Pediatrics

 

The world in pediatric dermatology has changed in incredible ways since 1967. In fact, pediatric dermatology was not an organized specialty until years later! This article will look back at some of the history of pediatric dermatology, exploring how different the field was 50 years ago, and how it has evolved into the vibrant field that it is. By looking at some disease states, and differences in practice in relation to the care of dermatologic conditions in children both by pediatricians and dermatologists, we can see the tremendous evolution in our understanding and management of pediatric skin conditions, and perhaps gain insight into the future.

Pediatric dermatology was fairly “neonatal” 50 years ago, with only a few practitioners in the field. Recognizing that up to 30% of pediatric primary care visits include a skin-related problem, and that there was limited training about skin diseases among primary care practitioners and inconsistent training amongst dermatologists, there was a clinical need for establishing the subspecialty of pediatric dermatology. The first international symposium was held in Mexico City in October 1972, and with this meeting the International Society of Pediatric Dermatology was founded. The Society for Pediatric Dermatology (SPD) began in 1973, with Alvin Jacobs, MD, Samuel Weinberg, MD, Nancy Esterly, MD, Sidney Hurwitz, MD, William Weston, MD, and Coleman Jacobson, MD, as some of the initial “founding mothers and fathers.” The journal Pediatric Dermatology released its first issue in 1982 (35 years ago), and the American Academy of Pediatrics did not have a section of dermatology until 1986.

Lori Farmer/Frontline Medical News

The field of pediatric dermatology has matured rapidly. With the expansion of clinical information over the past 5 decades, there are now multiple standard reference textbooks in pediatric dermatology and subspecialties of pediatric dermatology such as neonatal dermatology, formal fellowship programs around the world, and a formal subspecialty of pediatric dermatology developed by the American Board of Dermatology and recognized by the Accreditation Council of Graduate Medical Education.

Pediatrics and dermatology: The interface

Many of the first generation of pediatric dermatologists trained as pediatricians prior to pursuing their dermatology work, with some being “assigned” dermatology as pediatric experts, while others did formal residencies in dermatology. This history is important, as pediatric dermatology was, and remains, integrated with pediatrics, even while training in dermatology residencies became standard practice. An important part of the development of the field has been the education of pediatricians and dermatologists by pediatric dermatologists, with a strong sensibility that improved training for both generalists and specialists about pediatric skin disease would yield better care for patients and families.

Initially, there were very few pediatric or dermatology programs in the United States that had pediatric dermatologists. Over the succeeding decades, this is now less common, although even now there are still dermatology and pediatric residency programs that do not have a pediatric dermatologist for either training or to serve their patients. The founding leaders of the SPD set a tone of collaboration nationally and internationally, reaching out to pediatric colleagues and dermatology associates from around the world, and establishing superb educational programs for the exchange of ideas, presentation of challenging cases, and promoting state of the art knowledge of the field. Through annual meetings of the SPD, conferences immediately preceding the American Academy of Dermatology annual meetings, the World Congress of Pediatric Dermatology, and other regional and international meetings, the field developed as the number of practitioners grew, and as the specialized published literature reflected new knowledge in diagnosis and therapy.

LucaLorenzelli/Thinkstock

Meetings of the SPD have changed over time, reflecting changes in “communal knowledge” as well as in the ability of dermatologists (and patients and families) to communicate. Until the past decade, meetings often had a significant amount of time dedicated to communal input on “cases in search of a diagnosis” of “cases in search of therapy.” This reflected the important work of the field in the first 30-40 years, defining diseases and conditions, encouraging research work, and sharing clinical experiences and ideas about therapies. The attendees shared experiences and cases, and many disease descriptions were based upon presentations at meetings. An example I recollect was a case of an infant who presented with telangiectases on the face and inguinal area without other rash. This was figured out to be a rare presentation of neonatal lupus. The back story: I had been trained by Dr. Paul Honig to recognize that presentation, as he had seen some cases. It wasn’t in any literature or textbook. Rather than “publish it quickly as a case,” it was presented at an SPD meeting, with a request for others to share their cases if they had any. The resulting article included 7 children, establishing this as a distinct presentation pattern.

Building upon the history of collaboration and reflecting the maturation of the field with a desire to influence the breadth and quantity of research in pediatric dermatology, the Pediatric Dermatology Research Alliance (PeDRA) was formed in 2012. This organization was formed to promote and facilitate high quality collaborative clinical, translational, educational, and basic science research in pediatric dermatology with a vision to create sustainable, collaborative networks to better understand, prevent, treat, and cure dermatologic diseases in children. This network is now composed of over 230 members representing over 68 institutions from the United States and Canada, but including involvement globally from Mexico, Europe, and the Middle East.

 

Examples of changing perspectives: hemangiomas

A good way to look at evolution of the field is take a look at some of the similarities and differences in clinical practice in relation to common and uncommon disease states.

A great example is hemangiomas. Some of the first natural history studies on hemangiomas were done in the early 1960s, establishing that many lesions had a typical clinical course of fairly rapid growth, plateau, and involution over time. Of course, the identification of hemangiomas of infancy (or “HOI” in the trade), was confused with vascular malformations, and no one had recognized variant tumors that were distinct, such as rapidly involuting and noninvoluting congenital hemangiomas (RICHs or NICHs), tufted angiomas, and hemangioendotheliomas. PHACE syndrome (posterior fossa brain malformations) had yet to be described (that was done in 1996 by Ilona Frieden and her colleagues). For a time period, hemangiomas were treated with X-rays, before the negative impact of such radiation was acknowledged. For many years after that, even deforming and functionally significant lesions were “followed clinically” for natural involution, presumably a backlash from the radiation therapy interventions.

Courtesy of RegionalDerm.com

Of course, the breakthrough of propranolol for hemangioma treatment profoundly changed hemangioma management, shifting “state of the art treatment” from systemic steroids (and perhaps laser) to an incredibly effective medical therapy newly studied, tested, and approved by regulatory authorities. And how intriguing that this was developed after the chance (but skilled) observation that a child who developed hypertension as a side effect of systemic steroids for nasal hemangioma treatment, and was prescribed propranolol for the hypertension, had his nasal hemangioma rapidly shrink, with a response superior and much quicker than the response to corticosteroids.

This story also reflects how organized research efforts helped with the evolution of knowledge and clinical care. The Hemangioma of Infancy Group was formed to take a collaborative approach to characterize and study hemangiomas and related tumors. Beginning with energetic, insightful pediatric dermatologists, and little funding, they changed our knowledge base of how hemangiomas present, the risk factors for their development and the characteristics and multiple organ findings associated with PHACE and other syndromic hemangiomas.

Procedural pediatric dermatology: Tremendous revolution in surgery and laser

The first generation of pediatric dermatologists were considered medical dermatologist specialists. And how important this specialty work was! Acne, atopic dermatitis, psoriasis, diaper and seborrheic dermatitis, and rare genetic syndromes, these conditions were a major part of the work of early pediatric dermatologists (and remain so now). What was not common was for pediatric dermatologists to have procedural or surgical practices, while this now is routinely part of the work of specialists in the field. How did this shift occur?

The fundamental shift began to occur with the introduction of the pulsed dye laser in 1989 and the publication of a seminal article in the New England Journal of Medicine (1989 Feb 16;320[7]:416-21) on its utility in treating port-wine stains in children with minimal scarring. Vascular lesions including port-wine stains were common, and pediatric dermatologists managed these patients for both diagnosis and medical management. Also, dermatology residencies at this time offered training in cutaneous surgery, excisions (including Mohs surgery) and repairs, and trainees in pediatric dermatology were “trained up” to high levels of expertise. As lasers were incorporated into dermatology residency work and practices, pediatric dermatologists had the exposure and skill to do this work. An added advantage was having the pediatric knowledge of how to handle children and adolescents in an age appropriate manner, and consideration of methods to minimize the pain and anxiety of procedures. Within a few years, pediatric dermatologists were at the forefront of the use of topical anesthetics (EMLA and liposomal lidocaine) and had general anesthesia privileges for laser and excisional surgery.

So while pediatric dermatologists still do “small procedures” every hour in most practices (cryotherapy for warts, cantharidin for molluscum, shave and punch biopsies), a subset now have extensive procedural practices, which in recent years has extended to pigment lesion lasers (to treat nevus of Ota), hair lasers (to treat perineal areas to prevent pilonidal cyst recurrence or to treat hirsutism), and combinations of lasers to treat hypertrophic, constrictive, and/or deforming scars).

Inflammatory skin disorders: Bread and butter ... and peanut butter?

The care of pediatric inflammatory skin disorders has evolved, but more slowly for some diseases than others. Acne vulgaris now is recognized as much more common under age 12 years than previously, presumably reflecting earlier pubertal changes in our preteens. Over the past 30 years, therapy has evolved with the use of topical retinoids (still underused by pediatricians, considered a “practice gap”), hormonal therapy with combined oral contraceptives, and oral isotretinoin, a powerful but highly effective systemic agent for severe and refractory acne. Specific pediatric guidelines came much later. Pediatric acne expert recommendations were formulated by the American Acne and Rosacea Society and endorsed by the American Academy of Pediatrics in 2013 (Pediatrics. 2013;131:S163-86). Over the past few years, there is a push by experts for more judicious use of antibiotics for acne (oral and topical) to minimize the emergence of bacterial resistance.

 

Psoriasis has been a condition that has been “behind the revolution,” in that no biologic agent was approved for pediatric psoriasis in the United States until several months ago, lagging behind Europe and elsewhere in the world by almost a decade. Adult psoriasis has been recognized to be associated with a broad set of comorbidities, including obesity and early heart disease, and there is now research on how children are at risk as well, and new recommendations on how to screen children with psoriasis. Moderate to severe psoriasis in adults is now tremendously controllable with biologic agents targeting TNF-alpha, IL 12/23, and IL-17. Etanercept has been approved for children with psoriasis aged 4 years and older, and other biologic agents are under study.

Atopic dermatitis now is ready for its revolution! AD has increased in prevalence from around 5% of the pediatric population 30-plus years ago to 10%-15%. Treatment of most individuals has remained the same over the decades: Good skin care, frequent moisturizers, topical corticosteroids for flares, management of infection if noted. The topical calcineurin inhibitors (TCIs) broadened the therapeutic approach when introduced in 2000 and 2001, but the boxed warning resulted in some practitioners minimizing their utilization of these useful agents.

Unfortunately, the combination of minimal new therapies over decades and phobias about potential side effects of topical steroids and TCIs has resulted in a tremendous amount of undertreatment of AD, with many children walking around (and not sleeping too well) with high body surface area involvement, secondary infections, and sequelae including ADHD, anxiety, and depression. The pediatric dermatology community, together with adult dermatology (and allergy) specialists, are now working aggressively to minimize AD’s effects. New initiatives, including improving education of patients and families with learning tools, are being developed, based on studies showing how they can impact disease. A new agent, a topical PDE-4 inhibitor (crisaborole), was recently approved for AD for ages 2 years and older. This drug is not a corticosteroid nor a TCI, and was approved without a specific time limitation for its use. In addition, the first prospectively designed biologic agent developed for AD, a receptor blocker that influences IL4 and IL13, has been approved in adults with moderate to severe AD, and is already under study in children and adolescents. The use of biologic agents and/or small molecules targeting the inflammation of more severe AD in children may transform management.

It has been recognized for years that children with AD have higher risk of developing food allergies than children without AD. A changing understanding of how early food exposure may induce tolerance is changing the world of allergy and influencing the care of children with AD. This is where the peanut butter (or other processed peanut, such as “Bamba”) may be life saving. New guidelines have come from the National Institute of Allergy and Infectious Diseases recommending that infants with severe eczema (or egg allergy, or both) have introduction of age-appropriate peanut-containing food as early as 4-6 months of age to reduce the risk of development of peanut allergy. It is recommended that these infants undergo early evaluation for possible sensitization to peanut protein, with referral to allergists for skin prick tests or serum IgE screens (though if positive, referral to allergists is appropriate), and assess the safety of going ahead with early feeding. It is hoped that following these new guidelines can minimize the development of peanut allergy.

The future

Where will pediatric skin disease, or more importantly, skin health over a lifetime be in 50 years? Can we cure or prevent the consequences of our lethal and life altering genetic diseases such as epidermolysis bullosa or our neurocutaneous disorders? Will our new insights into birthmarks (they are mostly somatic mutations) allow us to form specific, personalized therapies to minimize their impact? Will we be using computers equipped with imaging devices and algorithms to assess our patients’ moles, papules, and nodules? Will our vaccines have wiped out warts, molluscum, and perhaps, acne? Will we have cured our inflammatory skin disorders, or perhaps prevented them by interventions in the neonatal period? No predictions will be offered here, other than that we can look forward to incredible changes for our future generations of health care practitioners, patients, and families.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Eichenfield has served as a consultant for Anacor/Pfizer and Regeneron/Sanofi. Email him at pdnews@frontlinemedcom.com.

 

The world in pediatric dermatology has changed in incredible ways since 1967. In fact, pediatric dermatology was not an organized specialty until years later! This article will look back at some of the history of pediatric dermatology, exploring how different the field was 50 years ago, and how it has evolved into the vibrant field that it is. By looking at some disease states, and differences in practice in relation to the care of dermatologic conditions in children both by pediatricians and dermatologists, we can see the tremendous evolution in our understanding and management of pediatric skin conditions, and perhaps gain insight into the future.

Pediatric dermatology was fairly “neonatal” 50 years ago, with only a few practitioners in the field. Recognizing that up to 30% of pediatric primary care visits include a skin-related problem, and that there was limited training about skin diseases among primary care practitioners and inconsistent training amongst dermatologists, there was a clinical need for establishing the subspecialty of pediatric dermatology. The first international symposium was held in Mexico City in October 1972, and with this meeting the International Society of Pediatric Dermatology was founded. The Society for Pediatric Dermatology (SPD) began in 1973, with Alvin Jacobs, MD, Samuel Weinberg, MD, Nancy Esterly, MD, Sidney Hurwitz, MD, William Weston, MD, and Coleman Jacobson, MD, as some of the initial “founding mothers and fathers.” The journal Pediatric Dermatology released its first issue in 1982 (35 years ago), and the American Academy of Pediatrics did not have a section of dermatology until 1986.

