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The first signs of elusive dysautonomia may appear on the skin
During the annual meeting of the Society for Pediatric Dermatology, Adelaide A. Hebert, MD, defined dysautonomia as an umbrella term describing conditions that result in a malfunction of the autonomic nervous system. “This encompasses both the sympathetic and the parasympathetic components of the nervous system,” said Dr. Hebert, professor of dermatology and pediatrics, and chief of pediatric dermatology at the University of Texas, Houston. “Clinical findings may be neurometabolic, developmental, and/or degenerative,” representing a “whole constellation of issues” that physicians may encounter in practice, she noted. Of particular interest is postural orthostatic tachycardia syndrome (POTS), which affects between 1 million and 3 million people in the United States. Typical symptoms include lightheadedness, fainting, and a rapid increase in heartbeat after standing up from a seated position. Other conditions associated with dysautonomia include neurocardiogenic syncope and multiple system atrophy.
Dysautonomia can impact the brain, heart, mouth, blood vessels, eyes, immune cells, and bladder, as well as the skin. Patient presentations vary with symptoms that can range from mild to debilitating. The average time from symptom onset to diagnosis of dysautonomia is 7 years. “It is very difficult to put together these mysterious symptoms that patients have unless one really thinks about dysautonomia as a possible diagnosis,” Dr. Hebert said.
One of the common symptoms that she has seen in her clinical practice is joint hypermobility. “There is a known association between dysautonomia and hypermobile-type Ehlers-Danlos syndrome (EDS), and these patients often have hyperhidrosis,” she said. “So, keep in mind that you could see hypermobility, especially in those with EDS, with associated hyperhidrosis and dysautonomia.” Two key references that she recommends to clinicians when evaluating patients with possible dysautonomia are a study on postural tachycardia in hypermobile EDS, and an article on cardiovascular autonomic dysfunction in hypermobile EDS.
The Beighton Scoring System, which measures joint mobility on a 9-point scale, involves assessment of the joint mobility of the knuckle of both pinky fingers, the base of both thumbs, the elbows, knees, and spine. An instructional video on how to perform a joint hypermobility assessment is available on the Ehler-Danlos Society website.
Literature review
In March 2021, Dr. Hebert and colleagues from other medical specialties published a summary of the literature on cutaneous manifestations in dysautonomia, with an emphasis on syndromes of orthostatic intolerance. “We had neurology, cardiology, along with dermatology involved in contributing the findings they had seen in the UTHealth McGovern Dysautonomia Center of Excellence as there was a dearth of literature that taught us about the cutaneous manifestations of orthostatic intolerance syndromes,” Dr. Hebert said.
One study included in the review showed that 23 out of 26 patients with POTS had at least one of the following cutaneous manifestations: flushing, Raynaud’s phenomenon, evanescent hyperemia, livedo reticularis, erythromelalgia, and hypo- or hyperhidrosis. “If you see a patient with any of these findings, you want to think about the possibility of dysautonomia,” she said, adding that urticaria can also be a finding.
To screen for dysautonomia, she advised, “ask patients if they have difficulty sitting or standing upright, if they have indigestion or other gastric symptoms, abnormal blood vessel functioning such as low or high blood pressure, increased or decreased sweating, changes in urinary frequency or urinary incontinence, or challenges with vision.”
If the patient answers yes to two or more of these questions, she said, consider a referral to neurology and/or cardiology or a center of excellence for further evaluation with tilt-table testing and other screening tools. She also recommended a review published in 2015 that describes the dermatological manifestations of postural tachycardia syndrome and includes illustrated cases.
One of Dr. Hebert’s future dermatology residents assembled a composite of data from the Dysautonomia Center of Excellence, and in the study, found that, compared with males, females with dysautonomia suffer more from excessive sweating, paleness of the face, pale extremities, swelling, cyanosis, cold intolerance, flushing, and hot flashes.
Dr. Hebert disclosed that she has been a consultant to and an adviser for several pharmaceutical companies.
During the annual meeting of the Society for Pediatric Dermatology, Adelaide A. Hebert, MD, defined dysautonomia as an umbrella term describing conditions that result in a malfunction of the autonomic nervous system. “This encompasses both the sympathetic and the parasympathetic components of the nervous system,” said Dr. Hebert, professor of dermatology and pediatrics, and chief of pediatric dermatology at the University of Texas, Houston. “Clinical findings may be neurometabolic, developmental, and/or degenerative,” representing a “whole constellation of issues” that physicians may encounter in practice, she noted. Of particular interest is postural orthostatic tachycardia syndrome (POTS), which affects between 1 million and 3 million people in the United States. Typical symptoms include lightheadedness, fainting, and a rapid increase in heartbeat after standing up from a seated position. Other conditions associated with dysautonomia include neurocardiogenic syncope and multiple system atrophy.
Dysautonomia can impact the brain, heart, mouth, blood vessels, eyes, immune cells, and bladder, as well as the skin. Patient presentations vary with symptoms that can range from mild to debilitating. The average time from symptom onset to diagnosis of dysautonomia is 7 years. “It is very difficult to put together these mysterious symptoms that patients have unless one really thinks about dysautonomia as a possible diagnosis,” Dr. Hebert said.
One of the common symptoms that she has seen in her clinical practice is joint hypermobility. “There is a known association between dysautonomia and hypermobile-type Ehlers-Danlos syndrome (EDS), and these patients often have hyperhidrosis,” she said. “So, keep in mind that you could see hypermobility, especially in those with EDS, with associated hyperhidrosis and dysautonomia.” Two key references that she recommends to clinicians when evaluating patients with possible dysautonomia are a study on postural tachycardia in hypermobile EDS, and an article on cardiovascular autonomic dysfunction in hypermobile EDS.
The Beighton Scoring System, which measures joint mobility on a 9-point scale, involves assessment of the joint mobility of the knuckle of both pinky fingers, the base of both thumbs, the elbows, knees, and spine. An instructional video on how to perform a joint hypermobility assessment is available on the Ehler-Danlos Society website.
Literature review
In March 2021, Dr. Hebert and colleagues from other medical specialties published a summary of the literature on cutaneous manifestations in dysautonomia, with an emphasis on syndromes of orthostatic intolerance. “We had neurology, cardiology, along with dermatology involved in contributing the findings they had seen in the UTHealth McGovern Dysautonomia Center of Excellence as there was a dearth of literature that taught us about the cutaneous manifestations of orthostatic intolerance syndromes,” Dr. Hebert said.
One study included in the review showed that 23 out of 26 patients with POTS had at least one of the following cutaneous manifestations: flushing, Raynaud’s phenomenon, evanescent hyperemia, livedo reticularis, erythromelalgia, and hypo- or hyperhidrosis. “If you see a patient with any of these findings, you want to think about the possibility of dysautonomia,” she said, adding that urticaria can also be a finding.
To screen for dysautonomia, she advised, “ask patients if they have difficulty sitting or standing upright, if they have indigestion or other gastric symptoms, abnormal blood vessel functioning such as low or high blood pressure, increased or decreased sweating, changes in urinary frequency or urinary incontinence, or challenges with vision.”
If the patient answers yes to two or more of these questions, she said, consider a referral to neurology and/or cardiology or a center of excellence for further evaluation with tilt-table testing and other screening tools. She also recommended a review published in 2015 that describes the dermatological manifestations of postural tachycardia syndrome and includes illustrated cases.
One of Dr. Hebert’s future dermatology residents assembled a composite of data from the Dysautonomia Center of Excellence, and in the study, found that, compared with males, females with dysautonomia suffer more from excessive sweating, paleness of the face, pale extremities, swelling, cyanosis, cold intolerance, flushing, and hot flashes.
Dr. Hebert disclosed that she has been a consultant to and an adviser for several pharmaceutical companies.
During the annual meeting of the Society for Pediatric Dermatology, Adelaide A. Hebert, MD, defined dysautonomia as an umbrella term describing conditions that result in a malfunction of the autonomic nervous system. “This encompasses both the sympathetic and the parasympathetic components of the nervous system,” said Dr. Hebert, professor of dermatology and pediatrics, and chief of pediatric dermatology at the University of Texas, Houston. “Clinical findings may be neurometabolic, developmental, and/or degenerative,” representing a “whole constellation of issues” that physicians may encounter in practice, she noted. Of particular interest is postural orthostatic tachycardia syndrome (POTS), which affects between 1 million and 3 million people in the United States. Typical symptoms include lightheadedness, fainting, and a rapid increase in heartbeat after standing up from a seated position. Other conditions associated with dysautonomia include neurocardiogenic syncope and multiple system atrophy.
Dysautonomia can impact the brain, heart, mouth, blood vessels, eyes, immune cells, and bladder, as well as the skin. Patient presentations vary with symptoms that can range from mild to debilitating. The average time from symptom onset to diagnosis of dysautonomia is 7 years. “It is very difficult to put together these mysterious symptoms that patients have unless one really thinks about dysautonomia as a possible diagnosis,” Dr. Hebert said.
One of the common symptoms that she has seen in her clinical practice is joint hypermobility. “There is a known association between dysautonomia and hypermobile-type Ehlers-Danlos syndrome (EDS), and these patients often have hyperhidrosis,” she said. “So, keep in mind that you could see hypermobility, especially in those with EDS, with associated hyperhidrosis and dysautonomia.” Two key references that she recommends to clinicians when evaluating patients with possible dysautonomia are a study on postural tachycardia in hypermobile EDS, and an article on cardiovascular autonomic dysfunction in hypermobile EDS.
The Beighton Scoring System, which measures joint mobility on a 9-point scale, involves assessment of the joint mobility of the knuckle of both pinky fingers, the base of both thumbs, the elbows, knees, and spine. An instructional video on how to perform a joint hypermobility assessment is available on the Ehler-Danlos Society website.
Literature review
In March 2021, Dr. Hebert and colleagues from other medical specialties published a summary of the literature on cutaneous manifestations in dysautonomia, with an emphasis on syndromes of orthostatic intolerance. “We had neurology, cardiology, along with dermatology involved in contributing the findings they had seen in the UTHealth McGovern Dysautonomia Center of Excellence as there was a dearth of literature that taught us about the cutaneous manifestations of orthostatic intolerance syndromes,” Dr. Hebert said.
One study included in the review showed that 23 out of 26 patients with POTS had at least one of the following cutaneous manifestations: flushing, Raynaud’s phenomenon, evanescent hyperemia, livedo reticularis, erythromelalgia, and hypo- or hyperhidrosis. “If you see a patient with any of these findings, you want to think about the possibility of dysautonomia,” she said, adding that urticaria can also be a finding.
To screen for dysautonomia, she advised, “ask patients if they have difficulty sitting or standing upright, if they have indigestion or other gastric symptoms, abnormal blood vessel functioning such as low or high blood pressure, increased or decreased sweating, changes in urinary frequency or urinary incontinence, or challenges with vision.”
If the patient answers yes to two or more of these questions, she said, consider a referral to neurology and/or cardiology or a center of excellence for further evaluation with tilt-table testing and other screening tools. She also recommended a review published in 2015 that describes the dermatological manifestations of postural tachycardia syndrome and includes illustrated cases.
One of Dr. Hebert’s future dermatology residents assembled a composite of data from the Dysautonomia Center of Excellence, and in the study, found that, compared with males, females with dysautonomia suffer more from excessive sweating, paleness of the face, pale extremities, swelling, cyanosis, cold intolerance, flushing, and hot flashes.
Dr. Hebert disclosed that she has been a consultant to and an adviser for several pharmaceutical companies.
FROM SPD 2021
PHM virtual conference promises practical pearls, plus Dr. Fauci
The Pediatric Hospital Medicine annual conference, though virtual in 2021, promises to retain its role as the premier educational event for pediatric hospitalists and other clinicians involved in treating pediatric patients.
The “can’t-miss” session, on August 5, at 6:30 p.m. ET, is a one-on-one discussion between Anthony S. Fauci, MD, and Lee Savio Beers, MD, president of the American Academic of Pediatrics, according to members of the meeting planning committee.
In addition to the conversation between Dr. Beers and Dr. Fauci, this year’s meeting offers a mix of workshops with pointers and pearls to improve practice, keynote and plenary sessions to inform and inspire, and abstract presentations of new research. Three members of the PHM Planning Committee shared their insights on the hot topics, advice for new clinicians, and tips for making the most of this year’s meeting.
Workshops worth watching
“The keynote plenary sessions by Julie Silver, MD, on ‘Accelerating Patient Care and Healthcare Workforce Diversity and Inclusion,’ and by Ilan Alhadeff, MD, on ‘Leading through Adversity’ should inspire even the least enthusiastic among us,” Mirna Giordano, MD, FHM, of Columbia University Medical Center, New York, said in an interview. A talk by Nathan T. Chomilo, MD, “will likely prompt reflection on how George Floyd’s death changed us, and how we practice medicine forever.” In addition, “PHM Stories are not to be missed, they are voices that speak loud and move mountains.”
The PHM Stories are concise, narrative talks with minimal use of slides; each PHM Stories session includes three distinct talks and a 15-minute question and answer session. PHM Stories sessions are scheduled for each day of the conference, and topics include “Practicing Medicine While Human: The Secrets Physicians Keep,” by Uchenna Ewulonu, MD; “Finding the Power of the Imposter: How I Learned to Be Exactly the Color I Am, Everywhere I Go,” by Alexandra Coria, MD; and “Purple Butterflies: A Reflection on Why I’m a Pediatric Hospitalist,” by Joanne Mendoza, MD.
“The PHM community has been through a lot in the aftermath of the pandemic,” said Dr. Giordano. “The mini-plenary session on the mental health needs of our patients, and clinical quick-hit sessions on verbal deescalation of the agitated patients and cardiac effects of COVID-19 will likely be not only very popular, but also useful in clinical endeavors. The workshop on how to navigate the adult issues in hospitalized patients will provide the Med-Peds pearls we all wish we heard earlier.”
Although a 75-minute workshop session may seem long, “the workshop choices will offer something for everyone’s taste: education, research, clinical topics, diversity, and advocacy,” Dr. Giordano said. “I suggest that attendees check in advance which sessions will be available after the meeting, so that they prioritize highly interactive sessions like workshops, and that they experience, even if virtual, small group/room gatherings and networking.” There will be time for fun, too, she emphasized, with social sessions “that we hope will break the screen monotony and bring smiles to everyone’s faces.”
For younger clinicians relatively new to practice, Dr. Giordano recommended several workshops for a wealth of advice and guidance, including “New Kids on the Block: Thriving in your First Faculty Position,” “Channeling Your Inner Coach: Techniques to Enhance Clinical Teaching & Feedback,” “Palliative Care Pearls for the Pediatric Hospitalist,” “Perioperative Medicine for Medically Complex Children: Case Studies in Programmatic Approaches,” “The Bare Necessities: Social Determinant of Health Screening for the Hospitalist,” and “Mentorship, Autonomy, and Supervising a PHM Fellow.”
Classic topics and new concepts
“We are so excited to be able to offer a full spectrum of offerings at this year’s virtual meeting,” Yemisi Jones, MD, FHM, of Cincinnati Children’s Hospital, said in an interview. “We are covering some classic topics that we can’t do without at PHM, such as clinical updates in the management of sick and well newborns; workshops on best practices for educators; as well as the latest in PHM scholarship.” Sessions include “timely topics such as equity for women in medicine with one of our plenary speakers, Julie Silver, MD, and new febrile infant guidelines,” she added.
In particular, the COVID-19 and mental health session will help address clinicians’ evolving understanding of the COVID-19 pandemic and its effects on hospitalized children, said Dr. Jones. “Attendees can expect practical, timely updates on the current state of the science and ways to improve their practice to provide the best care for our patients.”
Attendees will be able to maximize the virtual conference format by accessing archived recordings, including clinical quick hits, mini-plenaries, and PHM Stories, which can be viewed during the scheduled meeting time or after, Dr. Jones said. “Workshops and abstract presentations will involve real-time interaction with presenters, so would be highest yield to attend during the live meeting. We also encourage all participants to take full advantage of the platform and the various networking opportunities to engage with others in our PHM community.”
For residents and new fellows, Dr. Jones advised making the workshop, “A Whole New World: Tips and Tools to Soar Into Your First Year of Fellowship,” a priority. “For early-career faculty, the ‘New Kids on the Block: Thriving in your First Faculty Position workshop will be a valuable resource.”
