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50 years of pediatric dermatology
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.
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.
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.
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 [email protected].
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.
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.
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.
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 [email protected].
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.
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.
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.
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 [email protected].
FDA approves second adalimumab biosimilar for multiple conditions
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.
Find the Cyltezo labeling information here.
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.
Find the Cyltezo labeling information here.
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.
Find the Cyltezo labeling information here.
Noninvasive NASH test could help monitor hepatotoxicity in patients on methotrexate
A noninvasive test for nonalcoholic steatohepatitis (NASH) and hepatic fibrosis could be used to help detect worsening hepatic fibrosis in psoriasis patients who are on long-term methotrexate therapy, according to the authors of a retrospective study published online Aug. 23.
To evaluate the use of the noninvasive test to monitor for hepatic fibrosis in this group of patients and guide the management of methotrexate (MTX) without a liver biopsy, investigators conducted an analysis of 107 patients with psoriasis who were on long-term MTX treatment, for whom the NASH FibroSure test was used between January 2007 and December 2013. All the patients were white, fifty were men, the mean age was 83 years, and almost all of the patients had a body mass index of 28 or more (16% had a BMI between 28 and 30, and 81% had a BMI over 30).
The NASH FibroSure test, which was developed for use in patients suspected of having nonalcoholic fatty liver disease (NAFLD), combines analyses of 10 biochemical markers combined with age, sex, height, and weight to calculate the degree of hepatic fibrosis. The test has a reported sensitivity of 83% and a specificity of 78% in detecting risk of significant fibrosis, according to Bruce Bauer, MD, of Pariser Dermatology Specialists, Norfolk, Va., and his coinvestigators (JAMA Dermatol. 2017 Aug 23. doi: 10.1001/jamadermatol.2017.2083).
Among the 107 patients, the investigators found a statistically significant correlation “between worsening fibrosis scores and cumulative methotrexate” dose among women (P = .02), but not among men (P = .11). In addition, women with a BMI of 28 or more were more likely to have worsening fibrosis scores (P = .03). “There were no differences between men and women with regard to prevalence of a BMI of 28 or more, diabetes, age older than 65 years, or chronic kidney disease,” which they said, suggests that among women, “obesity influences the progression of fibrosis scores.”
The investigators advised providers not to disregard any potential warning signs when using FibroSure on men. “No differences between the cohorts were observed that would explain the association of worsening fibrosis scores and cumulative MTX dose among women but not men,” they wrote. “However, given the implications of the progression of hepatic fibrosis, we still recommend discontinuing MTX for male patients who demonstrate worsening fibrosis scores.”
While the test may not be able to replace liver biopsy, based on these results, the investigators noted that noninvasive tests such as this one could help significantly reduce the number of liver biopsies needed.
They pointed out that because the study was conducted at one center, the next step is to conduct “a prospective, randomized, multi-institutional analysis of NASH FibroSure and liver biopsies for patients with psoriasis receiving MTX vs. other treatments, including a larger cohort of men and women with different racial and ethnic backgrounds.”
One of the four authors reported receiving research funding from T2 Biosystems. Dr. Bauer and the two other authors reported no relevant financial disclosures. The study was funded by the Marshfield Clinic Resident Research Program.
[email protected]
On Twitter @eaztweets
A noninvasive test for nonalcoholic steatohepatitis (NASH) and hepatic fibrosis could be used to help detect worsening hepatic fibrosis in psoriasis patients who are on long-term methotrexate therapy, according to the authors of a retrospective study published online Aug. 23.
To evaluate the use of the noninvasive test to monitor for hepatic fibrosis in this group of patients and guide the management of methotrexate (MTX) without a liver biopsy, investigators conducted an analysis of 107 patients with psoriasis who were on long-term MTX treatment, for whom the NASH FibroSure test was used between January 2007 and December 2013. All the patients were white, fifty were men, the mean age was 83 years, and almost all of the patients had a body mass index of 28 or more (16% had a BMI between 28 and 30, and 81% had a BMI over 30).
The NASH FibroSure test, which was developed for use in patients suspected of having nonalcoholic fatty liver disease (NAFLD), combines analyses of 10 biochemical markers combined with age, sex, height, and weight to calculate the degree of hepatic fibrosis. The test has a reported sensitivity of 83% and a specificity of 78% in detecting risk of significant fibrosis, according to Bruce Bauer, MD, of Pariser Dermatology Specialists, Norfolk, Va., and his coinvestigators (JAMA Dermatol. 2017 Aug 23. doi: 10.1001/jamadermatol.2017.2083).
Among the 107 patients, the investigators found a statistically significant correlation “between worsening fibrosis scores and cumulative methotrexate” dose among women (P = .02), but not among men (P = .11). In addition, women with a BMI of 28 or more were more likely to have worsening fibrosis scores (P = .03). “There were no differences between men and women with regard to prevalence of a BMI of 28 or more, diabetes, age older than 65 years, or chronic kidney disease,” which they said, suggests that among women, “obesity influences the progression of fibrosis scores.”
The investigators advised providers not to disregard any potential warning signs when using FibroSure on men. “No differences between the cohorts were observed that would explain the association of worsening fibrosis scores and cumulative MTX dose among women but not men,” they wrote. “However, given the implications of the progression of hepatic fibrosis, we still recommend discontinuing MTX for male patients who demonstrate worsening fibrosis scores.”
While the test may not be able to replace liver biopsy, based on these results, the investigators noted that noninvasive tests such as this one could help significantly reduce the number of liver biopsies needed.
They pointed out that because the study was conducted at one center, the next step is to conduct “a prospective, randomized, multi-institutional analysis of NASH FibroSure and liver biopsies for patients with psoriasis receiving MTX vs. other treatments, including a larger cohort of men and women with different racial and ethnic backgrounds.”
One of the four authors reported receiving research funding from T2 Biosystems. Dr. Bauer and the two other authors reported no relevant financial disclosures. The study was funded by the Marshfield Clinic Resident Research Program.
[email protected]
On Twitter @eaztweets
A noninvasive test for nonalcoholic steatohepatitis (NASH) and hepatic fibrosis could be used to help detect worsening hepatic fibrosis in psoriasis patients who are on long-term methotrexate therapy, according to the authors of a retrospective study published online Aug. 23.
To evaluate the use of the noninvasive test to monitor for hepatic fibrosis in this group of patients and guide the management of methotrexate (MTX) without a liver biopsy, investigators conducted an analysis of 107 patients with psoriasis who were on long-term MTX treatment, for whom the NASH FibroSure test was used between January 2007 and December 2013. All the patients were white, fifty were men, the mean age was 83 years, and almost all of the patients had a body mass index of 28 or more (16% had a BMI between 28 and 30, and 81% had a BMI over 30).
The NASH FibroSure test, which was developed for use in patients suspected of having nonalcoholic fatty liver disease (NAFLD), combines analyses of 10 biochemical markers combined with age, sex, height, and weight to calculate the degree of hepatic fibrosis. The test has a reported sensitivity of 83% and a specificity of 78% in detecting risk of significant fibrosis, according to Bruce Bauer, MD, of Pariser Dermatology Specialists, Norfolk, Va., and his coinvestigators (JAMA Dermatol. 2017 Aug 23. doi: 10.1001/jamadermatol.2017.2083).
Among the 107 patients, the investigators found a statistically significant correlation “between worsening fibrosis scores and cumulative methotrexate” dose among women (P = .02), but not among men (P = .11). In addition, women with a BMI of 28 or more were more likely to have worsening fibrosis scores (P = .03). “There were no differences between men and women with regard to prevalence of a BMI of 28 or more, diabetes, age older than 65 years, or chronic kidney disease,” which they said, suggests that among women, “obesity influences the progression of fibrosis scores.”
The investigators advised providers not to disregard any potential warning signs when using FibroSure on men. “No differences between the cohorts were observed that would explain the association of worsening fibrosis scores and cumulative MTX dose among women but not men,” they wrote. “However, given the implications of the progression of hepatic fibrosis, we still recommend discontinuing MTX for male patients who demonstrate worsening fibrosis scores.”
While the test may not be able to replace liver biopsy, based on these results, the investigators noted that noninvasive tests such as this one could help significantly reduce the number of liver biopsies needed.
They pointed out that because the study was conducted at one center, the next step is to conduct “a prospective, randomized, multi-institutional analysis of NASH FibroSure and liver biopsies for patients with psoriasis receiving MTX vs. other treatments, including a larger cohort of men and women with different racial and ethnic backgrounds.”
One of the four authors reported receiving research funding from T2 Biosystems. Dr. Bauer and the two other authors reported no relevant financial disclosures. The study was funded by the Marshfield Clinic Resident Research Program.
[email protected]
On Twitter @eaztweets
FROM JAMA DERMATOLOGY
Key clinical point:
Major finding: There was a significant correlation between worsening fibrosis scores on the test and cumulative methotrexate dose among women (P = .02), but not among men (P = .11).
Data source: A retrospective single-center study analyzing the test in 107 psoriasis patients on methotrexate, collected between January 2007 and December 2013.
Disclosures: One of the four authors received research funding from T2 Biosystems. There were no other financial disclosures.
