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Doug Brunk is a San Diego-based award-winning reporter who began covering health care in 1991. Before joining the company, he wrote for the health sciences division of Columbia University and was an associate editor at Contemporary Long Term Care magazine when it won a Jesse H. Neal Award. His work has been syndicated by the Los Angeles Times and he is the author of two books related to the University of Kentucky Wildcats men's basketball program. Doug has a master’s degree in magazine journalism from the S.I. Newhouse School of Public Communications at Syracuse University. Follow him on Twitter @dougbrunk.
Autoinflammatory diseases ‘not so rare after all,’ expert says
Not long ago, after all.
“Patients with autoinflammatory diseases are all around us, but many go several years without a diagnosis,” Dr. Dissanayake, a rheumatologist at the Autoinflammatory Disease Clinic at the Hospital for Sick Children, Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “The median time to diagnosis has been estimated to be between 2.5 and 5 years. You can imagine that this type of delay can lead to significant issues, not only with quality of life but also morbidity due to unchecked inflammation that can cause organ damage, and in the most severe cases, can result in an early death.”
Effective treatment options such as biologic medications, however, can prevent these negative sequelae if the disease is recognized early. “Dermatologists are in a unique position because they will often be the first specialist to see these patients and therefore make the diagnosis early on and really alter the lives of these patients,” he said.
While it’s common to classify autoinflammatory diseases by presenting features, such as age of onset, associated symptoms, family history/ethnicity, and triggers/alleviating factors for episodes, Dr. Dissanayake prefers to classify them into one of three groups based on pathophysiology, the first being inflammasomopathies. “When activated, an inflammasome is responsible for processing cytokines from the [interleukin]-1 family from the pro form to the active form,” he explained. As a result, if there is dysregulation and overactivity of the inflammasome, there is excessive production of cytokines like IL-1 beta and IL-18 driving the disease.
Clinical characteristics include fevers and organ involvement, notably abdominal pain, nonvasculitic rashes, uveitis, arthritis, elevated white blood cell count/neutrophils, and highly elevated inflammatory markers. Potential treatments include IL-1 blockers.
The second category of autoinflammatory diseases are the interferonopathies, which are caused by overactivity of the antiviral side of the innate immune system. “For example, if you have overactivity of a sensor for a nucleic acid in your cytosol, the cell misinterprets this as a viral infection and will turn on type 1 interferon production,” said Dr. Dissanayake, who is also an assistant professor of pediatrics at the University of Toronto. “As a result, if you have dysregulation of these pathways, you will get excessive type 1 interferon that contributes to your disease manifestations.” Clinical characteristics include fevers and organ involvement, notably vasculitic rashes, interstitial lung disease, and intracranial calcifications. Inflammatory markers may not be as elevated, and autoantibodies may be present. Janus kinase inhibitors are a potential treatment, he said.
The third category of autoinflammatory diseases are the NF-kappaBopathies, which are caused by overactivity of the NF-kappaB signaling pathway. Clinical characteristics can include fevers with organ involvement that can be highly variable but may include mucocutaneous lesions or granulomatous disease as potential clues. Treatment options depend on the pathway that is involved but tumor necrosis factor blockers often play a role because of the importance of NF-KB in this signaling pathway.
From a skin perspective, most of the rashes Dr. Dissanayake and colleagues see in the rheumatology clinic consist of nonspecific dermohypodermatitis: macules, papules, patches, or plaques. The most common monogenic autoinflammatory disease is Familial Mediterranean Fever syndrome, which “commonly presents as an erysipelas-like rash of the lower extremities, typically below the knee, often over the malleolus,” he said.
Other monogenic autoinflammatory diseases with similar rashes include TNF receptor–associated periodic syndrome, Hyper-IgD syndrome, and systemic juvenile idiopathic arthritis.
Other patients present with urticarial rashes, most commonly cryopyrin-associated periodic syndrome (CAPS). “This is a neutrophilic urticaria, so it tends not to be pruritic and can actually sometimes be tender,” he said. “It also tends not to be as transient as your typical urticaria.” Urticarial rashes can also appear with NLRP12-associated autoinflammatory syndrome (familial cold autoinflammatory syndrome–2), PLCgamma2-associated antibody deficiency and immune dysregulation, and Schnitzler syndrome (monoclonal IgM gammopathy).
Patients can also present with pyogenic or pustular lesions, which can appear with pyoderma gangrenosum–related diseases, such as pyogenic arthritis, pyoderma gangrenosum, arthritis (PAPA) syndrome; pyrin-associated inflammation with neutrophilic dermatosis; deficiency of the IL-1 receptor antagonist; deficiency of IL-36 receptor antagonist; and Majeed syndrome, a mutation in the LPIN2 gene.
The mucocutaneous system can also be affected in autoinflammatory diseases, often presenting with symptoms such as periodic fever, aphthous stomatitis, and pharyngitis. Cervical adenitis syndrome is the most common autoinflammatory disease in childhood and can present with aphthous stomatitis, he said, while Behcet’s disease typically presents with oral and genital ulcers. “More recently, monogenic forms of Behcet’s disease have been described, with haploinsufficiency of A20 and RelA, which are both part of the NF-KB pathway,” he said.
Finally, the presence of vasculitic lesions often suggest interferonopathies such as STING-associated vasculopathy in infancy, proteasome-associated autoinflammatory syndrome and deficiency of adenosine deaminase 2.
Dr. Dissanayake noted that dermatologists should suspect an autoimmune disease if a patient has recurrent fevers, evidence of systemic inflammation on blood work, and if multiple organ systems are involved, especially the lungs, gut, joints, CNS system, and eyes. “Many of these patients have episodic and stereotypical attacks,” he said.
“One of the tools we use in the autoinflammatory clinic is to have patients and families keep a symptom diary where they track the dates of the various symptoms. We can review this during their appointment and try to come up with a diagnosis based on the pattern,” he said.
Since many of these diseases are due to a single gene defect, if there’s any evidence to suggest a monogenic cause, consider an autoinflammatory disease, he added. “If there’s a family history, if there’s consanguinity, or if there’s early age of onset – these may all lead you to think about monogenic autoinflammatory disease.”
During a question-and-answer session, a meeting attendee asked what type of workup he recommends when an autoinflammatory syndrome is suspected. “It partially depends on what organ systems you suspect to be involved,” Dr. Dissanayake said. “As a routine baseline, typically what we would check is CBC and differential, [erythrocyte sedimentation rate] and [C-reactive protein], and we screen for liver transaminases and creatinine to check for liver and kidney issues. A serum albumin will also tell you if the patient is hypoalbuminemic, that there’s been some chronic inflammation and they’re starting to leak the protein out. It’s good to check blood work during the flare and off the flare, to get a sense of the persistence of that inflammation.”
Dr. Dissanayake disclosed that he has received research finding from Gilead Sciences and speaker fees from Novartis.
*This story was updated on 9/20/2021.
Not long ago, after all.
“Patients with autoinflammatory diseases are all around us, but many go several years without a diagnosis,” Dr. Dissanayake, a rheumatologist at the Autoinflammatory Disease Clinic at the Hospital for Sick Children, Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “The median time to diagnosis has been estimated to be between 2.5 and 5 years. You can imagine that this type of delay can lead to significant issues, not only with quality of life but also morbidity due to unchecked inflammation that can cause organ damage, and in the most severe cases, can result in an early death.”
Effective treatment options such as biologic medications, however, can prevent these negative sequelae if the disease is recognized early. “Dermatologists are in a unique position because they will often be the first specialist to see these patients and therefore make the diagnosis early on and really alter the lives of these patients,” he said.
While it’s common to classify autoinflammatory diseases by presenting features, such as age of onset, associated symptoms, family history/ethnicity, and triggers/alleviating factors for episodes, Dr. Dissanayake prefers to classify them into one of three groups based on pathophysiology, the first being inflammasomopathies. “When activated, an inflammasome is responsible for processing cytokines from the [interleukin]-1 family from the pro form to the active form,” he explained. As a result, if there is dysregulation and overactivity of the inflammasome, there is excessive production of cytokines like IL-1 beta and IL-18 driving the disease.
Clinical characteristics include fevers and organ involvement, notably abdominal pain, nonvasculitic rashes, uveitis, arthritis, elevated white blood cell count/neutrophils, and highly elevated inflammatory markers. Potential treatments include IL-1 blockers.
The second category of autoinflammatory diseases are the interferonopathies, which are caused by overactivity of the antiviral side of the innate immune system. “For example, if you have overactivity of a sensor for a nucleic acid in your cytosol, the cell misinterprets this as a viral infection and will turn on type 1 interferon production,” said Dr. Dissanayake, who is also an assistant professor of pediatrics at the University of Toronto. “As a result, if you have dysregulation of these pathways, you will get excessive type 1 interferon that contributes to your disease manifestations.” Clinical characteristics include fevers and organ involvement, notably vasculitic rashes, interstitial lung disease, and intracranial calcifications. Inflammatory markers may not be as elevated, and autoantibodies may be present. Janus kinase inhibitors are a potential treatment, he said.
The third category of autoinflammatory diseases are the NF-kappaBopathies, which are caused by overactivity of the NF-kappaB signaling pathway. Clinical characteristics can include fevers with organ involvement that can be highly variable but may include mucocutaneous lesions or granulomatous disease as potential clues. Treatment options depend on the pathway that is involved but tumor necrosis factor blockers often play a role because of the importance of NF-KB in this signaling pathway.
From a skin perspective, most of the rashes Dr. Dissanayake and colleagues see in the rheumatology clinic consist of nonspecific dermohypodermatitis: macules, papules, patches, or plaques. The most common monogenic autoinflammatory disease is Familial Mediterranean Fever syndrome, which “commonly presents as an erysipelas-like rash of the lower extremities, typically below the knee, often over the malleolus,” he said.
Other monogenic autoinflammatory diseases with similar rashes include TNF receptor–associated periodic syndrome, Hyper-IgD syndrome, and systemic juvenile idiopathic arthritis.
Other patients present with urticarial rashes, most commonly cryopyrin-associated periodic syndrome (CAPS). “This is a neutrophilic urticaria, so it tends not to be pruritic and can actually sometimes be tender,” he said. “It also tends not to be as transient as your typical urticaria.” Urticarial rashes can also appear with NLRP12-associated autoinflammatory syndrome (familial cold autoinflammatory syndrome–2), PLCgamma2-associated antibody deficiency and immune dysregulation, and Schnitzler syndrome (monoclonal IgM gammopathy).
Patients can also present with pyogenic or pustular lesions, which can appear with pyoderma gangrenosum–related diseases, such as pyogenic arthritis, pyoderma gangrenosum, arthritis (PAPA) syndrome; pyrin-associated inflammation with neutrophilic dermatosis; deficiency of the IL-1 receptor antagonist; deficiency of IL-36 receptor antagonist; and Majeed syndrome, a mutation in the LPIN2 gene.
The mucocutaneous system can also be affected in autoinflammatory diseases, often presenting with symptoms such as periodic fever, aphthous stomatitis, and pharyngitis. Cervical adenitis syndrome is the most common autoinflammatory disease in childhood and can present with aphthous stomatitis, he said, while Behcet’s disease typically presents with oral and genital ulcers. “More recently, monogenic forms of Behcet’s disease have been described, with haploinsufficiency of A20 and RelA, which are both part of the NF-KB pathway,” he said.
Finally, the presence of vasculitic lesions often suggest interferonopathies such as STING-associated vasculopathy in infancy, proteasome-associated autoinflammatory syndrome and deficiency of adenosine deaminase 2.
Dr. Dissanayake noted that dermatologists should suspect an autoimmune disease if a patient has recurrent fevers, evidence of systemic inflammation on blood work, and if multiple organ systems are involved, especially the lungs, gut, joints, CNS system, and eyes. “Many of these patients have episodic and stereotypical attacks,” he said.
“One of the tools we use in the autoinflammatory clinic is to have patients and families keep a symptom diary where they track the dates of the various symptoms. We can review this during their appointment and try to come up with a diagnosis based on the pattern,” he said.
Since many of these diseases are due to a single gene defect, if there’s any evidence to suggest a monogenic cause, consider an autoinflammatory disease, he added. “If there’s a family history, if there’s consanguinity, or if there’s early age of onset – these may all lead you to think about monogenic autoinflammatory disease.”
During a question-and-answer session, a meeting attendee asked what type of workup he recommends when an autoinflammatory syndrome is suspected. “It partially depends on what organ systems you suspect to be involved,” Dr. Dissanayake said. “As a routine baseline, typically what we would check is CBC and differential, [erythrocyte sedimentation rate] and [C-reactive protein], and we screen for liver transaminases and creatinine to check for liver and kidney issues. A serum albumin will also tell you if the patient is hypoalbuminemic, that there’s been some chronic inflammation and they’re starting to leak the protein out. It’s good to check blood work during the flare and off the flare, to get a sense of the persistence of that inflammation.”
Dr. Dissanayake disclosed that he has received research finding from Gilead Sciences and speaker fees from Novartis.
*This story was updated on 9/20/2021.
Not long ago, after all.
“Patients with autoinflammatory diseases are all around us, but many go several years without a diagnosis,” Dr. Dissanayake, a rheumatologist at the Autoinflammatory Disease Clinic at the Hospital for Sick Children, Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “The median time to diagnosis has been estimated to be between 2.5 and 5 years. You can imagine that this type of delay can lead to significant issues, not only with quality of life but also morbidity due to unchecked inflammation that can cause organ damage, and in the most severe cases, can result in an early death.”
Effective treatment options such as biologic medications, however, can prevent these negative sequelae if the disease is recognized early. “Dermatologists are in a unique position because they will often be the first specialist to see these patients and therefore make the diagnosis early on and really alter the lives of these patients,” he said.
While it’s common to classify autoinflammatory diseases by presenting features, such as age of onset, associated symptoms, family history/ethnicity, and triggers/alleviating factors for episodes, Dr. Dissanayake prefers to classify them into one of three groups based on pathophysiology, the first being inflammasomopathies. “When activated, an inflammasome is responsible for processing cytokines from the [interleukin]-1 family from the pro form to the active form,” he explained. As a result, if there is dysregulation and overactivity of the inflammasome, there is excessive production of cytokines like IL-1 beta and IL-18 driving the disease.
Clinical characteristics include fevers and organ involvement, notably abdominal pain, nonvasculitic rashes, uveitis, arthritis, elevated white blood cell count/neutrophils, and highly elevated inflammatory markers. Potential treatments include IL-1 blockers.