Lori Farmer/Frontline Medical News

The field of pediatric dermatology has matured rapidly. With the expansion of clinical information over the past 5 decades, there are now multiple standard reference textbooks in pediatric dermatology and subspecialties of pediatric dermatology such as neonatal dermatology, formal fellowship programs around the world, and a formal subspecialty of pediatric dermatology developed by the American Board of Dermatology and recognized by the Accreditation Council of Graduate Medical Education.

Pediatrics and dermatology: The interface

Many of the first generation of pediatric dermatologists trained as pediatricians prior to pursuing their dermatology work, with some being “assigned” dermatology as pediatric experts, while others did formal residencies in dermatology. This history is important, as pediatric dermatology was, and remains, integrated with pediatrics, even while training in dermatology residencies became standard practice. An important part of the development of the field has been the education of pediatricians and dermatologists by pediatric dermatologists, with a strong sensibility that improved training for both generalists and specialists about pediatric skin disease would yield better care for patients and families.

Initially, there were very few pediatric or dermatology programs in the United States that had pediatric dermatologists. Over the succeeding decades, this is now less common, although even now there are still dermatology and pediatric residency programs that do not have a pediatric dermatologist for either training or to serve their patients. The founding leaders of the SPD set a tone of collaboration nationally and internationally, reaching out to pediatric colleagues and dermatology associates from around the world, and establishing superb educational programs for the exchange of ideas, presentation of challenging cases, and promoting state of the art knowledge of the field. Through annual meetings of the SPD, conferences immediately preceding the American Academy of Dermatology annual meetings, the World Congress of Pediatric Dermatology, and other regional and international meetings, the field developed as the number of practitioners grew, and as the specialized published literature reflected new knowledge in diagnosis and therapy.

LucaLorenzelli/Thinkstock

Meetings of the SPD have changed over time, reflecting changes in “communal knowledge” as well as in the ability of dermatologists (and patients and families) to communicate. Until the past decade, meetings often had a significant amount of time dedicated to communal input on “cases in search of a diagnosis” of “cases in search of therapy.” This reflected the important work of the field in the first 30-40 years, defining diseases and conditions, encouraging research work, and sharing clinical experiences and ideas about therapies. The attendees shared experiences and cases, and many disease descriptions were based upon presentations at meetings. An example I recollect was a case of an infant who presented with telangiectases on the face and inguinal area without other rash. This was figured out to be a rare presentation of neonatal lupus. The back story: I had been trained by Dr. Paul Honig to recognize that presentation, as he had seen some cases. It wasn’t in any literature or textbook. Rather than “publish it quickly as a case,” it was presented at an SPD meeting, with a request for others to share their cases if they had any. The resulting article included 7 children, establishing this as a distinct presentation pattern.

Building upon the history of collaboration and reflecting the maturation of the field with a desire to influence the breadth and quantity of research in pediatric dermatology, the Pediatric Dermatology Research Alliance (PeDRA) was formed in 2012. This organization was formed to promote and facilitate high quality collaborative clinical, translational, educational, and basic science research in pediatric dermatology with a vision to create sustainable, collaborative networks to better understand, prevent, treat, and cure dermatologic diseases in children. This network is now composed of over 230 members representing over 68 institutions from the United States and Canada, but including involvement globally from Mexico, Europe, and the Middle East.

 

Examples of changing perspectives: hemangiomas

A good way to look at evolution of the field is take a look at some of the similarities and differences in clinical practice in relation to common and uncommon disease states.

A great example is hemangiomas. Some of the first natural history studies on hemangiomas were done in the early 1960s, establishing that many lesions had a typical clinical course of fairly rapid growth, plateau, and involution over time. Of course, the identification of hemangiomas of infancy (or “HOI” in the trade), was confused with vascular malformations, and no one had recognized variant tumors that were distinct, such as rapidly involuting and noninvoluting congenital hemangiomas (RICHs or NICHs), tufted angiomas, and hemangioendotheliomas. PHACE syndrome (posterior fossa brain malformations) had yet to be described (that was done in 1996 by Ilona Frieden and her colleagues). For a time period, hemangiomas were treated with X-rays, before the negative impact of such radiation was acknowledged. For many years after that, even deforming and functionally significant lesions were “followed clinically” for natural involution, presumably a backlash from the radiation therapy interventions.

Courtesy of RegionalDerm.com

Of course, the breakthrough of propranolol for hemangioma treatment profoundly changed hemangioma management, shifting “state of the art treatment” from systemic steroids (and perhaps laser) to an incredibly effective medical therapy newly studied, tested, and approved by regulatory authorities. And how intriguing that this was developed after the chance (but skilled) observation that a child who developed hypertension as a side effect of systemic steroids for nasal hemangioma treatment, and was prescribed propranolol for the hypertension, had his nasal hemangioma rapidly shrink, with a response superior and much quicker than the response to corticosteroids.

This story also reflects how organized research efforts helped with the evolution of knowledge and clinical care. The Hemangioma of Infancy Group was formed to take a collaborative approach to characterize and study hemangiomas and related tumors. Beginning with energetic, insightful pediatric dermatologists, and little funding, they changed our knowledge base of how hemangiomas present, the risk factors for their development and the characteristics and multiple organ findings associated with PHACE and other syndromic hemangiomas.

Procedural pediatric dermatology: Tremendous revolution in surgery and laser

The first generation of pediatric dermatologists were considered medical dermatologist specialists. And how important this specialty work was! Acne, atopic dermatitis, psoriasis, diaper and seborrheic dermatitis, and rare genetic syndromes, these conditions were a major part of the work of early pediatric dermatologists (and remain so now). What was not common was for pediatric dermatologists to have procedural or surgical practices, while this now is routinely part of the work of specialists in the field. How did this shift occur?

The fundamental shift began to occur with the introduction of the pulsed dye laser in 1989 and the publication of a seminal article in the New England Journal of Medicine (1989 Feb 16;320[7]:416-21) on its utility in treating port-wine stains in children with minimal scarring. Vascular lesions including port-wine stains were common, and pediatric dermatologists managed these patients for both diagnosis and medical management. Also, dermatology residencies at this time offered training in cutaneous surgery, excisions (including Mohs surgery) and repairs, and trainees in pediatric dermatology were “trained up” to high levels of expertise. As lasers were incorporated into dermatology residency work and practices, pediatric dermatologists had the exposure and skill to do this work. An added advantage was having the pediatric knowledge of how to handle children and adolescents in an age appropriate manner, and consideration of methods to minimize the pain and anxiety of procedures. Within a few years, pediatric dermatologists were at the forefront of the use of topical anesthetics (EMLA and liposomal lidocaine) and had general anesthesia privileges for laser and excisional surgery.

So while pediatric dermatologists still do “small procedures” every hour in most practices (cryotherapy for warts, cantharidin for molluscum, shave and punch biopsies), a subset now have extensive procedural practices, which in recent years has extended to pigment lesion lasers (to treat nevus of Ota), hair lasers (to treat perineal areas to prevent pilonidal cyst recurrence or to treat hirsutism), and combinations of lasers to treat hypertrophic, constrictive, and/or deforming scars).

Inflammatory skin disorders: Bread and butter ... and peanut butter?

The care of pediatric inflammatory skin disorders has evolved, but more slowly for some diseases than others. Acne vulgaris now is recognized as much more common under age 12 years than previously, presumably reflecting earlier pubertal changes in our preteens. Over the past 30 years, therapy has evolved with the use of topical retinoids (still underused by pediatricians, considered a “practice gap”), hormonal therapy with combined oral contraceptives, and oral isotretinoin, a powerful but highly effective systemic agent for severe and refractory acne. Specific pediatric guidelines came much later. Pediatric acne expert recommendations were formulated by the American Acne and Rosacea Society and endorsed by the American Academy of Pediatrics in 2013 (Pediatrics. 2013;131:S163-86). Over the past few years, there is a push by experts for more judicious use of antibiotics for acne (oral and topical) to minimize the emergence of bacterial resistance.

 

Psoriasis has been a condition that has been “behind the revolution,” in that no biologic agent was approved for pediatric psoriasis in the United States until several months ago, lagging behind Europe and elsewhere in the world by almost a decade. Adult psoriasis has been recognized to be associated with a broad set of comorbidities, including obesity and early heart disease, and there is now research on how children are at risk as well, and new recommendations on how to screen children with psoriasis. Moderate to severe psoriasis in adults is now tremendously controllable with biologic agents targeting TNF-alpha, IL 12/23, and IL-17. Etanercept has been approved for children with psoriasis aged 4 years and older, and other biologic agents are under study.

Atopic dermatitis now is ready for its revolution! AD has increased in prevalence from around 5% of the pediatric population 30-plus years ago to 10%-15%. Treatment of most individuals has remained the same over the decades: Good skin care, frequent moisturizers, topical corticosteroids for flares, management of infection if noted. The topical calcineurin inhibitors (TCIs) broadened the therapeutic approach when introduced in 2000 and 2001, but the boxed warning resulted in some practitioners minimizing their utilization of these useful agents.

Unfortunately, the combination of minimal new therapies over decades and phobias about potential side effects of topical steroids and TCIs has resulted in a tremendous amount of undertreatment of AD, with many children walking around (and not sleeping too well) with high body surface area involvement, secondary infections, and sequelae including ADHD, anxiety, and depression. The pediatric dermatology community, together with adult dermatology (and allergy) specialists, are now working aggressively to minimize AD’s effects. New initiatives, including improving education of patients and families with learning tools, are being developed, based on studies showing how they can impact disease. A new agent, a topical PDE-4 inhibitor (crisaborole), was recently approved for AD for ages 2 years and older. This drug is not a corticosteroid nor a TCI, and was approved without a specific time limitation for its use. In addition, the first prospectively designed biologic agent developed for AD, a receptor blocker that influences IL4 and IL13, has been approved in adults with moderate to severe AD, and is already under study in children and adolescents. The use of biologic agents and/or small molecules targeting the inflammation of more severe AD in children may transform management.

It has been recognized for years that children with AD have higher risk of developing food allergies than children without AD. A changing understanding of how early food exposure may induce tolerance is changing the world of allergy and influencing the care of children with AD. This is where the peanut butter (or other processed peanut, such as “Bamba”) may be life saving. New guidelines have come from the National Institute of Allergy and Infectious Diseases recommending that infants with severe eczema (or egg allergy, or both) have introduction of age-appropriate peanut-containing food as early as 4-6 months of age to reduce the risk of development of peanut allergy. It is recommended that these infants undergo early evaluation for possible sensitization to peanut protein, with referral to allergists for skin prick tests or serum IgE screens (though if positive, referral to allergists is appropriate), and assess the safety of going ahead with early feeding. It is hoped that following these new guidelines can minimize the development of peanut allergy.

The future

Where will pediatric skin disease, or more importantly, skin health over a lifetime be in 50 years? Can we cure or prevent the consequences of our lethal and life altering genetic diseases such as epidermolysis bullosa or our neurocutaneous disorders? Will our new insights into birthmarks (they are mostly somatic mutations) allow us to form specific, personalized therapies to minimize their impact? Will we be using computers equipped with imaging devices and algorithms to assess our patients’ moles, papules, and nodules? Will our vaccines have wiped out warts, molluscum, and perhaps, acne? Will we have cured our inflammatory skin disorders, or perhaps prevented them by interventions in the neonatal period? No predictions will be offered here, other than that we can look forward to incredible changes for our future generations of health care practitioners, patients, and families.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Eichenfield has served as a consultant for Anacor/Pfizer and Regeneron/Sanofi. Email him at pdnews@frontlinemedcom.com.

 

The world in pediatric dermatology has changed in incredible ways since 1967. In fact, pediatric dermatology was not an organized specialty until years later! This article will look back at some of the history of pediatric dermatology, exploring how different the field was 50 years ago, and how it has evolved into the vibrant field that it is. By looking at some disease states, and differences in practice in relation to the care of dermatologic conditions in children both by pediatricians and dermatologists, we can see the tremendous evolution in our understanding and management of pediatric skin conditions, and perhaps gain insight into the future.

Pediatric dermatology was fairly “neonatal” 50 years ago, with only a few practitioners in the field. Recognizing that up to 30% of pediatric primary care visits include a skin-related problem, and that there was limited training about skin diseases among primary care practitioners and inconsistent training amongst dermatologists, there was a clinical need for establishing the subspecialty of pediatric dermatology. The first international symposium was held in Mexico City in October 1972, and with this meeting the International Society of Pediatric Dermatology was founded. The Society for Pediatric Dermatology (SPD) began in 1973, with Alvin Jacobs, MD, Samuel Weinberg, MD, Nancy Esterly, MD, Sidney Hurwitz, MD, William Weston, MD, and Coleman Jacobson, MD, as some of the initial “founding mothers and fathers.” The journal Pediatric Dermatology released its first issue in 1982 (35 years ago), and the American Academy of Pediatrics did not have a section of dermatology until 1986.

Lori Farmer/Frontline Medical News

The field of pediatric dermatology has matured rapidly. With the expansion of clinical information over the past 5 decades, there are now multiple standard reference textbooks in pediatric dermatology and subspecialties of pediatric dermatology such as neonatal dermatology, formal fellowship programs around the world, and a formal subspecialty of pediatric dermatology developed by the American Board of Dermatology and recognized by the Accreditation Council of Graduate Medical Education.

Pediatrics and dermatology: The interface

Many of the first generation of pediatric dermatologists trained as pediatricians prior to pursuing their dermatology work, with some being “assigned” dermatology as pediatric experts, while others did formal residencies in dermatology. This history is important, as pediatric dermatology was, and remains, integrated with pediatrics, even while training in dermatology residencies became standard practice. An important part of the development of the field has been the education of pediatricians and dermatologists by pediatric dermatologists, with a strong sensibility that improved training for both generalists and specialists about pediatric skin disease would yield better care for patients and families.