Psoriasis, psoriatic arthritis research makes headway at GRAPPA meeting
The agenda for this year’s Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting included sessions on juvenile psoriatic arthritis (PsA), the microbiome in psoriasis and PsA, and setting up longitudinal cohort studies. There was also a workshop to define the clinical fit and feasibility of PsA outcome measures for clinical trials and updates on several GRAPPA-associated projects.
The meeting, held July 13-15 in Amsterdam, opened with the annual trainee session. This year’s trainee session attracted more than 40 abstracts, of which 6 were selected for oral presentations on a variety of topics including outcome measure assessment, imaging, the microbiome in PsA, and T-cell subsets in synovial fluid.
The juvenile PsA session highlighted the similarities and differences between juvenile and adult PsA. For example, nearly half of children develop the arthritis prior to the skin symptoms, as opposed to adults where the vast majority develop psoriasis first.
The jPsA session also emphasized the need for efforts to better define this disease entity and to study outcomes related to it. The current International League of Associations for Rheumatology criteria for juvenile idiopathic arthritis split jPsA into other subgroups (for example, enthesitis-associated arthritis, undifferentiated arthritis, etc).
Three investigators – Matt Stoll, MD, PhD, Devy Zisman, MD, and Elizabeth Mellins, MD – also presented studies of the epidemiology of jPsA.
Among the most intriguing sessions at the GRAPPA meeting was a series of three talks by Jose Scher, MD, Hok Bing Thio, MD, PhD, and Dirk Elewaut, PhD, that introduced the audience to the complexity of the micro-organisms that call the human host “home” and the potential role in the development of inflammatory conditions, in particular psoriasis and PsA. These talks touched on the potential uses of the microbiome of the gut, skin, and oral mucosa in predicting therapy response and modulating the immune system.
Dafna Gladman, MD, led a session on “how to set up a cohort.” In this session, speakers provided a road map for setting up a longitudinal cohort and discussed opportunities and challenges along the way. This session provided a foundation for a meeting that followed the annual meeting, the GRAPPA Research Collaborative Network meeting (held July 15-16). The RCN meeting aimed to develop a plan for a GRAPPA research network supporting collaborative research to identify biomarkers and outcomes in psoriasis and PsA. Speakers/panelists from academics and industry kicked off the meeting with a discussion of prior experiences in establishing international cohort studies. Subsequent sessions presented individual aspects of beginning a longitudinal cohort study for biomarkers, including methods for sample collection, regulatory processes, and data collected at potential sites; capturing and harmonizing clinical data for such studies; and policies for publication of RCN studies.
This year’s workshop was focused on the GRAPPA-Outcome Measures in Rheumatology (OMERACT) working group’s plan to develop a Core Outcome Measure Set, a collection of outcome measurement instruments to be used in randomized, controlled trials (RCTs) for PsA. During the plenary session, the team presented a process for the group to evaluate instruments, including assessment of match to the domain or concept of interest, feasibility, construct validity, and discrimination (including reliability and the ability to distinguish between two groups such as responders and nonresponders). Breakout groups then discussed one of the six tools being considered and voted on match to the domain of interest and feasibility for RCTs.
In a skin session, ongoing efforts to standardize and simplify the measurement of skin psoriasis in both the clinic and RCTs were presented. While the Psoriasis Area and Severity Index (PASI) is the current standard for measuring psoriasis severity and response to therapy in RCTs, the PASI is challenging for use in clinical practice. Joseph Merola, MD, presented data to support the use of the psoriasis Physician Global Assessment (PGA) x body surface area (BSA), a simpler measure than the PASI, as a potential substitute for the PASI. Updates from the International Dermatology Outcome Measures board included reporting of the psoriasis core domain set and a summary of the PsA symptoms working group’s efforts to identify patient-reported outcomes to identify and measure PsA among patients enrolled in psoriasis RCTs. April Armstrong, MD, discussed the National Psoriasis Foundation’s efforts to develop treat-to-target goals for psoriasis. Finally, Laura Coates, MBChB, PhD, presented a report on her efforts to examine a variety of psoriasis cut points for minimal disease activity and very low disease activity outcomes.
Dr. Ogdie is director of the Penn Psoriatic Arthritis Clinic at the University of Pennsylvania, Philadelphia, and is a member of the GRAPPA Steering Committee.
The agenda for this year’s Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting included sessions on juvenile psoriatic arthritis (PsA), the microbiome in psoriasis and PsA, and setting up longitudinal cohort studies. There was also a workshop to define the clinical fit and feasibility of PsA outcome measures for clinical trials and updates on several GRAPPA-associated projects.
The meeting, held July 13-15 in Amsterdam, opened with the annual trainee session. This year’s trainee session attracted more than 40 abstracts, of which 6 were selected for oral presentations on a variety of topics including outcome measure assessment, imaging, the microbiome in PsA, and T-cell subsets in synovial fluid.
The juvenile PsA session highlighted the similarities and differences between juvenile and adult PsA. For example, nearly half of children develop the arthritis prior to the skin symptoms, as opposed to adults where the vast majority develop psoriasis first.
The jPsA session also emphasized the need for efforts to better define this disease entity and to study outcomes related to it. The current International League of Associations for Rheumatology criteria for juvenile idiopathic arthritis split jPsA into other subgroups (for example, enthesitis-associated arthritis, undifferentiated arthritis, etc).
Three investigators – Matt Stoll, MD, PhD, Devy Zisman, MD, and Elizabeth Mellins, MD – also presented studies of the epidemiology of jPsA.
Among the most intriguing sessions at the GRAPPA meeting was a series of three talks by Jose Scher, MD, Hok Bing Thio, MD, PhD, and Dirk Elewaut, PhD, that introduced the audience to the complexity of the micro-organisms that call the human host “home” and the potential role in the development of inflammatory conditions, in particular psoriasis and PsA. These talks touched on the potential uses of the microbiome of the gut, skin, and oral mucosa in predicting therapy response and modulating the immune system.
Dafna Gladman, MD, led a session on “how to set up a cohort.” In this session, speakers provided a road map for setting up a longitudinal cohort and discussed opportunities and challenges along the way. This session provided a foundation for a meeting that followed the annual meeting, the GRAPPA Research Collaborative Network meeting (held July 15-16). The RCN meeting aimed to develop a plan for a GRAPPA research network supporting collaborative research to identify biomarkers and outcomes in psoriasis and PsA. Speakers/panelists from academics and industry kicked off the meeting with a discussion of prior experiences in establishing international cohort studies. Subsequent sessions presented individual aspects of beginning a longitudinal cohort study for biomarkers, including methods for sample collection, regulatory processes, and data collected at potential sites; capturing and harmonizing clinical data for such studies; and policies for publication of RCN studies.
This year’s workshop was focused on the GRAPPA-Outcome Measures in Rheumatology (OMERACT) working group’s plan to develop a Core Outcome Measure Set, a collection of outcome measurement instruments to be used in randomized, controlled trials (RCTs) for PsA. During the plenary session, the team presented a process for the group to evaluate instruments, including assessment of match to the domain or concept of interest, feasibility, construct validity, and discrimination (including reliability and the ability to distinguish between two groups such as responders and nonresponders). Breakout groups then discussed one of the six tools being considered and voted on match to the domain of interest and feasibility for RCTs.
In a skin session, ongoing efforts to standardize and simplify the measurement of skin psoriasis in both the clinic and RCTs were presented. While the Psoriasis Area and Severity Index (PASI) is the current standard for measuring psoriasis severity and response to therapy in RCTs, the PASI is challenging for use in clinical practice. Joseph Merola, MD, presented data to support the use of the psoriasis Physician Global Assessment (PGA) x body surface area (BSA), a simpler measure than the PASI, as a potential substitute for the PASI. Updates from the International Dermatology Outcome Measures board included reporting of the psoriasis core domain set and a summary of the PsA symptoms working group’s efforts to identify patient-reported outcomes to identify and measure PsA among patients enrolled in psoriasis RCTs. April Armstrong, MD, discussed the National Psoriasis Foundation’s efforts to develop treat-to-target goals for psoriasis. Finally, Laura Coates, MBChB, PhD, presented a report on her efforts to examine a variety of psoriasis cut points for minimal disease activity and very low disease activity outcomes.
Dr. Ogdie is director of the Penn Psoriatic Arthritis Clinic at the University of Pennsylvania, Philadelphia, and is a member of the GRAPPA Steering Committee.
The agenda for this year’s Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting included sessions on juvenile psoriatic arthritis (PsA), the microbiome in psoriasis and PsA, and setting up longitudinal cohort studies. There was also a workshop to define the clinical fit and feasibility of PsA outcome measures for clinical trials and updates on several GRAPPA-associated projects.
The meeting, held July 13-15 in Amsterdam, opened with the annual trainee session. This year’s trainee session attracted more than 40 abstracts, of which 6 were selected for oral presentations on a variety of topics including outcome measure assessment, imaging, the microbiome in PsA, and T-cell subsets in synovial fluid.
The juvenile PsA session highlighted the similarities and differences between juvenile and adult PsA. For example, nearly half of children develop the arthritis prior to the skin symptoms, as opposed to adults where the vast majority develop psoriasis first.
The jPsA session also emphasized the need for efforts to better define this disease entity and to study outcomes related to it. The current International League of Associations for Rheumatology criteria for juvenile idiopathic arthritis split jPsA into other subgroups (for example, enthesitis-associated arthritis, undifferentiated arthritis, etc).