The second category of autoinflammatory diseases are the interferonopathies, which are caused by overactivity of the antiviral side of the innate immune system. “For example, if you have overactivity of a sensor for a nucleic acid in your cytosol, the cell misinterprets this as a viral infection and will turn on type 1 interferon production,” said Dr. Dissanayake, who is also an assistant professor of pediatrics at the University of Toronto. “As a result, if you have dysregulation of these pathways, you will get excessive type 1 interferon that contributes to your disease manifestations.” Clinical characteristics include fevers and organ involvement, notably vasculitic rashes, interstitial lung disease, and intracranial calcifications. Inflammatory markers may not be as elevated, and autoantibodies may be present. Janus kinase inhibitors are a potential treatment, he said.
The third category of autoinflammatory diseases are the NF-kappaBopathies, which are caused by overactivity of the NF-kappaB signaling pathway. Clinical characteristics can include fevers with organ involvement that can be highly variable but may include mucocutaneous lesions or granulomatous disease as potential clues. Treatment options depend on the pathway that is involved but tumor necrosis factor blockers often play a role because of the importance of NF-KB in this signaling pathway.
From a skin perspective, most of the rashes Dr. Dissanayake and colleagues see in the rheumatology clinic consist of nonspecific dermohypodermatitis: macules, papules, patches, or plaques. The most common monogenic autoinflammatory disease is Familial Mediterranean Fever syndrome, which “commonly presents as an erysipelas-like rash of the lower extremities, typically below the knee, often over the malleolus,” he said.
Other monogenic autoinflammatory diseases with similar rashes include TNF receptor–associated periodic syndrome, Hyper-IgD syndrome, and systemic juvenile idiopathic arthritis.
Other patients present with urticarial rashes, most commonly cryopyrin-associated periodic syndrome (CAPS). “This is a neutrophilic urticaria, so it tends not to be pruritic and can actually sometimes be tender,” he said. “It also tends not to be as transient as your typical urticaria.” Urticarial rashes can also appear with NLRP12-associated autoinflammatory syndrome (familial cold autoinflammatory syndrome–2), PLCgamma2-associated antibody deficiency and immune dysregulation, and Schnitzler syndrome (monoclonal IgM gammopathy).
Patients can also present with pyogenic or pustular lesions, which can appear with pyoderma gangrenosum–related diseases, such as pyogenic arthritis, pyoderma gangrenosum, arthritis (PAPA) syndrome; pyrin-associated inflammation with neutrophilic dermatosis; deficiency of the IL-1 receptor antagonist; deficiency of IL-36 receptor antagonist; and Majeed syndrome, a mutation in the LPIN2 gene.
The mucocutaneous system can also be affected in autoinflammatory diseases, often presenting with symptoms such as periodic fever, aphthous stomatitis, and pharyngitis. Cervical adenitis syndrome is the most common autoinflammatory disease in childhood and can present with aphthous stomatitis, he said, while Behcet’s disease typically presents with oral and genital ulcers. “More recently, monogenic forms of Behcet’s disease have been described, with haploinsufficiency of A20 and RelA, which are both part of the NF-KB pathway,” he said.
Finally, the presence of vasculitic lesions often suggest interferonopathies such as STING-associated vasculopathy in infancy, proteasome-associated autoinflammatory syndrome and deficiency of adenosine deaminase 2.
Dr. Dissanayake noted that dermatologists should suspect an autoimmune disease if a patient has recurrent fevers, evidence of systemic inflammation on blood work, and if multiple organ systems are involved, especially the lungs, gut, joints, CNS system, and eyes. “Many of these patients have episodic and stereotypical attacks,” he said.
“One of the tools we use in the autoinflammatory clinic is to have patients and families keep a symptom diary where they track the dates of the various symptoms. We can review this during their appointment and try to come up with a diagnosis based on the pattern,” he said.
Since many of these diseases are due to a single gene defect, if there’s any evidence to suggest a monogenic cause, consider an autoinflammatory disease, he added. “If there’s a family history, if there’s consanguinity, or if there’s early age of onset – these may all lead you to think about monogenic autoinflammatory disease.”
During a question-and-answer session, a meeting attendee asked what type of workup he recommends when an autoinflammatory syndrome is suspected. “It partially depends on what organ systems you suspect to be involved,” Dr. Dissanayake said. “As a routine baseline, typically what we would check is CBC and differential, [erythrocyte sedimentation rate] and [C-reactive protein], and we screen for liver transaminases and creatinine to check for liver and kidney issues. A serum albumin will also tell you if the patient is hypoalbuminemic, that there’s been some chronic inflammation and they’re starting to leak the protein out. It’s good to check blood work during the flare and off the flare, to get a sense of the persistence of that inflammation.”
Dr. Dissanayake disclosed that he has received research finding from Gilead Sciences and speaker fees from Novartis.
*This story was updated on 9/20/2021.
FROM SPD 2021
Expert proposes rethinking the classification of SJS/TEN
In the opinion of Neil H. Shear, MD, a stepwise approach is the best way to diagnose possible drug-induced skin disease and determine the root cause.
“Often, we need to think of more than one cause,” he said during the annual meeting of the Society for Pediatric Dermatology. “It could be drug X. It could be drug Y. It could be contrast media. We must think broadly and pay special attention to skin of color, overlapping syndromes, and the changing diagnostic assessment over time.”
His suggested diagnostic triangle includes appearance of the rash or lesion(s), systemic impact, and histology. “The first is the appearance,” said Dr. Shear, professor emeritus of dermatology, clinical pharmacology and toxicology, and medicine at the University of Toronto. “Is it exanthem? Is it blistering? Don’t just say drug ‘rash.’ That doesn’t work. You need to know if there are systemic features, and sometimes histologic information can change your approach or diagnosis, but not as often as one might think,” he said, noting that, in his view, the two main factors are appearance and systemic impact.
The presence of fever is a hallmark of systemic problems, he continued, “so if you see fever, you know you’re probably going to be dealing with a complex reaction, so we need to know the morphology.” Consider whether it is simple exanthem (a mild, uncomplicated rash) or complex exanthem (drug rash with eosinophilia and systemic symptoms or fever, malaise, and adenopathy).
As for other morphologies, urticarial lesions could be urticaria or a serum sickness-like reaction, pustular lesions could be acneiform or acute generalized exanthematous pustulosis, while
Dr. Shear considers SJS/TEN as a spectrum of blistering disease, “because there’s not a single diagnosis,” he said. “There’s a spectrum, if you will, depending on how advanced people are in their disease.” He coauthored a 1991 report describing eight cases of mycoplasma and Stevens-Johnson syndrome. “I was surprised at how long that stood up as about the only paper in that area,” he said. “But there’s much more happening now with a proliferation of terms,” he added, referring to MIRM (Mycoplasma pneumonia–induced rash and mucositis), RIME (reactive infectious mucocutaneous eruption); and Fuchs syndrome, or SJS without skin lesions.
What was not appreciated in the early classification of SJS, he continued, was a “side basket” of bullous erythema multiforme. “We didn’t know what to call it,” he said. “At one point we called it bullous erythema multiforme. At another point we called it erythema multiforme major. We just didn’t know what it was.”
The appearance and systemic effects of SJS comprise what he termed SJS type 2 – or the early stages of TEN. Taken together, he refers to these two conditions as TEN Spectrum, or TENS. “One of the traps is that TENS can look like varicella, and vice versa, especially in very dark brown or black skin,” Dr. Shear said. “You have to be careful. A biopsy might be worthwhile. Acute lupus has the pathology of TENS but the patients are not as systemically ill as true TENS.”
In 2011, Japanese researchers reported on 38 cases of SJS associated with M. pneumoniae, and 78 cases of drug-induced SJS. They found that 66% of adult patients with M. pneumoniae–associated SJS developed mucocutaneous lesions and fever/respiratory symptoms on the same day, mostly shortness of breath and cough. In contrast, most of the patients aged under 20 years developed fever/respiratory symptoms before mucocutaneous involvement.
“The big clinical differentiator between drug-induced SJS and mycoplasma-induced SJS was respiratory disorder,” said Dr. Shear, who was not affiliated with the study. “That means you’re probably looking at something that’s mycoplasma related [when respiratory problems are present]. Even if you can’t prove it’s mycoplasma related, that probably needs to be the target of your therapy. The idea ... is to make sure it’s clear at the end. One, so they get better, and two, so that we’re not giving drugs needlessly when it was really mycoplasma.”
Noting that HLA-B*15:02 is a marker for carbamazepine-induced SJS and TEN, he said, “a positive HLA test can support the diagnosis, confirm the suspected offending drug, and is valuable for familial genetic counseling.”
As for treatment of SJS, TEN, and other cytotoxic T-lymphocyte–mediated severe cutaneous adverse reactions, a randomized Japanese clinical trial evaluating prednisolone 1-1.5 mg/kg/day IV versus etanercept 25-50 mg subcutaneously twice per week in 96 patients with SJS-TEN found that etanercept decreased the mortality rate by 8.3%. In addition, etanercept reduced skin healing time, when compared with prednisolone (a median of 14 vs. 19 days, respectively; P = .010), and was associated with a lower incidence of GI hemorrhage (2.6% vs. 18.2%, respectively; P = .03).
Dr. Shear said that he would like to see better therapeutics for severe, complex patients. “After leaving the hospital, people with SJS or people with TEN need to have ongoing care, consultation, and explanation so they and their families know what drugs are safe in the future.”
Dr. Shear disclosed that he has been a consultant to AbbVie, Amgen, Bausch Medicine, Novartis, Sanofi-Genzyme, UCB, LEO Pharma, Otsuka, Janssen, Alpha Laboratories, Lilly, ChemoCentryx, Vivoryon, Galderma, Innovaderm, Chromocell, and Kyowa Kirin.
In the opinion of Neil H. Shear, MD, a stepwise approach is the best way to diagnose possible drug-induced skin disease and determine the root cause.
“Often, we need to think of more than one cause,” he said during the annual meeting of the Society for Pediatric Dermatology. “It could be drug X. It could be drug Y. It could be contrast media. We must think broadly and pay special attention to skin of color, overlapping syndromes, and the changing diagnostic assessment over time.”
His suggested diagnostic triangle includes appearance of the rash or lesion(s), systemic impact, and histology. “The first is the appearance,” said Dr. Shear, professor emeritus of dermatology, clinical pharmacology and toxicology, and medicine at the University of Toronto. “Is it exanthem? Is it blistering? Don’t just say drug ‘rash.’ That doesn’t work. You need to know if there are systemic features, and sometimes histologic information can change your approach or diagnosis, but not as often as one might think,” he said, noting that, in his view, the two main factors are appearance and systemic impact.
The presence of fever is a hallmark of systemic problems, he continued, “so if you see fever, you know you’re probably going to be dealing with a complex reaction, so we need to know the morphology.” Consider whether it is simple exanthem (a mild, uncomplicated rash) or complex exanthem (drug rash with eosinophilia and systemic symptoms or fever, malaise, and adenopathy).
As for other morphologies, urticarial lesions could be urticaria or a serum sickness-like reaction, pustular lesions could be acneiform or acute generalized exanthematous pustulosis, while
Dr. Shear considers SJS/TEN as a spectrum of blistering disease, “because there’s not a single diagnosis,” he said. “There’s a spectrum, if you will, depending on how advanced people are in their disease.” He coauthored a 1991 report describing eight cases of mycoplasma and Stevens-Johnson syndrome. “I was surprised at how long that stood up as about the only paper in that area,” he said. “But there’s much more happening now with a proliferation of terms,” he added, referring to MIRM (Mycoplasma pneumonia–induced rash and mucositis), RIME (reactive infectious mucocutaneous eruption); and Fuchs syndrome, or SJS without skin lesions.
What was not appreciated in the early classification of SJS, he continued, was a “side basket” of bullous erythema multiforme. “We didn’t know what to call it,” he said. “At one point we called it bullous erythema multiforme. At another point we called it erythema multiforme major. We just didn’t know what it was.”
The appearance and systemic effects of SJS comprise what he termed SJS type 2 – or the early stages of TEN. Taken together, he refers to these two conditions as TEN Spectrum, or TENS. “One of the traps is that TENS can look like varicella, and vice versa, especially in very dark brown or black skin,” Dr. Shear said. “You have to be careful. A biopsy might be worthwhile. Acute lupus has the pathology of TENS but the patients are not as systemically ill as true TENS.”
In 2011, Japanese researchers reported on 38 cases of SJS associated with M. pneumoniae, and 78 cases of drug-induced SJS. They found that 66% of adult patients with M. pneumoniae–associated SJS developed mucocutaneous lesions and fever/respiratory symptoms on the same day, mostly shortness of breath and cough. In contrast, most of the patients aged under 20 years developed fever/respiratory symptoms before mucocutaneous involvement.
“The big clinical differentiator between drug-induced SJS and mycoplasma-induced SJS was respiratory disorder,” said Dr. Shear, who was not affiliated with the study. “That means you’re probably looking at something that’s mycoplasma related [when respiratory problems are present]. Even if you can’t prove it’s mycoplasma related, that probably needs to be the target of your therapy. The idea ... is to make sure it’s clear at the end. One, so they get better, and two, so that we’re not giving drugs needlessly when it was really mycoplasma.”
Noting that HLA-B*15:02 is a marker for carbamazepine-induced SJS and TEN, he said, “a positive HLA test can support the diagnosis, confirm the suspected offending drug, and is valuable for familial genetic counseling.”
As for treatment of SJS, TEN, and other cytotoxic T-lymphocyte–mediated severe cutaneous adverse reactions, a randomized Japanese clinical trial evaluating prednisolone 1-1.5 mg/kg/day IV versus etanercept 25-50 mg subcutaneously twice per week in 96 patients with SJS-TEN found that etanercept decreased the mortality rate by 8.3%. In addition, etanercept reduced skin healing time, when compared with prednisolone (a median of 14 vs. 19 days, respectively; P = .010), and was associated with a lower incidence of GI hemorrhage (2.6% vs. 18.2%, respectively; P = .03).
Dr. Shear said that he would like to see better therapeutics for severe, complex patients. “After leaving the hospital, people with SJS or people with TEN need to have ongoing care, consultation, and explanation so they and their families know what drugs are safe in the future.”
Dr. Shear disclosed that he has been a consultant to AbbVie, Amgen, Bausch Medicine, Novartis, Sanofi-Genzyme, UCB, LEO Pharma, Otsuka, Janssen, Alpha Laboratories, Lilly, ChemoCentryx, Vivoryon, Galderma, Innovaderm, Chromocell, and Kyowa Kirin.
In the opinion of Neil H. Shear, MD, a stepwise approach is the best way to diagnose possible drug-induced skin disease and determine the root cause.
“Often, we need to think of more than one cause,” he said during the annual meeting of the Society for Pediatric Dermatology. “It could be drug X. It could be drug Y. It could be contrast media. We must think broadly and pay special attention to skin of color, overlapping syndromes, and the changing diagnostic assessment over time.”
