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PAH care turns corner with new therapies, intensified monitoring
Aggressive up-front combination therapy, more lofty treatment goals, and earlier and more frequent reassessments to guide treatment are improving care of patients with pulmonary arterial hypertension (PAH) while at the same time making it more complex.
A larger number of oral and generic treatment options have in some respects ushered in more management ease. But overall, “I don’t know if management of these patients has ever been more complicated, given the treatment options and strategies,” said Murali M. Chakinala, MD, professor of medicine at Washington University, St. Louis. “We’re always thinking through approaches.”
Diagnosis continues to be challenging given the rarity of PAH and its nonspecific presentation – and in some cases it’s now harder. Experts such as Dr. Chakinala are seeing increasing number of aging patients with left heart disease, chronic kidney disease, and other comorbidities who have significant precapillary pulmonary hypertension and who exhibit hemodynamics consistent with PAH, or group 1 PH.
The question experts face is, do such patients have “true PAH,” as do a reported 25-50 people per million, or do they have another type of PH in the classification schema – or a mixture?
Deciding which patients “really fit into group 1 and should be managed like group 1,” Dr. Chakinala said, requires clinical acumen and has important implications, as patients with PAH are the main beneficiaries of vasodilator therapy. Most other patients with PH will not respond to or tolerate such treatment.
“These older patients may be getting PAH through different mechanisms than our younger patients, but because we define PAH through hemodynamic criteria and by ruling out other obvious explanations, they all get lumped together,” said Dr. Chakinala. “We need to parse these patients out better in the future, much like our oncology colleagues are doing.”
Personalized medicine hopefully is the next horizon for this condition, characterized by severe remodeling of the distal pulmonary arteries. Researchers are pushing to achieve deep phenotyping, identify biomarkers and improve risk assessment tools.
And with 80 or so centers now accredited by the Pulmonary Hypertension Association as Pulmonary Hypertension Care Centers, referred patients are accessing clinical trials of new nonvasodilatory drugs. Currently available therapies improve hemodynamics and symptoms, and can slow disease progression, but are not truly disease modifying, sources say.
“The endothelin, nitric oxide, and prostacyclin pathways have been exhaustively studied and we now have great drugs for those pathways,” said Dr. Chakinala, who leads the PHA’s scientific leadership council. But “we’re not going to put a greater dent into this disease until we have new drugs that work on different biologic pathways.”
Diagnostic challenges
The diagnosis of PAH – a remarkably heterogeneous condition that encompasses heritable forms and idiopathic forms, and that comprises a broad mix of predisposing conditions and exposures, from scleroderma to methamphetamine use – is still too often missed or delayed. Delayed diagnoses and misdiagnoses of PAH and other types of PH have been reported in up to 85% of at-risk patients, according to a 2016 literature review.
Being able to pivot from thinking about common pulmonary ailments or heart failure to considering PAH is a key part of earlier diagnosis and better treatment outcomes. “If someone has unexplained dyspnea or if they’re treated for other lung diseases and are not improving, think about a screening echocardiogram,” said Timothy L. Williamson, MD, vice president of quality and safety and a pulmonary and critical care physician at the University of Kansas Health Center, Kansas City.
One of the most common reasons Dr. Chakinala sees for missed diagnoses are right heart catheterizations that are incomplete or misinterpreted. (Right heart catheterizations are required to confirm the diagnosis.) “One can’t simply measure pressures and stop,” he said. “We need the full hemodynamic profile to know that it’s truly precapillary PAH ... and we need proper interpretation of [elements like] the waveforms.”
The 2019 World Symposium on Pulmonary Hypertension shifted the definition of PH from an arbitrarily defined mean pulmonary arterial pressure of at least 25 mm Hg at rest (as measured by right heart catheterization) to a more scientifically determined mPAP of at least 20 mm Hg.
The classification document also requires pulmonary vascular resistance (PVR) of at least 3 Wood units in the definition of all forms of precapillary PH. PAH specifically is defined as the presence of mPAP of at least 20 mm Hg, PVR of at least 3 Wood units, and pulmonary arterial wedge pressure 15 mm Hg or less.
Trends in treatment
The value of initial combination therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase-5 (PDE5) inhibitor in treatment-naive PAH was cemented in 2015 by the AMBITION trial. The primary endpoint (death, PAH hospitalization, or unsatisfactory clinical response) occurred in 18%, 34%, and 28% of patients who were randomized, respectively, to combination therapy, monotherapy with the ERA ambrisentan, or monotherapy with the PDE-5 inhibitor tadalafil – and in 31% of the two monotherapy groups combined.
The trial reported a 50% reduction in the primary endpoint in the combination-therapy group versus the pooled monotherapy group, as well as greater reductions in N-terminal of the prohormone brain natriuretic peptide levels, more satisfactory clinical response and greater improvement in 6-minute walking distance.
In practice, a minority of patients – typically older patients with multiple comorbidities – still receive initial monotherapy with sequential add-on therapies based on tolerance, but “for the most part PAH patients will start on combination therapy, most commonly with a ERA and PDE5 inhibitor,” Dr. Chakinala said.
For patients who are not improving on the ERA-PDE5 inhibitor approach – typically those who remain in the intermediate-risk category for intermediate-term mortality – substitution of the PDE5 inhibitor with the soluble guanylate cyclase stimulator riociguat may be considered, he and Dr. Williamson said. Clinical improvement with this substitution was demonstrated in the REPLACE trial.
Experts at PH care centers are also utilizing triple therapy for patients who do not improve to low-risk status after 2-4 months of dual combination therapy. The availability of oral prostacyclin analogues (selexipag and treprostinil) makes it easier to consider adding these agents early on, Dr. Chakinala and Dr. Richardson said.
Patients who fall into the high-risk category, at any point, are still best managed with parenteral prostacyclin analogues, Dr. Chakinala said.
In general, said Dr. Williamson, who also directs the University of Kansas Pulmonary Hypertension Comprehensive Care Center, “the PH community tends to be fairly aggressive up front, and with a low threshold for using prostacyclin analogues.”
The agents are “always part of the picture for someone who is really ill, in functional class IV, or has really impaired right ventricular function,” he said. “And we’re finding increased roles in patients who are not as ill but still have decompensated right ventricular dysfunction. It’s something we now consider.”
Recently published research on up-front oral triple therapy suggests possible benefit for some patients – but it’s far from conclusive, said Dr. Chakinala. The TRITON study randomized treatment-naive patients to the traditional ERA-PDE5 combination and either oral selexipag (a selective prostacyclin receptor agonist) or placebo as a third agent. It found no significant difference in reduction in PVR, the primary outcome, at week 26. However, the authors reported a “possible signal” for improved long-term outcomes with triple therapy.
“Based on this best evidence from a randomized clinical trial, I think it’s unfair to say that all patients should be on triple combination therapy right out of the gate,” he said. “Having said that, more recent [European] data showed that two drugs fell short of the mark in some patients, with high rates of clinical progression. And even in AMBITION, there were a number of patients in the combination arm who didn’t have a robust response.”
A 2021 retrospective analysis from the French Pulmonary Hypertension Registry – one of the European studies – assessed survival with monotherapy, dual therapy, or triple-combination therapy (two orals with a parenteral prostacyclin), and found no difference between monotherapy and dual therapy in high-risk patients.
Experts have been upping the ante, therefore, on early assessment and frequent reassessment of treatment response. Not long ago, patients were typically reassessed 6-12 months after the initiation of treatment. Now, experts at the PH care centers want to assess patients at 3-4 months and adjust or intensify treatment regimens for those who don’t yet qualify as low risk using a multidimensional risk score calculator.
The REVEAL (Registry to Evaluate Early and Long-Term PAH Management) risk score calculator, for instance, predicts the probability of 1-year survival and assigns patients to a strata of risk level based on either 12 or 6 variables (for the full or “lite” versions).]
Even better monitoring and risk assessment is needed, however, to “help sift out which patients are not improving enough on initial therapy or who are starting to fall off after being on a regimen for a period of time,” Dr. Chakinala said.
Today, with a network of accredited centers of expertise and a desire and need for many patients to remain close to home, Dr. Chakinala encourages finding a balance. Well-resourced clinicians can strive for early diagnosis and management – potentially initiating ERA–PDE-5 inhibitor combination therapy – but still should collaborate with PH experts.
“It’s a good idea to comanage these patients and let the experts see them periodically to help you determine when your patient may be declining,” he said. “The timetable for reassessment, the complexity of the reassessment, and the need to escalate to more advanced therapies has never been more important.”
Research highlights
Therapies that target inflammation and altered metabolism – including metformin – are among those being investigated for PAH. So are therapies targeting dysfunctional bone morphogenetic protein pathway signaling, which has been shown to be associated with hereditary, idiopathic, and likely other forms of PAH; one such drug, called sotatercept, is currently at the phase 3 trial stage.
Most promising for PAH may be the research efforts involving deep phenotyping, said Andrew J. Sweatt, MD, of Stanford (Calif.) University and the Vera Moulton Wall Center for Pulmonary Vascular Disease.
“It’s where a lot of research is headed – deep phenotyping to deconstruct the molecular and clinical heterogeneity that exists within PAH ... to detect distinct subphenotypes of patients who would respond to particular therapies,” said Dr. Sweatt, who led a review of PH clinical research presented at the 2020 American Thoracic Society International Conference
“Right now, we largely treat all patients the same ... [while] we know that patients have a wide response to therapies and there’s a lot of clinical heterogeneity in how their disease evolves over time,” he said.
Data from a large National Institutes of Health–funded multicenter phenotyping study of PH is being analyzed and should yield findings and publications starting this year, said Anna R. Hemnes, MD, associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., and an investigator with the initiative, coined “Redefining Pulmonary Hypertension through Pulmonary Disease Phenomics (PVDOMICS).”
Patients have undergone advanced imaging (for example, echocardiography, cardiac MRI, chest CT, ventilation/perfusion scans), advanced testing through right heart catheterization, body composition testing, quality of life questionnaires, and blood draws that have been analyzed for DNA and RNA expression, proteomics, and metabolomics, said Dr. Hemnes, assistant director of Vanderbilt’s Pulmonary Vascular Center.
The initiative aims to refine the classification of all kinds of PH and “to bring precision medicine to the field so we’re no longer characterizing somebody [based on imaging] and right heart catheterization, but we also incorporating molecular pieces and biomarkers into the diagnostic evaluation,” she said.
In the short term, the results of deep phenotyping should “allow us to be more effective with our therapy recommendations,” Dr. Hemnes said. “Then hopefully in the longer term, [identified biomarkers] will help us to develop new, more effective therapies.”
Dr. Sweatt and Dr. Williamson reported that they have no relevant financial disclosures. Dr. Hemnes reported that she holds stock in Tenax (which is studying a tyrosine kinase inhibitor for PAH) and serves as a consultant for Acceleron, Bayer, GossamerBio, United Therapeutics, and Janssen. She also receives research funding from Imara. Dr. Chakinala reported that he is an investigator on clinical trials for a number of pharmaceutical companies. He also serves on advisory boards for Phase Bio, Liquidia/Rare Gen, Bayer, Janssen, Trio Health Analytics, and Aerovate.
Aggressive up-front combination therapy, more lofty treatment goals, and earlier and more frequent reassessments to guide treatment are improving care of patients with pulmonary arterial hypertension (PAH) while at the same time making it more complex.
A larger number of oral and generic treatment options have in some respects ushered in more management ease. But overall, “I don’t know if management of these patients has ever been more complicated, given the treatment options and strategies,” said Murali M. Chakinala, MD, professor of medicine at Washington University, St. Louis. “We’re always thinking through approaches.”
Diagnosis continues to be challenging given the rarity of PAH and its nonspecific presentation – and in some cases it’s now harder. Experts such as Dr. Chakinala are seeing increasing number of aging patients with left heart disease, chronic kidney disease, and other comorbidities who have significant precapillary pulmonary hypertension and who exhibit hemodynamics consistent with PAH, or group 1 PH.
The question experts face is, do such patients have “true PAH,” as do a reported 25-50 people per million, or do they have another type of PH in the classification schema – or a mixture?
Deciding which patients “really fit into group 1 and should be managed like group 1,” Dr. Chakinala said, requires clinical acumen and has important implications, as patients with PAH are the main beneficiaries of vasodilator therapy. Most other patients with PH will not respond to or tolerate such treatment.
“These older patients may be getting PAH through different mechanisms than our younger patients, but because we define PAH through hemodynamic criteria and by ruling out other obvious explanations, they all get lumped together,” said Dr. Chakinala. “We need to parse these patients out better in the future, much like our oncology colleagues are doing.”
Personalized medicine hopefully is the next horizon for this condition, characterized by severe remodeling of the distal pulmonary arteries. Researchers are pushing to achieve deep phenotyping, identify biomarkers and improve risk assessment tools.
And with 80 or so centers now accredited by the Pulmonary Hypertension Association as Pulmonary Hypertension Care Centers, referred patients are accessing clinical trials of new nonvasodilatory drugs. Currently available therapies improve hemodynamics and symptoms, and can slow disease progression, but are not truly disease modifying, sources say.
“The endothelin, nitric oxide, and prostacyclin pathways have been exhaustively studied and we now have great drugs for those pathways,” said Dr. Chakinala, who leads the PHA’s scientific leadership council. But “we’re not going to put a greater dent into this disease until we have new drugs that work on different biologic pathways.”
Diagnostic challenges
The diagnosis of PAH – a remarkably heterogeneous condition that encompasses heritable forms and idiopathic forms, and that comprises a broad mix of predisposing conditions and exposures, from scleroderma to methamphetamine use – is still too often missed or delayed. Delayed diagnoses and misdiagnoses of PAH and other types of PH have been reported in up to 85% of at-risk patients, according to a 2016 literature review.
Being able to pivot from thinking about common pulmonary ailments or heart failure to considering PAH is a key part of earlier diagnosis and better treatment outcomes. “If someone has unexplained dyspnea or if they’re treated for other lung diseases and are not improving, think about a screening echocardiogram,” said Timothy L. Williamson, MD, vice president of quality and safety and a pulmonary and critical care physician at the University of Kansas Health Center, Kansas City.
One of the most common reasons Dr. Chakinala sees for missed diagnoses are right heart catheterizations that are incomplete or misinterpreted. (Right heart catheterizations are required to confirm the diagnosis.) “One can’t simply measure pressures and stop,” he said. “We need the full hemodynamic profile to know that it’s truly precapillary PAH ... and we need proper interpretation of [elements like] the waveforms.”
The 2019 World Symposium on Pulmonary Hypertension shifted the definition of PH from an arbitrarily defined mean pulmonary arterial pressure of at least 25 mm Hg at rest (as measured by right heart catheterization) to a more scientifically determined mPAP of at least 20 mm Hg.
The classification document also requires pulmonary vascular resistance (PVR) of at least 3 Wood units in the definition of all forms of precapillary PH. PAH specifically is defined as the presence of mPAP of at least 20 mm Hg, PVR of at least 3 Wood units, and pulmonary arterial wedge pressure 15 mm Hg or less.
Trends in treatment
The value of initial combination therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase-5 (PDE5) inhibitor in treatment-naive PAH was cemented in 2015 by the AMBITION trial. The primary endpoint (death, PAH hospitalization, or unsatisfactory clinical response) occurred in 18%, 34%, and 28% of patients who were randomized, respectively, to combination therapy, monotherapy with the ERA ambrisentan, or monotherapy with the PDE-5 inhibitor tadalafil – and in 31% of the two monotherapy groups combined.
The trial reported a 50% reduction in the primary endpoint in the combination-therapy group versus the pooled monotherapy group, as well as greater reductions in N-terminal of the prohormone brain natriuretic peptide levels, more satisfactory clinical response and greater improvement in 6-minute walking distance.
In practice, a minority of patients – typically older patients with multiple comorbidities – still receive initial monotherapy with sequential add-on therapies based on tolerance, but “for the most part PAH patients will start on combination therapy, most commonly with a ERA and PDE5 inhibitor,” Dr. Chakinala said.
For patients who are not improving on the ERA-PDE5 inhibitor approach – typically those who remain in the intermediate-risk category for intermediate-term mortality – substitution of the PDE5 inhibitor with the soluble guanylate cyclase stimulator riociguat may be considered, he and Dr. Williamson said. Clinical improvement with this substitution was demonstrated in the REPLACE trial.
Experts at PH care centers are also utilizing triple therapy for patients who do not improve to low-risk status after 2-4 months of dual combination therapy. The availability of oral prostacyclin analogues (selexipag and treprostinil) makes it easier to consider adding these agents early on, Dr. Chakinala and Dr. Richardson said.
Patients who fall into the high-risk category, at any point, are still best managed with parenteral prostacyclin analogues, Dr. Chakinala said.
In general, said Dr. Williamson, who also directs the University of Kansas Pulmonary Hypertension Comprehensive Care Center, “the PH community tends to be fairly aggressive up front, and with a low threshold for using prostacyclin analogues.”
The agents are “always part of the picture for someone who is really ill, in functional class IV, or has really impaired right ventricular function,” he said. “And we’re finding increased roles in patients who are not as ill but still have decompensated right ventricular dysfunction. It’s something we now consider.”
Recently published research on up-front oral triple therapy suggests possible benefit for some patients – but it’s far from conclusive, said Dr. Chakinala. The TRITON study randomized treatment-naive patients to the traditional ERA-PDE5 combination and either oral selexipag (a selective prostacyclin receptor agonist) or placebo as a third agent. It found no significant difference in reduction in PVR, the primary outcome, at week 26. However, the authors reported a “possible signal” for improved long-term outcomes with triple therapy.
“Based on this best evidence from a randomized clinical trial, I think it’s unfair to say that all patients should be on triple combination therapy right out of the gate,” he said. “Having said that, more recent [European] data showed that two drugs fell short of the mark in some patients, with high rates of clinical progression. And even in AMBITION, there were a number of patients in the combination arm who didn’t have a robust response.”
A 2021 retrospective analysis from the French Pulmonary Hypertension Registry – one of the European studies – assessed survival with monotherapy, dual therapy, or triple-combination therapy (two orals with a parenteral prostacyclin), and found no difference between monotherapy and dual therapy in high-risk patients.
Experts have been upping the ante, therefore, on early assessment and frequent reassessment of treatment response. Not long ago, patients were typically reassessed 6-12 months after the initiation of treatment. Now, experts at the PH care centers want to assess patients at 3-4 months and adjust or intensify treatment regimens for those who don’t yet qualify as low risk using a multidimensional risk score calculator.
The REVEAL (Registry to Evaluate Early and Long-Term PAH Management) risk score calculator, for instance, predicts the probability of 1-year survival and assigns patients to a strata of risk level based on either 12 or 6 variables (for the full or “lite” versions).]
Even better monitoring and risk assessment is needed, however, to “help sift out which patients are not improving enough on initial therapy or who are starting to fall off after being on a regimen for a period of time,” Dr. Chakinala said.