Initially, there were very few pediatric or dermatology programs in the United States that had pediatric dermatologists. Over the succeeding decades, this is now less common, although even now there are still dermatology and pediatric residency programs that do not have a pediatric dermatologist for either training or to serve their patients. The founding leaders of the SPD set a tone of collaboration nationally and internationally, reaching out to pediatric colleagues and dermatology associates from around the world, and establishing superb educational programs for the exchange of ideas, presentation of challenging cases, and promoting state of the art knowledge of the field. Through annual meetings of the SPD, conferences immediately preceding the American Academy of Dermatology annual meetings, the World Congress of Pediatric Dermatology, and other regional and international meetings, the field developed as the number of practitioners grew, and as the specialized published literature reflected new knowledge in diagnosis and therapy.

LucaLorenzelli/Thinkstock

Meetings of the SPD have changed over time, reflecting changes in “communal knowledge” as well as in the ability of dermatologists (and patients and families) to communicate. Until the past decade, meetings often had a significant amount of time dedicated to communal input on “cases in search of a diagnosis” of “cases in search of therapy.” This reflected the important work of the field in the first 30-40 years, defining diseases and conditions, encouraging research work, and sharing clinical experiences and ideas about therapies. The attendees shared experiences and cases, and many disease descriptions were based upon presentations at meetings. An example I recollect was a case of an infant who presented with telangiectases on the face and inguinal area without other rash. This was figured out to be a rare presentation of neonatal lupus. The back story: I had been trained by Dr. Paul Honig to recognize that presentation, as he had seen some cases. It wasn’t in any literature or textbook. Rather than “publish it quickly as a case,” it was presented at an SPD meeting, with a request for others to share their cases if they had any. The resulting article included 7 children, establishing this as a distinct presentation pattern.

Building upon the history of collaboration and reflecting the maturation of the field with a desire to influence the breadth and quantity of research in pediatric dermatology, the Pediatric Dermatology Research Alliance (PeDRA) was formed in 2012. This organization was formed to promote and facilitate high quality collaborative clinical, translational, educational, and basic science research in pediatric dermatology with a vision to create sustainable, collaborative networks to better understand, prevent, treat, and cure dermatologic diseases in children. This network is now composed of over 230 members representing over 68 institutions from the United States and Canada, but including involvement globally from Mexico, Europe, and the Middle East.

 

Examples of changing perspectives: hemangiomas

A good way to look at evolution of the field is take a look at some of the similarities and differences in clinical practice in relation to common and uncommon disease states.

A great example is hemangiomas. Some of the first natural history studies on hemangiomas were done in the early 1960s, establishing that many lesions had a typical clinical course of fairly rapid growth, plateau, and involution over time. Of course, the identification of hemangiomas of infancy (or “HOI” in the trade), was confused with vascular malformations, and no one had recognized variant tumors that were distinct, such as rapidly involuting and noninvoluting congenital hemangiomas (RICHs or NICHs), tufted angiomas, and hemangioendotheliomas. PHACE syndrome (posterior fossa brain malformations) had yet to be described (that was done in 1996 by Ilona Frieden and her colleagues). For a time period, hemangiomas were treated with X-rays, before the negative impact of such radiation was acknowledged. For many years after that, even deforming and functionally significant lesions were “followed clinically” for natural involution, presumably a backlash from the radiation therapy interventions.

Courtesy of RegionalDerm.com

Of course, the breakthrough of propranolol for hemangioma treatment profoundly changed hemangioma management, shifting “state of the art treatment” from systemic steroids (and perhaps laser) to an incredibly effective medical therapy newly studied, tested, and approved by regulatory authorities. And how intriguing that this was developed after the chance (but skilled) observation that a child who developed hypertension as a side effect of systemic steroids for nasal hemangioma treatment, and was prescribed propranolol for the hypertension, had his nasal hemangioma rapidly shrink, with a response superior and much quicker than the response to corticosteroids.

This story also reflects how organized research efforts helped with the evolution of knowledge and clinical care. The Hemangioma of Infancy Group was formed to take a collaborative approach to characterize and study hemangiomas and related tumors. Beginning with energetic, insightful pediatric dermatologists, and little funding, they changed our knowledge base of how hemangiomas present, the risk factors for their development and the characteristics and multiple organ findings associated with PHACE and other syndromic hemangiomas.

Procedural pediatric dermatology: Tremendous revolution in surgery and laser

The first generation of pediatric dermatologists were considered medical dermatologist specialists. And how important this specialty work was! Acne, atopic dermatitis, psoriasis, diaper and seborrheic dermatitis, and rare genetic syndromes, these conditions were a major part of the work of early pediatric dermatologists (and remain so now). What was not common was for pediatric dermatologists to have procedural or surgical practices, while this now is routinely part of the work of specialists in the field. How did this shift occur?

The fundamental shift began to occur with the introduction of the pulsed dye laser in 1989 and the publication of a seminal article in the New England Journal of Medicine (1989 Feb 16;320[7]:416-21) on its utility in treating port-wine stains in children with minimal scarring. Vascular lesions including port-wine stains were common, and pediatric dermatologists managed these patients for both diagnosis and medical management. Also, dermatology residencies at this time offered training in cutaneous surgery, excisions (including Mohs surgery) and repairs, and trainees in pediatric dermatology were “trained up” to high levels of expertise. As lasers were incorporated into dermatology residency work and practices, pediatric dermatologists had the exposure and skill to do this work. An added advantage was having the pediatric knowledge of how to handle children and adolescents in an age appropriate manner, and consideration of methods to minimize the pain and anxiety of procedures. Within a few years, pediatric dermatologists were at the forefront of the use of topical anesthetics (EMLA and liposomal lidocaine) and had general anesthesia privileges for laser and excisional surgery.

So while pediatric dermatologists still do “small procedures” every hour in most practices (cryotherapy for warts, cantharidin for molluscum, shave and punch biopsies), a subset now have extensive procedural practices, which in recent years has extended to pigment lesion lasers (to treat nevus of Ota), hair lasers (to treat perineal areas to prevent pilonidal cyst recurrence or to treat hirsutism), and combinations of lasers to treat hypertrophic, constrictive, and/or deforming scars).

Inflammatory skin disorders: Bread and butter ... and peanut butter?

The care of pediatric inflammatory skin disorders has evolved, but more slowly for some diseases than others. Acne vulgaris now is recognized as much more common under age 12 years than previously, presumably reflecting earlier pubertal changes in our preteens. Over the past 30 years, therapy has evolved with the use of topical retinoids (still underused by pediatricians, considered a “practice gap”), hormonal therapy with combined oral contraceptives, and oral isotretinoin, a powerful but highly effective systemic agent for severe and refractory acne. Specific pediatric guidelines came much later. Pediatric acne expert recommendations were formulated by the American Acne and Rosacea Society and endorsed by the American Academy of Pediatrics in 2013 (Pediatrics. 2013;131:S163-86). Over the past few years, there is a push by experts for more judicious use of antibiotics for acne (oral and topical) to minimize the emergence of bacterial resistance.

 

Psoriasis has been a condition that has been “behind the revolution,” in that no biologic agent was approved for pediatric psoriasis in the United States until several months ago, lagging behind Europe and elsewhere in the world by almost a decade. Adult psoriasis has been recognized to be associated with a broad set of comorbidities, including obesity and early heart disease, and there is now research on how children are at risk as well, and new recommendations on how to screen children with psoriasis. Moderate to severe psoriasis in adults is now tremendously controllable with biologic agents targeting TNF-alpha, IL 12/23, and IL-17. Etanercept has been approved for children with psoriasis aged 4 years and older, and other biologic agents are under study.

Atopic dermatitis now is ready for its revolution! AD has increased in prevalence from around 5% of the pediatric population 30-plus years ago to 10%-15%. Treatment of most individuals has remained the same over the decades: Good skin care, frequent moisturizers, topical corticosteroids for flares, management of infection if noted. The topical calcineurin inhibitors (TCIs) broadened the therapeutic approach when introduced in 2000 and 2001, but the boxed warning resulted in some practitioners minimizing their utilization of these useful agents.

Unfortunately, the combination of minimal new therapies over decades and phobias about potential side effects of topical steroids and TCIs has resulted in a tremendous amount of undertreatment of AD, with many children walking around (and not sleeping too well) with high body surface area involvement, secondary infections, and sequelae including ADHD, anxiety, and depression. The pediatric dermatology community, together with adult dermatology (and allergy) specialists, are now working aggressively to minimize AD’s effects. New initiatives, including improving education of patients and families with learning tools, are being developed, based on studies showing how they can impact disease. A new agent, a topical PDE-4 inhibitor (crisaborole), was recently approved for AD for ages 2 years and older. This drug is not a corticosteroid nor a TCI, and was approved without a specific time limitation for its use. In addition, the first prospectively designed biologic agent developed for AD, a receptor blocker that influences IL4 and IL13, has been approved in adults with moderate to severe AD, and is already under study in children and adolescents. The use of biologic agents and/or small molecules targeting the inflammation of more severe AD in children may transform management.

It has been recognized for years that children with AD have higher risk of developing food allergies than children without AD. A changing understanding of how early food exposure may induce tolerance is changing the world of allergy and influencing the care of children with AD. This is where the peanut butter (or other processed peanut, such as “Bamba”) may be life saving. New guidelines have come from the National Institute of Allergy and Infectious Diseases recommending that infants with severe eczema (or egg allergy, or both) have introduction of age-appropriate peanut-containing food as early as 4-6 months of age to reduce the risk of development of peanut allergy. It is recommended that these infants undergo early evaluation for possible sensitization to peanut protein, with referral to allergists for skin prick tests or serum IgE screens (though if positive, referral to allergists is appropriate), and assess the safety of going ahead with early feeding. It is hoped that following these new guidelines can minimize the development of peanut allergy.

The future

Where will pediatric skin disease, or more importantly, skin health over a lifetime be in 50 years? Can we cure or prevent the consequences of our lethal and life altering genetic diseases such as epidermolysis bullosa or our neurocutaneous disorders? Will our new insights into birthmarks (they are mostly somatic mutations) allow us to form specific, personalized therapies to minimize their impact? Will we be using computers equipped with imaging devices and algorithms to assess our patients’ moles, papules, and nodules? Will our vaccines have wiped out warts, molluscum, and perhaps, acne? Will we have cured our inflammatory skin disorders, or perhaps prevented them by interventions in the neonatal period? No predictions will be offered here, other than that we can look forward to incredible changes for our future generations of health care practitioners, patients, and families.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Eichenfield has served as a consultant for Anacor/Pfizer and Regeneron/Sanofi. Email him at pdnews@frontlinemedcom.com.

Pregnant women may receive any licensed, recommended influenza vaccine at any time during pregnancy, according to new recommendations from the Centers for Disease Control and Prevention.
 

This change from the CDC’s previous guidance that pregnant women receive a seasonal inactivated influenza vaccine (IIV) was recommended by the Advisory Committee on Immunization Practices after some heated debate among committee members over evidence presented to support the change in wording (MMWR. 2017 Aug 25;66[(RR-2]:1-20).

The new update gives women the ability to choose between receiving an IIV and FluBlok, a recombinant influenza vaccine (RIV) that is not egg based and can be manufactured more quickly, making it ideal in cases of pandemic or supply shortages, according to the CDC.

Although pregnant women may choose to receive a vaccination during the first trimester, the CDC warns there may be some risk involved.

“Although experience with the use of IIVs is substantial, and data from observational studies are available to support the safety of these vaccines in pregnancy, data are more limited for vaccination during the first trimester,” according to the CDC. “Moreover, there is substantially less experience with more recently licensed IIV products (e.g., quadrivalent, cell culture-based, and adjuvanted vaccines) during pregnancy in general.”

Data also are limited regarding RIVs, the CDC said, with the data used to determine safety among pregnant women “limited to reports of pregnancies occurring incidentally during clinical trials, Vaccine Adverse Event Reporting System (VAERS) reports, and pregnancy registry reports.”

Changes for children

The CDC chose to accept ACIP recommendations regarding Afluria (IIV3), expanding the age of children who can receive the vaccine from 9 years and older to 5 years and older.

Similar labeling changes were accepted for FluLaval Quadrivalent (IIV4), which had previously been given to children 3 years and older but now but will be available for children starting at 6 months of age.

CAP53/iStockphoto.com

New products

Recent product licensures included in the MMWR report are Afluria Quadrivalent (IIV4) and Flublok Quadrivalent (RIV4), both for persons over 18 years.

According to the CDC, Flublok Quadrivalent (an RIV) met noninferiority measures, compared with a similar IIV quadrivalent vaccine, for the A(H3H2) and B/Yamagata viruses but not for A(H1N1) or B/Victoria viruses.

Vaccine composition for 2017-2018

Approved viruses for the 2017-2018 season trivalent vaccines are an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008–like virus (Victoria lineage), according to the MMWR. Quadrivalent vaccines will include those viruses, with the addition of an B/Phuket/3073/2013–like virus (Yamagata lineage).

The CDC continues to recommend that the quadrivalent live attenuated influenza vaccine FluMist not be used by anyone for the 2017-2018 season, a decision that was made after evidence showed poor effectiveness against influenza A(H1N1)pdm09 viruses in the 2013-2014 and 2015-2016 seasons.

Vaccine updates published in this report were recommended by ACIP during meetings held in October 2016 and February and June 2017.

ezimmerman@frontlinemedcom.com

On Twitter @eaztweets

Pregnant women may receive any licensed, recommended influenza vaccine at any time during pregnancy, according to new recommendations from the Centers for Disease Control and Prevention.
 

This change from the CDC’s previous guidance that pregnant women receive a seasonal inactivated influenza vaccine (IIV) was recommended by the Advisory Committee on Immunization Practices after some heated debate among committee members over evidence presented to support the change in wording (MMWR. 2017 Aug 25;66[(RR-2]:1-20).

