment used.

If the conference you planned to attend was postponed, the registration fee may be assigned to the new meeting dates and the money may not be refunded. Registration fees for the Minimally Invasive Surgery Symposium, for example, delayed until an unconfirmed date, and for the European Association of Urology (EAU) meeting, postponed until July, will be automatically credited to the rescheduled meeting, according to the websites. If attendees cannot attend the rescheduled EAU meeting, the association will not provide a refund and the registration will not apply to the 2021 meeting, according to its website. However, the group is providing registrants with a free access code for the EAU20 Resource Centre, which contains websites of sessions and scientific content.

A number of physicians have expressed disappointment with the EAU’s postponement on social media. On Twitter, some doctors wrote that the rescheduled dates were bad timing, while others lamented the refund refusal.

The EAU said it regrets that some delegates will experience financial losses, but that the organization has already experienced a significant outlay that cannot be recovered including venue, logistics, travel, and accommodation costs.  

"We are doing what we can to absorb costs, but we need to be realistic about what is affordable; should the organization have to refund all or even most registrations, it would significantly jeopardize the viability of the organization," the EAU said in a statement.  "These are difficult times, not only for the EAU, but on a global scale. Where there are specific cases of hardship or very extenuating financial circumstances, we will be willing to review individual cases. So far, we believe that we have done what we can do to meet the conflicting demands presented by the postponement of the congress, but this is a situation which changes from day to day, and we need to continuously evaluate what might be the best course of action." * 

Contact your medical association directly for details on postponements.
 

What if I’m a presenter?

In an attempt to save the hard work and time that planners and presenters have invested into now-canceled meetings, some conferences are moving to a digital format. The Conference on Retroviruses and Opportunistic Infections (CROI) was the first to convert its in-person conference to a virtual meeting, held from March 8 to 11, 2020. At-home attendees logged onto CROI’s digital platform to hear plenaries, oral abstracts, themed discussion sessions, and symposia.

Dr. Radix was one of many CROI speakers who changed his presentation on HIV prevalence among transgender men to a virtual format.

“We were provided with detailed instructions from CROI about how to do this,” said Dr. Radix, who tweeted about the experience. “For my presentation, I used the video option in PowerPoint; it seemed the most straightforward and didn’t require buying additional software. It was fairly easy to follow the instructions to create the video but it was disappointing to present to an empty room.”

Matthew Spinelli, MD, an HIV researcher with the University of California, San Francisco, who also presented virtually, said it was remarkable that CROI leaders were able to put together the virtual program in such a short time. He delivered his presentation on the accuracy of a real-time urine tenofovir test using PowerPoint and a podcast microphone.

“It seemed to work pretty well,” he said in an interview. “It’s not the same as being there in person, there’s a lot of networking and chance conversations that happen when you’re all in the same place, but it was the right decision to cancel. If I have to be at home or at work doing social distancing, this was the best possible way of doing it.”

Following in CROI’s footsteps, the National Kidney Foundation’s spring conference has moved to a live virtual conference. The 2020 Healthcare Information and Management Systems Society (HIMSS) global health conference also will move to a digital format. Other societies are considering similar virtual options. Check with your meeting website for more details on digital options and attendee access.

agallegos@mdedge.com

*The article was updated on 03/16/2020.

Pediatric cases of COVID-19 infection are typically mild, but underlying coinfection may be more common in children than in adults, according to an analysis of clinical, laboratory, and chest CT features of pediatric inpatients in Wuhan, China.

Robert Wei/iStock/Getty Images Plus

The findings point toward a need for early chest CT with corresponding pathogen detection in children with suspected COVID-19 infection, Wei Xia, MD, of Huazhong University of Science and Technology, Wuhan, China, and colleagues reported in Pediatric Pulmonology.

The most common symptoms in 20 pediatric patients hospitalized between Jan. 23 and Feb. 8, 2020, with COVID-19 infection confirmed by the pharyngeal swab COVID-19 nucleic acid test were fever and cough, which occurred in 60% and 65% of patients, respectively. Coinfection was detected in eight patients (40%), they noted.

Clinical manifestations were similar to those seen in adults, but overall symptoms were relatively mild and overall prognosis was good. Of particular note, 7 of the 20 (35%) patients had a previously diagnosed congenital or acquired diseases, suggesting that children with underlying conditions may be more susceptible, Dr. Xia and colleagues wrote.

Laboratory findings also were notable in that 80% of the children had procalcitonin (PCT) elevations not typically seen in adults with COVID-19. PCT is a marker for bacterial infection and “[this finding] may suggest that routine antibacterial treatment should be considered in pediatric patients,” the investigators wrote.

As for imaging results, chest CT findings in children were similar to those in adults.“The typical manifestations were unilateral or bilateral subpleural ground-glass opacities, and consolidations with surrounding halo signs,” Dr. Xia and associates wrote, adding that consolidations with surrounding halo sign accounted for about half the pediatric cases and should be considered as “typical signs in pediatric patients.”

Pediatric cases were “rather rare” in the early days of the COVID-19 outbreak in Wuhan, where the first cases of infection were reported.

“As a pediatric group is usually susceptible to upper respiratory tract infection, because of their developing immune system, the delayed presence of pediatric patients is confusing,” the investigators wrote, noting that a low detection rate of pharyngeal swab COVID-19 nucleic acid test, distinguishing the virus from other common respiratory tract infectious pathogens in pediatric patients, “is still a problem.”

To better characterize the clinical and imaging features in children versus adults with COVID-19, Dr. Xia and associates reviewed these 20 pediatric cases, including 13 boys and 7 girls with ages ranging from less than 1 month to 14 years, 7 months (median 2 years, 1.5 months). Thirteen had an identified close contact with a COVID-19–diagnosed family member, and all were treated in an isolation ward. A total of 18 children were cured and discharged after an average stay of 13 days, and 2 neonates remained under observation because of positive swab results with negative CT findings. The investigators speculated that the different findings in neonates were perhaps caused by the influence of delivery on sampling or the specific CT manifestations for neonates, adding that more samples are needed for further clarification.

Based on these findings, “the CT imaging of COVID-19 infection should be differentiated with other virus pneumonias such as influenza virus, parainfluenza virus, respiratory syncytial virus, and adenovirus,” they concluded. It also should “be differentiated from bacterial pneumonia, mycoplasma pneumonia, and chlamydia pneumonia ... the density of pneumonia lesions caused by the latter pathogens is relatively higher.”

However, Dr. Xia and colleagues noted that chest CT manifestations of pneumonia caused by different pathogens overlap, and COVID-19 pneumonia “can be superimposed with serious and complex imaging manifestations, so epidemiological and etiological examinations should be combined.”

The investigators concluded that COVID-19 virus pneumonia in children is generally mild, and that the characteristic changes of subpleural ground-glass opacities and consolidations with surrounding halo on chest CT provide an “effective means for follow-up and evaluating the changes of lung lesions.”

“In the case that the positive rate of COVID-19 nucleic acid test from pharyngeal swab samples is not high, the early detection of lesions by CT is conducive to reasonable management and early treatment for pediatric patients. However, the diagnosis of COVID-19 pneumonia by CT imaging alone is not sufficient enough, especially in the case of coinfection with other pathogens,” Dr. Xia and associates wrote. “Therefore, early chest CT screening and timely follow-up, combined with corresponding pathogen detection, is a feasible clinical protocol in children.”

An early study

In a separate retrospective analysis described in a letter to the editor of the New England Journal of Medicine, Weiyong Liu, PhD, of Tongji Hospital of Huazhong University of Science and Technology and colleagues found that the most frequently detected pathogens in 366 children under the age of 16 years hospitalized with respiratory infections in Wuhan during Jan. 7-15, 2020, were influenza A virus (6.3% of cases) and influenza B virus (5.5% of cases), whereas COVID-19 was detected in 1.6% of cases.

The median age of the COVID-19 patients in that series was 3 years (range 1-7 years), and in contrast to the findings of Xia et al., all previously had been “completely healthy.” Common characteristics were high fever and cough in all six patients, and vomiting in four patients. Five had pneumonia as assessed by X-ray, and CTs showed typical viral pneumonia patterns.

One patient was admitted to a pediatric ICU. All patients received antiviral agents, antibiotic agents, and supportive therapies; all recovered after a median hospital stay of 7.5 days (median range, 5-13 days).

In contrast with the findings of Xia et al., the findings of Liu et al. showed COVID-19 caused moderate to severe respiratory illness in children, and that infections in children were occurring early in the epidemic.
 

Some perspective

In an interview regarding the findings by Xia et al., Stephen I. Pelton, MD, professor of pediatrics and epidemiology at Boston University, and director of pediatric infectious diseases at Boston Medical Center, noted the absence of fever in 40% of cases.

“This is important, as the criteria for testing by public health departments has been high fever, cough, and shortness of breath,” he said. “The absence of fever is not inconsistent with COVID-19 disease.”

Another important point regarding the findings by Xia et al. is that the highest attack rates appear to be in children under 1 year of age, he said, further noting that the finding of concurrent influenza A, influenza B, or respiratory syncytial virus underscores that “concurrent infection can occur, and the presence of another virus in diagnostic tests does not mean that COVID-19 is not causal.”

As for whether the finding of elevated procalcitonin levels in 80% of cases reflects COVID-19 disease or coinfection with bacteria, the answer is unclear. But none of the children in the study were proven to have bacterial disease, he said, adding that “this marker will need to be interpreted with caution in the setting of COVID-19 disease.”

Dr. Xia and colleagues reported having no disclosures. Dr. Liu and associates also reported having no disclosures. The study by Liu et al. was supported by the Ministry of Science and Technology of China, the National Mega Project on Major Infectious Disease Prevention, and the National Key Research and Development Program of China.

sworcester@mdedge.com

SOURCES: Xia W et al. Ped Pulmonol. 2020 Mar 5. doi: 10.1002/ppul.24718; Liu W et al. N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMc2003717.

Pediatric cases of COVID-19 infection are typically mild, but underlying coinfection may be more common in children than in adults, according to an analysis of clinical, laboratory, and chest CT features of pediatric inpatients in Wuhan, China.

Robert Wei/iStock/Getty Images Plus

The findings point toward a need for early chest CT with corresponding pathogen detection in children with suspected COVID-19 infection, Wei Xia, MD, of Huazhong University of Science and Technology, Wuhan, China, and colleagues reported in Pediatric Pulmonology.

The most common symptoms in 20 pediatric patients hospitalized between Jan. 23 and Feb. 8, 2020, with COVID-19 infection confirmed by the pharyngeal swab COVID-19 nucleic acid test were fever and cough, which occurred in 60% and 65% of patients, respectively. Coinfection was detected in eight patients (40%), they noted.

Clinical manifestations were similar to those seen in adults, but overall symptoms were relatively mild and overall prognosis was good. Of particular note, 7 of the 20 (35%) patients had a previously diagnosed congenital or acquired diseases, suggesting that children with underlying conditions may be more susceptible, Dr. Xia and colleagues wrote.

Laboratory findings also were notable in that 80% of the children had procalcitonin (PCT) elevations not typically seen in adults with COVID-19. PCT is a marker for bacterial infection and “[this finding] may suggest that routine antibacterial treatment should be considered in pediatric patients,” the investigators wrote.

As for imaging results, chest CT findings in children were similar to those in adults.“The typical manifestations were unilateral or bilateral subpleural ground-glass opacities, and consolidations with surrounding halo signs,” Dr. Xia and associates wrote, adding that consolidations with surrounding halo sign accounted for about half the pediatric cases and should be considered as “typical signs in pediatric patients.”

Pediatric cases were “rather rare” in the early days of the COVID-19 outbreak in Wuhan, where the first cases of infection were reported.

“As a pediatric group is usually susceptible to upper respiratory tract infection, because of their developing immune system, the delayed presence of pediatric patients is confusing,” the investigators wrote, noting that a low detection rate of pharyngeal swab COVID-19 nucleic acid test, distinguishing the virus from other common respiratory tract infectious pathogens in pediatric patients, “is still a problem.”

To better characterize the clinical and imaging features in children versus adults with COVID-19, Dr. Xia and associates reviewed these 20 pediatric cases, including 13 boys and 7 girls with ages ranging from less than 1 month to 14 years, 7 months (median 2 years, 1.5 months). Thirteen had an identified close contact with a COVID-19–diagnosed family member, and all were treated in an isolation ward. A total of 18 children were cured and discharged after an average stay of 13 days, and 2 neonates remained under observation because of positive swab results with negative CT findings. The investigators speculated that the different findings in neonates were perhaps caused by the influence of delivery on sampling or the specific CT manifestations for neonates, adding that more samples are needed for further clarification.