Today, with a network of accredited centers of expertise and a desire and need for many patients to remain close to home, Dr. Chakinala encourages finding a balance. Well-resourced clinicians can strive for early diagnosis and management – potentially initiating ERA–PDE-5 inhibitor combination therapy – but still should collaborate with PH experts.
“It’s a good idea to comanage these patients and let the experts see them periodically to help you determine when your patient may be declining,” he said. “The timetable for reassessment, the complexity of the reassessment, and the need to escalate to more advanced therapies has never been more important.”
Research highlights
Therapies that target inflammation and altered metabolism – including metformin – are among those being investigated for PAH. So are therapies targeting dysfunctional bone morphogenetic protein pathway signaling, which has been shown to be associated with hereditary, idiopathic, and likely other forms of PAH; one such drug, called sotatercept, is currently at the phase 3 trial stage.
Most promising for PAH may be the research efforts involving deep phenotyping, said Andrew J. Sweatt, MD, of Stanford (Calif.) University and the Vera Moulton Wall Center for Pulmonary Vascular Disease.
“It’s where a lot of research is headed – deep phenotyping to deconstruct the molecular and clinical heterogeneity that exists within PAH ... to detect distinct subphenotypes of patients who would respond to particular therapies,” said Dr. Sweatt, who led a review of PH clinical research presented at the 2020 American Thoracic Society International Conference
“Right now, we largely treat all patients the same ... [while] we know that patients have a wide response to therapies and there’s a lot of clinical heterogeneity in how their disease evolves over time,” he said.
Data from a large National Institutes of Health–funded multicenter phenotyping study of PH is being analyzed and should yield findings and publications starting this year, said Anna R. Hemnes, MD, associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., and an investigator with the initiative, coined “Redefining Pulmonary Hypertension through Pulmonary Disease Phenomics (PVDOMICS).”
Patients have undergone advanced imaging (for example, echocardiography, cardiac MRI, chest CT, ventilation/perfusion scans), advanced testing through right heart catheterization, body composition testing, quality of life questionnaires, and blood draws that have been analyzed for DNA and RNA expression, proteomics, and metabolomics, said Dr. Hemnes, assistant director of Vanderbilt’s Pulmonary Vascular Center.
The initiative aims to refine the classification of all kinds of PH and “to bring precision medicine to the field so we’re no longer characterizing somebody [based on imaging] and right heart catheterization, but we also incorporating molecular pieces and biomarkers into the diagnostic evaluation,” she said.
In the short term, the results of deep phenotyping should “allow us to be more effective with our therapy recommendations,” Dr. Hemnes said. “Then hopefully in the longer term, [identified biomarkers] will help us to develop new, more effective therapies.”
Dr. Sweatt and Dr. Williamson reported that they have no relevant financial disclosures. Dr. Hemnes reported that she holds stock in Tenax (which is studying a tyrosine kinase inhibitor for PAH) and serves as a consultant for Acceleron, Bayer, GossamerBio, United Therapeutics, and Janssen. She also receives research funding from Imara. Dr. Chakinala reported that he is an investigator on clinical trials for a number of pharmaceutical companies. He also serves on advisory boards for Phase Bio, Liquidia/Rare Gen, Bayer, Janssen, Trio Health Analytics, and Aerovate.
Aggressive up-front combination therapy, more lofty treatment goals, and earlier and more frequent reassessments to guide treatment are improving care of patients with pulmonary arterial hypertension (PAH) while at the same time making it more complex.
A larger number of oral and generic treatment options have in some respects ushered in more management ease. But overall, “I don’t know if management of these patients has ever been more complicated, given the treatment options and strategies,” said Murali M. Chakinala, MD, professor of medicine at Washington University, St. Louis. “We’re always thinking through approaches.”
Diagnosis continues to be challenging given the rarity of PAH and its nonspecific presentation – and in some cases it’s now harder. Experts such as Dr. Chakinala are seeing increasing number of aging patients with left heart disease, chronic kidney disease, and other comorbidities who have significant precapillary pulmonary hypertension and who exhibit hemodynamics consistent with PAH, or group 1 PH.
The question experts face is, do such patients have “true PAH,” as do a reported 25-50 people per million, or do they have another type of PH in the classification schema – or a mixture?
Deciding which patients “really fit into group 1 and should be managed like group 1,” Dr. Chakinala said, requires clinical acumen and has important implications, as patients with PAH are the main beneficiaries of vasodilator therapy. Most other patients with PH will not respond to or tolerate such treatment.
“These older patients may be getting PAH through different mechanisms than our younger patients, but because we define PAH through hemodynamic criteria and by ruling out other obvious explanations, they all get lumped together,” said Dr. Chakinala. “We need to parse these patients out better in the future, much like our oncology colleagues are doing.”
Personalized medicine hopefully is the next horizon for this condition, characterized by severe remodeling of the distal pulmonary arteries. Researchers are pushing to achieve deep phenotyping, identify biomarkers and improve risk assessment tools.
And with 80 or so centers now accredited by the Pulmonary Hypertension Association as Pulmonary Hypertension Care Centers, referred patients are accessing clinical trials of new nonvasodilatory drugs. Currently available therapies improve hemodynamics and symptoms, and can slow disease progression, but are not truly disease modifying, sources say.
“The endothelin, nitric oxide, and prostacyclin pathways have been exhaustively studied and we now have great drugs for those pathways,” said Dr. Chakinala, who leads the PHA’s scientific leadership council. But “we’re not going to put a greater dent into this disease until we have new drugs that work on different biologic pathways.”
Diagnostic challenges
The diagnosis of PAH – a remarkably heterogeneous condition that encompasses heritable forms and idiopathic forms, and that comprises a broad mix of predisposing conditions and exposures, from scleroderma to methamphetamine use – is still too often missed or delayed. Delayed diagnoses and misdiagnoses of PAH and other types of PH have been reported in up to 85% of at-risk patients, according to a 2016 literature review.
Being able to pivot from thinking about common pulmonary ailments or heart failure to considering PAH is a key part of earlier diagnosis and better treatment outcomes. “If someone has unexplained dyspnea or if they’re treated for other lung diseases and are not improving, think about a screening echocardiogram,” said Timothy L. Williamson, MD, vice president of quality and safety and a pulmonary and critical care physician at the University of Kansas Health Center, Kansas City.
One of the most common reasons Dr. Chakinala sees for missed diagnoses are right heart catheterizations that are incomplete or misinterpreted. (Right heart catheterizations are required to confirm the diagnosis.) “One can’t simply measure pressures and stop,” he said. “We need the full hemodynamic profile to know that it’s truly precapillary PAH ... and we need proper interpretation of [elements like] the waveforms.”
The 2019 World Symposium on Pulmonary Hypertension shifted the definition of PH from an arbitrarily defined mean pulmonary arterial pressure of at least 25 mm Hg at rest (as measured by right heart catheterization) to a more scientifically determined mPAP of at least 20 mm Hg.
The classification document also requires pulmonary vascular resistance (PVR) of at least 3 Wood units in the definition of all forms of precapillary PH. PAH specifically is defined as the presence of mPAP of at least 20 mm Hg, PVR of at least 3 Wood units, and pulmonary arterial wedge pressure 15 mm Hg or less.
Trends in treatment
The value of initial combination therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase-5 (PDE5) inhibitor in treatment-naive PAH was cemented in 2015 by the AMBITION trial. The primary endpoint (death, PAH hospitalization, or unsatisfactory clinical response) occurred in 18%, 34%, and 28% of patients who were randomized, respectively, to combination therapy, monotherapy with the ERA ambrisentan, or monotherapy with the PDE-5 inhibitor tadalafil – and in 31% of the two monotherapy groups combined.
The trial reported a 50% reduction in the primary endpoint in the combination-therapy group versus the pooled monotherapy group, as well as greater reductions in N-terminal of the prohormone brain natriuretic peptide levels, more satisfactory clinical response and greater improvement in 6-minute walking distance.
In practice, a minority of patients – typically older patients with multiple comorbidities – still receive initial monotherapy with sequential add-on therapies based on tolerance, but “for the most part PAH patients will start on combination therapy, most commonly with a ERA and PDE5 inhibitor,” Dr. Chakinala said.
For patients who are not improving on the ERA-PDE5 inhibitor approach – typically those who remain in the intermediate-risk category for intermediate-term mortality – substitution of the PDE5 inhibitor with the soluble guanylate cyclase stimulator riociguat may be considered, he and Dr. Williamson said. Clinical improvement with this substitution was demonstrated in the REPLACE trial.
Experts at PH care centers are also utilizing triple therapy for patients who do not improve to low-risk status after 2-4 months of dual combination therapy. The availability of oral prostacyclin analogues (selexipag and treprostinil) makes it easier to consider adding these agents early on, Dr. Chakinala and Dr. Richardson said.
Patients who fall into the high-risk category, at any point, are still best managed with parenteral prostacyclin analogues, Dr. Chakinala said.
In general, said Dr. Williamson, who also directs the University of Kansas Pulmonary Hypertension Comprehensive Care Center, “the PH community tends to be fairly aggressive up front, and with a low threshold for using prostacyclin analogues.”
The agents are “always part of the picture for someone who is really ill, in functional class IV, or has really impaired right ventricular function,” he said. “And we’re finding increased roles in patients who are not as ill but still have decompensated right ventricular dysfunction. It’s something we now consider.”
Recently published research on up-front oral triple therapy suggests possible benefit for some patients – but it’s far from conclusive, said Dr. Chakinala. The TRITON study randomized treatment-naive patients to the traditional ERA-PDE5 combination and either oral selexipag (a selective prostacyclin receptor agonist) or placebo as a third agent. It found no significant difference in reduction in PVR, the primary outcome, at week 26. However, the authors reported a “possible signal” for improved long-term outcomes with triple therapy.
“Based on this best evidence from a randomized clinical trial, I think it’s unfair to say that all patients should be on triple combination therapy right out of the gate,” he said. “Having said that, more recent [European] data showed that two drugs fell short of the mark in some patients, with high rates of clinical progression. And even in AMBITION, there were a number of patients in the combination arm who didn’t have a robust response.”
A 2021 retrospective analysis from the French Pulmonary Hypertension Registry – one of the European studies – assessed survival with monotherapy, dual therapy, or triple-combination therapy (two orals with a parenteral prostacyclin), and found no difference between monotherapy and dual therapy in high-risk patients.
Experts have been upping the ante, therefore, on early assessment and frequent reassessment of treatment response. Not long ago, patients were typically reassessed 6-12 months after the initiation of treatment. Now, experts at the PH care centers want to assess patients at 3-4 months and adjust or intensify treatment regimens for those who don’t yet qualify as low risk using a multidimensional risk score calculator.
The REVEAL (Registry to Evaluate Early and Long-Term PAH Management) risk score calculator, for instance, predicts the probability of 1-year survival and assigns patients to a strata of risk level based on either 12 or 6 variables (for the full or “lite” versions).]
Even better monitoring and risk assessment is needed, however, to “help sift out which patients are not improving enough on initial therapy or who are starting to fall off after being on a regimen for a period of time,” Dr. Chakinala said.
Today, with a network of accredited centers of expertise and a desire and need for many patients to remain close to home, Dr. Chakinala encourages finding a balance. Well-resourced clinicians can strive for early diagnosis and management – potentially initiating ERA–PDE-5 inhibitor combination therapy – but still should collaborate with PH experts.
“It’s a good idea to comanage these patients and let the experts see them periodically to help you determine when your patient may be declining,” he said. “The timetable for reassessment, the complexity of the reassessment, and the need to escalate to more advanced therapies has never been more important.”
Research highlights
Therapies that target inflammation and altered metabolism – including metformin – are among those being investigated for PAH. So are therapies targeting dysfunctional bone morphogenetic protein pathway signaling, which has been shown to be associated with hereditary, idiopathic, and likely other forms of PAH; one such drug, called sotatercept, is currently at the phase 3 trial stage.
Most promising for PAH may be the research efforts involving deep phenotyping, said Andrew J. Sweatt, MD, of Stanford (Calif.) University and the Vera Moulton Wall Center for Pulmonary Vascular Disease.
“It’s where a lot of research is headed – deep phenotyping to deconstruct the molecular and clinical heterogeneity that exists within PAH ... to detect distinct subphenotypes of patients who would respond to particular therapies,” said Dr. Sweatt, who led a review of PH clinical research presented at the 2020 American Thoracic Society International Conference
“Right now, we largely treat all patients the same ... [while] we know that patients have a wide response to therapies and there’s a lot of clinical heterogeneity in how their disease evolves over time,” he said.
Data from a large National Institutes of Health–funded multicenter phenotyping study of PH is being analyzed and should yield findings and publications starting this year, said Anna R. Hemnes, MD, associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., and an investigator with the initiative, coined “Redefining Pulmonary Hypertension through Pulmonary Disease Phenomics (PVDOMICS).”
Patients have undergone advanced imaging (for example, echocardiography, cardiac MRI, chest CT, ventilation/perfusion scans), advanced testing through right heart catheterization, body composition testing, quality of life questionnaires, and blood draws that have been analyzed for DNA and RNA expression, proteomics, and metabolomics, said Dr. Hemnes, assistant director of Vanderbilt’s Pulmonary Vascular Center.
The initiative aims to refine the classification of all kinds of PH and “to bring precision medicine to the field so we’re no longer characterizing somebody [based on imaging] and right heart catheterization, but we also incorporating molecular pieces and biomarkers into the diagnostic evaluation,” she said.
In the short term, the results of deep phenotyping should “allow us to be more effective with our therapy recommendations,” Dr. Hemnes said. “Then hopefully in the longer term, [identified biomarkers] will help us to develop new, more effective therapies.”
Dr. Sweatt and Dr. Williamson reported that they have no relevant financial disclosures. Dr. Hemnes reported that she holds stock in Tenax (which is studying a tyrosine kinase inhibitor for PAH) and serves as a consultant for Acceleron, Bayer, GossamerBio, United Therapeutics, and Janssen. She also receives research funding from Imara. Dr. Chakinala reported that he is an investigator on clinical trials for a number of pharmaceutical companies. He also serves on advisory boards for Phase Bio, Liquidia/Rare Gen, Bayer, Janssen, Trio Health Analytics, and Aerovate.
A dermatologist-led model for CVD prevention in psoriasis may be feasible
A – may be feasible, given the positive perspectives expressed by both clinicians and patients in a set of electronic surveys, researchers say.
In an analysis of survey responses from 183 dermatologists and 322 patients, John S. Barbieri, MD, MBA, and coinvestigators found that more than two-thirds of dermatologists (69.3%) agreed it “seems doable” to check lipids and calculate a 10-year cardiovascular risk score, and over one-third (36.1%) agreed they could prescribe statins when indicated.
The patient survey was distributed through the National Psoriasis Foundation to individuals who were seeing a dermatologist or rheumatologist for psoriatic disease; the clinician survey was distributed through the American Academy of Dermatology to dermatologists who reported caring for patients with psoriasis. (A survey of rheumatologists was similarly conducted, but the number of participants fell short of the needed sample size.)
Most patients surveyed indicated they would be receptive to their dermatologist (or rheumatologist) playing a larger role in screening and managing CVD risk, and that they would be similarly likely to follow recommendations regarding risk screening and management whether the advice came their dermatologist/rheumatologist or from their PCP.
The clinician survey focused on lipids and statin use, and did not address other elements of risk management. Still, the researchers see their findings as an early but promising step in finding better models to improve cardiovascular outcomes for patients with psoriatic disease, who too often do not engage with their PCPs despite their increased risk of CVD and a higher risk of premature mortality from CVD.
Fewer than half of commercially insured adults aged under 65 years visit a PCP each year, the researchers noted. And among the patients in their survey, approximately 20% did not have a PCP or had not seen their PCP in the past year.
Other research has shown that only a small minority of patients with psoriasis have an encounter with their PCP within a year of establishing care with their dermatologist, and that “over half of patients with psoriasis have undetected risk factors like dyslipidemia or hypertension,” Dr. Barbieri, of the department of dermatology at Brigham and Women’s Hospital, Boston, said in an interview.
“There’s a gap here, a missing link in the chain of cardiovascular disease prevention,” he said. “What if the dermatologist or rheumatologist could be more engaged in [CV] risk protection? ... It’s the idea of meeting the patients where they are.”
The surveys
The clinician survey focused on statins because of their ease of use, efficacy and safety, and the need for minimal monitoring, Dr. Barbieri said in the interview. “On the spectrum of things you can do for cardiovascular disease prevention, it’s one of the easiest ones.”
In an accompanying editorial, cardiologists Michael S. Garshick, MD, MS, and Jeffrey S. Berger, MD, MS, both of the department of medicine, New York University, wrote that, “despite the well-described association between psoriasis and CVD, only 35% of patients with psoriasis diagnosed with hyperlipidemia are adequately treated with statin therapy.”
“For many of these patients, their dermatologist or rheumatologist may be their only source of contact with the health care system,” they added.
Most studies targeting CVD risk in psoriasis have focused on targeting psoriatic inflammation, and few studies have explored strategies to improve modifiable CVD risk factor control with pharmacological therapy, they said.
In addition to the questions about receptiveness to identifying and potentially treating CVD risk with statins, the dermatologist survey included a best-worst scaling choice experiment to assess preferences for implementation approaches. Dermatologists were asked to rank their preferences for eight implementation strategies that have been shown in published studies to help increase statin prescribing rates.
The three highest-ranked strategies among dermatologists were clinical decision support, physician educational outreach, and patient education materials. The lowest-ranked strategies were comparisons with peers, a pay-for-performance option, and a mobile app/texting service to remind patients to undergo CVD risk screening.
Of the 183 dermatologists in the survey, 28.4% were from academic settings, 11.5% were from multispecialty groups, and 45.4% were from dermatology groups. (A low response rate of 5.2% for dermatologists raises some questions about the generalizability of the findings, Dr. Garshick and Dr. Berger noted in their editorial.)
Where to go from here?
Asked to comment on the results, Jashin J. Wu, MD, founder and CEO of the Dermatology Research and Education Foundation, Irvine, Calif., who was not involved with the study, said that a larger role in CVD risk management is “not likely to find traction with everyday dermatologists.”
“It’s already a big ask for community dermatologists to go through the approval process to get biologics for patients, so I don’t think many would be willing to add more to their plate by taking a bigger role in CVD management,” he said in an interview. He generally has not prescribed statins, “as I don’t feel that is in my scope of work.”
In the interview, Dr. Barbieri said that a parallel qualitative study, not yet published, has looked at the facilitators and barriers – including time constraints and concern about scope of practice – to statin prescribing and other elements of cardiovascular risk reduction.
All told, he said, a centralized care coordinator model may be the best approach to engage the dermatologist more in CVD prevention, including lipid management, but to also “offload some of the management responsibility.”
In this model, which is partially described by Dr. Barbieri and colleagues, the dermatologist (or rheumatologist) would educate the patient, measure blood pressure and check a lipid panel, and refer the patient to a coordinator who would, in turn, collect more information and calculate a 10-year CVD risk score.