The new update gives women the ability to choose between receiving an IIV and FluBlok, a recombinant influenza vaccine (RIV) that is not egg based and can be manufactured more quickly, making it ideal in cases of pandemic or supply shortages, according to the CDC.

Although pregnant women may choose to receive a vaccination during the first trimester, the CDC warns there may be some risk involved.

“Although experience with the use of IIVs is substantial, and data from observational studies are available to support the safety of these vaccines in pregnancy, data are more limited for vaccination during the first trimester,” according to the CDC. “Moreover, there is substantially less experience with more recently licensed IIV products (e.g., quadrivalent, cell culture-based, and adjuvanted vaccines) during pregnancy in general.”

Data also are limited regarding RIVs, the CDC said, with the data used to determine safety among pregnant women “limited to reports of pregnancies occurring incidentally during clinical trials, Vaccine Adverse Event Reporting System (VAERS) reports, and pregnancy registry reports.”

Changes for children

The CDC chose to accept ACIP recommendations regarding Afluria (IIV3), expanding the age of children who can receive the vaccine from 9 years and older to 5 years and older.

Similar labeling changes were accepted for FluLaval Quadrivalent (IIV4), which had previously been given to children 3 years and older but now but will be available for children starting at 6 months of age.

CAP53/iStockphoto.com

New products

Recent product licensures included in the MMWR report are Afluria Quadrivalent (IIV4) and Flublok Quadrivalent (RIV4), both for persons over 18 years.

According to the CDC, Flublok Quadrivalent (an RIV) met noninferiority measures, compared with a similar IIV quadrivalent vaccine, for the A(H3H2) and B/Yamagata viruses but not for A(H1N1) or B/Victoria viruses.

Vaccine composition for 2017-2018

Approved viruses for the 2017-2018 season trivalent vaccines are an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008–like virus (Victoria lineage), according to the MMWR. Quadrivalent vaccines will include those viruses, with the addition of an B/Phuket/3073/2013–like virus (Yamagata lineage).

The CDC continues to recommend that the quadrivalent live attenuated influenza vaccine FluMist not be used by anyone for the 2017-2018 season, a decision that was made after evidence showed poor effectiveness against influenza A(H1N1)pdm09 viruses in the 2013-2014 and 2015-2016 seasons.

Vaccine updates published in this report were recommended by ACIP during meetings held in October 2016 and February and June 2017.

ezimmerman@frontlinemedcom.com

On Twitter @eaztweets

Pregnant women may receive any licensed, recommended influenza vaccine at any time during pregnancy, according to new recommendations from the Centers for Disease Control and Prevention.
 

This change from the CDC’s previous guidance that pregnant women receive a seasonal inactivated influenza vaccine (IIV) was recommended by the Advisory Committee on Immunization Practices after some heated debate among committee members over evidence presented to support the change in wording (MMWR. 2017 Aug 25;66[(RR-2]:1-20).

The new update gives women the ability to choose between receiving an IIV and FluBlok, a recombinant influenza vaccine (RIV) that is not egg based and can be manufactured more quickly, making it ideal in cases of pandemic or supply shortages, according to the CDC.

Although pregnant women may choose to receive a vaccination during the first trimester, the CDC warns there may be some risk involved.

“Although experience with the use of IIVs is substantial, and data from observational studies are available to support the safety of these vaccines in pregnancy, data are more limited for vaccination during the first trimester,” according to the CDC. “Moreover, there is substantially less experience with more recently licensed IIV products (e.g., quadrivalent, cell culture-based, and adjuvanted vaccines) during pregnancy in general.”

Data also are limited regarding RIVs, the CDC said, with the data used to determine safety among pregnant women “limited to reports of pregnancies occurring incidentally during clinical trials, Vaccine Adverse Event Reporting System (VAERS) reports, and pregnancy registry reports.”

Changes for children

The CDC chose to accept ACIP recommendations regarding Afluria (IIV3), expanding the age of children who can receive the vaccine from 9 years and older to 5 years and older.

Similar labeling changes were accepted for FluLaval Quadrivalent (IIV4), which had previously been given to children 3 years and older but now but will be available for children starting at 6 months of age.

CAP53/iStockphoto.com

New products

Recent product licensures included in the MMWR report are Afluria Quadrivalent (IIV4) and Flublok Quadrivalent (RIV4), both for persons over 18 years.

According to the CDC, Flublok Quadrivalent (an RIV) met noninferiority measures, compared with a similar IIV quadrivalent vaccine, for the A(H3H2) and B/Yamagata viruses but not for A(H1N1) or B/Victoria viruses.

Vaccine composition for 2017-2018

Approved viruses for the 2017-2018 season trivalent vaccines are an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008–like virus (Victoria lineage), according to the MMWR. Quadrivalent vaccines will include those viruses, with the addition of an B/Phuket/3073/2013–like virus (Yamagata lineage).

The CDC continues to recommend that the quadrivalent live attenuated influenza vaccine FluMist not be used by anyone for the 2017-2018 season, a decision that was made after evidence showed poor effectiveness against influenza A(H1N1)pdm09 viruses in the 2013-2014 and 2015-2016 seasons.

Vaccine updates published in this report were recommended by ACIP during meetings held in October 2016 and February and June 2017.

ezimmerman@frontlinemedcom.com

On Twitter @eaztweets

 

All newborns with a birth weight of at least 2,000 grams (4.4 pounds) should receive the hepatitis B vaccine within 24 hours of birth, according to a new policy statement by the American Academy of Pediatrics that brings its recommendations in line with those of the Advisory Committee on Immunization Practices at the Centers for Disease Control and Prevention.

“The birth dose can prevent infection of infants born to infected mothers in situations in which the mother’s results are never obtained, are misinterpreted, are falsely negative, are transcribed or reported to the infant care team inaccurately, or simply not communicated to the nursery,” announced the new statement from the AAP Committee on Infectious Diseases and the Committee on Fetus and Newborn (Pediatrics. 2017 Aug 28. doi: 10.1542/peds.2017-1870).

A dose of the hepatitis B vaccine within 24 hours of birth is 75%-95% effective at preventing perinatal hepatitis B transmission. “When postexposure prophylaxis with both hepatitis B vaccine and hepatitis B immune globulin (HBIG) is given, is timed appropriately, and is followed by completion of the infant hepatitis B immunization series, perinatal infection rates range from 0.7% to 1.1%,” according to the statement.

CDC/Dr. Erskine Palmer

“The birth dose also provides protection to infants at risk from household exposure after the perinatal period,” the statement indicated. “Because the consequences of perinatally acquired hepatitis B are enduring and potentially fatal, the safety net of the birth dose is critically important.”

Approximately 1,000 newborns still contract perinatal hepatitis B infections every year. Of these, 90% will develop chronic hepatitis B infections, and a quarter of those who don’t receive treatment will die from liver cirrhosis or cancer. There has been an increase in the incidence of new hepatitis B infections in some states because of opioid epidemic in the United States, according to MMWR reports.

The cost effectiveness of preventing hepatitis B with the vaccine and, when necessary, HBIG, is estimated at $2,600 per quality-adjusted year of life. The most common side effects reported after hepatitis B administration are pain (3%-29%), erythema (3%), swelling (3%), fever (1%-6%) and headache (3%).

There has been extensive analysis of the safety of hepatitis B vaccines, the policy statement indicated. Analysis of Vaccine Safety Datalink data has found no causal link between administration of the hepatitis B vaccine and the following: neonatal sepsis or death, rheumatoid arthritis, Bell’s palsy, autoimmune thyroid disease, hemolytic anemia in children, anaphylaxis, optic neuritis, Guillain-Barré syndrome, sudden-onset sensorineural hearing loss, or other chronic illnesses.

Specific recommendations

• Infants born to mothers who test positive for hepatitis B surface antigen (HBsAg): Administer the hepatitis B vaccine and HBIG within 12 hours of birth.

• Infants weighing at least 2,000 g and born to mothers who are HBsAg negative: Administer the hepatitis B vaccine within 24 hours of birth.

• Infants weighing less than 2,000 g and born to mothers who are HBsAg negative: Administer the hepatitis B vaccine at hospital discharge or at age 1 month (whichever is first).

• Infants weighing at least 2,000 g and born to mothers with an unknown HBsAg status: Administer the hepatitis B vaccine within 12 hours of birth and HBIG by hospital discharge or age 7 days (whichever is first) if HBsAg status remains unknown or is confirmed positive.

• Infants weighing less than 2,000 g and born to mothers with an unknown HBsAg status: Administer the hepatitis B vaccine within 12 hours of birth and then HBIG within 12 hours unless the mother tests negative for HBsAg by then.

 

All newborns with a birth weight of at least 2,000 grams (4.4 pounds) should receive the hepatitis B vaccine within 24 hours of birth, according to a new policy statement by the American Academy of Pediatrics that brings its recommendations in line with those of the Advisory Committee on Immunization Practices at the Centers for Disease Control and Prevention.

“The birth dose can prevent infection of infants born to infected mothers in situations in which the mother’s results are never obtained, are misinterpreted, are falsely negative, are transcribed or reported to the infant care team inaccurately, or simply not communicated to the nursery,” announced the new statement from the AAP Committee on Infectious Diseases and the Committee on Fetus and Newborn (Pediatrics. 2017 Aug 28. doi: 10.1542/peds.2017-1870).

A dose of the hepatitis B vaccine within 24 hours of birth is 75%-95% effective at preventing perinatal hepatitis B transmission. “When postexposure prophylaxis with both hepatitis B vaccine and hepatitis B immune globulin (HBIG) is given, is timed appropriately, and is followed by completion of the infant hepatitis B immunization series, perinatal infection rates range from 0.7% to 1.1%,” according to the statement.

CDC/Dr. Erskine Palmer

“The birth dose also provides protection to infants at risk from household exposure after the perinatal period,” the statement indicated. “Because the consequences of perinatally acquired hepatitis B are enduring and potentially fatal, the safety net of the birth dose is critically important.”

Approximately 1,000 newborns still contract perinatal hepatitis B infections every year. Of these, 90% will develop chronic hepatitis B infections, and a quarter of those who don’t receive treatment will die from liver cirrhosis or cancer. There has been an increase in the incidence of new hepatitis B infections in some states because of opioid epidemic in the United States, according to MMWR reports.

The cost effectiveness of preventing hepatitis B with the vaccine and, when necessary, HBIG, is estimated at $2,600 per quality-adjusted year of life. The most common side effects reported after hepatitis B administration are pain (3%-29%), erythema (3%), swelling (3%), fever (1%-6%) and headache (3%).

There has been extensive analysis of the safety of hepatitis B vaccines, the policy statement indicated. Analysis of Vaccine Safety Datalink data has found no causal link between administration of the hepatitis B vaccine and the following: neonatal sepsis or death, rheumatoid arthritis, Bell’s palsy, autoimmune thyroid disease, hemolytic anemia in children, anaphylaxis, optic neuritis, Guillain-Barré syndrome, sudden-onset sensorineural hearing loss, or other chronic illnesses.

Specific recommendations

• Infants born to mothers who test positive for hepatitis B surface antigen (HBsAg): Administer the hepatitis B vaccine and HBIG within 12 hours of birth.

• Infants weighing at least 2,000 g and born to mothers who are HBsAg negative: Administer the hepatitis B vaccine within 24 hours of birth.

• Infants weighing less than 2,000 g and born to mothers who are HBsAg negative: Administer the hepatitis B vaccine at hospital discharge or at age 1 month (whichever is first).

• Infants weighing at least 2,000 g and born to mothers with an unknown HBsAg status: Administer the hepatitis B vaccine within 12 hours of birth and HBIG by hospital discharge or age 7 days (whichever is first) if HBsAg status remains unknown or is confirmed positive.

• Infants weighing less than 2,000 g and born to mothers with an unknown HBsAg status: Administer the hepatitis B vaccine within 12 hours of birth and then HBIG within 12 hours unless the mother tests negative for HBsAg by then.

 

All newborns with a birth weight of at least 2,000 grams (4.4 pounds) should receive the hepatitis B vaccine within 24 hours of birth, according to a new policy statement by the American Academy of Pediatrics that brings its recommendations in line with those of the Advisory Committee on Immunization Practices at the Centers for Disease Control and Prevention.

“The birth dose can prevent infection of infants born to infected mothers in situations in which the mother’s results are never obtained, are misinterpreted, are falsely negative, are transcribed or reported to the infant care team inaccurately, or simply not communicated to the nursery,” announced the new statement from the AAP Committee on Infectious Diseases and the Committee on Fetus and Newborn (Pediatrics. 2017 Aug 28. doi: 10.1542/peds.2017-1870).

A dose of the hepatitis B vaccine within 24 hours of birth is 75%-95% effective at preventing perinatal hepatitis B transmission. “When postexposure prophylaxis with both hepatitis B vaccine and hepatitis B immune globulin (HBIG) is given, is timed appropriately, and is followed by completion of the infant hepatitis B immunization series, perinatal infection rates range from 0.7% to 1.1%,” according to the statement.

CDC/Dr. Erskine Palmer

“The birth dose also provides protection to infants at risk from household exposure after the perinatal period,” the statement indicated. “Because the consequences of perinatally acquired hepatitis B are enduring and potentially fatal, the safety net of the birth dose is critically important.”

Approximately 1,000 newborns still contract perinatal hepatitis B infections every year. Of these, 90% will develop chronic hepatitis B infections, and a quarter of those who don’t receive treatment will die from liver cirrhosis or cancer. There has been an increase in the incidence of new hepatitis B infections in some states because of opioid epidemic in the United States, according to MMWR reports.

The cost effectiveness of preventing hepatitis B with the vaccine and, when necessary, HBIG, is estimated at $2,600 per quality-adjusted year of life. The most common side effects reported after hepatitis B administration are pain (3%-29%), erythema (3%), swelling (3%), fever (1%-6%) and headache (3%).