Based on these findings, “the CT imaging of COVID-19 infection should be differentiated with other virus pneumonias such as influenza virus, parainfluenza virus, respiratory syncytial virus, and adenovirus,” they concluded. It also should “be differentiated from bacterial pneumonia, mycoplasma pneumonia, and chlamydia pneumonia ... the density of pneumonia lesions caused by the latter pathogens is relatively higher.”

However, Dr. Xia and colleagues noted that chest CT manifestations of pneumonia caused by different pathogens overlap, and COVID-19 pneumonia “can be superimposed with serious and complex imaging manifestations, so epidemiological and etiological examinations should be combined.”

The investigators concluded that COVID-19 virus pneumonia in children is generally mild, and that the characteristic changes of subpleural ground-glass opacities and consolidations with surrounding halo on chest CT provide an “effective means for follow-up and evaluating the changes of lung lesions.”

“In the case that the positive rate of COVID-19 nucleic acid test from pharyngeal swab samples is not high, the early detection of lesions by CT is conducive to reasonable management and early treatment for pediatric patients. However, the diagnosis of COVID-19 pneumonia by CT imaging alone is not sufficient enough, especially in the case of coinfection with other pathogens,” Dr. Xia and associates wrote. “Therefore, early chest CT screening and timely follow-up, combined with corresponding pathogen detection, is a feasible clinical protocol in children.”

An early study

In a separate retrospective analysis described in a letter to the editor of the New England Journal of Medicine, Weiyong Liu, PhD, of Tongji Hospital of Huazhong University of Science and Technology and colleagues found that the most frequently detected pathogens in 366 children under the age of 16 years hospitalized with respiratory infections in Wuhan during Jan. 7-15, 2020, were influenza A virus (6.3% of cases) and influenza B virus (5.5% of cases), whereas COVID-19 was detected in 1.6% of cases.

The median age of the COVID-19 patients in that series was 3 years (range 1-7 years), and in contrast to the findings of Xia et al., all previously had been “completely healthy.” Common characteristics were high fever and cough in all six patients, and vomiting in four patients. Five had pneumonia as assessed by X-ray, and CTs showed typical viral pneumonia patterns.

One patient was admitted to a pediatric ICU. All patients received antiviral agents, antibiotic agents, and supportive therapies; all recovered after a median hospital stay of 7.5 days (median range, 5-13 days).

In contrast with the findings of Xia et al., the findings of Liu et al. showed COVID-19 caused moderate to severe respiratory illness in children, and that infections in children were occurring early in the epidemic.
 

Some perspective

In an interview regarding the findings by Xia et al., Stephen I. Pelton, MD, professor of pediatrics and epidemiology at Boston University, and director of pediatric infectious diseases at Boston Medical Center, noted the absence of fever in 40% of cases.

“This is important, as the criteria for testing by public health departments has been high fever, cough, and shortness of breath,” he said. “The absence of fever is not inconsistent with COVID-19 disease.”

Another important point regarding the findings by Xia et al. is that the highest attack rates appear to be in children under 1 year of age, he said, further noting that the finding of concurrent influenza A, influenza B, or respiratory syncytial virus underscores that “concurrent infection can occur, and the presence of another virus in diagnostic tests does not mean that COVID-19 is not causal.”

As for whether the finding of elevated procalcitonin levels in 80% of cases reflects COVID-19 disease or coinfection with bacteria, the answer is unclear. But none of the children in the study were proven to have bacterial disease, he said, adding that “this marker will need to be interpreted with caution in the setting of COVID-19 disease.”

Dr. Xia and colleagues reported having no disclosures. Dr. Liu and associates also reported having no disclosures. The study by Liu et al. was supported by the Ministry of Science and Technology of China, the National Mega Project on Major Infectious Disease Prevention, and the National Key Research and Development Program of China.

sworcester@mdedge.com

SOURCES: Xia W et al. Ped Pulmonol. 2020 Mar 5. doi: 10.1002/ppul.24718; Liu W et al. N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMc2003717.

Pediatric cases of COVID-19 infection are typically mild, but underlying coinfection may be more common in children than in adults, according to an analysis of clinical, laboratory, and chest CT features of pediatric inpatients in Wuhan, China.

Robert Wei/iStock/Getty Images Plus

The findings point toward a need for early chest CT with corresponding pathogen detection in children with suspected COVID-19 infection, Wei Xia, MD, of Huazhong University of Science and Technology, Wuhan, China, and colleagues reported in Pediatric Pulmonology.

The most common symptoms in 20 pediatric patients hospitalized between Jan. 23 and Feb. 8, 2020, with COVID-19 infection confirmed by the pharyngeal swab COVID-19 nucleic acid test were fever and cough, which occurred in 60% and 65% of patients, respectively. Coinfection was detected in eight patients (40%), they noted.

Clinical manifestations were similar to those seen in adults, but overall symptoms were relatively mild and overall prognosis was good. Of particular note, 7 of the 20 (35%) patients had a previously diagnosed congenital or acquired diseases, suggesting that children with underlying conditions may be more susceptible, Dr. Xia and colleagues wrote.

Laboratory findings also were notable in that 80% of the children had procalcitonin (PCT) elevations not typically seen in adults with COVID-19. PCT is a marker for bacterial infection and “[this finding] may suggest that routine antibacterial treatment should be considered in pediatric patients,” the investigators wrote.

As for imaging results, chest CT findings in children were similar to those in adults.“The typical manifestations were unilateral or bilateral subpleural ground-glass opacities, and consolidations with surrounding halo signs,” Dr. Xia and associates wrote, adding that consolidations with surrounding halo sign accounted for about half the pediatric cases and should be considered as “typical signs in pediatric patients.”

Pediatric cases were “rather rare” in the early days of the COVID-19 outbreak in Wuhan, where the first cases of infection were reported.

“As a pediatric group is usually susceptible to upper respiratory tract infection, because of their developing immune system, the delayed presence of pediatric patients is confusing,” the investigators wrote, noting that a low detection rate of pharyngeal swab COVID-19 nucleic acid test, distinguishing the virus from other common respiratory tract infectious pathogens in pediatric patients, “is still a problem.”

To better characterize the clinical and imaging features in children versus adults with COVID-19, Dr. Xia and associates reviewed these 20 pediatric cases, including 13 boys and 7 girls with ages ranging from less than 1 month to 14 years, 7 months (median 2 years, 1.5 months). Thirteen had an identified close contact with a COVID-19–diagnosed family member, and all were treated in an isolation ward. A total of 18 children were cured and discharged after an average stay of 13 days, and 2 neonates remained under observation because of positive swab results with negative CT findings. The investigators speculated that the different findings in neonates were perhaps caused by the influence of delivery on sampling or the specific CT manifestations for neonates, adding that more samples are needed for further clarification.

Based on these findings, “the CT imaging of COVID-19 infection should be differentiated with other virus pneumonias such as influenza virus, parainfluenza virus, respiratory syncytial virus, and adenovirus,” they concluded. It also should “be differentiated from bacterial pneumonia, mycoplasma pneumonia, and chlamydia pneumonia ... the density of pneumonia lesions caused by the latter pathogens is relatively higher.”

However, Dr. Xia and colleagues noted that chest CT manifestations of pneumonia caused by different pathogens overlap, and COVID-19 pneumonia “can be superimposed with serious and complex imaging manifestations, so epidemiological and etiological examinations should be combined.”

The investigators concluded that COVID-19 virus pneumonia in children is generally mild, and that the characteristic changes of subpleural ground-glass opacities and consolidations with surrounding halo on chest CT provide an “effective means for follow-up and evaluating the changes of lung lesions.”

“In the case that the positive rate of COVID-19 nucleic acid test from pharyngeal swab samples is not high, the early detection of lesions by CT is conducive to reasonable management and early treatment for pediatric patients. However, the diagnosis of COVID-19 pneumonia by CT imaging alone is not sufficient enough, especially in the case of coinfection with other pathogens,” Dr. Xia and associates wrote. “Therefore, early chest CT screening and timely follow-up, combined with corresponding pathogen detection, is a feasible clinical protocol in children.”

An early study

In a separate retrospective analysis described in a letter to the editor of the New England Journal of Medicine, Weiyong Liu, PhD, of Tongji Hospital of Huazhong University of Science and Technology and colleagues found that the most frequently detected pathogens in 366 children under the age of 16 years hospitalized with respiratory infections in Wuhan during Jan. 7-15, 2020, were influenza A virus (6.3% of cases) and influenza B virus (5.5% of cases), whereas COVID-19 was detected in 1.6% of cases.

The median age of the COVID-19 patients in that series was 3 years (range 1-7 years), and in contrast to the findings of Xia et al., all previously had been “completely healthy.” Common characteristics were high fever and cough in all six patients, and vomiting in four patients. Five had pneumonia as assessed by X-ray, and CTs showed typical viral pneumonia patterns.

One patient was admitted to a pediatric ICU. All patients received antiviral agents, antibiotic agents, and supportive therapies; all recovered after a median hospital stay of 7.5 days (median range, 5-13 days).

In contrast with the findings of Xia et al., the findings of Liu et al. showed COVID-19 caused moderate to severe respiratory illness in children, and that infections in children were occurring early in the epidemic.
 

Some perspective

In an interview regarding the findings by Xia et al., Stephen I. Pelton, MD, professor of pediatrics and epidemiology at Boston University, and director of pediatric infectious diseases at Boston Medical Center, noted the absence of fever in 40% of cases.

“This is important, as the criteria for testing by public health departments has been high fever, cough, and shortness of breath,” he said. “The absence of fever is not inconsistent with COVID-19 disease.”

Another important point regarding the findings by Xia et al. is that the highest attack rates appear to be in children under 1 year of age, he said, further noting that the finding of concurrent influenza A, influenza B, or respiratory syncytial virus underscores that “concurrent infection can occur, and the presence of another virus in diagnostic tests does not mean that COVID-19 is not causal.”

As for whether the finding of elevated procalcitonin levels in 80% of cases reflects COVID-19 disease or coinfection with bacteria, the answer is unclear. But none of the children in the study were proven to have bacterial disease, he said, adding that “this marker will need to be interpreted with caution in the setting of COVID-19 disease.”

Dr. Xia and colleagues reported having no disclosures. Dr. Liu and associates also reported having no disclosures. The study by Liu et al. was supported by the Ministry of Science and Technology of China, the National Mega Project on Major Infectious Disease Prevention, and the National Key Research and Development Program of China.

sworcester@mdedge.com

SOURCES: Xia W et al. Ped Pulmonol. 2020 Mar 5. doi: 10.1002/ppul.24718; Liu W et al. N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMc2003717.

Patients with sickle cell disease (SCD) plus vitamin D deficiency were found to have more hospitalization outcomes, including number of emergency department (ED) visits, the number of hospital admissions for pain crisis, and the length of hospital admission, according to a study published online by researchers from New York-Presbyterian Brooklyn Methodist Hospital.

Dr_Microbe/Thinkstock

The researchers performed a retrospective chart review of all 134 pediatric patients with SCD (aged 1-21 years) from January 2015 to January 2016 in an urban-based hospital setting. Ninety patients with at least one reported vitamin D level who maintained follow-up during the time studied were enrolled. Hospitalization rates were compared between vitamin D deficiency (< 20 ng/mL) and sufficiency (> 20 ng/mL) patients.

When compared to patients with SCD and sufficient vitamin D levels, patients with both SCD and vitamin D deficiency were more likely to have at least one ED visit (P < .01), at least one admission for pain crisis (P < .01), and a longer length of admission (^P < .0001), the researchers found.

“Screening and treatment for vitamin D deficiency is generally cost effective and readily available, potentially having a significant impact on the quality of life for those living with sickle cell disease,” the researchers concluded.

The authors reported that there was no study funding and that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Brown B et al. Blood Cells Mol Dis. 2020. doi: 10.1016/j.bcmd.2020.102415.

Patients with sickle cell disease (SCD) plus vitamin D deficiency were found to have more hospitalization outcomes, including number of emergency department (ED) visits, the number of hospital admissions for pain crisis, and the length of hospital admission, according to a study published online by researchers from New York-Presbyterian Brooklyn Methodist Hospital.

Dr_Microbe/Thinkstock

The researchers performed a retrospective chart review of all 134 pediatric patients with SCD (aged 1-21 years) from January 2015 to January 2016 in an urban-based hospital setting. Ninety patients with at least one reported vitamin D level who maintained follow-up during the time studied were enrolled. Hospitalization rates were compared between vitamin D deficiency (< 20 ng/mL) and sufficiency (> 20 ng/mL) patients.