Three investigators – Matt Stoll, MD, PhD, Devy Zisman, MD, and Elizabeth Mellins, MD – also presented studies of the epidemiology of jPsA.
Among the most intriguing sessions at the GRAPPA meeting was a series of three talks by Jose Scher, MD, Hok Bing Thio, MD, PhD, and Dirk Elewaut, PhD, that introduced the audience to the complexity of the micro-organisms that call the human host “home” and the potential role in the development of inflammatory conditions, in particular psoriasis and PsA. These talks touched on the potential uses of the microbiome of the gut, skin, and oral mucosa in predicting therapy response and modulating the immune system.
Dafna Gladman, MD, led a session on “how to set up a cohort.” In this session, speakers provided a road map for setting up a longitudinal cohort and discussed opportunities and challenges along the way. This session provided a foundation for a meeting that followed the annual meeting, the GRAPPA Research Collaborative Network meeting (held July 15-16). The RCN meeting aimed to develop a plan for a GRAPPA research network supporting collaborative research to identify biomarkers and outcomes in psoriasis and PsA. Speakers/panelists from academics and industry kicked off the meeting with a discussion of prior experiences in establishing international cohort studies. Subsequent sessions presented individual aspects of beginning a longitudinal cohort study for biomarkers, including methods for sample collection, regulatory processes, and data collected at potential sites; capturing and harmonizing clinical data for such studies; and policies for publication of RCN studies.
This year’s workshop was focused on the GRAPPA-Outcome Measures in Rheumatology (OMERACT) working group’s plan to develop a Core Outcome Measure Set, a collection of outcome measurement instruments to be used in randomized, controlled trials (RCTs) for PsA. During the plenary session, the team presented a process for the group to evaluate instruments, including assessment of match to the domain or concept of interest, feasibility, construct validity, and discrimination (including reliability and the ability to distinguish between two groups such as responders and nonresponders). Breakout groups then discussed one of the six tools being considered and voted on match to the domain of interest and feasibility for RCTs.
In a skin session, ongoing efforts to standardize and simplify the measurement of skin psoriasis in both the clinic and RCTs were presented. While the Psoriasis Area and Severity Index (PASI) is the current standard for measuring psoriasis severity and response to therapy in RCTs, the PASI is challenging for use in clinical practice. Joseph Merola, MD, presented data to support the use of the psoriasis Physician Global Assessment (PGA) x body surface area (BSA), a simpler measure than the PASI, as a potential substitute for the PASI. Updates from the International Dermatology Outcome Measures board included reporting of the psoriasis core domain set and a summary of the PsA symptoms working group’s efforts to identify patient-reported outcomes to identify and measure PsA among patients enrolled in psoriasis RCTs. April Armstrong, MD, discussed the National Psoriasis Foundation’s efforts to develop treat-to-target goals for psoriasis. Finally, Laura Coates, MBChB, PhD, presented a report on her efforts to examine a variety of psoriasis cut points for minimal disease activity and very low disease activity outcomes.
Dr. Ogdie is director of the Penn Psoriatic Arthritis Clinic at the University of Pennsylvania, Philadelphia, and is a member of the GRAPPA Steering Committee.
Study finds secukinumab effective for moderate to severe scalp psoriasis
Secukinumab is a safe and effective treatment option for patients with moderate to severe scalp psoriasis, according to Dr. Jerry Bagel of the Psoriasis Treatment Center of Central New Jersey, and his associates.
After 12 weeks of treatment with 300 mg of secukinumab, administered subcutaneously, 52.9% of the 50 patients who received secukinumab achieved a 90% reduction in their Psoriasis Scalp Severity Index score, and 35.3% achieved complete clearance of scalp psoriasis. Only 2% of the 47 patients in the placebo group achieved PSSI 90, and no one achieved complete clearance, in the phase 3b study.
“These promising results demonstrate the possibility of establishing PSSI 90 as a new benchmark for scalp psoriasis treatment outcome,” the investigators noted. Secukinumab (Cosentyx) is approved for moderate to severe plaque psoriasis, active psoriatic arthritis, and in adult patients who are candidates for systemic therapy or phototherapy, and ankylosing spondylitis.
Find the study in the Journal of the American Academy of Dermatology (doi: 10.1016/j.jaad.2017.05.033).
Secukinumab is a safe and effective treatment option for patients with moderate to severe scalp psoriasis, according to Dr. Jerry Bagel of the Psoriasis Treatment Center of Central New Jersey, and his associates.
After 12 weeks of treatment with 300 mg of secukinumab, administered subcutaneously, 52.9% of the 50 patients who received secukinumab achieved a 90% reduction in their Psoriasis Scalp Severity Index score, and 35.3% achieved complete clearance of scalp psoriasis. Only 2% of the 47 patients in the placebo group achieved PSSI 90, and no one achieved complete clearance, in the phase 3b study.
“These promising results demonstrate the possibility of establishing PSSI 90 as a new benchmark for scalp psoriasis treatment outcome,” the investigators noted. Secukinumab (Cosentyx) is approved for moderate to severe plaque psoriasis, active psoriatic arthritis, and in adult patients who are candidates for systemic therapy or phototherapy, and ankylosing spondylitis.
Find the study in the Journal of the American Academy of Dermatology (doi: 10.1016/j.jaad.2017.05.033).
Secukinumab is a safe and effective treatment option for patients with moderate to severe scalp psoriasis, according to Dr. Jerry Bagel of the Psoriasis Treatment Center of Central New Jersey, and his associates.
After 12 weeks of treatment with 300 mg of secukinumab, administered subcutaneously, 52.9% of the 50 patients who received secukinumab achieved a 90% reduction in their Psoriasis Scalp Severity Index score, and 35.3% achieved complete clearance of scalp psoriasis. Only 2% of the 47 patients in the placebo group achieved PSSI 90, and no one achieved complete clearance, in the phase 3b study.
“These promising results demonstrate the possibility of establishing PSSI 90 as a new benchmark for scalp psoriasis treatment outcome,” the investigators noted. Secukinumab (Cosentyx) is approved for moderate to severe plaque psoriasis, active psoriatic arthritis, and in adult patients who are candidates for systemic therapy or phototherapy, and ankylosing spondylitis.
Find the study in the Journal of the American Academy of Dermatology (doi: 10.1016/j.jaad.2017.05.033).
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Alopecia may be permanent in one in four pediatric HSCT patients
CHICAGO – Late dermatologic manifestations in children who have received hematopoietic stem cell transplants may be more common than previously thought, according to results of a new study.
Johanna Song, MD, and her collaborators reported that, in their prospective pediatric study, 25% of patients had permanent alopecia and 16% had psoriasis, noting that late nonmalignant skin effects of hematopoietic stem cell transplantation (HSCT) have been studied primarily retrospectively, and in adults. Vitiligo and nail changes were also seen.
In a poster presentation at the World Congress of Dermatology, Dr. Song and her colleagues noted that these figures are higher than the previously reported pediatric rates of 1.7% for vitiligo and 15.6% for permanent alopecia. “Early recognition of these late effects can facilitate prompt and appropriate treatment, if desired,” they said.
The single-center, cross-sectional cohort study tracked pediatric patients over an 18-month period and included patients who were at least 1 year post allogeneic HSCT and had not relapsed. Patients who were not English speaking were excluded.
The median age of the 85 patients enrolled in the study was 13.8 years, and participants were a median of 3.6 years post transplant at the time of enrollment. The study’s analysis attempted to determine which patient, transplant, and disease factors might be associated with the late nonmalignant skin changes, according to Dr. Song, a resident dermatologist at Harvard University, Boston, and her colleagues.
Most – 52– of the patients (61.2%) had hematologic malignancies; 12 patients (14.1%) received their transplant for bone marrow failure, and 11 patients (12.5%) had immunodeficiency. Three patients (3.5%) received HSCT for other malignancies, and seven (8.2%) for nonmalignant diseases.
Diffuse hair thinning was seen in 13 (62%) of the 21 patients who had alopecia, while 11 (52%) of the patients with alopecia had an androgenetic hair loss pattern. Chronic graft versus host disease (GVHD), skin chronic GVHD, a HSCT regimen that included busulfan conditioning, and a family history of early male-pattern alopecia were all significantly associated with post-HSCT permanent alopecia (P less than .05 for all).
The patients with androgenetic alopecia may be experiencing an accelerated time course of a condition to which they are already genetically disposed, noted Dr. Song and her colleagues.
Psoriasis was commonly seen on the scalp, affecting 11 of the 14 patients with psoriasis (79%), and involved the face in five of the patients (36%). Just one patient had psoriasis elsewhere on the body. There was a nonsignificant trend towards human leukocyte antigen mismatch among patients who had psoriasis. Although “psoriasis may be a marker of persistent immune dysregulation,” the investigators said, they did not identify any associated risk factors that would point toward this mechanism in their analysis.
Twelve patients (14%) had vitiligo, with halo nevi seen in four of these patients. Children who were younger than age 10 years and those who received their transplant for primary immunodeficiency were significantly more likely to have vitiligo (P less than .05 for both). Specific possible mechanisms triggering vitiligo could include thymic dysfunction resulting in loss of self-tolerance, and donor alloreactivity against the patient’s host antigens, according to the authors.