Make the meeting content a priority
This year’s conference has an exceptional slate of plenary speakers, Michelle Marks, DO, SFHM, of the Cleveland Clinic said in an interview. In addition to the much-anticipated session on vaccinations, school guidelines, and other topics with Dr. Fauci and Dr. Beers, the sessions on leading through adversity and workforce diversity and inclusion are “important topics to the PHM community and to our greater communities as a whole.”
Dr. Marks also highlighted the value of the COVID-19 and mental health session, as the long-term impact of COVID-19 on mental health of children and adults continues to grab headlines. “From this session specifically, I hope the attendees will gain awareness of the special mental health needs for child during a global disaster like a pandemic, which can be generalized to other situations and gain skills and resources to help meet and advocate for children’s mental health needs.”
For clinicians attending the virtual conference, “The most important strategy is to schedule time off of clinical work for the virtual meeting if you can so you can focus on the content,” said Dr. Marks. “For the longer sessions, it would be very important to block time in your day to fully attend the session, attend in a private space if possible since there will be breakouts with discussion, have your camera on, and engage with the workshop group as much as possible. The virtual format can be challenging because of all the external distractions, so intentional focus is necessary,” to get the most out of the experience.
The mini-plenary session on “The New AAP Clinical Practice Guideline on the Evaluation and Management of Febrile Infants 8-60 Days Old,” is an important session for all attendees, Dr. Marks said. She also recommended the Clinical Quick Hits sessions for anyone seeking “a diverse array of practical knowledge which can be easily applied to everyday practice.” The Clinical Quick Hits are designed as 35-minute, rapid-fire presentations focused on clinical knowledge. Each of these presentations will focus on the latest updates or evolutions in clinical practice in one area. Some key topics include counseling parents when a child has an abnormal exam finding, assessing pelvic pain in adolescent girls, and preventing venous thromboembolism in the inpatient setting.
“I would also recommend that younger clinicians take in at least one or two workshops or sessions on nonclinical topics to see the breath of content at the meeting and to develop a niche interest for themselves outside of clinical work,” Dr. Marks noted.
Nonclinical sessions at PHM 2021 include workshops on a pilot for a comprehensive LGBTQ+ curriculum, using media tools for public health messaging, and practicing health literacy.
To register for the Pediatric Hospital Medicine 2021 virtual conference, visit https://apaevents.regfox.com/phm21-virtual-conference.
Dr. Giordano, Dr. Jones, and Dr. Marks are members of the PHM conference planning committee and had no relevant financial conflicts to disclose.
The Pediatric Hospital Medicine annual conference, though virtual in 2021, promises to retain its role as the premier educational event for pediatric hospitalists and other clinicians involved in treating pediatric patients.
The “can’t-miss” session, on August 5, at 6:30 p.m. ET, is a one-on-one discussion between Anthony S. Fauci, MD, and Lee Savio Beers, MD, president of the American Academic of Pediatrics, according to members of the meeting planning committee.
In addition to the conversation between Dr. Beers and Dr. Fauci, this year’s meeting offers a mix of workshops with pointers and pearls to improve practice, keynote and plenary sessions to inform and inspire, and abstract presentations of new research. Three members of the PHM Planning Committee shared their insights on the hot topics, advice for new clinicians, and tips for making the most of this year’s meeting.
Workshops worth watching
“The keynote plenary sessions by Julie Silver, MD, on ‘Accelerating Patient Care and Healthcare Workforce Diversity and Inclusion,’ and by Ilan Alhadeff, MD, on ‘Leading through Adversity’ should inspire even the least enthusiastic among us,” Mirna Giordano, MD, FHM, of Columbia University Medical Center, New York, said in an interview. A talk by Nathan T. Chomilo, MD, “will likely prompt reflection on how George Floyd’s death changed us, and how we practice medicine forever.” In addition, “PHM Stories are not to be missed, they are voices that speak loud and move mountains.”
The PHM Stories are concise, narrative talks with minimal use of slides; each PHM Stories session includes three distinct talks and a 15-minute question and answer session. PHM Stories sessions are scheduled for each day of the conference, and topics include “Practicing Medicine While Human: The Secrets Physicians Keep,” by Uchenna Ewulonu, MD; “Finding the Power of the Imposter: How I Learned to Be Exactly the Color I Am, Everywhere I Go,” by Alexandra Coria, MD; and “Purple Butterflies: A Reflection on Why I’m a Pediatric Hospitalist,” by Joanne Mendoza, MD.
“The PHM community has been through a lot in the aftermath of the pandemic,” said Dr. Giordano. “The mini-plenary session on the mental health needs of our patients, and clinical quick-hit sessions on verbal deescalation of the agitated patients and cardiac effects of COVID-19 will likely be not only very popular, but also useful in clinical endeavors. The workshop on how to navigate the adult issues in hospitalized patients will provide the Med-Peds pearls we all wish we heard earlier.”
Although a 75-minute workshop session may seem long, “the workshop choices will offer something for everyone’s taste: education, research, clinical topics, diversity, and advocacy,” Dr. Giordano said. “I suggest that attendees check in advance which sessions will be available after the meeting, so that they prioritize highly interactive sessions like workshops, and that they experience, even if virtual, small group/room gatherings and networking.” There will be time for fun, too, she emphasized, with social sessions “that we hope will break the screen monotony and bring smiles to everyone’s faces.”
For younger clinicians relatively new to practice, Dr. Giordano recommended several workshops for a wealth of advice and guidance, including “New Kids on the Block: Thriving in your First Faculty Position,” “Channeling Your Inner Coach: Techniques to Enhance Clinical Teaching & Feedback,” “Palliative Care Pearls for the Pediatric Hospitalist,” “Perioperative Medicine for Medically Complex Children: Case Studies in Programmatic Approaches,” “The Bare Necessities: Social Determinant of Health Screening for the Hospitalist,” and “Mentorship, Autonomy, and Supervising a PHM Fellow.”
Classic topics and new concepts
“We are so excited to be able to offer a full spectrum of offerings at this year’s virtual meeting,” Yemisi Jones, MD, FHM, of Cincinnati Children’s Hospital, said in an interview. “We are covering some classic topics that we can’t do without at PHM, such as clinical updates in the management of sick and well newborns; workshops on best practices for educators; as well as the latest in PHM scholarship.” Sessions include “timely topics such as equity for women in medicine with one of our plenary speakers, Julie Silver, MD, and new febrile infant guidelines,” she added.
In particular, the COVID-19 and mental health session will help address clinicians’ evolving understanding of the COVID-19 pandemic and its effects on hospitalized children, said Dr. Jones. “Attendees can expect practical, timely updates on the current state of the science and ways to improve their practice to provide the best care for our patients.”
Attendees will be able to maximize the virtual conference format by accessing archived recordings, including clinical quick hits, mini-plenaries, and PHM Stories, which can be viewed during the scheduled meeting time or after, Dr. Jones said. “Workshops and abstract presentations will involve real-time interaction with presenters, so would be highest yield to attend during the live meeting. We also encourage all participants to take full advantage of the platform and the various networking opportunities to engage with others in our PHM community.”
For residents and new fellows, Dr. Jones advised making the workshop, “A Whole New World: Tips and Tools to Soar Into Your First Year of Fellowship,” a priority. “For early-career faculty, the ‘New Kids on the Block: Thriving in your First Faculty Position workshop will be a valuable resource.”
Make the meeting content a priority
This year’s conference has an exceptional slate of plenary speakers, Michelle Marks, DO, SFHM, of the Cleveland Clinic said in an interview. In addition to the much-anticipated session on vaccinations, school guidelines, and other topics with Dr. Fauci and Dr. Beers, the sessions on leading through adversity and workforce diversity and inclusion are “important topics to the PHM community and to our greater communities as a whole.”
Dr. Marks also highlighted the value of the COVID-19 and mental health session, as the long-term impact of COVID-19 on mental health of children and adults continues to grab headlines. “From this session specifically, I hope the attendees will gain awareness of the special mental health needs for child during a global disaster like a pandemic, which can be generalized to other situations and gain skills and resources to help meet and advocate for children’s mental health needs.”
For clinicians attending the virtual conference, “The most important strategy is to schedule time off of clinical work for the virtual meeting if you can so you can focus on the content,” said Dr. Marks. “For the longer sessions, it would be very important to block time in your day to fully attend the session, attend in a private space if possible since there will be breakouts with discussion, have your camera on, and engage with the workshop group as much as possible. The virtual format can be challenging because of all the external distractions, so intentional focus is necessary,” to get the most out of the experience.
The mini-plenary session on “The New AAP Clinical Practice Guideline on the Evaluation and Management of Febrile Infants 8-60 Days Old,” is an important session for all attendees, Dr. Marks said. She also recommended the Clinical Quick Hits sessions for anyone seeking “a diverse array of practical knowledge which can be easily applied to everyday practice.” The Clinical Quick Hits are designed as 35-minute, rapid-fire presentations focused on clinical knowledge. Each of these presentations will focus on the latest updates or evolutions in clinical practice in one area. Some key topics include counseling parents when a child has an abnormal exam finding, assessing pelvic pain in adolescent girls, and preventing venous thromboembolism in the inpatient setting.
“I would also recommend that younger clinicians take in at least one or two workshops or sessions on nonclinical topics to see the breath of content at the meeting and to develop a niche interest for themselves outside of clinical work,” Dr. Marks noted.
Nonclinical sessions at PHM 2021 include workshops on a pilot for a comprehensive LGBTQ+ curriculum, using media tools for public health messaging, and practicing health literacy.
To register for the Pediatric Hospital Medicine 2021 virtual conference, visit https://apaevents.regfox.com/phm21-virtual-conference.
Dr. Giordano, Dr. Jones, and Dr. Marks are members of the PHM conference planning committee and had no relevant financial conflicts to disclose.
The Pediatric Hospital Medicine annual conference, though virtual in 2021, promises to retain its role as the premier educational event for pediatric hospitalists and other clinicians involved in treating pediatric patients.
The “can’t-miss” session, on August 5, at 6:30 p.m. ET, is a one-on-one discussion between Anthony S. Fauci, MD, and Lee Savio Beers, MD, president of the American Academic of Pediatrics, according to members of the meeting planning committee.
In addition to the conversation between Dr. Beers and Dr. Fauci, this year’s meeting offers a mix of workshops with pointers and pearls to improve practice, keynote and plenary sessions to inform and inspire, and abstract presentations of new research. Three members of the PHM Planning Committee shared their insights on the hot topics, advice for new clinicians, and tips for making the most of this year’s meeting.
Workshops worth watching
“The keynote plenary sessions by Julie Silver, MD, on ‘Accelerating Patient Care and Healthcare Workforce Diversity and Inclusion,’ and by Ilan Alhadeff, MD, on ‘Leading through Adversity’ should inspire even the least enthusiastic among us,” Mirna Giordano, MD, FHM, of Columbia University Medical Center, New York, said in an interview. A talk by Nathan T. Chomilo, MD, “will likely prompt reflection on how George Floyd’s death changed us, and how we practice medicine forever.” In addition, “PHM Stories are not to be missed, they are voices that speak loud and move mountains.”
The PHM Stories are concise, narrative talks with minimal use of slides; each PHM Stories session includes three distinct talks and a 15-minute question and answer session. PHM Stories sessions are scheduled for each day of the conference, and topics include “Practicing Medicine While Human: The Secrets Physicians Keep,” by Uchenna Ewulonu, MD; “Finding the Power of the Imposter: How I Learned to Be Exactly the Color I Am, Everywhere I Go,” by Alexandra Coria, MD; and “Purple Butterflies: A Reflection on Why I’m a Pediatric Hospitalist,” by Joanne Mendoza, MD.
“The PHM community has been through a lot in the aftermath of the pandemic,” said Dr. Giordano. “The mini-plenary session on the mental health needs of our patients, and clinical quick-hit sessions on verbal deescalation of the agitated patients and cardiac effects of COVID-19 will likely be not only very popular, but also useful in clinical endeavors. The workshop on how to navigate the adult issues in hospitalized patients will provide the Med-Peds pearls we all wish we heard earlier.”
Although a 75-minute workshop session may seem long, “the workshop choices will offer something for everyone’s taste: education, research, clinical topics, diversity, and advocacy,” Dr. Giordano said. “I suggest that attendees check in advance which sessions will be available after the meeting, so that they prioritize highly interactive sessions like workshops, and that they experience, even if virtual, small group/room gatherings and networking.” There will be time for fun, too, she emphasized, with social sessions “that we hope will break the screen monotony and bring smiles to everyone’s faces.”
For younger clinicians relatively new to practice, Dr. Giordano recommended several workshops for a wealth of advice and guidance, including “New Kids on the Block: Thriving in your First Faculty Position,” “Channeling Your Inner Coach: Techniques to Enhance Clinical Teaching & Feedback,” “Palliative Care Pearls for the Pediatric Hospitalist,” “Perioperative Medicine for Medically Complex Children: Case Studies in Programmatic Approaches,” “The Bare Necessities: Social Determinant of Health Screening for the Hospitalist,” and “Mentorship, Autonomy, and Supervising a PHM Fellow.”
Classic topics and new concepts
“We are so excited to be able to offer a full spectrum of offerings at this year’s virtual meeting,” Yemisi Jones, MD, FHM, of Cincinnati Children’s Hospital, said in an interview. “We are covering some classic topics that we can’t do without at PHM, such as clinical updates in the management of sick and well newborns; workshops on best practices for educators; as well as the latest in PHM scholarship.” Sessions include “timely topics such as equity for women in medicine with one of our plenary speakers, Julie Silver, MD, and new febrile infant guidelines,” she added.
In particular, the COVID-19 and mental health session will help address clinicians’ evolving understanding of the COVID-19 pandemic and its effects on hospitalized children, said Dr. Jones. “Attendees can expect practical, timely updates on the current state of the science and ways to improve their practice to provide the best care for our patients.”
Attendees will be able to maximize the virtual conference format by accessing archived recordings, including clinical quick hits, mini-plenaries, and PHM Stories, which can be viewed during the scheduled meeting time or after, Dr. Jones said. “Workshops and abstract presentations will involve real-time interaction with presenters, so would be highest yield to attend during the live meeting. We also encourage all participants to take full advantage of the platform and the various networking opportunities to engage with others in our PHM community.”
For residents and new fellows, Dr. Jones advised making the workshop, “A Whole New World: Tips and Tools to Soar Into Your First Year of Fellowship,” a priority. “For early-career faculty, the ‘New Kids on the Block: Thriving in your First Faculty Position workshop will be a valuable resource.”
Make the meeting content a priority
This year’s conference has an exceptional slate of plenary speakers, Michelle Marks, DO, SFHM, of the Cleveland Clinic said in an interview. In addition to the much-anticipated session on vaccinations, school guidelines, and other topics with Dr. Fauci and Dr. Beers, the sessions on leading through adversity and workforce diversity and inclusion are “important topics to the PHM community and to our greater communities as a whole.”
Dr. Marks also highlighted the value of the COVID-19 and mental health session, as the long-term impact of COVID-19 on mental health of children and adults continues to grab headlines. “From this session specifically, I hope the attendees will gain awareness of the special mental health needs for child during a global disaster like a pandemic, which can be generalized to other situations and gain skills and resources to help meet and advocate for children’s mental health needs.”
For clinicians attending the virtual conference, “The most important strategy is to schedule time off of clinical work for the virtual meeting if you can so you can focus on the content,” said Dr. Marks. “For the longer sessions, it would be very important to block time in your day to fully attend the session, attend in a private space if possible since there will be breakouts with discussion, have your camera on, and engage with the workshop group as much as possible. The virtual format can be challenging because of all the external distractions, so intentional focus is necessary,” to get the most out of the experience.
The mini-plenary session on “The New AAP Clinical Practice Guideline on the Evaluation and Management of Febrile Infants 8-60 Days Old,” is an important session for all attendees, Dr. Marks said. She also recommended the Clinical Quick Hits sessions for anyone seeking “a diverse array of practical knowledge which can be easily applied to everyday practice.” The Clinical Quick Hits are designed as 35-minute, rapid-fire presentations focused on clinical knowledge. Each of these presentations will focus on the latest updates or evolutions in clinical practice in one area. Some key topics include counseling parents when a child has an abnormal exam finding, assessing pelvic pain in adolescent girls, and preventing venous thromboembolism in the inpatient setting.