When compared to patients with SCD and sufficient vitamin D levels, patients with both SCD and vitamin D deficiency were more likely to have at least one ED visit (P < .01), at least one admission for pain crisis (P < .01), and a longer length of admission (^P < .0001), the researchers found.

“Screening and treatment for vitamin D deficiency is generally cost effective and readily available, potentially having a significant impact on the quality of life for those living with sickle cell disease,” the researchers concluded.

The authors reported that there was no study funding and that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Brown B et al. Blood Cells Mol Dis. 2020. doi: 10.1016/j.bcmd.2020.102415.

Patients with sickle cell disease (SCD) plus vitamin D deficiency were found to have more hospitalization outcomes, including number of emergency department (ED) visits, the number of hospital admissions for pain crisis, and the length of hospital admission, according to a study published online by researchers from New York-Presbyterian Brooklyn Methodist Hospital.

Dr_Microbe/Thinkstock

The researchers performed a retrospective chart review of all 134 pediatric patients with SCD (aged 1-21 years) from January 2015 to January 2016 in an urban-based hospital setting. Ninety patients with at least one reported vitamin D level who maintained follow-up during the time studied were enrolled. Hospitalization rates were compared between vitamin D deficiency (< 20 ng/mL) and sufficiency (> 20 ng/mL) patients.

When compared to patients with SCD and sufficient vitamin D levels, patients with both SCD and vitamin D deficiency were more likely to have at least one ED visit (P < .01), at least one admission for pain crisis (P < .01), and a longer length of admission (^P < .0001), the researchers found.

“Screening and treatment for vitamin D deficiency is generally cost effective and readily available, potentially having a significant impact on the quality of life for those living with sickle cell disease,” the researchers concluded.

The authors reported that there was no study funding and that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Brown B et al. Blood Cells Mol Dis. 2020. doi: 10.1016/j.bcmd.2020.102415.

NATIONAL HARBOR, MD. – In a pooled analysis of three trials conducted with the transcatheter Carillon Mitral Contour System for mitral valve repair, the 5-year survival is 56.2%, which is an encouraging outcome that justifies the ongoing multinational pivotal Carillon trial, according to the principal investigator of the analysis presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

In patients with functional mitral valve regurgitation (FMR), “the Carillon device shows extremely encouraging long-term mortality data from prospective controlled trials in comparison with guideline-directed medical therapy or with the COAPT results,” according to Janusz Lipiecki, MD, PhD, department of cardiology, University Hospital, Clermont-Ferrand, France.

The COAPT trial is an important benchmark, because it was the first large, randomized trial to show benefit for a percutaneous device in the treatment of heart failure patients with moderate to severe FMR (N Engl J Med. 2018;379:2307-18). The study associated the MitraClip with a nearly 40% reduction in all-cause mortality (29.1% vs. 46.1%) at 24 months, relative to guideline-directed medical therapy (GDMT).

The Carillon device, which is also delivered percutaneously, does not engage the valve leaflets to treat FMR. Rather, it is anchored in coronary sinus to reform the mitral annulus. This reduces FMR without damage to the mitral valve, thus preserving the potential for future valve repairs, according to Dr. Lipiecki, who reported that more than 1,100 devices have now been implanted, mostly in Europe.

The data so far are encouraging, said Dr. Lipiecki, who provided survival data in 74 patients followed for at least 5 years. Of these, 23 were drawn from the REDUCE FMR trial, which was blinded and sham controlled, and the remainder from the TITAN and TITAN II studies, which were prospective but not controlled.

In this series of 74 patients, there were no serious complications associated with the procedure, and all achieved a reduction in mitral regurgitation at 12 months, Dr. Lipiecki said. Furthermore, the reduction in FMR was associated with improvements in symptoms and “favorable remodeling” reflected in reduced left ventricular volume, he said.

In this series, the 5-year survival is 56%, which substantially exceeds what would be expected with GDMT, according to Dr. Lipiecki.

There were no baseline predictors of long-term survival, but improvements within the 6 months in functional heart class, 6-minute walk distance (6MWD), and mitral regurgitation were significantly associated with a greater likelihood of being alive at 5 years.

Although there is no comparable follow-up with other devices, including the MitraClip, Dr. Lipiecki did compare the 67.9% survival at 3 years in this series to that of the COAPT trial. He restricted the comparison to those treated for grade 3+ or 4+ mitral regurgitation. At 36 months, survival rates were 57.2% and 44.5% for those treated with MitraClip and GDMT, respectively.

“COAPT patients might not be comparable for a variety of reasons, including the anatomic restrictions important to the use of either of these devices,” Dr. Lipiecki acknowledged, but he said the long-term data with the Carillon device provide support for the pivotal Carillon trial now enrolling.

In this blinded trial, more than 350 patients at 75 sites are being randomized to placement of the Carillon device, which has been available in Europe since 2011, or a sham procedure. The trial is scheduled for completion in 2025.

NATIONAL HARBOR, MD. – In a pooled analysis of three trials conducted with the transcatheter Carillon Mitral Contour System for mitral valve repair, the 5-year survival is 56.2%, which is an encouraging outcome that justifies the ongoing multinational pivotal Carillon trial, according to the principal investigator of the analysis presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

In patients with functional mitral valve regurgitation (FMR), “the Carillon device shows extremely encouraging long-term mortality data from prospective controlled trials in comparison with guideline-directed medical therapy or with the COAPT results,” according to Janusz Lipiecki, MD, PhD, department of cardiology, University Hospital, Clermont-Ferrand, France.

The COAPT trial is an important benchmark, because it was the first large, randomized trial to show benefit for a percutaneous device in the treatment of heart failure patients with moderate to severe FMR (N Engl J Med. 2018;379:2307-18). The study associated the MitraClip with a nearly 40% reduction in all-cause mortality (29.1% vs. 46.1%) at 24 months, relative to guideline-directed medical therapy (GDMT).

The Carillon device, which is also delivered percutaneously, does not engage the valve leaflets to treat FMR. Rather, it is anchored in coronary sinus to reform the mitral annulus. This reduces FMR without damage to the mitral valve, thus preserving the potential for future valve repairs, according to Dr. Lipiecki, who reported that more than 1,100 devices have now been implanted, mostly in Europe.

The data so far are encouraging, said Dr. Lipiecki, who provided survival data in 74 patients followed for at least 5 years. Of these, 23 were drawn from the REDUCE FMR trial, which was blinded and sham controlled, and the remainder from the TITAN and TITAN II studies, which were prospective but not controlled.

In this series of 74 patients, there were no serious complications associated with the procedure, and all achieved a reduction in mitral regurgitation at 12 months, Dr. Lipiecki said. Furthermore, the reduction in FMR was associated with improvements in symptoms and “favorable remodeling” reflected in reduced left ventricular volume, he said.

In this series, the 5-year survival is 56%, which substantially exceeds what would be expected with GDMT, according to Dr. Lipiecki.

There were no baseline predictors of long-term survival, but improvements within the 6 months in functional heart class, 6-minute walk distance (6MWD), and mitral regurgitation were significantly associated with a greater likelihood of being alive at 5 years.

Although there is no comparable follow-up with other devices, including the MitraClip, Dr. Lipiecki did compare the 67.9% survival at 3 years in this series to that of the COAPT trial. He restricted the comparison to those treated for grade 3+ or 4+ mitral regurgitation. At 36 months, survival rates were 57.2% and 44.5% for those treated with MitraClip and GDMT, respectively.

“COAPT patients might not be comparable for a variety of reasons, including the anatomic restrictions important to the use of either of these devices,” Dr. Lipiecki acknowledged, but he said the long-term data with the Carillon device provide support for the pivotal Carillon trial now enrolling.

In this blinded trial, more than 350 patients at 75 sites are being randomized to placement of the Carillon device, which has been available in Europe since 2011, or a sham procedure. The trial is scheduled for completion in 2025.

NATIONAL HARBOR, MD. – In a pooled analysis of three trials conducted with the transcatheter Carillon Mitral Contour System for mitral valve repair, the 5-year survival is 56.2%, which is an encouraging outcome that justifies the ongoing multinational pivotal Carillon trial, according to the principal investigator of the analysis presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

In patients with functional mitral valve regurgitation (FMR), “the Carillon device shows extremely encouraging long-term mortality data from prospective controlled trials in comparison with guideline-directed medical therapy or with the COAPT results,” according to Janusz Lipiecki, MD, PhD, department of cardiology, University Hospital, Clermont-Ferrand, France.

The COAPT trial is an important benchmark, because it was the first large, randomized trial to show benefit for a percutaneous device in the treatment of heart failure patients with moderate to severe FMR (N Engl J Med. 2018;379:2307-18). The study associated the MitraClip with a nearly 40% reduction in all-cause mortality (29.1% vs. 46.1%) at 24 months, relative to guideline-directed medical therapy (GDMT).

The Carillon device, which is also delivered percutaneously, does not engage the valve leaflets to treat FMR. Rather, it is anchored in coronary sinus to reform the mitral annulus. This reduces FMR without damage to the mitral valve, thus preserving the potential for future valve repairs, according to Dr. Lipiecki, who reported that more than 1,100 devices have now been implanted, mostly in Europe.

The data so far are encouraging, said Dr. Lipiecki, who provided survival data in 74 patients followed for at least 5 years. Of these, 23 were drawn from the REDUCE FMR trial, which was blinded and sham controlled, and the remainder from the TITAN and TITAN II studies, which were prospective but not controlled.

In this series of 74 patients, there were no serious complications associated with the procedure, and all achieved a reduction in mitral regurgitation at 12 months, Dr. Lipiecki said. Furthermore, the reduction in FMR was associated with improvements in symptoms and “favorable remodeling” reflected in reduced left ventricular volume, he said.

In this series, the 5-year survival is 56%, which substantially exceeds what would be expected with GDMT, according to Dr. Lipiecki.

There were no baseline predictors of long-term survival, but improvements within the 6 months in functional heart class, 6-minute walk distance (6MWD), and mitral regurgitation were significantly associated with a greater likelihood of being alive at 5 years.

Although there is no comparable follow-up with other devices, including the MitraClip, Dr. Lipiecki did compare the 67.9% survival at 3 years in this series to that of the COAPT trial. He restricted the comparison to those treated for grade 3+ or 4+ mitral regurgitation. At 36 months, survival rates were 57.2% and 44.5% for those treated with MitraClip and GDMT, respectively.

“COAPT patients might not be comparable for a variety of reasons, including the anatomic restrictions important to the use of either of these devices,” Dr. Lipiecki acknowledged, but he said the long-term data with the Carillon device provide support for the pivotal Carillon trial now enrolling.

In this blinded trial, more than 350 patients at 75 sites are being randomized to placement of the Carillon device, which has been available in Europe since 2011, or a sham procedure. The trial is scheduled for completion in 2025.

Patients with atopic dermatitis are at risk for developing the herpes simplex virus (HSV)–related skin complication “eczema herpeticum,” also known as Kaposi’s varicelliform eruption. Eczema herpeticum is characterized by cutaneous pain and vesicular skin lesions, most commonly secondary to infection with HSV-1. The condition may affect individuals with atopic dermatitis or other inflammatory skin disorders. Eczema herpeticum develops when the virus infects large areas of skin, rather than being confined to a small area as in the common cold sore. Eczema herpeticum often appears on the face and neck, although it can appear anywhere on the body. In some cases, the rash may be difficult to distinguish from a patient’s baseline eczema if the latter is poorly controlled. Skin symptoms of eczema herpeticum include clusters of small blisters that are itchy and painful; vesicles that appear red, purple, or black; purulent blisters; or crusting. Classically, the morphology of vesicles or crusted lesions shows a “cluster of grapes” appearance. Eczema herpeticum may present with a high fever, chills, and swollen lymph glands.

Courtesy Dr. Lawrence F. Eichenfield

While a clinical diagnosis based on the history, physical findings, and morphologic appearance of the rash is reasonable, testing may confirm the diagnosis. The most sensitive and specific tests are polymerase chain reaction sequencing for HSV, direct fluorescent antibody stain, and/or viral culture, while Tzanck smear may show characteristic histologic changes. Treatment is with oral antiviral therapy and treatment of the eczema.