Nail changes such as pterygium and nail pitting, ridging, or thickening were seen in just five patients, all of whom had chronic GVHD of the skin. “Nail changes are likely a result of persistent inflammation and immune dysregulation from chronic GVHD,” said Dr. Song.
These late effects “can significantly impact patients’ quality of life,” according to the authors, who called for larger studies that follow pediatric HSCT patients longitudinally, beginning before the transplant – and for more investigation into the pathogenesis of specific late effects.
Dr. Song reported no relevant conflicts of interest.
[email protected]
On Twitter @karioakes
CHICAGO – Late dermatologic manifestations in children who have received hematopoietic stem cell transplants may be more common than previously thought, according to results of a new study.
Johanna Song, MD, and her collaborators reported that, in their prospective pediatric study, 25% of patients had permanent alopecia and 16% had psoriasis, noting that late nonmalignant skin effects of hematopoietic stem cell transplantation (HSCT) have been studied primarily retrospectively, and in adults. Vitiligo and nail changes were also seen.
In a poster presentation at the World Congress of Dermatology, Dr. Song and her colleagues noted that these figures are higher than the previously reported pediatric rates of 1.7% for vitiligo and 15.6% for permanent alopecia. “Early recognition of these late effects can facilitate prompt and appropriate treatment, if desired,” they said.
The single-center, cross-sectional cohort study tracked pediatric patients over an 18-month period and included patients who were at least 1 year post allogeneic HSCT and had not relapsed. Patients who were not English speaking were excluded.
The median age of the 85 patients enrolled in the study was 13.8 years, and participants were a median of 3.6 years post transplant at the time of enrollment. The study’s analysis attempted to determine which patient, transplant, and disease factors might be associated with the late nonmalignant skin changes, according to Dr. Song, a resident dermatologist at Harvard University, Boston, and her colleagues.
Most – 52– of the patients (61.2%) had hematologic malignancies; 12 patients (14.1%) received their transplant for bone marrow failure, and 11 patients (12.5%) had immunodeficiency. Three patients (3.5%) received HSCT for other malignancies, and seven (8.2%) for nonmalignant diseases.
Diffuse hair thinning was seen in 13 (62%) of the 21 patients who had alopecia, while 11 (52%) of the patients with alopecia had an androgenetic hair loss pattern. Chronic graft versus host disease (GVHD), skin chronic GVHD, a HSCT regimen that included busulfan conditioning, and a family history of early male-pattern alopecia were all significantly associated with post-HSCT permanent alopecia (P less than .05 for all).
The patients with androgenetic alopecia may be experiencing an accelerated time course of a condition to which they are already genetically disposed, noted Dr. Song and her colleagues.
Psoriasis was commonly seen on the scalp, affecting 11 of the 14 patients with psoriasis (79%), and involved the face in five of the patients (36%). Just one patient had psoriasis elsewhere on the body. There was a nonsignificant trend towards human leukocyte antigen mismatch among patients who had psoriasis. Although “psoriasis may be a marker of persistent immune dysregulation,” the investigators said, they did not identify any associated risk factors that would point toward this mechanism in their analysis.
Twelve patients (14%) had vitiligo, with halo nevi seen in four of these patients. Children who were younger than age 10 years and those who received their transplant for primary immunodeficiency were significantly more likely to have vitiligo (P less than .05 for both). Specific possible mechanisms triggering vitiligo could include thymic dysfunction resulting in loss of self-tolerance, and donor alloreactivity against the patient’s host antigens, according to the authors.
Nail changes such as pterygium and nail pitting, ridging, or thickening were seen in just five patients, all of whom had chronic GVHD of the skin. “Nail changes are likely a result of persistent inflammation and immune dysregulation from chronic GVHD,” said Dr. Song.
These late effects “can significantly impact patients’ quality of life,” according to the authors, who called for larger studies that follow pediatric HSCT patients longitudinally, beginning before the transplant – and for more investigation into the pathogenesis of specific late effects.
Dr. Song reported no relevant conflicts of interest.
[email protected]
On Twitter @karioakes
CHICAGO – Late dermatologic manifestations in children who have received hematopoietic stem cell transplants may be more common than previously thought, according to results of a new study.
Johanna Song, MD, and her collaborators reported that, in their prospective pediatric study, 25% of patients had permanent alopecia and 16% had psoriasis, noting that late nonmalignant skin effects of hematopoietic stem cell transplantation (HSCT) have been studied primarily retrospectively, and in adults. Vitiligo and nail changes were also seen.
In a poster presentation at the World Congress of Dermatology, Dr. Song and her colleagues noted that these figures are higher than the previously reported pediatric rates of 1.7% for vitiligo and 15.6% for permanent alopecia. “Early recognition of these late effects can facilitate prompt and appropriate treatment, if desired,” they said.
The single-center, cross-sectional cohort study tracked pediatric patients over an 18-month period and included patients who were at least 1 year post allogeneic HSCT and had not relapsed. Patients who were not English speaking were excluded.
The median age of the 85 patients enrolled in the study was 13.8 years, and participants were a median of 3.6 years post transplant at the time of enrollment. The study’s analysis attempted to determine which patient, transplant, and disease factors might be associated with the late nonmalignant skin changes, according to Dr. Song, a resident dermatologist at Harvard University, Boston, and her colleagues.
Most – 52– of the patients (61.2%) had hematologic malignancies; 12 patients (14.1%) received their transplant for bone marrow failure, and 11 patients (12.5%) had immunodeficiency. Three patients (3.5%) received HSCT for other malignancies, and seven (8.2%) for nonmalignant diseases.
Diffuse hair thinning was seen in 13 (62%) of the 21 patients who had alopecia, while 11 (52%) of the patients with alopecia had an androgenetic hair loss pattern. Chronic graft versus host disease (GVHD), skin chronic GVHD, a HSCT regimen that included busulfan conditioning, and a family history of early male-pattern alopecia were all significantly associated with post-HSCT permanent alopecia (P less than .05 for all).
The patients with androgenetic alopecia may be experiencing an accelerated time course of a condition to which they are already genetically disposed, noted Dr. Song and her colleagues.
Psoriasis was commonly seen on the scalp, affecting 11 of the 14 patients with psoriasis (79%), and involved the face in five of the patients (36%). Just one patient had psoriasis elsewhere on the body. There was a nonsignificant trend towards human leukocyte antigen mismatch among patients who had psoriasis. Although “psoriasis may be a marker of persistent immune dysregulation,” the investigators said, they did not identify any associated risk factors that would point toward this mechanism in their analysis.
Twelve patients (14%) had vitiligo, with halo nevi seen in four of these patients. Children who were younger than age 10 years and those who received their transplant for primary immunodeficiency were significantly more likely to have vitiligo (P less than .05 for both). Specific possible mechanisms triggering vitiligo could include thymic dysfunction resulting in loss of self-tolerance, and donor alloreactivity against the patient’s host antigens, according to the authors.
Nail changes such as pterygium and nail pitting, ridging, or thickening were seen in just five patients, all of whom had chronic GVHD of the skin. “Nail changes are likely a result of persistent inflammation and immune dysregulation from chronic GVHD,” said Dr. Song.
These late effects “can significantly impact patients’ quality of life,” according to the authors, who called for larger studies that follow pediatric HSCT patients longitudinally, beginning before the transplant – and for more investigation into the pathogenesis of specific late effects.
Dr. Song reported no relevant conflicts of interest.
[email protected]
On Twitter @karioakes
AT WCPD 2017
Key clinical point:
Major finding: Permanent alopecia was seen in 25% of patients, and 16% had psoriasis a median of 3.6 years after transplant.
Data source: A single-center prospective study of 85 children in routine post-HSCT follow-up.
Disclosures: Dr. Song reported no conflicts of interest.
Adalimumab for Hidradenitis Suppurativa
We applaud Kimball et al1 on their report that adalimumab demonstrated clinical improvement in patients with hidradenitis suppurativa (HS) versus placebo in 2 phase 3 trials. Hidradenitis suppurativa is a chronic relapsing condition with painful subcutaneous abscesses, malodorous drainage, sinus tract formation, and scarring that typically occurs in the axillae and anogenital region. It impairs the quality of life for these patients, as evidenced by higher Dermatology Life Quality Index scores compared to psoriasis, pimples, hand rash, atopic eczema, or control.2
The exact pathogenesis of HS is unknown but likely involves a complex interaction of genetic, hormonal, immunologic, and environmental factors.3 The levels of inflammatory cytokines are elevated in HS lesions, specifically IL-1β, tumor necrosis factor α, IL-10, and CXCL9, as well as monokines from IFN-γ, IL-11, and IL-17A. Additionally, the dermis of affected regions contains IL-12– and IL-23–containing macrophages along with IL-17–producing T cells.3 These findings reveal many potential therapeutic targets for the treatment of HS.
PIONEER I and PIONEER II are similarly designed 36-week phase 3 trials of 633 patients with HS who were unresponsive to oral antibiotic treatment.1 By week 12, a significantly greater proportion of patients receiving adalimumab demonstrated clinical improvement (≥50% reduction in total abscess and nodule count) compared to placebo in both trials (PIONEER I: 41.8% vs 26.0%, P=.003; PIONEER II: 58.9% vs 27.6%, P<.001). Secondary end points (inflammatory-nodule count, pain score, and disease severity) were only achieved in PIONEER II. The difference in clinical improvement between the trials is likely due to higher baseline disease severity in the HS patients in PIONEER I versus PIONEER II. No new safety risks were reported and were in accordance with prior adalimumab trials for other diseases. Notably, 10 paradoxical psoriasislike eruptions were reported.