“I would also recommend that younger clinicians take in at least one or two workshops or sessions on nonclinical topics to see the breath of content at the meeting and to develop a niche interest for themselves outside of clinical work,” Dr. Marks noted.
Nonclinical sessions at PHM 2021 include workshops on a pilot for a comprehensive LGBTQ+ curriculum, using media tools for public health messaging, and practicing health literacy.
To register for the Pediatric Hospital Medicine 2021 virtual conference, visit https://apaevents.regfox.com/phm21-virtual-conference.
Dr. Giordano, Dr. Jones, and Dr. Marks are members of the PHM conference planning committee and had no relevant financial conflicts to disclose.
FDA okays extended-release exenatide for children with T2D
the agency announced July 22.
Previously approved in adults, the injectable is now the second glucagonlike peptide-1 receptor agonist approved for use in pediatric type 2 diabetes, after liraglutide (Victoza, Novo Nordisk) in 2019, and the first with once-weekly administration.
The two extended-release Bydureon products – which differ in delivery device and mixing procedure – are now indicated for use in addition to diet and exercise to improve glycemic control in pediatric patients 10 years of age or older with type 2 diabetes.
Exenatide extended release is not recommended as first-line treatment following diet and exercise.
The approval was based on a 24-week, double-blind, placebo-controlled study in 82 children with type 2 diabetes aged 10 and older. They were randomized to 2 mg once-weekly exenatide extended release or placebo. At week 24, hemoglobin A1c in those randomized to the drug had dropped by 0.25 percentage points, compared with a 0.45 percentage point increase in the placebo group.
Side effects were similar to those seen in adults, including injection site reactions, headaches, and gastrointestinal discomfort.
Currently, metformin is the only oral medication approved for treating pediatric type 2 diabetes, while the injectables also include insulin in addition to the two GLP-1 receptor agonists. During a symposium held in June 2021 at the annual scientific sessions of the American Diabetes Association, speakers expressed alarm about the rise in youth developing type 2 diabetes, noting that the condition typically progresses more rapidly and is less likely to respond well to metformin, compared with adults.
But, the panelists were also optimistic about extended-release exenatide as well as several other therapies for pediatric patients with type 2 diabetes in ongoing phase 3 trials, including the sodium-glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin, and the dipeptidyl peptidase–4 inhibitors alogliptin and linagliptin. Results are expected in the next 1-2 years.
the agency announced July 22.
Previously approved in adults, the injectable is now the second glucagonlike peptide-1 receptor agonist approved for use in pediatric type 2 diabetes, after liraglutide (Victoza, Novo Nordisk) in 2019, and the first with once-weekly administration.
The two extended-release Bydureon products – which differ in delivery device and mixing procedure – are now indicated for use in addition to diet and exercise to improve glycemic control in pediatric patients 10 years of age or older with type 2 diabetes.
Exenatide extended release is not recommended as first-line treatment following diet and exercise.
The approval was based on a 24-week, double-blind, placebo-controlled study in 82 children with type 2 diabetes aged 10 and older. They were randomized to 2 mg once-weekly exenatide extended release or placebo. At week 24, hemoglobin A1c in those randomized to the drug had dropped by 0.25 percentage points, compared with a 0.45 percentage point increase in the placebo group.
Side effects were similar to those seen in adults, including injection site reactions, headaches, and gastrointestinal discomfort.
Currently, metformin is the only oral medication approved for treating pediatric type 2 diabetes, while the injectables also include insulin in addition to the two GLP-1 receptor agonists. During a symposium held in June 2021 at the annual scientific sessions of the American Diabetes Association, speakers expressed alarm about the rise in youth developing type 2 diabetes, noting that the condition typically progresses more rapidly and is less likely to respond well to metformin, compared with adults.
But, the panelists were also optimistic about extended-release exenatide as well as several other therapies for pediatric patients with type 2 diabetes in ongoing phase 3 trials, including the sodium-glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin, and the dipeptidyl peptidase–4 inhibitors alogliptin and linagliptin. Results are expected in the next 1-2 years.
the agency announced July 22.
Previously approved in adults, the injectable is now the second glucagonlike peptide-1 receptor agonist approved for use in pediatric type 2 diabetes, after liraglutide (Victoza, Novo Nordisk) in 2019, and the first with once-weekly administration.
The two extended-release Bydureon products – which differ in delivery device and mixing procedure – are now indicated for use in addition to diet and exercise to improve glycemic control in pediatric patients 10 years of age or older with type 2 diabetes.
Exenatide extended release is not recommended as first-line treatment following diet and exercise.
The approval was based on a 24-week, double-blind, placebo-controlled study in 82 children with type 2 diabetes aged 10 and older. They were randomized to 2 mg once-weekly exenatide extended release or placebo. At week 24, hemoglobin A1c in those randomized to the drug had dropped by 0.25 percentage points, compared with a 0.45 percentage point increase in the placebo group.
Side effects were similar to those seen in adults, including injection site reactions, headaches, and gastrointestinal discomfort.
Currently, metformin is the only oral medication approved for treating pediatric type 2 diabetes, while the injectables also include insulin in addition to the two GLP-1 receptor agonists. During a symposium held in June 2021 at the annual scientific sessions of the American Diabetes Association, speakers expressed alarm about the rise in youth developing type 2 diabetes, noting that the condition typically progresses more rapidly and is less likely to respond well to metformin, compared with adults.
But, the panelists were also optimistic about extended-release exenatide as well as several other therapies for pediatric patients with type 2 diabetes in ongoing phase 3 trials, including the sodium-glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin, and the dipeptidyl peptidase–4 inhibitors alogliptin and linagliptin. Results are expected in the next 1-2 years.
Autoinflammatory diseases ‘not so rare after all,’ expert says
Not long ago, after all.
“Patients with autoinflammatory diseases are all around us, but many go several years without a diagnosis,” Dr. Dissanayake, a rheumatologist at the Autoinflammatory Disease Clinic at the Hospital for Sick Children, Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “The median time to diagnosis has been estimated to be between 2.5 and 5 years. You can imagine that this type of delay can lead to significant issues, not only with quality of life but also morbidity due to unchecked inflammation that can cause organ damage, and in the most severe cases, can result in an early death.”
Effective treatment options such as biologic medications, however, can prevent these negative sequelae if the disease is recognized early. “Dermatologists are in a unique position because they will often be the first specialist to see these patients and therefore make the diagnosis early on and really alter the lives of these patients,” he said.
While it’s common to classify autoinflammatory diseases by presenting features, such as age of onset, associated symptoms, family history/ethnicity, and triggers/alleviating factors for episodes, Dr. Dissanayake prefers to classify them into one of three groups based on pathophysiology, the first being inflammasomopathies. “When activated, an inflammasome is responsible for processing cytokines from the [interleukin]-1 family from the pro form to the active form,” he explained. As a result, if there is dysregulation and overactivity of the inflammasome, there is excessive production of cytokines like IL-1 beta and IL-18 driving the disease.
Clinical characteristics include fevers and organ involvement, notably abdominal pain, nonvasculitic rashes, uveitis, arthritis, elevated white blood cell count/neutrophils, and highly elevated inflammatory markers. Potential treatments include IL-1 blockers.
The second category of autoinflammatory diseases are the interferonopathies, which are caused by overactivity of the antiviral side of the innate immune system. “For example, if you have overactivity of a sensor for a nucleic acid in your cytosol, the cell misinterprets this as a viral infection and will turn on type 1 interferon production,” said Dr. Dissanayake, who is also an assistant professor of pediatrics at the University of Toronto. “As a result, if you have dysregulation of these pathways, you will get excessive type 1 interferon that contributes to your disease manifestations.” Clinical characteristics include fevers and organ involvement, notably vasculitic rashes, interstitial lung disease, and intracranial calcifications. Inflammatory markers may not be as elevated, and autoantibodies may be present. Janus kinase inhibitors are a potential treatment, he said.
The third category of autoinflammatory diseases are the NF-kappaBopathies, which are caused by overactivity of the NF-kappaB signaling pathway. Clinical characteristics can include fevers with organ involvement that can be highly variable but may include mucocutaneous lesions or granulomatous disease as potential clues. Treatment options depend on the pathway that is involved but tumor necrosis factor blockers often play a role because of the importance of NF-KB in this signaling pathway.
From a skin perspective, most of the rashes Dr. Dissanayake and colleagues see in the rheumatology clinic consist of nonspecific dermohypodermatitis: macules, papules, patches, or plaques. The most common monogenic autoinflammatory disease is Familial Mediterranean Fever syndrome, which “commonly presents as an erysipelas-like rash of the lower extremities, typically below the knee, often over the malleolus,” he said.
Other monogenic autoinflammatory diseases with similar rashes include TNF receptor–associated periodic syndrome, Hyper-IgD syndrome, and systemic juvenile idiopathic arthritis.
Other patients present with urticarial rashes, most commonly cryopyrin-associated periodic syndrome (CAPS). “This is a neutrophilic urticaria, so it tends not to be pruritic and can actually sometimes be tender,” he said. “It also tends not to be as transient as your typical urticaria.” Urticarial rashes can also appear with NLRP12-associated autoinflammatory syndrome (familial cold autoinflammatory syndrome–2), PLCgamma2-associated antibody deficiency and immune dysregulation, and Schnitzler syndrome (monoclonal IgM gammopathy).
Patients can also present with pyogenic or pustular lesions, which can appear with pyoderma gangrenosum–related diseases, such as pyogenic arthritis, pyoderma gangrenosum, arthritis (PAPA) syndrome; pyrin-associated inflammation with neutrophilic dermatosis; deficiency of the IL-1 receptor antagonist; deficiency of IL-36 receptor antagonist; and Majeed syndrome, a mutation in the LPIN2 gene.
The mucocutaneous system can also be affected in autoinflammatory diseases, often presenting with symptoms such as periodic fever, aphthous stomatitis, and pharyngitis. Cervical adenitis syndrome is the most common autoinflammatory disease in childhood and can present with aphthous stomatitis, he said, while Behcet’s disease typically presents with oral and genital ulcers. “More recently, monogenic forms of Behcet’s disease have been described, with haploinsufficiency of A20 and RelA, which are both part of the NF-KB pathway,” he said.
Finally, the presence of vasculitic lesions often suggest interferonopathies such as STING-associated vasculopathy in infancy, proteasome-associated autoinflammatory syndrome and deficiency of adenosine deaminase 2.
Dr. Dissanayake noted that dermatologists should suspect an autoimmune disease if a patient has recurrent fevers, evidence of systemic inflammation on blood work, and if multiple organ systems are involved, especially the lungs, gut, joints, CNS system, and eyes. “Many of these patients have episodic and stereotypical attacks,” he said.
“One of the tools we use in the autoinflammatory clinic is to have patients and families keep a symptom diary where they track the dates of the various symptoms. We can review this during their appointment and try to come up with a diagnosis based on the pattern,” he said.
Since many of these diseases are due to a single gene defect, if there’s any evidence to suggest a monogenic cause, consider an autoinflammatory disease, he added. “If there’s a family history, if there’s consanguinity, or if there’s early age of onset – these may all lead you to think about monogenic autoinflammatory disease.”
During a question-and-answer session, a meeting attendee asked what type of workup he recommends when an autoinflammatory syndrome is suspected. “It partially depends on what organ systems you suspect to be involved,” Dr. Dissanayake said. “As a routine baseline, typically what we would check is CBC and differential, [erythrocyte sedimentation rate] and [C-reactive protein], and we screen for liver transaminases and creatinine to check for liver and kidney issues. A serum albumin will also tell you if the patient is hypoalbuminemic, that there’s been some chronic inflammation and they’re starting to leak the protein out. It’s good to check blood work during the flare and off the flare, to get a sense of the persistence of that inflammation.”
Dr. Dissanayake disclosed that he has received research finding from Gilead Sciences and speaker fees from Novartis.
*This story was updated on 9/20/2021.
Not long ago, after all.
“Patients with autoinflammatory diseases are all around us, but many go several years without a diagnosis,” Dr. Dissanayake, a rheumatologist at the Autoinflammatory Disease Clinic at the Hospital for Sick Children, Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “The median time to diagnosis has been estimated to be between 2.5 and 5 years. You can imagine that this type of delay can lead to significant issues, not only with quality of life but also morbidity due to unchecked inflammation that can cause organ damage, and in the most severe cases, can result in an early death.”
Effective treatment options such as biologic medications, however, can prevent these negative sequelae if the disease is recognized early. “Dermatologists are in a unique position because they will often be the first specialist to see these patients and therefore make the diagnosis early on and really alter the lives of these patients,” he said.
While it’s common to classify autoinflammatory diseases by presenting features, such as age of onset, associated symptoms, family history/ethnicity, and triggers/alleviating factors for episodes, Dr. Dissanayake prefers to classify them into one of three groups based on pathophysiology, the first being inflammasomopathies. “When activated, an inflammasome is responsible for processing cytokines from the [interleukin]-1 family from the pro form to the active form,” he explained. As a result, if there is dysregulation and overactivity of the inflammasome, there is excessive production of cytokines like IL-1 beta and IL-18 driving the disease.
Clinical characteristics include fevers and organ involvement, notably abdominal pain, nonvasculitic rashes, uveitis, arthritis, elevated white blood cell count/neutrophils, and highly elevated inflammatory markers. Potential treatments include IL-1 blockers.
The second category of autoinflammatory diseases are the interferonopathies, which are caused by overactivity of the antiviral side of the innate immune system. “For example, if you have overactivity of a sensor for a nucleic acid in your cytosol, the cell misinterprets this as a viral infection and will turn on type 1 interferon production,” said Dr. Dissanayake, who is also an assistant professor of pediatrics at the University of Toronto. “As a result, if you have dysregulation of these pathways, you will get excessive type 1 interferon that contributes to your disease manifestations.” Clinical characteristics include fevers and organ involvement, notably vasculitic rashes, interstitial lung disease, and intracranial calcifications. Inflammatory markers may not be as elevated, and autoantibodies may be present. Janus kinase inhibitors are a potential treatment, he said.
The third category of autoinflammatory diseases are the NF-kappaBopathies, which are caused by overactivity of the NF-kappaB signaling pathway. Clinical characteristics can include fevers with organ involvement that can be highly variable but may include mucocutaneous lesions or granulomatous disease as potential clues. Treatment options depend on the pathway that is involved but tumor necrosis factor blockers often play a role because of the importance of NF-KB in this signaling pathway.
From a skin perspective, most of the rashes Dr. Dissanayake and colleagues see in the rheumatology clinic consist of nonspecific dermohypodermatitis: macules, papules, patches, or plaques. The most common monogenic autoinflammatory disease is Familial Mediterranean Fever syndrome, which “commonly presents as an erysipelas-like rash of the lower extremities, typically below the knee, often over the malleolus,” he said.
Other monogenic autoinflammatory diseases with similar rashes include TNF receptor–associated periodic syndrome, Hyper-IgD syndrome, and systemic juvenile idiopathic arthritis.
Other patients present with urticarial rashes, most commonly cryopyrin-associated periodic syndrome (CAPS). “This is a neutrophilic urticaria, so it tends not to be pruritic and can actually sometimes be tender,” he said. “It also tends not to be as transient as your typical urticaria.” Urticarial rashes can also appear with NLRP12-associated autoinflammatory syndrome (familial cold autoinflammatory syndrome–2), PLCgamma2-associated antibody deficiency and immune dysregulation, and Schnitzler syndrome (monoclonal IgM gammopathy).
Patients can also present with pyogenic or pustular lesions, which can appear with pyoderma gangrenosum–related diseases, such as pyogenic arthritis, pyoderma gangrenosum, arthritis (PAPA) syndrome; pyrin-associated inflammation with neutrophilic dermatosis; deficiency of the IL-1 receptor antagonist; deficiency of IL-36 receptor antagonist; and Majeed syndrome, a mutation in the LPIN2 gene.
The mucocutaneous system can also be affected in autoinflammatory diseases, often presenting with symptoms such as periodic fever, aphthous stomatitis, and pharyngitis. Cervical adenitis syndrome is the most common autoinflammatory disease in childhood and can present with aphthous stomatitis, he said, while Behcet’s disease typically presents with oral and genital ulcers. “More recently, monogenic forms of Behcet’s disease have been described, with haploinsufficiency of A20 and RelA, which are both part of the NF-KB pathway,” he said.