Hand, foot, and mouth disease (HFMD) is a common viral illness usually affecting infants and children. The infection often involves the hands, feet, mouth, and sometimes, the genitals and buttocks. The viral exanthem is most commonly caused by the coxsackievirus, of the enterovirus family. Coxsackievirus A16 and enterovirus A71 are the serotypes that are most commonly implicated as the causative agents. HFMD initially presents with a low-grade fever, reduced appetite, and general malaise. About 1-2 days later, the child may develop painful mouth sores with an exanthem that involves the dorsum of the hands, soles of the feet, buttocks, legs, and arms. The exanthem consists of vesicles surrounded by a thin halo of erythema, eventually rupturing and forming superficial ulcers with a gray-yellow base and erythematous rim. The exanthem is itchy, and can be macular, papular, or vesicular. The lesions are nonpruritic, and typically not painful. The diagnosis of HFMD usually is made clinically, although a physician can swab the mouth or get a stool sample for polymerase chain reaction, which will show the virus; treatment is supportive. In children with atopic dermatitis, lesions also can tend to concentrate in areas previously or currently affected by the dermatitis, similar to eczema herpeticum, and the terms eczema coxsackium or atypical HFMD are applicable. In young adults, the disease may present with erythematous papulovesicular lesions on the face, oral mucosa, extensor surfaces of the upper and lower extremities, and palms and soles; confluent, hemorrhagic, and crusted lesions also can be seen on the extremities. Systemic symptoms usually subside in a few days; the skin lesions resolve without scarring in days to weeks.

Secondary bacterial infection is not uncommon in eczema herpeticum patients, reflecting common Staphylococcus aureus infection in atopic dermatitis patients. Streptococcus also may be seen as a concurrent infection. Treatment of secondary bacterial infection may be considered based on clinic context and culture.

Impetiginized eczema also is in the differential diagnosis of eczema herpeticum. S. aureus and Streptococci are the most important causative organisms. Lesions can manifest as a single red papule or macule that quickly becomes vesicular or eroded. Subsequently, the content dries, forming honey-colored crusts. Impetigo may resolve spontaneously, although in the context of infected eczema both topical anti-inflammatory agents (e.g. topical corticosteroids) along with systemic antibiotics may be a reasonable treatment option. Although our patient had honey-colored crusting, the wound culture showed normal bacterial flora.

Primary varicella infection causes acute fever and rash, with an initial exanthem of disseminated pruritic erythematous macules that progress beyond the papular stage, forming clear, fluid-filled vesicles (like dewdrops on a rose petal). In children, the rash presents on the stomach, back, and face, and then spreads to other parts of the body. Blisters also can arise inside the mouth.

In this patient, perioral HSV PCR 1 was positive, and wound culture showed normal oral flora with no organisms or white blood cells seen. The patient responded well to oral acyclovir, and treatment of his underlying atopic dermatitis with low-potency topical corticosteroids.
 

Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Neither of the physicians had relevant financial disclosures. Email them at pdnews@mdedge.com.

Sources

Can Fam Physician. 2012 Dec;58(12):1358-61.

William L Weston, MD., William Howe, MD. UpToDate. Treatment of atopic dermatitis (eczema).

Christine Johnson, MD, Anna Wald, MD, MPH. UpToDate. Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection.

Robert Sidbury, MD, MPH. UpToDate. Atypical exanthems in children.

National Eczema Association. Eczema herpeticum.

Centers for Disease Control and Prevention. Symptoms and diagnosis of hand, foot, and mouth disease (HFMD).

Patients with atopic dermatitis are at risk for developing the herpes simplex virus (HSV)–related skin complication “eczema herpeticum,” also known as Kaposi’s varicelliform eruption. Eczema herpeticum is characterized by cutaneous pain and vesicular skin lesions, most commonly secondary to infection with HSV-1. The condition may affect individuals with atopic dermatitis or other inflammatory skin disorders. Eczema herpeticum develops when the virus infects large areas of skin, rather than being confined to a small area as in the common cold sore. Eczema herpeticum often appears on the face and neck, although it can appear anywhere on the body. In some cases, the rash may be difficult to distinguish from a patient’s baseline eczema if the latter is poorly controlled. Skin symptoms of eczema herpeticum include clusters of small blisters that are itchy and painful; vesicles that appear red, purple, or black; purulent blisters; or crusting. Classically, the morphology of vesicles or crusted lesions shows a “cluster of grapes” appearance. Eczema herpeticum may present with a high fever, chills, and swollen lymph glands.

Courtesy Dr. Lawrence F. Eichenfield

While a clinical diagnosis based on the history, physical findings, and morphologic appearance of the rash is reasonable, testing may confirm the diagnosis. The most sensitive and specific tests are polymerase chain reaction sequencing for HSV, direct fluorescent antibody stain, and/or viral culture, while Tzanck smear may show characteristic histologic changes. Treatment is with oral antiviral therapy and treatment of the eczema.

Hand, foot, and mouth disease (HFMD) is a common viral illness usually affecting infants and children. The infection often involves the hands, feet, mouth, and sometimes, the genitals and buttocks. The viral exanthem is most commonly caused by the coxsackievirus, of the enterovirus family. Coxsackievirus A16 and enterovirus A71 are the serotypes that are most commonly implicated as the causative agents. HFMD initially presents with a low-grade fever, reduced appetite, and general malaise. About 1-2 days later, the child may develop painful mouth sores with an exanthem that involves the dorsum of the hands, soles of the feet, buttocks, legs, and arms. The exanthem consists of vesicles surrounded by a thin halo of erythema, eventually rupturing and forming superficial ulcers with a gray-yellow base and erythematous rim. The exanthem is itchy, and can be macular, papular, or vesicular. The lesions are nonpruritic, and typically not painful. The diagnosis of HFMD usually is made clinically, although a physician can swab the mouth or get a stool sample for polymerase chain reaction, which will show the virus; treatment is supportive. In children with atopic dermatitis, lesions also can tend to concentrate in areas previously or currently affected by the dermatitis, similar to eczema herpeticum, and the terms eczema coxsackium or atypical HFMD are applicable. In young adults, the disease may present with erythematous papulovesicular lesions on the face, oral mucosa, extensor surfaces of the upper and lower extremities, and palms and soles; confluent, hemorrhagic, and crusted lesions also can be seen on the extremities. Systemic symptoms usually subside in a few days; the skin lesions resolve without scarring in days to weeks.

Secondary bacterial infection is not uncommon in eczema herpeticum patients, reflecting common Staphylococcus aureus infection in atopic dermatitis patients. Streptococcus also may be seen as a concurrent infection. Treatment of secondary bacterial infection may be considered based on clinic context and culture.

Impetiginized eczema also is in the differential diagnosis of eczema herpeticum. S. aureus and Streptococci are the most important causative organisms. Lesions can manifest as a single red papule or macule that quickly becomes vesicular or eroded. Subsequently, the content dries, forming honey-colored crusts. Impetigo may resolve spontaneously, although in the context of infected eczema both topical anti-inflammatory agents (e.g. topical corticosteroids) along with systemic antibiotics may be a reasonable treatment option. Although our patient had honey-colored crusting, the wound culture showed normal bacterial flora.

Primary varicella infection causes acute fever and rash, with an initial exanthem of disseminated pruritic erythematous macules that progress beyond the papular stage, forming clear, fluid-filled vesicles (like dewdrops on a rose petal). In children, the rash presents on the stomach, back, and face, and then spreads to other parts of the body. Blisters also can arise inside the mouth.

In this patient, perioral HSV PCR 1 was positive, and wound culture showed normal oral flora with no organisms or white blood cells seen. The patient responded well to oral acyclovir, and treatment of his underlying atopic dermatitis with low-potency topical corticosteroids.
 

Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Neither of the physicians had relevant financial disclosures. Email them at pdnews@mdedge.com.

Sources

Can Fam Physician. 2012 Dec;58(12):1358-61.

William L Weston, MD., William Howe, MD. UpToDate. Treatment of atopic dermatitis (eczema).

Christine Johnson, MD, Anna Wald, MD, MPH. UpToDate. Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection.

Robert Sidbury, MD, MPH. UpToDate. Atypical exanthems in children.

National Eczema Association. Eczema herpeticum.

Centers for Disease Control and Prevention. Symptoms and diagnosis of hand, foot, and mouth disease (HFMD).

Patients with atopic dermatitis are at risk for developing the herpes simplex virus (HSV)–related skin complication “eczema herpeticum,” also known as Kaposi’s varicelliform eruption. Eczema herpeticum is characterized by cutaneous pain and vesicular skin lesions, most commonly secondary to infection with HSV-1. The condition may affect individuals with atopic dermatitis or other inflammatory skin disorders. Eczema herpeticum develops when the virus infects large areas of skin, rather than being confined to a small area as in the common cold sore. Eczema herpeticum often appears on the face and neck, although it can appear anywhere on the body. In some cases, the rash may be difficult to distinguish from a patient’s baseline eczema if the latter is poorly controlled. Skin symptoms of eczema herpeticum include clusters of small blisters that are itchy and painful; vesicles that appear red, purple, or black; purulent blisters; or crusting. Classically, the morphology of vesicles or crusted lesions shows a “cluster of grapes” appearance. Eczema herpeticum may present with a high fever, chills, and swollen lymph glands.

Courtesy Dr. Lawrence F. Eichenfield

While a clinical diagnosis based on the history, physical findings, and morphologic appearance of the rash is reasonable, testing may confirm the diagnosis. The most sensitive and specific tests are polymerase chain reaction sequencing for HSV, direct fluorescent antibody stain, and/or viral culture, while Tzanck smear may show characteristic histologic changes. Treatment is with oral antiviral therapy and treatment of the eczema.

Hand, foot, and mouth disease (HFMD) is a common viral illness usually affecting infants and children. The infection often involves the hands, feet, mouth, and sometimes, the genitals and buttocks. The viral exanthem is most commonly caused by the coxsackievirus, of the enterovirus family. Coxsackievirus A16 and enterovirus A71 are the serotypes that are most commonly implicated as the causative agents. HFMD initially presents with a low-grade fever, reduced appetite, and general malaise. About 1-2 days later, the child may develop painful mouth sores with an exanthem that involves the dorsum of the hands, soles of the feet, buttocks, legs, and arms. The exanthem consists of vesicles surrounded by a thin halo of erythema, eventually rupturing and forming superficial ulcers with a gray-yellow base and erythematous rim. The exanthem is itchy, and can be macular, papular, or vesicular. The lesions are nonpruritic, and typically not painful. The diagnosis of HFMD usually is made clinically, although a physician can swab the mouth or get a stool sample for polymerase chain reaction, which will show the virus; treatment is supportive. In children with atopic dermatitis, lesions also can tend to concentrate in areas previously or currently affected by the dermatitis, similar to eczema herpeticum, and the terms eczema coxsackium or atypical HFMD are applicable. In young adults, the disease may present with erythematous papulovesicular lesions on the face, oral mucosa, extensor surfaces of the upper and lower extremities, and palms and soles; confluent, hemorrhagic, and crusted lesions also can be seen on the extremities. Systemic symptoms usually subside in a few days; the skin lesions resolve without scarring in days to weeks.

Secondary bacterial infection is not uncommon in eczema herpeticum patients, reflecting common Staphylococcus aureus infection in atopic dermatitis patients. Streptococcus also may be seen as a concurrent infection. Treatment of secondary bacterial infection may be considered based on clinic context and culture.

Impetiginized eczema also is in the differential diagnosis of eczema herpeticum. S. aureus and Streptococci are the most important causative organisms. Lesions can manifest as a single red papule or macule that quickly becomes vesicular or eroded. Subsequently, the content dries, forming honey-colored crusts. Impetigo may resolve spontaneously, although in the context of infected eczema both topical anti-inflammatory agents (e.g. topical corticosteroids) along with systemic antibiotics may be a reasonable treatment option. Although our patient had honey-colored crusting, the wound culture showed normal bacterial flora.

Primary varicella infection causes acute fever and rash, with an initial exanthem of disseminated pruritic erythematous macules that progress beyond the papular stage, forming clear, fluid-filled vesicles (like dewdrops on a rose petal). In children, the rash presents on the stomach, back, and face, and then spreads to other parts of the body. Blisters also can arise inside the mouth.

In this patient, perioral HSV PCR 1 was positive, and wound culture showed normal oral flora with no organisms or white blood cells seen. The patient responded well to oral acyclovir, and treatment of his underlying atopic dermatitis with low-potency topical corticosteroids.
 

Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Neither of the physicians had relevant financial disclosures. Email them at pdnews@mdedge.com.

Sources

Can Fam Physician. 2012 Dec;58(12):1358-61.

William L Weston, MD., William Howe, MD. UpToDate. Treatment of atopic dermatitis (eczema).

Christine Johnson, MD, Anna Wald, MD, MPH. UpToDate. Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection.

Robert Sidbury, MD, MPH. UpToDate. Atypical exanthems in children.

National Eczema Association. Eczema herpeticum.