His suggested diagnostic triangle includes appearance of the rash or lesion(s), systemic impact, and histology. “The first is the appearance,” said Dr. Shear, professor emeritus of dermatology, clinical pharmacology and toxicology, and medicine at the University of Toronto. “Is it exanthem? Is it blistering? Don’t just say drug ‘rash.’ That doesn’t work. You need to know if there are systemic features, and sometimes histologic information can change your approach or diagnosis, but not as often as one might think,” he said, noting that, in his view, the two main factors are appearance and systemic impact.
The presence of fever is a hallmark of systemic problems, he continued, “so if you see fever, you know you’re probably going to be dealing with a complex reaction, so we need to know the morphology.” Consider whether it is simple exanthem (a mild, uncomplicated rash) or complex exanthem (drug rash with eosinophilia and systemic symptoms or fever, malaise, and adenopathy).
As for other morphologies, urticarial lesions could be urticaria or a serum sickness-like reaction, pustular lesions could be acneiform or acute generalized exanthematous pustulosis, while
Dr. Shear considers SJS/TEN as a spectrum of blistering disease, “because there’s not a single diagnosis,” he said. “There’s a spectrum, if you will, depending on how advanced people are in their disease.” He coauthored a 1991 report describing eight cases of mycoplasma and Stevens-Johnson syndrome. “I was surprised at how long that stood up as about the only paper in that area,” he said. “But there’s much more happening now with a proliferation of terms,” he added, referring to MIRM (Mycoplasma pneumonia–induced rash and mucositis), RIME (reactive infectious mucocutaneous eruption); and Fuchs syndrome, or SJS without skin lesions.
What was not appreciated in the early classification of SJS, he continued, was a “side basket” of bullous erythema multiforme. “We didn’t know what to call it,” he said. “At one point we called it bullous erythema multiforme. At another point we called it erythema multiforme major. We just didn’t know what it was.”
The appearance and systemic effects of SJS comprise what he termed SJS type 2 – or the early stages of TEN. Taken together, he refers to these two conditions as TEN Spectrum, or TENS. “One of the traps is that TENS can look like varicella, and vice versa, especially in very dark brown or black skin,” Dr. Shear said. “You have to be careful. A biopsy might be worthwhile. Acute lupus has the pathology of TENS but the patients are not as systemically ill as true TENS.”
In 2011, Japanese researchers reported on 38 cases of SJS associated with M. pneumoniae, and 78 cases of drug-induced SJS. They found that 66% of adult patients with M. pneumoniae–associated SJS developed mucocutaneous lesions and fever/respiratory symptoms on the same day, mostly shortness of breath and cough. In contrast, most of the patients aged under 20 years developed fever/respiratory symptoms before mucocutaneous involvement.
“The big clinical differentiator between drug-induced SJS and mycoplasma-induced SJS was respiratory disorder,” said Dr. Shear, who was not affiliated with the study. “That means you’re probably looking at something that’s mycoplasma related [when respiratory problems are present]. Even if you can’t prove it’s mycoplasma related, that probably needs to be the target of your therapy. The idea ... is to make sure it’s clear at the end. One, so they get better, and two, so that we’re not giving drugs needlessly when it was really mycoplasma.”
Noting that HLA-B*15:02 is a marker for carbamazepine-induced SJS and TEN, he said, “a positive HLA test can support the diagnosis, confirm the suspected offending drug, and is valuable for familial genetic counseling.”
As for treatment of SJS, TEN, and other cytotoxic T-lymphocyte–mediated severe cutaneous adverse reactions, a randomized Japanese clinical trial evaluating prednisolone 1-1.5 mg/kg/day IV versus etanercept 25-50 mg subcutaneously twice per week in 96 patients with SJS-TEN found that etanercept decreased the mortality rate by 8.3%. In addition, etanercept reduced skin healing time, when compared with prednisolone (a median of 14 vs. 19 days, respectively; P = .010), and was associated with a lower incidence of GI hemorrhage (2.6% vs. 18.2%, respectively; P = .03).
Dr. Shear said that he would like to see better therapeutics for severe, complex patients. “After leaving the hospital, people with SJS or people with TEN need to have ongoing care, consultation, and explanation so they and their families know what drugs are safe in the future.”
Dr. Shear disclosed that he has been a consultant to AbbVie, Amgen, Bausch Medicine, Novartis, Sanofi-Genzyme, UCB, LEO Pharma, Otsuka, Janssen, Alpha Laboratories, Lilly, ChemoCentryx, Vivoryon, Galderma, Innovaderm, Chromocell, and Kyowa Kirin.
FROM SPD 2021
Pediatric alopecia areata in the U.S. has increased twofold since 2009, study finds
according to results from the largest study to date on the topic.
“Alopecia areata is a relatively common cause of nonscarring hair loss in children,” Paige McKenzie said during the annual meeting of the Society for Pediatric Dermatology. “The only two epidemiologic studies that have been performed in children have been based on registry or survey data which is inherently at risk for bias,” she added, referring to studies published in 2017 and 2018. “Additionally, epidemiologic descriptions of alopecia areata in adults are limited and overall estimates have varied from 0.2% to 2%. Current understanding is also largely based on population studies in Olmsted County, Minnesota, an area with mostly White racial demographics, so it’s not representative of the U.S. population as a whole.”
To identify the incidence and prevalence of pediatric AA over time, and across age, race/ethnicity, and sex, Ms. McKenzie and colleagues conducted a retrospective cohort study from 2009 to 2020 using PEDSnet, a network of seven U.S. pediatric health institutions with a database of more than 6.5 million children. “PEDSnet is unique because it uses a common data model to standardize EHR data across different health systems and uses SNOMED [Systematized Nomenclature of Medicine]–Clinical Terms to identify specific patient populations,” said Ms. McKenzie, who was a clinical research fellow in the section of dermatology at the Children’s Hospital of Philadelphia during the 2020-2021 academic year.
She and her coauthors limited their analysis to children younger than age 18 who were assigned a SNOMED code for AA during at least one dermatology physician visit or at least two nondermatology physician visits. They also identified an incidence cohort that was a subset of the study cohort who had at least 12 months of follow-up. “To determine the accuracy of AA patient identification, we also reviewed 100 cases at random from one institution with a threshold of greater than 95% accuracy,” said Ms. McKenzie, who is now a fourth-year medical student at the University of Texas Southwestern Medical Center, Dallas.
Of 5,409,919 children included in the study, 5,801 had AA, for an overall prevalence of 0.11%. The prevalence doubled from 0.04% in 2009 to 0.08% in 2019. “It fell in 2020, which we believe is a result of the COVID-19 pandemic’s effects on health care utilization,” she said. AA prevalence peaked at 9 years of age and was higher among females, compared with males (0.12% vs. 0.09%, respectively). The prevalence was highest among Hispanic children (0.23%), followed by Asian children (0.17%), Black children (0.12%), and White children (0.08%).
The incidence cohort consisted of 2,896,241 children. Of these, 2,398 had AA between 2009-2020, for an overall incidence of 13.6 cases per 100,000 patient-years. The incidence rate of AA by age was normally distributed and peaked at 6 years of age. Rates were 22.8% higher in female patients than in male patients. In addition, incidence rates were highest among Hispanics (31.5/100,000 person-years), followed by Asians (23.1/100,000 person-years), Blacks (17.0/100,000 person-years), and Whites (8.8/100,000).
Logistic regression analysis showed general agreement with the unadjusted incidence data. Males were less likely to be diagnosed with AA, compared with females (adjusted odds ratio, 0.80; P < .001). Analysis across race/ethnicity revealed significantly increased rates among children from minority backgrounds when compared with white children. Hispanic children had the greatest risk of developing AA (aOR, 3.07), followed by Asian children (aOR, 2.02), and Black children (aOR, 1.73) (P < .001 for all associations). Patients with atopic dermatitis, thyroid disease, psoriasis, vitiligo, and trisomy 21 prior to AA diagnosis all had a significantly higher risk of developing AA, compared with those without those diagnoses.
“This is the largest description of pediatric AA to date,” Ms. McKenzie said. “The prevalence has increased steadily, with a twofold increase over the last 10 years, which mirrors other autoimmune disorders. Children who identify as Hispanic, Asian, and Black have significantly higher incidence rates of alopecia areata compared to those who identify as White.”
Moving forward, she added, “efforts should focus on increasing education and awareness of AA in diverse communities and in community pediatricians so that patients can be diagnosed correctly early on. We can also use this data to ensure that representative populations are included in clinical trials for patients with AA.”
Asked to comment on the results Maria Hordinsky, MD, professor and chair of the department of dermatology at the University of Minnesota, Minneapolis, said that the study “is a great contribution to our understanding of the epidemiology of pediatric alopecia areata and also highlights how common alopecia areata is in children.” In an interview, she said that it would be interesting to see if this is a worldwide phenomenon or unique to the United States.
Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study, characterized the work as being “very informative. Looking at a large cohort of pediatric patients with alopecia areata diagnosed by a dermatologist or two or more nondermatologists, the authors found a higher incidence and prevalence in nonwhite children here in the United States. I am worried in fact, the true incidence could be even higher than noted in the searched database because nonwhite children can often come from underserved and undercared for areas.”
The other authors were Christopher B. Forrest, MD, PhD, Mitchell Maltenfort, PhD, and Leslie Castelo-Soccio, MD, PhD, of Children’s Hospital of Philadelphia. Dr. Castelo-Soccio is a consultant for Pfizer; the other authors reported having no financial disclosures. Dr. Hordinsky disclosed receiving grant support for clinical research work on hair diseases from Pfizer, Eli Lilly, Concert Pharmaceuticals, and Target Derm and grant support from the National Alopecia Areata Foundation; and is on an advisory panel for Cassiopea. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.
*This story was updated on 7/19/21.
according to results from the largest study to date on the topic.
“Alopecia areata is a relatively common cause of nonscarring hair loss in children,” Paige McKenzie said during the annual meeting of the Society for Pediatric Dermatology. “The only two epidemiologic studies that have been performed in children have been based on registry or survey data which is inherently at risk for bias,” she added, referring to studies published in 2017 and 2018. “Additionally, epidemiologic descriptions of alopecia areata in adults are limited and overall estimates have varied from 0.2% to 2%. Current understanding is also largely based on population studies in Olmsted County, Minnesota, an area with mostly White racial demographics, so it’s not representative of the U.S. population as a whole.”
To identify the incidence and prevalence of pediatric AA over time, and across age, race/ethnicity, and sex, Ms. McKenzie and colleagues conducted a retrospective cohort study from 2009 to 2020 using PEDSnet, a network of seven U.S. pediatric health institutions with a database of more than 6.5 million children. “PEDSnet is unique because it uses a common data model to standardize EHR data across different health systems and uses SNOMED [Systematized Nomenclature of Medicine]–Clinical Terms to identify specific patient populations,” said Ms. McKenzie, who was a clinical research fellow in the section of dermatology at the Children’s Hospital of Philadelphia during the 2020-2021 academic year.
She and her coauthors limited their analysis to children younger than age 18 who were assigned a SNOMED code for AA during at least one dermatology physician visit or at least two nondermatology physician visits. They also identified an incidence cohort that was a subset of the study cohort who had at least 12 months of follow-up. “To determine the accuracy of AA patient identification, we also reviewed 100 cases at random from one institution with a threshold of greater than 95% accuracy,” said Ms. McKenzie, who is now a fourth-year medical student at the University of Texas Southwestern Medical Center, Dallas.
Of 5,409,919 children included in the study, 5,801 had AA, for an overall prevalence of 0.11%. The prevalence doubled from 0.04% in 2009 to 0.08% in 2019. “It fell in 2020, which we believe is a result of the COVID-19 pandemic’s effects on health care utilization,” she said. AA prevalence peaked at 9 years of age and was higher among females, compared with males (0.12% vs. 0.09%, respectively). The prevalence was highest among Hispanic children (0.23%), followed by Asian children (0.17%), Black children (0.12%), and White children (0.08%).
The incidence cohort consisted of 2,896,241 children. Of these, 2,398 had AA between 2009-2020, for an overall incidence of 13.6 cases per 100,000 patient-years. The incidence rate of AA by age was normally distributed and peaked at 6 years of age. Rates were 22.8% higher in female patients than in male patients. In addition, incidence rates were highest among Hispanics (31.5/100,000 person-years), followed by Asians (23.1/100,000 person-years), Blacks (17.0/100,000 person-years), and Whites (8.8/100,000).
Logistic regression analysis showed general agreement with the unadjusted incidence data. Males were less likely to be diagnosed with AA, compared with females (adjusted odds ratio, 0.80; P < .001). Analysis across race/ethnicity revealed significantly increased rates among children from minority backgrounds when compared with white children. Hispanic children had the greatest risk of developing AA (aOR, 3.07), followed by Asian children (aOR, 2.02), and Black children (aOR, 1.73) (P < .001 for all associations). Patients with atopic dermatitis, thyroid disease, psoriasis, vitiligo, and trisomy 21 prior to AA diagnosis all had a significantly higher risk of developing AA, compared with those without those diagnoses.
“This is the largest description of pediatric AA to date,” Ms. McKenzie said. “The prevalence has increased steadily, with a twofold increase over the last 10 years, which mirrors other autoimmune disorders. Children who identify as Hispanic, Asian, and Black have significantly higher incidence rates of alopecia areata compared to those who identify as White.”
Moving forward, she added, “efforts should focus on increasing education and awareness of AA in diverse communities and in community pediatricians so that patients can be diagnosed correctly early on. We can also use this data to ensure that representative populations are included in clinical trials for patients with AA.”
Asked to comment on the results Maria Hordinsky, MD, professor and chair of the department of dermatology at the University of Minnesota, Minneapolis, said that the study “is a great contribution to our understanding of the epidemiology of pediatric alopecia areata and also highlights how common alopecia areata is in children.” In an interview, she said that it would be interesting to see if this is a worldwide phenomenon or unique to the United States.
Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study, characterized the work as being “very informative. Looking at a large cohort of pediatric patients with alopecia areata diagnosed by a dermatologist or two or more nondermatologists, the authors found a higher incidence and prevalence in nonwhite children here in the United States. I am worried in fact, the true incidence could be even higher than noted in the searched database because nonwhite children can often come from underserved and undercared for areas.”
The other authors were Christopher B. Forrest, MD, PhD, Mitchell Maltenfort, PhD, and Leslie Castelo-Soccio, MD, PhD, of Children’s Hospital of Philadelphia. Dr. Castelo-Soccio is a consultant for Pfizer; the other authors reported having no financial disclosures. Dr. Hordinsky disclosed receiving grant support for clinical research work on hair diseases from Pfizer, Eli Lilly, Concert Pharmaceuticals, and Target Derm and grant support from the National Alopecia Areata Foundation; and is on an advisory panel for Cassiopea. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.