Finally, the presence of vasculitic lesions often suggest interferonopathies such as STING-associated vasculopathy in infancy, proteasome-associated autoinflammatory syndrome and deficiency of adenosine deaminase 2.
Dr. Dissanayake noted that dermatologists should suspect an autoimmune disease if a patient has recurrent fevers, evidence of systemic inflammation on blood work, and if multiple organ systems are involved, especially the lungs, gut, joints, CNS system, and eyes. “Many of these patients have episodic and stereotypical attacks,” he said.
“One of the tools we use in the autoinflammatory clinic is to have patients and families keep a symptom diary where they track the dates of the various symptoms. We can review this during their appointment and try to come up with a diagnosis based on the pattern,” he said.
Since many of these diseases are due to a single gene defect, if there’s any evidence to suggest a monogenic cause, consider an autoinflammatory disease, he added. “If there’s a family history, if there’s consanguinity, or if there’s early age of onset – these may all lead you to think about monogenic autoinflammatory disease.”
During a question-and-answer session, a meeting attendee asked what type of workup he recommends when an autoinflammatory syndrome is suspected. “It partially depends on what organ systems you suspect to be involved,” Dr. Dissanayake said. “As a routine baseline, typically what we would check is CBC and differential, [erythrocyte sedimentation rate] and [C-reactive protein], and we screen for liver transaminases and creatinine to check for liver and kidney issues. A serum albumin will also tell you if the patient is hypoalbuminemic, that there’s been some chronic inflammation and they’re starting to leak the protein out. It’s good to check blood work during the flare and off the flare, to get a sense of the persistence of that inflammation.”
Dr. Dissanayake disclosed that he has received research finding from Gilead Sciences and speaker fees from Novartis.
*This story was updated on 9/20/2021.
Not long ago, after all.
“Patients with autoinflammatory diseases are all around us, but many go several years without a diagnosis,” Dr. Dissanayake, a rheumatologist at the Autoinflammatory Disease Clinic at the Hospital for Sick Children, Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “The median time to diagnosis has been estimated to be between 2.5 and 5 years. You can imagine that this type of delay can lead to significant issues, not only with quality of life but also morbidity due to unchecked inflammation that can cause organ damage, and in the most severe cases, can result in an early death.”
Effective treatment options such as biologic medications, however, can prevent these negative sequelae if the disease is recognized early. “Dermatologists are in a unique position because they will often be the first specialist to see these patients and therefore make the diagnosis early on and really alter the lives of these patients,” he said.
While it’s common to classify autoinflammatory diseases by presenting features, such as age of onset, associated symptoms, family history/ethnicity, and triggers/alleviating factors for episodes, Dr. Dissanayake prefers to classify them into one of three groups based on pathophysiology, the first being inflammasomopathies. “When activated, an inflammasome is responsible for processing cytokines from the [interleukin]-1 family from the pro form to the active form,” he explained. As a result, if there is dysregulation and overactivity of the inflammasome, there is excessive production of cytokines like IL-1 beta and IL-18 driving the disease.
Clinical characteristics include fevers and organ involvement, notably abdominal pain, nonvasculitic rashes, uveitis, arthritis, elevated white blood cell count/neutrophils, and highly elevated inflammatory markers. Potential treatments include IL-1 blockers.
The second category of autoinflammatory diseases are the interferonopathies, which are caused by overactivity of the antiviral side of the innate immune system. “For example, if you have overactivity of a sensor for a nucleic acid in your cytosol, the cell misinterprets this as a viral infection and will turn on type 1 interferon production,” said Dr. Dissanayake, who is also an assistant professor of pediatrics at the University of Toronto. “As a result, if you have dysregulation of these pathways, you will get excessive type 1 interferon that contributes to your disease manifestations.” Clinical characteristics include fevers and organ involvement, notably vasculitic rashes, interstitial lung disease, and intracranial calcifications. Inflammatory markers may not be as elevated, and autoantibodies may be present. Janus kinase inhibitors are a potential treatment, he said.
The third category of autoinflammatory diseases are the NF-kappaBopathies, which are caused by overactivity of the NF-kappaB signaling pathway. Clinical characteristics can include fevers with organ involvement that can be highly variable but may include mucocutaneous lesions or granulomatous disease as potential clues. Treatment options depend on the pathway that is involved but tumor necrosis factor blockers often play a role because of the importance of NF-KB in this signaling pathway.
From a skin perspective, most of the rashes Dr. Dissanayake and colleagues see in the rheumatology clinic consist of nonspecific dermohypodermatitis: macules, papules, patches, or plaques. The most common monogenic autoinflammatory disease is Familial Mediterranean Fever syndrome, which “commonly presents as an erysipelas-like rash of the lower extremities, typically below the knee, often over the malleolus,” he said.
Other monogenic autoinflammatory diseases with similar rashes include TNF receptor–associated periodic syndrome, Hyper-IgD syndrome, and systemic juvenile idiopathic arthritis.
Other patients present with urticarial rashes, most commonly cryopyrin-associated periodic syndrome (CAPS). “This is a neutrophilic urticaria, so it tends not to be pruritic and can actually sometimes be tender,” he said. “It also tends not to be as transient as your typical urticaria.” Urticarial rashes can also appear with NLRP12-associated autoinflammatory syndrome (familial cold autoinflammatory syndrome–2), PLCgamma2-associated antibody deficiency and immune dysregulation, and Schnitzler syndrome (monoclonal IgM gammopathy).
Patients can also present with pyogenic or pustular lesions, which can appear with pyoderma gangrenosum–related diseases, such as pyogenic arthritis, pyoderma gangrenosum, arthritis (PAPA) syndrome; pyrin-associated inflammation with neutrophilic dermatosis; deficiency of the IL-1 receptor antagonist; deficiency of IL-36 receptor antagonist; and Majeed syndrome, a mutation in the LPIN2 gene.
The mucocutaneous system can also be affected in autoinflammatory diseases, often presenting with symptoms such as periodic fever, aphthous stomatitis, and pharyngitis. Cervical adenitis syndrome is the most common autoinflammatory disease in childhood and can present with aphthous stomatitis, he said, while Behcet’s disease typically presents with oral and genital ulcers. “More recently, monogenic forms of Behcet’s disease have been described, with haploinsufficiency of A20 and RelA, which are both part of the NF-KB pathway,” he said.
Finally, the presence of vasculitic lesions often suggest interferonopathies such as STING-associated vasculopathy in infancy, proteasome-associated autoinflammatory syndrome and deficiency of adenosine deaminase 2.
Dr. Dissanayake noted that dermatologists should suspect an autoimmune disease if a patient has recurrent fevers, evidence of systemic inflammation on blood work, and if multiple organ systems are involved, especially the lungs, gut, joints, CNS system, and eyes. “Many of these patients have episodic and stereotypical attacks,” he said.
“One of the tools we use in the autoinflammatory clinic is to have patients and families keep a symptom diary where they track the dates of the various symptoms. We can review this during their appointment and try to come up with a diagnosis based on the pattern,” he said.
Since many of these diseases are due to a single gene defect, if there’s any evidence to suggest a monogenic cause, consider an autoinflammatory disease, he added. “If there’s a family history, if there’s consanguinity, or if there’s early age of onset – these may all lead you to think about monogenic autoinflammatory disease.”
During a question-and-answer session, a meeting attendee asked what type of workup he recommends when an autoinflammatory syndrome is suspected. “It partially depends on what organ systems you suspect to be involved,” Dr. Dissanayake said. “As a routine baseline, typically what we would check is CBC and differential, [erythrocyte sedimentation rate] and [C-reactive protein], and we screen for liver transaminases and creatinine to check for liver and kidney issues. A serum albumin will also tell you if the patient is hypoalbuminemic, that there’s been some chronic inflammation and they’re starting to leak the protein out. It’s good to check blood work during the flare and off the flare, to get a sense of the persistence of that inflammation.”
Dr. Dissanayake disclosed that he has received research finding from Gilead Sciences and speaker fees from Novartis.
*This story was updated on 9/20/2021.
FROM SPD 2021
Expert proposes rethinking the classification of SJS/TEN
In the opinion of Neil H. Shear, MD, a stepwise approach is the best way to diagnose possible drug-induced skin disease and determine the root cause.
“Often, we need to think of more than one cause,” he said during the annual meeting of the Society for Pediatric Dermatology. “It could be drug X. It could be drug Y. It could be contrast media. We must think broadly and pay special attention to skin of color, overlapping syndromes, and the changing diagnostic assessment over time.”
His suggested diagnostic triangle includes appearance of the rash or lesion(s), systemic impact, and histology. “The first is the appearance,” said Dr. Shear, professor emeritus of dermatology, clinical pharmacology and toxicology, and medicine at the University of Toronto. “Is it exanthem? Is it blistering? Don’t just say drug ‘rash.’ That doesn’t work. You need to know if there are systemic features, and sometimes histologic information can change your approach or diagnosis, but not as often as one might think,” he said, noting that, in his view, the two main factors are appearance and systemic impact.
The presence of fever is a hallmark of systemic problems, he continued, “so if you see fever, you know you’re probably going to be dealing with a complex reaction, so we need to know the morphology.” Consider whether it is simple exanthem (a mild, uncomplicated rash) or complex exanthem (drug rash with eosinophilia and systemic symptoms or fever, malaise, and adenopathy).
As for other morphologies, urticarial lesions could be urticaria or a serum sickness-like reaction, pustular lesions could be acneiform or acute generalized exanthematous pustulosis, while
Dr. Shear considers SJS/TEN as a spectrum of blistering disease, “because there’s not a single diagnosis,” he said. “There’s a spectrum, if you will, depending on how advanced people are in their disease.” He coauthored a 1991 report describing eight cases of mycoplasma and Stevens-Johnson syndrome. “I was surprised at how long that stood up as about the only paper in that area,” he said. “But there’s much more happening now with a proliferation of terms,” he added, referring to MIRM (Mycoplasma pneumonia–induced rash and mucositis), RIME (reactive infectious mucocutaneous eruption); and Fuchs syndrome, or SJS without skin lesions.
What was not appreciated in the early classification of SJS, he continued, was a “side basket” of bullous erythema multiforme. “We didn’t know what to call it,” he said. “At one point we called it bullous erythema multiforme. At another point we called it erythema multiforme major. We just didn’t know what it was.”
The appearance and systemic effects of SJS comprise what he termed SJS type 2 – or the early stages of TEN. Taken together, he refers to these two conditions as TEN Spectrum, or TENS. “One of the traps is that TENS can look like varicella, and vice versa, especially in very dark brown or black skin,” Dr. Shear said. “You have to be careful. A biopsy might be worthwhile. Acute lupus has the pathology of TENS but the patients are not as systemically ill as true TENS.”
In 2011, Japanese researchers reported on 38 cases of SJS associated with M. pneumoniae, and 78 cases of drug-induced SJS. They found that 66% of adult patients with M. pneumoniae–associated SJS developed mucocutaneous lesions and fever/respiratory symptoms on the same day, mostly shortness of breath and cough. In contrast, most of the patients aged under 20 years developed fever/respiratory symptoms before mucocutaneous involvement.
“The big clinical differentiator between drug-induced SJS and mycoplasma-induced SJS was respiratory disorder,” said Dr. Shear, who was not affiliated with the study. “That means you’re probably looking at something that’s mycoplasma related [when respiratory problems are present]. Even if you can’t prove it’s mycoplasma related, that probably needs to be the target of your therapy. The idea ... is to make sure it’s clear at the end. One, so they get better, and two, so that we’re not giving drugs needlessly when it was really mycoplasma.”
Noting that HLA-B*15:02 is a marker for carbamazepine-induced SJS and TEN, he said, “a positive HLA test can support the diagnosis, confirm the suspected offending drug, and is valuable for familial genetic counseling.”
As for treatment of SJS, TEN, and other cytotoxic T-lymphocyte–mediated severe cutaneous adverse reactions, a randomized Japanese clinical trial evaluating prednisolone 1-1.5 mg/kg/day IV versus etanercept 25-50 mg subcutaneously twice per week in 96 patients with SJS-TEN found that etanercept decreased the mortality rate by 8.3%. In addition, etanercept reduced skin healing time, when compared with prednisolone (a median of 14 vs. 19 days, respectively; P = .010), and was associated with a lower incidence of GI hemorrhage (2.6% vs. 18.2%, respectively; P = .03).
Dr. Shear said that he would like to see better therapeutics for severe, complex patients. “After leaving the hospital, people with SJS or people with TEN need to have ongoing care, consultation, and explanation so they and their families know what drugs are safe in the future.”
Dr. Shear disclosed that he has been a consultant to AbbVie, Amgen, Bausch Medicine, Novartis, Sanofi-Genzyme, UCB, LEO Pharma, Otsuka, Janssen, Alpha Laboratories, Lilly, ChemoCentryx, Vivoryon, Galderma, Innovaderm, Chromocell, and Kyowa Kirin.
In the opinion of Neil H. Shear, MD, a stepwise approach is the best way to diagnose possible drug-induced skin disease and determine the root cause.
“Often, we need to think of more than one cause,” he said during the annual meeting of the Society for Pediatric Dermatology. “It could be drug X. It could be drug Y. It could be contrast media. We must think broadly and pay special attention to skin of color, overlapping syndromes, and the changing diagnostic assessment over time.”
His suggested diagnostic triangle includes appearance of the rash or lesion(s), systemic impact, and histology. “The first is the appearance,” said Dr. Shear, professor emeritus of dermatology, clinical pharmacology and toxicology, and medicine at the University of Toronto. “Is it exanthem? Is it blistering? Don’t just say drug ‘rash.’ That doesn’t work. You need to know if there are systemic features, and sometimes histologic information can change your approach or diagnosis, but not as often as one might think,” he said, noting that, in his view, the two main factors are appearance and systemic impact.
The presence of fever is a hallmark of systemic problems, he continued, “so if you see fever, you know you’re probably going to be dealing with a complex reaction, so we need to know the morphology.” Consider whether it is simple exanthem (a mild, uncomplicated rash) or complex exanthem (drug rash with eosinophilia and systemic symptoms or fever, malaise, and adenopathy).
As for other morphologies, urticarial lesions could be urticaria or a serum sickness-like reaction, pustular lesions could be acneiform or acute generalized exanthematous pustulosis, while
Dr. Shear considers SJS/TEN as a spectrum of blistering disease, “because there’s not a single diagnosis,” he said. “There’s a spectrum, if you will, depending on how advanced people are in their disease.” He coauthored a 1991 report describing eight cases of mycoplasma and Stevens-Johnson syndrome. “I was surprised at how long that stood up as about the only paper in that area,” he said. “But there’s much more happening now with a proliferation of terms,” he added, referring to MIRM (Mycoplasma pneumonia–induced rash and mucositis), RIME (reactive infectious mucocutaneous eruption); and Fuchs syndrome, or SJS without skin lesions.
What was not appreciated in the early classification of SJS, he continued, was a “side basket” of bullous erythema multiforme. “We didn’t know what to call it,” he said. “At one point we called it bullous erythema multiforme. At another point we called it erythema multiforme major. We just didn’t know what it was.”
The appearance and systemic effects of SJS comprise what he termed SJS type 2 – or the early stages of TEN. Taken together, he refers to these two conditions as TEN Spectrum, or TENS. “One of the traps is that TENS can look like varicella, and vice versa, especially in very dark brown or black skin,” Dr. Shear said. “You have to be careful. A biopsy might be worthwhile. Acute lupus has the pathology of TENS but the patients are not as systemically ill as true TENS.”
In 2011, Japanese researchers reported on 38 cases of SJS associated with M. pneumoniae, and 78 cases of drug-induced SJS. They found that 66% of adult patients with M. pneumoniae–associated SJS developed mucocutaneous lesions and fever/respiratory symptoms on the same day, mostly shortness of breath and cough. In contrast, most of the patients aged under 20 years developed fever/respiratory symptoms before mucocutaneous involvement.
“The big clinical differentiator between drug-induced SJS and mycoplasma-induced SJS was respiratory disorder,” said Dr. Shear, who was not affiliated with the study. “That means you’re probably looking at something that’s mycoplasma related [when respiratory problems are present]. Even if you can’t prove it’s mycoplasma related, that probably needs to be the target of your therapy. The idea ... is to make sure it’s clear at the end. One, so they get better, and two, so that we’re not giving drugs needlessly when it was really mycoplasma.”