Centers for Disease Control and Prevention. Symptoms and diagnosis of hand, foot, and mouth disease (HFMD).

Accelerated fetal growth was associated with acute myeloid leukemia (AML), especially in infant boys and those with minimally differentiated leukemia, according to researchers from the Childhood Leukemia International Consortium (CLIC).

They assessed data from 22 studies involving a total of 3,564 cases to determine if there was an association between fetal growth and AML. The researchers also examined whether this association might vary by age, sex and disease subtype, according to their report published in the European Journal of Cancer.

The researchers calculated pooled estimates by age, sex and overall for harmonized fetal growth markers in association with AML. They used data from 17 International Fetal and Newborn Growth Consortium for the 21st Century Project studies and performed meta-analyses on 5 more studies. They also did subanalyses based on AML subtype.

They found a nearly 50% increased risk of AML among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.14), reduced to 34% in boys aged less than 2 years (OR: 1.34, 95% CI: 1.05-1.71) and 25% in boys aged 0-14 years (OR: 1.25, 95% CI: 1.06-1.46). The association of large for gestational age was stronger in boys with the M0/M1 subtype (OR: 1.80, 95% CI: 1.15-2.83). In addition, large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00-1.92) in boys. By contrast, there, none of these factors were associated with AML in girls, nor were there associates for girls with respect to decelerated fetal growth markers.

“Although the absolute risk seems to be low at a population level, given the rarity of childhood AML, it would be worth exploring whether modifiable factors leading to macrosomia may also affect AML risk to stimulate future monitoring and preventive interventions before and during pregnancy,” the researchers suggested.

The authors reported that they had no conflicts of interest.
 

mlesney@mdedge.com

SOURCE: Karalexi MA et al. Eur J Canc. 2020;130:1-11.

Accelerated fetal growth was associated with acute myeloid leukemia (AML), especially in infant boys and those with minimally differentiated leukemia, according to researchers from the Childhood Leukemia International Consortium (CLIC).

They assessed data from 22 studies involving a total of 3,564 cases to determine if there was an association between fetal growth and AML. The researchers also examined whether this association might vary by age, sex and disease subtype, according to their report published in the European Journal of Cancer.

The researchers calculated pooled estimates by age, sex and overall for harmonized fetal growth markers in association with AML. They used data from 17 International Fetal and Newborn Growth Consortium for the 21st Century Project studies and performed meta-analyses on 5 more studies. They also did subanalyses based on AML subtype.

They found a nearly 50% increased risk of AML among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.14), reduced to 34% in boys aged less than 2 years (OR: 1.34, 95% CI: 1.05-1.71) and 25% in boys aged 0-14 years (OR: 1.25, 95% CI: 1.06-1.46). The association of large for gestational age was stronger in boys with the M0/M1 subtype (OR: 1.80, 95% CI: 1.15-2.83). In addition, large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00-1.92) in boys. By contrast, there, none of these factors were associated with AML in girls, nor were there associates for girls with respect to decelerated fetal growth markers.

“Although the absolute risk seems to be low at a population level, given the rarity of childhood AML, it would be worth exploring whether modifiable factors leading to macrosomia may also affect AML risk to stimulate future monitoring and preventive interventions before and during pregnancy,” the researchers suggested.

The authors reported that they had no conflicts of interest.
 

mlesney@mdedge.com

SOURCE: Karalexi MA et al. Eur J Canc. 2020;130:1-11.

Accelerated fetal growth was associated with acute myeloid leukemia (AML), especially in infant boys and those with minimally differentiated leukemia, according to researchers from the Childhood Leukemia International Consortium (CLIC).

They assessed data from 22 studies involving a total of 3,564 cases to determine if there was an association between fetal growth and AML. The researchers also examined whether this association might vary by age, sex and disease subtype, according to their report published in the European Journal of Cancer.

The researchers calculated pooled estimates by age, sex and overall for harmonized fetal growth markers in association with AML. They used data from 17 International Fetal and Newborn Growth Consortium for the 21st Century Project studies and performed meta-analyses on 5 more studies. They also did subanalyses based on AML subtype.

They found a nearly 50% increased risk of AML among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.14), reduced to 34% in boys aged less than 2 years (OR: 1.34, 95% CI: 1.05-1.71) and 25% in boys aged 0-14 years (OR: 1.25, 95% CI: 1.06-1.46). The association of large for gestational age was stronger in boys with the M0/M1 subtype (OR: 1.80, 95% CI: 1.15-2.83). In addition, large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00-1.92) in boys. By contrast, there, none of these factors were associated with AML in girls, nor were there associates for girls with respect to decelerated fetal growth markers.

“Although the absolute risk seems to be low at a population level, given the rarity of childhood AML, it would be worth exploring whether modifiable factors leading to macrosomia may also affect AML risk to stimulate future monitoring and preventive interventions before and during pregnancy,” the researchers suggested.

The authors reported that they had no conflicts of interest.
 

mlesney@mdedge.com

SOURCE: Karalexi MA et al. Eur J Canc. 2020;130:1-11.

From colonoscopies to endoscopic ultrasound, gastroenterology is fundamentally a procedure-based specialty. Given that reality, making a decision to have as much control as possible over the entire process just makes sense for many GI practices.

Back in 2008, I was in charge of the process to develop a pathology lab at Arizona Digestive Health, a physician group with 26 locations throughout the state, as part of our decision to form a supergroup with eight ambulatory surgery centers. For us, having ambulatory surgery centers had been a game changer. We learned we could double our efficiency with procedures when we controlled the process from start to finish. We began to consider other processes – in this case pathology – that we could improve.

Prior to running our own pathology lab, doctors who read our slides were general pathologists who did not always understand the language of gastroenterology. We had results that came back by fax that were often cumbersome to read and did not always give us the information we needed in the way we needed it. Consistency was a problem. We knew we needed a change.

I cannot lie – setting up and running your own pathology lab is not always easy. But with the right factors in place, here are some benefits to consider when you are making a decision about joining a practice.
 

Quality, efficiency can lead to opportunity

Our lab has three GI fellowship–trained pathologists reading our slides. That means they are highly specialized and know exactly what we are looking for in a pathology report. We have a 24-hour turnaround for results. A courier service delivers biopsy specimens from our endoscopy centers to our path lab every day, and each morning our gastropathologists have a stack of pathology slides waiting for them. It’s added predictability and stability to the process, and we get the level of quality, specificity, and uniformity we need in a report.

The efficiencies are beneficial and it has given us more leverage in our negotiations with payers. We know what our costs are and have great quality metrics as well as read rates that we can provide. This signals to health plans that quality is a top priority for us.

We have also gained a reputational benefit with patients. Although much of the work is happening behind the scenes for our patients, they get results faster and a consistency with costs. It also allows us to easily access the slides of patients we have been seeing for years, giving us a richer data set and more confidence in our diagnosis.

Now that we have our own lab, we can look at our pathology data and conduct studies that will benefit all patients. For example, a few of our GI fellows were able to work with our pathologists to conduct a study on adenoma detection rates, exhausting a tissue block when no adenoma was found on initial review. We found a significant increase in adenoma detection using this method; we plan to publish results soon. The ability to conduct this kind of research is worth considering when early career gastroenterologists are selecting a practice to join.

And last but not least, having our own pathology lab acts as a unifying force for our group, which is spread out across 26 offices. When diagnoses are available and we get a call from our pathologist, we know to pick up the phone immediately.
 

What to consider before jumping in

Setting up our own pathology lab from the ground up was a learning process. We had enough patient volume for the move to make sense, so it is possible that smaller practices might not be able to make the investment if they have lower patient volume or cannot control their specimen flow. One option is to set up a technical lab and contract out for the slide reading. We felt it was important for our pathologists to also be our practice partners, and time has proven this to be a good decision for us.

We designed a lab with our work flow in mind, and it helped to have a pathologist on board from the beginning who knows gastroenterology. We even created our own lab information system with the help of a software engineer. It took a little bit over a year from conception to a functioning comprehensive lab.

Of course, there are regulatory factors to consider – the federal physician self-referral (Stark) law and the federal Anti-Markup Rule – come to mind. But we made sure to get a legal opinion that allows us to comply with the law. That’s something anyone who wants to make a move in this direction should do.

Looking back over the experience, I would not do anything differently. Yes, there are startup costs and a learning curve. But the quality we get from having our own pathology lab dedicated to GI and the efficiencies we have gained are well worth it.

Dr. Berggreen is the president of Arizona Digestive Health and chief strategy officer of the GI Alliance. He is also a board member of the Digestive Health Physicians Association. He received his doctorate at Louisiana State University, New Orleans. He is the former site director of the Good Samaritan GI Fellowship Program and named one of Phoenix Magazine’s “Top Docs.”

From colonoscopies to endoscopic ultrasound, gastroenterology is fundamentally a procedure-based specialty. Given that reality, making a decision to have as much control as possible over the entire process just makes sense for many GI practices.

Back in 2008, I was in charge of the process to develop a pathology lab at Arizona Digestive Health, a physician group with 26 locations throughout the state, as part of our decision to form a supergroup with eight ambulatory surgery centers. For us, having ambulatory surgery centers had been a game changer. We learned we could double our efficiency with procedures when we controlled the process from start to finish. We began to consider other processes – in this case pathology – that we could improve.

Prior to running our own pathology lab, doctors who read our slides were general pathologists who did not always understand the language of gastroenterology. We had results that came back by fax that were often cumbersome to read and did not always give us the information we needed in the way we needed it. Consistency was a problem. We knew we needed a change.

I cannot lie – setting up and running your own pathology lab is not always easy. But with the right factors in place, here are some benefits to consider when you are making a decision about joining a practice.
 

Quality, efficiency can lead to opportunity

Our lab has three GI fellowship–trained pathologists reading our slides. That means they are highly specialized and know exactly what we are looking for in a pathology report. We have a 24-hour turnaround for results. A courier service delivers biopsy specimens from our endoscopy centers to our path lab every day, and each morning our gastropathologists have a stack of pathology slides waiting for them. It’s added predictability and stability to the process, and we get the level of quality, specificity, and uniformity we need in a report.

The efficiencies are beneficial and it has given us more leverage in our negotiations with payers. We know what our costs are and have great quality metrics as well as read rates that we can provide. This signals to health plans that quality is a top priority for us.

We have also gained a reputational benefit with patients. Although much of the work is happening behind the scenes for our patients, they get results faster and a consistency with costs. It also allows us to easily access the slides of patients we have been seeing for years, giving us a richer data set and more confidence in our diagnosis.

Now that we have our own lab, we can look at our pathology data and conduct studies that will benefit all patients. For example, a few of our GI fellows were able to work with our pathologists to conduct a study on adenoma detection rates, exhausting a tissue block when no adenoma was found on initial review. We found a significant increase in adenoma detection using this method; we plan to publish results soon. The ability to conduct this kind of research is worth considering when early career gastroenterologists are selecting a practice to join.

And last but not least, having our own pathology lab acts as a unifying force for our group, which is spread out across 26 offices. When diagnoses are available and we get a call from our pathologist, we know to pick up the phone immediately.
 

What to consider before jumping in

Setting up our own pathology lab from the ground up was a learning process. We had enough patient volume for the move to make sense, so it is possible that smaller practices might not be able to make the investment if they have lower patient volume or cannot control their specimen flow. One option is to set up a technical lab and contract out for the slide reading. We felt it was important for our pathologists to also be our practice partners, and time has proven this to be a good decision for us.

We designed a lab with our work flow in mind, and it helped to have a pathologist on board from the beginning who knows gastroenterology. We even created our own lab information system with the help of a software engineer. It took a little bit over a year from conception to a functioning comprehensive lab.

Of course, there are regulatory factors to consider – the federal physician self-referral (Stark) law and the federal Anti-Markup Rule – come to mind. But we made sure to get a legal opinion that allows us to comply with the law. That’s something anyone who wants to make a move in this direction should do.

Looking back over the experience, I would not do anything differently. Yes, there are startup costs and a learning curve. But the quality we get from having our own pathology lab dedicated to GI and the efficiencies we have gained are well worth it.

Dr. Berggreen is the president of Arizona Digestive Health and chief strategy officer of the GI Alliance. He is also a board member of the Digestive Health Physicians Association. He received his doctorate at Louisiana State University, New Orleans. He is the former site director of the Good Samaritan GI Fellowship Program and named one of Phoenix Magazine’s “Top Docs.”

From colonoscopies to endoscopic ultrasound, gastroenterology is fundamentally a procedure-based specialty. Given that reality, making a decision to have as much control as possible over the entire process just makes sense for many GI practices.