*This story was updated on 7/19/21.
according to results from the largest study to date on the topic.
“Alopecia areata is a relatively common cause of nonscarring hair loss in children,” Paige McKenzie said during the annual meeting of the Society for Pediatric Dermatology. “The only two epidemiologic studies that have been performed in children have been based on registry or survey data which is inherently at risk for bias,” she added, referring to studies published in 2017 and 2018. “Additionally, epidemiologic descriptions of alopecia areata in adults are limited and overall estimates have varied from 0.2% to 2%. Current understanding is also largely based on population studies in Olmsted County, Minnesota, an area with mostly White racial demographics, so it’s not representative of the U.S. population as a whole.”
To identify the incidence and prevalence of pediatric AA over time, and across age, race/ethnicity, and sex, Ms. McKenzie and colleagues conducted a retrospective cohort study from 2009 to 2020 using PEDSnet, a network of seven U.S. pediatric health institutions with a database of more than 6.5 million children. “PEDSnet is unique because it uses a common data model to standardize EHR data across different health systems and uses SNOMED [Systematized Nomenclature of Medicine]–Clinical Terms to identify specific patient populations,” said Ms. McKenzie, who was a clinical research fellow in the section of dermatology at the Children’s Hospital of Philadelphia during the 2020-2021 academic year.
She and her coauthors limited their analysis to children younger than age 18 who were assigned a SNOMED code for AA during at least one dermatology physician visit or at least two nondermatology physician visits. They also identified an incidence cohort that was a subset of the study cohort who had at least 12 months of follow-up. “To determine the accuracy of AA patient identification, we also reviewed 100 cases at random from one institution with a threshold of greater than 95% accuracy,” said Ms. McKenzie, who is now a fourth-year medical student at the University of Texas Southwestern Medical Center, Dallas.
Of 5,409,919 children included in the study, 5,801 had AA, for an overall prevalence of 0.11%. The prevalence doubled from 0.04% in 2009 to 0.08% in 2019. “It fell in 2020, which we believe is a result of the COVID-19 pandemic’s effects on health care utilization,” she said. AA prevalence peaked at 9 years of age and was higher among females, compared with males (0.12% vs. 0.09%, respectively). The prevalence was highest among Hispanic children (0.23%), followed by Asian children (0.17%), Black children (0.12%), and White children (0.08%).
The incidence cohort consisted of 2,896,241 children. Of these, 2,398 had AA between 2009-2020, for an overall incidence of 13.6 cases per 100,000 patient-years. The incidence rate of AA by age was normally distributed and peaked at 6 years of age. Rates were 22.8% higher in female patients than in male patients. In addition, incidence rates were highest among Hispanics (31.5/100,000 person-years), followed by Asians (23.1/100,000 person-years), Blacks (17.0/100,000 person-years), and Whites (8.8/100,000).
Logistic regression analysis showed general agreement with the unadjusted incidence data. Males were less likely to be diagnosed with AA, compared with females (adjusted odds ratio, 0.80; P < .001). Analysis across race/ethnicity revealed significantly increased rates among children from minority backgrounds when compared with white children. Hispanic children had the greatest risk of developing AA (aOR, 3.07), followed by Asian children (aOR, 2.02), and Black children (aOR, 1.73) (P < .001 for all associations). Patients with atopic dermatitis, thyroid disease, psoriasis, vitiligo, and trisomy 21 prior to AA diagnosis all had a significantly higher risk of developing AA, compared with those without those diagnoses.
“This is the largest description of pediatric AA to date,” Ms. McKenzie said. “The prevalence has increased steadily, with a twofold increase over the last 10 years, which mirrors other autoimmune disorders. Children who identify as Hispanic, Asian, and Black have significantly higher incidence rates of alopecia areata compared to those who identify as White.”
Moving forward, she added, “efforts should focus on increasing education and awareness of AA in diverse communities and in community pediatricians so that patients can be diagnosed correctly early on. We can also use this data to ensure that representative populations are included in clinical trials for patients with AA.”
Asked to comment on the results Maria Hordinsky, MD, professor and chair of the department of dermatology at the University of Minnesota, Minneapolis, said that the study “is a great contribution to our understanding of the epidemiology of pediatric alopecia areata and also highlights how common alopecia areata is in children.” In an interview, she said that it would be interesting to see if this is a worldwide phenomenon or unique to the United States.
Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study, characterized the work as being “very informative. Looking at a large cohort of pediatric patients with alopecia areata diagnosed by a dermatologist or two or more nondermatologists, the authors found a higher incidence and prevalence in nonwhite children here in the United States. I am worried in fact, the true incidence could be even higher than noted in the searched database because nonwhite children can often come from underserved and undercared for areas.”
The other authors were Christopher B. Forrest, MD, PhD, Mitchell Maltenfort, PhD, and Leslie Castelo-Soccio, MD, PhD, of Children’s Hospital of Philadelphia. Dr. Castelo-Soccio is a consultant for Pfizer; the other authors reported having no financial disclosures. Dr. Hordinsky disclosed receiving grant support for clinical research work on hair diseases from Pfizer, Eli Lilly, Concert Pharmaceuticals, and Target Derm and grant support from the National Alopecia Areata Foundation; and is on an advisory panel for Cassiopea. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.
*This story was updated on 7/19/21.
FROM SPD 2021
Proposed classification framework for atopic dermatitis unveiled
The heterogeneous clinical course of atopic dermatitis (AD) and its differing signs, symptoms, burden, and response to treatment can pose a quandary for physicians.
This is behind facilitate tailoring of therapy to individual patient characteristics, and better identify therapeutically relevant disease subsets.
Dr. Silverberg, director of clinical research in the department of dermatology at George Washington University, Washington, debuted DESCRIBE-AD during the Revolutionizing Atopic Dermatitis symposium. The “D” in the mnemonic stands for dermatitis morphology and phenotype, the “E” for evolution of disease, the “S” for symptom severity, the “C” for comorbid health disorders, the “R” for response to therapy, the “I” for intensity of lesions, the “B” for burden of disease, and the “E” for extent of lesions.
At the meeting, he discussed the concepts behind each letter of the mnemonic.
Dermatitis morphology and phenotype
In the dermatitis morphology and phenotype component of DESCRIBE-AD, “there’s a lot to consider,” he said. “There are chronic signs like lichenification and prurigo nodules, which have treatment ramifications,” such as the length of time patients may need to be treated, and possibly “the use of more potent, targeted options to go after some of these lesions.”
Recent studies suggest that nummular lesions have a different underlying pathogenesis suggesting an overlap between Th2 and Th17 cell–mediated lesions. “How does that impact response to targeted therapies?” he asked. “We have no idea. We need to learn that.” He noted that psoriasiform lesions are not limited to Asian patients, but also appear in elderly patients with AD. “They look different [in elderly patients] and they may respond differently; they have more psoriasiform lesions and it’s not exactly clear why.”
Other morphologic variants of AD to be aware of include follicular eczema, xerosis, and the itch-dominant form, which Dr. Silverberg and colleagues addressed in a recently published study. “There are some patients who have milder-looking lesions, but their itch is just out of control,” he said. “This is a pattern that we need to recognize.”
Evolution of disease, symptom severity
Factors to consider for the evolution of disease component of the proposed classification include age of AD onset or disease recurrence, frequency and duration of flares, disease activity between flares, periods of disease clearance, and the overall disease trajectory. “We do get patients who say that every year their disease seems to get worse over time, for reasons that are not always clear,” Dr. Silverberg said.
Assessment tools he recommends for the symptom severity component of DESCRIBE-AD include the patient-reported global AD severity, numerical rating scale (NRS) worst or average itch in the past 7 days, the Skin Pain NRS, and the Sleep Quality NRS, which each take fewer than 30 seconds to complete. “You can have your nurses do this or can you have the patients fill out the form in the waiting area before they see you,” Dr. Silverberg said.
He also advises asking patients about the number of nights they experience sleep disturbance and if they have difficulty falling asleep or have nighttime awakenings because of their AD. Symptoms of anxiety and depression can be assessed with the Hospital Anxiety and Depression Scale and the Patient-Health Questionnaire–9, which each take 2-3 minutes to complete.
Recommended assessment tools for other symptoms – such as bleeding, oozing, and xerosis – include the Patient-Oriented Eczema Measure, which takes 2-3 minutes to complete, and the Atopic Dermatitis Control Tool or the Recap of Atopic Eczema, which each take 2-3 minutes to complete.
Comorbid health disorders
Comorbid health disorders linked to AD are varied and include atopic comorbidities such as asthma or wheeze, hay fever or oculonasal symptoms, food allergy, recurrent infections such as herpes simplex virus, mental health disorders, alopecia areata, Th1-mediated comorbidities, and adverse events to medication such as venous thromboembolism, hypertension, and impaired renal or liver function. “All of these are important because if the patients have these at baseline, they may not be good candidates for some therapies that cause these types of side effects,” Dr. Silverberg said.
Response to therapy, intensity of lesions
As for response to therapy, clinicians can ask patients, “How do you feel you’re improving?” But it’s also important to assess the signs, symptoms, frequency of flares, and comorbidities as part of that response to therapy, “and of course the adverse events and treatment burden,” he said.
For the intensity of lesions component of DESCRIBE-AD, Dr. Silverberg said that the Investigator’s Global Assessment–AD is an effective tool for clinical use. “You can also use tools like the Eczema Area and Severity Index or the Scoring AD, but recognize these are challenging,” and can be difficult to use if not well trained to use them, he said. “At the very least, do an Investigator’s Global Assessment and do a body surface area measurement.”
In his opinion, four key signs that should be assessed in clinical trials are erythema, edema/papulation, excoriation, and lichenification/prurigo nodules.
Burden of disease
In terms of assessing AD disease burden, guidelines from the American Academy of Dermatology don’t give a specific tool to use, but recommend asking open-ended questions, Dr. Silverberg said. “I would not recommend that, because when you ask an open-ended question, the flood gates open up because most patients are suffering miserably with this disease when it’s uncontrolled.
“That’s why it’s valuable to use structured, validated tools like the Dermatology Life Quality Index and the Patient Reported Outcome Measurement Information System. They don’t take a lot of time to complete, and you can look at the score and determine how burdensome their disease is, even in a busy clinical practice. They’re not going to slow you down; they’re going to speed you up and make you better at your therapeutic decision-making. I can guarantee you that most patients will love you for it. Sometimes patients say to me, ‘you’re the first doctor to ask these questions.’ ”
Extent of disease
Finally, for the extent of disease component of DESCRIBE-AD, he emphasized the importance of doing a full-body exam to appreciate the affected body surface area, flexural versus extensor distribution, and involvement and severity of disease on special sites such as the face, hands, feet, genitals, and scalp.
Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
The heterogeneous clinical course of atopic dermatitis (AD) and its differing signs, symptoms, burden, and response to treatment can pose a quandary for physicians.
This is behind facilitate tailoring of therapy to individual patient characteristics, and better identify therapeutically relevant disease subsets.
Dr. Silverberg, director of clinical research in the department of dermatology at George Washington University, Washington, debuted DESCRIBE-AD during the Revolutionizing Atopic Dermatitis symposium. The “D” in the mnemonic stands for dermatitis morphology and phenotype, the “E” for evolution of disease, the “S” for symptom severity, the “C” for comorbid health disorders, the “R” for response to therapy, the “I” for intensity of lesions, the “B” for burden of disease, and the “E” for extent of lesions.
At the meeting, he discussed the concepts behind each letter of the mnemonic.
Dermatitis morphology and phenotype
In the dermatitis morphology and phenotype component of DESCRIBE-AD, “there’s a lot to consider,” he said. “There are chronic signs like lichenification and prurigo nodules, which have treatment ramifications,” such as the length of time patients may need to be treated, and possibly “the use of more potent, targeted options to go after some of these lesions.”
Recent studies suggest that nummular lesions have a different underlying pathogenesis suggesting an overlap between Th2 and Th17 cell–mediated lesions. “How does that impact response to targeted therapies?” he asked. “We have no idea. We need to learn that.” He noted that psoriasiform lesions are not limited to Asian patients, but also appear in elderly patients with AD. “They look different [in elderly patients] and they may respond differently; they have more psoriasiform lesions and it’s not exactly clear why.”
Other morphologic variants of AD to be aware of include follicular eczema, xerosis, and the itch-dominant form, which Dr. Silverberg and colleagues addressed in a recently published study. “There are some patients who have milder-looking lesions, but their itch is just out of control,” he said. “This is a pattern that we need to recognize.”
Evolution of disease, symptom severity
Factors to consider for the evolution of disease component of the proposed classification include age of AD onset or disease recurrence, frequency and duration of flares, disease activity between flares, periods of disease clearance, and the overall disease trajectory. “We do get patients who say that every year their disease seems to get worse over time, for reasons that are not always clear,” Dr. Silverberg said.
Assessment tools he recommends for the symptom severity component of DESCRIBE-AD include the patient-reported global AD severity, numerical rating scale (NRS) worst or average itch in the past 7 days, the Skin Pain NRS, and the Sleep Quality NRS, which each take fewer than 30 seconds to complete. “You can have your nurses do this or can you have the patients fill out the form in the waiting area before they see you,” Dr. Silverberg said.
He also advises asking patients about the number of nights they experience sleep disturbance and if they have difficulty falling asleep or have nighttime awakenings because of their AD. Symptoms of anxiety and depression can be assessed with the Hospital Anxiety and Depression Scale and the Patient-Health Questionnaire–9, which each take 2-3 minutes to complete.
Recommended assessment tools for other symptoms – such as bleeding, oozing, and xerosis – include the Patient-Oriented Eczema Measure, which takes 2-3 minutes to complete, and the Atopic Dermatitis Control Tool or the Recap of Atopic Eczema, which each take 2-3 minutes to complete.
Comorbid health disorders
Comorbid health disorders linked to AD are varied and include atopic comorbidities such as asthma or wheeze, hay fever or oculonasal symptoms, food allergy, recurrent infections such as herpes simplex virus, mental health disorders, alopecia areata, Th1-mediated comorbidities, and adverse events to medication such as venous thromboembolism, hypertension, and impaired renal or liver function. “All of these are important because if the patients have these at baseline, they may not be good candidates for some therapies that cause these types of side effects,” Dr. Silverberg said.
Response to therapy, intensity of lesions
As for response to therapy, clinicians can ask patients, “How do you feel you’re improving?” But it’s also important to assess the signs, symptoms, frequency of flares, and comorbidities as part of that response to therapy, “and of course the adverse events and treatment burden,” he said.