Noting that HLA-B*15:02 is a marker for carbamazepine-induced SJS and TEN, he said, “a positive HLA test can support the diagnosis, confirm the suspected offending drug, and is valuable for familial genetic counseling.”
As for treatment of SJS, TEN, and other cytotoxic T-lymphocyte–mediated severe cutaneous adverse reactions, a randomized Japanese clinical trial evaluating prednisolone 1-1.5 mg/kg/day IV versus etanercept 25-50 mg subcutaneously twice per week in 96 patients with SJS-TEN found that etanercept decreased the mortality rate by 8.3%. In addition, etanercept reduced skin healing time, when compared with prednisolone (a median of 14 vs. 19 days, respectively; P = .010), and was associated with a lower incidence of GI hemorrhage (2.6% vs. 18.2%, respectively; P = .03).
Dr. Shear said that he would like to see better therapeutics for severe, complex patients. “After leaving the hospital, people with SJS or people with TEN need to have ongoing care, consultation, and explanation so they and their families know what drugs are safe in the future.”
Dr. Shear disclosed that he has been a consultant to AbbVie, Amgen, Bausch Medicine, Novartis, Sanofi-Genzyme, UCB, LEO Pharma, Otsuka, Janssen, Alpha Laboratories, Lilly, ChemoCentryx, Vivoryon, Galderma, Innovaderm, Chromocell, and Kyowa Kirin.
In the opinion of Neil H. Shear, MD, a stepwise approach is the best way to diagnose possible drug-induced skin disease and determine the root cause.
“Often, we need to think of more than one cause,” he said during the annual meeting of the Society for Pediatric Dermatology. “It could be drug X. It could be drug Y. It could be contrast media. We must think broadly and pay special attention to skin of color, overlapping syndromes, and the changing diagnostic assessment over time.”
His suggested diagnostic triangle includes appearance of the rash or lesion(s), systemic impact, and histology. “The first is the appearance,” said Dr. Shear, professor emeritus of dermatology, clinical pharmacology and toxicology, and medicine at the University of Toronto. “Is it exanthem? Is it blistering? Don’t just say drug ‘rash.’ That doesn’t work. You need to know if there are systemic features, and sometimes histologic information can change your approach or diagnosis, but not as often as one might think,” he said, noting that, in his view, the two main factors are appearance and systemic impact.
The presence of fever is a hallmark of systemic problems, he continued, “so if you see fever, you know you’re probably going to be dealing with a complex reaction, so we need to know the morphology.” Consider whether it is simple exanthem (a mild, uncomplicated rash) or complex exanthem (drug rash with eosinophilia and systemic symptoms or fever, malaise, and adenopathy).
As for other morphologies, urticarial lesions could be urticaria or a serum sickness-like reaction, pustular lesions could be acneiform or acute generalized exanthematous pustulosis, while
Dr. Shear considers SJS/TEN as a spectrum of blistering disease, “because there’s not a single diagnosis,” he said. “There’s a spectrum, if you will, depending on how advanced people are in their disease.” He coauthored a 1991 report describing eight cases of mycoplasma and Stevens-Johnson syndrome. “I was surprised at how long that stood up as about the only paper in that area,” he said. “But there’s much more happening now with a proliferation of terms,” he added, referring to MIRM (Mycoplasma pneumonia–induced rash and mucositis), RIME (reactive infectious mucocutaneous eruption); and Fuchs syndrome, or SJS without skin lesions.
What was not appreciated in the early classification of SJS, he continued, was a “side basket” of bullous erythema multiforme. “We didn’t know what to call it,” he said. “At one point we called it bullous erythema multiforme. At another point we called it erythema multiforme major. We just didn’t know what it was.”
The appearance and systemic effects of SJS comprise what he termed SJS type 2 – or the early stages of TEN. Taken together, he refers to these two conditions as TEN Spectrum, or TENS. “One of the traps is that TENS can look like varicella, and vice versa, especially in very dark brown or black skin,” Dr. Shear said. “You have to be careful. A biopsy might be worthwhile. Acute lupus has the pathology of TENS but the patients are not as systemically ill as true TENS.”
In 2011, Japanese researchers reported on 38 cases of SJS associated with M. pneumoniae, and 78 cases of drug-induced SJS. They found that 66% of adult patients with M. pneumoniae–associated SJS developed mucocutaneous lesions and fever/respiratory symptoms on the same day, mostly shortness of breath and cough. In contrast, most of the patients aged under 20 years developed fever/respiratory symptoms before mucocutaneous involvement.
“The big clinical differentiator between drug-induced SJS and mycoplasma-induced SJS was respiratory disorder,” said Dr. Shear, who was not affiliated with the study. “That means you’re probably looking at something that’s mycoplasma related [when respiratory problems are present]. Even if you can’t prove it’s mycoplasma related, that probably needs to be the target of your therapy. The idea ... is to make sure it’s clear at the end. One, so they get better, and two, so that we’re not giving drugs needlessly when it was really mycoplasma.”
Noting that HLA-B*15:02 is a marker for carbamazepine-induced SJS and TEN, he said, “a positive HLA test can support the diagnosis, confirm the suspected offending drug, and is valuable for familial genetic counseling.”
As for treatment of SJS, TEN, and other cytotoxic T-lymphocyte–mediated severe cutaneous adverse reactions, a randomized Japanese clinical trial evaluating prednisolone 1-1.5 mg/kg/day IV versus etanercept 25-50 mg subcutaneously twice per week in 96 patients with SJS-TEN found that etanercept decreased the mortality rate by 8.3%. In addition, etanercept reduced skin healing time, when compared with prednisolone (a median of 14 vs. 19 days, respectively; P = .010), and was associated with a lower incidence of GI hemorrhage (2.6% vs. 18.2%, respectively; P = .03).
Dr. Shear said that he would like to see better therapeutics for severe, complex patients. “After leaving the hospital, people with SJS or people with TEN need to have ongoing care, consultation, and explanation so they and their families know what drugs are safe in the future.”
Dr. Shear disclosed that he has been a consultant to AbbVie, Amgen, Bausch Medicine, Novartis, Sanofi-Genzyme, UCB, LEO Pharma, Otsuka, Janssen, Alpha Laboratories, Lilly, ChemoCentryx, Vivoryon, Galderma, Innovaderm, Chromocell, and Kyowa Kirin.
FROM SPD 2021
FDA OKs odevixibat for pruritus associated with rare liver disease
The U.S. Food and Drug Administration has approved odevixibat (Bylvay, Albireo Pharma), the first treatment for pruritus associated with all types of progressive familial intrahepatic cholestasis (PFIC).
PFIC is a rare disorder affecting an estimated one to two people per 100,000. The disorder usually appears within the first few months of life and causes progressive, life-threatening liver disease, often leading to cirrhosis and liver failure before age 10.
In PFIC, liver cells are unable to drain bile acids, leading to the buildup of toxic substances in the liver. While the precise cause of severe itching in patients with PFIC is unknown, it may involve increased levels of bile acids in the body and skin.
Odevixibat is a potent, nonsystemic ileal bile acid transport inhibitor that does not need refrigeration and is given as a once-daily capsule or opened and sprinkled onto soft foods, the company said in a news release announcing the approval.
There are at least three types of PFIC; all are inherited genetic conditions caused by gene mutations. Odevixibat is indicated to treat all subtypes.
“Treating children with PFIC can be difficult and frustrating given the current treatment options. Bylvay gives us a nonsurgical option and will change how we treat PFIC,” Richard Thompson, MD, principal investigator for the two trials that led to the approval, said in the news release.
“With this approval, my colleagues and I now have the opportunity to revisit how PFIC patients are being managed, and we are hopeful for better outcomes for these children,” said Dr. Thompson, professor of molecular hepatology at King’s College London.
The approval of odevixibat was supported by data from the PEDFIC 1 and PEDFIC 2 trials.
PEDFIC 1 enrolled 62 children with PFIC and severe itching, with 20 assigned to placebo and 42 to odevixibat, given once daily with a meal in the morning. Odevixibat met both of its primary endpoints, with the drug improving pruritus (P = .004) and reducing serum bile acid responses (P = .003).
In PEDFIC 2, a long-term, open-label extension study, the effects of odevixibat on pruritis and serum bile acids were sustained up to 48 weeks.
Odevixibat was well tolerated in both trials, with the most common treatment-related gastrointestinal adverse events being diarrhea/frequent stools. There were no serious treatment-related adverse events.
Children taking the drug should undergo liver test monitoring periodically during treatment, the FDA said when announcing the approval. Odevixibat may affect absorption of fat-soluble vitamins such as A, D, E, and K. Patients should be monitored for fat-soluble vitamin deficiency while taking the drug.
Full prescribing information is available online.
“Until now, invasive surgery was the only approved treatment option. With the approval of Bylvay, parents may find hope in having a less invasive treatment option available,” Emily Ventura, leader of the PFIC Advocacy and Resource Network and mother to a child with PFIC, said in the news release.
The company said it will launch odevixibat “immediately” to accelerate availability for patients and families affected by PFIC.
Odevixibat is also being studied in other rare pediatric cholestatic liver diseases, including biliary atresia and Alagille syndrome.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved odevixibat (Bylvay, Albireo Pharma), the first treatment for pruritus associated with all types of progressive familial intrahepatic cholestasis (PFIC).
PFIC is a rare disorder affecting an estimated one to two people per 100,000. The disorder usually appears within the first few months of life and causes progressive, life-threatening liver disease, often leading to cirrhosis and liver failure before age 10.
In PFIC, liver cells are unable to drain bile acids, leading to the buildup of toxic substances in the liver. While the precise cause of severe itching in patients with PFIC is unknown, it may involve increased levels of bile acids in the body and skin.
Odevixibat is a potent, nonsystemic ileal bile acid transport inhibitor that does not need refrigeration and is given as a once-daily capsule or opened and sprinkled onto soft foods, the company said in a news release announcing the approval.
There are at least three types of PFIC; all are inherited genetic conditions caused by gene mutations. Odevixibat is indicated to treat all subtypes.
“Treating children with PFIC can be difficult and frustrating given the current treatment options. Bylvay gives us a nonsurgical option and will change how we treat PFIC,” Richard Thompson, MD, principal investigator for the two trials that led to the approval, said in the news release.
“With this approval, my colleagues and I now have the opportunity to revisit how PFIC patients are being managed, and we are hopeful for better outcomes for these children,” said Dr. Thompson, professor of molecular hepatology at King’s College London.
The approval of odevixibat was supported by data from the PEDFIC 1 and PEDFIC 2 trials.
PEDFIC 1 enrolled 62 children with PFIC and severe itching, with 20 assigned to placebo and 42 to odevixibat, given once daily with a meal in the morning. Odevixibat met both of its primary endpoints, with the drug improving pruritus (P = .004) and reducing serum bile acid responses (P = .003).
In PEDFIC 2, a long-term, open-label extension study, the effects of odevixibat on pruritis and serum bile acids were sustained up to 48 weeks.
Odevixibat was well tolerated in both trials, with the most common treatment-related gastrointestinal adverse events being diarrhea/frequent stools. There were no serious treatment-related adverse events.
Children taking the drug should undergo liver test monitoring periodically during treatment, the FDA said when announcing the approval. Odevixibat may affect absorption of fat-soluble vitamins such as A, D, E, and K. Patients should be monitored for fat-soluble vitamin deficiency while taking the drug.
Full prescribing information is available online.
“Until now, invasive surgery was the only approved treatment option. With the approval of Bylvay, parents may find hope in having a less invasive treatment option available,” Emily Ventura, leader of the PFIC Advocacy and Resource Network and mother to a child with PFIC, said in the news release.
The company said it will launch odevixibat “immediately” to accelerate availability for patients and families affected by PFIC.
Odevixibat is also being studied in other rare pediatric cholestatic liver diseases, including biliary atresia and Alagille syndrome.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved odevixibat (Bylvay, Albireo Pharma), the first treatment for pruritus associated with all types of progressive familial intrahepatic cholestasis (PFIC).
PFIC is a rare disorder affecting an estimated one to two people per 100,000. The disorder usually appears within the first few months of life and causes progressive, life-threatening liver disease, often leading to cirrhosis and liver failure before age 10.
In PFIC, liver cells are unable to drain bile acids, leading to the buildup of toxic substances in the liver. While the precise cause of severe itching in patients with PFIC is unknown, it may involve increased levels of bile acids in the body and skin.
Odevixibat is a potent, nonsystemic ileal bile acid transport inhibitor that does not need refrigeration and is given as a once-daily capsule or opened and sprinkled onto soft foods, the company said in a news release announcing the approval.
There are at least three types of PFIC; all are inherited genetic conditions caused by gene mutations. Odevixibat is indicated to treat all subtypes.
“Treating children with PFIC can be difficult and frustrating given the current treatment options. Bylvay gives us a nonsurgical option and will change how we treat PFIC,” Richard Thompson, MD, principal investigator for the two trials that led to the approval, said in the news release.
“With this approval, my colleagues and I now have the opportunity to revisit how PFIC patients are being managed, and we are hopeful for better outcomes for these children,” said Dr. Thompson, professor of molecular hepatology at King’s College London.
The approval of odevixibat was supported by data from the PEDFIC 1 and PEDFIC 2 trials.
PEDFIC 1 enrolled 62 children with PFIC and severe itching, with 20 assigned to placebo and 42 to odevixibat, given once daily with a meal in the morning. Odevixibat met both of its primary endpoints, with the drug improving pruritus (P = .004) and reducing serum bile acid responses (P = .003).
In PEDFIC 2, a long-term, open-label extension study, the effects of odevixibat on pruritis and serum bile acids were sustained up to 48 weeks.
Odevixibat was well tolerated in both trials, with the most common treatment-related gastrointestinal adverse events being diarrhea/frequent stools. There were no serious treatment-related adverse events.
Children taking the drug should undergo liver test monitoring periodically during treatment, the FDA said when announcing the approval. Odevixibat may affect absorption of fat-soluble vitamins such as A, D, E, and K. Patients should be monitored for fat-soluble vitamin deficiency while taking the drug.
Full prescribing information is available online.
“Until now, invasive surgery was the only approved treatment option. With the approval of Bylvay, parents may find hope in having a less invasive treatment option available,” Emily Ventura, leader of the PFIC Advocacy and Resource Network and mother to a child with PFIC, said in the news release.
The company said it will launch odevixibat “immediately” to accelerate availability for patients and families affected by PFIC.
Odevixibat is also being studied in other rare pediatric cholestatic liver diseases, including biliary atresia and Alagille syndrome.
A version of this article first appeared on Medscape.com.
Children and COVID: New vaccinations increase as cases continue to climb
Children aged 12-15 years represented 13.5% of all first vaccinations received during the 2 weeks ending July 19, compared with 11.5% for the 2 weeks ending July 12, marking the first increase since the end of May. First vaccinations in 16- and 17-year-olds, who make up a much smaller share of the U.S. population, also went up, topping 5%, the Centers for Disease Control and Prevention said in its COVID Data Tracker.
The total number of vaccine initiations was almost 250,000 for the week ending July 19, after dropping to a low of 201,000 the previous week. Before that, first vaccinations had fallen in 5 of the previous 6 weeks, going from 1.4 million on May 24 to 307,000 on July 5, the CDC said.
New cases of COVID-19, unfortunately, continued to follow the trend among the larger population: As of July 15, weekly cases in children were up by 179% since dropping to 8,400 on June 24, the American Academy of Pediatrics and the Children’s Hospital Association said in a joint report. The 23,551 new cases in children for the week ending July 15 were 15.9% of all cases reported.
With those new cases, the total number of children infected with COVID-19 comes to almost 4.1 million since the start of the pandemic, the AAP and CHA said. The CDC data indicate that just over 5.35 million children aged 12-15 years and 3.53 million 16- and 17-year-olds have received at least one dose of the COVID-19 vaccine and that 6.8 million children aged 12-17 are fully vaccinated.
Fully vaccinated children represent 26.4% of all 12- to 15-year-olds and 38.3% of the 16- 17-year-olds as of July 19. The corresponding numbers for those who have received at least one dose are 35.2% (ages 12-15) and 46.8% (16-17), the CDC said.
The AAP recently recommended in-person learning with universal masking in schools this fall “because a significant portion of the student population is not yet eligible for vaccines. ... Many schools will not have a system to monitor vaccine status of students, teachers and staff, and some communities overall have low vaccination uptake where the virus may be circulating more prominently.”