Adalimumab is the first and only US Food and Drug Administration–approved therapy for HS. Further understanding of the pathogenesis of HS may result in additional biologic treatments for HS. We encourage the manufacturers of other biologic therapies, such as infliximab,4 ustekinumab,5 anakinra,6 secukinumab, ixekizumab, and brodalumab, to consider conducting further clinical trials in HS to enhance the therapeutic options available for this debilitating disease.
- Kimball AB, Okun MM, Williams DA, et al. Two Phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375:422-434.
- Vinding GR, Knudsen KM, Ellervik C, et al. Self-reported skin morbidities and health-related quality of life: a population-based nested case-control study. Dermatology. 2014;228:261-268.
- Deckers IE, van der Zee HH, Prens EP. Epidemiology of hidradenitis suppurativa: prevalence, pathogenesis, and factors associated with the development of HS. Curr Dermatol Rep. 2014;3:54-60.
- Ingram JR, Woo PN, Chua SL, et al. Interventions for hidradenitis suppurativa: a Cochrane systematic review incorporating GRADE assessment of evidence quality. Br J Dermatol. 2016;174:970-978.
- Blok JL, Li K, Brodmerkel C, et al. Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum. Br J Dermatol. 2016;174:839-846.
- Tzanetakou V, Kanni T, Giatrakou S, et al. Safety and efficacy of anakinra in severe hidradenitis suppurativa: a randomized clinical trial. JAMA Dermatol. 2016;152:52-59.
We applaud Kimball et al1 on their report that adalimumab demonstrated clinical improvement in patients with hidradenitis suppurativa (HS) versus placebo in 2 phase 3 trials. Hidradenitis suppurativa is a chronic relapsing condition with painful subcutaneous abscesses, malodorous drainage, sinus tract formation, and scarring that typically occurs in the axillae and anogenital region. It impairs the quality of life for these patients, as evidenced by higher Dermatology Life Quality Index scores compared to psoriasis, pimples, hand rash, atopic eczema, or control.2
The exact pathogenesis of HS is unknown but likely involves a complex interaction of genetic, hormonal, immunologic, and environmental factors.3 The levels of inflammatory cytokines are elevated in HS lesions, specifically IL-1β, tumor necrosis factor α, IL-10, and CXCL9, as well as monokines from IFN-γ, IL-11, and IL-17A. Additionally, the dermis of affected regions contains IL-12– and IL-23–containing macrophages along with IL-17–producing T cells.3 These findings reveal many potential therapeutic targets for the treatment of HS.
PIONEER I and PIONEER II are similarly designed 36-week phase 3 trials of 633 patients with HS who were unresponsive to oral antibiotic treatment.1 By week 12, a significantly greater proportion of patients receiving adalimumab demonstrated clinical improvement (≥50% reduction in total abscess and nodule count) compared to placebo in both trials (PIONEER I: 41.8% vs 26.0%, P=.003; PIONEER II: 58.9% vs 27.6%, P<.001). Secondary end points (inflammatory-nodule count, pain score, and disease severity) were only achieved in PIONEER II. The difference in clinical improvement between the trials is likely due to higher baseline disease severity in the HS patients in PIONEER I versus PIONEER II. No new safety risks were reported and were in accordance with prior adalimumab trials for other diseases. Notably, 10 paradoxical psoriasislike eruptions were reported.
Adalimumab is the first and only US Food and Drug Administration–approved therapy for HS. Further understanding of the pathogenesis of HS may result in additional biologic treatments for HS. We encourage the manufacturers of other biologic therapies, such as infliximab,4 ustekinumab,5 anakinra,6 secukinumab, ixekizumab, and brodalumab, to consider conducting further clinical trials in HS to enhance the therapeutic options available for this debilitating disease.
We applaud Kimball et al1 on their report that adalimumab demonstrated clinical improvement in patients with hidradenitis suppurativa (HS) versus placebo in 2 phase 3 trials. Hidradenitis suppurativa is a chronic relapsing condition with painful subcutaneous abscesses, malodorous drainage, sinus tract formation, and scarring that typically occurs in the axillae and anogenital region. It impairs the quality of life for these patients, as evidenced by higher Dermatology Life Quality Index scores compared to psoriasis, pimples, hand rash, atopic eczema, or control.2
The exact pathogenesis of HS is unknown but likely involves a complex interaction of genetic, hormonal, immunologic, and environmental factors.3 The levels of inflammatory cytokines are elevated in HS lesions, specifically IL-1β, tumor necrosis factor α, IL-10, and CXCL9, as well as monokines from IFN-γ, IL-11, and IL-17A. Additionally, the dermis of affected regions contains IL-12– and IL-23–containing macrophages along with IL-17–producing T cells.3 These findings reveal many potential therapeutic targets for the treatment of HS.
PIONEER I and PIONEER II are similarly designed 36-week phase 3 trials of 633 patients with HS who were unresponsive to oral antibiotic treatment.1 By week 12, a significantly greater proportion of patients receiving adalimumab demonstrated clinical improvement (≥50% reduction in total abscess and nodule count) compared to placebo in both trials (PIONEER I: 41.8% vs 26.0%, P=.003; PIONEER II: 58.9% vs 27.6%, P<.001). Secondary end points (inflammatory-nodule count, pain score, and disease severity) were only achieved in PIONEER II. The difference in clinical improvement between the trials is likely due to higher baseline disease severity in the HS patients in PIONEER I versus PIONEER II. No new safety risks were reported and were in accordance with prior adalimumab trials for other diseases. Notably, 10 paradoxical psoriasislike eruptions were reported.
Adalimumab is the first and only US Food and Drug Administration–approved therapy for HS. Further understanding of the pathogenesis of HS may result in additional biologic treatments for HS. We encourage the manufacturers of other biologic therapies, such as infliximab,4 ustekinumab,5 anakinra,6 secukinumab, ixekizumab, and brodalumab, to consider conducting further clinical trials in HS to enhance the therapeutic options available for this debilitating disease.
- Kimball AB, Okun MM, Williams DA, et al. Two Phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375:422-434.
- Vinding GR, Knudsen KM, Ellervik C, et al. Self-reported skin morbidities and health-related quality of life: a population-based nested case-control study. Dermatology. 2014;228:261-268.
- Deckers IE, van der Zee HH, Prens EP. Epidemiology of hidradenitis suppurativa: prevalence, pathogenesis, and factors associated with the development of HS. Curr Dermatol Rep. 2014;3:54-60.
- Ingram JR, Woo PN, Chua SL, et al. Interventions for hidradenitis suppurativa: a Cochrane systematic review incorporating GRADE assessment of evidence quality. Br J Dermatol. 2016;174:970-978.
- Blok JL, Li K, Brodmerkel C, et al. Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum. Br J Dermatol. 2016;174:839-846.
- Tzanetakou V, Kanni T, Giatrakou S, et al. Safety and efficacy of anakinra in severe hidradenitis suppurativa: a randomized clinical trial. JAMA Dermatol. 2016;152:52-59.
- Kimball AB, Okun MM, Williams DA, et al. Two Phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375:422-434.
- Vinding GR, Knudsen KM, Ellervik C, et al. Self-reported skin morbidities and health-related quality of life: a population-based nested case-control study. Dermatology. 2014;228:261-268.
- Deckers IE, van der Zee HH, Prens EP. Epidemiology of hidradenitis suppurativa: prevalence, pathogenesis, and factors associated with the development of HS. Curr Dermatol Rep. 2014;3:54-60.
- Ingram JR, Woo PN, Chua SL, et al. Interventions for hidradenitis suppurativa: a Cochrane systematic review incorporating GRADE assessment of evidence quality. Br J Dermatol. 2016;174:970-978.
- Blok JL, Li K, Brodmerkel C, et al. Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum. Br J Dermatol. 2016;174:839-846.
- Tzanetakou V, Kanni T, Giatrakou S, et al. Safety and efficacy of anakinra in severe hidradenitis suppurativa: a randomized clinical trial. JAMA Dermatol. 2016;152:52-59.
First interchangeability study for an adalimumab biosimilar has begun
The VOLTAIRE-X study of a biosimilar candidate for adalimumab (Humira) for chronic plaque psoriasis has enrolled its first patient, announced Boehringer Ingelheim, the biosimilar’s developer, on July 27.
This is the first study in the United States to investigate whether a biosimilar candidate should be granted an interchangeability designation with adalimumab. The candidate, BI 695501, is up against adalimumab’s 40-mg injection.
In VOLTAIRE-X, some patients will alternate between adalimumab and BI 695501, and others will take adalimumab continuously. The study will compare the pharmacokinetics, clinical outcomes, safety, immunogenicity, and efficacy between the two groups of patients. The estimated enrollment of adult patients with moderate to severe chronic plaque psoriasis is 240, and the study is expected to conclude in July 2019.
A phase 3 study of BI 695501’s performance for rheumatoid arthritis patients, completed in 2016, demonstrated similar efficacy, safety, and immunogenicity.
The VOLTAIRE-X study of a biosimilar candidate for adalimumab (Humira) for chronic plaque psoriasis has enrolled its first patient, announced Boehringer Ingelheim, the biosimilar’s developer, on July 27.