For the intensity of lesions component of DESCRIBE-AD, Dr. Silverberg said that the Investigator’s Global Assessment–AD is an effective tool for clinical use. “You can also use tools like the Eczema Area and Severity Index or the Scoring AD, but recognize these are challenging,” and can be difficult to use if not well trained to use them, he said. “At the very least, do an Investigator’s Global Assessment and do a body surface area measurement.”
In his opinion, four key signs that should be assessed in clinical trials are erythema, edema/papulation, excoriation, and lichenification/prurigo nodules.
Burden of disease
In terms of assessing AD disease burden, guidelines from the American Academy of Dermatology don’t give a specific tool to use, but recommend asking open-ended questions, Dr. Silverberg said. “I would not recommend that, because when you ask an open-ended question, the flood gates open up because most patients are suffering miserably with this disease when it’s uncontrolled.
“That’s why it’s valuable to use structured, validated tools like the Dermatology Life Quality Index and the Patient Reported Outcome Measurement Information System. They don’t take a lot of time to complete, and you can look at the score and determine how burdensome their disease is, even in a busy clinical practice. They’re not going to slow you down; they’re going to speed you up and make you better at your therapeutic decision-making. I can guarantee you that most patients will love you for it. Sometimes patients say to me, ‘you’re the first doctor to ask these questions.’ ”
Extent of disease
Finally, for the extent of disease component of DESCRIBE-AD, he emphasized the importance of doing a full-body exam to appreciate the affected body surface area, flexural versus extensor distribution, and involvement and severity of disease on special sites such as the face, hands, feet, genitals, and scalp.
Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
The heterogeneous clinical course of atopic dermatitis (AD) and its differing signs, symptoms, burden, and response to treatment can pose a quandary for physicians.
This is behind facilitate tailoring of therapy to individual patient characteristics, and better identify therapeutically relevant disease subsets.
Dr. Silverberg, director of clinical research in the department of dermatology at George Washington University, Washington, debuted DESCRIBE-AD during the Revolutionizing Atopic Dermatitis symposium. The “D” in the mnemonic stands for dermatitis morphology and phenotype, the “E” for evolution of disease, the “S” for symptom severity, the “C” for comorbid health disorders, the “R” for response to therapy, the “I” for intensity of lesions, the “B” for burden of disease, and the “E” for extent of lesions.
At the meeting, he discussed the concepts behind each letter of the mnemonic.
Dermatitis morphology and phenotype
In the dermatitis morphology and phenotype component of DESCRIBE-AD, “there’s a lot to consider,” he said. “There are chronic signs like lichenification and prurigo nodules, which have treatment ramifications,” such as the length of time patients may need to be treated, and possibly “the use of more potent, targeted options to go after some of these lesions.”
Recent studies suggest that nummular lesions have a different underlying pathogenesis suggesting an overlap between Th2 and Th17 cell–mediated lesions. “How does that impact response to targeted therapies?” he asked. “We have no idea. We need to learn that.” He noted that psoriasiform lesions are not limited to Asian patients, but also appear in elderly patients with AD. “They look different [in elderly patients] and they may respond differently; they have more psoriasiform lesions and it’s not exactly clear why.”
Other morphologic variants of AD to be aware of include follicular eczema, xerosis, and the itch-dominant form, which Dr. Silverberg and colleagues addressed in a recently published study. “There are some patients who have milder-looking lesions, but their itch is just out of control,” he said. “This is a pattern that we need to recognize.”
Evolution of disease, symptom severity
Factors to consider for the evolution of disease component of the proposed classification include age of AD onset or disease recurrence, frequency and duration of flares, disease activity between flares, periods of disease clearance, and the overall disease trajectory. “We do get patients who say that every year their disease seems to get worse over time, for reasons that are not always clear,” Dr. Silverberg said.
Assessment tools he recommends for the symptom severity component of DESCRIBE-AD include the patient-reported global AD severity, numerical rating scale (NRS) worst or average itch in the past 7 days, the Skin Pain NRS, and the Sleep Quality NRS, which each take fewer than 30 seconds to complete. “You can have your nurses do this or can you have the patients fill out the form in the waiting area before they see you,” Dr. Silverberg said.
He also advises asking patients about the number of nights they experience sleep disturbance and if they have difficulty falling asleep or have nighttime awakenings because of their AD. Symptoms of anxiety and depression can be assessed with the Hospital Anxiety and Depression Scale and the Patient-Health Questionnaire–9, which each take 2-3 minutes to complete.
Recommended assessment tools for other symptoms – such as bleeding, oozing, and xerosis – include the Patient-Oriented Eczema Measure, which takes 2-3 minutes to complete, and the Atopic Dermatitis Control Tool or the Recap of Atopic Eczema, which each take 2-3 minutes to complete.
Comorbid health disorders
Comorbid health disorders linked to AD are varied and include atopic comorbidities such as asthma or wheeze, hay fever or oculonasal symptoms, food allergy, recurrent infections such as herpes simplex virus, mental health disorders, alopecia areata, Th1-mediated comorbidities, and adverse events to medication such as venous thromboembolism, hypertension, and impaired renal or liver function. “All of these are important because if the patients have these at baseline, they may not be good candidates for some therapies that cause these types of side effects,” Dr. Silverberg said.
Response to therapy, intensity of lesions
As for response to therapy, clinicians can ask patients, “How do you feel you’re improving?” But it’s also important to assess the signs, symptoms, frequency of flares, and comorbidities as part of that response to therapy, “and of course the adverse events and treatment burden,” he said.
For the intensity of lesions component of DESCRIBE-AD, Dr. Silverberg said that the Investigator’s Global Assessment–AD is an effective tool for clinical use. “You can also use tools like the Eczema Area and Severity Index or the Scoring AD, but recognize these are challenging,” and can be difficult to use if not well trained to use them, he said. “At the very least, do an Investigator’s Global Assessment and do a body surface area measurement.”
In his opinion, four key signs that should be assessed in clinical trials are erythema, edema/papulation, excoriation, and lichenification/prurigo nodules.
Burden of disease
In terms of assessing AD disease burden, guidelines from the American Academy of Dermatology don’t give a specific tool to use, but recommend asking open-ended questions, Dr. Silverberg said. “I would not recommend that, because when you ask an open-ended question, the flood gates open up because most patients are suffering miserably with this disease when it’s uncontrolled.
“That’s why it’s valuable to use structured, validated tools like the Dermatology Life Quality Index and the Patient Reported Outcome Measurement Information System. They don’t take a lot of time to complete, and you can look at the score and determine how burdensome their disease is, even in a busy clinical practice. They’re not going to slow you down; they’re going to speed you up and make you better at your therapeutic decision-making. I can guarantee you that most patients will love you for it. Sometimes patients say to me, ‘you’re the first doctor to ask these questions.’ ”
Extent of disease
Finally, for the extent of disease component of DESCRIBE-AD, he emphasized the importance of doing a full-body exam to appreciate the affected body surface area, flexural versus extensor distribution, and involvement and severity of disease on special sites such as the face, hands, feet, genitals, and scalp.
Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
FROM REVOLUTIONIZING AD 2021
Nadolol bests propranolol for infantile hemangioma treatment out to 52 weeks
of 71 patients showed.
“In clinical practice, we notice that nadolol works very well in terms of controlling the size and the appearance of the hemangioma,” lead study author Elena Pope, MD, MSc, said during the annual meeting of the Society for Pediatric Dermatology. Hence, she and her colleagues were interested in comparing their clinical experience with the standard treatment with propranolol, and designed a prospective, randomized, controlled, double-blinded study, with the aim of proving that “nadolol is noninferior to propranolol, with a margin of noninferiority of 10%.”
Between 2016 and 2020, Dr. Pope and colleagues at two academic Canadian pediatric dermatology centers enrolled 71 infants aged 1-6 months with significant hemangioma that had either the potential for functional impairment or cosmetic deformity, defined as a lesion greater than 1.5 cm on the face or greater than 3 cm on another body part. Treatment consisted of oral propranolol or nadolol in escalating doses up to 2 mg/kg per day. “The blinding portion of the study was for 24 weeks with a follow-up up to 52 weeks,” said Dr. Pope, professor of pediatrics at the University of Toronto and section head of pediatric dermatology at The Hospital for Sick Children, also in Toronto. “After the unblinding at 24 weeks, patients were allowed to switch their intervention if they were not happy with the results.”
Of the 71 patients, 35 received nadolol and 36 received propranolol. The two groups were similar in terms of clinical and demographic characteristics. Their mean age at enrollment was 3.15 months, 80% were female, 61% were White, 20% were Asian, and the rest were from other ethnic backgrounds.
At 24 weeks, the researchers found that the mean size involution was 97.94% in the nadolol group and 89.14% in the propranolol group (P = .005), while the mean color fading on the visual analogue scale (VAS) was 94.47% in the nadolol group and 80.54% in the propranolol group (P < .001). At 52 weeks, the mean size involution was 99.63% in the nadolol group and 93.63% in the propranolol group (P = .001), while the mean VAS color fading was 97.34% in the nadolol group and 87.23% in the propranolol group (P = .001).
According to Dr. Pope, Kaplan-Meir analysis showed that patients in the propranolol group responded slower to treatment (P = .019), while safety data was similar between the two groups. For example, between weeks 25 and 52, 84.2% of patients in the nadolol group experienced an adverse event, compared with 74.2% of patients in the propranolol group (P = .466). The most common respiratory adverse event was upper respiratory tract infection, which affected 87.5% of patients in the nadolol group, compared with 100% of patients in the propranolol group (P = 0.341).
The most common gastrointestinal adverse event was diarrhea, which affected 66.7% of patients in both groups. One patient in the propranolol group was admitted to the hospital with pneumonia and fully recovered. The incident was not suspected to be related to the medication.
“We believe that this data backs up our clinical experience and it may offer an alternative treatment in other centers where patients experience propranolol unresponsiveness, side effects, or intolerance, or where a fast response is needed,” Dr. Pope said. As for the potential cost implications, “nadolol is cheaper than the Hemangiol but comparable with the compounded formulation of propranolol.”
Concern over the safety of nadolol was raised in a case report published in Pediatrics in 2020. Authors from Alberta reported the case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity,” the authors wrote.
In a reply to the authors in the same issue of Pediatrics, Dr. Pope, Cathryn Sibbald, MD, and Erin Chung, PhD, pointed out that postmortem redistribution of medications “is complex and measured postmortem cardiac blood concentrations may be significantly higher than the true blood nadolol concentration at the time of death due to significant diffusion from the peripheral tissues.”
They added that the report did not address “other potential errors such as in compounding, dispensing, and administration of the solution,” they wrote, adding: “Finally, we are aware of a Canadian case of death in an infant receiving propranolol, although the cause of death in that case was unable to be determined (ISMP Canada 2016 Safety Bulletin).We agree with the authors that careful consideration of the risks and benefits of beta-blocker therapy should be employed, parents need to be informed when to discontinue therapy and that further research into the pharmacokinetics and pharmacogenetics of beta-blockers are warranted.”
Following publication of the case report in Pediatrics, Dr. Pope said that the only change she made in her practice was to ask families to temporarily discontinue nadolol if their child had constipation for more than 5 days.
The study was supported by a grant from Physician Services, Inc. Dr. Pope reported having no financial disclosures.
of 71 patients showed.
“In clinical practice, we notice that nadolol works very well in terms of controlling the size and the appearance of the hemangioma,” lead study author Elena Pope, MD, MSc, said during the annual meeting of the Society for Pediatric Dermatology. Hence, she and her colleagues were interested in comparing their clinical experience with the standard treatment with propranolol, and designed a prospective, randomized, controlled, double-blinded study, with the aim of proving that “nadolol is noninferior to propranolol, with a margin of noninferiority of 10%.”
Between 2016 and 2020, Dr. Pope and colleagues at two academic Canadian pediatric dermatology centers enrolled 71 infants aged 1-6 months with significant hemangioma that had either the potential for functional impairment or cosmetic deformity, defined as a lesion greater than 1.5 cm on the face or greater than 3 cm on another body part. Treatment consisted of oral propranolol or nadolol in escalating doses up to 2 mg/kg per day. “The blinding portion of the study was for 24 weeks with a follow-up up to 52 weeks,” said Dr. Pope, professor of pediatrics at the University of Toronto and section head of pediatric dermatology at The Hospital for Sick Children, also in Toronto. “After the unblinding at 24 weeks, patients were allowed to switch their intervention if they were not happy with the results.”
Of the 71 patients, 35 received nadolol and 36 received propranolol. The two groups were similar in terms of clinical and demographic characteristics. Their mean age at enrollment was 3.15 months, 80% were female, 61% were White, 20% were Asian, and the rest were from other ethnic backgrounds.
At 24 weeks, the researchers found that the mean size involution was 97.94% in the nadolol group and 89.14% in the propranolol group (P = .005), while the mean color fading on the visual analogue scale (VAS) was 94.47% in the nadolol group and 80.54% in the propranolol group (P < .001). At 52 weeks, the mean size involution was 99.63% in the nadolol group and 93.63% in the propranolol group (P = .001), while the mean VAS color fading was 97.34% in the nadolol group and 87.23% in the propranolol group (P = .001).
According to Dr. Pope, Kaplan-Meir analysis showed that patients in the propranolol group responded slower to treatment (P = .019), while safety data was similar between the two groups. For example, between weeks 25 and 52, 84.2% of patients in the nadolol group experienced an adverse event, compared with 74.2% of patients in the propranolol group (P = .466). The most common respiratory adverse event was upper respiratory tract infection, which affected 87.5% of patients in the nadolol group, compared with 100% of patients in the propranolol group (P = 0.341).
The most common gastrointestinal adverse event was diarrhea, which affected 66.7% of patients in both groups. One patient in the propranolol group was admitted to the hospital with pneumonia and fully recovered. The incident was not suspected to be related to the medication.
“We believe that this data backs up our clinical experience and it may offer an alternative treatment in other centers where patients experience propranolol unresponsiveness, side effects, or intolerance, or where a fast response is needed,” Dr. Pope said. As for the potential cost implications, “nadolol is cheaper than the Hemangiol but comparable with the compounded formulation of propranolol.”
Concern over the safety of nadolol was raised in a case report published in Pediatrics in 2020. Authors from Alberta reported the case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity,” the authors wrote.
In a reply to the authors in the same issue of Pediatrics, Dr. Pope, Cathryn Sibbald, MD, and Erin Chung, PhD, pointed out that postmortem redistribution of medications “is complex and measured postmortem cardiac blood concentrations may be significantly higher than the true blood nadolol concentration at the time of death due to significant diffusion from the peripheral tissues.”
They added that the report did not address “other potential errors such as in compounding, dispensing, and administration of the solution,” they wrote, adding: “Finally, we are aware of a Canadian case of death in an infant receiving propranolol, although the cause of death in that case was unable to be determined (ISMP Canada 2016 Safety Bulletin).We agree with the authors that careful consideration of the risks and benefits of beta-blocker therapy should be employed, parents need to be informed when to discontinue therapy and that further research into the pharmacokinetics and pharmacogenetics of beta-blockers are warranted.”