Children aged 12-15 years represented 13.5% of all first vaccinations received during the 2 weeks ending July 19, compared with 11.5% for the 2 weeks ending July 12, marking the first increase since the end of May. First vaccinations in 16- and 17-year-olds, who make up a much smaller share of the U.S. population, also went up, topping 5%, the Centers for Disease Control and Prevention said in its COVID Data Tracker.
The total number of vaccine initiations was almost 250,000 for the week ending July 19, after dropping to a low of 201,000 the previous week. Before that, first vaccinations had fallen in 5 of the previous 6 weeks, going from 1.4 million on May 24 to 307,000 on July 5, the CDC said.
New cases of COVID-19, unfortunately, continued to follow the trend among the larger population: As of July 15, weekly cases in children were up by 179% since dropping to 8,400 on June 24, the American Academy of Pediatrics and the Children’s Hospital Association said in a joint report. The 23,551 new cases in children for the week ending July 15 were 15.9% of all cases reported.
With those new cases, the total number of children infected with COVID-19 comes to almost 4.1 million since the start of the pandemic, the AAP and CHA said. The CDC data indicate that just over 5.35 million children aged 12-15 years and 3.53 million 16- and 17-year-olds have received at least one dose of the COVID-19 vaccine and that 6.8 million children aged 12-17 are fully vaccinated.
Fully vaccinated children represent 26.4% of all 12- to 15-year-olds and 38.3% of the 16- 17-year-olds as of July 19. The corresponding numbers for those who have received at least one dose are 35.2% (ages 12-15) and 46.8% (16-17), the CDC said.
The AAP recently recommended in-person learning with universal masking in schools this fall “because a significant portion of the student population is not yet eligible for vaccines. ... Many schools will not have a system to monitor vaccine status of students, teachers and staff, and some communities overall have low vaccination uptake where the virus may be circulating more prominently.”
Children aged 12-15 years represented 13.5% of all first vaccinations received during the 2 weeks ending July 19, compared with 11.5% for the 2 weeks ending July 12, marking the first increase since the end of May. First vaccinations in 16- and 17-year-olds, who make up a much smaller share of the U.S. population, also went up, topping 5%, the Centers for Disease Control and Prevention said in its COVID Data Tracker.
The total number of vaccine initiations was almost 250,000 for the week ending July 19, after dropping to a low of 201,000 the previous week. Before that, first vaccinations had fallen in 5 of the previous 6 weeks, going from 1.4 million on May 24 to 307,000 on July 5, the CDC said.
New cases of COVID-19, unfortunately, continued to follow the trend among the larger population: As of July 15, weekly cases in children were up by 179% since dropping to 8,400 on June 24, the American Academy of Pediatrics and the Children’s Hospital Association said in a joint report. The 23,551 new cases in children for the week ending July 15 were 15.9% of all cases reported.
With those new cases, the total number of children infected with COVID-19 comes to almost 4.1 million since the start of the pandemic, the AAP and CHA said. The CDC data indicate that just over 5.35 million children aged 12-15 years and 3.53 million 16- and 17-year-olds have received at least one dose of the COVID-19 vaccine and that 6.8 million children aged 12-17 are fully vaccinated.
Fully vaccinated children represent 26.4% of all 12- to 15-year-olds and 38.3% of the 16- 17-year-olds as of July 19. The corresponding numbers for those who have received at least one dose are 35.2% (ages 12-15) and 46.8% (16-17), the CDC said.
The AAP recently recommended in-person learning with universal masking in schools this fall “because a significant portion of the student population is not yet eligible for vaccines. ... Many schools will not have a system to monitor vaccine status of students, teachers and staff, and some communities overall have low vaccination uptake where the virus may be circulating more prominently.”
Erythematous ear with drainage
A 6-year-old boy was seen in the hospital in consultation for a 3-week history of suspected cellulitis of the right ear. Drainage from the right ear was refractory to treatment with a 7-day course of cephalexin 15 mL po bid of 250 mg/5 mL solution and clindamycin 24.4 mL po tid of 75 mg/5 mL solution. Treatment was followed by admission to the hospital for treatment with intravenous (IV) cefazolin 1000 mg q6h and IV vancomycin 825 mg q6h for 1 week.
The patient had a significant past medical history for asthma, allergic rhinitis, and severe atopic dermatitis that had been treated with methotrexate 10 mg per week for 6 months beginning when the child was 5 years of age. When the methotrexate proved to be ineffective, the patient was started on Aquaphor and mometasone 0.1% ointment. A 6-month trial of these agents failed as well.
Physical examination revealed that the right ear and skin around it were edematous, erythematous, pruritic, and tender. There was also purulent drainage coming from the ear (FIGURE 1).
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Infectious eczematoid dermatitis
The patient was referred to a dermatologist after seeing an ear, nose, and throat (ENT) specialist who made the diagnosis of otitis externa when the rash failed to respond to topical and systemic antibiotics. The patient’s tender, pruritic, oozing, edematous eruption was recognized as an infectious eczematoid dermatitis (IED).
Although it is not an uncommon condition, IED may be underrecognized. It accounted for 2.9% of admissions to a dermatology-run inpatient service between 2000 and 2010.1 IED results from cutaneous sensitization to purulent drainage secondary to acute otitis externa or another primary infection.2 In fact, cultures from the purulent drainage in this patient grew methicillin-resistant Staphylococcus aureus. The patient’s right otitis externa drainage may have been associated with the previous history of atopic dermatitis. Atopic dermatitis is associated with an increased risk of skin infections due to decreased inflammatory mediators (defensins).
Cellulitis and herpes zoster oticus are part of the differential
The differential diagnosis in this case includes bacterial cellulitis, acute otitis media, and herpes zoster oticus.
Bacterial cellulitis manifests with erythema, edema, and tenderness with blistering when associated with bullous impetigo rather than pruritus. The clinical appearance of the patient’s diffuse, weeping, edematous external ear, the lack of response to guided antibiotic therapy, and the pruritus experienced by the patient argue against the diagnosis of bacterial cellulitis.
Acute otitis media, like otitis externa, produces ear discharge usually associated with significant pain. Thus, it is important when working through the differential to define the source of the ear discharge. In this case, a consultation with an ENT specialist confirmed that there was an intact tympanic membrane with no middle ear involvement, ruling out the diagnosis of acute otitis media.
Continue to: Herpes zoster oticus
Herpes zoster oticus. The absence of grouped vesicles at any point during the eruption, itching rather than pain, and negative viral culture and polymerase chain reaction studies for herpes simplex and varicella zoster virus excluded the diagnosis of herpes zoster oticus.
Diagnostic criteria were met
This case was compatible with the characterizations of IED as initially described by Engman3 in 1902 and further detailed by Sutton,4 who provided the following criteria for diagnosis:
- an initial eczematous or pustular lesion
- extension peripherally by autoinoculation
- an absence of central clearing
- Staphylococcus on culture of the initial lesion
- a history of infection.
Case reports have added to our understanding of the mechanism of autosensitization of surrounding skin.5 Yamany and Schwartz have proposed the diagnostic criteria summarized in the TABLE.2
Age factors into location. The ears, nose, and face are predominantly involved in cases of IED in the pediatric population, while the lower extremities are predominantly involved in adults.6 Laboratory tests and imaging may aid in excluding other potential diagnoses or complications, but the diagnosis remains clinical and requires the clinician to avoid jumping to the conclusion that every moist, erythematous crusting eruption is purely infectious in nature.
Tx and prevention hinge on a combination of antibiotics, steroids
The management of IED should be aimed at fighting the infection, eliminating the allergic contact dermatitis associated with infectious products, and improving barrier protection. Topical and/or systemic antibiotics guided by culture focus on killing bacteria. The allergic immune response is dampened by systemic steroids. Topical steroids, however, are difficult to utilize on moist, draining skin. In the case of otitis externa, a combination topical antibiotic and steroid otic drop can be utilized. As healing begins, emollients are applied to aid in skin repair.2 Topical antibiotics containing neomycin or polymyxin should be avoided to eliminate the possibility of developing contact sensitivity to these agents.
For our patient, inpatient wound cultures demonstrated methicillin-resistant S aureus, and empiric treatment with IV cefepime and vancomycin was transitioned to IV clindamycin based on sensitivities and then transitioned to a 12-day course of oral clindamycin 150 mg bid. In addition, the patient received ciprofloxacin/dexamethasone otic drops 3 times/d to treat his otitis externa. After initiating prednisone 30 mg (1 mg/kg/d) for 10 days to cover the allergic component, the patient showed prompt clinical improvement. Gentle cleansing of the right ear with hypoallergenic soap and water followed by application of petrolatum ointment 4 times/d was used to promote healing and improve barrier function (FIGURE 2). The patient’s mother indicated during a follow-up call that the affected area had dramatically improved.
1. Storan ER, McEvoy MT, Wetter DA, et al. Experience with the dermatology inpatient hospital service for adults: Mayo Clinic, 2000–2010. J Eur Acad Dermatol Venereol. 2013;27:1360-1365. doi: 10.1111/jdv.12010
2. Yamany T, Schwartz RA. Infectious eczematoid dermatitis: a comprehensive review. J Eur Acad Dermatol Venereol. 2015;29:203-208. doi: 10.1111/jdv.12715
. An infectious form of an eczematoid dermatitis. St. Louis Courier of Med. 1902;27:401414.
4. Infectious eczematoid dermatitis. J Am Med Assoc. 1920;75:976-979.
, , . Autosensitization dermatitis: report of five cases and protocol of an experiment. Arch Derm Syphilol. 1949;59:68-77. doi: 10.1001/archderm.1949.01520260072010
, . Autosensitization in infectious eczematoid dermatitis. AMA Arch Derm Syphilol. 1950;62:703-704. doi: 10.1001/archderm.1950.01530180092021
A 6-year-old boy was seen in the hospital in consultation for a 3-week history of suspected cellulitis of the right ear. Drainage from the right ear was refractory to treatment with a 7-day course of cephalexin 15 mL po bid of 250 mg/5 mL solution and clindamycin 24.4 mL po tid of 75 mg/5 mL solution. Treatment was followed by admission to the hospital for treatment with intravenous (IV) cefazolin 1000 mg q6h and IV vancomycin 825 mg q6h for 1 week.
The patient had a significant past medical history for asthma, allergic rhinitis, and severe atopic dermatitis that had been treated with methotrexate 10 mg per week for 6 months beginning when the child was 5 years of age. When the methotrexate proved to be ineffective, the patient was started on Aquaphor and mometasone 0.1% ointment. A 6-month trial of these agents failed as well.
Physical examination revealed that the right ear and skin around it were edematous, erythematous, pruritic, and tender. There was also purulent drainage coming from the ear (FIGURE 1).
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Infectious eczematoid dermatitis
The patient was referred to a dermatologist after seeing an ear, nose, and throat (ENT) specialist who made the diagnosis of otitis externa when the rash failed to respond to topical and systemic antibiotics. The patient’s tender, pruritic, oozing, edematous eruption was recognized as an infectious eczematoid dermatitis (IED).
Although it is not an uncommon condition, IED may be underrecognized. It accounted for 2.9% of admissions to a dermatology-run inpatient service between 2000 and 2010.1 IED results from cutaneous sensitization to purulent drainage secondary to acute otitis externa or another primary infection.2 In fact, cultures from the purulent drainage in this patient grew methicillin-resistant Staphylococcus aureus. The patient’s right otitis externa drainage may have been associated with the previous history of atopic dermatitis. Atopic dermatitis is associated with an increased risk of skin infections due to decreased inflammatory mediators (defensins).
Cellulitis and herpes zoster oticus are part of the differential
The differential diagnosis in this case includes bacterial cellulitis, acute otitis media, and herpes zoster oticus.
Bacterial cellulitis manifests with erythema, edema, and tenderness with blistering when associated with bullous impetigo rather than pruritus. The clinical appearance of the patient’s diffuse, weeping, edematous external ear, the lack of response to guided antibiotic therapy, and the pruritus experienced by the patient argue against the diagnosis of bacterial cellulitis.
Acute otitis media, like otitis externa, produces ear discharge usually associated with significant pain. Thus, it is important when working through the differential to define the source of the ear discharge. In this case, a consultation with an ENT specialist confirmed that there was an intact tympanic membrane with no middle ear involvement, ruling out the diagnosis of acute otitis media.
Continue to: Herpes zoster oticus
Herpes zoster oticus. The absence of grouped vesicles at any point during the eruption, itching rather than pain, and negative viral culture and polymerase chain reaction studies for herpes simplex and varicella zoster virus excluded the diagnosis of herpes zoster oticus.
Diagnostic criteria were met
This case was compatible with the characterizations of IED as initially described by Engman3 in 1902 and further detailed by Sutton,4 who provided the following criteria for diagnosis:
- an initial eczematous or pustular lesion
- extension peripherally by autoinoculation
- an absence of central clearing
- Staphylococcus on culture of the initial lesion
- a history of infection.
Case reports have added to our understanding of the mechanism of autosensitization of surrounding skin.5 Yamany and Schwartz have proposed the diagnostic criteria summarized in the TABLE.2
Age factors into location. The ears, nose, and face are predominantly involved in cases of IED in the pediatric population, while the lower extremities are predominantly involved in adults.6 Laboratory tests and imaging may aid in excluding other potential diagnoses or complications, but the diagnosis remains clinical and requires the clinician to avoid jumping to the conclusion that every moist, erythematous crusting eruption is purely infectious in nature.
Tx and prevention hinge on a combination of antibiotics, steroids
The management of IED should be aimed at fighting the infection, eliminating the allergic contact dermatitis associated with infectious products, and improving barrier protection. Topical and/or systemic antibiotics guided by culture focus on killing bacteria. The allergic immune response is dampened by systemic steroids. Topical steroids, however, are difficult to utilize on moist, draining skin. In the case of otitis externa, a combination topical antibiotic and steroid otic drop can be utilized. As healing begins, emollients are applied to aid in skin repair.2 Topical antibiotics containing neomycin or polymyxin should be avoided to eliminate the possibility of developing contact sensitivity to these agents.
For our patient, inpatient wound cultures demonstrated methicillin-resistant S aureus, and empiric treatment with IV cefepime and vancomycin was transitioned to IV clindamycin based on sensitivities and then transitioned to a 12-day course of oral clindamycin 150 mg bid. In addition, the patient received ciprofloxacin/dexamethasone otic drops 3 times/d to treat his otitis externa. After initiating prednisone 30 mg (1 mg/kg/d) for 10 days to cover the allergic component, the patient showed prompt clinical improvement. Gentle cleansing of the right ear with hypoallergenic soap and water followed by application of petrolatum ointment 4 times/d was used to promote healing and improve barrier function (FIGURE 2). The patient’s mother indicated during a follow-up call that the affected area had dramatically improved.
A 6-year-old boy was seen in the hospital in consultation for a 3-week history of suspected cellulitis of the right ear. Drainage from the right ear was refractory to treatment with a 7-day course of cephalexin 15 mL po bid of 250 mg/5 mL solution and clindamycin 24.4 mL po tid of 75 mg/5 mL solution. Treatment was followed by admission to the hospital for treatment with intravenous (IV) cefazolin 1000 mg q6h and IV vancomycin 825 mg q6h for 1 week.
The patient had a significant past medical history for asthma, allergic rhinitis, and severe atopic dermatitis that had been treated with methotrexate 10 mg per week for 6 months beginning when the child was 5 years of age. When the methotrexate proved to be ineffective, the patient was started on Aquaphor and mometasone 0.1% ointment. A 6-month trial of these agents failed as well.
Physical examination revealed that the right ear and skin around it were edematous, erythematous, pruritic, and tender. There was also purulent drainage coming from the ear (FIGURE 1).
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Infectious eczematoid dermatitis
The patient was referred to a dermatologist after seeing an ear, nose, and throat (ENT) specialist who made the diagnosis of otitis externa when the rash failed to respond to topical and systemic antibiotics. The patient’s tender, pruritic, oozing, edematous eruption was recognized as an infectious eczematoid dermatitis (IED).
Although it is not an uncommon condition, IED may be underrecognized. It accounted for 2.9% of admissions to a dermatology-run inpatient service between 2000 and 2010.1 IED results from cutaneous sensitization to purulent drainage secondary to acute otitis externa or another primary infection.2 In fact, cultures from the purulent drainage in this patient grew methicillin-resistant Staphylococcus aureus. The patient’s right otitis externa drainage may have been associated with the previous history of atopic dermatitis. Atopic dermatitis is associated with an increased risk of skin infections due to decreased inflammatory mediators (defensins).