This is the first study in the United States to investigate whether a biosimilar candidate should be granted an interchangeability designation with adalimumab. The candidate, BI 695501, is up against adalimumab’s 40-mg injection.
In VOLTAIRE-X, some patients will alternate between adalimumab and BI 695501, and others will take adalimumab continuously. The study will compare the pharmacokinetics, clinical outcomes, safety, immunogenicity, and efficacy between the two groups of patients. The estimated enrollment of adult patients with moderate to severe chronic plaque psoriasis is 240, and the study is expected to conclude in July 2019.
A phase 3 study of BI 695501’s performance for rheumatoid arthritis patients, completed in 2016, demonstrated similar efficacy, safety, and immunogenicity.
The VOLTAIRE-X study of a biosimilar candidate for adalimumab (Humira) for chronic plaque psoriasis has enrolled its first patient, announced Boehringer Ingelheim, the biosimilar’s developer, on July 27.
This is the first study in the United States to investigate whether a biosimilar candidate should be granted an interchangeability designation with adalimumab. The candidate, BI 695501, is up against adalimumab’s 40-mg injection.
In VOLTAIRE-X, some patients will alternate between adalimumab and BI 695501, and others will take adalimumab continuously. The study will compare the pharmacokinetics, clinical outcomes, safety, immunogenicity, and efficacy between the two groups of patients. The estimated enrollment of adult patients with moderate to severe chronic plaque psoriasis is 240, and the study is expected to conclude in July 2019.
A phase 3 study of BI 695501’s performance for rheumatoid arthritis patients, completed in 2016, demonstrated similar efficacy, safety, and immunogenicity.
Unresolved fatigue lingers for most PsA patients
MADRID – Fatigue is an important symptom in patients with psoriatic arthritis but often goes unaddressed when treatment only involves disease modifying drugs.
A survey of more than 1,000 patients with psoriatic arthritis (PsA) in Denmark found that more than half had moderate or severe levels of fatigue, and a principal component analysis of the sources of fatigue found three factors responsible for the majority of reported patient fatigue: chronic inflammation, chronic pain, and chronification of the PsA, Tanja S. Jørgensen, PhD, said at the European Congress of Rheumatology.
“Pain is the most important symptom in patients with psoriatic arthritis, but fatigue is second-most important. It has a huge impact on patient quality of life,” she said.
“Just treating inflammation doesn’t do it all. We need to do more, think differently, think outside the box” of relying primarily on disease-modifying antirheumatic drugs, especially biological drugs, to resolve symptoms in PsA patients. “We should not think that biologicals do it all.”
The upshot is that PsA patients may have their inflammatory markers under control with treatment but still report that they don’t feel well, have pain, are tired, and have no energy.
But Dr. Jørgensen admitted that she couldn’t say with any certainty what additional interventions might help resolve pain and fatigue in PsA patients.
“I tell them to walk and be active; I think that may help. But we don’t really know what to do,” she said in an interview.
Her study included 1,062 PsA patients enrolled during December 2013-December 2014 in the Danish DANBIO registry of patients with inflammatory arthritides who received treatment with a biological drug. These participants also agreed to both complete a painDETECT Questionnaire and to rate their fatigue on a visual analog scale.
Dr. Jørgensen and her associates designated a visual analog scale score of at least 57 out of 100 as representing moderate or severe fatigue and found that 542 (51%) of the patients had fatigue self-ratings that fell in this range. Patients with this higher fatigue level also had significantly worse PsA with significantly higher numbers of swollen and tender joints, higher painDETECT scores, and higher scores on their Health Assessment Questionnaire and their 28-joint Disease Activity Score using C-reactive protein.
When the researchers ran a principal component analysis on these data, they identified three primary factors contributing to fatigue. Chronic inflammation contributed 31% of the fatigue effect, chronification contributed 17%, and chronic pain contributed 15%, Dr. Jørgensen reported.
Dr. Jørgensen has received research support from AbbVie, Biogen, Novartis, Pfizer, Roche, and UCB.
[email protected]
On Twitter @mitchelzoler
MADRID – Fatigue is an important symptom in patients with psoriatic arthritis but often goes unaddressed when treatment only involves disease modifying drugs.
A survey of more than 1,000 patients with psoriatic arthritis (PsA) in Denmark found that more than half had moderate or severe levels of fatigue, and a principal component analysis of the sources of fatigue found three factors responsible for the majority of reported patient fatigue: chronic inflammation, chronic pain, and chronification of the PsA, Tanja S. Jørgensen, PhD, said at the European Congress of Rheumatology.
“Pain is the most important symptom in patients with psoriatic arthritis, but fatigue is second-most important. It has a huge impact on patient quality of life,” she said.
“Just treating inflammation doesn’t do it all. We need to do more, think differently, think outside the box” of relying primarily on disease-modifying antirheumatic drugs, especially biological drugs, to resolve symptoms in PsA patients. “We should not think that biologicals do it all.”
The upshot is that PsA patients may have their inflammatory markers under control with treatment but still report that they don’t feel well, have pain, are tired, and have no energy.
But Dr. Jørgensen admitted that she couldn’t say with any certainty what additional interventions might help resolve pain and fatigue in PsA patients.
“I tell them to walk and be active; I think that may help. But we don’t really know what to do,” she said in an interview.
Her study included 1,062 PsA patients enrolled during December 2013-December 2014 in the Danish DANBIO registry of patients with inflammatory arthritides who received treatment with a biological drug. These participants also agreed to both complete a painDETECT Questionnaire and to rate their fatigue on a visual analog scale.
Dr. Jørgensen and her associates designated a visual analog scale score of at least 57 out of 100 as representing moderate or severe fatigue and found that 542 (51%) of the patients had fatigue self-ratings that fell in this range. Patients with this higher fatigue level also had significantly worse PsA with significantly higher numbers of swollen and tender joints, higher painDETECT scores, and higher scores on their Health Assessment Questionnaire and their 28-joint Disease Activity Score using C-reactive protein.
When the researchers ran a principal component analysis on these data, they identified three primary factors contributing to fatigue. Chronic inflammation contributed 31% of the fatigue effect, chronification contributed 17%, and chronic pain contributed 15%, Dr. Jørgensen reported.
Dr. Jørgensen has received research support from AbbVie, Biogen, Novartis, Pfizer, Roche, and UCB.
[email protected]
On Twitter @mitchelzoler
MADRID – Fatigue is an important symptom in patients with psoriatic arthritis but often goes unaddressed when treatment only involves disease modifying drugs.
A survey of more than 1,000 patients with psoriatic arthritis (PsA) in Denmark found that more than half had moderate or severe levels of fatigue, and a principal component analysis of the sources of fatigue found three factors responsible for the majority of reported patient fatigue: chronic inflammation, chronic pain, and chronification of the PsA, Tanja S. Jørgensen, PhD, said at the European Congress of Rheumatology.
“Pain is the most important symptom in patients with psoriatic arthritis, but fatigue is second-most important. It has a huge impact on patient quality of life,” she said.
“Just treating inflammation doesn’t do it all. We need to do more, think differently, think outside the box” of relying primarily on disease-modifying antirheumatic drugs, especially biological drugs, to resolve symptoms in PsA patients. “We should not think that biologicals do it all.”
The upshot is that PsA patients may have their inflammatory markers under control with treatment but still report that they don’t feel well, have pain, are tired, and have no energy.
But Dr. Jørgensen admitted that she couldn’t say with any certainty what additional interventions might help resolve pain and fatigue in PsA patients.
“I tell them to walk and be active; I think that may help. But we don’t really know what to do,” she said in an interview.
Her study included 1,062 PsA patients enrolled during December 2013-December 2014 in the Danish DANBIO registry of patients with inflammatory arthritides who received treatment with a biological drug. These participants also agreed to both complete a painDETECT Questionnaire and to rate their fatigue on a visual analog scale.
Dr. Jørgensen and her associates designated a visual analog scale score of at least 57 out of 100 as representing moderate or severe fatigue and found that 542 (51%) of the patients had fatigue self-ratings that fell in this range. Patients with this higher fatigue level also had significantly worse PsA with significantly higher numbers of swollen and tender joints, higher painDETECT scores, and higher scores on their Health Assessment Questionnaire and their 28-joint Disease Activity Score using C-reactive protein.
When the researchers ran a principal component analysis on these data, they identified three primary factors contributing to fatigue. Chronic inflammation contributed 31% of the fatigue effect, chronification contributed 17%, and chronic pain contributed 15%, Dr. Jørgensen reported.
Dr. Jørgensen has received research support from AbbVie, Biogen, Novartis, Pfizer, Roche, and UCB.
[email protected]
On Twitter @mitchelzoler
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Visual analog scoring showed 51% of patients rated their fatigue as 57 or higher on a 0-100 scale.
Data source: A review of 1,062 Danish psoriatic arthritis patients treated with a biological drug and enrolled in the DANBIO registry
Disclosures: Dr. Jørgensen has received research support from AbbVie, Biogen, Novartis, Pfizer, Roche, and UCB.
Children with psoriasis face multitude of comorbidities
CHICAGO – Children with psoriasis face a multitude of potential problems and comorbidities, ranging from anxiety and depression to obesity and metabolic disease, so early and proactive identification is key.