Using a protocol-driven clinical decision support approach, the care coordinator would provide counseling about diet, exercise, and smoking cessation, and about whether statin therapy or blood pressure management is indicated.
“That coordinator would be in a good position to help the patient work with their PCP, if they have one, to find a PCP if they don’t, or to use telemedicine or work with their dermatologist or rheumatologist,” Dr. Barbieri said.
The centralized care coordinator service could be funded through grants, charitable funds, and patient assistance funds so that it is free to patients, he said, and could possibly be “housed in the National Psoriasis Foundation.”
Dr. Barbieri said he and his colleagues plan to design a clinical trial to test whether such a model can be adopted in practice and whether it can improve outcomes associated with CVD risk management.
In their editorial, Dr. Garshick and Dr. Berger, who is director of NYU Langone’s Center for the Prevention of Cardiovascular Disease, wrote that many patients with psoriatic disease have or are at risk for cardiometabolic conditions, and that CVD risk reduction should extend beyond lipid management to include blood pressure, glucose lowering, obesity management, and antiplatelet therapy.
The joint AAD-NPF guidelines for the management and treatment of psoriasis with awareness and attention to comorbidities, published in 2019, were among the first to formally recognize the enhanced CVD risk of patients with psoriasis, they noted.
The guidelines call upon dermatologists to inform patients of the psoriasis-CVD association and ensure their patients are engaged with their PCP or cardiologist for appropriate screening. Now, the editorialists say, “moving the needle forward includes refining and developing modifiable CVD risk reduction strategies for patients with psoriasis, and collaboration between the fields of dermatology, rheumatology, and cardiology is key.”
Incorporating a preventive cardiologist into combined dermatology-rheumatology clinics, or partnering as a freestanding cardioinflammatory clinic, also have potential to improve CVD risk, they wrote.
The survey study was supported by a grant from the NPF Psoriasis Prevention Initiative. Dr. Barbieri reported no conflicts of interest. Several authors disclosed consulting fees and grants from numerous pharmaceutical companies. Dr. Berger reported receiving personal fees from Janssen and grants from AstraZeneca outside of the submitted work. Dr. Garshick reported receiving personal fees from AbbVie outside of the submitted work.
A – may be feasible, given the positive perspectives expressed by both clinicians and patients in a set of electronic surveys, researchers say.
In an analysis of survey responses from 183 dermatologists and 322 patients, John S. Barbieri, MD, MBA, and coinvestigators found that more than two-thirds of dermatologists (69.3%) agreed it “seems doable” to check lipids and calculate a 10-year cardiovascular risk score, and over one-third (36.1%) agreed they could prescribe statins when indicated.
The patient survey was distributed through the National Psoriasis Foundation to individuals who were seeing a dermatologist or rheumatologist for psoriatic disease; the clinician survey was distributed through the American Academy of Dermatology to dermatologists who reported caring for patients with psoriasis. (A survey of rheumatologists was similarly conducted, but the number of participants fell short of the needed sample size.)
Most patients surveyed indicated they would be receptive to their dermatologist (or rheumatologist) playing a larger role in screening and managing CVD risk, and that they would be similarly likely to follow recommendations regarding risk screening and management whether the advice came their dermatologist/rheumatologist or from their PCP.
The clinician survey focused on lipids and statin use, and did not address other elements of risk management. Still, the researchers see their findings as an early but promising step in finding better models to improve cardiovascular outcomes for patients with psoriatic disease, who too often do not engage with their PCPs despite their increased risk of CVD and a higher risk of premature mortality from CVD.
Fewer than half of commercially insured adults aged under 65 years visit a PCP each year, the researchers noted. And among the patients in their survey, approximately 20% did not have a PCP or had not seen their PCP in the past year.
Other research has shown that only a small minority of patients with psoriasis have an encounter with their PCP within a year of establishing care with their dermatologist, and that “over half of patients with psoriasis have undetected risk factors like dyslipidemia or hypertension,” Dr. Barbieri, of the department of dermatology at Brigham and Women’s Hospital, Boston, said in an interview.
“There’s a gap here, a missing link in the chain of cardiovascular disease prevention,” he said. “What if the dermatologist or rheumatologist could be more engaged in [CV] risk protection? ... It’s the idea of meeting the patients where they are.”
The surveys
The clinician survey focused on statins because of their ease of use, efficacy and safety, and the need for minimal monitoring, Dr. Barbieri said in the interview. “On the spectrum of things you can do for cardiovascular disease prevention, it’s one of the easiest ones.”
In an accompanying editorial, cardiologists Michael S. Garshick, MD, MS, and Jeffrey S. Berger, MD, MS, both of the department of medicine, New York University, wrote that, “despite the well-described association between psoriasis and CVD, only 35% of patients with psoriasis diagnosed with hyperlipidemia are adequately treated with statin therapy.”
“For many of these patients, their dermatologist or rheumatologist may be their only source of contact with the health care system,” they added.
Most studies targeting CVD risk in psoriasis have focused on targeting psoriatic inflammation, and few studies have explored strategies to improve modifiable CVD risk factor control with pharmacological therapy, they said.
In addition to the questions about receptiveness to identifying and potentially treating CVD risk with statins, the dermatologist survey included a best-worst scaling choice experiment to assess preferences for implementation approaches. Dermatologists were asked to rank their preferences for eight implementation strategies that have been shown in published studies to help increase statin prescribing rates.
The three highest-ranked strategies among dermatologists were clinical decision support, physician educational outreach, and patient education materials. The lowest-ranked strategies were comparisons with peers, a pay-for-performance option, and a mobile app/texting service to remind patients to undergo CVD risk screening.
Of the 183 dermatologists in the survey, 28.4% were from academic settings, 11.5% were from multispecialty groups, and 45.4% were from dermatology groups. (A low response rate of 5.2% for dermatologists raises some questions about the generalizability of the findings, Dr. Garshick and Dr. Berger noted in their editorial.)
Where to go from here?
Asked to comment on the results, Jashin J. Wu, MD, founder and CEO of the Dermatology Research and Education Foundation, Irvine, Calif., who was not involved with the study, said that a larger role in CVD risk management is “not likely to find traction with everyday dermatologists.”
“It’s already a big ask for community dermatologists to go through the approval process to get biologics for patients, so I don’t think many would be willing to add more to their plate by taking a bigger role in CVD management,” he said in an interview. He generally has not prescribed statins, “as I don’t feel that is in my scope of work.”
In the interview, Dr. Barbieri said that a parallel qualitative study, not yet published, has looked at the facilitators and barriers – including time constraints and concern about scope of practice – to statin prescribing and other elements of cardiovascular risk reduction.
All told, he said, a centralized care coordinator model may be the best approach to engage the dermatologist more in CVD prevention, including lipid management, but to also “offload some of the management responsibility.”
In this model, which is partially described by Dr. Barbieri and colleagues, the dermatologist (or rheumatologist) would educate the patient, measure blood pressure and check a lipid panel, and refer the patient to a coordinator who would, in turn, collect more information and calculate a 10-year CVD risk score.
Using a protocol-driven clinical decision support approach, the care coordinator would provide counseling about diet, exercise, and smoking cessation, and about whether statin therapy or blood pressure management is indicated.
“That coordinator would be in a good position to help the patient work with their PCP, if they have one, to find a PCP if they don’t, or to use telemedicine or work with their dermatologist or rheumatologist,” Dr. Barbieri said.
The centralized care coordinator service could be funded through grants, charitable funds, and patient assistance funds so that it is free to patients, he said, and could possibly be “housed in the National Psoriasis Foundation.”
Dr. Barbieri said he and his colleagues plan to design a clinical trial to test whether such a model can be adopted in practice and whether it can improve outcomes associated with CVD risk management.
In their editorial, Dr. Garshick and Dr. Berger, who is director of NYU Langone’s Center for the Prevention of Cardiovascular Disease, wrote that many patients with psoriatic disease have or are at risk for cardiometabolic conditions, and that CVD risk reduction should extend beyond lipid management to include blood pressure, glucose lowering, obesity management, and antiplatelet therapy.
The joint AAD-NPF guidelines for the management and treatment of psoriasis with awareness and attention to comorbidities, published in 2019, were among the first to formally recognize the enhanced CVD risk of patients with psoriasis, they noted.
The guidelines call upon dermatologists to inform patients of the psoriasis-CVD association and ensure their patients are engaged with their PCP or cardiologist for appropriate screening. Now, the editorialists say, “moving the needle forward includes refining and developing modifiable CVD risk reduction strategies for patients with psoriasis, and collaboration between the fields of dermatology, rheumatology, and cardiology is key.”
Incorporating a preventive cardiologist into combined dermatology-rheumatology clinics, or partnering as a freestanding cardioinflammatory clinic, also have potential to improve CVD risk, they wrote.
The survey study was supported by a grant from the NPF Psoriasis Prevention Initiative. Dr. Barbieri reported no conflicts of interest. Several authors disclosed consulting fees and grants from numerous pharmaceutical companies. Dr. Berger reported receiving personal fees from Janssen and grants from AstraZeneca outside of the submitted work. Dr. Garshick reported receiving personal fees from AbbVie outside of the submitted work.
A – may be feasible, given the positive perspectives expressed by both clinicians and patients in a set of electronic surveys, researchers say.
In an analysis of survey responses from 183 dermatologists and 322 patients, John S. Barbieri, MD, MBA, and coinvestigators found that more than two-thirds of dermatologists (69.3%) agreed it “seems doable” to check lipids and calculate a 10-year cardiovascular risk score, and over one-third (36.1%) agreed they could prescribe statins when indicated.
The patient survey was distributed through the National Psoriasis Foundation to individuals who were seeing a dermatologist or rheumatologist for psoriatic disease; the clinician survey was distributed through the American Academy of Dermatology to dermatologists who reported caring for patients with psoriasis. (A survey of rheumatologists was similarly conducted, but the number of participants fell short of the needed sample size.)
Most patients surveyed indicated they would be receptive to their dermatologist (or rheumatologist) playing a larger role in screening and managing CVD risk, and that they would be similarly likely to follow recommendations regarding risk screening and management whether the advice came their dermatologist/rheumatologist or from their PCP.
The clinician survey focused on lipids and statin use, and did not address other elements of risk management. Still, the researchers see their findings as an early but promising step in finding better models to improve cardiovascular outcomes for patients with psoriatic disease, who too often do not engage with their PCPs despite their increased risk of CVD and a higher risk of premature mortality from CVD.
Fewer than half of commercially insured adults aged under 65 years visit a PCP each year, the researchers noted. And among the patients in their survey, approximately 20% did not have a PCP or had not seen their PCP in the past year.
Other research has shown that only a small minority of patients with psoriasis have an encounter with their PCP within a year of establishing care with their dermatologist, and that “over half of patients with psoriasis have undetected risk factors like dyslipidemia or hypertension,” Dr. Barbieri, of the department of dermatology at Brigham and Women’s Hospital, Boston, said in an interview.
“There’s a gap here, a missing link in the chain of cardiovascular disease prevention,” he said. “What if the dermatologist or rheumatologist could be more engaged in [CV] risk protection? ... It’s the idea of meeting the patients where they are.”
The surveys
The clinician survey focused on statins because of their ease of use, efficacy and safety, and the need for minimal monitoring, Dr. Barbieri said in the interview. “On the spectrum of things you can do for cardiovascular disease prevention, it’s one of the easiest ones.”
In an accompanying editorial, cardiologists Michael S. Garshick, MD, MS, and Jeffrey S. Berger, MD, MS, both of the department of medicine, New York University, wrote that, “despite the well-described association between psoriasis and CVD, only 35% of patients with psoriasis diagnosed with hyperlipidemia are adequately treated with statin therapy.”
“For many of these patients, their dermatologist or rheumatologist may be their only source of contact with the health care system,” they added.
Most studies targeting CVD risk in psoriasis have focused on targeting psoriatic inflammation, and few studies have explored strategies to improve modifiable CVD risk factor control with pharmacological therapy, they said.
In addition to the questions about receptiveness to identifying and potentially treating CVD risk with statins, the dermatologist survey included a best-worst scaling choice experiment to assess preferences for implementation approaches. Dermatologists were asked to rank their preferences for eight implementation strategies that have been shown in published studies to help increase statin prescribing rates.
The three highest-ranked strategies among dermatologists were clinical decision support, physician educational outreach, and patient education materials. The lowest-ranked strategies were comparisons with peers, a pay-for-performance option, and a mobile app/texting service to remind patients to undergo CVD risk screening.
Of the 183 dermatologists in the survey, 28.4% were from academic settings, 11.5% were from multispecialty groups, and 45.4% were from dermatology groups. (A low response rate of 5.2% for dermatologists raises some questions about the generalizability of the findings, Dr. Garshick and Dr. Berger noted in their editorial.)
Where to go from here?
Asked to comment on the results, Jashin J. Wu, MD, founder and CEO of the Dermatology Research and Education Foundation, Irvine, Calif., who was not involved with the study, said that a larger role in CVD risk management is “not likely to find traction with everyday dermatologists.”
“It’s already a big ask for community dermatologists to go through the approval process to get biologics for patients, so I don’t think many would be willing to add more to their plate by taking a bigger role in CVD management,” he said in an interview. He generally has not prescribed statins, “as I don’t feel that is in my scope of work.”
In the interview, Dr. Barbieri said that a parallel qualitative study, not yet published, has looked at the facilitators and barriers – including time constraints and concern about scope of practice – to statin prescribing and other elements of cardiovascular risk reduction.
All told, he said, a centralized care coordinator model may be the best approach to engage the dermatologist more in CVD prevention, including lipid management, but to also “offload some of the management responsibility.”
In this model, which is partially described by Dr. Barbieri and colleagues, the dermatologist (or rheumatologist) would educate the patient, measure blood pressure and check a lipid panel, and refer the patient to a coordinator who would, in turn, collect more information and calculate a 10-year CVD risk score.
Using a protocol-driven clinical decision support approach, the care coordinator would provide counseling about diet, exercise, and smoking cessation, and about whether statin therapy or blood pressure management is indicated.
“That coordinator would be in a good position to help the patient work with their PCP, if they have one, to find a PCP if they don’t, or to use telemedicine or work with their dermatologist or rheumatologist,” Dr. Barbieri said.
The centralized care coordinator service could be funded through grants, charitable funds, and patient assistance funds so that it is free to patients, he said, and could possibly be “housed in the National Psoriasis Foundation.”
Dr. Barbieri said he and his colleagues plan to design a clinical trial to test whether such a model can be adopted in practice and whether it can improve outcomes associated with CVD risk management.
In their editorial, Dr. Garshick and Dr. Berger, who is director of NYU Langone’s Center for the Prevention of Cardiovascular Disease, wrote that many patients with psoriatic disease have or are at risk for cardiometabolic conditions, and that CVD risk reduction should extend beyond lipid management to include blood pressure, glucose lowering, obesity management, and antiplatelet therapy.
The joint AAD-NPF guidelines for the management and treatment of psoriasis with awareness and attention to comorbidities, published in 2019, were among the first to formally recognize the enhanced CVD risk of patients with psoriasis, they noted.
The guidelines call upon dermatologists to inform patients of the psoriasis-CVD association and ensure their patients are engaged with their PCP or cardiologist for appropriate screening. Now, the editorialists say, “moving the needle forward includes refining and developing modifiable CVD risk reduction strategies for patients with psoriasis, and collaboration between the fields of dermatology, rheumatology, and cardiology is key.”
Incorporating a preventive cardiologist into combined dermatology-rheumatology clinics, or partnering as a freestanding cardioinflammatory clinic, also have potential to improve CVD risk, they wrote.
The survey study was supported by a grant from the NPF Psoriasis Prevention Initiative. Dr. Barbieri reported no conflicts of interest. Several authors disclosed consulting fees and grants from numerous pharmaceutical companies. Dr. Berger reported receiving personal fees from Janssen and grants from AstraZeneca outside of the submitted work. Dr. Garshick reported receiving personal fees from AbbVie outside of the submitted work.
FROM JAMA DERMATOLOGY
Antibiotic choices for inpatients with SSTIs vary by race
– in a national cross-sectional study involving over 1,000 patients in 91 hospitals.
The potential racial disparity in management of SSTI was detected after data were adjusted for penicillin allergy history and for MRSA colonization/infection. The data were also adjusted for hospital day (since admission) in order to control for the administration of more empiric therapy early on.
Clindamycin, a beta-lactam alternative, is not recommended as an SSTI treatment given its frequent dosing requirements and high potential for adverse events including Clostridioides difficile infection (DCI). “Clindamycin is an option but it’s considered inferior. ... It covers MRSA but it shouldn’t be a go-to for skin and soft-tissue infections,” said senior author Kimberly Blumenthal, MD, MSc, assistant professor of medicine at Harvard University, and an allergist, immunologist, and drug allergy and epidemiology researcher at Massachusetts General Hospital, both in Boston.
Cefazolin, on the other hand, does not cover MRSA but is “a guideline-recommended first-line antibiotic for cellulitis SSTI in the hospital,” she said in an interview.
The findings, recently published in JAMA Network Open, offer a valuable portrait of the antibiotics being prescribed in the inpatient setting for SSTIs. Vancomycin, which typically is reserved for MRSA, was the most commonly prescribed antibiotic, regardless of race. Piperacillin-tazobactam, a beta-lactam, was the second most commonly prescribed antibiotic, again regardless of race.
Intravenously administered cefazolin was used in 13% of White inpatients versus 5% of Black inpatients. After controlling for kidney disease, diabetes, and ICU location (in addition to hospital day, penicillin allergy history, and MRSA), White inpatients had an increased likelihood of being prescribed cefazolin (adjusted odds ratio, 2.82; 95% confidence interval, 1.41-5.63) and a decreased likelihood of clindamycin use (aOR, 0.54; 95% CI, 0.30-0.96), compared with Black inpatients.
The investigators utilized the Acute Care Hospital Groups network within Vizient, a member-driven health care performance improvement company, to collect data for the study. Most of the hospitals (91%) that submitted data on adult inpatients with cellulitis or SSTIs (without other infections) were in urban settings and 9% were in rural settings; 60% were community hospitals and 40% were academic medical centers. The researchers accounted for “clustering by hospital” – such as the use of internal guidelines – in their methodology.
Differential management and prescribing practices associated with race and ethnicity have been demonstrated for cardiovascular disease and other chronic problems, but “to see such racial differences play out in acute care is striking,” Utibe R. Essien, MD, MPH, assistant professor of medicine at the University of Pittsburgh and a core investigator with the Center for Health Equity Research and Promotion at the Veterans Affairs Pittsburgh Healthcare System, said in an interview.
“In acute care, we tend to practice pretty similarly across the board ... so the findings give me pause,” said Dr. Essien, an internist and a coauthor of the study, who also works with the University of Pittsburgh’s Center for Pharmaceutical Policy and Prescribing.