Following publication of the case report in Pediatrics, Dr. Pope said that the only change she made in her practice was to ask families to temporarily discontinue nadolol if their child had constipation for more than 5 days.
The study was supported by a grant from Physician Services, Inc. Dr. Pope reported having no financial disclosures.
of 71 patients showed.
“In clinical practice, we notice that nadolol works very well in terms of controlling the size and the appearance of the hemangioma,” lead study author Elena Pope, MD, MSc, said during the annual meeting of the Society for Pediatric Dermatology. Hence, she and her colleagues were interested in comparing their clinical experience with the standard treatment with propranolol, and designed a prospective, randomized, controlled, double-blinded study, with the aim of proving that “nadolol is noninferior to propranolol, with a margin of noninferiority of 10%.”
Between 2016 and 2020, Dr. Pope and colleagues at two academic Canadian pediatric dermatology centers enrolled 71 infants aged 1-6 months with significant hemangioma that had either the potential for functional impairment or cosmetic deformity, defined as a lesion greater than 1.5 cm on the face or greater than 3 cm on another body part. Treatment consisted of oral propranolol or nadolol in escalating doses up to 2 mg/kg per day. “The blinding portion of the study was for 24 weeks with a follow-up up to 52 weeks,” said Dr. Pope, professor of pediatrics at the University of Toronto and section head of pediatric dermatology at The Hospital for Sick Children, also in Toronto. “After the unblinding at 24 weeks, patients were allowed to switch their intervention if they were not happy with the results.”
Of the 71 patients, 35 received nadolol and 36 received propranolol. The two groups were similar in terms of clinical and demographic characteristics. Their mean age at enrollment was 3.15 months, 80% were female, 61% were White, 20% were Asian, and the rest were from other ethnic backgrounds.
At 24 weeks, the researchers found that the mean size involution was 97.94% in the nadolol group and 89.14% in the propranolol group (P = .005), while the mean color fading on the visual analogue scale (VAS) was 94.47% in the nadolol group and 80.54% in the propranolol group (P < .001). At 52 weeks, the mean size involution was 99.63% in the nadolol group and 93.63% in the propranolol group (P = .001), while the mean VAS color fading was 97.34% in the nadolol group and 87.23% in the propranolol group (P = .001).
According to Dr. Pope, Kaplan-Meir analysis showed that patients in the propranolol group responded slower to treatment (P = .019), while safety data was similar between the two groups. For example, between weeks 25 and 52, 84.2% of patients in the nadolol group experienced an adverse event, compared with 74.2% of patients in the propranolol group (P = .466). The most common respiratory adverse event was upper respiratory tract infection, which affected 87.5% of patients in the nadolol group, compared with 100% of patients in the propranolol group (P = 0.341).
The most common gastrointestinal adverse event was diarrhea, which affected 66.7% of patients in both groups. One patient in the propranolol group was admitted to the hospital with pneumonia and fully recovered. The incident was not suspected to be related to the medication.
“We believe that this data backs up our clinical experience and it may offer an alternative treatment in other centers where patients experience propranolol unresponsiveness, side effects, or intolerance, or where a fast response is needed,” Dr. Pope said. As for the potential cost implications, “nadolol is cheaper than the Hemangiol but comparable with the compounded formulation of propranolol.”
Concern over the safety of nadolol was raised in a case report published in Pediatrics in 2020. Authors from Alberta reported the case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity,” the authors wrote.
In a reply to the authors in the same issue of Pediatrics, Dr. Pope, Cathryn Sibbald, MD, and Erin Chung, PhD, pointed out that postmortem redistribution of medications “is complex and measured postmortem cardiac blood concentrations may be significantly higher than the true blood nadolol concentration at the time of death due to significant diffusion from the peripheral tissues.”
They added that the report did not address “other potential errors such as in compounding, dispensing, and administration of the solution,” they wrote, adding: “Finally, we are aware of a Canadian case of death in an infant receiving propranolol, although the cause of death in that case was unable to be determined (ISMP Canada 2016 Safety Bulletin).We agree with the authors that careful consideration of the risks and benefits of beta-blocker therapy should be employed, parents need to be informed when to discontinue therapy and that further research into the pharmacokinetics and pharmacogenetics of beta-blockers are warranted.”
Following publication of the case report in Pediatrics, Dr. Pope said that the only change she made in her practice was to ask families to temporarily discontinue nadolol if their child had constipation for more than 5 days.
The study was supported by a grant from Physician Services, Inc. Dr. Pope reported having no financial disclosures.
FROM SPD 2021
Study eyes impact of isotretinoin on triglycerides, other lab measures
.
“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”
To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.
Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.
Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.
“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”
She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”
In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”
The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.
.
“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”
To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.
Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.
Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.
“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”
She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”
In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”
The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.
.
“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”
To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.
Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.
Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.
“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”
She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”
In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”
The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.
FROM SPD 2021
Isotretinoin benefits similar in overweight, obese adolescents, and those in normal weight range
a retrospective cohort study found.
“Oral isotretinoin is among the most effective treatments for acne and is indicated for the treatment of severe acne or when first-line regimens have failed,” Maggie Tallmadge said at the annual meeting of the Society for Pediatric Dermatology. In adolescents with acne, isotretinoin is prescribed at a dose of 0.5-1 mg/kg per day “with the goal of reaching a cumulative dose of 120-150 mg/kg and clinical clearance with durable remission,” she said. “Most providers do not prescribe a daily dose over 80 mg due to perceived increased risk of side effects, including xerosis, cheilitis, liver dysfunction, and acne flare. However, many adolescents weigh over 80 kg and are therefore effectively underdosed, prolonging treatment time and possibly increasing the risk of side effects due to prolonged therapy.”
To evaluate differences in treatment courses among normal-weight, overweight, and obese adolescents, and the efficacy and safety of treatment, Ms. Tallmadge, a third-year medical student at the Medical College of Wisconsin, Milwaukee, and colleagues completed a retrospective chart review of 550 dermatology patients at Children’s Wisconsin, also in Milwaukee, who completed at least 2 months of isotretinoin treatment for acne when they were between the ages of 10 and 24, from November 2012 to January 2020. They collected data on age, weight, height, daily dose, cumulative dose, time to acne clearance, side effects, and acne recurrence after treatment, and classified patients as normal weight, overweight, or obese based on their body mass index for age percentile.
Of the 550 patients, 367 (67%) were normal weight, 101 (18%) were overweight, and 82 (15%) were obese. The median age of those in the normal-weight and overweight groups was 16, and was 15 in the obese group.
There was were significant differences in the median cumulative dose in each weight group: 143.7 mg/kg for normal-weight patients, 138.2 mg/kg for overweight patients, and 140.6 mg/kg for obese patients (P < .001).
“Despite achieving different cumulative doses, there was no difference in acne clearance, relapse, and most side effects among the three [body mass index] cohorts,” Ms. Tallmadge said. “Thus, it appears that current treatment strategies may be appropriate for overweight and obese adolescents.”
The proportion of patients with acne clearance did not differ significantly among the three groups of patients: 62% who were in the normal weight range, 60% who were overweight, and 59% who were obese had clearance of facial acne with treatment (P = .84).
Of patients whose treatment course was completed by the time of data collection, the proportion with acne recurrences was similar between the three groups: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients (P > .05). Of patients whose treatment course was completed by the time of data collection, there was no significant differences in acne recurrence: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients.
However, the proportion of patients reporting headaches differed significantly between the groups: 29% of normal-weight patients, compared with 40% of both overweight and obese patients (P = .035). The researchers also observed a significant positive correlation between increased BMI and increased triglyceride and ALT levels during treatment (P < .001 for both associations), yet no elevations required clinical action.
Funding for the study was provided by the MCW Medical Student Summer Research Program and the American Acne & Rosacea Society.
a retrospective cohort study found.
“Oral isotretinoin is among the most effective treatments for acne and is indicated for the treatment of severe acne or when first-line regimens have failed,” Maggie Tallmadge said at the annual meeting of the Society for Pediatric Dermatology. In adolescents with acne, isotretinoin is prescribed at a dose of 0.5-1 mg/kg per day “with the goal of reaching a cumulative dose of 120-150 mg/kg and clinical clearance with durable remission,” she said. “Most providers do not prescribe a daily dose over 80 mg due to perceived increased risk of side effects, including xerosis, cheilitis, liver dysfunction, and acne flare. However, many adolescents weigh over 80 kg and are therefore effectively underdosed, prolonging treatment time and possibly increasing the risk of side effects due to prolonged therapy.”
To evaluate differences in treatment courses among normal-weight, overweight, and obese adolescents, and the efficacy and safety of treatment, Ms. Tallmadge, a third-year medical student at the Medical College of Wisconsin, Milwaukee, and colleagues completed a retrospective chart review of 550 dermatology patients at Children’s Wisconsin, also in Milwaukee, who completed at least 2 months of isotretinoin treatment for acne when they were between the ages of 10 and 24, from November 2012 to January 2020. They collected data on age, weight, height, daily dose, cumulative dose, time to acne clearance, side effects, and acne recurrence after treatment, and classified patients as normal weight, overweight, or obese based on their body mass index for age percentile.
Of the 550 patients, 367 (67%) were normal weight, 101 (18%) were overweight, and 82 (15%) were obese. The median age of those in the normal-weight and overweight groups was 16, and was 15 in the obese group.
There was were significant differences in the median cumulative dose in each weight group: 143.7 mg/kg for normal-weight patients, 138.2 mg/kg for overweight patients, and 140.6 mg/kg for obese patients (P < .001).
“Despite achieving different cumulative doses, there was no difference in acne clearance, relapse, and most side effects among the three [body mass index] cohorts,” Ms. Tallmadge said. “Thus, it appears that current treatment strategies may be appropriate for overweight and obese adolescents.”
The proportion of patients with acne clearance did not differ significantly among the three groups of patients: 62% who were in the normal weight range, 60% who were overweight, and 59% who were obese had clearance of facial acne with treatment (P = .84).
Of patients whose treatment course was completed by the time of data collection, the proportion with acne recurrences was similar between the three groups: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients (P > .05). Of patients whose treatment course was completed by the time of data collection, there was no significant differences in acne recurrence: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients.
However, the proportion of patients reporting headaches differed significantly between the groups: 29% of normal-weight patients, compared with 40% of both overweight and obese patients (P = .035). The researchers also observed a significant positive correlation between increased BMI and increased triglyceride and ALT levels during treatment (P < .001 for both associations), yet no elevations required clinical action.
Funding for the study was provided by the MCW Medical Student Summer Research Program and the American Acne & Rosacea Society.
a retrospective cohort study found.
“Oral isotretinoin is among the most effective treatments for acne and is indicated for the treatment of severe acne or when first-line regimens have failed,” Maggie Tallmadge said at the annual meeting of the Society for Pediatric Dermatology. In adolescents with acne, isotretinoin is prescribed at a dose of 0.5-1 mg/kg per day “with the goal of reaching a cumulative dose of 120-150 mg/kg and clinical clearance with durable remission,” she said. “Most providers do not prescribe a daily dose over 80 mg due to perceived increased risk of side effects, including xerosis, cheilitis, liver dysfunction, and acne flare. However, many adolescents weigh over 80 kg and are therefore effectively underdosed, prolonging treatment time and possibly increasing the risk of side effects due to prolonged therapy.”
To evaluate differences in treatment courses among normal-weight, overweight, and obese adolescents, and the efficacy and safety of treatment, Ms. Tallmadge, a third-year medical student at the Medical College of Wisconsin, Milwaukee, and colleagues completed a retrospective chart review of 550 dermatology patients at Children’s Wisconsin, also in Milwaukee, who completed at least 2 months of isotretinoin treatment for acne when they were between the ages of 10 and 24, from November 2012 to January 2020. They collected data on age, weight, height, daily dose, cumulative dose, time to acne clearance, side effects, and acne recurrence after treatment, and classified patients as normal weight, overweight, or obese based on their body mass index for age percentile.
Of the 550 patients, 367 (67%) were normal weight, 101 (18%) were overweight, and 82 (15%) were obese. The median age of those in the normal-weight and overweight groups was 16, and was 15 in the obese group.
There was were significant differences in the median cumulative dose in each weight group: 143.7 mg/kg for normal-weight patients, 138.2 mg/kg for overweight patients, and 140.6 mg/kg for obese patients (P < .001).
“Despite achieving different cumulative doses, there was no difference in acne clearance, relapse, and most side effects among the three [body mass index] cohorts,” Ms. Tallmadge said. “Thus, it appears that current treatment strategies may be appropriate for overweight and obese adolescents.”
The proportion of patients with acne clearance did not differ significantly among the three groups of patients: 62% who were in the normal weight range, 60% who were overweight, and 59% who were obese had clearance of facial acne with treatment (P = .84).
Of patients whose treatment course was completed by the time of data collection, the proportion with acne recurrences was similar between the three groups: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients (P > .05). Of patients whose treatment course was completed by the time of data collection, there was no significant differences in acne recurrence: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients.
However, the proportion of patients reporting headaches differed significantly between the groups: 29% of normal-weight patients, compared with 40% of both overweight and obese patients (P = .035). The researchers also observed a significant positive correlation between increased BMI and increased triglyceride and ALT levels during treatment (P < .001 for both associations), yet no elevations required clinical action.
Funding for the study was provided by the MCW Medical Student Summer Research Program and the American Acne & Rosacea Society.
FROM SPD 2021
Study spanning 2 decades offers insights into pediatric psoriasis trends
, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.
Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.
“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”
To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.
Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).
Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).
Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.
The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.
Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”
Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).
“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”
In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.
“Though methodologies and patient populations differ among studies, what is striking,” she said, is the percentage of overweight/obese patients (37%; defined as a body mass index ≥ 85th percentile) “in our 2-decade single institution dataset.” This “is nearly identical” to the percentage of patients with excess adiposity – 37.9% (also defined as BMI ≥ 85th percentile) – in an international cross-sectional study, which also identified an association between obesity (BMI ≥ 95th percentile) and psoriasis severity in children, she noted.
“What is clear is the strong association between obesity and childhood psoriasis, as multiple studies, including ours, confirm obesity as a major comorbidity of pediatric psoriasis,” Dr. Cordoro said. “Both conditions must be adequately managed to reduce the risk of adverse health outcomes for obese patients with psoriasis.”
The other study coauthors were Dana Feigenbaum, MD, and Alana Ju, MD. The work was supported by the UCSF Yearlong Inquiry Program. The researchers reported having no relevant financial disclosures.
, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.
Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.
“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”
To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.
Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).
Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).
Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.
The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.
Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”
Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).
“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”
In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.
“Though methodologies and patient populations differ among studies, what is striking,” she said, is the percentage of overweight/obese patients (37%; defined as a body mass index ≥ 85th percentile) “in our 2-decade single institution dataset.” This “is nearly identical” to the percentage of patients with excess adiposity – 37.9% (also defined as BMI ≥ 85th percentile) – in an international cross-sectional study, which also identified an association between obesity (BMI ≥ 95th percentile) and psoriasis severity in children, she noted.
“What is clear is the strong association between obesity and childhood psoriasis, as multiple studies, including ours, confirm obesity as a major comorbidity of pediatric psoriasis,” Dr. Cordoro said. “Both conditions must be adequately managed to reduce the risk of adverse health outcomes for obese patients with psoriasis.”
The other study coauthors were Dana Feigenbaum, MD, and Alana Ju, MD. The work was supported by the UCSF Yearlong Inquiry Program. The researchers reported having no relevant financial disclosures.
, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.
Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.
“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”
To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.
Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).
Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).
Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.
The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.
Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”
Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).
“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”
In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.
“Though methodologies and patient populations differ among studies, what is striking,” she said, is the percentage of overweight/obese patients (37%; defined as a body mass index ≥ 85th percentile) “in our 2-decade single institution dataset.” This “is nearly identical” to the percentage of patients with excess adiposity – 37.9% (also defined as BMI ≥ 85th percentile) – in an international cross-sectional study, which also identified an association between obesity (BMI ≥ 95th percentile) and psoriasis severity in children, she noted.
“What is clear is the strong association between obesity and childhood psoriasis, as multiple studies, including ours, confirm obesity as a major comorbidity of pediatric psoriasis,” Dr. Cordoro said. “Both conditions must be adequately managed to reduce the risk of adverse health outcomes for obese patients with psoriasis.”
The other study coauthors were Dana Feigenbaum, MD, and Alana Ju, MD. The work was supported by the UCSF Yearlong Inquiry Program. The researchers reported having no relevant financial disclosures.
FROM SPD 2021
How well do JAK inhibitors work for atopic dermatitis?
largely because of the heterogeneous nature of the disease.
“Atopic dermatitis patients have different complaints,” Jacob P. Thyssen, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Some of them have repeated infections. Some have psychiatric symptoms. Others have widespread eczema. When you talk about how well they work, it really depends on what aspects of AD, what subgroups of AD, and how well they work with comorbidities of AD.”
Baricitinib, a JAK1/JAK2 inhibitor in 2-mg and 4-mg tablets, is available in the European Union, and is under Food and Drug Administration review for AD in the United States. Two JAK1 inhibitors continue to be evaluated in AD clinical trials and are also under FDA review for AD: abrocitinib (100 mg and 200 mg) and upadacitinib (15 mg and 30 mg). None of these agents have been tested in head-to-head trials and only one (abrocitinib) has been compared with the interleukin-4 receptor–alpha antagonist dupilumab, which makes meaningful direct comparisons impossible. (Baricitinib and upadacitinib are approved for treating RA in the United States.)
In his informal assessment from clinical trial data of how these three JAK inhibitors compare with the biologic agents dupilumab and tralokinumab, with potency as an indication, Dr. Thyssen, professor of dermatology at the University of Copenhagen, observed that abrocitinib and dupilumab “are somewhere in the middle,” tralokinumab and baricitinib are “slightly weaker,” while upadacitinib is “very potent.” (Dupilumab is approved by the FDA for treating AD ages 6 and older, and tralokinumab, a fully human monoclonal antibody that binds to IL-13, is under FDA review for AD.)
However, he cautioned that making direct comparisons of these drugs is limited by differences in clinical trial designs, trial length, severity of disease at baseline, and demographics. “Placebo effects also differ between trials, and the speed of onset is different between JAK inhibitors and biologic agents. Because of this, efficacy can be difficult to assess over 12-16 weeks. That’s why long-term studies are necessary.”
It’s also tricky to compare safety signals with baricitinib, abrocitinib, and upadacitinib, “because some of them are JAK1 inhibitors; others are JAK1/JAK2 inhibitors,” he continued. “Even the molecules that inhibit JAK1 are different, so making a comparison between abrocitinib and upadacitinib requires studies that do this is in the best way and over a long period of time.”
Safety signals
Common safety signals in this drug class include nasopharyngitis, nausea, and headache. “Many of these are short lasting, meaning that patients will perhaps have a headache for a day or two and then it will be over,” said Dr. Thyssen, who is also a consultant dermatologist at Bispebjerg Hospital in Copenhagen. “This means that even though we see high proportions of safety signals, this is probably not going to limit the use of JAK inhibitors in most of our patients. Then we have an acne signal in higher proportions for abrocitinib and upadacitinib than for baricitinib, so perhaps this is related to the potency.”
There is also an increased risk for infections, including herpes zoster. “Is this a class effect?” he asked. “We see quite a bit for baricitinib, particularly when it’s used for rheumatoid arthritis. We also see it in AD patients, but we don’t know to what degree yet. We need the real-world evidence before we can make any conclusions.” Routine blood monitoring tests are also required in patients taking JAK inhibitors, because of the risk for leukopenia and effects on liver enzymes.
Then there’s the risk of deep vein thrombosis/pulmonary embolism. “This is mostly linked to baricitinib use, but is this a class effect or is it specific to baricitinib?” he asked. “We’ll have to wait and see, but I think overall, this is not something I have great fear of because we see that AD patients are young, usually with a normal [body mass index], at least in Europe. But we have to study this closely.”
From a clinical standpoint, JAK1/2 inhibitors work well on every measurable aspect of AD, he said, including eczema severity, itch, skin pain, sleep, and quality of life. “Based on conference abstracts and publications, they seem to work equally well independent of race, BMI, atopy status, age, and whether their AD is extrinsic or intrinsic,” Dr. Thyssen added. “One thing we haven’t learned from the companies is, what patients have the highest likelihood of getting a good treatment response? We don’t have good biomarkers yet, but anything the companies can do to help us identify the patients with the greatest chance of success would be so welcome.”
The best available data suggest that JAK inhibitors benefit AD patients with certain comorbidities, including inflammatory bowel disease (with upadacitinib), RA (with both baricitinib and upadacitinib), and alopecia areata (with baricitinib). “These drugs also have been shown to work well for the psychiatric symptoms of disease,” he said.
“As for patients with type 2 inflammation in the airways such as asthma and rhinitis, dupilumab works, but do the JAK inhibitors work? It’s possible from a mode of action standpoint, but we don’t know.” It also remains unclear how JAK inhibitors will fare in the treatment of chronic hand eczema and ocular surface disease, like allergic conjunctivitis, he said.
Despite the unknowns, Dr. Thyssen emphasized the promise that JAK inhibitors hold for AD patients. “We know they provide good AD control,” he said. “For some, like baricitinib, you may need to instruct the patient to use topical corticosteroids as well, but this does not seem to be necessary for upadacitinib and abrocitinib. You really have a single bullet here that will take away most of the problems for many patients, with very fast onset of action, which is important for our patients.”
Dr. Thyssen disclosed that he is a speaker, advisory board member, and/or investigator for Regeneron, Sanofi-Genzyme, Eli Lilly, Pfizer, LEO Pharma, AbbVie, and Almirall.
largely because of the heterogeneous nature of the disease.
“Atopic dermatitis patients have different complaints,” Jacob P. Thyssen, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Some of them have repeated infections. Some have psychiatric symptoms. Others have widespread eczema. When you talk about how well they work, it really depends on what aspects of AD, what subgroups of AD, and how well they work with comorbidities of AD.”
Baricitinib, a JAK1/JAK2 inhibitor in 2-mg and 4-mg tablets, is available in the European Union, and is under Food and Drug Administration review for AD in the United States. Two JAK1 inhibitors continue to be evaluated in AD clinical trials and are also under FDA review for AD: abrocitinib (100 mg and 200 mg) and upadacitinib (15 mg and 30 mg). None of these agents have been tested in head-to-head trials and only one (abrocitinib) has been compared with the interleukin-4 receptor–alpha antagonist dupilumab, which makes meaningful direct comparisons impossible. (Baricitinib and upadacitinib are approved for treating RA in the United States.)
In his informal assessment from clinical trial data of how these three JAK inhibitors compare with the biologic agents dupilumab and tralokinumab, with potency as an indication, Dr. Thyssen, professor of dermatology at the University of Copenhagen, observed that abrocitinib and dupilumab “are somewhere in the middle,” tralokinumab and baricitinib are “slightly weaker,” while upadacitinib is “very potent.” (Dupilumab is approved by the FDA for treating AD ages 6 and older, and tralokinumab, a fully human monoclonal antibody that binds to IL-13, is under FDA review for AD.)
However, he cautioned that making direct comparisons of these drugs is limited by differences in clinical trial designs, trial length, severity of disease at baseline, and demographics. “Placebo effects also differ between trials, and the speed of onset is different between JAK inhibitors and biologic agents. Because of this, efficacy can be difficult to assess over 12-16 weeks. That’s why long-term studies are necessary.”
It’s also tricky to compare safety signals with baricitinib, abrocitinib, and upadacitinib, “because some of them are JAK1 inhibitors; others are JAK1/JAK2 inhibitors,” he continued. “Even the molecules that inhibit JAK1 are different, so making a comparison between abrocitinib and upadacitinib requires studies that do this is in the best way and over a long period of time.”
Safety signals
Common safety signals in this drug class include nasopharyngitis, nausea, and headache. “Many of these are short lasting, meaning that patients will perhaps have a headache for a day or two and then it will be over,” said Dr. Thyssen, who is also a consultant dermatologist at Bispebjerg Hospital in Copenhagen. “This means that even though we see high proportions of safety signals, this is probably not going to limit the use of JAK inhibitors in most of our patients. Then we have an acne signal in higher proportions for abrocitinib and upadacitinib than for baricitinib, so perhaps this is related to the potency.”
There is also an increased risk for infections, including herpes zoster. “Is this a class effect?” he asked. “We see quite a bit for baricitinib, particularly when it’s used for rheumatoid arthritis. We also see it in AD patients, but we don’t know to what degree yet. We need the real-world evidence before we can make any conclusions.” Routine blood monitoring tests are also required in patients taking JAK inhibitors, because of the risk for leukopenia and effects on liver enzymes.
Then there’s the risk of deep vein thrombosis/pulmonary embolism. “This is mostly linked to baricitinib use, but is this a class effect or is it specific to baricitinib?” he asked. “We’ll have to wait and see, but I think overall, this is not something I have great fear of because we see that AD patients are young, usually with a normal [body mass index], at least in Europe. But we have to study this closely.”
From a clinical standpoint, JAK1/2 inhibitors work well on every measurable aspect of AD, he said, including eczema severity, itch, skin pain, sleep, and quality of life. “Based on conference abstracts and publications, they seem to work equally well independent of race, BMI, atopy status, age, and whether their AD is extrinsic or intrinsic,” Dr. Thyssen added. “One thing we haven’t learned from the companies is, what patients have the highest likelihood of getting a good treatment response? We don’t have good biomarkers yet, but anything the companies can do to help us identify the patients with the greatest chance of success would be so welcome.”
The best available data suggest that JAK inhibitors benefit AD patients with certain comorbidities, including inflammatory bowel disease (with upadacitinib), RA (with both baricitinib and upadacitinib), and alopecia areata (with baricitinib). “These drugs also have been shown to work well for the psychiatric symptoms of disease,” he said.
“As for patients with type 2 inflammation in the airways such as asthma and rhinitis, dupilumab works, but do the JAK inhibitors work? It’s possible from a mode of action standpoint, but we don’t know.” It also remains unclear how JAK inhibitors will fare in the treatment of chronic hand eczema and ocular surface disease, like allergic conjunctivitis, he said.
Despite the unknowns, Dr. Thyssen emphasized the promise that JAK inhibitors hold for AD patients. “We know they provide good AD control,” he said. “For some, like baricitinib, you may need to instruct the patient to use topical corticosteroids as well, but this does not seem to be necessary for upadacitinib and abrocitinib. You really have a single bullet here that will take away most of the problems for many patients, with very fast onset of action, which is important for our patients.”
Dr. Thyssen disclosed that he is a speaker, advisory board member, and/or investigator for Regeneron, Sanofi-Genzyme, Eli Lilly, Pfizer, LEO Pharma, AbbVie, and Almirall.
largely because of the heterogeneous nature of the disease.
“Atopic dermatitis patients have different complaints,” Jacob P. Thyssen, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Some of them have repeated infections. Some have psychiatric symptoms. Others have widespread eczema. When you talk about how well they work, it really depends on what aspects of AD, what subgroups of AD, and how well they work with comorbidities of AD.”
Baricitinib, a JAK1/JAK2 inhibitor in 2-mg and 4-mg tablets, is available in the European Union, and is under Food and Drug Administration review for AD in the United States. Two JAK1 inhibitors continue to be evaluated in AD clinical trials and are also under FDA review for AD: abrocitinib (100 mg and 200 mg) and upadacitinib (15 mg and 30 mg). None of these agents have been tested in head-to-head trials and only one (abrocitinib) has been compared with the interleukin-4 receptor–alpha antagonist dupilumab, which makes meaningful direct comparisons impossible. (Baricitinib and upadacitinib are approved for treating RA in the United States.)
In his informal assessment from clinical trial data of how these three JAK inhibitors compare with the biologic agents dupilumab and tralokinumab, with potency as an indication, Dr. Thyssen, professor of dermatology at the University of Copenhagen, observed that abrocitinib and dupilumab “are somewhere in the middle,” tralokinumab and baricitinib are “slightly weaker,” while upadacitinib is “very potent.” (Dupilumab is approved by the FDA for treating AD ages 6 and older, and tralokinumab, a fully human monoclonal antibody that binds to IL-13, is under FDA review for AD.)
However, he cautioned that making direct comparisons of these drugs is limited by differences in clinical trial designs, trial length, severity of disease at baseline, and demographics. “Placebo effects also differ between trials, and the speed of onset is different between JAK inhibitors and biologic agents. Because of this, efficacy can be difficult to assess over 12-16 weeks. That’s why long-term studies are necessary.”
It’s also tricky to compare safety signals with baricitinib, abrocitinib, and upadacitinib, “because some of them are JAK1 inhibitors; others are JAK1/JAK2 inhibitors,” he continued. “Even the molecules that inhibit JAK1 are different, so making a comparison between abrocitinib and upadacitinib requires studies that do this is in the best way and over a long period of time.”