“These children are more likely to engage in high-risk behavior such as use of alcohol, tobacco, and drugs – a trend that continues into adult ages,” Kelly M. Cordoro, MD, said at the World Congress for Pediatric Dermatology. “They also have a higher association with inflammatory bowel disease, among other conditions. Those of us who care for pediatric psoriasis patients are on the front lines of recognition of these potential comorbidities, which allow for, ideally, prevention and certainly, early intervention.”
Arthritis is one of the first understood comorbidities of psoriasis in adults and children, said Dr. Cordoro, a pediatric dermatologist at the University of California, San Francisco Medical Center. In children with the condition, arthritis commonly affects the hands and feet, but it can also impact larger joints such as the hips, the knees, and the back. “The prevalence range is very broad, probably between 10% and 40%,” she said. “Severe nail and distal digital psoriasis is predictive of arthritis, so we need to be thinking of that and not forgetting that children can get arthritis.”
Obesity ranks as the most well understood comorbidity of psoriasis in children. Study after study has demonstrated this association. In addition, obese children with psoriasis may also harbor components of the metabolic syndrome – hypertension, dyslipidemia, and diabetes. “They’re not as much at risk for metabolic syndrome in the absence of obesity, but there’s still a small signal,” Dr. Cordoro said. “We ask ourselves this question as clinicians: Are these pediatric patients at risk for cardiovascular and cerebrovascular disease as they get older? In other words, what is the health of a 6-year-old, obese child with severe psoriasis, who may also have other components of the metabolic syndrome, going to be like when he is 35 or 40? Are these the children who go on to have cardiovascular events as documented in adult studies of psoriasis?”
To date, several studies have identified a clear link between psoriasis and obesity, and between psoriasis and hypertension, diabetes, and dyslipidemia in certain populations. “There is a dose-response effect,” Dr. Cordoro said. “The more severe the psoriasis, the more likely the patient is to be obese, and vice versa.” In one study, researchers analyzed 409 psoriasis patients up to age 17 years in nine countries (JAMA Dermatol. 2013;149:166-76). They concluded that globally, children with psoriasis have excess adiposity and increased central adiposity regardless of psoriasis severity. The researchers used multiple measures of adiposity, not just body mass index, but also waist circumference and waist-to-height ratio. “Waist circumference and waist-to-height ratio are surrogates for central and visceral adiposity,” said Dr. Cordoro, who was involved with the study. “And central adiposity may be a more sensitive indicator of metabolic disease and cardiovascular risk than BMI [body mass index] alone.”
Another study demonstrated that high adiposity preceded psoriasis by up to 2 years in 93% of overweight or obese psoriatic children (JAMA Dermatol. 2014;150:573-4).
In a more recent analysis, researchers evaluated lipid function in 44 psoriatic children (J Invest Dermatol. 2016;136[1]:67-73). Compared with age-matched controls, children with psoriasis were found to have higher waist-to-hip ratio, higher insulin resistance, and 27% were obese. “There was no difference in fasting lipid levels but the blood profiles had atherogenic markers that are worrisome for ongoing risk for atherosclerosis, cardiovascular disease, and cerebrovascular disease,” Dr. Cordoro said.
Research among adults has demonstrated that psoriasis confers an independent risk of atherosclerosis, MI, stroke, and early cardiovascular-related mortality, the so-called “psoriatic march.” Theoretically, Dr. Cordoro said, severe psoriasis sets up a state of chronic systemic inflammation, which leads to insulin resistance, which predisposes affected individuals to endothelial dysfunction, and eventually can lead to atherosclerosis. “When atherosclerosis becomes unstable, now you’ve gone from having severe psoriasis into a situation where the chronic inflammation may have predisposed you to having a thrombotic event such as a heart attack or stroke,” she said. “Obesity replicates that same pattern. What does this all mean? Is this real or is this just a theory? We don’t know, but it’s certainly biologically plausible. It’s not been proven with long-term prospective studies, which we need.”
Dr. Cordoro went on to discuss the importance of assessing young psoriasis patients for psychiatric and emotional comorbidities, including anxiety, depression, and eating disorders. “These kids can become socially isolated, which can lead to more downstream effects: more anxiety, more depression, sometimes overeating and obesity,” she said. “It’s not only that the patient has situational anxiety or depression, the notion that ‘My skin looks terrible. I’m really depressed about it;’ it’s more than that. It turns out that the same inflammatory milieu in psoriasis lesions can be replicated in the brain inflammatory milieu in patients with depression and other psychiatric disorders. That’s fascinating to recognize that these comorbidities can be intrinsic. There’s a biological basis and not just a downstream effect.”
She advises clinicians who care for children with psoriasis to keep potential comorbidities in mind, and to make sure families understand that there can be psychiatric, emotional, and physical consequences to undertreated disease. “We do not yet know how to risk stratify these patients. At the very least, you want to identify overweight or obese children with moderate to severe disease for early intervention,” Dr. Cordoro said. “Weight loss and lifestyle interventions are the hardest goals to accomplish but are really critical. Prevention is the best strategy. We can help ourselves and help our patients by referring to obesity and nutrition experts who can not only help the child but get the entire family involved.”
In a consensus statement published online in JAMA Dermatology, a multidisciplinary panel of experts including Dr. Cordoro offer an evidence- and consensus-based approach to screening children with psoriasis, based on a review of 153 manuscripts in the medical literature. The panel recommends that all psoriasis patients 2-21 years of age should undergo annual measurements of blood pressure and BMI, and screenings for arthritis and mood disorders. “These don’t have to be formal mood disorder screens,” Dr. Cordoro said. “They can be informal questioning about anxiety and depression, like ‘How is your psoriasis impacting you? How do you feel about your psoriasis? What do you say when people ask you about your psoriasis?’ It’s also important to ask overweight patients what they’re doing to keep their weight in check. Oftentimes when you ask a question about mood or impact of disease or stigma or bullying, the child will be completely silent and either stay silent or start crying or start telling you their stories. It’s really important to ask, because it validates that their concerns are more than just about vanity but about their overall health, and that is a critical difference.”
Dr. Cordoro disclosed that she is a consultant for Pfizer and Valeant.
CHICAGO – Children with psoriasis face a multitude of potential problems and comorbidities, ranging from anxiety and depression to obesity and metabolic disease, so early and proactive identification is key.
“These children are more likely to engage in high-risk behavior such as use of alcohol, tobacco, and drugs – a trend that continues into adult ages,” Kelly M. Cordoro, MD, said at the World Congress for Pediatric Dermatology. “They also have a higher association with inflammatory bowel disease, among other conditions. Those of us who care for pediatric psoriasis patients are on the front lines of recognition of these potential comorbidities, which allow for, ideally, prevention and certainly, early intervention.”
Arthritis is one of the first understood comorbidities of psoriasis in adults and children, said Dr. Cordoro, a pediatric dermatologist at the University of California, San Francisco Medical Center. In children with the condition, arthritis commonly affects the hands and feet, but it can also impact larger joints such as the hips, the knees, and the back. “The prevalence range is very broad, probably between 10% and 40%,” she said. “Severe nail and distal digital psoriasis is predictive of arthritis, so we need to be thinking of that and not forgetting that children can get arthritis.”
Obesity ranks as the most well understood comorbidity of psoriasis in children. Study after study has demonstrated this association. In addition, obese children with psoriasis may also harbor components of the metabolic syndrome – hypertension, dyslipidemia, and diabetes. “They’re not as much at risk for metabolic syndrome in the absence of obesity, but there’s still a small signal,” Dr. Cordoro said. “We ask ourselves this question as clinicians: Are these pediatric patients at risk for cardiovascular and cerebrovascular disease as they get older? In other words, what is the health of a 6-year-old, obese child with severe psoriasis, who may also have other components of the metabolic syndrome, going to be like when he is 35 or 40? Are these the children who go on to have cardiovascular events as documented in adult studies of psoriasis?”
To date, several studies have identified a clear link between psoriasis and obesity, and between psoriasis and hypertension, diabetes, and dyslipidemia in certain populations. “There is a dose-response effect,” Dr. Cordoro said. “The more severe the psoriasis, the more likely the patient is to be obese, and vice versa.” In one study, researchers analyzed 409 psoriasis patients up to age 17 years in nine countries (JAMA Dermatol. 2013;149:166-76). They concluded that globally, children with psoriasis have excess adiposity and increased central adiposity regardless of psoriasis severity. The researchers used multiple measures of adiposity, not just body mass index, but also waist circumference and waist-to-height ratio. “Waist circumference and waist-to-height ratio are surrogates for central and visceral adiposity,” said Dr. Cordoro, who was involved with the study. “And central adiposity may be a more sensitive indicator of metabolic disease and cardiovascular risk than BMI [body mass index] alone.”
Another study demonstrated that high adiposity preceded psoriasis by up to 2 years in 93% of overweight or obese psoriatic children (JAMA Dermatol. 2014;150:573-4).
In a more recent analysis, researchers evaluated lipid function in 44 psoriatic children (J Invest Dermatol. 2016;136[1]:67-73). Compared with age-matched controls, children with psoriasis were found to have higher waist-to-hip ratio, higher insulin resistance, and 27% were obese. “There was no difference in fasting lipid levels but the blood profiles had atherogenic markers that are worrisome for ongoing risk for atherosclerosis, cardiovascular disease, and cerebrovascular disease,” Dr. Cordoro said.