There has been extensive analysis of the safety of hepatitis B vaccines, the policy statement indicated. Analysis of Vaccine Safety Datalink data has found no causal link between administration of the hepatitis B vaccine and the following: neonatal sepsis or death, rheumatoid arthritis, Bell’s palsy, autoimmune thyroid disease, hemolytic anemia in children, anaphylaxis, optic neuritis, Guillain-Barré syndrome, sudden-onset sensorineural hearing loss, or other chronic illnesses.

Specific recommendations

• Infants born to mothers who test positive for hepatitis B surface antigen (HBsAg): Administer the hepatitis B vaccine and HBIG within 12 hours of birth.

• Infants weighing at least 2,000 g and born to mothers who are HBsAg negative: Administer the hepatitis B vaccine within 24 hours of birth.

• Infants weighing less than 2,000 g and born to mothers who are HBsAg negative: Administer the hepatitis B vaccine at hospital discharge or at age 1 month (whichever is first).

• Infants weighing at least 2,000 g and born to mothers with an unknown HBsAg status: Administer the hepatitis B vaccine within 12 hours of birth and HBIG by hospital discharge or age 7 days (whichever is first) if HBsAg status remains unknown or is confirmed positive.

• Infants weighing less than 2,000 g and born to mothers with an unknown HBsAg status: Administer the hepatitis B vaccine within 12 hours of birth and then HBIG within 12 hours unless the mother tests negative for HBsAg by then.

 

Titers of postdose three G1 serum-neutralizing antibody (PD3 G1 SNA) appear to be the best correlate of protection for pentavalent rotavirus vaccine (RV5), reported G. Frank Liu, PhD, and his associates at Merck in Kenilworth, N.J.

The researchers discovered this by analyzing data from five clinical trials of RV5 at both the individual and aggregated population level. Also, by looking at immunogenicity measures and case status of individuals from phase 2 and 3 trials of RV5, they found that “higher PD3 G1 SNA titers are associated with lower odds of contracting any [rotavirus gastroenteritis].”

CDC/Dr. Erskine Palmer

In the phase 2 and 3 studies, better RV5 efficacy was linked to higher PD3 G1 SNA geometric mean titers (GMT) ratios and higher PD3 serum anti-RV IgA GMT ratios. In analyses of both individual- and population-level data, the PD3 G1 SNA titer correlated more closely with efficacy for RV5 than did serum anti-RV IgA, Dr. Liu and his associates concluded.

Read more at (Hum Vaccin Immunother. 2017. doi: 10.1080/21645515.2017.1356522).

cnellist@frontlinemedcom.com

 

Titers of postdose three G1 serum-neutralizing antibody (PD3 G1 SNA) appear to be the best correlate of protection for pentavalent rotavirus vaccine (RV5), reported G. Frank Liu, PhD, and his associates at Merck in Kenilworth, N.J.

The researchers discovered this by analyzing data from five clinical trials of RV5 at both the individual and aggregated population level. Also, by looking at immunogenicity measures and case status of individuals from phase 2 and 3 trials of RV5, they found that “higher PD3 G1 SNA titers are associated with lower odds of contracting any [rotavirus gastroenteritis].”

CDC/Dr. Erskine Palmer

In the phase 2 and 3 studies, better RV5 efficacy was linked to higher PD3 G1 SNA geometric mean titers (GMT) ratios and higher PD3 serum anti-RV IgA GMT ratios. In analyses of both individual- and population-level data, the PD3 G1 SNA titer correlated more closely with efficacy for RV5 than did serum anti-RV IgA, Dr. Liu and his associates concluded.

Read more at (Hum Vaccin Immunother. 2017. doi: 10.1080/21645515.2017.1356522).

cnellist@frontlinemedcom.com

 

Titers of postdose three G1 serum-neutralizing antibody (PD3 G1 SNA) appear to be the best correlate of protection for pentavalent rotavirus vaccine (RV5), reported G. Frank Liu, PhD, and his associates at Merck in Kenilworth, N.J.

The researchers discovered this by analyzing data from five clinical trials of RV5 at both the individual and aggregated population level. Also, by looking at immunogenicity measures and case status of individuals from phase 2 and 3 trials of RV5, they found that “higher PD3 G1 SNA titers are associated with lower odds of contracting any [rotavirus gastroenteritis].”

CDC/Dr. Erskine Palmer

In the phase 2 and 3 studies, better RV5 efficacy was linked to higher PD3 G1 SNA geometric mean titers (GMT) ratios and higher PD3 serum anti-RV IgA GMT ratios. In analyses of both individual- and population-level data, the PD3 G1 SNA titer correlated more closely with efficacy for RV5 than did serum anti-RV IgA, Dr. Liu and his associates concluded.

Read more at (Hum Vaccin Immunother. 2017. doi: 10.1080/21645515.2017.1356522).

cnellist@frontlinemedcom.com

Reported rates of side effects of a bivalent serogroup B meningococcal vaccine given to college students were lower or similar to those in clinical trials, said Theresa M. Fiorito, MD, of Brown University, Providence, R.I., and her associates.

In February 2015, two unlinked, culture-confirmed cases of Neisseria meningitidis serogroup B (MenB) disease occurred at a local college in Rhode Island, and a bivalent MenB vaccine subsequently was administered. After the first-dose vaccination clinic, a 94% coverage rate was achieved, and there were no other cases of MenB disease. Injection site pain occurred in 78% of 1,736 students after dose one, in 64% of 1,395 after dose two, and in 71% of 609 students after dose three.

Micah Young/istockphoto

Fatigue occurred in 35% of 1,707 students after dose one, in 31% of 1,395 after dose two, and in 39% of 609 students after dose three. Myalgia was a side effect in 47% of 1,726 students after dose one, in 37% of 1,395 after dose two, and in 16% of 609 students after dose three. Headache was an adverse event in 16% of 1,725 students after one dose, 11% of 1,395 after two doses, and 16% of 609 after three doses. Adverse events such as chills and fever occurred in 15% or fewer students after any of the three doses.

Serious adverse events, such as any allergic reaction; difficulty breathing; hives, welts, or a severe rash; and swelling of the face, mouth, or throat occurred in fewer than 5% of students after any of the three doses, the investigators reported.

“We found an overall lower rate of headache within our sample relative to the rates in reported clinical trials. The rates of injection site pain, fatigue, thermometer-confirmed fevers (100.4° F or higher), and chills were approximately similar in our study as in clinical trials. The rate of myalgia was higher for our sample than in clinical trials following the first and second doses of the vaccine, but similar after the third dose of vaccine,” Dr. Fiorito and her associates wrote.

Read more at (Pediatr Infect Dis J. 2017. doi: 10.1097/INF.0000000000001742).

cnellist@frontlinemedcom.com

Reported rates of side effects of a bivalent serogroup B meningococcal vaccine given to college students were lower or similar to those in clinical trials, said Theresa M. Fiorito, MD, of Brown University, Providence, R.I., and her associates.

In February 2015, two unlinked, culture-confirmed cases of Neisseria meningitidis serogroup B (MenB) disease occurred at a local college in Rhode Island, and a bivalent MenB vaccine subsequently was administered. After the first-dose vaccination clinic, a 94% coverage rate was achieved, and there were no other cases of MenB disease. Injection site pain occurred in 78% of 1,736 students after dose one, in 64% of 1,395 after dose two, and in 71% of 609 students after dose three.

Micah Young/istockphoto

Fatigue occurred in 35% of 1,707 students after dose one, in 31% of 1,395 after dose two, and in 39% of 609 students after dose three. Myalgia was a side effect in 47% of 1,726 students after dose one, in 37% of 1,395 after dose two, and in 16% of 609 students after dose three. Headache was an adverse event in 16% of 1,725 students after one dose, 11% of 1,395 after two doses, and 16% of 609 after three doses. Adverse events such as chills and fever occurred in 15% or fewer students after any of the three doses.

Serious adverse events, such as any allergic reaction; difficulty breathing; hives, welts, or a severe rash; and swelling of the face, mouth, or throat occurred in fewer than 5% of students after any of the three doses, the investigators reported.

“We found an overall lower rate of headache within our sample relative to the rates in reported clinical trials. The rates of injection site pain, fatigue, thermometer-confirmed fevers (100.4° F or higher), and chills were approximately similar in our study as in clinical trials. The rate of myalgia was higher for our sample than in clinical trials following the first and second doses of the vaccine, but similar after the third dose of vaccine,” Dr. Fiorito and her associates wrote.

Read more at (Pediatr Infect Dis J. 2017. doi: 10.1097/INF.0000000000001742).

cnellist@frontlinemedcom.com

Reported rates of side effects of a bivalent serogroup B meningococcal vaccine given to college students were lower or similar to those in clinical trials, said Theresa M. Fiorito, MD, of Brown University, Providence, R.I., and her associates.

In February 2015, two unlinked, culture-confirmed cases of Neisseria meningitidis serogroup B (MenB) disease occurred at a local college in Rhode Island, and a bivalent MenB vaccine subsequently was administered. After the first-dose vaccination clinic, a 94% coverage rate was achieved, and there were no other cases of MenB disease. Injection site pain occurred in 78% of 1,736 students after dose one, in 64% of 1,395 after dose two, and in 71% of 609 students after dose three.

Micah Young/istockphoto

Fatigue occurred in 35% of 1,707 students after dose one, in 31% of 1,395 after dose two, and in 39% of 609 students after dose three. Myalgia was a side effect in 47% of 1,726 students after dose one, in 37% of 1,395 after dose two, and in 16% of 609 students after dose three. Headache was an adverse event in 16% of 1,725 students after one dose, 11% of 1,395 after two doses, and 16% of 609 after three doses. Adverse events such as chills and fever occurred in 15% or fewer students after any of the three doses.

Serious adverse events, such as any allergic reaction; difficulty breathing; hives, welts, or a severe rash; and swelling of the face, mouth, or throat occurred in fewer than 5% of students after any of the three doses, the investigators reported.

“We found an overall lower rate of headache within our sample relative to the rates in reported clinical trials. The rates of injection site pain, fatigue, thermometer-confirmed fevers (100.4° F or higher), and chills were approximately similar in our study as in clinical trials. The rate of myalgia was higher for our sample than in clinical trials following the first and second doses of the vaccine, but similar after the third dose of vaccine,” Dr. Fiorito and her associates wrote.

Read more at (Pediatr Infect Dis J. 2017. doi: 10.1097/INF.0000000000001742).

cnellist@frontlinemedcom.com

 

The Food and Drug Administration has approved Cyltezo (adalimumab-adbm) for multiple conditions.

Cyltezo is an injectable tumor necrosis factor blocker, and is a biosimilar to adalimumab (Humira). The drug is indicated to treat moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active Crohn’s disease, moderate to severe active ulcerative colitis, moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older, and moderate to severe plaque psoriasis.

The most common side effects are injection site infections, infection, rash, and headache. There is an increased risk of serious infection and malignancies such as lymphoma, and patients with active infections should not be started on Cyltezo.

Find the Cyltezo labeling information here.

lfranki@frontlinemedcom.com

 

The Food and Drug Administration has approved Cyltezo (adalimumab-adbm) for multiple conditions.

Cyltezo is an injectable tumor necrosis factor blocker, and is a biosimilar to adalimumab (Humira). The drug is indicated to treat moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active Crohn’s disease, moderate to severe active ulcerative colitis, moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older, and moderate to severe plaque psoriasis.

The most common side effects are injection site infections, infection, rash, and headache. There is an increased risk of serious infection and malignancies such as lymphoma, and patients with active infections should not be started on Cyltezo.

Find the Cyltezo labeling information here.

lfranki@frontlinemedcom.com

 

The Food and Drug Administration has approved Cyltezo (adalimumab-adbm) for multiple conditions.

Cyltezo is an injectable tumor necrosis factor blocker, and is a biosimilar to adalimumab (Humira). The drug is indicated to treat moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active Crohn’s disease, moderate to severe active ulcerative colitis, moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older, and moderate to severe plaque psoriasis.

The most common side effects are injection site infections, infection, rash, and headache. There is an increased risk of serious infection and malignancies such as lymphoma, and patients with active infections should not be started on Cyltezo.

Find the Cyltezo labeling information here.

lfranki@frontlinemedcom.com

NASHVILLE, TENN. – At the University of North Carolina at Chapel Hill, many infants who would previously have been transferred to the NICU for asymptomatic hypoglycemia now are staying with their moms, thanks to a new protocol that holds off on blood glucose testing until infants are fed for the first time and glucose homeostasis can begin.

Not too long ago, the university realized it had a problem that’s probably familiar to other institutions: Its system to monitor newborns at risk for hypoglycemia – those born to diabetic mothers, or who are small or large for gestational age – put too many infants with asymptomatic hypoglycemia into the NICU when they didn’t really need to be there.

Nurse practitioners “were tired of transferring babies they felt were responsive to feeding and did not actually require NICU care,” and “a growing number of families were unhappy with being separated from infants that were well-appearing and feeding well at a time when moms were trying to establish breast feeding and bonding. There was frustration with our protocol,” which “seemed rigid and outdated,” said Ashley Sutton, MD, a pediatric hospitalist at the university.

Under the old system, blood glucose was checked within an hour of birth whether the infant had fed or not, and infants were sent to the NICU if glucose levels were below 25 mg/dL; the protocol didn’t take into account the normal physiologic glucose nadir after birth, or allow enough time for the initiation of glucose homeostasis. While nursery staff waited for NICU personnel to arrive, “[We’d do] nothing, when moms were there with milk,” Dr. Sutton said at the Pediatric Hospital Medicine annual meeting.

To fix the problem, Dr. Sutton and others on a multidisciplinary team implemented the American Academy of Pediatrics’ 2011 guidelines for monitoring glucose homeostasis in late-preterm and term newborns at-risk for hypoglycemia, with an additional mandate to initiate immediate, continual skin-to-skin contact at delivery (Pediatrics. 2011 Mar;127[3]:575-9).