Also notable was the prevalence of historical penicillin allergy documented in the dataset: 23% in Black inpatients and 18% in White inpatients with SSTI. It’s a surprisingly high prevalence overall, Dr. Blumenthal said, and the racial difference was surprising because penicillin allergy has been commonly described in the literature as being more common in the White population.
Even though penicillin allergy was controlled for in the study, “given that historical penicillin allergies are associated with increased clindamycin use and risk of CDI, but are often disproved with formal testing, racial disparities in penicillin allergy documentation and assessment require additional study,” she and her coauthors wrote.
Ideally, Dr. Blumenthal said, all inpatients would have access to allergy consultations or testing or some sort of infrastructure for assessing a history of penicillin allergy. At Mass General, allergy consults and challenge doses of beta-lactams (also called graded challenges) are frequently employed.
The study did not collect data on income, educational level, and other structural vulnerability factors. More research is needed to better understand “what’s going on in acute care settings and what the potential drivers of disparities may be,” said Dr. Essien, who co-authored a recent JAMA editorial on “achieving pharmacoequity” to reduce health disparities.
“If guidelines suggest that medication A is the ideal and optimal treatment, we really have to do our best to ensure that every patient, regardless of race or ethnicity, can get that treatment,” he said.
In the study, race was extracted from the medical record and may not have been correctly assigned, the authors noted. “Other race” was not specified in the dataset, and Hispanic ethnicity was not captured. The number of individuals identified as Asian and other races was small, prompting the researchers to focus on antibiotic use in Black and White patients (224 and 854 patients, respectively).
Dr. Blumenthal and Dr. Essien both reported that they had no relevant disclosures. The study was supported with National Institutes of Health grants and the Massachusetts General Hospital department of medicine transformative scholar program.
– in a national cross-sectional study involving over 1,000 patients in 91 hospitals.
The potential racial disparity in management of SSTI was detected after data were adjusted for penicillin allergy history and for MRSA colonization/infection. The data were also adjusted for hospital day (since admission) in order to control for the administration of more empiric therapy early on.
Clindamycin, a beta-lactam alternative, is not recommended as an SSTI treatment given its frequent dosing requirements and high potential for adverse events including Clostridioides difficile infection (DCI). “Clindamycin is an option but it’s considered inferior. ... It covers MRSA but it shouldn’t be a go-to for skin and soft-tissue infections,” said senior author Kimberly Blumenthal, MD, MSc, assistant professor of medicine at Harvard University, and an allergist, immunologist, and drug allergy and epidemiology researcher at Massachusetts General Hospital, both in Boston.
Cefazolin, on the other hand, does not cover MRSA but is “a guideline-recommended first-line antibiotic for cellulitis SSTI in the hospital,” she said in an interview.
The findings, recently published in JAMA Network Open, offer a valuable portrait of the antibiotics being prescribed in the inpatient setting for SSTIs. Vancomycin, which typically is reserved for MRSA, was the most commonly prescribed antibiotic, regardless of race. Piperacillin-tazobactam, a beta-lactam, was the second most commonly prescribed antibiotic, again regardless of race.
Intravenously administered cefazolin was used in 13% of White inpatients versus 5% of Black inpatients. After controlling for kidney disease, diabetes, and ICU location (in addition to hospital day, penicillin allergy history, and MRSA), White inpatients had an increased likelihood of being prescribed cefazolin (adjusted odds ratio, 2.82; 95% confidence interval, 1.41-5.63) and a decreased likelihood of clindamycin use (aOR, 0.54; 95% CI, 0.30-0.96), compared with Black inpatients.
The investigators utilized the Acute Care Hospital Groups network within Vizient, a member-driven health care performance improvement company, to collect data for the study. Most of the hospitals (91%) that submitted data on adult inpatients with cellulitis or SSTIs (without other infections) were in urban settings and 9% were in rural settings; 60% were community hospitals and 40% were academic medical centers. The researchers accounted for “clustering by hospital” – such as the use of internal guidelines – in their methodology.
Differential management and prescribing practices associated with race and ethnicity have been demonstrated for cardiovascular disease and other chronic problems, but “to see such racial differences play out in acute care is striking,” Utibe R. Essien, MD, MPH, assistant professor of medicine at the University of Pittsburgh and a core investigator with the Center for Health Equity Research and Promotion at the Veterans Affairs Pittsburgh Healthcare System, said in an interview.
“In acute care, we tend to practice pretty similarly across the board ... so the findings give me pause,” said Dr. Essien, an internist and a coauthor of the study, who also works with the University of Pittsburgh’s Center for Pharmaceutical Policy and Prescribing.
Also notable was the prevalence of historical penicillin allergy documented in the dataset: 23% in Black inpatients and 18% in White inpatients with SSTI. It’s a surprisingly high prevalence overall, Dr. Blumenthal said, and the racial difference was surprising because penicillin allergy has been commonly described in the literature as being more common in the White population.
Even though penicillin allergy was controlled for in the study, “given that historical penicillin allergies are associated with increased clindamycin use and risk of CDI, but are often disproved with formal testing, racial disparities in penicillin allergy documentation and assessment require additional study,” she and her coauthors wrote.
Ideally, Dr. Blumenthal said, all inpatients would have access to allergy consultations or testing or some sort of infrastructure for assessing a history of penicillin allergy. At Mass General, allergy consults and challenge doses of beta-lactams (also called graded challenges) are frequently employed.
The study did not collect data on income, educational level, and other structural vulnerability factors. More research is needed to better understand “what’s going on in acute care settings and what the potential drivers of disparities may be,” said Dr. Essien, who co-authored a recent JAMA editorial on “achieving pharmacoequity” to reduce health disparities.
“If guidelines suggest that medication A is the ideal and optimal treatment, we really have to do our best to ensure that every patient, regardless of race or ethnicity, can get that treatment,” he said.
In the study, race was extracted from the medical record and may not have been correctly assigned, the authors noted. “Other race” was not specified in the dataset, and Hispanic ethnicity was not captured. The number of individuals identified as Asian and other races was small, prompting the researchers to focus on antibiotic use in Black and White patients (224 and 854 patients, respectively).
Dr. Blumenthal and Dr. Essien both reported that they had no relevant disclosures. The study was supported with National Institutes of Health grants and the Massachusetts General Hospital department of medicine transformative scholar program.
– in a national cross-sectional study involving over 1,000 patients in 91 hospitals.
The potential racial disparity in management of SSTI was detected after data were adjusted for penicillin allergy history and for MRSA colonization/infection. The data were also adjusted for hospital day (since admission) in order to control for the administration of more empiric therapy early on.
Clindamycin, a beta-lactam alternative, is not recommended as an SSTI treatment given its frequent dosing requirements and high potential for adverse events including Clostridioides difficile infection (DCI). “Clindamycin is an option but it’s considered inferior. ... It covers MRSA but it shouldn’t be a go-to for skin and soft-tissue infections,” said senior author Kimberly Blumenthal, MD, MSc, assistant professor of medicine at Harvard University, and an allergist, immunologist, and drug allergy and epidemiology researcher at Massachusetts General Hospital, both in Boston.
Cefazolin, on the other hand, does not cover MRSA but is “a guideline-recommended first-line antibiotic for cellulitis SSTI in the hospital,” she said in an interview.
The findings, recently published in JAMA Network Open, offer a valuable portrait of the antibiotics being prescribed in the inpatient setting for SSTIs. Vancomycin, which typically is reserved for MRSA, was the most commonly prescribed antibiotic, regardless of race. Piperacillin-tazobactam, a beta-lactam, was the second most commonly prescribed antibiotic, again regardless of race.
Intravenously administered cefazolin was used in 13% of White inpatients versus 5% of Black inpatients. After controlling for kidney disease, diabetes, and ICU location (in addition to hospital day, penicillin allergy history, and MRSA), White inpatients had an increased likelihood of being prescribed cefazolin (adjusted odds ratio, 2.82; 95% confidence interval, 1.41-5.63) and a decreased likelihood of clindamycin use (aOR, 0.54; 95% CI, 0.30-0.96), compared with Black inpatients.
The investigators utilized the Acute Care Hospital Groups network within Vizient, a member-driven health care performance improvement company, to collect data for the study. Most of the hospitals (91%) that submitted data on adult inpatients with cellulitis or SSTIs (without other infections) were in urban settings and 9% were in rural settings; 60% were community hospitals and 40% were academic medical centers. The researchers accounted for “clustering by hospital” – such as the use of internal guidelines – in their methodology.
Differential management and prescribing practices associated with race and ethnicity have been demonstrated for cardiovascular disease and other chronic problems, but “to see such racial differences play out in acute care is striking,” Utibe R. Essien, MD, MPH, assistant professor of medicine at the University of Pittsburgh and a core investigator with the Center for Health Equity Research and Promotion at the Veterans Affairs Pittsburgh Healthcare System, said in an interview.
“In acute care, we tend to practice pretty similarly across the board ... so the findings give me pause,” said Dr. Essien, an internist and a coauthor of the study, who also works with the University of Pittsburgh’s Center for Pharmaceutical Policy and Prescribing.
Also notable was the prevalence of historical penicillin allergy documented in the dataset: 23% in Black inpatients and 18% in White inpatients with SSTI. It’s a surprisingly high prevalence overall, Dr. Blumenthal said, and the racial difference was surprising because penicillin allergy has been commonly described in the literature as being more common in the White population.
Even though penicillin allergy was controlled for in the study, “given that historical penicillin allergies are associated with increased clindamycin use and risk of CDI, but are often disproved with formal testing, racial disparities in penicillin allergy documentation and assessment require additional study,” she and her coauthors wrote.
Ideally, Dr. Blumenthal said, all inpatients would have access to allergy consultations or testing or some sort of infrastructure for assessing a history of penicillin allergy. At Mass General, allergy consults and challenge doses of beta-lactams (also called graded challenges) are frequently employed.
The study did not collect data on income, educational level, and other structural vulnerability factors. More research is needed to better understand “what’s going on in acute care settings and what the potential drivers of disparities may be,” said Dr. Essien, who co-authored a recent JAMA editorial on “achieving pharmacoequity” to reduce health disparities.
“If guidelines suggest that medication A is the ideal and optimal treatment, we really have to do our best to ensure that every patient, regardless of race or ethnicity, can get that treatment,” he said.
In the study, race was extracted from the medical record and may not have been correctly assigned, the authors noted. “Other race” was not specified in the dataset, and Hispanic ethnicity was not captured. The number of individuals identified as Asian and other races was small, prompting the researchers to focus on antibiotic use in Black and White patients (224 and 854 patients, respectively).
Dr. Blumenthal and Dr. Essien both reported that they had no relevant disclosures. The study was supported with National Institutes of Health grants and the Massachusetts General Hospital department of medicine transformative scholar program.
FROM JAMA NETWORK OPEN
Prurigo nodularis has two disease endotypes, a cluster analysis shows
A cluster analysis of circulating plasma biomarkers in prurigo nodularis (PN) has identified two disease endotypes with inflammatory and noninflammatory biomarker profiles.
said senior author Shawn G. Kwatra, MD, of the department of dermatology at Johns Hopkins University, Baltimore. “This is the beginning of personalized medicine in prurigo nodularis.”
He and others have long observed significant clinical heterogeneity both in the presentation of PN – with the nodules in African American patients, for instance, appearing larger, thicker, and more fibrotic – and in patients’ response to immunomodulating and neuromodulating therapies.
To avoid the introduction of bias, the researchers used an unsupervised machine-learning approach to analyze the levels of 12 inflammatory biomarkers in 20 patients with PN and in matched healthy controls. The biomarkers were chosen based on their demonstrated dysregulation in PN and other inflammatory dermatoses.
The researchers then conducted a population-level analysis using multicenter electronic medical record data to explore inflammatory markers and verify findings from the cluster analysis. The study was published online Oct. 27, 2021, in the Journal of Investigative Dermatology.
One cluster of the 20 patients had higher levels of nine inflammatory biomarkers representing multiple immune axes: Higher interleukin-1 alpha, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, and IL-25. This cluster had a higher percentage of Black patients, a higher severity of itch, and lower quality of life scores, the authors report in the preprint.
The other cluster – without such an inflammatory profile – had fewer Black patients and a higher percentage of patients with myelopathy (e.g. spinal stenosis, spinal trauma, degenerative disc disease). The rates of inflammatory comorbidities and of immune- and neuromodulating treatments at the time of blood draw were relatively equivalent between the two clusters.
In the subsequent population-level analysis, using data from a global health research network of EMRs from almost 50 health care organizations, Black patients with PN were found to have higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils, and lower transferrin, than White patients with PN. (The analysis included only Black and White patients.)
There are no Food and Drug Administration–approved therapies for PN, and “clinicians need to be really creative in managing these patients,” Dr. Kwatra said.
“There may be suggestions at the bedside that patients have more immune dysregulation, or maybe I’ll see increased circulating blood eosinophils,” he said. “And there are those who don’t seem to have any immune dysregulation and have more features of neurosensitization ... who may have a history of neck pain or back injury.”
The existence of endotypes in PN suggests that patients may benefit from personalized therapies with either immunomodulating or neuromodulating treatments, he and his colleagues wrote. “Further neuroimmune phenotyping studies of PN may pave the way for a future precision medicine management approach.”
Studies of PN conducted in Europe have been almost exclusively in White patients, Dr. Kwatra noted, even though PN has been shown to disproportionately affect Black and other racial/ethnic-minority patients.
Black patients with PN were found to have the highest all-cause mortality over 20 years post diagnosis in a separate analysis of over 22,000 patients with PN. Using data from the same health research network, Dr. Kwatra and coinvestigators stratified patients by race/ethnicity and compared each subgroup with a corresponding subgroup of similar race/ethnicity to control for inherent differences in mortality.
Overall, patients with PN had higher all-cause mortality than controls (hazard ratio, 1.70), likely because of a high comorbidity burden, they wrote in their research letter. Black patients with PN had the highest mortality (HR, 2.07), followed by White (HR, 1.74) and Hispanic (HR, 1.62) patients.
PN may exacerbate existing racial disparities in the social determinants of health, and Black patients may suffer from greater systemic inflammation, Dr. Kwatra and coauthors wrote. Certainly, he said, these findings, as well as the finding of a distinct inflammatory signature in Black patients with PN, support “that the disease burden is much higher” in these patients.
Dr Kwatra disclosed that he is an advisory board member/consultant for Celldex Therapeutics, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals and has received grant funding from several companies. His research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grants from the Dermatology Foundation and the Skin of Color Society also helped fund the cluster analysis.
A cluster analysis of circulating plasma biomarkers in prurigo nodularis (PN) has identified two disease endotypes with inflammatory and noninflammatory biomarker profiles.
said senior author Shawn G. Kwatra, MD, of the department of dermatology at Johns Hopkins University, Baltimore. “This is the beginning of personalized medicine in prurigo nodularis.”
He and others have long observed significant clinical heterogeneity both in the presentation of PN – with the nodules in African American patients, for instance, appearing larger, thicker, and more fibrotic – and in patients’ response to immunomodulating and neuromodulating therapies.
To avoid the introduction of bias, the researchers used an unsupervised machine-learning approach to analyze the levels of 12 inflammatory biomarkers in 20 patients with PN and in matched healthy controls. The biomarkers were chosen based on their demonstrated dysregulation in PN and other inflammatory dermatoses.
The researchers then conducted a population-level analysis using multicenter electronic medical record data to explore inflammatory markers and verify findings from the cluster analysis. The study was published online Oct. 27, 2021, in the Journal of Investigative Dermatology.
One cluster of the 20 patients had higher levels of nine inflammatory biomarkers representing multiple immune axes: Higher interleukin-1 alpha, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, and IL-25. This cluster had a higher percentage of Black patients, a higher severity of itch, and lower quality of life scores, the authors report in the preprint.
The other cluster – without such an inflammatory profile – had fewer Black patients and a higher percentage of patients with myelopathy (e.g. spinal stenosis, spinal trauma, degenerative disc disease). The rates of inflammatory comorbidities and of immune- and neuromodulating treatments at the time of blood draw were relatively equivalent between the two clusters.
In the subsequent population-level analysis, using data from a global health research network of EMRs from almost 50 health care organizations, Black patients with PN were found to have higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils, and lower transferrin, than White patients with PN. (The analysis included only Black and White patients.)
There are no Food and Drug Administration–approved therapies for PN, and “clinicians need to be really creative in managing these patients,” Dr. Kwatra said.
“There may be suggestions at the bedside that patients have more immune dysregulation, or maybe I’ll see increased circulating blood eosinophils,” he said. “And there are those who don’t seem to have any immune dysregulation and have more features of neurosensitization ... who may have a history of neck pain or back injury.”
The existence of endotypes in PN suggests that patients may benefit from personalized therapies with either immunomodulating or neuromodulating treatments, he and his colleagues wrote. “Further neuroimmune phenotyping studies of PN may pave the way for a future precision medicine management approach.”
Studies of PN conducted in Europe have been almost exclusively in White patients, Dr. Kwatra noted, even though PN has been shown to disproportionately affect Black and other racial/ethnic-minority patients.
Black patients with PN were found to have the highest all-cause mortality over 20 years post diagnosis in a separate analysis of over 22,000 patients with PN. Using data from the same health research network, Dr. Kwatra and coinvestigators stratified patients by race/ethnicity and compared each subgroup with a corresponding subgroup of similar race/ethnicity to control for inherent differences in mortality.
Overall, patients with PN had higher all-cause mortality than controls (hazard ratio, 1.70), likely because of a high comorbidity burden, they wrote in their research letter. Black patients with PN had the highest mortality (HR, 2.07), followed by White (HR, 1.74) and Hispanic (HR, 1.62) patients.
PN may exacerbate existing racial disparities in the social determinants of health, and Black patients may suffer from greater systemic inflammation, Dr. Kwatra and coauthors wrote. Certainly, he said, these findings, as well as the finding of a distinct inflammatory signature in Black patients with PN, support “that the disease burden is much higher” in these patients.
Dr Kwatra disclosed that he is an advisory board member/consultant for Celldex Therapeutics, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals and has received grant funding from several companies. His research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grants from the Dermatology Foundation and the Skin of Color Society also helped fund the cluster analysis.
A cluster analysis of circulating plasma biomarkers in prurigo nodularis (PN) has identified two disease endotypes with inflammatory and noninflammatory biomarker profiles.
said senior author Shawn G. Kwatra, MD, of the department of dermatology at Johns Hopkins University, Baltimore. “This is the beginning of personalized medicine in prurigo nodularis.”
He and others have long observed significant clinical heterogeneity both in the presentation of PN – with the nodules in African American patients, for instance, appearing larger, thicker, and more fibrotic – and in patients’ response to immunomodulating and neuromodulating therapies.
To avoid the introduction of bias, the researchers used an unsupervised machine-learning approach to analyze the levels of 12 inflammatory biomarkers in 20 patients with PN and in matched healthy controls. The biomarkers were chosen based on their demonstrated dysregulation in PN and other inflammatory dermatoses.