Back in 2008, I was in charge of the process to develop a pathology lab at Arizona Digestive Health, a physician group with 26 locations throughout the state, as part of our decision to form a supergroup with eight ambulatory surgery centers. For us, having ambulatory surgery centers had been a game changer. We learned we could double our efficiency with procedures when we controlled the process from start to finish. We began to consider other processes – in this case pathology – that we could improve.

Prior to running our own pathology lab, doctors who read our slides were general pathologists who did not always understand the language of gastroenterology. We had results that came back by fax that were often cumbersome to read and did not always give us the information we needed in the way we needed it. Consistency was a problem. We knew we needed a change.

I cannot lie – setting up and running your own pathology lab is not always easy. But with the right factors in place, here are some benefits to consider when you are making a decision about joining a practice.
 

Quality, efficiency can lead to opportunity

Our lab has three GI fellowship–trained pathologists reading our slides. That means they are highly specialized and know exactly what we are looking for in a pathology report. We have a 24-hour turnaround for results. A courier service delivers biopsy specimens from our endoscopy centers to our path lab every day, and each morning our gastropathologists have a stack of pathology slides waiting for them. It’s added predictability and stability to the process, and we get the level of quality, specificity, and uniformity we need in a report.

The efficiencies are beneficial and it has given us more leverage in our negotiations with payers. We know what our costs are and have great quality metrics as well as read rates that we can provide. This signals to health plans that quality is a top priority for us.

We have also gained a reputational benefit with patients. Although much of the work is happening behind the scenes for our patients, they get results faster and a consistency with costs. It also allows us to easily access the slides of patients we have been seeing for years, giving us a richer data set and more confidence in our diagnosis.

Now that we have our own lab, we can look at our pathology data and conduct studies that will benefit all patients. For example, a few of our GI fellows were able to work with our pathologists to conduct a study on adenoma detection rates, exhausting a tissue block when no adenoma was found on initial review. We found a significant increase in adenoma detection using this method; we plan to publish results soon. The ability to conduct this kind of research is worth considering when early career gastroenterologists are selecting a practice to join.

And last but not least, having our own pathology lab acts as a unifying force for our group, which is spread out across 26 offices. When diagnoses are available and we get a call from our pathologist, we know to pick up the phone immediately.
 

What to consider before jumping in

Setting up our own pathology lab from the ground up was a learning process. We had enough patient volume for the move to make sense, so it is possible that smaller practices might not be able to make the investment if they have lower patient volume or cannot control their specimen flow. One option is to set up a technical lab and contract out for the slide reading. We felt it was important for our pathologists to also be our practice partners, and time has proven this to be a good decision for us.

We designed a lab with our work flow in mind, and it helped to have a pathologist on board from the beginning who knows gastroenterology. We even created our own lab information system with the help of a software engineer. It took a little bit over a year from conception to a functioning comprehensive lab.

Of course, there are regulatory factors to consider – the federal physician self-referral (Stark) law and the federal Anti-Markup Rule – come to mind. But we made sure to get a legal opinion that allows us to comply with the law. That’s something anyone who wants to make a move in this direction should do.

Looking back over the experience, I would not do anything differently. Yes, there are startup costs and a learning curve. But the quality we get from having our own pathology lab dedicated to GI and the efficiencies we have gained are well worth it.

Dr. Berggreen is the president of Arizona Digestive Health and chief strategy officer of the GI Alliance. He is also a board member of the Digestive Health Physicians Association. He received his doctorate at Louisiana State University, New Orleans. He is the former site director of the Good Samaritan GI Fellowship Program and named one of Phoenix Magazine’s “Top Docs.”

“Cannabis sativa is a weed and it causes reactions just like any other pollen allergy,” said William Silvers, MD, from the University of Colorado School of Medicine in Aurora.

Silvers’ clinic began to see people with allergic reactions to the plant after the increase in direct exposure that accompanied the legalization of recreational marijuana in Colorado. For people with allergic tendencies, first- and second-hand exposure to C. sativa will increase “classic responses,” such as allergic rhinitis, sneezing, wheezing, itching, and asthma, he told Medscape Medical News.

Smoking the weed, direct exposure to the plant, contact with others who have touched plants, and breathing air in a grow operation “can all cause reactions,” he said. “And the more exposure they had, the greater the reaction, especially those who have allergic tendency,” he said.

The type of exposure to C. sativa is also a factor. Smoking the plant can induce typical allergic responses, the ingestion of hemp seed has been known to induce anaphylaxis, and “working with the plant can lead to dermatitis or contact urticaria,” he explained.

Edibles made with C. sativa have led to overdoses because dosing is difficult to determine. “It takes an hour or so to have an effect, so you don›t have as much control as inhaling it,” Silvers explained.
 

Stoned Fruit, Stoned Patient

A 2018 case report describes a 24-year-old daily marijuana smoker who experienced anaphylaxis after ingesting hemp seed. He had a history of allergies to stoned fruits, nuts, crustaceans, and aeroallergens. It was his first known exposure to hemp seed.

The patient developed urticaria on his arms after contact with C. sativa leaves and flowers, but had no reaction when smoking marijuana. This case indicates how important mode of exposure is.

“There are only a few cases of anaphylaxis known from ingestion of hemp seed,” Silvers said, “but the ‘stoned fruit, stoned patients’ cross-reactivity looks to be a real thing.”

People allergic to ragweed and sage are more likely than others to have a reaction to cantaloupe and other fruits in the melon family, he explained. There is a common antigen in the C. sativa pollen and in certain foods with cross-reacting proteins, such as tomato, peach, and hazelnut. “We see a pollen and food cross-reactivity via nonspecific lipid transfer proteins.”

A 2017 review of C. sativa allergy points out that few reports of IgE-dependent allergic reactions have been published because of the illegal status of cannabis. However, it is becoming more prevalent as a potential allergen. For example, in Nebraska, C. sativa pollen accounts for 36% of the total pollen count.

People with IgE-mediated cannabis allergy can have a sensitization to the nonspecific lipid transfer protein of C. sativa, Can s 3, which might explain the secondary plant-derived food allergies seen in European patients with a cannabis allergy, according to the review. Can s 3 cross-reacts with various plant homologues.

“This is the sort of information that allergists need to have,” Silvers said.

Stigma Limits Discussion

The fact that federal law prohibits cannabis use in the United States has made research difficult.

A strain distributed by the University of Mississippi can be used for research, “but its potency is very low, at 5% or 7%,” Silvers explained. At medical marijuana dispensaries, the potency of the flower can be as high as 25%, and in other forms, the THC content can be above 80%.

The legal status makes cannabis allergy difficult to diagnose and impossible to treat. Immunotherapy is out of the question. “With federal illegality, we need to stay out of trouble in that regard,” said Silvers, adding that, currently, avoidance is advised.

But research is emerging from Canada, where medicinal and recreational marijuana use is legal.

Stigma around cannabis is still high. “Nobody wants to be seen as a ‘pot doctor’,” said Silvers. But after it became legal in Colorado in 2015, he was asked to give a talk and decided to speak up.

“I have never written a medical prescription for marijuana,” he said, explaining that he is involved with the Center for Bioethics and Humanities at the University of Colorado. “I try to take a societal as well as a medical perspective, looking at the value and concerns for abuse and misuse.”

“As it becomes more available, more legalized, patients are having more reactions,” he said. “Allergists need to get in the game.”

Attitudes need to change. Physicians and allergists need to understand what’s happening in the population “and be open-minded about it so they know what to do,” he added.
 

Patients Don’t Want to Be Told to Stop

Users of medical marijuana can become dependent, said Ellen Burnham, MD, also from the University of Colorado.

“Patients want a blessing from care providers that it’s okay to use,” she told Medscape Medical News. “We’re in a state where people are really interested in holistic approaches to health, and cannabis is a natural product, but it may exacerbate allergies.”

Some components of cannabis might have bronchodilator properties but there are so many unknowns at this time. “I don’t think allergists should be recommending or condoning cannabis as part of a patient’s therapy,” she said. “It’s not okay for everybody.”

As business flourishes for operators in the cannabis industry and for the legal profession, Burnham said she worries that there isn’t enough protection for workers. “Do workers exposed to plant material on a daily basis have adequate workplace protection,” such as masks and gowns? “There’s a downstream effect that impacts people that nobody has really thought about,” she pointed out.

If the cannabis industry becomes driven by money, with a lobby like the tobacco industry, there will be no way to keep people who are vulnerable from using cannabis.

Is an occasional joint, much like an occasional glass of wine, okay? “We don’t know,” said Burnham. “We just don’t have enough information about it.”

Research is needed to develop medicinal strains of cannabidiol, cannabigerol, and cannabinol, which offer “medicinal and anti-inflammatory relief without the psychologic affects,” Silvers added.

This article first appeared on Medscape.com.

“Cannabis sativa is a weed and it causes reactions just like any other pollen allergy,” said William Silvers, MD, from the University of Colorado School of Medicine in Aurora.

Silvers’ clinic began to see people with allergic reactions to the plant after the increase in direct exposure that accompanied the legalization of recreational marijuana in Colorado. For people with allergic tendencies, first- and second-hand exposure to C. sativa will increase “classic responses,” such as allergic rhinitis, sneezing, wheezing, itching, and asthma, he told Medscape Medical News.

Smoking the weed, direct exposure to the plant, contact with others who have touched plants, and breathing air in a grow operation “can all cause reactions,” he said. “And the more exposure they had, the greater the reaction, especially those who have allergic tendency,” he said.

The type of exposure to C. sativa is also a factor. Smoking the plant can induce typical allergic responses, the ingestion of hemp seed has been known to induce anaphylaxis, and “working with the plant can lead to dermatitis or contact urticaria,” he explained.

Edibles made with C. sativa have led to overdoses because dosing is difficult to determine. “It takes an hour or so to have an effect, so you don›t have as much control as inhaling it,” Silvers explained.
 

Stoned Fruit, Stoned Patient

A 2018 case report describes a 24-year-old daily marijuana smoker who experienced anaphylaxis after ingesting hemp seed. He had a history of allergies to stoned fruits, nuts, crustaceans, and aeroallergens. It was his first known exposure to hemp seed.

The patient developed urticaria on his arms after contact with C. sativa leaves and flowers, but had no reaction when smoking marijuana. This case indicates how important mode of exposure is.

“There are only a few cases of anaphylaxis known from ingestion of hemp seed,” Silvers said, “but the ‘stoned fruit, stoned patients’ cross-reactivity looks to be a real thing.”

People allergic to ragweed and sage are more likely than others to have a reaction to cantaloupe and other fruits in the melon family, he explained. There is a common antigen in the C. sativa pollen and in certain foods with cross-reacting proteins, such as tomato, peach, and hazelnut. “We see a pollen and food cross-reactivity via nonspecific lipid transfer proteins.”

A 2017 review of C. sativa allergy points out that few reports of IgE-dependent allergic reactions have been published because of the illegal status of cannabis. However, it is becoming more prevalent as a potential allergen. For example, in Nebraska, C. sativa pollen accounts for 36% of the total pollen count.

People with IgE-mediated cannabis allergy can have a sensitization to the nonspecific lipid transfer protein of C. sativa, Can s 3, which might explain the secondary plant-derived food allergies seen in European patients with a cannabis allergy, according to the review. Can s 3 cross-reacts with various plant homologues.

“This is the sort of information that allergists need to have,” Silvers said.

Stigma Limits Discussion

The fact that federal law prohibits cannabis use in the United States has made research difficult.

A strain distributed by the University of Mississippi can be used for research, “but its potency is very low, at 5% or 7%,” Silvers explained. At medical marijuana dispensaries, the potency of the flower can be as high as 25%, and in other forms, the THC content can be above 80%.

The legal status makes cannabis allergy difficult to diagnose and impossible to treat. Immunotherapy is out of the question. “With federal illegality, we need to stay out of trouble in that regard,” said Silvers, adding that, currently, avoidance is advised.

But research is emerging from Canada, where medicinal and recreational marijuana use is legal.

Stigma around cannabis is still high. “Nobody wants to be seen as a ‘pot doctor’,” said Silvers. But after it became legal in Colorado in 2015, he was asked to give a talk and decided to speak up.

“I have never written a medical prescription for marijuana,” he said, explaining that he is involved with the Center for Bioethics and Humanities at the University of Colorado. “I try to take a societal as well as a medical perspective, looking at the value and concerns for abuse and misuse.”

“As it becomes more available, more legalized, patients are having more reactions,” he said. “Allergists need to get in the game.”

Attitudes need to change. Physicians and allergists need to understand what’s happening in the population “and be open-minded about it so they know what to do,” he added.
 