Cellulitis and herpes zoster oticus are part of the differential
The differential diagnosis in this case includes bacterial cellulitis, acute otitis media, and herpes zoster oticus.
Bacterial cellulitis manifests with erythema, edema, and tenderness with blistering when associated with bullous impetigo rather than pruritus. The clinical appearance of the patient’s diffuse, weeping, edematous external ear, the lack of response to guided antibiotic therapy, and the pruritus experienced by the patient argue against the diagnosis of bacterial cellulitis.
Acute otitis media, like otitis externa, produces ear discharge usually associated with significant pain. Thus, it is important when working through the differential to define the source of the ear discharge. In this case, a consultation with an ENT specialist confirmed that there was an intact tympanic membrane with no middle ear involvement, ruling out the diagnosis of acute otitis media.
Continue to: Herpes zoster oticus
Herpes zoster oticus. The absence of grouped vesicles at any point during the eruption, itching rather than pain, and negative viral culture and polymerase chain reaction studies for herpes simplex and varicella zoster virus excluded the diagnosis of herpes zoster oticus.
Diagnostic criteria were met
This case was compatible with the characterizations of IED as initially described by Engman3 in 1902 and further detailed by Sutton,4 who provided the following criteria for diagnosis:
- an initial eczematous or pustular lesion
- extension peripherally by autoinoculation
- an absence of central clearing
- Staphylococcus on culture of the initial lesion
- a history of infection.
Case reports have added to our understanding of the mechanism of autosensitization of surrounding skin.5 Yamany and Schwartz have proposed the diagnostic criteria summarized in the TABLE.2
Age factors into location. The ears, nose, and face are predominantly involved in cases of IED in the pediatric population, while the lower extremities are predominantly involved in adults.6 Laboratory tests and imaging may aid in excluding other potential diagnoses or complications, but the diagnosis remains clinical and requires the clinician to avoid jumping to the conclusion that every moist, erythematous crusting eruption is purely infectious in nature.
Tx and prevention hinge on a combination of antibiotics, steroids
The management of IED should be aimed at fighting the infection, eliminating the allergic contact dermatitis associated with infectious products, and improving barrier protection. Topical and/or systemic antibiotics guided by culture focus on killing bacteria. The allergic immune response is dampened by systemic steroids. Topical steroids, however, are difficult to utilize on moist, draining skin. In the case of otitis externa, a combination topical antibiotic and steroid otic drop can be utilized. As healing begins, emollients are applied to aid in skin repair.2 Topical antibiotics containing neomycin or polymyxin should be avoided to eliminate the possibility of developing contact sensitivity to these agents.
For our patient, inpatient wound cultures demonstrated methicillin-resistant S aureus, and empiric treatment with IV cefepime and vancomycin was transitioned to IV clindamycin based on sensitivities and then transitioned to a 12-day course of oral clindamycin 150 mg bid. In addition, the patient received ciprofloxacin/dexamethasone otic drops 3 times/d to treat his otitis externa. After initiating prednisone 30 mg (1 mg/kg/d) for 10 days to cover the allergic component, the patient showed prompt clinical improvement. Gentle cleansing of the right ear with hypoallergenic soap and water followed by application of petrolatum ointment 4 times/d was used to promote healing and improve barrier function (FIGURE 2). The patient’s mother indicated during a follow-up call that the affected area had dramatically improved.
1. Storan ER, McEvoy MT, Wetter DA, et al. Experience with the dermatology inpatient hospital service for adults: Mayo Clinic, 2000–2010. J Eur Acad Dermatol Venereol. 2013;27:1360-1365. doi: 10.1111/jdv.12010
2. Yamany T, Schwartz RA. Infectious eczematoid dermatitis: a comprehensive review. J Eur Acad Dermatol Venereol. 2015;29:203-208. doi: 10.1111/jdv.12715
. An infectious form of an eczematoid dermatitis. St. Louis Courier of Med. 1902;27:401414.
4. Infectious eczematoid dermatitis. J Am Med Assoc. 1920;75:976-979.
, , . Autosensitization dermatitis: report of five cases and protocol of an experiment. Arch Derm Syphilol. 1949;59:68-77. doi: 10.1001/archderm.1949.01520260072010
, . Autosensitization in infectious eczematoid dermatitis. AMA Arch Derm Syphilol. 1950;62:703-704. doi: 10.1001/archderm.1950.01530180092021
1. Storan ER, McEvoy MT, Wetter DA, et al. Experience with the dermatology inpatient hospital service for adults: Mayo Clinic, 2000–2010. J Eur Acad Dermatol Venereol. 2013;27:1360-1365. doi: 10.1111/jdv.12010
2. Yamany T, Schwartz RA. Infectious eczematoid dermatitis: a comprehensive review. J Eur Acad Dermatol Venereol. 2015;29:203-208. doi: 10.1111/jdv.12715
. An infectious form of an eczematoid dermatitis. St. Louis Courier of Med. 1902;27:401414.
4. Infectious eczematoid dermatitis. J Am Med Assoc. 1920;75:976-979.
, , . Autosensitization dermatitis: report of five cases and protocol of an experiment. Arch Derm Syphilol. 1949;59:68-77. doi: 10.1001/archderm.1949.01520260072010
, . Autosensitization in infectious eczematoid dermatitis. AMA Arch Derm Syphilol. 1950;62:703-704. doi: 10.1001/archderm.1950.01530180092021
Pandemic drives drop in prescription drugs for children
The amount of prescription drugs given to children in the United States decreased by 27.1% between April and December 2020, compared with the same period in 2019, based on data from a national database.
Overall, dispensing of prescription drugs to all patients in the United States decreased in the wake of COVID-19 but has since rebounded, wrote Kao-Ping Chua, MD, of the University of Michigan, Ann Arbor, and colleagues. “However, whether these same trends occurred for children is unknown.”
In a study published in Pediatrics, the researchers used the IQVIA National Prescription Audit, a database that contains monthly dispensing details from 92% of retail pharmacies in the United States. They compared changes in the dispensing of prescriptions with children aged 0-19 years during 2018-2020.
In the April 2020–December 2020 time period, prescriptions for children aged 1-2 years, 3-9 years, and 10-19 years decreased by 48.7%, 40.6%, and 16.8%, respectively, compared with the same time period in 2019.
The overall dispensing total for children from April 2020 to December 2020 was 160,630,406, representing a 27.1% reduction, compared with the 220,284,613 total from April 2019 to December 2019.
By drug class, prescriptions for antibiotics, ADHD medications, and antidepressants decreased by 55.6%, 11.8%, and 0.1%, respectively, in comparing the two time periods. Prescriptions for drug classes used typically for acute infections decreased by 51.3%, and those used for chronic diseases decreased by 17.4%.
From January 2018 to February 2020, a median of 25,744,758 prescriptions were dispensed to children aged 0-19 years each month. The total prescriptions decreased from 25,684,219 in March 2020 to 16,742,568 in April 2020, increased to 19,657,289 in October 2020, and decreased again to 15,821,914 during December 2020.
In a subgroup analysis, the decline in prescriptions was greater in children aged 0-9 years, compared with those aged 10-19 years. “Because young children have a higher rate of antibiotic use than older children, declines in antibiotic dispensing might affect overall dispensing totals to a greater degree in young children,” the researchers said.
The study findings were limited by several factors including the lack of information on clinical outcomes, disease severity, and details of new versus ongoing prescriptions, as well as the possible heterogeneity in indications within drug classes, and lack of data from small pharmacies, the researchers noted. However, the results were strengthened by the use of a national all-payer database that including most prescriptions dispensed in the United States, and the use of objective measurements of prescribing practices rather than self-reports.
Despite concerns for the decreased dispensing of chronic disease drugs to children during the pandemic, “declines in dispensing of infection-related drugs, such as antitussives and antibiotics, may be welcome developments,” the researchers said. “These declines reveal that substantial reductions in prescribing of these drugs are possible,” and ongoing monitoring is needed to follow whether the reductions continue long term.
COVID precautions contributed to prescription declines
The mask-wearing and social distancing imposed by the COVID-19 pandemic has contributed to reduced rates of other illnesses, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.
“On the surface, with masks and social isolation, we have seen a drastic reduction in infectious disease,” she said. Fewer infections mean a reduced need for prescriptions to treat them. However, Dr. Kinsella expects the situation to change as more venues and activities open. “I expect that, as things continue to open, we will continue to see more infectious disease,” which will likely lead to more prescription drug use.
Part of the study data were provided through the IQVIA Institute’s Human Data Science Research Collaborative. Lead author Dr. Chua was supported by a career development award from the National Institute on Drug Abuse, but had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.
The amount of prescription drugs given to children in the United States decreased by 27.1% between April and December 2020, compared with the same period in 2019, based on data from a national database.
Overall, dispensing of prescription drugs to all patients in the United States decreased in the wake of COVID-19 but has since rebounded, wrote Kao-Ping Chua, MD, of the University of Michigan, Ann Arbor, and colleagues. “However, whether these same trends occurred for children is unknown.”
In a study published in Pediatrics, the researchers used the IQVIA National Prescription Audit, a database that contains monthly dispensing details from 92% of retail pharmacies in the United States. They compared changes in the dispensing of prescriptions with children aged 0-19 years during 2018-2020.
In the April 2020–December 2020 time period, prescriptions for children aged 1-2 years, 3-9 years, and 10-19 years decreased by 48.7%, 40.6%, and 16.8%, respectively, compared with the same time period in 2019.
The overall dispensing total for children from April 2020 to December 2020 was 160,630,406, representing a 27.1% reduction, compared with the 220,284,613 total from April 2019 to December 2019.
By drug class, prescriptions for antibiotics, ADHD medications, and antidepressants decreased by 55.6%, 11.8%, and 0.1%, respectively, in comparing the two time periods. Prescriptions for drug classes used typically for acute infections decreased by 51.3%, and those used for chronic diseases decreased by 17.4%.
From January 2018 to February 2020, a median of 25,744,758 prescriptions were dispensed to children aged 0-19 years each month. The total prescriptions decreased from 25,684,219 in March 2020 to 16,742,568 in April 2020, increased to 19,657,289 in October 2020, and decreased again to 15,821,914 during December 2020.
In a subgroup analysis, the decline in prescriptions was greater in children aged 0-9 years, compared with those aged 10-19 years. “Because young children have a higher rate of antibiotic use than older children, declines in antibiotic dispensing might affect overall dispensing totals to a greater degree in young children,” the researchers said.
The study findings were limited by several factors including the lack of information on clinical outcomes, disease severity, and details of new versus ongoing prescriptions, as well as the possible heterogeneity in indications within drug classes, and lack of data from small pharmacies, the researchers noted. However, the results were strengthened by the use of a national all-payer database that including most prescriptions dispensed in the United States, and the use of objective measurements of prescribing practices rather than self-reports.
Despite concerns for the decreased dispensing of chronic disease drugs to children during the pandemic, “declines in dispensing of infection-related drugs, such as antitussives and antibiotics, may be welcome developments,” the researchers said. “These declines reveal that substantial reductions in prescribing of these drugs are possible,” and ongoing monitoring is needed to follow whether the reductions continue long term.
COVID precautions contributed to prescription declines
The mask-wearing and social distancing imposed by the COVID-19 pandemic has contributed to reduced rates of other illnesses, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.
“On the surface, with masks and social isolation, we have seen a drastic reduction in infectious disease,” she said. Fewer infections mean a reduced need for prescriptions to treat them. However, Dr. Kinsella expects the situation to change as more venues and activities open. “I expect that, as things continue to open, we will continue to see more infectious disease,” which will likely lead to more prescription drug use.
Part of the study data were provided through the IQVIA Institute’s Human Data Science Research Collaborative. Lead author Dr. Chua was supported by a career development award from the National Institute on Drug Abuse, but had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.
The amount of prescription drugs given to children in the United States decreased by 27.1% between April and December 2020, compared with the same period in 2019, based on data from a national database.
Overall, dispensing of prescription drugs to all patients in the United States decreased in the wake of COVID-19 but has since rebounded, wrote Kao-Ping Chua, MD, of the University of Michigan, Ann Arbor, and colleagues. “However, whether these same trends occurred for children is unknown.”
In a study published in Pediatrics, the researchers used the IQVIA National Prescription Audit, a database that contains monthly dispensing details from 92% of retail pharmacies in the United States. They compared changes in the dispensing of prescriptions with children aged 0-19 years during 2018-2020.
In the April 2020–December 2020 time period, prescriptions for children aged 1-2 years, 3-9 years, and 10-19 years decreased by 48.7%, 40.6%, and 16.8%, respectively, compared with the same time period in 2019.
The overall dispensing total for children from April 2020 to December 2020 was 160,630,406, representing a 27.1% reduction, compared with the 220,284,613 total from April 2019 to December 2019.
By drug class, prescriptions for antibiotics, ADHD medications, and antidepressants decreased by 55.6%, 11.8%, and 0.1%, respectively, in comparing the two time periods. Prescriptions for drug classes used typically for acute infections decreased by 51.3%, and those used for chronic diseases decreased by 17.4%.
From January 2018 to February 2020, a median of 25,744,758 prescriptions were dispensed to children aged 0-19 years each month. The total prescriptions decreased from 25,684,219 in March 2020 to 16,742,568 in April 2020, increased to 19,657,289 in October 2020, and decreased again to 15,821,914 during December 2020.
In a subgroup analysis, the decline in prescriptions was greater in children aged 0-9 years, compared with those aged 10-19 years. “Because young children have a higher rate of antibiotic use than older children, declines in antibiotic dispensing might affect overall dispensing totals to a greater degree in young children,” the researchers said.
The study findings were limited by several factors including the lack of information on clinical outcomes, disease severity, and details of new versus ongoing prescriptions, as well as the possible heterogeneity in indications within drug classes, and lack of data from small pharmacies, the researchers noted. However, the results were strengthened by the use of a national all-payer database that including most prescriptions dispensed in the United States, and the use of objective measurements of prescribing practices rather than self-reports.
Despite concerns for the decreased dispensing of chronic disease drugs to children during the pandemic, “declines in dispensing of infection-related drugs, such as antitussives and antibiotics, may be welcome developments,” the researchers said. “These declines reveal that substantial reductions in prescribing of these drugs are possible,” and ongoing monitoring is needed to follow whether the reductions continue long term.
COVID precautions contributed to prescription declines
The mask-wearing and social distancing imposed by the COVID-19 pandemic has contributed to reduced rates of other illnesses, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.
“On the surface, with masks and social isolation, we have seen a drastic reduction in infectious disease,” she said. Fewer infections mean a reduced need for prescriptions to treat them. However, Dr. Kinsella expects the situation to change as more venues and activities open. “I expect that, as things continue to open, we will continue to see more infectious disease,” which will likely lead to more prescription drug use.
Part of the study data were provided through the IQVIA Institute’s Human Data Science Research Collaborative. Lead author Dr. Chua was supported by a career development award from the National Institute on Drug Abuse, but had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.
FROM PEDIATRICS
The febrile infant: New AAP guidance for the first 2 months of life
Sixteen years in the making, the American Academy of Pediatrics just released a new clinical practice guideline (CPG), “Evaluation and Management of Well-Appearing Febrile Infants 8-60 Days Old”. The recommendations were derived from interpretations of sequential studies in young, febrile, but well-appearing infants that covered invasive bacterial infection (IBI) incidence, diagnostic modalities, and treatment during the first 2 months of life, further refining approaches to evaluation and empirical treatment.
Pediatricians have long had solid information to help assess the risk for IBI among febrile infants aged 0-3 months, but there has been an ongoing desire to further refine the suggested evaluation of these very young infants. A study of febrile infants from the Pediatric Research in Office Settings network along with subsequent evidence has identified the first 3 weeks of life as the period of highest risk for IBI, with risk declining in a graded fashion aged between 22 and 56 days.