The researchers then conducted a population-level analysis using multicenter electronic medical record data to explore inflammatory markers and verify findings from the cluster analysis. The study was published online Oct. 27, 2021, in the Journal of Investigative Dermatology.
One cluster of the 20 patients had higher levels of nine inflammatory biomarkers representing multiple immune axes: Higher interleukin-1 alpha, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, and IL-25. This cluster had a higher percentage of Black patients, a higher severity of itch, and lower quality of life scores, the authors report in the preprint.
The other cluster – without such an inflammatory profile – had fewer Black patients and a higher percentage of patients with myelopathy (e.g. spinal stenosis, spinal trauma, degenerative disc disease). The rates of inflammatory comorbidities and of immune- and neuromodulating treatments at the time of blood draw were relatively equivalent between the two clusters.
In the subsequent population-level analysis, using data from a global health research network of EMRs from almost 50 health care organizations, Black patients with PN were found to have higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils, and lower transferrin, than White patients with PN. (The analysis included only Black and White patients.)
There are no Food and Drug Administration–approved therapies for PN, and “clinicians need to be really creative in managing these patients,” Dr. Kwatra said.
“There may be suggestions at the bedside that patients have more immune dysregulation, or maybe I’ll see increased circulating blood eosinophils,” he said. “And there are those who don’t seem to have any immune dysregulation and have more features of neurosensitization ... who may have a history of neck pain or back injury.”
The existence of endotypes in PN suggests that patients may benefit from personalized therapies with either immunomodulating or neuromodulating treatments, he and his colleagues wrote. “Further neuroimmune phenotyping studies of PN may pave the way for a future precision medicine management approach.”
Studies of PN conducted in Europe have been almost exclusively in White patients, Dr. Kwatra noted, even though PN has been shown to disproportionately affect Black and other racial/ethnic-minority patients.
Black patients with PN were found to have the highest all-cause mortality over 20 years post diagnosis in a separate analysis of over 22,000 patients with PN. Using data from the same health research network, Dr. Kwatra and coinvestigators stratified patients by race/ethnicity and compared each subgroup with a corresponding subgroup of similar race/ethnicity to control for inherent differences in mortality.
Overall, patients with PN had higher all-cause mortality than controls (hazard ratio, 1.70), likely because of a high comorbidity burden, they wrote in their research letter. Black patients with PN had the highest mortality (HR, 2.07), followed by White (HR, 1.74) and Hispanic (HR, 1.62) patients.
PN may exacerbate existing racial disparities in the social determinants of health, and Black patients may suffer from greater systemic inflammation, Dr. Kwatra and coauthors wrote. Certainly, he said, these findings, as well as the finding of a distinct inflammatory signature in Black patients with PN, support “that the disease burden is much higher” in these patients.
Dr Kwatra disclosed that he is an advisory board member/consultant for Celldex Therapeutics, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals and has received grant funding from several companies. His research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grants from the Dermatology Foundation and the Skin of Color Society also helped fund the cluster analysis.
FROM THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
Lung transplantation in the era of COVID-19: New issues and paradigms
Data is sparse thus far, but there is concern in lung transplant medicine about the long-term risk of chronic lung allograft dysfunction (CLAD) and a potentially shortened longevity of transplanted lungs in recipients who become ill with COVID-19.
“My fear is that we’re potentially sitting on this iceberg worth of people who, come 6 months or a year from [the acute phase of] their COVID illness, will in fact have earlier and progressive, chronic rejection,” said Cameron R. Wolfe, MBBS, MPH, associate professor of medicine in transplant infectious disease at Duke University, Durham, N.C.
Lower respiratory viral infections have long been concerning for lung transplant recipients given their propensity to cause scarring, a decline in lung function, and a heightened risk of allograft rejection. Time will tell whether lung transplant recipients who survive COVID-19 follow a similar path, or one that is worse, he said.
Short-term data
Outcomes beyond hospitalization and acute illness for lung transplant recipients affected by COVID-19 have been reported in the literature by only a few lung transplant programs. These reports – as well as anecdotal experiences being informally shared among transplant programs – have raised the specter of more severe dysfunction following the acute phase and more early CLAD, said Tathagat Narula, MD, assistant professor of medicine at the Mayo Medical School, Rochester, Minn., and a consultant in lung transplantation at the Mayo Clinic’s Jacksonville program.
“The available data cover only 3-6 months out. We don’t know what will happen in the next 6 months and beyond,” Dr. Narula said in an interview.
The risks of COVID-19 in already-transplanted patients and issues relating to the inadequate antibody responses to vaccination are just some of the challenges of lung transplant medicine in the era of SARS-CoV-2. “COVID-19,” said Dr. Narula, “has completely changed the way we practice lung transplant medicine – the way we’re looking both at our recipients and our donors.”
Potential donors are being evaluated with lower respiratory SARS-CoV-2 testing and an abundance of caution. And patients with severe COVID-19 affecting their own lungs are roundly expected to drive up lung transplant volume in the near future. “The whole paradigm has changed,” Dr. Narula said.
Post-acute trajectories
A chart review study published in October by the lung transplant team at the University of Texas Southwestern Medical Center, Dallas, covered 44 consecutive survivors at a median follow-up of 4.5 months from hospital discharge or acute illness (the survival rate was 83.3%). Patients had significantly impaired functional status, and 18 of the 44 (40.9%) had a significant and persistent loss of forced vital capacity or forced expiratory volume in 1 second (>10% from pre–COVID-19 baseline).
Three patients met the criteria for new CLAD after COVID-19 infection, with all three classified as restrictive allograft syndrome (RAS) phenotype.
Moreover, the majority of COVID-19 survivors who had CT chest scans (22 of 28) showed persistent parenchymal opacities – a finding that, regardless of symptomatology, suggests persistent allograft injury, said Amit Banga, MD, associate professor of medicine and medical director of the ex vivo lung perfusion program in UT Southwestern’s lung transplant program.
“The implication is that there may be long-term consequences of COVID-19, perhaps related to some degree of ongoing inflammation and damage,” said Dr. Banga, a coauthor of the postinfection outcomes paper.
The UT Southwestern lung transplant program, which normally performs 60-80 transplants a year, began routine CT scanning 4-5 months into the pandemic, after “stumbling into a few patients who had no symptoms indicative of COVID pneumonia and no changes on an x-ray but significant involvement on a CT,” he said.
Without routine scanning in the general population of COVID-19 patients, Dr. Banga noted, “we’re limited in convincingly saying that COVID is uniquely doing this to lung transplant recipients.” Nor can they conclude that SARS-CoV-2 is unique from other respiratory viruses such as respiratory syncytial virus (RSV) in this regard. (The program has added CT scanning to its protocol for lung transplant recipients afflicted with other respiratory viruses to learn more.)
However, in the big picture, COVID-19 has proven to be far worse for lung transplant recipients than illness with other respiratory viruses, including RSV. “Patients have more frequent and greater loss of lung function, and worse debility from the acute illness,” Dr. Banga said.
“The cornerstones of treatment of both these viruses are very similar, but both the in-hospital course and the postdischarge outcomes are significantly different.”
In an initial paper published in September 2021, Dr. Banga and colleagues compared their first 25 lung transplant patients testing positive for SARS-CoV-2 with a historical cohort of 36 patients with RSV treated during 2016-2018.
Patients with COVID-19 had significantly worse morbidity and mortality, including worse postinfection lung function loss, functional decline, and 3-month survival.
More time, he said, will shed light on the risks of CLAD and the long-term potential for recovery of lung function. Currently, at UT Southwestern, it appears that patients who survive acute illness and the “first 3-6 months after COVID-19, when we’re seeing all the postinfection morbidity, may [enter] a period of stability,” Dr. Banga said.
Overall, he said, patients in their initial cohort are “holding steady” without unusual morbidity, readmissions, or “other setbacks to their allografts.”
At the Mayo Clinic in Jacksonville, which normally performs 40-50 lung transplants a year, transplant physicians have similarly observed significant declines in lung function beyond the acute phase of COVID-19. “Anecdotally, we’re seeing that some patients are beginning to recover some of their lung function, while others have not,” said Dr. Narula. “And we don’t have predictors as to who will progress to CLAD. It’s a big knowledge gap.”
Dr. Narula noted that patients with restrictive allograft syndrome, such as those reported by the UT Southwestern team, “have scarring of the lung and a much worse prognosis than the obstructive type of chronic rejection.” Whether there’s a role for antifibrotic therapy is a question worthy of research.
In UT Southwestern’s analysis, persistently lower absolute lymphocyte counts (< 600/dL) and higher ferritin levels (>150 ng/mL) at the time of hospital discharge were independently associated with significant lung function loss. This finding, reported in their October paper, has helped guide their management practices, Dr. Banga said.
“Persistently elevated ferritin may indicate ongoing inflammation at the allograft level,” he said. “We now send [such patients] home on a longer course of oral corticosteroids.”
At the front end of care for infected lung transplant recipients, Dr. Banga said that his team and physicians at other lung transplant programs are holding the cell-cycle inhibitor component of patients’ maintenance immunosuppression therapy (commonly mycophenolate or azathioprine) once infection is diagnosed to maximize chances of a better outcome.
“There may be variation on how long [the regimens are adjusted],” he said. “We changed our duration from 4 weeks to 2 due to patients developing a rebound worsening in the third and fourth week of acute illness.”
There is significant variation from institution to institution in how viral infections are managed in lung transplant recipients, he and Dr. Narula said. “Our numbers are so small in lung transplant, and we don’t have standardized protocols – it’s one of the biggest challenges in our field,” said Dr. Narula.
Vaccination issues, evaluation of donors
Whether or not immunosuppression regimens should be adjusted prior to vaccination is a controversial question, but is “an absolutely valid one” and is currently being studied in at least one National Institutes of Health–funded trial involving solid organ transplant recipients, said Dr. Wolfe.
“Some have jumped to the conclusion [based on some earlier data] that they should reduce immunosuppression regimens for everyone at the time of vaccination ... but I don’t know the answer yet,” he said. “Balancing staying rejection free with potentially gaining more immune response is complicated ... and it may depend on where the pandemic is going in your area and other factors.”
Reductions aside, Dr. Wolfe tells lung transplant recipients that, based on his approximation of a number of different studies in solid organ transplant recipients, approximately 40%-50% of patients who are immunized with two doses of the COVID-19 mRNA vaccines will develop meaningful antibody levels – and that this rises to 50%-60% after a third dose.
It is difficult to glean from available studies the level of vaccine response for lung transplant recipients specifically. But given that their level of maintenance immunosuppression is higher than for recipients of other donor organs, “as a broad sweep, lung transplant recipients tend to be lower in the pecking order of response,” he said.
Still, “there’s a lot to gain,” he said, pointing to a recent study from the Morbidity and Mortality Weekly Report (2021 Nov 5. doi: 10.15585/mmwr.mm7044e3) showing that effectiveness of mRNA vaccination against COVID-19–associated hospitalization was 77% among immunocompromised adults (compared with 90% in immunocompetent adults).
“This is good vindication to keep vaccinating,” he said, “and perhaps speaks to how difficult it is to assess the vaccine response [through measurement of antibody only].”
Neither Duke University’s transplant program, which performed 100-120 lung transplants a year pre-COVID, nor the programs at UT Southwestern or the Mayo Clinic in Jacksonville require that solid organ transplant candidates be vaccinated against SARS-CoV-2 in order to receive transplants, as some other transplant programs have done. (When asked about the issue, Dr. Banga and Dr. Narula each said that they have had no or little trouble convincing patients awaiting lung transplants of the need for COVID-19 vaccination.)
In an August statement, the American Society of Transplantation recommended vaccination for all solid organ transplant recipients, preferably prior to transplantation, and said that it “support[s] the development of institutional policies regarding pretransplant vaccination.”
The Society is not tracking centers’ vaccination policies. But Kaiser Health News reported in October that a growing number of transplant programs, such as UCHealth in Denver and UW Medicine in Seattle, have decided to either bar patients who refuse to be vaccinated from receiving transplants or give them lower priority on waitlists.
Potential lung donors, meanwhile, must be evaluated with lower respiratory COVID-19 testing, with results available prior to transplantation, according to policy developed by the Organ Procurement and Transplantation Network and effective in May 2021. The policy followed three published cases of donor-derived COVID-19 in lung transplant recipients, said Dr. Wolfe, who wrote about use of COVID-positive donors in an editorial published in October.
In each case, the donor had a negative COVID-19 nasopharyngeal swab at the time of organ procurement but was later found to have the virus on bronchoalveolar lavage, he said.
(The use of other organs from COVID-positive donors is appearing thus far to be safe, Dr. Wolfe noted. In the editorial, he references 13 cases of solid organ transplantation from SARS-CoV-2–infected donors into noninfected recipients; none of the 13 transplant recipients developed COVID-19).
Some questions remain, such as how many lower respiratory tests should be run, and how donors should be evaluated in cases of discordant results. Dr. Banga shared the case of a donor with one positive lower respiratory test result followed by two negative results. After internal debate, and consideration of potential false positives and other issues, the team at UT Southwestern decided to decline the donor, Dr. Banga said.
Other programs are likely making similar, appropriately cautious decisions, said Dr. Wolfe. “There’s no way in real-time donor evaluation to know whether the positive test is active virus that could infect the recipient and replicate ... or whether it’s [picking up] inactive or dead fragments of virus that was there several weeks ago. Our tests don’t differentiate that.”
Transplants in COVID-19 patients
Decision-making about lung transplant candidacy among patients with COVID-19 acute respiratory distress syndrome is complex and in need of a new paradigm.
“Some of these patients have the potential to recover, and they’re going to recover way later than what we’re used to,” said Dr. Banga. “We can’t extrapolate for COVID ARDS what we’ve learned for any other virus-related ARDS.”
Dr. Narula also has recently seen at least one COVID-19 patient on ECMO and under evaluation for transplantation recover. “We do not want to transplant too early,” he said, noting that there is consensus that lung transplant should be pursued only when the damage is deemed irreversible clinically and radiologically in the best judgment of the team. Still, “for many of these patients the only exit route will be lung transplants. For the next 12-24 months, a significant proportion of our lung transplant patients will have had post-COVID–related lung damage.”
As of October 2021, 233 lung transplants had been performed in the United States in recipients whose primary diagnosis was reported as COVID related, said Anne Paschke, media relations specialist with the United Network for Organ Sharing.
Dr. Banga, Dr. Wolfe, and Dr. Narula reported that they have no relevant disclosures.
Data is sparse thus far, but there is concern in lung transplant medicine about the long-term risk of chronic lung allograft dysfunction (CLAD) and a potentially shortened longevity of transplanted lungs in recipients who become ill with COVID-19.
“My fear is that we’re potentially sitting on this iceberg worth of people who, come 6 months or a year from [the acute phase of] their COVID illness, will in fact have earlier and progressive, chronic rejection,” said Cameron R. Wolfe, MBBS, MPH, associate professor of medicine in transplant infectious disease at Duke University, Durham, N.C.
Lower respiratory viral infections have long been concerning for lung transplant recipients given their propensity to cause scarring, a decline in lung function, and a heightened risk of allograft rejection. Time will tell whether lung transplant recipients who survive COVID-19 follow a similar path, or one that is worse, he said.
Short-term data
Outcomes beyond hospitalization and acute illness for lung transplant recipients affected by COVID-19 have been reported in the literature by only a few lung transplant programs. These reports – as well as anecdotal experiences being informally shared among transplant programs – have raised the specter of more severe dysfunction following the acute phase and more early CLAD, said Tathagat Narula, MD, assistant professor of medicine at the Mayo Medical School, Rochester, Minn., and a consultant in lung transplantation at the Mayo Clinic’s Jacksonville program.
“The available data cover only 3-6 months out. We don’t know what will happen in the next 6 months and beyond,” Dr. Narula said in an interview.
The risks of COVID-19 in already-transplanted patients and issues relating to the inadequate antibody responses to vaccination are just some of the challenges of lung transplant medicine in the era of SARS-CoV-2. “COVID-19,” said Dr. Narula, “has completely changed the way we practice lung transplant medicine – the way we’re looking both at our recipients and our donors.”
Potential donors are being evaluated with lower respiratory SARS-CoV-2 testing and an abundance of caution. And patients with severe COVID-19 affecting their own lungs are roundly expected to drive up lung transplant volume in the near future. “The whole paradigm has changed,” Dr. Narula said.
Post-acute trajectories
A chart review study published in October by the lung transplant team at the University of Texas Southwestern Medical Center, Dallas, covered 44 consecutive survivors at a median follow-up of 4.5 months from hospital discharge or acute illness (the survival rate was 83.3%). Patients had significantly impaired functional status, and 18 of the 44 (40.9%) had a significant and persistent loss of forced vital capacity or forced expiratory volume in 1 second (>10% from pre–COVID-19 baseline).
Three patients met the criteria for new CLAD after COVID-19 infection, with all three classified as restrictive allograft syndrome (RAS) phenotype.
Moreover, the majority of COVID-19 survivors who had CT chest scans (22 of 28) showed persistent parenchymal opacities – a finding that, regardless of symptomatology, suggests persistent allograft injury, said Amit Banga, MD, associate professor of medicine and medical director of the ex vivo lung perfusion program in UT Southwestern’s lung transplant program.
“The implication is that there may be long-term consequences of COVID-19, perhaps related to some degree of ongoing inflammation and damage,” said Dr. Banga, a coauthor of the postinfection outcomes paper.
The UT Southwestern lung transplant program, which normally performs 60-80 transplants a year, began routine CT scanning 4-5 months into the pandemic, after “stumbling into a few patients who had no symptoms indicative of COVID pneumonia and no changes on an x-ray but significant involvement on a CT,” he said.
Without routine scanning in the general population of COVID-19 patients, Dr. Banga noted, “we’re limited in convincingly saying that COVID is uniquely doing this to lung transplant recipients.” Nor can they conclude that SARS-CoV-2 is unique from other respiratory viruses such as respiratory syncytial virus (RSV) in this regard. (The program has added CT scanning to its protocol for lung transplant recipients afflicted with other respiratory viruses to learn more.)
However, in the big picture, COVID-19 has proven to be far worse for lung transplant recipients than illness with other respiratory viruses, including RSV. “Patients have more frequent and greater loss of lung function, and worse debility from the acute illness,” Dr. Banga said.
“The cornerstones of treatment of both these viruses are very similar, but both the in-hospital course and the postdischarge outcomes are significantly different.”
In an initial paper published in September 2021, Dr. Banga and colleagues compared their first 25 lung transplant patients testing positive for SARS-CoV-2 with a historical cohort of 36 patients with RSV treated during 2016-2018.
Patients with COVID-19 had significantly worse morbidity and mortality, including worse postinfection lung function loss, functional decline, and 3-month survival.