Patients Don’t Want to Be Told to Stop

Users of medical marijuana can become dependent, said Ellen Burnham, MD, also from the University of Colorado.

“Patients want a blessing from care providers that it’s okay to use,” she told Medscape Medical News. “We’re in a state where people are really interested in holistic approaches to health, and cannabis is a natural product, but it may exacerbate allergies.”

Some components of cannabis might have bronchodilator properties but there are so many unknowns at this time. “I don’t think allergists should be recommending or condoning cannabis as part of a patient’s therapy,” she said. “It’s not okay for everybody.”

As business flourishes for operators in the cannabis industry and for the legal profession, Burnham said she worries that there isn’t enough protection for workers. “Do workers exposed to plant material on a daily basis have adequate workplace protection,” such as masks and gowns? “There’s a downstream effect that impacts people that nobody has really thought about,” she pointed out.

If the cannabis industry becomes driven by money, with a lobby like the tobacco industry, there will be no way to keep people who are vulnerable from using cannabis.

Is an occasional joint, much like an occasional glass of wine, okay? “We don’t know,” said Burnham. “We just don’t have enough information about it.”

Research is needed to develop medicinal strains of cannabidiol, cannabigerol, and cannabinol, which offer “medicinal and anti-inflammatory relief without the psychologic affects,” Silvers added.

This article first appeared on Medscape.com.

“Cannabis sativa is a weed and it causes reactions just like any other pollen allergy,” said William Silvers, MD, from the University of Colorado School of Medicine in Aurora.

Silvers’ clinic began to see people with allergic reactions to the plant after the increase in direct exposure that accompanied the legalization of recreational marijuana in Colorado. For people with allergic tendencies, first- and second-hand exposure to C. sativa will increase “classic responses,” such as allergic rhinitis, sneezing, wheezing, itching, and asthma, he told Medscape Medical News.

Smoking the weed, direct exposure to the plant, contact with others who have touched plants, and breathing air in a grow operation “can all cause reactions,” he said. “And the more exposure they had, the greater the reaction, especially those who have allergic tendency,” he said.

The type of exposure to C. sativa is also a factor. Smoking the plant can induce typical allergic responses, the ingestion of hemp seed has been known to induce anaphylaxis, and “working with the plant can lead to dermatitis or contact urticaria,” he explained.

Edibles made with C. sativa have led to overdoses because dosing is difficult to determine. “It takes an hour or so to have an effect, so you don›t have as much control as inhaling it,” Silvers explained.
 

Stoned Fruit, Stoned Patient

A 2018 case report describes a 24-year-old daily marijuana smoker who experienced anaphylaxis after ingesting hemp seed. He had a history of allergies to stoned fruits, nuts, crustaceans, and aeroallergens. It was his first known exposure to hemp seed.

The patient developed urticaria on his arms after contact with C. sativa leaves and flowers, but had no reaction when smoking marijuana. This case indicates how important mode of exposure is.

“There are only a few cases of anaphylaxis known from ingestion of hemp seed,” Silvers said, “but the ‘stoned fruit, stoned patients’ cross-reactivity looks to be a real thing.”

People allergic to ragweed and sage are more likely than others to have a reaction to cantaloupe and other fruits in the melon family, he explained. There is a common antigen in the C. sativa pollen and in certain foods with cross-reacting proteins, such as tomato, peach, and hazelnut. “We see a pollen and food cross-reactivity via nonspecific lipid transfer proteins.”

A 2017 review of C. sativa allergy points out that few reports of IgE-dependent allergic reactions have been published because of the illegal status of cannabis. However, it is becoming more prevalent as a potential allergen. For example, in Nebraska, C. sativa pollen accounts for 36% of the total pollen count.

People with IgE-mediated cannabis allergy can have a sensitization to the nonspecific lipid transfer protein of C. sativa, Can s 3, which might explain the secondary plant-derived food allergies seen in European patients with a cannabis allergy, according to the review. Can s 3 cross-reacts with various plant homologues.

“This is the sort of information that allergists need to have,” Silvers said.

Stigma Limits Discussion

The fact that federal law prohibits cannabis use in the United States has made research difficult.

A strain distributed by the University of Mississippi can be used for research, “but its potency is very low, at 5% or 7%,” Silvers explained. At medical marijuana dispensaries, the potency of the flower can be as high as 25%, and in other forms, the THC content can be above 80%.

The legal status makes cannabis allergy difficult to diagnose and impossible to treat. Immunotherapy is out of the question. “With federal illegality, we need to stay out of trouble in that regard,” said Silvers, adding that, currently, avoidance is advised.

But research is emerging from Canada, where medicinal and recreational marijuana use is legal.

Stigma around cannabis is still high. “Nobody wants to be seen as a ‘pot doctor’,” said Silvers. But after it became legal in Colorado in 2015, he was asked to give a talk and decided to speak up.

“I have never written a medical prescription for marijuana,” he said, explaining that he is involved with the Center for Bioethics and Humanities at the University of Colorado. “I try to take a societal as well as a medical perspective, looking at the value and concerns for abuse and misuse.”

“As it becomes more available, more legalized, patients are having more reactions,” he said. “Allergists need to get in the game.”

Attitudes need to change. Physicians and allergists need to understand what’s happening in the population “and be open-minded about it so they know what to do,” he added.
 

Patients Don’t Want to Be Told to Stop

Users of medical marijuana can become dependent, said Ellen Burnham, MD, also from the University of Colorado.

“Patients want a blessing from care providers that it’s okay to use,” she told Medscape Medical News. “We’re in a state where people are really interested in holistic approaches to health, and cannabis is a natural product, but it may exacerbate allergies.”

Some components of cannabis might have bronchodilator properties but there are so many unknowns at this time. “I don’t think allergists should be recommending or condoning cannabis as part of a patient’s therapy,” she said. “It’s not okay for everybody.”

As business flourishes for operators in the cannabis industry and for the legal profession, Burnham said she worries that there isn’t enough protection for workers. “Do workers exposed to plant material on a daily basis have adequate workplace protection,” such as masks and gowns? “There’s a downstream effect that impacts people that nobody has really thought about,” she pointed out.

If the cannabis industry becomes driven by money, with a lobby like the tobacco industry, there will be no way to keep people who are vulnerable from using cannabis.

Is an occasional joint, much like an occasional glass of wine, okay? “We don’t know,” said Burnham. “We just don’t have enough information about it.”

Research is needed to develop medicinal strains of cannabidiol, cannabigerol, and cannabinol, which offer “medicinal and anti-inflammatory relief without the psychologic affects,” Silvers added.

This article first appeared on Medscape.com.

Efforts toward early identification and treatment are an important facet of the public health work in autism spectrum disorder (ASD).

O_Lypa/iStock/Getty Images

The prevalence of ASD is rising. With the most recent estimate from the Centers from Disease Control and Prevention of 1 in 59* children aged 8 years,¹ it is important for pediatric health care providers to have an understanding of current recommendations for treatment so they can counsel and guide affected families. ASD is a heterogeneous condition, so this article seeks to touch on broad principles, recognizing that clinicians must take into account the full clinical picture of each individual and family.

It is important to acknowledge that while there is no cure for ASD, there are treatment modalities that have an evidence base for addressing specific areas that may be impaired in children with autism. While it is beyond the scope of this article to review all of the potential areas of intervention in children with ASD, it is important to be keep in mind a few important principles.

1. The best evidenced treatment for addressing challenging and problematic behavior as well as improving a host of outcomes in children with ASD is itself behavioral in nature. These treatments are based on the principles of applied behavioral analysis,² an educational and therapeutic approach which involves looking at antecedents and consequences of behaviors. This approach also looks to shape, motivate, and reinforce functional behaviors while discouraging harmful and disruptive ones.

2. Because communication often is impaired in children with ASD, providers always should investigate for possible medical causes of pain or discomfort that might explain sudden behavior change, as well as environmental changes that could be involved.

3. The overarching principle of psychopharmacology in ASD is to start low, and go slow – because children with ASD often are particularly sensitive to medication side effects.
 

Irritability/aggression/extreme mood lability

There are only two medications with Food and Drug Administration labeling for an autism specific condition, and those are aripiprazole and risperidone, two second-generation antipsychotic agents approved for irritability associated with ASD on the basis of randomized controlled trials (RCTs) demonstrating their efficacy.^3,4 Included under the umbrella of irritability are aggression, deliberate self-injurious behavior, extreme temper tantrums, and quick and extreme mood changes. For aripiprazole the approved ages are 6-17 years; a dosing range of 2-15 mg/day is recommended. For risperidone, the approved age range is 5-17 years; the recommended dosing range is 0.25-4 mg/day. Prior to starting either of these medications, a cardiac history should be obtained, and baseline laboratory values, particularly lipid levels and hemoglobin A_1c (HbA_1c) are recommended. All second-generation antipsychotics carry the risk of tardive dyskinesia (a movement disorder), as well as risk of weight gain and metabolic effects. Baseline weight prior to medication initiation with routine follow-up measurement is encouraged. In light of the burden of potential side effects, these medications tend to be reserved by clinicians for circumstances where there is a significant impact on functioning. Both medications are available in liquid form for children with difficulty swallowing pills.

ADHD

There are positive RCTs of methylphenidate in co-occurring ASD and ADHD,⁵ making it the preferred first line agent for treatment. Amphetamine salt based stimulant preparations do not have any RCTs in co-occurring ASD, but theoretically should be similarly effective. Again, the principle of starting low and going slow is applicable. Second line are the alpha 2 adrenergic agonists guanfacine and clonidine, both of whose long-acting formulations are approved for treatment of ADHD in children and adolescents without ASD, as well as atomoxetine, a selective norepinephrine reuptake inhibitor approved for ADHD. Guanfacine and atomoxetine have the stronger evidence base in the co-occurring condition. None of the second-line medications come in liquid preparation, although the immediate-release forms of guanfacine and clonidine both can be crushed and are used in clinical practice when the extended-release forms are not practicable.

Anxiety disorders and depression

Repetitive behaviors and insistence on sameness are broad headings that can be thought of as similar to obsessive compulsive disorder in children without ASD. However, controlled studies of SSRIs and clomipramine (a tricyclic antidepressant) have not shown a clear benefit in these behaviors in children with autism. There are no RCTs looking specifically at treatment of anxiety disorders in children with ASD, but expert consensus is that pharmacologic treatment is similar to that of children without ASD, with the SSRIs fluoxetine and sertraline the first-line agents due to the robust evidence for these two medications in treatment of anxiety disorders in children.⁶ Especially for kids with higher functioning ASD, cognitive behavioral therapy (CBT) should be considered and has some evidence for the co-occurring condition. Similarly, there are no RCTs for co-occurring depression in ASD, and clinical practice is to treat it as you would depression in the non-ASD population. Be aware that the studies of SSRIs in children with ASD reported higher than typical rates of behavioral activation on these medications, and again the principle of starting low and going slow is emphasized. Fluoxetine and sertraline both come in liquid form.

Insomnia

Insomnia is a common occurrence in children with ASD, and studies suggest melatonin can be effective, with immediate release clonidine a consideration with some limited evidence, if melatonin is not successful.

Finally I would be remiss in not mentioning that there is preliminary evidence from review⁷ and meta-analysis⁸ articles to suggest that regular exercise for individuals with ASD has a positive effect on multiple symptom domains, suggesting that this is an important additional treatment recommendation for children and families.

In conclusion, identification and treatment of ASD and co-occurring syndromes is often challenging, and while specialty referral often will be necessary, it is hoped that this overview provides a helpful frame of reference for primary care providers who encounter these conditions in clinical practice.

For further reading on this important subject, I recommend the American Academy of Child and Adolescent Psychiatry Practice Parameter for the Assessment and Treatment of Children and Adolescents with ASD and the Parents Medication Guide for Autism Spectrum Disorders.
 

Dr. Hoffnung is a pediatric psychiatrist at the University of Vermont Children’s Hospital and an assistant professor of psychiatry at the Robert Larner, M.D. College of Medicine at the University of Vermont, both in Burlington. He has no relevant financial disclosures. Email him at pdnews@mdedge.com.

References

1. ​MMWR Surveill Summ 2018;67(No. SS-6):1–23*

2. National Standards Project, Phase 2. National Autism Center 2015.

3. N Engl J Med. 2002 Aug 1;347(5):314-21.

4. J Am Acad Child Adolesc Psychiatry. 2009 Nov;48(11):1110-9.

5. Arch Gen Psychiatry. 2005 Nov;62(11):1266-74.

6. Pediatrics. 2016 Feb;137(Supplement 2):S115-S123.

7. Research in Autism Spectrum Disorders. 2010 Dec;4(4):565-76.

8. Research in Autism Spectrum Disorders. 2012;6(1):46-57.

*This article was updated 4/2/2020.