Research among adults has demonstrated that psoriasis confers an independent risk of atherosclerosis, MI, stroke, and early cardiovascular-related mortality, the so-called “psoriatic march.” Theoretically, Dr. Cordoro said, severe psoriasis sets up a state of chronic systemic inflammation, which leads to insulin resistance, which predisposes affected individuals to endothelial dysfunction, and eventually can lead to atherosclerosis. “When atherosclerosis becomes unstable, now you’ve gone from having severe psoriasis into a situation where the chronic inflammation may have predisposed you to having a thrombotic event such as a heart attack or stroke,” she said. “Obesity replicates that same pattern. What does this all mean? Is this real or is this just a theory? We don’t know, but it’s certainly biologically plausible. It’s not been proven with long-term prospective studies, which we need.”
Dr. Cordoro went on to discuss the importance of assessing young psoriasis patients for psychiatric and emotional comorbidities, including anxiety, depression, and eating disorders. “These kids can become socially isolated, which can lead to more downstream effects: more anxiety, more depression, sometimes overeating and obesity,” she said. “It’s not only that the patient has situational anxiety or depression, the notion that ‘My skin looks terrible. I’m really depressed about it;’ it’s more than that. It turns out that the same inflammatory milieu in psoriasis lesions can be replicated in the brain inflammatory milieu in patients with depression and other psychiatric disorders. That’s fascinating to recognize that these comorbidities can be intrinsic. There’s a biological basis and not just a downstream effect.”
She advises clinicians who care for children with psoriasis to keep potential comorbidities in mind, and to make sure families understand that there can be psychiatric, emotional, and physical consequences to undertreated disease. “We do not yet know how to risk stratify these patients. At the very least, you want to identify overweight or obese children with moderate to severe disease for early intervention,” Dr. Cordoro said. “Weight loss and lifestyle interventions are the hardest goals to accomplish but are really critical. Prevention is the best strategy. We can help ourselves and help our patients by referring to obesity and nutrition experts who can not only help the child but get the entire family involved.”
In a consensus statement published online in JAMA Dermatology, a multidisciplinary panel of experts including Dr. Cordoro offer an evidence- and consensus-based approach to screening children with psoriasis, based on a review of 153 manuscripts in the medical literature. The panel recommends that all psoriasis patients 2-21 years of age should undergo annual measurements of blood pressure and BMI, and screenings for arthritis and mood disorders. “These don’t have to be formal mood disorder screens,” Dr. Cordoro said. “They can be informal questioning about anxiety and depression, like ‘How is your psoriasis impacting you? How do you feel about your psoriasis? What do you say when people ask you about your psoriasis?’ It’s also important to ask overweight patients what they’re doing to keep their weight in check. Oftentimes when you ask a question about mood or impact of disease or stigma or bullying, the child will be completely silent and either stay silent or start crying or start telling you their stories. It’s really important to ask, because it validates that their concerns are more than just about vanity but about their overall health, and that is a critical difference.”
Dr. Cordoro disclosed that she is a consultant for Pfizer and Valeant.
CHICAGO – Children with psoriasis face a multitude of potential problems and comorbidities, ranging from anxiety and depression to obesity and metabolic disease, so early and proactive identification is key.
“These children are more likely to engage in high-risk behavior such as use of alcohol, tobacco, and drugs – a trend that continues into adult ages,” Kelly M. Cordoro, MD, said at the World Congress for Pediatric Dermatology. “They also have a higher association with inflammatory bowel disease, among other conditions. Those of us who care for pediatric psoriasis patients are on the front lines of recognition of these potential comorbidities, which allow for, ideally, prevention and certainly, early intervention.”
Arthritis is one of the first understood comorbidities of psoriasis in adults and children, said Dr. Cordoro, a pediatric dermatologist at the University of California, San Francisco Medical Center. In children with the condition, arthritis commonly affects the hands and feet, but it can also impact larger joints such as the hips, the knees, and the back. “The prevalence range is very broad, probably between 10% and 40%,” she said. “Severe nail and distal digital psoriasis is predictive of arthritis, so we need to be thinking of that and not forgetting that children can get arthritis.”
Obesity ranks as the most well understood comorbidity of psoriasis in children. Study after study has demonstrated this association. In addition, obese children with psoriasis may also harbor components of the metabolic syndrome – hypertension, dyslipidemia, and diabetes. “They’re not as much at risk for metabolic syndrome in the absence of obesity, but there’s still a small signal,” Dr. Cordoro said. “We ask ourselves this question as clinicians: Are these pediatric patients at risk for cardiovascular and cerebrovascular disease as they get older? In other words, what is the health of a 6-year-old, obese child with severe psoriasis, who may also have other components of the metabolic syndrome, going to be like when he is 35 or 40? Are these the children who go on to have cardiovascular events as documented in adult studies of psoriasis?”
To date, several studies have identified a clear link between psoriasis and obesity, and between psoriasis and hypertension, diabetes, and dyslipidemia in certain populations. “There is a dose-response effect,” Dr. Cordoro said. “The more severe the psoriasis, the more likely the patient is to be obese, and vice versa.” In one study, researchers analyzed 409 psoriasis patients up to age 17 years in nine countries (JAMA Dermatol. 2013;149:166-76). They concluded that globally, children with psoriasis have excess adiposity and increased central adiposity regardless of psoriasis severity. The researchers used multiple measures of adiposity, not just body mass index, but also waist circumference and waist-to-height ratio. “Waist circumference and waist-to-height ratio are surrogates for central and visceral adiposity,” said Dr. Cordoro, who was involved with the study. “And central adiposity may be a more sensitive indicator of metabolic disease and cardiovascular risk than BMI [body mass index] alone.”
Another study demonstrated that high adiposity preceded psoriasis by up to 2 years in 93% of overweight or obese psoriatic children (JAMA Dermatol. 2014;150:573-4).
In a more recent analysis, researchers evaluated lipid function in 44 psoriatic children (J Invest Dermatol. 2016;136[1]:67-73). Compared with age-matched controls, children with psoriasis were found to have higher waist-to-hip ratio, higher insulin resistance, and 27% were obese. “There was no difference in fasting lipid levels but the blood profiles had atherogenic markers that are worrisome for ongoing risk for atherosclerosis, cardiovascular disease, and cerebrovascular disease,” Dr. Cordoro said.
Research among adults has demonstrated that psoriasis confers an independent risk of atherosclerosis, MI, stroke, and early cardiovascular-related mortality, the so-called “psoriatic march.” Theoretically, Dr. Cordoro said, severe psoriasis sets up a state of chronic systemic inflammation, which leads to insulin resistance, which predisposes affected individuals to endothelial dysfunction, and eventually can lead to atherosclerosis. “When atherosclerosis becomes unstable, now you’ve gone from having severe psoriasis into a situation where the chronic inflammation may have predisposed you to having a thrombotic event such as a heart attack or stroke,” she said. “Obesity replicates that same pattern. What does this all mean? Is this real or is this just a theory? We don’t know, but it’s certainly biologically plausible. It’s not been proven with long-term prospective studies, which we need.”
Dr. Cordoro went on to discuss the importance of assessing young psoriasis patients for psychiatric and emotional comorbidities, including anxiety, depression, and eating disorders. “These kids can become socially isolated, which can lead to more downstream effects: more anxiety, more depression, sometimes overeating and obesity,” she said. “It’s not only that the patient has situational anxiety or depression, the notion that ‘My skin looks terrible. I’m really depressed about it;’ it’s more than that. It turns out that the same inflammatory milieu in psoriasis lesions can be replicated in the brain inflammatory milieu in patients with depression and other psychiatric disorders. That’s fascinating to recognize that these comorbidities can be intrinsic. There’s a biological basis and not just a downstream effect.”
She advises clinicians who care for children with psoriasis to keep potential comorbidities in mind, and to make sure families understand that there can be psychiatric, emotional, and physical consequences to undertreated disease. “We do not yet know how to risk stratify these patients. At the very least, you want to identify overweight or obese children with moderate to severe disease for early intervention,” Dr. Cordoro said. “Weight loss and lifestyle interventions are the hardest goals to accomplish but are really critical. Prevention is the best strategy. We can help ourselves and help our patients by referring to obesity and nutrition experts who can not only help the child but get the entire family involved.”
In a consensus statement published online in JAMA Dermatology, a multidisciplinary panel of experts including Dr. Cordoro offer an evidence- and consensus-based approach to screening children with psoriasis, based on a review of 153 manuscripts in the medical literature. The panel recommends that all psoriasis patients 2-21 years of age should undergo annual measurements of blood pressure and BMI, and screenings for arthritis and mood disorders. “These don’t have to be formal mood disorder screens,” Dr. Cordoro said. “They can be informal questioning about anxiety and depression, like ‘How is your psoriasis impacting you? How do you feel about your psoriasis? What do you say when people ask you about your psoriasis?’ It’s also important to ask overweight patients what they’re doing to keep their weight in check. Oftentimes when you ask a question about mood or impact of disease or stigma or bullying, the child will be completely silent and either stay silent or start crying or start telling you their stories. It’s really important to ask, because it validates that their concerns are more than just about vanity but about their overall health, and that is a critical difference.”
Dr. Cordoro disclosed that she is a consultant for Pfizer and Valeant.
AT WCPD 2017