More time, he said, will shed light on the risks of CLAD and the long-term potential for recovery of lung function. Currently, at UT Southwestern, it appears that patients who survive acute illness and the “first 3-6 months after COVID-19, when we’re seeing all the postinfection morbidity, may [enter] a period of stability,” Dr. Banga said.
Overall, he said, patients in their initial cohort are “holding steady” without unusual morbidity, readmissions, or “other setbacks to their allografts.”
At the Mayo Clinic in Jacksonville, which normally performs 40-50 lung transplants a year, transplant physicians have similarly observed significant declines in lung function beyond the acute phase of COVID-19. “Anecdotally, we’re seeing that some patients are beginning to recover some of their lung function, while others have not,” said Dr. Narula. “And we don’t have predictors as to who will progress to CLAD. It’s a big knowledge gap.”
Dr. Narula noted that patients with restrictive allograft syndrome, such as those reported by the UT Southwestern team, “have scarring of the lung and a much worse prognosis than the obstructive type of chronic rejection.” Whether there’s a role for antifibrotic therapy is a question worthy of research.
In UT Southwestern’s analysis, persistently lower absolute lymphocyte counts (< 600/dL) and higher ferritin levels (>150 ng/mL) at the time of hospital discharge were independently associated with significant lung function loss. This finding, reported in their October paper, has helped guide their management practices, Dr. Banga said.
“Persistently elevated ferritin may indicate ongoing inflammation at the allograft level,” he said. “We now send [such patients] home on a longer course of oral corticosteroids.”
At the front end of care for infected lung transplant recipients, Dr. Banga said that his team and physicians at other lung transplant programs are holding the cell-cycle inhibitor component of patients’ maintenance immunosuppression therapy (commonly mycophenolate or azathioprine) once infection is diagnosed to maximize chances of a better outcome.
“There may be variation on how long [the regimens are adjusted],” he said. “We changed our duration from 4 weeks to 2 due to patients developing a rebound worsening in the third and fourth week of acute illness.”
There is significant variation from institution to institution in how viral infections are managed in lung transplant recipients, he and Dr. Narula said. “Our numbers are so small in lung transplant, and we don’t have standardized protocols – it’s one of the biggest challenges in our field,” said Dr. Narula.
Vaccination issues, evaluation of donors
Whether or not immunosuppression regimens should be adjusted prior to vaccination is a controversial question, but is “an absolutely valid one” and is currently being studied in at least one National Institutes of Health–funded trial involving solid organ transplant recipients, said Dr. Wolfe.
“Some have jumped to the conclusion [based on some earlier data] that they should reduce immunosuppression regimens for everyone at the time of vaccination ... but I don’t know the answer yet,” he said. “Balancing staying rejection free with potentially gaining more immune response is complicated ... and it may depend on where the pandemic is going in your area and other factors.”
Reductions aside, Dr. Wolfe tells lung transplant recipients that, based on his approximation of a number of different studies in solid organ transplant recipients, approximately 40%-50% of patients who are immunized with two doses of the COVID-19 mRNA vaccines will develop meaningful antibody levels – and that this rises to 50%-60% after a third dose.
It is difficult to glean from available studies the level of vaccine response for lung transplant recipients specifically. But given that their level of maintenance immunosuppression is higher than for recipients of other donor organs, “as a broad sweep, lung transplant recipients tend to be lower in the pecking order of response,” he said.
Still, “there’s a lot to gain,” he said, pointing to a recent study from the Morbidity and Mortality Weekly Report (2021 Nov 5. doi: 10.15585/mmwr.mm7044e3) showing that effectiveness of mRNA vaccination against COVID-19–associated hospitalization was 77% among immunocompromised adults (compared with 90% in immunocompetent adults).
“This is good vindication to keep vaccinating,” he said, “and perhaps speaks to how difficult it is to assess the vaccine response [through measurement of antibody only].”
Neither Duke University’s transplant program, which performed 100-120 lung transplants a year pre-COVID, nor the programs at UT Southwestern or the Mayo Clinic in Jacksonville require that solid organ transplant candidates be vaccinated against SARS-CoV-2 in order to receive transplants, as some other transplant programs have done. (When asked about the issue, Dr. Banga and Dr. Narula each said that they have had no or little trouble convincing patients awaiting lung transplants of the need for COVID-19 vaccination.)
In an August statement, the American Society of Transplantation recommended vaccination for all solid organ transplant recipients, preferably prior to transplantation, and said that it “support[s] the development of institutional policies regarding pretransplant vaccination.”
The Society is not tracking centers’ vaccination policies. But Kaiser Health News reported in October that a growing number of transplant programs, such as UCHealth in Denver and UW Medicine in Seattle, have decided to either bar patients who refuse to be vaccinated from receiving transplants or give them lower priority on waitlists.
Potential lung donors, meanwhile, must be evaluated with lower respiratory COVID-19 testing, with results available prior to transplantation, according to policy developed by the Organ Procurement and Transplantation Network and effective in May 2021. The policy followed three published cases of donor-derived COVID-19 in lung transplant recipients, said Dr. Wolfe, who wrote about use of COVID-positive donors in an editorial published in October.
In each case, the donor had a negative COVID-19 nasopharyngeal swab at the time of organ procurement but was later found to have the virus on bronchoalveolar lavage, he said.
(The use of other organs from COVID-positive donors is appearing thus far to be safe, Dr. Wolfe noted. In the editorial, he references 13 cases of solid organ transplantation from SARS-CoV-2–infected donors into noninfected recipients; none of the 13 transplant recipients developed COVID-19).
Some questions remain, such as how many lower respiratory tests should be run, and how donors should be evaluated in cases of discordant results. Dr. Banga shared the case of a donor with one positive lower respiratory test result followed by two negative results. After internal debate, and consideration of potential false positives and other issues, the team at UT Southwestern decided to decline the donor, Dr. Banga said.
Other programs are likely making similar, appropriately cautious decisions, said Dr. Wolfe. “There’s no way in real-time donor evaluation to know whether the positive test is active virus that could infect the recipient and replicate ... or whether it’s [picking up] inactive or dead fragments of virus that was there several weeks ago. Our tests don’t differentiate that.”
Transplants in COVID-19 patients
Decision-making about lung transplant candidacy among patients with COVID-19 acute respiratory distress syndrome is complex and in need of a new paradigm.
“Some of these patients have the potential to recover, and they’re going to recover way later than what we’re used to,” said Dr. Banga. “We can’t extrapolate for COVID ARDS what we’ve learned for any other virus-related ARDS.”
Dr. Narula also has recently seen at least one COVID-19 patient on ECMO and under evaluation for transplantation recover. “We do not want to transplant too early,” he said, noting that there is consensus that lung transplant should be pursued only when the damage is deemed irreversible clinically and radiologically in the best judgment of the team. Still, “for many of these patients the only exit route will be lung transplants. For the next 12-24 months, a significant proportion of our lung transplant patients will have had post-COVID–related lung damage.”
As of October 2021, 233 lung transplants had been performed in the United States in recipients whose primary diagnosis was reported as COVID related, said Anne Paschke, media relations specialist with the United Network for Organ Sharing.
Dr. Banga, Dr. Wolfe, and Dr. Narula reported that they have no relevant disclosures.
Data is sparse thus far, but there is concern in lung transplant medicine about the long-term risk of chronic lung allograft dysfunction (CLAD) and a potentially shortened longevity of transplanted lungs in recipients who become ill with COVID-19.
“My fear is that we’re potentially sitting on this iceberg worth of people who, come 6 months or a year from [the acute phase of] their COVID illness, will in fact have earlier and progressive, chronic rejection,” said Cameron R. Wolfe, MBBS, MPH, associate professor of medicine in transplant infectious disease at Duke University, Durham, N.C.
Lower respiratory viral infections have long been concerning for lung transplant recipients given their propensity to cause scarring, a decline in lung function, and a heightened risk of allograft rejection. Time will tell whether lung transplant recipients who survive COVID-19 follow a similar path, or one that is worse, he said.
Short-term data
Outcomes beyond hospitalization and acute illness for lung transplant recipients affected by COVID-19 have been reported in the literature by only a few lung transplant programs. These reports – as well as anecdotal experiences being informally shared among transplant programs – have raised the specter of more severe dysfunction following the acute phase and more early CLAD, said Tathagat Narula, MD, assistant professor of medicine at the Mayo Medical School, Rochester, Minn., and a consultant in lung transplantation at the Mayo Clinic’s Jacksonville program.
“The available data cover only 3-6 months out. We don’t know what will happen in the next 6 months and beyond,” Dr. Narula said in an interview.
The risks of COVID-19 in already-transplanted patients and issues relating to the inadequate antibody responses to vaccination are just some of the challenges of lung transplant medicine in the era of SARS-CoV-2. “COVID-19,” said Dr. Narula, “has completely changed the way we practice lung transplant medicine – the way we’re looking both at our recipients and our donors.”
Potential donors are being evaluated with lower respiratory SARS-CoV-2 testing and an abundance of caution. And patients with severe COVID-19 affecting their own lungs are roundly expected to drive up lung transplant volume in the near future. “The whole paradigm has changed,” Dr. Narula said.
Post-acute trajectories
A chart review study published in October by the lung transplant team at the University of Texas Southwestern Medical Center, Dallas, covered 44 consecutive survivors at a median follow-up of 4.5 months from hospital discharge or acute illness (the survival rate was 83.3%). Patients had significantly impaired functional status, and 18 of the 44 (40.9%) had a significant and persistent loss of forced vital capacity or forced expiratory volume in 1 second (>10% from pre–COVID-19 baseline).
Three patients met the criteria for new CLAD after COVID-19 infection, with all three classified as restrictive allograft syndrome (RAS) phenotype.
Moreover, the majority of COVID-19 survivors who had CT chest scans (22 of 28) showed persistent parenchymal opacities – a finding that, regardless of symptomatology, suggests persistent allograft injury, said Amit Banga, MD, associate professor of medicine and medical director of the ex vivo lung perfusion program in UT Southwestern’s lung transplant program.
“The implication is that there may be long-term consequences of COVID-19, perhaps related to some degree of ongoing inflammation and damage,” said Dr. Banga, a coauthor of the postinfection outcomes paper.
The UT Southwestern lung transplant program, which normally performs 60-80 transplants a year, began routine CT scanning 4-5 months into the pandemic, after “stumbling into a few patients who had no symptoms indicative of COVID pneumonia and no changes on an x-ray but significant involvement on a CT,” he said.
Without routine scanning in the general population of COVID-19 patients, Dr. Banga noted, “we’re limited in convincingly saying that COVID is uniquely doing this to lung transplant recipients.” Nor can they conclude that SARS-CoV-2 is unique from other respiratory viruses such as respiratory syncytial virus (RSV) in this regard. (The program has added CT scanning to its protocol for lung transplant recipients afflicted with other respiratory viruses to learn more.)
However, in the big picture, COVID-19 has proven to be far worse for lung transplant recipients than illness with other respiratory viruses, including RSV. “Patients have more frequent and greater loss of lung function, and worse debility from the acute illness,” Dr. Banga said.
“The cornerstones of treatment of both these viruses are very similar, but both the in-hospital course and the postdischarge outcomes are significantly different.”
In an initial paper published in September 2021, Dr. Banga and colleagues compared their first 25 lung transplant patients testing positive for SARS-CoV-2 with a historical cohort of 36 patients with RSV treated during 2016-2018.
Patients with COVID-19 had significantly worse morbidity and mortality, including worse postinfection lung function loss, functional decline, and 3-month survival.
More time, he said, will shed light on the risks of CLAD and the long-term potential for recovery of lung function. Currently, at UT Southwestern, it appears that patients who survive acute illness and the “first 3-6 months after COVID-19, when we’re seeing all the postinfection morbidity, may [enter] a period of stability,” Dr. Banga said.
Overall, he said, patients in their initial cohort are “holding steady” without unusual morbidity, readmissions, or “other setbacks to their allografts.”
At the Mayo Clinic in Jacksonville, which normally performs 40-50 lung transplants a year, transplant physicians have similarly observed significant declines in lung function beyond the acute phase of COVID-19. “Anecdotally, we’re seeing that some patients are beginning to recover some of their lung function, while others have not,” said Dr. Narula. “And we don’t have predictors as to who will progress to CLAD. It’s a big knowledge gap.”
Dr. Narula noted that patients with restrictive allograft syndrome, such as those reported by the UT Southwestern team, “have scarring of the lung and a much worse prognosis than the obstructive type of chronic rejection.” Whether there’s a role for antifibrotic therapy is a question worthy of research.
In UT Southwestern’s analysis, persistently lower absolute lymphocyte counts (< 600/dL) and higher ferritin levels (>150 ng/mL) at the time of hospital discharge were independently associated with significant lung function loss. This finding, reported in their October paper, has helped guide their management practices, Dr. Banga said.
“Persistently elevated ferritin may indicate ongoing inflammation at the allograft level,” he said. “We now send [such patients] home on a longer course of oral corticosteroids.”
At the front end of care for infected lung transplant recipients, Dr. Banga said that his team and physicians at other lung transplant programs are holding the cell-cycle inhibitor component of patients’ maintenance immunosuppression therapy (commonly mycophenolate or azathioprine) once infection is diagnosed to maximize chances of a better outcome.
“There may be variation on how long [the regimens are adjusted],” he said. “We changed our duration from 4 weeks to 2 due to patients developing a rebound worsening in the third and fourth week of acute illness.”
There is significant variation from institution to institution in how viral infections are managed in lung transplant recipients, he and Dr. Narula said. “Our numbers are so small in lung transplant, and we don’t have standardized protocols – it’s one of the biggest challenges in our field,” said Dr. Narula.
Vaccination issues, evaluation of donors
Whether or not immunosuppression regimens should be adjusted prior to vaccination is a controversial question, but is “an absolutely valid one” and is currently being studied in at least one National Institutes of Health–funded trial involving solid organ transplant recipients, said Dr. Wolfe.
“Some have jumped to the conclusion [based on some earlier data] that they should reduce immunosuppression regimens for everyone at the time of vaccination ... but I don’t know the answer yet,” he said. “Balancing staying rejection free with potentially gaining more immune response is complicated ... and it may depend on where the pandemic is going in your area and other factors.”
Reductions aside, Dr. Wolfe tells lung transplant recipients that, based on his approximation of a number of different studies in solid organ transplant recipients, approximately 40%-50% of patients who are immunized with two doses of the COVID-19 mRNA vaccines will develop meaningful antibody levels – and that this rises to 50%-60% after a third dose.
It is difficult to glean from available studies the level of vaccine response for lung transplant recipients specifically. But given that their level of maintenance immunosuppression is higher than for recipients of other donor organs, “as a broad sweep, lung transplant recipients tend to be lower in the pecking order of response,” he said.
Still, “there’s a lot to gain,” he said, pointing to a recent study from the Morbidity and Mortality Weekly Report (2021 Nov 5. doi: 10.15585/mmwr.mm7044e3) showing that effectiveness of mRNA vaccination against COVID-19–associated hospitalization was 77% among immunocompromised adults (compared with 90% in immunocompetent adults).
“This is good vindication to keep vaccinating,” he said, “and perhaps speaks to how difficult it is to assess the vaccine response [through measurement of antibody only].”
Neither Duke University’s transplant program, which performed 100-120 lung transplants a year pre-COVID, nor the programs at UT Southwestern or the Mayo Clinic in Jacksonville require that solid organ transplant candidates be vaccinated against SARS-CoV-2 in order to receive transplants, as some other transplant programs have done. (When asked about the issue, Dr. Banga and Dr. Narula each said that they have had no or little trouble convincing patients awaiting lung transplants of the need for COVID-19 vaccination.)
In an August statement, the American Society of Transplantation recommended vaccination for all solid organ transplant recipients, preferably prior to transplantation, and said that it “support[s] the development of institutional policies regarding pretransplant vaccination.”
The Society is not tracking centers’ vaccination policies. But Kaiser Health News reported in October that a growing number of transplant programs, such as UCHealth in Denver and UW Medicine in Seattle, have decided to either bar patients who refuse to be vaccinated from receiving transplants or give them lower priority on waitlists.
Potential lung donors, meanwhile, must be evaluated with lower respiratory COVID-19 testing, with results available prior to transplantation, according to policy developed by the Organ Procurement and Transplantation Network and effective in May 2021. The policy followed three published cases of donor-derived COVID-19 in lung transplant recipients, said Dr. Wolfe, who wrote about use of COVID-positive donors in an editorial published in October.
In each case, the donor had a negative COVID-19 nasopharyngeal swab at the time of organ procurement but was later found to have the virus on bronchoalveolar lavage, he said.
(The use of other organs from COVID-positive donors is appearing thus far to be safe, Dr. Wolfe noted. In the editorial, he references 13 cases of solid organ transplantation from SARS-CoV-2–infected donors into noninfected recipients; none of the 13 transplant recipients developed COVID-19).
Some questions remain, such as how many lower respiratory tests should be run, and how donors should be evaluated in cases of discordant results. Dr. Banga shared the case of a donor with one positive lower respiratory test result followed by two negative results. After internal debate, and consideration of potential false positives and other issues, the team at UT Southwestern decided to decline the donor, Dr. Banga said.
Other programs are likely making similar, appropriately cautious decisions, said Dr. Wolfe. “There’s no way in real-time donor evaluation to know whether the positive test is active virus that could infect the recipient and replicate ... or whether it’s [picking up] inactive or dead fragments of virus that was there several weeks ago. Our tests don’t differentiate that.”
Transplants in COVID-19 patients
Decision-making about lung transplant candidacy among patients with COVID-19 acute respiratory distress syndrome is complex and in need of a new paradigm.
“Some of these patients have the potential to recover, and they’re going to recover way later than what we’re used to,” said Dr. Banga. “We can’t extrapolate for COVID ARDS what we’ve learned for any other virus-related ARDS.”
Dr. Narula also has recently seen at least one COVID-19 patient on ECMO and under evaluation for transplantation recover. “We do not want to transplant too early,” he said, noting that there is consensus that lung transplant should be pursued only when the damage is deemed irreversible clinically and radiologically in the best judgment of the team. Still, “for many of these patients the only exit route will be lung transplants. For the next 12-24 months, a significant proportion of our lung transplant patients will have had post-COVID–related lung damage.”
As of October 2021, 233 lung transplants had been performed in the United States in recipients whose primary diagnosis was reported as COVID related, said Anne Paschke, media relations specialist with the United Network for Organ Sharing.
Dr. Banga, Dr. Wolfe, and Dr. Narula reported that they have no relevant disclosures.
Coping with a shattered immune system: COVID and beyond
The co-opting and weakening of the immune system by hematologic malignancies and many of their treatments – and the blunting of the immune system’s response to vaccines – may be more salient during the COVID-19 pandemic than ever before.
Hematologic malignancies have been associated in large cancer-and-COVID-19 registries with more severe COVID-19 outcomes than solid tumors, and COVID-19 mRNA vaccines have yielded suboptimal responses across multiple studies. Clinicians and researchers have no shortage of questions, like what is the optimal timing of vaccines relative to cancer-directed therapy? What is the durability and impact of the immune response? What is the status of the immune system in patients who do not produce antispike antibodies after COVID-19 vaccination?