Efforts toward early identification and treatment are an important facet of the public health work in autism spectrum disorder (ASD).

O_Lypa/iStock/Getty Images

The prevalence of ASD is rising. With the most recent estimate from the Centers from Disease Control and Prevention of 1 in 59* children aged 8 years,¹ it is important for pediatric health care providers to have an understanding of current recommendations for treatment so they can counsel and guide affected families. ASD is a heterogeneous condition, so this article seeks to touch on broad principles, recognizing that clinicians must take into account the full clinical picture of each individual and family.

It is important to acknowledge that while there is no cure for ASD, there are treatment modalities that have an evidence base for addressing specific areas that may be impaired in children with autism. While it is beyond the scope of this article to review all of the potential areas of intervention in children with ASD, it is important to be keep in mind a few important principles.

1. The best evidenced treatment for addressing challenging and problematic behavior as well as improving a host of outcomes in children with ASD is itself behavioral in nature. These treatments are based on the principles of applied behavioral analysis,² an educational and therapeutic approach which involves looking at antecedents and consequences of behaviors. This approach also looks to shape, motivate, and reinforce functional behaviors while discouraging harmful and disruptive ones.

2. Because communication often is impaired in children with ASD, providers always should investigate for possible medical causes of pain or discomfort that might explain sudden behavior change, as well as environmental changes that could be involved.

3. The overarching principle of psychopharmacology in ASD is to start low, and go slow – because children with ASD often are particularly sensitive to medication side effects.
 

Irritability/aggression/extreme mood lability

There are only two medications with Food and Drug Administration labeling for an autism specific condition, and those are aripiprazole and risperidone, two second-generation antipsychotic agents approved for irritability associated with ASD on the basis of randomized controlled trials (RCTs) demonstrating their efficacy.^3,4 Included under the umbrella of irritability are aggression, deliberate self-injurious behavior, extreme temper tantrums, and quick and extreme mood changes. For aripiprazole the approved ages are 6-17 years; a dosing range of 2-15 mg/day is recommended. For risperidone, the approved age range is 5-17 years; the recommended dosing range is 0.25-4 mg/day. Prior to starting either of these medications, a cardiac history should be obtained, and baseline laboratory values, particularly lipid levels and hemoglobin A_1c (HbA_1c) are recommended. All second-generation antipsychotics carry the risk of tardive dyskinesia (a movement disorder), as well as risk of weight gain and metabolic effects. Baseline weight prior to medication initiation with routine follow-up measurement is encouraged. In light of the burden of potential side effects, these medications tend to be reserved by clinicians for circumstances where there is a significant impact on functioning. Both medications are available in liquid form for children with difficulty swallowing pills.

ADHD

There are positive RCTs of methylphenidate in co-occurring ASD and ADHD,⁵ making it the preferred first line agent for treatment. Amphetamine salt based stimulant preparations do not have any RCTs in co-occurring ASD, but theoretically should be similarly effective. Again, the principle of starting low and going slow is applicable. Second line are the alpha 2 adrenergic agonists guanfacine and clonidine, both of whose long-acting formulations are approved for treatment of ADHD in children and adolescents without ASD, as well as atomoxetine, a selective norepinephrine reuptake inhibitor approved for ADHD. Guanfacine and atomoxetine have the stronger evidence base in the co-occurring condition. None of the second-line medications come in liquid preparation, although the immediate-release forms of guanfacine and clonidine both can be crushed and are used in clinical practice when the extended-release forms are not practicable.

Anxiety disorders and depression

Repetitive behaviors and insistence on sameness are broad headings that can be thought of as similar to obsessive compulsive disorder in children without ASD. However, controlled studies of SSRIs and clomipramine (a tricyclic antidepressant) have not shown a clear benefit in these behaviors in children with autism. There are no RCTs looking specifically at treatment of anxiety disorders in children with ASD, but expert consensus is that pharmacologic treatment is similar to that of children without ASD, with the SSRIs fluoxetine and sertraline the first-line agents due to the robust evidence for these two medications in treatment of anxiety disorders in children.⁶ Especially for kids with higher functioning ASD, cognitive behavioral therapy (CBT) should be considered and has some evidence for the co-occurring condition. Similarly, there are no RCTs for co-occurring depression in ASD, and clinical practice is to treat it as you would depression in the non-ASD population. Be aware that the studies of SSRIs in children with ASD reported higher than typical rates of behavioral activation on these medications, and again the principle of starting low and going slow is emphasized. Fluoxetine and sertraline both come in liquid form.

Insomnia

Insomnia is a common occurrence in children with ASD, and studies suggest melatonin can be effective, with immediate release clonidine a consideration with some limited evidence, if melatonin is not successful.

Finally I would be remiss in not mentioning that there is preliminary evidence from review⁷ and meta-analysis⁸ articles to suggest that regular exercise for individuals with ASD has a positive effect on multiple symptom domains, suggesting that this is an important additional treatment recommendation for children and families.

In conclusion, identification and treatment of ASD and co-occurring syndromes is often challenging, and while specialty referral often will be necessary, it is hoped that this overview provides a helpful frame of reference for primary care providers who encounter these conditions in clinical practice.

For further reading on this important subject, I recommend the American Academy of Child and Adolescent Psychiatry Practice Parameter for the Assessment and Treatment of Children and Adolescents with ASD and the Parents Medication Guide for Autism Spectrum Disorders.
 

Dr. Hoffnung is a pediatric psychiatrist at the University of Vermont Children’s Hospital and an assistant professor of psychiatry at the Robert Larner, M.D. College of Medicine at the University of Vermont, both in Burlington. He has no relevant financial disclosures. Email him at pdnews@mdedge.com.

References

1. ​MMWR Surveill Summ 2018;67(No. SS-6):1–23*

2. National Standards Project, Phase 2. National Autism Center 2015.

3. N Engl J Med. 2002 Aug 1;347(5):314-21.

4. J Am Acad Child Adolesc Psychiatry. 2009 Nov;48(11):1110-9.

5. Arch Gen Psychiatry. 2005 Nov;62(11):1266-74.

6. Pediatrics. 2016 Feb;137(Supplement 2):S115-S123.

7. Research in Autism Spectrum Disorders. 2010 Dec;4(4):565-76.

8. Research in Autism Spectrum Disorders. 2012;6(1):46-57.

*This article was updated 4/2/2020.

Efforts toward early identification and treatment are an important facet of the public health work in autism spectrum disorder (ASD).

O_Lypa/iStock/Getty Images

The prevalence of ASD is rising. With the most recent estimate from the Centers from Disease Control and Prevention of 1 in 59* children aged 8 years,¹ it is important for pediatric health care providers to have an understanding of current recommendations for treatment so they can counsel and guide affected families. ASD is a heterogeneous condition, so this article seeks to touch on broad principles, recognizing that clinicians must take into account the full clinical picture of each individual and family.

It is important to acknowledge that while there is no cure for ASD, there are treatment modalities that have an evidence base for addressing specific areas that may be impaired in children with autism. While it is beyond the scope of this article to review all of the potential areas of intervention in children with ASD, it is important to be keep in mind a few important principles.

1. The best evidenced treatment for addressing challenging and problematic behavior as well as improving a host of outcomes in children with ASD is itself behavioral in nature. These treatments are based on the principles of applied behavioral analysis,² an educational and therapeutic approach which involves looking at antecedents and consequences of behaviors. This approach also looks to shape, motivate, and reinforce functional behaviors while discouraging harmful and disruptive ones.

2. Because communication often is impaired in children with ASD, providers always should investigate for possible medical causes of pain or discomfort that might explain sudden behavior change, as well as environmental changes that could be involved.

3. The overarching principle of psychopharmacology in ASD is to start low, and go slow – because children with ASD often are particularly sensitive to medication side effects.
 

Irritability/aggression/extreme mood lability

There are only two medications with Food and Drug Administration labeling for an autism specific condition, and those are aripiprazole and risperidone, two second-generation antipsychotic agents approved for irritability associated with ASD on the basis of randomized controlled trials (RCTs) demonstrating their efficacy.^3,4 Included under the umbrella of irritability are aggression, deliberate self-injurious behavior, extreme temper tantrums, and quick and extreme mood changes. For aripiprazole the approved ages are 6-17 years; a dosing range of 2-15 mg/day is recommended. For risperidone, the approved age range is 5-17 years; the recommended dosing range is 0.25-4 mg/day. Prior to starting either of these medications, a cardiac history should be obtained, and baseline laboratory values, particularly lipid levels and hemoglobin A_1c (HbA_1c) are recommended. All second-generation antipsychotics carry the risk of tardive dyskinesia (a movement disorder), as well as risk of weight gain and metabolic effects. Baseline weight prior to medication initiation with routine follow-up measurement is encouraged. In light of the burden of potential side effects, these medications tend to be reserved by clinicians for circumstances where there is a significant impact on functioning. Both medications are available in liquid form for children with difficulty swallowing pills.

ADHD

There are positive RCTs of methylphenidate in co-occurring ASD and ADHD,⁵ making it the preferred first line agent for treatment. Amphetamine salt based stimulant preparations do not have any RCTs in co-occurring ASD, but theoretically should be similarly effective. Again, the principle of starting low and going slow is applicable. Second line are the alpha 2 adrenergic agonists guanfacine and clonidine, both of whose long-acting formulations are approved for treatment of ADHD in children and adolescents without ASD, as well as atomoxetine, a selective norepinephrine reuptake inhibitor approved for ADHD. Guanfacine and atomoxetine have the stronger evidence base in the co-occurring condition. None of the second-line medications come in liquid preparation, although the immediate-release forms of guanfacine and clonidine both can be crushed and are used in clinical practice when the extended-release forms are not practicable.

Anxiety disorders and depression

Repetitive behaviors and insistence on sameness are broad headings that can be thought of as similar to obsessive compulsive disorder in children without ASD. However, controlled studies of SSRIs and clomipramine (a tricyclic antidepressant) have not shown a clear benefit in these behaviors in children with autism. There are no RCTs looking specifically at treatment of anxiety disorders in children with ASD, but expert consensus is that pharmacologic treatment is similar to that of children without ASD, with the SSRIs fluoxetine and sertraline the first-line agents due to the robust evidence for these two medications in treatment of anxiety disorders in children.⁶ Especially for kids with higher functioning ASD, cognitive behavioral therapy (CBT) should be considered and has some evidence for the co-occurring condition. Similarly, there are no RCTs for co-occurring depression in ASD, and clinical practice is to treat it as you would depression in the non-ASD population. Be aware that the studies of SSRIs in children with ASD reported higher than typical rates of behavioral activation on these medications, and again the principle of starting low and going slow is emphasized. Fluoxetine and sertraline both come in liquid form.

Insomnia

Insomnia is a common occurrence in children with ASD, and studies suggest melatonin can be effective, with immediate release clonidine a consideration with some limited evidence, if melatonin is not successful.

Finally I would be remiss in not mentioning that there is preliminary evidence from review⁷ and meta-analysis⁸ articles to suggest that regular exercise for individuals with ASD has a positive effect on multiple symptom domains, suggesting that this is an important additional treatment recommendation for children and families.

In conclusion, identification and treatment of ASD and co-occurring syndromes is often challenging, and while specialty referral often will be necessary, it is hoped that this overview provides a helpful frame of reference for primary care providers who encounter these conditions in clinical practice.

For further reading on this important subject, I recommend the American Academy of Child and Adolescent Psychiatry Practice Parameter for the Assessment and Treatment of Children and Adolescents with ASD and the Parents Medication Guide for Autism Spectrum Disorders.
 

Dr. Hoffnung is a pediatric psychiatrist at the University of Vermont Children’s Hospital and an assistant professor of psychiatry at the Robert Larner, M.D. College of Medicine at the University of Vermont, both in Burlington. He has no relevant financial disclosures. Email him at pdnews@mdedge.com.

References

1. ​MMWR Surveill Summ 2018;67(No. SS-6):1–23*

2. National Standards Project, Phase 2. National Autism Center 2015.

3. N Engl J Med. 2002 Aug 1;347(5):314-21.

4. J Am Acad Child Adolesc Psychiatry. 2009 Nov;48(11):1110-9.

5. Arch Gen Psychiatry. 2005 Nov;62(11):1266-74.

6. Pediatrics. 2016 Feb;137(Supplement 2):S115-S123.

7. Research in Autism Spectrum Disorders. 2010 Dec;4(4):565-76.

8. Research in Autism Spectrum Disorders. 2012;6(1):46-57.

*This article was updated 4/2/2020.