Critical caveats
First, some caveats. Infants 0-7 days are not addressed in the CPG, and all should be treated as high risk and receive full IBI evaluation according to newborn protocols. Second, the recommendations apply only to “well-appearing” infants. Any ill-appearing infant should be treated as high risk and receive full IBI evaluation and begun on empirical antimicrobials. Third, even though the CPG deals with infants as young as 8-21 days old, the recommendations are to treat all infants in this age group as high risk, even if well-appearing, and complete full IBI evaluation and empirical therapy while awaiting results. Fourth, these guidelines apply only to infants born at 37 weeks’ gestation or more. Finally, the new CPG action statements are meant to be recommendations rather than a standard of medical care, leaving some leeway for clinician interpretation of individual patient scenarios. Where appropriate, parents’ values and preferences should be incorporated as part of shared decision-making.
The CPG divides young, febrile infants into three cohorts based on age:
- 8-21 days old
- 22-28 days old
- 29-60 days old
Age 8-21 days
For well-appearing febrile infants 8-21 days old, the CPG recommends a complete IBI evaluation that includes urine, blood, and cerebrospinal fluid (CSF) for culture, approaching all infants in this cohort as high risk. Inflammatory markers may be obtained, but the evidence is not comprehensive enough to evaluate their role in decision-making for this age group. A two-step urine evaluation method (urine analysis followed by culture if the urine analysis looks concerning) is not recommended for infants aged 8-21 days. Urine samples for culture from these young infants should be obtained by catheterization or suprapubic aspiration.
The CPG recommends drawing blood cultures and CSF by lumbar puncture from this cohort. These infants should be admitted to the hospital, treated empirically with antimicrobials, and actively monitored. However, if the cultures are negative at 24-36 hours, the clinician should discontinue antimicrobials and discharge the infant if there is no other reason for continued hospitalization.
Age 22-28 days
Well-appearing, febrile infants 22-28 days old are in an intermediate-risk zone. The recommendation for infants in this cohort is to obtain a urine specimen by catheterization or suprapubic aspiration for both urine analysis and culture. Clinicians may consider obtaining urine samples for analysis noninvasively (e.g., urine bag) in this cohort, but this is not the preferred method.
Blood culture should be obtained from all infants in this group. Inflammatory markers can help clinicians identify infants at greater risk for IBI, including meningitis. Previous data suggested that inflammatory markers such as serum white blood cell counts greater than 11,000/mcL, a serum absolute neutrophil count of greater than 4,000/mcL, and elevated C-reactive protein and procalcitonin levels could help providers identify febrile infants with true IBI. A 2008 study demonstrated that procalcitonin had the best receiver operating characteristic curve in regard to predicting IBI in young febrile infants. Other research backed up that finding and identified cutoff values for procalcitonin levels greater than 1.0 ng/mL. The CPG recommends considering a procalcitonin value of 0.5 ng/mL or higher as positive, indicating that the infant is at greater risk for IBI and potentially should undergo an expanded IBI workup. Therefore, in infants aged 22-28 days, inflammatory markers can play a role in deciding whether to perform a lumbar puncture.
Many more nuanced recommendations for whether to and how to empirically treat with antimicrobials in this cohort can be found in the CPG, including whether to manage in the hospital or at home. Treatment recommendations vary greatly for this cohort on the basis of the tests obtained and whether tests were positive or negative at the initial evaluation.
Age 29-60 days
The CPG will be most helpful when clinicians are faced with well-appearing, febrile infants in the 29- to 60-day age group. As with the other groups, a urine evaluation is recommended; however, the CPG suggests that the two-step approach – obtaining a urine analysis by a noninvasive method and only obtaining culture if the urine analysis is positive – is reasonable. This means that a bag or free-flowing urine specimen would be appropriate for urinalysis, followed by catheterization/suprapubic aspiration if a culture is necessary. This would save approximately 90% of infants from invasive urine collection. Regardless, only catheter or suprapubic specimens are appropriate for urine culture.
The CPG also recommends that clinicians obtain blood culture on all of these infants. Inflammatory markers should be assessed in this cohort because avoiding lumbar puncture for CSF culture would be appropriate in this cohort if the inflammatory markers are negative. If CSF is obtained in this age cohort, enterovirus testing should be added to the testing regimen. Again, for any infant considered at higher risk for IBI on the basis of screening tests, the CPG recommends a 24- to 36-hour rule-out period with empirical antimicrobial treatment and active monitoring in the hospital.
Summary
The recommended approach for febrile infants 8-21 days old is relatively aggressive, with urine, blood, and CSF evaluation for IBI. Clinicians gain some leeway for infants age 22-28 days, but the guidelines recommend a more flexible approach to evaluating well-appearing, febrile infants age 29-60 days, when a two-step urine evaluation and inflammatory marker assessment can help clinicians and parents have a better discussion about the risk-benefit trade-offs of more aggressive testing and empirical treatment.
The author would like to thank Ken Roberts, MD, for his review and helpful comments on this summary of the CPG highlights. Summary points of the CPG were presented by the writing group at the 2021 Pediatric Academic Societies meeting.
William T. Basco, Jr, MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.
A version of this article first appeared on Medscape.com.
Sixteen years in the making, the American Academy of Pediatrics just released a new clinical practice guideline (CPG), “Evaluation and Management of Well-Appearing Febrile Infants 8-60 Days Old”. The recommendations were derived from interpretations of sequential studies in young, febrile, but well-appearing infants that covered invasive bacterial infection (IBI) incidence, diagnostic modalities, and treatment during the first 2 months of life, further refining approaches to evaluation and empirical treatment.
Pediatricians have long had solid information to help assess the risk for IBI among febrile infants aged 0-3 months, but there has been an ongoing desire to further refine the suggested evaluation of these very young infants. A study of febrile infants from the Pediatric Research in Office Settings network along with subsequent evidence has identified the first 3 weeks of life as the period of highest risk for IBI, with risk declining in a graded fashion aged between 22 and 56 days.
Critical caveats
First, some caveats. Infants 0-7 days are not addressed in the CPG, and all should be treated as high risk and receive full IBI evaluation according to newborn protocols. Second, the recommendations apply only to “well-appearing” infants. Any ill-appearing infant should be treated as high risk and receive full IBI evaluation and begun on empirical antimicrobials. Third, even though the CPG deals with infants as young as 8-21 days old, the recommendations are to treat all infants in this age group as high risk, even if well-appearing, and complete full IBI evaluation and empirical therapy while awaiting results. Fourth, these guidelines apply only to infants born at 37 weeks’ gestation or more. Finally, the new CPG action statements are meant to be recommendations rather than a standard of medical care, leaving some leeway for clinician interpretation of individual patient scenarios. Where appropriate, parents’ values and preferences should be incorporated as part of shared decision-making.
The CPG divides young, febrile infants into three cohorts based on age:
- 8-21 days old
- 22-28 days old
- 29-60 days old
Age 8-21 days
For well-appearing febrile infants 8-21 days old, the CPG recommends a complete IBI evaluation that includes urine, blood, and cerebrospinal fluid (CSF) for culture, approaching all infants in this cohort as high risk. Inflammatory markers may be obtained, but the evidence is not comprehensive enough to evaluate their role in decision-making for this age group. A two-step urine evaluation method (urine analysis followed by culture if the urine analysis looks concerning) is not recommended for infants aged 8-21 days. Urine samples for culture from these young infants should be obtained by catheterization or suprapubic aspiration.
The CPG recommends drawing blood cultures and CSF by lumbar puncture from this cohort. These infants should be admitted to the hospital, treated empirically with antimicrobials, and actively monitored. However, if the cultures are negative at 24-36 hours, the clinician should discontinue antimicrobials and discharge the infant if there is no other reason for continued hospitalization.
Age 22-28 days
Well-appearing, febrile infants 22-28 days old are in an intermediate-risk zone. The recommendation for infants in this cohort is to obtain a urine specimen by catheterization or suprapubic aspiration for both urine analysis and culture. Clinicians may consider obtaining urine samples for analysis noninvasively (e.g., urine bag) in this cohort, but this is not the preferred method.
Blood culture should be obtained from all infants in this group. Inflammatory markers can help clinicians identify infants at greater risk for IBI, including meningitis. Previous data suggested that inflammatory markers such as serum white blood cell counts greater than 11,000/mcL, a serum absolute neutrophil count of greater than 4,000/mcL, and elevated C-reactive protein and procalcitonin levels could help providers identify febrile infants with true IBI. A 2008 study demonstrated that procalcitonin had the best receiver operating characteristic curve in regard to predicting IBI in young febrile infants. Other research backed up that finding and identified cutoff values for procalcitonin levels greater than 1.0 ng/mL. The CPG recommends considering a procalcitonin value of 0.5 ng/mL or higher as positive, indicating that the infant is at greater risk for IBI and potentially should undergo an expanded IBI workup. Therefore, in infants aged 22-28 days, inflammatory markers can play a role in deciding whether to perform a lumbar puncture.
Many more nuanced recommendations for whether to and how to empirically treat with antimicrobials in this cohort can be found in the CPG, including whether to manage in the hospital or at home. Treatment recommendations vary greatly for this cohort on the basis of the tests obtained and whether tests were positive or negative at the initial evaluation.
Age 29-60 days
The CPG will be most helpful when clinicians are faced with well-appearing, febrile infants in the 29- to 60-day age group. As with the other groups, a urine evaluation is recommended; however, the CPG suggests that the two-step approach – obtaining a urine analysis by a noninvasive method and only obtaining culture if the urine analysis is positive – is reasonable. This means that a bag or free-flowing urine specimen would be appropriate for urinalysis, followed by catheterization/suprapubic aspiration if a culture is necessary. This would save approximately 90% of infants from invasive urine collection. Regardless, only catheter or suprapubic specimens are appropriate for urine culture.
The CPG also recommends that clinicians obtain blood culture on all of these infants. Inflammatory markers should be assessed in this cohort because avoiding lumbar puncture for CSF culture would be appropriate in this cohort if the inflammatory markers are negative. If CSF is obtained in this age cohort, enterovirus testing should be added to the testing regimen. Again, for any infant considered at higher risk for IBI on the basis of screening tests, the CPG recommends a 24- to 36-hour rule-out period with empirical antimicrobial treatment and active monitoring in the hospital.
Summary
The recommended approach for febrile infants 8-21 days old is relatively aggressive, with urine, blood, and CSF evaluation for IBI. Clinicians gain some leeway for infants age 22-28 days, but the guidelines recommend a more flexible approach to evaluating well-appearing, febrile infants age 29-60 days, when a two-step urine evaluation and inflammatory marker assessment can help clinicians and parents have a better discussion about the risk-benefit trade-offs of more aggressive testing and empirical treatment.
The author would like to thank Ken Roberts, MD, for his review and helpful comments on this summary of the CPG highlights. Summary points of the CPG were presented by the writing group at the 2021 Pediatric Academic Societies meeting.
William T. Basco, Jr, MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.
A version of this article first appeared on Medscape.com.
Sixteen years in the making, the American Academy of Pediatrics just released a new clinical practice guideline (CPG), “Evaluation and Management of Well-Appearing Febrile Infants 8-60 Days Old”. The recommendations were derived from interpretations of sequential studies in young, febrile, but well-appearing infants that covered invasive bacterial infection (IBI) incidence, diagnostic modalities, and treatment during the first 2 months of life, further refining approaches to evaluation and empirical treatment.
Pediatricians have long had solid information to help assess the risk for IBI among febrile infants aged 0-3 months, but there has been an ongoing desire to further refine the suggested evaluation of these very young infants. A study of febrile infants from the Pediatric Research in Office Settings network along with subsequent evidence has identified the first 3 weeks of life as the period of highest risk for IBI, with risk declining in a graded fashion aged between 22 and 56 days.
Critical caveats
First, some caveats. Infants 0-7 days are not addressed in the CPG, and all should be treated as high risk and receive full IBI evaluation according to newborn protocols. Second, the recommendations apply only to “well-appearing” infants. Any ill-appearing infant should be treated as high risk and receive full IBI evaluation and begun on empirical antimicrobials. Third, even though the CPG deals with infants as young as 8-21 days old, the recommendations are to treat all infants in this age group as high risk, even if well-appearing, and complete full IBI evaluation and empirical therapy while awaiting results. Fourth, these guidelines apply only to infants born at 37 weeks’ gestation or more. Finally, the new CPG action statements are meant to be recommendations rather than a standard of medical care, leaving some leeway for clinician interpretation of individual patient scenarios. Where appropriate, parents’ values and preferences should be incorporated as part of shared decision-making.
The CPG divides young, febrile infants into three cohorts based on age:
- 8-21 days old
- 22-28 days old
- 29-60 days old
Age 8-21 days
For well-appearing febrile infants 8-21 days old, the CPG recommends a complete IBI evaluation that includes urine, blood, and cerebrospinal fluid (CSF) for culture, approaching all infants in this cohort as high risk. Inflammatory markers may be obtained, but the evidence is not comprehensive enough to evaluate their role in decision-making for this age group. A two-step urine evaluation method (urine analysis followed by culture if the urine analysis looks concerning) is not recommended for infants aged 8-21 days. Urine samples for culture from these young infants should be obtained by catheterization or suprapubic aspiration.
The CPG recommends drawing blood cultures and CSF by lumbar puncture from this cohort. These infants should be admitted to the hospital, treated empirically with antimicrobials, and actively monitored. However, if the cultures are negative at 24-36 hours, the clinician should discontinue antimicrobials and discharge the infant if there is no other reason for continued hospitalization.
Age 22-28 days
Well-appearing, febrile infants 22-28 days old are in an intermediate-risk zone. The recommendation for infants in this cohort is to obtain a urine specimen by catheterization or suprapubic aspiration for both urine analysis and culture. Clinicians may consider obtaining urine samples for analysis noninvasively (e.g., urine bag) in this cohort, but this is not the preferred method.
Blood culture should be obtained from all infants in this group. Inflammatory markers can help clinicians identify infants at greater risk for IBI, including meningitis. Previous data suggested that inflammatory markers such as serum white blood cell counts greater than 11,000/mcL, a serum absolute neutrophil count of greater than 4,000/mcL, and elevated C-reactive protein and procalcitonin levels could help providers identify febrile infants with true IBI. A 2008 study demonstrated that procalcitonin had the best receiver operating characteristic curve in regard to predicting IBI in young febrile infants. Other research backed up that finding and identified cutoff values for procalcitonin levels greater than 1.0 ng/mL. The CPG recommends considering a procalcitonin value of 0.5 ng/mL or higher as positive, indicating that the infant is at greater risk for IBI and potentially should undergo an expanded IBI workup. Therefore, in infants aged 22-28 days, inflammatory markers can play a role in deciding whether to perform a lumbar puncture.
Many more nuanced recommendations for whether to and how to empirically treat with antimicrobials in this cohort can be found in the CPG, including whether to manage in the hospital or at home. Treatment recommendations vary greatly for this cohort on the basis of the tests obtained and whether tests were positive or negative at the initial evaluation.
Age 29-60 days
The CPG will be most helpful when clinicians are faced with well-appearing, febrile infants in the 29- to 60-day age group. As with the other groups, a urine evaluation is recommended; however, the CPG suggests that the two-step approach – obtaining a urine analysis by a noninvasive method and only obtaining culture if the urine analysis is positive – is reasonable. This means that a bag or free-flowing urine specimen would be appropriate for urinalysis, followed by catheterization/suprapubic aspiration if a culture is necessary. This would save approximately 90% of infants from invasive urine collection. Regardless, only catheter or suprapubic specimens are appropriate for urine culture.
The CPG also recommends that clinicians obtain blood culture on all of these infants. Inflammatory markers should be assessed in this cohort because avoiding lumbar puncture for CSF culture would be appropriate in this cohort if the inflammatory markers are negative. If CSF is obtained in this age cohort, enterovirus testing should be added to the testing regimen. Again, for any infant considered at higher risk for IBI on the basis of screening tests, the CPG recommends a 24- to 36-hour rule-out period with empirical antimicrobial treatment and active monitoring in the hospital.
Summary
The recommended approach for febrile infants 8-21 days old is relatively aggressive, with urine, blood, and CSF evaluation for IBI. Clinicians gain some leeway for infants age 22-28 days, but the guidelines recommend a more flexible approach to evaluating well-appearing, febrile infants age 29-60 days, when a two-step urine evaluation and inflammatory marker assessment can help clinicians and parents have a better discussion about the risk-benefit trade-offs of more aggressive testing and empirical treatment.
The author would like to thank Ken Roberts, MD, for his review and helpful comments on this summary of the CPG highlights. Summary points of the CPG were presented by the writing group at the 2021 Pediatric Academic Societies meeting.
William T. Basco, Jr, MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.
A version of this article first appeared on Medscape.com.