Safety signals
Common safety signals in this drug class include nasopharyngitis, nausea, and headache. “Many of these are short lasting, meaning that patients will perhaps have a headache for a day or two and then it will be over,” said Dr. Thyssen, who is also a consultant dermatologist at Bispebjerg Hospital in Copenhagen. “This means that even though we see high proportions of safety signals, this is probably not going to limit the use of JAK inhibitors in most of our patients. Then we have an acne signal in higher proportions for abrocitinib and upadacitinib than for baricitinib, so perhaps this is related to the potency.”
There is also an increased risk for infections, including herpes zoster. “Is this a class effect?” he asked. “We see quite a bit for baricitinib, particularly when it’s used for rheumatoid arthritis. We also see it in AD patients, but we don’t know to what degree yet. We need the real-world evidence before we can make any conclusions.” Routine blood monitoring tests are also required in patients taking JAK inhibitors, because of the risk for leukopenia and effects on liver enzymes.
Then there’s the risk of deep vein thrombosis/pulmonary embolism. “This is mostly linked to baricitinib use, but is this a class effect or is it specific to baricitinib?” he asked. “We’ll have to wait and see, but I think overall, this is not something I have great fear of because we see that AD patients are young, usually with a normal [body mass index], at least in Europe. But we have to study this closely.”
From a clinical standpoint, JAK1/2 inhibitors work well on every measurable aspect of AD, he said, including eczema severity, itch, skin pain, sleep, and quality of life. “Based on conference abstracts and publications, they seem to work equally well independent of race, BMI, atopy status, age, and whether their AD is extrinsic or intrinsic,” Dr. Thyssen added. “One thing we haven’t learned from the companies is, what patients have the highest likelihood of getting a good treatment response? We don’t have good biomarkers yet, but anything the companies can do to help us identify the patients with the greatest chance of success would be so welcome.”
The best available data suggest that JAK inhibitors benefit AD patients with certain comorbidities, including inflammatory bowel disease (with upadacitinib), RA (with both baricitinib and upadacitinib), and alopecia areata (with baricitinib). “These drugs also have been shown to work well for the psychiatric symptoms of disease,” he said.
“As for patients with type 2 inflammation in the airways such as asthma and rhinitis, dupilumab works, but do the JAK inhibitors work? It’s possible from a mode of action standpoint, but we don’t know.” It also remains unclear how JAK inhibitors will fare in the treatment of chronic hand eczema and ocular surface disease, like allergic conjunctivitis, he said.
Despite the unknowns, Dr. Thyssen emphasized the promise that JAK inhibitors hold for AD patients. “We know they provide good AD control,” he said. “For some, like baricitinib, you may need to instruct the patient to use topical corticosteroids as well, but this does not seem to be necessary for upadacitinib and abrocitinib. You really have a single bullet here that will take away most of the problems for many patients, with very fast onset of action, which is important for our patients.”
Dr. Thyssen disclosed that he is a speaker, advisory board member, and/or investigator for Regeneron, Sanofi-Genzyme, Eli Lilly, Pfizer, LEO Pharma, AbbVie, and Almirall.
FROM REVOLUTIONIZING AD 2021
Expert shares practical considerations when prescribing dupilumab
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This scenario was illustrated in a 2020 retrospective study of 179 adults with AD who were cared for at the University of Pittsburgh Medical Center, which found that 37% did not start dupilumab, mainly due to insurance denial (19%) and high copay (11%).
“We’ve all seen this in our practice,” Amy S. Paller, MD, said during the Revolutionizing Atopic Dermatitis symposium. “We’ve also seen the denials until we get step therapy in there, so if I have a child whom I want to treat with dupilumab for safety reasons, I don’t like being told that I’m going to have to use cyclosporine or methotrexate or a medication that I think may have higher risks and certainly [would] require blood monitoring–yet that’s the state for some patients.”
Dupilumab, an interleukin-4 receptor alpha antagonist, is approved for treatment of moderate to severe AD in patients ages 6 and older.
When working to obtain insurance approval of dupilumab, Dr. Paller reminded dermatologists to document that the patient has moderate to severe AD “and document the negative effect on quality of life in order to try to help make it easier to get these medications for our patients.”
Starting patients on dupilumab
Dr. Paller, the Walter J. Hamlin Chair and Professor of Dermatology at Northwestern University, Chicago, said that if patients are on another systemic medication prior to starting dupilumab, she allows a transition period of 1-2 months. “Don’t just stop that drug because it’s ‘not working,’ ” she said. “I usually do a full dose for the first month, and a half dose for the next month before starting dupilumab. Also, don’t stop the use of topical corticosteroids. They can increase treatment response by 10%-20%, even when patients are on dupilumab.”
She recommends a 3- to 4-month trial of dupilumab while monitoring changes in disease severity, itch, and quality of life. “Usually there’s evidence of early improvement by 2 months in those who are going to do well enough to stay on the drug by about 4 months out,” she said. “In my experience, most pediatric patients do very well. In those with an inadequate response, about 50% will do better if you can increase the dose or frequency. Flares can still occur in those who do well. I usually push topicals when that happens.”
If patients respond well after starting dupilumab, Dr. Paller recommends that they continue on the drug for at least a year before considering a taper with the hope of “resetting” the immune system and having sustained improvement off drug. “Some parents and patients don’t want to stop the drug,” but for those who do, she tells them that she does not want to abruptly stop treatment, but to “space out the dosing” instead. “If someone is pretty much clear with the medication and is able to continue with topicals as you dial down, that’s great. But don’t even think about taking them off if somebody’s not clear or virtually clear, particularly if they start to flare with lower frequency.”
Data on effectiveness
Real-world data suggest that the effectiveness of dupilumab is similar to the efficacy seen in clinical trials. For example, a recently published systematic review and meta-analysis of 3,303 AD patients on dupilumab found that after 16 weeks of therapy, 60% achieved a 75% improvement in the Eczema Area and Severity (EASI75) score, and 27% achieved an EASI90. In a Dutch study of 210 adults treated with dupilumab for 52 weeks, enrolled in a Dutch registry, the mean percent reduction in EASI score was 70% at 16 weeks and 76.6% by 52 weeks.
In addition, there was at least a 4-point improvement in the Patient-Oriented Eczema Measure (POEM) score and at least a 4-point improvement in the Itch Numeric Rating Scale (NRS), said Dr. Paller, who was not involved in the study. “These patient-reported improvements were seen very early on,” she noted.
What about drug survival at 1 year? In a retrospective cohort study that drew from insurance databases, 1,963 adults given dupilumab were studied for a mean of 315 days. The rate of persistence was 92% at 6 months and 77% at 12 months. “That means that it’s still effective,” Dr. Paller said.
While that is a short period of time, she compared these results with long-term survival of nonsteroid systemic immunosuppressants such as cyclosporine, referring to a study of adults with AD treated with systemic immunosuppressants, which found “a 32% persistence rate at 12 months in drugs that require more monitoring, so more burden.”
Dr. Paller disclosed that she is a consultant to and/or an investigator for dupilumab (Dupixent) manufacturers Regeneron and Sanofi, AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, and RAPT Therapeutics.
.
This scenario was illustrated in a 2020 retrospective study of 179 adults with AD who were cared for at the University of Pittsburgh Medical Center, which found that 37% did not start dupilumab, mainly due to insurance denial (19%) and high copay (11%).
“We’ve all seen this in our practice,” Amy S. Paller, MD, said during the Revolutionizing Atopic Dermatitis symposium. “We’ve also seen the denials until we get step therapy in there, so if I have a child whom I want to treat with dupilumab for safety reasons, I don’t like being told that I’m going to have to use cyclosporine or methotrexate or a medication that I think may have higher risks and certainly [would] require blood monitoring–yet that’s the state for some patients.”
Dupilumab, an interleukin-4 receptor alpha antagonist, is approved for treatment of moderate to severe AD in patients ages 6 and older.
When working to obtain insurance approval of dupilumab, Dr. Paller reminded dermatologists to document that the patient has moderate to severe AD “and document the negative effect on quality of life in order to try to help make it easier to get these medications for our patients.”
Starting patients on dupilumab
Dr. Paller, the Walter J. Hamlin Chair and Professor of Dermatology at Northwestern University, Chicago, said that if patients are on another systemic medication prior to starting dupilumab, she allows a transition period of 1-2 months. “Don’t just stop that drug because it’s ‘not working,’ ” she said. “I usually do a full dose for the first month, and a half dose for the next month before starting dupilumab. Also, don’t stop the use of topical corticosteroids. They can increase treatment response by 10%-20%, even when patients are on dupilumab.”
She recommends a 3- to 4-month trial of dupilumab while monitoring changes in disease severity, itch, and quality of life. “Usually there’s evidence of early improvement by 2 months in those who are going to do well enough to stay on the drug by about 4 months out,” she said. “In my experience, most pediatric patients do very well. In those with an inadequate response, about 50% will do better if you can increase the dose or frequency. Flares can still occur in those who do well. I usually push topicals when that happens.”
If patients respond well after starting dupilumab, Dr. Paller recommends that they continue on the drug for at least a year before considering a taper with the hope of “resetting” the immune system and having sustained improvement off drug. “Some parents and patients don’t want to stop the drug,” but for those who do, she tells them that she does not want to abruptly stop treatment, but to “space out the dosing” instead. “If someone is pretty much clear with the medication and is able to continue with topicals as you dial down, that’s great. But don’t even think about taking them off if somebody’s not clear or virtually clear, particularly if they start to flare with lower frequency.”
Data on effectiveness
Real-world data suggest that the effectiveness of dupilumab is similar to the efficacy seen in clinical trials. For example, a recently published systematic review and meta-analysis of 3,303 AD patients on dupilumab found that after 16 weeks of therapy, 60% achieved a 75% improvement in the Eczema Area and Severity (EASI75) score, and 27% achieved an EASI90. In a Dutch study of 210 adults treated with dupilumab for 52 weeks, enrolled in a Dutch registry, the mean percent reduction in EASI score was 70% at 16 weeks and 76.6% by 52 weeks.
In addition, there was at least a 4-point improvement in the Patient-Oriented Eczema Measure (POEM) score and at least a 4-point improvement in the Itch Numeric Rating Scale (NRS), said Dr. Paller, who was not involved in the study. “These patient-reported improvements were seen very early on,” she noted.
What about drug survival at 1 year? In a retrospective cohort study that drew from insurance databases, 1,963 adults given dupilumab were studied for a mean of 315 days. The rate of persistence was 92% at 6 months and 77% at 12 months. “That means that it’s still effective,” Dr. Paller said.
While that is a short period of time, she compared these results with long-term survival of nonsteroid systemic immunosuppressants such as cyclosporine, referring to a study of adults with AD treated with systemic immunosuppressants, which found “a 32% persistence rate at 12 months in drugs that require more monitoring, so more burden.”
Dr. Paller disclosed that she is a consultant to and/or an investigator for dupilumab (Dupixent) manufacturers Regeneron and Sanofi, AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, and RAPT Therapeutics.
.
This scenario was illustrated in a 2020 retrospective study of 179 adults with AD who were cared for at the University of Pittsburgh Medical Center, which found that 37% did not start dupilumab, mainly due to insurance denial (19%) and high copay (11%).
“We’ve all seen this in our practice,” Amy S. Paller, MD, said during the Revolutionizing Atopic Dermatitis symposium. “We’ve also seen the denials until we get step therapy in there, so if I have a child whom I want to treat with dupilumab for safety reasons, I don’t like being told that I’m going to have to use cyclosporine or methotrexate or a medication that I think may have higher risks and certainly [would] require blood monitoring–yet that’s the state for some patients.”
Dupilumab, an interleukin-4 receptor alpha antagonist, is approved for treatment of moderate to severe AD in patients ages 6 and older.
When working to obtain insurance approval of dupilumab, Dr. Paller reminded dermatologists to document that the patient has moderate to severe AD “and document the negative effect on quality of life in order to try to help make it easier to get these medications for our patients.”
Starting patients on dupilumab
Dr. Paller, the Walter J. Hamlin Chair and Professor of Dermatology at Northwestern University, Chicago, said that if patients are on another systemic medication prior to starting dupilumab, she allows a transition period of 1-2 months. “Don’t just stop that drug because it’s ‘not working,’ ” she said. “I usually do a full dose for the first month, and a half dose for the next month before starting dupilumab. Also, don’t stop the use of topical corticosteroids. They can increase treatment response by 10%-20%, even when patients are on dupilumab.”
She recommends a 3- to 4-month trial of dupilumab while monitoring changes in disease severity, itch, and quality of life. “Usually there’s evidence of early improvement by 2 months in those who are going to do well enough to stay on the drug by about 4 months out,” she said. “In my experience, most pediatric patients do very well. In those with an inadequate response, about 50% will do better if you can increase the dose or frequency. Flares can still occur in those who do well. I usually push topicals when that happens.”
If patients respond well after starting dupilumab, Dr. Paller recommends that they continue on the drug for at least a year before considering a taper with the hope of “resetting” the immune system and having sustained improvement off drug. “Some parents and patients don’t want to stop the drug,” but for those who do, she tells them that she does not want to abruptly stop treatment, but to “space out the dosing” instead. “If someone is pretty much clear with the medication and is able to continue with topicals as you dial down, that’s great. But don’t even think about taking them off if somebody’s not clear or virtually clear, particularly if they start to flare with lower frequency.”
Data on effectiveness
Real-world data suggest that the effectiveness of dupilumab is similar to the efficacy seen in clinical trials. For example, a recently published systematic review and meta-analysis of 3,303 AD patients on dupilumab found that after 16 weeks of therapy, 60% achieved a 75% improvement in the Eczema Area and Severity (EASI75) score, and 27% achieved an EASI90. In a Dutch study of 210 adults treated with dupilumab for 52 weeks, enrolled in a Dutch registry, the mean percent reduction in EASI score was 70% at 16 weeks and 76.6% by 52 weeks.
In addition, there was at least a 4-point improvement in the Patient-Oriented Eczema Measure (POEM) score and at least a 4-point improvement in the Itch Numeric Rating Scale (NRS), said Dr. Paller, who was not involved in the study. “These patient-reported improvements were seen very early on,” she noted.
What about drug survival at 1 year? In a retrospective cohort study that drew from insurance databases, 1,963 adults given dupilumab were studied for a mean of 315 days. The rate of persistence was 92% at 6 months and 77% at 12 months. “That means that it’s still effective,” Dr. Paller said.
While that is a short period of time, she compared these results with long-term survival of nonsteroid systemic immunosuppressants such as cyclosporine, referring to a study of adults with AD treated with systemic immunosuppressants, which found “a 32% persistence rate at 12 months in drugs that require more monitoring, so more burden.”
Dr. Paller disclosed that she is a consultant to and/or an investigator for dupilumab (Dupixent) manufacturers Regeneron and Sanofi, AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, and RAPT Therapeutics.
FROM REVOLUTIONIZING AD 2021