Under the new system, children are fed with either their mom’s or a donor’s breast milk within an hour of birth, and the initial glucose check comes at 90 minutes; infants are transferred if blood glucose remains below 25 mg/dL after the second feeding. After 4 hours of life, glucose levels below 35 mg/dL trigger an evaluation for symptoms, not necessarily an automatic NICU transfer.

Labor and delivery nurses also are empowered “to immediately feed the baby no matter what number [they are] seeing,” Dr. Sutton said at the meeting, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

The efforts have made a difference. The transfer rate for at-risk infants has fallen from 17% to 3%, and skin-to-skin contact is initiated within the first hour of life in 64%, up from 45%. Feeding of at-risk infants within the first hour has increased from 43% to 61%, and the first glucose check comes at an average of 97 minutes. The number of unnecessary NICU transfers of at-risk infants has fallen sharply.

Meanwhile, there’s been no increase in sepsis evaluations, adverse events, readmissions, and the rates of symptomatic hypoglycemia.

Dr. Sutton and her colleagues had no industry disclosures. The work was funded by the National Institutes of Health.

aotto@frontlinemedcom.com

NASHVILLE, TENN. – At the University of North Carolina at Chapel Hill, many infants who would previously have been transferred to the NICU for asymptomatic hypoglycemia now are staying with their moms, thanks to a new protocol that holds off on blood glucose testing until infants are fed for the first time and glucose homeostasis can begin.

Not too long ago, the university realized it had a problem that’s probably familiar to other institutions: Its system to monitor newborns at risk for hypoglycemia – those born to diabetic mothers, or who are small or large for gestational age – put too many infants with asymptomatic hypoglycemia into the NICU when they didn’t really need to be there.

Nurse practitioners “were tired of transferring babies they felt were responsive to feeding and did not actually require NICU care,” and “a growing number of families were unhappy with being separated from infants that were well-appearing and feeding well at a time when moms were trying to establish breast feeding and bonding. There was frustration with our protocol,” which “seemed rigid and outdated,” said Ashley Sutton, MD, a pediatric hospitalist at the university.

Under the old system, blood glucose was checked within an hour of birth whether the infant had fed or not, and infants were sent to the NICU if glucose levels were below 25 mg/dL; the protocol didn’t take into account the normal physiologic glucose nadir after birth, or allow enough time for the initiation of glucose homeostasis. While nursery staff waited for NICU personnel to arrive, “[We’d do] nothing, when moms were there with milk,” Dr. Sutton said at the Pediatric Hospital Medicine annual meeting.

To fix the problem, Dr. Sutton and others on a multidisciplinary team implemented the American Academy of Pediatrics’ 2011 guidelines for monitoring glucose homeostasis in late-preterm and term newborns at-risk for hypoglycemia, with an additional mandate to initiate immediate, continual skin-to-skin contact at delivery (Pediatrics. 2011 Mar;127[3]:575-9).

Under the new system, children are fed with either their mom’s or a donor’s breast milk within an hour of birth, and the initial glucose check comes at 90 minutes; infants are transferred if blood glucose remains below 25 mg/dL after the second feeding. After 4 hours of life, glucose levels below 35 mg/dL trigger an evaluation for symptoms, not necessarily an automatic NICU transfer.

Labor and delivery nurses also are empowered “to immediately feed the baby no matter what number [they are] seeing,” Dr. Sutton said at the meeting, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

The efforts have made a difference. The transfer rate for at-risk infants has fallen from 17% to 3%, and skin-to-skin contact is initiated within the first hour of life in 64%, up from 45%. Feeding of at-risk infants within the first hour has increased from 43% to 61%, and the first glucose check comes at an average of 97 minutes. The number of unnecessary NICU transfers of at-risk infants has fallen sharply.

Meanwhile, there’s been no increase in sepsis evaluations, adverse events, readmissions, and the rates of symptomatic hypoglycemia.

Dr. Sutton and her colleagues had no industry disclosures. The work was funded by the National Institutes of Health.

aotto@frontlinemedcom.com

NASHVILLE, TENN. – At the University of North Carolina at Chapel Hill, many infants who would previously have been transferred to the NICU for asymptomatic hypoglycemia now are staying with their moms, thanks to a new protocol that holds off on blood glucose testing until infants are fed for the first time and glucose homeostasis can begin.

Not too long ago, the university realized it had a problem that’s probably familiar to other institutions: Its system to monitor newborns at risk for hypoglycemia – those born to diabetic mothers, or who are small or large for gestational age – put too many infants with asymptomatic hypoglycemia into the NICU when they didn’t really need to be there.

Nurse practitioners “were tired of transferring babies they felt were responsive to feeding and did not actually require NICU care,” and “a growing number of families were unhappy with being separated from infants that were well-appearing and feeding well at a time when moms were trying to establish breast feeding and bonding. There was frustration with our protocol,” which “seemed rigid and outdated,” said Ashley Sutton, MD, a pediatric hospitalist at the university.

Under the old system, blood glucose was checked within an hour of birth whether the infant had fed or not, and infants were sent to the NICU if glucose levels were below 25 mg/dL; the protocol didn’t take into account the normal physiologic glucose nadir after birth, or allow enough time for the initiation of glucose homeostasis. While nursery staff waited for NICU personnel to arrive, “[We’d do] nothing, when moms were there with milk,” Dr. Sutton said at the Pediatric Hospital Medicine annual meeting.

To fix the problem, Dr. Sutton and others on a multidisciplinary team implemented the American Academy of Pediatrics’ 2011 guidelines for monitoring glucose homeostasis in late-preterm and term newborns at-risk for hypoglycemia, with an additional mandate to initiate immediate, continual skin-to-skin contact at delivery (Pediatrics. 2011 Mar;127[3]:575-9).

Under the new system, children are fed with either their mom’s or a donor’s breast milk within an hour of birth, and the initial glucose check comes at 90 minutes; infants are transferred if blood glucose remains below 25 mg/dL after the second feeding. After 4 hours of life, glucose levels below 35 mg/dL trigger an evaluation for symptoms, not necessarily an automatic NICU transfer.

Labor and delivery nurses also are empowered “to immediately feed the baby no matter what number [they are] seeing,” Dr. Sutton said at the meeting, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

The efforts have made a difference. The transfer rate for at-risk infants has fallen from 17% to 3%, and skin-to-skin contact is initiated within the first hour of life in 64%, up from 45%. Feeding of at-risk infants within the first hour has increased from 43% to 61%, and the first glucose check comes at an average of 97 minutes. The number of unnecessary NICU transfers of at-risk infants has fallen sharply.

Meanwhile, there’s been no increase in sepsis evaluations, adverse events, readmissions, and the rates of symptomatic hypoglycemia.

Dr. Sutton and her colleagues had no industry disclosures. The work was funded by the National Institutes of Health.

aotto@frontlinemedcom.com

 

BARCELONA – Inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer in the groundbreaking phase III CANTOS trial, Paul M. Ridker, MD, reported at the annual congress of the European Society of Cardiology.

“These data provide the first proof that inflammation inhibition in the absence of lipid lowering can improve atherogenic outcomes and potentially alter progression of some fatal cancers,” declared Dr. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.

Bruce Jancin/Frontline Medical News

“Just like we’ve learned that lower LDL is better, I think we’re now learning that lower inflammation is better,” he said.

CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) was a randomized, double-blind, placebo-controlled trial involving 10,061 patients in 39 countries, all of whom had a previous MI and a chronically high level of systemic inflammation as reflected in a median baseline high-sensitivity C-reactive protein (CRP) level of 4.1 mg/L. Ninety-one percent of participants were on statin therapy, with a median LDL cholesterol of 82 mg/dL when randomized to subcutaneous canakinumab at 50, 150, or 300 mg or to placebo once every 3 months.

Canakinumab is a fully human monoclonal antibody targeting IL-1B, a key player in systemic inflammation. The cytokine is activated by the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, a part of the innate immune system. Canakinumab is approved as Ilaris for treatment of several uncommon rheumatologic diseases, including cryopryin-associated periodic syndrome and systemic juvenile idiopathic arthritis.

At a median follow-up of 3.7 years, the incidence of the primary composite efficacy endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death was 4.5 events per 100 person-years in the control group, significantly higher than the 3.86 and 3.9 events per 100 person-years in patients on canakinumab at 150 and 300 mg, respectively.

Since event rates were virtually identical in the 150- and 300-mg study arms, Dr. Ridker combined those two patient groups in his analysis. They showed a 15% reduction in the risk of the primary efficacy endpoint, compared with placebo-treated controls, along with a 39% reduction from baseline in CRP. They also were 30% less likely to undergo percutaneous coronary intervention or coronary artery bypass graft during follow-up.

“That’s quite important, because that’s a progression-of-atherosclerosis endpoint and also obviously a cost and financial endpoint,” he observed.

A key finding in CANTOS was that patients with a reduction in CRP at or exceeding the median decrease just 3 months into the study – that is, after a single injection – had a 27% reduction in major vascular events during follow-up. Patients with a lesser reduction in CRP at that point did not experience a significant reduction in the primary endpoint, compared with placebo.

“The clinician in me would say we probably ought to give a single dose of the drug, see what happens, and if you get a large inflammation reduction we could perhaps consider treating that patient, but if you did not get a large reduction perhaps this is not a therapy for that patient. Why not avoid the toxicity in people who aren’t going to respond?” Dr. Ridker said.

Side effects related to canakinumab consisted of mild leukopenia and a small but statistically significant increase in fatal infections, which he called “not surprising.”

“It’s in the same range as one gets in treating rheumatoid arthritis with a biologic drug, which rheumatologists are very comfortable doing. You would imagine that if this does become a treatment, physicians will get much better at bringing patients in early when they have signs and symptoms of infection,” the cardiologist continued.

Patients on canakinumab showed significant reductions in incident rheumatoid arthritis, gout, and osteoarthritis. The drug had no kidney or liver adverse events.

Cancer was a prespecified secondary outcome in CANTOS. The investigators saw the trial as an opportunity to test a longstanding hypothesis that inhibiting IL-1B would have a positive impact on lung cancer in particular.

“Smoking, exposure to diesel fuel, inhalation of asbestos or other silicates – these cause inflammation which activates the NLRP3 inflammasome, but in the pulmonary system rather than the arteries,” Dr. Ridker explained.

An entry requirement in CANTOS was that patients needed to be free of known cancer. During study follow-up, 129 patients were diagnosed with lung cancer. The risk was reduced in dose-dependent fashion with canakinumab: by 39% relative to placebo in the 150-mg group and by 67% in the 300-mg group. Lung cancer mortality was reduced by 77% in the canakinumab 300-mg group.

“I don’t think this is about oncogenesis per se. I think the tumors are already there, but they don’t progress because we’ve altered the tumor’s inflammatory microenvironment,” he continued.

Since CANTOS was first and foremost a study of atherosclerotic disease prevention, the cancer results need to be replicated on a high-priority basis. Dr. Ridker predicted that Novartis, which sponsored CANTOS, will quickly mount a clinical trial examining canakinumab’s potential as an adjunctive treatment to either chemotherapy or radiation following resection of lung cancer.

He stressed that CANTOS is only the beginning stanza in what will be an entirely new approach to preventive cardiology. Numerous other inflammatory pathways also might serve as targets.

“I think this is going to open up all kinds of approaches using a variety of agents that have really been in the rheumatology and immunology world,” the cardiologist predicted.

For example, he is principal investigator in the ongoing National Heart, Lung, and Blood Institute–sponsored Cardiovascular Inflammation Reduction Trial (CIRT), a randomized, double-blind, placebo-controlled study of low-dose methotrexate for prevention of cardiovascular events in a planned 7,000 patients with type 2 diabetes or metabolic syndrome who’ve had an MI or have multivessel CAD. Results are probably 4-6 years off.

“Right now, we know canakinumab works. If methotrexate were to work, then we’d have a generic, inexpensive approach as well,” Dr. Ridker noted.

Novartis officials indicated that, on the basis of the positive CANTOS results, the company plans to file for an expanded indication for canakinumab for cardiovascular prevention. The company also is gearing up for studies of the drug in oncology.

Simultaneous with Dr. Ridker’s presentation in Barcelona, both the atherosclerotic disease findings (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914) and the cancer findings (Lancet. 2017 Aug 27. doi: 10.1016/S0140-6736(17)32247-X) were published.

He reported serving as a consultant to Novartis.

 

bjancin@frontlinemedcom.com

 

BARCELONA – Inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer in the groundbreaking phase III CANTOS trial, Paul M. Ridker, MD, reported at the annual congress of the European Society of Cardiology.

“These data provide the first proof that inflammation inhibition in the absence of lipid lowering can improve atherogenic outcomes and potentially alter progression of some fatal cancers,” declared Dr. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.

Bruce Jancin/Frontline Medical News

“Just like we’ve learned that lower LDL is better, I think we’re now learning that lower inflammation is better,” he said.

CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) was a randomized, double-blind, placebo-controlled trial involving 10,061 patients in 39 countries, all of whom had a previous MI and a chronically high level of systemic inflammation as reflected in a median baseline high-sensitivity C-reactive protein (CRP) level of 4.1 mg/L. Ninety-one percent of participants were on statin therapy, with a median LDL cholesterol of 82 mg/dL when randomized to subcutaneous canakinumab at 50, 150, or 300 mg or to placebo once every 3 months.

Canakinumab is a fully human monoclonal antibody targeting IL-1B, a key player in systemic inflammation. The cytokine is activated by the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, a part of the innate immune system. Canakinumab is approved as Ilaris for treatment of several uncommon rheumatologic diseases, including cryopryin-associated periodic syndrome and systemic juvenile idiopathic arthritis.

At a median follow-up of 3.7 years, the incidence of the primary composite efficacy endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death was 4.5 events per 100 person-years in the control group, significantly higher than the 3.86 and 3.9 events per 100 person-years in patients on canakinumab at 150 and 300 mg, respectively.