Moreover, will there be novel nonvaccine strategies – such as antibody cocktails or convalescent plasma – to ensure protection against COVID-19 and other future viral threats? And what really defines immunocompromise today and moving forward?
“We don’t know what we don’t know,” said Jeremy L. Warner, MD, associate professor of medicine (hematology/oncology) and biomedical informatics at Vanderbilt University, Nashville, Tenn., and cofounder of the international COVID-19 and Cancer Consortium. “The immune system is incredibly complex and there are numerous defenses, in addition to the humoral response that we routinely measure.”
Another of the pressing pandemic-time questions for infectious disease specialists working in cancer centers concerns a different infectious threat: measles. “There is a lot of concern in this space about the reported drop in childhood vaccinations and the possibility of measles outbreaks as a follow-up to COVID-19,” said Steven A. Pergam, MD, MPH, associate professor in the vaccine and infectious disease division and the clinical research division of the Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance.
Whether recipients of hematopoietic cell transplantation (HCT) and cellular therapy should be revaccinated earlier than 2 years post treatment is a question worthy of preemptive discussion, he said.
What about timing?
“A silver lining of the pandemic is that it’s improving our understanding of response to vaccinations and outcomes with respiratory viruses in patients with hematologic malignancies,” said Samuel Rubinstein, MD, of the division of hematology at the University of North Carolina at Chapel Hill. “We’re going to learn a lot more about how to ensure that our patients are optimally protected from respiratory viruses.”
Dr. Rubinstein focuses on plasma cell disorders, mostly multiple myeloma, and routinely explains to patients consenting to use daratumumab, an anti-CD38 monoclonal antibody, or a BCMA-directed therapy, that these therapies “in particular probably do impair vaccine immune response.”
He has handled the timing of the COVID-19 vaccines – currently boosters, in most cases – as he has with influenza and other immunizations such as the pneumococcal vaccine, administering the vaccines agnostic to therapy unless the patient is about to start daratumumab or a BCMA-directed therapy. In this case, he considers vaccinating and waiting 2 weeks (for an immune response to occur) before starting therapy.
However, “if I have any concern that a delay will result in suboptimal cancer control, then I don’t wait,” Dr. Rubinstein said. Poor control of a primary malignancy has been consistently associated with worse COVID-19–specific outcomes in cancer–COVID-19 studies, he said, including an analysis of almost 5,000 patients recorded to the COVID-19 and Cancer Consortium .1
(The analysis also documented that patients with a hematologic malignancy had an odds ratio of higher COVID-19 severity of 1.7, compared with patients with a solid tumor, and an odds ratio of 30-day mortality of 1.44.)
Ideally, said Dr. Warner, patients will get vaccinated with the COVID-19 vaccines or others, “before starting on any cytotoxic chemotherapy and when they do not have low blood counts or perhaps autoimmune complications of immunotherapy.” However, “perfect being the enemy of good, it’s better to get vaccinated than to wait for the exact ideal time.”
Peter Paul Yu, MD, physician-in-chief at Hartford (Conn.) Healthcare Cancer Institute, said that for most patients, there’s no evidence to support an optimal timing of vaccine administration during the chemotherapy cycle. “We looked into that [to guide administration of the COVID-19 vaccines], thinking there might be some data about influenza vaccination,” he said. “But there isn’t much. … And if we make things more complicated than the evidence suggests, we may have fewer people getting vaccinations.”
The National Comprehensive Cancer Network offered several timing recommendations in its August 2021 COVID-19 vaccination guidance – mainly that patients receiving intensive cytotoxic chemotherapy (such as those on cytarabine/anthracycline-based induction regimens for acute myeloid leukemia) delay COVID-19 vaccination until absolute neutrophil count recovery, and that patients on long-term maintenance therapy (for instance, targeted agents for chronic lymphocytic leukemia or myeloproliferative neoplasms) be vaccinated as soon as possible.
Vaccination should be delayed for at least 3 months, the NCCN noted, following HCT or engineered cell therapy (for example, chimeric antigen receptor [CAR] T cells) “in order to maximize vaccine efficacy.”
More known unknowns
The tempered efficacy of the COVID-19 vaccines in patients with hematologic malignancies “has been shown in multiple studies of multiple myeloma, chronic lymphocytic leukemia (CLL), and other malignancies, and we know it’s true in transplant,” said Dr. Pergam.
In a study of 67 patients with hematologic malignancies at the University of Pittsburgh Medical Center Hillman Cancer Center, for instance, 46.3% did not generate IgG antibodies against the SARS-CoV-2 spike protein receptor–binding domain after completing their two-dose mRNA vaccine series. Patients with B-cell CLL were especially unlikely to develop antibodies.2A much larger study of more than 1,400 patients from investigators at the Mayo Clinics in Rochester, Minn., and Jacksonville, Fla., found that approximately 25% of all patients with hematologic malignancies did not produce antispike IgG antibodies, and that those with the most common B-cell malignancies had the lowest rate of seropositivity (44%-79%).3There’s a clear but challenging delineation between antibody testing in the research space and in clinical practice, however. Various national and cancer societies recommended earlier this year against routine postvaccine serological monitoring outside of clinical trials, and the sources interviewed for this story all emphasized that antibody titer measurements should not guide decisions about boosters or about the precautions advised for patients.
Titers checked at a single point in time do not capture the kinetics, multidimensional nature, or durability of an immune response, Dr. Warner said. “There are papers out there that say zero patients with CCL seroconverted … but they do still have some immunity, and maybe even a lot of immunity.”
Antibody testing can create a false sense of security, or a false sense of dread, he said. Yet in practice, the use of serological monitoring “has been all over the place [with] no consistency … and decisions probably being made at the individual clinic level or health system level,” he said.
To a lesser degree, so have definitions of what composes significant immunocompromise in the context of COVID-19 vaccine eligibility. “The question comes up, what does immunocompromised really mean?” said Dr. Yu, whose institution is a member of the Memorial Sloan Kettering (MSK) Cancer Alliance.
As of September, the MSK Cancer Center had taken a more granular approach to describing moderate to severe immunocompromise than did the Centers for Disease Control and Prevention. The CDC said this level of immunocompromise includes people receiving active cancer treatment for tumors or cancers of the blood, and those who’ve received a stem cell transplant within the past 2 years. MSK extended the recommendation, as it concerns hematologic malignancies, to patients who are within 12 months after treatment with B-cell depleting drugs, patients who have been treated for blood cancers within the last 6 months, and patients who received CAR T therapy within the past 2 years.
Dr. Yu, who was not involved in creating the MSK recommendations for third COVID-19 vaccines, said that he has been thinking more broadly during the pandemic about the notion of immunocompetence. “It’s my opinion that patients with hematologic malignancies, even if they’re not on treatment, are not fully immune competent,” he said. This includes patients with CLL stage 0 and patients with plasma cell dyscrasias who don’t yet meet the criteria for multiple myeloma but have a monoclonal gammopathy, and those with lower-risk myelodysplastic syndromes, he said.
“We’re seeing [variable] recommendations based on expert opinion, and I think that’s justifiable in such a dynamic situation,” Dr. Yu said. “I would [even] argue it’s desirable so we can learn from different approaches” and collect more rigorous observational data.
Immunocompetence needs to be “viewed in the context of the threat,” he added. “COVID changes the equation. … What’s immunocompromised in my mind has changed [from prepandemic times].”
Preparing for measles
Measles lit up on Dr. Pergam’s radar screen in 2019, when an outbreak occurred in nearby Clark County, Wash. This and other outbreaks in New York, California, and other states highlighted declines in measles herd immunity in the United States and prompted him to investigate the seroprevalence of measles antibodies in the Fred Hutchinson Cancer Research Center’s outpatient population.
Of 959 consecutive patients seen at the center, they found, 25% lacked protective antibodies for measles. For patients with hematologic malignancies and those with a history of HCT, seroprevalence was worse: 37% and 54%, respectively, were without the IgG antibodies.4 Measles “is the most contagious human virus we have at the moment,” he said, and “revaccinating people is hard when it comes to cancer because it is a live virus vaccine.”
Vaccine hesitancy, a rise in nonmedical exemptions, and other factors were threatening herd immunity before the pandemic began. Now, with declines in routine childhood medical visits and other vaccination opportunities and resources here and in other countries – and declining immunization rates documented by the CDC in May 2021 – the pandemic has made measles outbreaks more likely, he said. (Measles outbreaks in West Africa on the tail end of the Ebola outbreak in 2014-2015 caused more deaths in children than Ebola, he noted.)
The first priority is vaccination “cocooning,” a strategy that has long been important for patients with hematologic malignancies. But it also possible, Dr. Pergam said, that in the setting of any future community transmission, revaccination for HCT recipients could occur earlier than the standard 2-year post-transplantation recommendation.
In a 2019 position statement endorsed by the American Society for Transplantation and Cellular Therapy, Dr. Pergam and other infectious disease physicians and oncologists provide criteria for considering early revaccination on a case-by-case basis for patients on minimal immunosuppressive therapy who are at least 1-year post transplantation.5
“Our thinking was that there may be lower-risk patients to whom we could offer the vaccine” – patients for whom the risk of developing measles might outweigh the risk of potential vaccine-related complications, he said.
And if there were community cases, he added, there might be a place for testing antibody levels in post-transplant patients, however imperfect the window to immunity may be. “We’re thinking through potential scenarios,” he said. “Oncologists should think about measles again and have it on their back burner.”
References
1. Grivas P et al. Ann Oncol. 2021 Jun;32(6):787-800.
2. Agha ME et al. Open Forum Infect Dis. 2021 July;8(7):ofab353.
3. Greenberger LM et al. Cancer Cell. 2021 Aug 9;39(8):1031-3.
4. Marquis SR et al. JAMA Netw Open. 2021 July;4(7):e2118508.
5. Pergam SA et al. Biol Blood Marrow Transplant. 2019 Nov;25:e321-30.
The co-opting and weakening of the immune system by hematologic malignancies and many of their treatments – and the blunting of the immune system’s response to vaccines – may be more salient during the COVID-19 pandemic than ever before.
Hematologic malignancies have been associated in large cancer-and-COVID-19 registries with more severe COVID-19 outcomes than solid tumors, and COVID-19 mRNA vaccines have yielded suboptimal responses across multiple studies. Clinicians and researchers have no shortage of questions, like what is the optimal timing of vaccines relative to cancer-directed therapy? What is the durability and impact of the immune response? What is the status of the immune system in patients who do not produce antispike antibodies after COVID-19 vaccination?
Moreover, will there be novel nonvaccine strategies – such as antibody cocktails or convalescent plasma – to ensure protection against COVID-19 and other future viral threats? And what really defines immunocompromise today and moving forward?
“We don’t know what we don’t know,” said Jeremy L. Warner, MD, associate professor of medicine (hematology/oncology) and biomedical informatics at Vanderbilt University, Nashville, Tenn., and cofounder of the international COVID-19 and Cancer Consortium. “The immune system is incredibly complex and there are numerous defenses, in addition to the humoral response that we routinely measure.”
Another of the pressing pandemic-time questions for infectious disease specialists working in cancer centers concerns a different infectious threat: measles. “There is a lot of concern in this space about the reported drop in childhood vaccinations and the possibility of measles outbreaks as a follow-up to COVID-19,” said Steven A. Pergam, MD, MPH, associate professor in the vaccine and infectious disease division and the clinical research division of the Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance.
Whether recipients of hematopoietic cell transplantation (HCT) and cellular therapy should be revaccinated earlier than 2 years post treatment is a question worthy of preemptive discussion, he said.
What about timing?
“A silver lining of the pandemic is that it’s improving our understanding of response to vaccinations and outcomes with respiratory viruses in patients with hematologic malignancies,” said Samuel Rubinstein, MD, of the division of hematology at the University of North Carolina at Chapel Hill. “We’re going to learn a lot more about how to ensure that our patients are optimally protected from respiratory viruses.”
Dr. Rubinstein focuses on plasma cell disorders, mostly multiple myeloma, and routinely explains to patients consenting to use daratumumab, an anti-CD38 monoclonal antibody, or a BCMA-directed therapy, that these therapies “in particular probably do impair vaccine immune response.”
He has handled the timing of the COVID-19 vaccines – currently boosters, in most cases – as he has with influenza and other immunizations such as the pneumococcal vaccine, administering the vaccines agnostic to therapy unless the patient is about to start daratumumab or a BCMA-directed therapy. In this case, he considers vaccinating and waiting 2 weeks (for an immune response to occur) before starting therapy.
However, “if I have any concern that a delay will result in suboptimal cancer control, then I don’t wait,” Dr. Rubinstein said. Poor control of a primary malignancy has been consistently associated with worse COVID-19–specific outcomes in cancer–COVID-19 studies, he said, including an analysis of almost 5,000 patients recorded to the COVID-19 and Cancer Consortium .1
(The analysis also documented that patients with a hematologic malignancy had an odds ratio of higher COVID-19 severity of 1.7, compared with patients with a solid tumor, and an odds ratio of 30-day mortality of 1.44.)
Ideally, said Dr. Warner, patients will get vaccinated with the COVID-19 vaccines or others, “before starting on any cytotoxic chemotherapy and when they do not have low blood counts or perhaps autoimmune complications of immunotherapy.” However, “perfect being the enemy of good, it’s better to get vaccinated than to wait for the exact ideal time.”
Peter Paul Yu, MD, physician-in-chief at Hartford (Conn.) Healthcare Cancer Institute, said that for most patients, there’s no evidence to support an optimal timing of vaccine administration during the chemotherapy cycle. “We looked into that [to guide administration of the COVID-19 vaccines], thinking there might be some data about influenza vaccination,” he said. “But there isn’t much. … And if we make things more complicated than the evidence suggests, we may have fewer people getting vaccinations.”
The National Comprehensive Cancer Network offered several timing recommendations in its August 2021 COVID-19 vaccination guidance – mainly that patients receiving intensive cytotoxic chemotherapy (such as those on cytarabine/anthracycline-based induction regimens for acute myeloid leukemia) delay COVID-19 vaccination until absolute neutrophil count recovery, and that patients on long-term maintenance therapy (for instance, targeted agents for chronic lymphocytic leukemia or myeloproliferative neoplasms) be vaccinated as soon as possible.
Vaccination should be delayed for at least 3 months, the NCCN noted, following HCT or engineered cell therapy (for example, chimeric antigen receptor [CAR] T cells) “in order to maximize vaccine efficacy.”
More known unknowns
The tempered efficacy of the COVID-19 vaccines in patients with hematologic malignancies “has been shown in multiple studies of multiple myeloma, chronic lymphocytic leukemia (CLL), and other malignancies, and we know it’s true in transplant,” said Dr. Pergam.
In a study of 67 patients with hematologic malignancies at the University of Pittsburgh Medical Center Hillman Cancer Center, for instance, 46.3% did not generate IgG antibodies against the SARS-CoV-2 spike protein receptor–binding domain after completing their two-dose mRNA vaccine series. Patients with B-cell CLL were especially unlikely to develop antibodies.2A much larger study of more than 1,400 patients from investigators at the Mayo Clinics in Rochester, Minn., and Jacksonville, Fla., found that approximately 25% of all patients with hematologic malignancies did not produce antispike IgG antibodies, and that those with the most common B-cell malignancies had the lowest rate of seropositivity (44%-79%).3There’s a clear but challenging delineation between antibody testing in the research space and in clinical practice, however. Various national and cancer societies recommended earlier this year against routine postvaccine serological monitoring outside of clinical trials, and the sources interviewed for this story all emphasized that antibody titer measurements should not guide decisions about boosters or about the precautions advised for patients.
Titers checked at a single point in time do not capture the kinetics, multidimensional nature, or durability of an immune response, Dr. Warner said. “There are papers out there that say zero patients with CCL seroconverted … but they do still have some immunity, and maybe even a lot of immunity.”
Antibody testing can create a false sense of security, or a false sense of dread, he said. Yet in practice, the use of serological monitoring “has been all over the place [with] no consistency … and decisions probably being made at the individual clinic level or health system level,” he said.
To a lesser degree, so have definitions of what composes significant immunocompromise in the context of COVID-19 vaccine eligibility. “The question comes up, what does immunocompromised really mean?” said Dr. Yu, whose institution is a member of the Memorial Sloan Kettering (MSK) Cancer Alliance.
As of September, the MSK Cancer Center had taken a more granular approach to describing moderate to severe immunocompromise than did the Centers for Disease Control and Prevention. The CDC said this level of immunocompromise includes people receiving active cancer treatment for tumors or cancers of the blood, and those who’ve received a stem cell transplant within the past 2 years. MSK extended the recommendation, as it concerns hematologic malignancies, to patients who are within 12 months after treatment with B-cell depleting drugs, patients who have been treated for blood cancers within the last 6 months, and patients who received CAR T therapy within the past 2 years.
Dr. Yu, who was not involved in creating the MSK recommendations for third COVID-19 vaccines, said that he has been thinking more broadly during the pandemic about the notion of immunocompetence. “It’s my opinion that patients with hematologic malignancies, even if they’re not on treatment, are not fully immune competent,” he said. This includes patients with CLL stage 0 and patients with plasma cell dyscrasias who don’t yet meet the criteria for multiple myeloma but have a monoclonal gammopathy, and those with lower-risk myelodysplastic syndromes, he said.
“We’re seeing [variable] recommendations based on expert opinion, and I think that’s justifiable in such a dynamic situation,” Dr. Yu said. “I would [even] argue it’s desirable so we can learn from different approaches” and collect more rigorous observational data.
Immunocompetence needs to be “viewed in the context of the threat,” he added. “COVID changes the equation. … What’s immunocompromised in my mind has changed [from prepandemic times].”
Preparing for measles
Measles lit up on Dr. Pergam’s radar screen in 2019, when an outbreak occurred in nearby Clark County, Wash. This and other outbreaks in New York, California, and other states highlighted declines in measles herd immunity in the United States and prompted him to investigate the seroprevalence of measles antibodies in the Fred Hutchinson Cancer Research Center’s outpatient population.
Of 959 consecutive patients seen at the center, they found, 25% lacked protective antibodies for measles. For patients with hematologic malignancies and those with a history of HCT, seroprevalence was worse: 37% and 54%, respectively, were without the IgG antibodies.4 Measles “is the most contagious human virus we have at the moment,” he said, and “revaccinating people is hard when it comes to cancer because it is a live virus vaccine.”
Vaccine hesitancy, a rise in nonmedical exemptions, and other factors were threatening herd immunity before the pandemic began. Now, with declines in routine childhood medical visits and other vaccination opportunities and resources here and in other countries – and declining immunization rates documented by the CDC in May 2021 – the pandemic has made measles outbreaks more likely, he said. (Measles outbreaks in West Africa on the tail end of the Ebola outbreak in 2014-2015 caused more deaths in children than Ebola, he noted.)