Since event rates were virtually identical in the 150- and 300-mg study arms, Dr. Ridker combined those two patient groups in his analysis. They showed a 15% reduction in the risk of the primary efficacy endpoint, compared with placebo-treated controls, along with a 39% reduction from baseline in CRP. They also were 30% less likely to undergo percutaneous coronary intervention or coronary artery bypass graft during follow-up.

“That’s quite important, because that’s a progression-of-atherosclerosis endpoint and also obviously a cost and financial endpoint,” he observed.

A key finding in CANTOS was that patients with a reduction in CRP at or exceeding the median decrease just 3 months into the study – that is, after a single injection – had a 27% reduction in major vascular events during follow-up. Patients with a lesser reduction in CRP at that point did not experience a significant reduction in the primary endpoint, compared with placebo.

“The clinician in me would say we probably ought to give a single dose of the drug, see what happens, and if you get a large inflammation reduction we could perhaps consider treating that patient, but if you did not get a large reduction perhaps this is not a therapy for that patient. Why not avoid the toxicity in people who aren’t going to respond?” Dr. Ridker said.

Side effects related to canakinumab consisted of mild leukopenia and a small but statistically significant increase in fatal infections, which he called “not surprising.”

“It’s in the same range as one gets in treating rheumatoid arthritis with a biologic drug, which rheumatologists are very comfortable doing. You would imagine that if this does become a treatment, physicians will get much better at bringing patients in early when they have signs and symptoms of infection,” the cardiologist continued.

Patients on canakinumab showed significant reductions in incident rheumatoid arthritis, gout, and osteoarthritis. The drug had no kidney or liver adverse events.

Cancer was a prespecified secondary outcome in CANTOS. The investigators saw the trial as an opportunity to test a longstanding hypothesis that inhibiting IL-1B would have a positive impact on lung cancer in particular.

“Smoking, exposure to diesel fuel, inhalation of asbestos or other silicates – these cause inflammation which activates the NLRP3 inflammasome, but in the pulmonary system rather than the arteries,” Dr. Ridker explained.

An entry requirement in CANTOS was that patients needed to be free of known cancer. During study follow-up, 129 patients were diagnosed with lung cancer. The risk was reduced in dose-dependent fashion with canakinumab: by 39% relative to placebo in the 150-mg group and by 67% in the 300-mg group. Lung cancer mortality was reduced by 77% in the canakinumab 300-mg group.

“I don’t think this is about oncogenesis per se. I think the tumors are already there, but they don’t progress because we’ve altered the tumor’s inflammatory microenvironment,” he continued.

Since CANTOS was first and foremost a study of atherosclerotic disease prevention, the cancer results need to be replicated on a high-priority basis. Dr. Ridker predicted that Novartis, which sponsored CANTOS, will quickly mount a clinical trial examining canakinumab’s potential as an adjunctive treatment to either chemotherapy or radiation following resection of lung cancer.

He stressed that CANTOS is only the beginning stanza in what will be an entirely new approach to preventive cardiology. Numerous other inflammatory pathways also might serve as targets.

“I think this is going to open up all kinds of approaches using a variety of agents that have really been in the rheumatology and immunology world,” the cardiologist predicted.

For example, he is principal investigator in the ongoing National Heart, Lung, and Blood Institute–sponsored Cardiovascular Inflammation Reduction Trial (CIRT), a randomized, double-blind, placebo-controlled study of low-dose methotrexate for prevention of cardiovascular events in a planned 7,000 patients with type 2 diabetes or metabolic syndrome who’ve had an MI or have multivessel CAD. Results are probably 4-6 years off.

“Right now, we know canakinumab works. If methotrexate were to work, then we’d have a generic, inexpensive approach as well,” Dr. Ridker noted.

Novartis officials indicated that, on the basis of the positive CANTOS results, the company plans to file for an expanded indication for canakinumab for cardiovascular prevention. The company also is gearing up for studies of the drug in oncology.

Simultaneous with Dr. Ridker’s presentation in Barcelona, both the atherosclerotic disease findings (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914) and the cancer findings (Lancet. 2017 Aug 27. doi: 10.1016/S0140-6736(17)32247-X) were published.

He reported serving as a consultant to Novartis.

 

bjancin@frontlinemedcom.com

 

BARCELONA – Inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer in the groundbreaking phase III CANTOS trial, Paul M. Ridker, MD, reported at the annual congress of the European Society of Cardiology.

“These data provide the first proof that inflammation inhibition in the absence of lipid lowering can improve atherogenic outcomes and potentially alter progression of some fatal cancers,” declared Dr. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.

Bruce Jancin/Frontline Medical News

“Just like we’ve learned that lower LDL is better, I think we’re now learning that lower inflammation is better,” he said.

CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) was a randomized, double-blind, placebo-controlled trial involving 10,061 patients in 39 countries, all of whom had a previous MI and a chronically high level of systemic inflammation as reflected in a median baseline high-sensitivity C-reactive protein (CRP) level of 4.1 mg/L. Ninety-one percent of participants were on statin therapy, with a median LDL cholesterol of 82 mg/dL when randomized to subcutaneous canakinumab at 50, 150, or 300 mg or to placebo once every 3 months.

Canakinumab is a fully human monoclonal antibody targeting IL-1B, a key player in systemic inflammation. The cytokine is activated by the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, a part of the innate immune system. Canakinumab is approved as Ilaris for treatment of several uncommon rheumatologic diseases, including cryopryin-associated periodic syndrome and systemic juvenile idiopathic arthritis.

At a median follow-up of 3.7 years, the incidence of the primary composite efficacy endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death was 4.5 events per 100 person-years in the control group, significantly higher than the 3.86 and 3.9 events per 100 person-years in patients on canakinumab at 150 and 300 mg, respectively.

Since event rates were virtually identical in the 150- and 300-mg study arms, Dr. Ridker combined those two patient groups in his analysis. They showed a 15% reduction in the risk of the primary efficacy endpoint, compared with placebo-treated controls, along with a 39% reduction from baseline in CRP. They also were 30% less likely to undergo percutaneous coronary intervention or coronary artery bypass graft during follow-up.

“That’s quite important, because that’s a progression-of-atherosclerosis endpoint and also obviously a cost and financial endpoint,” he observed.

A key finding in CANTOS was that patients with a reduction in CRP at or exceeding the median decrease just 3 months into the study – that is, after a single injection – had a 27% reduction in major vascular events during follow-up. Patients with a lesser reduction in CRP at that point did not experience a significant reduction in the primary endpoint, compared with placebo.

“The clinician in me would say we probably ought to give a single dose of the drug, see what happens, and if you get a large inflammation reduction we could perhaps consider treating that patient, but if you did not get a large reduction perhaps this is not a therapy for that patient. Why not avoid the toxicity in people who aren’t going to respond?” Dr. Ridker said.

Side effects related to canakinumab consisted of mild leukopenia and a small but statistically significant increase in fatal infections, which he called “not surprising.”

“It’s in the same range as one gets in treating rheumatoid arthritis with a biologic drug, which rheumatologists are very comfortable doing. You would imagine that if this does become a treatment, physicians will get much better at bringing patients in early when they have signs and symptoms of infection,” the cardiologist continued.

Patients on canakinumab showed significant reductions in incident rheumatoid arthritis, gout, and osteoarthritis. The drug had no kidney or liver adverse events.

Cancer was a prespecified secondary outcome in CANTOS. The investigators saw the trial as an opportunity to test a longstanding hypothesis that inhibiting IL-1B would have a positive impact on lung cancer in particular.

“Smoking, exposure to diesel fuel, inhalation of asbestos or other silicates – these cause inflammation which activates the NLRP3 inflammasome, but in the pulmonary system rather than the arteries,” Dr. Ridker explained.

An entry requirement in CANTOS was that patients needed to be free of known cancer. During study follow-up, 129 patients were diagnosed with lung cancer. The risk was reduced in dose-dependent fashion with canakinumab: by 39% relative to placebo in the 150-mg group and by 67% in the 300-mg group. Lung cancer mortality was reduced by 77% in the canakinumab 300-mg group.

“I don’t think this is about oncogenesis per se. I think the tumors are already there, but they don’t progress because we’ve altered the tumor’s inflammatory microenvironment,” he continued.

Since CANTOS was first and foremost a study of atherosclerotic disease prevention, the cancer results need to be replicated on a high-priority basis. Dr. Ridker predicted that Novartis, which sponsored CANTOS, will quickly mount a clinical trial examining canakinumab’s potential as an adjunctive treatment to either chemotherapy or radiation following resection of lung cancer.

He stressed that CANTOS is only the beginning stanza in what will be an entirely new approach to preventive cardiology. Numerous other inflammatory pathways also might serve as targets.

“I think this is going to open up all kinds of approaches using a variety of agents that have really been in the rheumatology and immunology world,” the cardiologist predicted.

For example, he is principal investigator in the ongoing National Heart, Lung, and Blood Institute–sponsored Cardiovascular Inflammation Reduction Trial (CIRT), a randomized, double-blind, placebo-controlled study of low-dose methotrexate for prevention of cardiovascular events in a planned 7,000 patients with type 2 diabetes or metabolic syndrome who’ve had an MI or have multivessel CAD. Results are probably 4-6 years off.

“Right now, we know canakinumab works. If methotrexate were to work, then we’d have a generic, inexpensive approach as well,” Dr. Ridker noted.

Novartis officials indicated that, on the basis of the positive CANTOS results, the company plans to file for an expanded indication for canakinumab for cardiovascular prevention. The company also is gearing up for studies of the drug in oncology.

Simultaneous with Dr. Ridker’s presentation in Barcelona, both the atherosclerotic disease findings (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914) and the cancer findings (Lancet. 2017 Aug 27. doi: 10.1016/S0140-6736(17)32247-X) were published.

He reported serving as a consultant to Novartis.

 

bjancin@frontlinemedcom.com

Reimmunization appears to be safe for patients with mild to moderate adverse events following immunization (AEFI), but there are not enough data to make firm conclusions about severe AEFIs, according to a systematic review of studies that were published in English and French between 1982 and 2016 and were made available to Medline via PubMed, Embase, and the Cochrane library.

dina2001/Thinkstock

The review, published in Pediatrics (2017 Aug. doi: 10.1542.peds.2016-3707), looked at 29 studies. Of those, eight collectively found that allergic-like events recurred in 30 of 594 patients (5%; 95% confidence interval, 3.3-6.8), Joseline Guetsop Zafack, MD, MPH, of the department of social and preventive medicine at Laval University in Quebec, and her coauthors reported. They noted that “recurrences did not dissuade patients from continuing immunization.” In the six studies that looked at recurrence of hypotonic-hyporesponsive episodes, only 3 of 398 patients had a recurrence (0.8%; 95% CI, 0.2-2.2). None of three studies found recurrence of seizure in children who were reimmunized..

Apnea was found to be of concern only in children under the age of 1 year and usually found only in lower birth weight babies and those with ongoing hospitalization for complications related to prematurity, the investigators said. A 10-g increase in birth weight was associated with a 6% reduction in risk of apnea recurrence (odds ratio, 0.94; 95% CI, 0.89-1.00), and odds of recurrence were 23 times higher in infants hospitalized for complications related to prematurity (OR, 23; 95% CI, 2-272).

Some of the studies also evaluated for injection site reactions, Henoch-Schönlein purpura, or other AEFI, Dr. Zafack and her coauthors continued. Injection site reactions varied depending on vaccine and number of doses, but all children recovered within 19 days of immunization. Only one child in one study had a recurrence of Henoch-Schönlein purpura. Vomiting, persistent crying, decreased appetite, and drowsiness recurred in 15%, 24%, 25%, and 35% of the reimmunized patients, respectively, across all the studies.

“In a context of vaccine hesitancy and growing concerns regarding vaccine safety, evaluating the risk of recurrence of all AEFIs should become part of the standard evaluation of vaccine safety,” the researchers wrote. “Reimmunization appears to be safe for patients with mild to moderate AEFIs. However, the data are insufficient to draw firm conclusions regarding the safety of reimmunization after a severe AEFI.”

In this study, “it appears that the risk of recurrence of serious AEFIs (anaphylaxis, seizures, or apnea in term infants) was low (less than 1%). For minor to moderate AEFIs (fever, extensive limb swelling, oculorespiratory syndrome, allergic-like events, sleepiness, thrombocytopenia, decreased appetite, vomiting, or persistent crying), the risk of recurrence ranged from 4% to 48%,” the investigators concluded.

The study was funded by the Canadian Immunization Research Network, which is sponsored by the Public Health Agency of Canada and the Canadian Institutes of Health Research. Dr. Zafack reported no financial disclosures. Some of her coauthors reported financial support from GlaxoSmithKline and Pfizer.

Reimmunization appears to be safe for patients with mild to moderate adverse events following immunization (AEFI), but there are not enough data to make firm conclusions about severe AEFIs, according to a systematic review of studies that were published in English and French between 1982 and 2016 and were made available to Medline via PubMed, Embase, and the Cochrane library.

dina2001/Thinkstock

The review, published in Pediatrics (2017 Aug. doi: 10.1542.peds.2016-3707), looked at 29 studies. Of those, eight collectively found that allergic-like events recurred in 30 of 594 patients (5%; 95% confidence interval, 3.3-6.8), Joseline Guetsop Zafack, MD, MPH, of the department of social and preventive medicine at Laval University in Quebec, and her coauthors reported. They noted that “recurrences did not dissuade patients from continuing immunization.” In the six studies that looked at recurrence of hypotonic-hyporesponsive episodes, only 3 of 398 patients had a recurrence (0.8%; 95% CI, 0.2-2.2). None of three studies found recurrence of seizure in children who were reimmunized..

Apnea was found to be of concern only in children under the age of 1 year and usually found only in lower birth weight babies and those with ongoing hospitalization for complications related to prematurity, the investigators said. A 10-g increase in birth weight was associated with a 6% reduction in risk of apnea recurrence (odds ratio, 0.94; 95% CI, 0.89-1.00), and odds of recurrence were 23 times higher in infants hospitalized for complications related to prematurity (OR, 23; 95% CI, 2-272).

Some of the studies also evaluated for injection site reactions, Henoch-Schönlein purpura, or other AEFI, Dr. Zafack and her coauthors continued. Injection site reactions varied depending on vaccine and number of doses, but all children recovered within 19 days of immunization. Only one child in one study had a recurrence of Henoch-Schönlein purpura. Vomiting, persistent crying, decreased appetite, and drowsiness recurred in 15%, 24%, 25%, and 35% of the reimmunized patients, respectively, across all the studies.

“In a context of vaccine hesitancy and growing concerns regarding vaccine safety, evaluating the risk of recurrence of all AEFIs should become part of the standard evaluation of vaccine safety,” the researchers wrote. “Reimmunization appears to be safe for patients with mild to moderate AEFIs. However, the data are insufficient to draw firm conclusions regarding the safety of reimmunization after a severe AEFI.”

In this study, “it appears that the risk of recurrence of serious AEFIs (anaphylaxis, seizures, or apnea in term infants) was low (less than 1%). For minor to moderate AEFIs (fever, extensive limb swelling, oculorespiratory syndrome, allergic-like events, sleepiness, thrombocytopenia, decreased appetite, vomiting, or persistent crying), the risk of recurrence ranged from 4% to 48%,” the investigators concluded.

The study was funded by the Canadian Immunization Research Network, which is sponsored by the Public Health Agency of Canada and the Canadian Institutes of Health Research. Dr. Zafack reported no financial disclosures. Some of her coauthors reported financial support from GlaxoSmithKline and Pfizer.

Reimmunization appears to be safe for patients with mild to moderate adverse events following immunization (AEFI), but there are not enough data to make firm conclusions about severe AEFIs, according to a systematic review of studies that were published in English and French between 1982 and 2016 and were made available to Medline via PubMed, Embase, and the Cochrane library.

dina2001/Thinkstock

The review, published in Pediatrics (2017 Aug. doi: 10.1542.peds.2016-3707), looked at 29 studies. Of those, eight collectively found that allergic-like events recurred in 30 of 594 patients (5%; 95% confidence interval, 3.3-6.8), Joseline Guetsop Zafack, MD, MPH, of the department of social and preventive medicine at Laval University in Quebec, and her coauthors reported. They noted that “recurrences did not dissuade patients from continuing immunization.” In the six studies that looked at recurrence of hypotonic-hyporesponsive episodes, only 3 of 398 patients had a recurrence (0.8%; 95% CI, 0.2-2.2). None of three studies found recurrence of seizure in children who were reimmunized..

Apnea was found to be of concern only in children under the age of 1 year and usually found only in lower birth weight babies and those with ongoing hospitalization for complications related to prematurity, the investigators said. A 10-g increase in birth weight was associated with a 6% reduction in risk of apnea recurrence (odds ratio, 0.94; 95% CI, 0.89-1.00), and odds of recurrence were 23 times higher in infants hospitalized for complications related to prematurity (OR, 23; 95% CI, 2-272).

Some of the studies also evaluated for injection site reactions, Henoch-Schönlein purpura, or other AEFI, Dr. Zafack and her coauthors continued. Injection site reactions varied depending on vaccine and number of doses, but all children recovered within 19 days of immunization. Only one child in one study had a recurrence of Henoch-Schönlein purpura. Vomiting, persistent crying, decreased appetite, and drowsiness recurred in 15%, 24%, 25%, and 35% of the reimmunized patients, respectively, across all the studies.

“In a context of vaccine hesitancy and growing concerns regarding vaccine safety, evaluating the risk of recurrence of all AEFIs should become part of the standard evaluation of vaccine safety,” the researchers wrote. “Reimmunization appears to be safe for patients with mild to moderate AEFIs. However, the data are insufficient to draw firm conclusions regarding the safety of reimmunization after a severe AEFI.”

In this study, “it appears that the risk of recurrence of serious AEFIs (anaphylaxis, seizures, or apnea in term infants) was low (less than 1%). For minor to moderate AEFIs (fever, extensive limb swelling, oculorespiratory syndrome, allergic-like events, sleepiness, thrombocytopenia, decreased appetite, vomiting, or persistent crying), the risk of recurrence ranged from 4% to 48%,” the investigators concluded.

The study was funded by the Canadian Immunization Research Network, which is sponsored by the Public Health Agency of Canada and the Canadian Institutes of Health Research. Dr. Zafack reported no financial disclosures. Some of her coauthors reported financial support from GlaxoSmithKline and Pfizer.

 

NASHVILLE, TENN. – Axillary thermometry outperformed both rectal and temporal artery thermometry in 205 newborns aged 12-72 hours in a study performed at the University of North Carolina at Chapel Hill.

The infants had two temperatures taken by each method over a period of 15 minutes, for a total of six readings per child and 1,230 measurements overall. Axillary thermometry proved both accurate and reliable. Rectal thermometry was accurate but less reliable, and temporal thermometry was reliable but less accurate.

M. Alexander Otto/Frontline Medical News

The American Academy of Pediatrics recommends rectal thermometers as the gold standard for children under 3 years old, but axillary thermometers are widely used, and temporal artery thermometers are becoming common. Nurses at the University of North Carolina generally have been using axillary thermometers in the nursery; they’re more convenient and less traumatic than rectal thermometers – especially for the provider – and there’s no risk of rectal injury. Parents, however, have been told to use rectal thermometers when they take their baby home.

Lead investigator Ketan Nadkarni, MD, a 3rd-year pediatrics resident, and his colleagues wanted to compare the three methods head-to-head to make sure axillary thermometers were okay to use in the nursery, and to see if it really was necessary to tell parents to use rectal thermometers; many are reluctant to use them. Plus, “there’s been a lot of controversy” in pediatrics “over the best way to measure temperature,” Dr. Nadkarni said at the Pediatric Hospital Medicine annual meeting.

“With our data, we think axillary is what we should continue to use in the newborn nursery,” he said. Some attending physicians still are hesitant to recommend axillary thermometers to new parents, but “all of the nurses are aware of” the study findings “and a lot of the residents are, too, so I think we are starting to move” in that direction.

The study had some unexpected findings as well: “The biggest surprise was how wide the distribution of rectal temperatures was. The distribution” around the mean “was way larger than we had thought, so [rectal thermometry was] not very reliable at all. Our study surprisingly exhibited suboptimal performance in terms of reliability,” for rectal thermometry, he said at the meeting, which was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

Specifically, the average distance of any given rectal measurement from the mean rectal temperature of 98.3º F was 0.45º F. The second rectal temperature in the study sometimes varied a half a degree or more from the first taken shortly before, in the same infant.

The average distance of an axillary temperature from the axillary mean of 98.32º F was 0.32º F; for temporal thermometry it was 0.34º F from a mean of 98.55º F.

Another surprise was that temporal thermometry overestimated temperature by an average of about a quarter of a degree, compared with rectal readings. Even small overestimates could lead to unnecessary sepsis work-ups; “the last thing we want is to hospitalize these kids when they don’t need to be,” Dr. Nadkarni said.

The mean axillary and rectal temperatures, meanwhile, were only 0.02º F apart, which was not statistically significant. “Axillary was absolutely interchangeable with rectal in terms of accuracy,” he said.

The children were born at 37 weeks’ gestation or later, and were excluded if they had a temperature of 100.4º F or higher by any method. Rectal and axillary temperatures were taken with a Welch Allyn SureTemp Plus 690. Temple temperatures were taken with an Exergen TAT-2000c.

The investigators plan to run a similar trial in the ED with children up to 3 months old.

There was no external funding for the work, and Dr. Nadkarni had no relevant financial disclosures.

aotto@frontlinemedcom.com

 

NASHVILLE, TENN. – Axillary thermometry outperformed both rectal and temporal artery thermometry in 205 newborns aged 12-72 hours in a study performed at the University of North Carolina at Chapel Hill.

The infants had two temperatures taken by each method over a period of 15 minutes, for a total of six readings per child and 1,230 measurements overall. Axillary thermometry proved both accurate and reliable. Rectal thermometry was accurate but less reliable, and temporal thermometry was reliable but less accurate.

M. Alexander Otto/Frontline Medical News

The American Academy of Pediatrics recommends rectal thermometers as the gold standard for children under 3 years old, but axillary thermometers are widely used, and temporal artery thermometers are becoming common. Nurses at the University of North Carolina generally have been using axillary thermometers in the nursery; they’re more convenient and less traumatic than rectal thermometers – especially for the provider – and there’s no risk of rectal injury. Parents, however, have been told to use rectal thermometers when they take their baby home.

Lead investigator Ketan Nadkarni, MD, a 3rd-year pediatrics resident, and his colleagues wanted to compare the three methods head-to-head to make sure axillary thermometers were okay to use in the nursery, and to see if it really was necessary to tell parents to use rectal thermometers; many are reluctant to use them. Plus, “there’s been a lot of controversy” in pediatrics “over the best way to measure temperature,” Dr. Nadkarni said at the Pediatric Hospital Medicine annual meeting.

“With our data, we think axillary is what we should continue to use in the newborn nursery,” he said. Some attending physicians still are hesitant to recommend axillary thermometers to new parents, but “all of the nurses are aware of” the study findings “and a lot of the residents are, too, so I think we are starting to move” in that direction.

The study had some unexpected findings as well: “The biggest surprise was how wide the distribution of rectal temperatures was. The distribution” around the mean “was way larger than we had thought, so [rectal thermometry was] not very reliable at all. Our study surprisingly exhibited suboptimal performance in terms of reliability,” for rectal thermometry, he said at the meeting, which was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

Specifically, the average distance of any given rectal measurement from the mean rectal temperature of 98.3º F was 0.45º F. The second rectal temperature in the study sometimes varied a half a degree or more from the first taken shortly before, in the same infant.

The average distance of an axillary temperature from the axillary mean of 98.32º F was 0.32º F; for temporal thermometry it was 0.34º F from a mean of 98.55º F.

Another surprise was that temporal thermometry overestimated temperature by an average of about a quarter of a degree, compared with rectal readings. Even small overestimates could lead to unnecessary sepsis work-ups; “the last thing we want is to hospitalize these kids when they don’t need to be,” Dr. Nadkarni said.

The mean axillary and rectal temperatures, meanwhile, were only 0.02º F apart, which was not statistically significant. “Axillary was absolutely interchangeable with rectal in terms of accuracy,” he said.

The children were born at 37 weeks’ gestation or later, and were excluded if they had a temperature of 100.4º F or higher by any method. Rectal and axillary temperatures were taken with a Welch Allyn SureTemp Plus 690. Temple temperatures were taken with an Exergen TAT-2000c.

The investigators plan to run a similar trial in the ED with children up to 3 months old.

There was no external funding for the work, and Dr. Nadkarni had no relevant financial disclosures.

aotto@frontlinemedcom.com

 

NASHVILLE, TENN. – Axillary thermometry outperformed both rectal and temporal artery thermometry in 205 newborns aged 12-72 hours in a study performed at the University of North Carolina at Chapel Hill.

The infants had two temperatures taken by each method over a period of 15 minutes, for a total of six readings per child and 1,230 measurements overall. Axillary thermometry proved both accurate and reliable. Rectal thermometry was accurate but less reliable, and temporal thermometry was reliable but less accurate.

M. Alexander Otto/Frontline Medical News

The American Academy of Pediatrics recommends rectal thermometers as the gold standard for children under 3 years old, but axillary thermometers are widely used, and temporal artery thermometers are becoming common. Nurses at the University of North Carolina generally have been using axillary thermometers in the nursery; they’re more convenient and less traumatic than rectal thermometers – especially for the provider – and there’s no risk of rectal injury. Parents, however, have been told to use rectal thermometers when they take their baby home.

Lead investigator Ketan Nadkarni, MD, a 3rd-year pediatrics resident, and his colleagues wanted to compare the three methods head-to-head to make sure axillary thermometers were okay to use in the nursery, and to see if it really was necessary to tell parents to use rectal thermometers; many are reluctant to use them. Plus, “there’s been a lot of controversy” in pediatrics “over the best way to measure temperature,” Dr. Nadkarni said at the Pediatric Hospital Medicine annual meeting.

“With our data, we think axillary is what we should continue to use in the newborn nursery,” he said. Some attending physicians still are hesitant to recommend axillary thermometers to new parents, but “all of the nurses are aware of” the study findings “and a lot of the residents are, too, so I think we are starting to move” in that direction.

The study had some unexpected findings as well: “The biggest surprise was how wide the distribution of rectal temperatures was. The distribution” around the mean “was way larger than we had thought, so [rectal thermometry was] not very reliable at all. Our study surprisingly exhibited suboptimal performance in terms of reliability,” for rectal thermometry, he said at the meeting, which was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

Specifically, the average distance of any given rectal measurement from the mean rectal temperature of 98.3º F was 0.45º F. The second rectal temperature in the study sometimes varied a half a degree or more from the first taken shortly before, in the same infant.

The average distance of an axillary temperature from the axillary mean of 98.32º F was 0.32º F; for temporal thermometry it was 0.34º F from a mean of 98.55º F.

Another surprise was that temporal thermometry overestimated temperature by an average of about a quarter of a degree, compared with rectal readings. Even small overestimates could lead to unnecessary sepsis work-ups; “the last thing we want is to hospitalize these kids when they don’t need to be,” Dr. Nadkarni said.

The mean axillary and rectal temperatures, meanwhile, were only 0.02º F apart, which was not statistically significant. “Axillary was absolutely interchangeable with rectal in terms of accuracy,” he said.

The children were born at 37 weeks’ gestation or later, and were excluded if they had a temperature of 100.4º F or higher by any method. Rectal and axillary temperatures were taken with a Welch Allyn SureTemp Plus 690. Temple temperatures were taken with an Exergen TAT-2000c.

The investigators plan to run a similar trial in the ED with children up to 3 months old.

There was no external funding for the work, and Dr. Nadkarni had no relevant financial disclosures.

aotto@frontlinemedcom.com