The first priority is vaccination “cocooning,” a strategy that has long been important for patients with hematologic malignancies. But it also possible, Dr. Pergam said, that in the setting of any future community transmission, revaccination for HCT recipients could occur earlier than the standard 2-year post-transplantation recommendation.
In a 2019 position statement endorsed by the American Society for Transplantation and Cellular Therapy, Dr. Pergam and other infectious disease physicians and oncologists provide criteria for considering early revaccination on a case-by-case basis for patients on minimal immunosuppressive therapy who are at least 1-year post transplantation.5
“Our thinking was that there may be lower-risk patients to whom we could offer the vaccine” – patients for whom the risk of developing measles might outweigh the risk of potential vaccine-related complications, he said.
And if there were community cases, he added, there might be a place for testing antibody levels in post-transplant patients, however imperfect the window to immunity may be. “We’re thinking through potential scenarios,” he said. “Oncologists should think about measles again and have it on their back burner.”
References
1. Grivas P et al. Ann Oncol. 2021 Jun;32(6):787-800.
2. Agha ME et al. Open Forum Infect Dis. 2021 July;8(7):ofab353.
3. Greenberger LM et al. Cancer Cell. 2021 Aug 9;39(8):1031-3.
4. Marquis SR et al. JAMA Netw Open. 2021 July;4(7):e2118508.
5. Pergam SA et al. Biol Blood Marrow Transplant. 2019 Nov;25:e321-30.
The co-opting and weakening of the immune system by hematologic malignancies and many of their treatments – and the blunting of the immune system’s response to vaccines – may be more salient during the COVID-19 pandemic than ever before.
Hematologic malignancies have been associated in large cancer-and-COVID-19 registries with more severe COVID-19 outcomes than solid tumors, and COVID-19 mRNA vaccines have yielded suboptimal responses across multiple studies. Clinicians and researchers have no shortage of questions, like what is the optimal timing of vaccines relative to cancer-directed therapy? What is the durability and impact of the immune response? What is the status of the immune system in patients who do not produce antispike antibodies after COVID-19 vaccination?
Moreover, will there be novel nonvaccine strategies – such as antibody cocktails or convalescent plasma – to ensure protection against COVID-19 and other future viral threats? And what really defines immunocompromise today and moving forward?
“We don’t know what we don’t know,” said Jeremy L. Warner, MD, associate professor of medicine (hematology/oncology) and biomedical informatics at Vanderbilt University, Nashville, Tenn., and cofounder of the international COVID-19 and Cancer Consortium. “The immune system is incredibly complex and there are numerous defenses, in addition to the humoral response that we routinely measure.”
Another of the pressing pandemic-time questions for infectious disease specialists working in cancer centers concerns a different infectious threat: measles. “There is a lot of concern in this space about the reported drop in childhood vaccinations and the possibility of measles outbreaks as a follow-up to COVID-19,” said Steven A. Pergam, MD, MPH, associate professor in the vaccine and infectious disease division and the clinical research division of the Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance.
Whether recipients of hematopoietic cell transplantation (HCT) and cellular therapy should be revaccinated earlier than 2 years post treatment is a question worthy of preemptive discussion, he said.
What about timing?
“A silver lining of the pandemic is that it’s improving our understanding of response to vaccinations and outcomes with respiratory viruses in patients with hematologic malignancies,” said Samuel Rubinstein, MD, of the division of hematology at the University of North Carolina at Chapel Hill. “We’re going to learn a lot more about how to ensure that our patients are optimally protected from respiratory viruses.”
Dr. Rubinstein focuses on plasma cell disorders, mostly multiple myeloma, and routinely explains to patients consenting to use daratumumab, an anti-CD38 monoclonal antibody, or a BCMA-directed therapy, that these therapies “in particular probably do impair vaccine immune response.”
He has handled the timing of the COVID-19 vaccines – currently boosters, in most cases – as he has with influenza and other immunizations such as the pneumococcal vaccine, administering the vaccines agnostic to therapy unless the patient is about to start daratumumab or a BCMA-directed therapy. In this case, he considers vaccinating and waiting 2 weeks (for an immune response to occur) before starting therapy.
However, “if I have any concern that a delay will result in suboptimal cancer control, then I don’t wait,” Dr. Rubinstein said. Poor control of a primary malignancy has been consistently associated with worse COVID-19–specific outcomes in cancer–COVID-19 studies, he said, including an analysis of almost 5,000 patients recorded to the COVID-19 and Cancer Consortium .1
(The analysis also documented that patients with a hematologic malignancy had an odds ratio of higher COVID-19 severity of 1.7, compared with patients with a solid tumor, and an odds ratio of 30-day mortality of 1.44.)
Ideally, said Dr. Warner, patients will get vaccinated with the COVID-19 vaccines or others, “before starting on any cytotoxic chemotherapy and when they do not have low blood counts or perhaps autoimmune complications of immunotherapy.” However, “perfect being the enemy of good, it’s better to get vaccinated than to wait for the exact ideal time.”
Peter Paul Yu, MD, physician-in-chief at Hartford (Conn.) Healthcare Cancer Institute, said that for most patients, there’s no evidence to support an optimal timing of vaccine administration during the chemotherapy cycle. “We looked into that [to guide administration of the COVID-19 vaccines], thinking there might be some data about influenza vaccination,” he said. “But there isn’t much. … And if we make things more complicated than the evidence suggests, we may have fewer people getting vaccinations.”
The National Comprehensive Cancer Network offered several timing recommendations in its August 2021 COVID-19 vaccination guidance – mainly that patients receiving intensive cytotoxic chemotherapy (such as those on cytarabine/anthracycline-based induction regimens for acute myeloid leukemia) delay COVID-19 vaccination until absolute neutrophil count recovery, and that patients on long-term maintenance therapy (for instance, targeted agents for chronic lymphocytic leukemia or myeloproliferative neoplasms) be vaccinated as soon as possible.
Vaccination should be delayed for at least 3 months, the NCCN noted, following HCT or engineered cell therapy (for example, chimeric antigen receptor [CAR] T cells) “in order to maximize vaccine efficacy.”
More known unknowns
The tempered efficacy of the COVID-19 vaccines in patients with hematologic malignancies “has been shown in multiple studies of multiple myeloma, chronic lymphocytic leukemia (CLL), and other malignancies, and we know it’s true in transplant,” said Dr. Pergam.
In a study of 67 patients with hematologic malignancies at the University of Pittsburgh Medical Center Hillman Cancer Center, for instance, 46.3% did not generate IgG antibodies against the SARS-CoV-2 spike protein receptor–binding domain after completing their two-dose mRNA vaccine series. Patients with B-cell CLL were especially unlikely to develop antibodies.2A much larger study of more than 1,400 patients from investigators at the Mayo Clinics in Rochester, Minn., and Jacksonville, Fla., found that approximately 25% of all patients with hematologic malignancies did not produce antispike IgG antibodies, and that those with the most common B-cell malignancies had the lowest rate of seropositivity (44%-79%).3There’s a clear but challenging delineation between antibody testing in the research space and in clinical practice, however. Various national and cancer societies recommended earlier this year against routine postvaccine serological monitoring outside of clinical trials, and the sources interviewed for this story all emphasized that antibody titer measurements should not guide decisions about boosters or about the precautions advised for patients.
Titers checked at a single point in time do not capture the kinetics, multidimensional nature, or durability of an immune response, Dr. Warner said. “There are papers out there that say zero patients with CCL seroconverted … but they do still have some immunity, and maybe even a lot of immunity.”
Antibody testing can create a false sense of security, or a false sense of dread, he said. Yet in practice, the use of serological monitoring “has been all over the place [with] no consistency … and decisions probably being made at the individual clinic level or health system level,” he said.
To a lesser degree, so have definitions of what composes significant immunocompromise in the context of COVID-19 vaccine eligibility. “The question comes up, what does immunocompromised really mean?” said Dr. Yu, whose institution is a member of the Memorial Sloan Kettering (MSK) Cancer Alliance.
As of September, the MSK Cancer Center had taken a more granular approach to describing moderate to severe immunocompromise than did the Centers for Disease Control and Prevention. The CDC said this level of immunocompromise includes people receiving active cancer treatment for tumors or cancers of the blood, and those who’ve received a stem cell transplant within the past 2 years. MSK extended the recommendation, as it concerns hematologic malignancies, to patients who are within 12 months after treatment with B-cell depleting drugs, patients who have been treated for blood cancers within the last 6 months, and patients who received CAR T therapy within the past 2 years.
Dr. Yu, who was not involved in creating the MSK recommendations for third COVID-19 vaccines, said that he has been thinking more broadly during the pandemic about the notion of immunocompetence. “It’s my opinion that patients with hematologic malignancies, even if they’re not on treatment, are not fully immune competent,” he said. This includes patients with CLL stage 0 and patients with plasma cell dyscrasias who don’t yet meet the criteria for multiple myeloma but have a monoclonal gammopathy, and those with lower-risk myelodysplastic syndromes, he said.
“We’re seeing [variable] recommendations based on expert opinion, and I think that’s justifiable in such a dynamic situation,” Dr. Yu said. “I would [even] argue it’s desirable so we can learn from different approaches” and collect more rigorous observational data.
Immunocompetence needs to be “viewed in the context of the threat,” he added. “COVID changes the equation. … What’s immunocompromised in my mind has changed [from prepandemic times].”
Preparing for measles
Measles lit up on Dr. Pergam’s radar screen in 2019, when an outbreak occurred in nearby Clark County, Wash. This and other outbreaks in New York, California, and other states highlighted declines in measles herd immunity in the United States and prompted him to investigate the seroprevalence of measles antibodies in the Fred Hutchinson Cancer Research Center’s outpatient population.
Of 959 consecutive patients seen at the center, they found, 25% lacked protective antibodies for measles. For patients with hematologic malignancies and those with a history of HCT, seroprevalence was worse: 37% and 54%, respectively, were without the IgG antibodies.4 Measles “is the most contagious human virus we have at the moment,” he said, and “revaccinating people is hard when it comes to cancer because it is a live virus vaccine.”
Vaccine hesitancy, a rise in nonmedical exemptions, and other factors were threatening herd immunity before the pandemic began. Now, with declines in routine childhood medical visits and other vaccination opportunities and resources here and in other countries – and declining immunization rates documented by the CDC in May 2021 – the pandemic has made measles outbreaks more likely, he said. (Measles outbreaks in West Africa on the tail end of the Ebola outbreak in 2014-2015 caused more deaths in children than Ebola, he noted.)
The first priority is vaccination “cocooning,” a strategy that has long been important for patients with hematologic malignancies. But it also possible, Dr. Pergam said, that in the setting of any future community transmission, revaccination for HCT recipients could occur earlier than the standard 2-year post-transplantation recommendation.
In a 2019 position statement endorsed by the American Society for Transplantation and Cellular Therapy, Dr. Pergam and other infectious disease physicians and oncologists provide criteria for considering early revaccination on a case-by-case basis for patients on minimal immunosuppressive therapy who are at least 1-year post transplantation.5
“Our thinking was that there may be lower-risk patients to whom we could offer the vaccine” – patients for whom the risk of developing measles might outweigh the risk of potential vaccine-related complications, he said.
And if there were community cases, he added, there might be a place for testing antibody levels in post-transplant patients, however imperfect the window to immunity may be. “We’re thinking through potential scenarios,” he said. “Oncologists should think about measles again and have it on their back burner.”
References
1. Grivas P et al. Ann Oncol. 2021 Jun;32(6):787-800.
2. Agha ME et al. Open Forum Infect Dis. 2021 July;8(7):ofab353.
3. Greenberger LM et al. Cancer Cell. 2021 Aug 9;39(8):1031-3.
4. Marquis SR et al. JAMA Netw Open. 2021 July;4(7):e2118508.
5. Pergam SA et al. Biol Blood Marrow Transplant. 2019 Nov;25:e321-30.
Hair follicle miniaturization common in persistent chemo-induced alopecia, case series suggests
and treatment with minoxidil (sometimes with antiandrogen therapy) was associated with improved hair density, according to a recently published retrospective case series.
“An improvement in hair density was observed in most of the patients treated with topical minoxidil or LDOM [low-dose oral minoxidil], with a more favorable outcome seen with LDOM with or without antiandrogens,” reported Bevin Bhoyrul, MBBS, of Sinclair Dermatology in Melbourne and coauthors from the United Kingdom and Germany.
The findings, published in JAMA Dermatology, suggest that pCIA “may be at least partly reversible,” they wrote.
The investigators analyzed the clinicopathologic characteristics of pCIA in 100 patients presenting to the hair clinics, as well as the results of trichoscopy performed in 90 of the patients and biopsies in 18. The researchers also assessed the effectiveness of treatment in 49 of these patients who met their criteria of completing at least 6 months of therapy with minoxidil.
Almost all patients in their series – 92% – were treated with taxanes and had more severe alopecia than those who weren’t exposed to taxanes (a median Sinclair scale grade of 4 vs. 2). Defined as absent or incomplete hair regrowth 6 months or more after completion of chemotherapy, pCIA has been increasingly reported in the literature, the authors note.
Of the 100 patients, all but one of whom were women, 39 had globally-reduced hair density that also involved the occipital area (diffuse alopecia), and 55 patients had thinning of the centroparietal scalp hair in a female pattern hair loss (FPHL) distribution. Patients presented between November 2011 and February 2020 and had a mean age of 54. The Sinclair scale, which grades from 1 to 5, was used to assess the severity of hair loss in these patients.
Five female patients had bitemporal recession or balding of the crown in a male pattern hair loss (MPHL) distribution, and the one male patient had extensive baldness resembling Hamilton-Norwood type VII.
The vast majority of patients who had trichoscopy performed – 88% – had trichoscopic features that were “indistinguishable from those of androgenetic alopecia,” most commonly hair shaft diameter variability, increased vellus hairs, and predominant single-hair follicular units, the authors reported.
Of the 18 patients who had biopsies, 14 had androgenetic alopecia-like features with decreased terminal hairs, increased vellus hairs, and fibrous streamers. The reduced terminal-to-vellus ratio characterizes hair follicle miniaturization, a hallmark of androgenetic alopecia, they said. (Two patients had cicatricial alopecia, and two had features of both.)
“The predominant phenotypes of pCIA show prominent vellus hairs both clinically and histologically, suggesting that terminal hair follicles undergo miniaturization,” Dr. Bhoyrul and coauthors wrote. Among the 49 patients who completed 6 months or more of treatment, the median Sinclair grade improved from 4 to 3 in 21 patients who received topical minoxidil for a median duration of 17 months; from 4 to 2.5 in 18 patients who received LDOM for a median duration of 29 months; and from 5 to 3 in 10 patients who received LDOM combined with an antiandrogen, such as spironolactone, for a median of 33 months.
Almost three-quarters of the patients in the series received adjuvant hormone therapy, which is independently associated with hair loss, the authors noted. However, there was no statistically significant difference in the pattern or severity of alopecia between patients who were treated with endocrine therapy and those who weren’t.
Asked to comment on the study and on the care of patients with pCIA, Maria K. Hordinsky, MD, professor and chair of dermatology at the University of Minnesota, Minneapolis, and an expert in hair diseases, said the case series points to the value of biopsies in patients with pCIA.
“Some patients really do have a loss of hair follicles,” she said. “But if you do a biopsy and see this miniaturization of the hair follicles, then we have tools to stimulate the hair follicles to become more normal. ... These patients can be successfully treated.”
For patients who do not want to do a biopsy, a therapeutic trial is acceptable. “But knowing helps set expectations for people,” she said. “If the follicles are really small, it will take months [of therapy].”
In addition to topical minoxidil, which she said “is always a good tool,” and LDOM, which is “becoming very popular,” Dr. Hordinsky has used low-level laser light successfully. She cautioned against the use of spironolactone and other hair-growth promoting therapies with potentially significant hormonal impacts unless there is discussion between the dermatologist, oncologist, and patient.
The authors of the case series called in their conclusion for wider use of hair-protective strategies such as scalp hypothermia. But Dr. Hordinsky said that, in the United States, there are divergent opinions among oncologists and among cancer centers on the use of scalp cooling and whether or not it might lessen response to chemotherapy.
More research is needed, she noted, on chemotherapy-induced hair loss in patients of different races and ethnicities. Of the 100 patients in the case series, 91 were European; others were Afro Caribbean, Middle Eastern, and South Asian.
Dr. Bhoyrul is supported by the Geoffrey Dowling Fellowship from the British Association of Dermatologists. One coauthor disclosed serving as a principal investigator and/or scientific board member for various pharmaceutical companies, outside of the submitted study. There were no other disclosures reported. Dr. Hordinsky, the immediate past president of the American Hair Research Society and a section editor for hair diseases in UpToDate, had no relevant disclosures.
and treatment with minoxidil (sometimes with antiandrogen therapy) was associated with improved hair density, according to a recently published retrospective case series.
“An improvement in hair density was observed in most of the patients treated with topical minoxidil or LDOM [low-dose oral minoxidil], with a more favorable outcome seen with LDOM with or without antiandrogens,” reported Bevin Bhoyrul, MBBS, of Sinclair Dermatology in Melbourne and coauthors from the United Kingdom and Germany.
The findings, published in JAMA Dermatology, suggest that pCIA “may be at least partly reversible,” they wrote.
The investigators analyzed the clinicopathologic characteristics of pCIA in 100 patients presenting to the hair clinics, as well as the results of trichoscopy performed in 90 of the patients and biopsies in 18. The researchers also assessed the effectiveness of treatment in 49 of these patients who met their criteria of completing at least 6 months of therapy with minoxidil.
Almost all patients in their series – 92% – were treated with taxanes and had more severe alopecia than those who weren’t exposed to taxanes (a median Sinclair scale grade of 4 vs. 2). Defined as absent or incomplete hair regrowth 6 months or more after completion of chemotherapy, pCIA has been increasingly reported in the literature, the authors note.
Of the 100 patients, all but one of whom were women, 39 had globally-reduced hair density that also involved the occipital area (diffuse alopecia), and 55 patients had thinning of the centroparietal scalp hair in a female pattern hair loss (FPHL) distribution. Patients presented between November 2011 and February 2020 and had a mean age of 54. The Sinclair scale, which grades from 1 to 5, was used to assess the severity of hair loss in these patients.
Five female patients had bitemporal recession or balding of the crown in a male pattern hair loss (MPHL) distribution, and the one male patient had extensive baldness resembling Hamilton-Norwood type VII.
The vast majority of patients who had trichoscopy performed – 88% – had trichoscopic features that were “indistinguishable from those of androgenetic alopecia,” most commonly hair shaft diameter variability, increased vellus hairs, and predominant single-hair follicular units, the authors reported.
Of the 18 patients who had biopsies, 14 had androgenetic alopecia-like features with decreased terminal hairs, increased vellus hairs, and fibrous streamers. The reduced terminal-to-vellus ratio characterizes hair follicle miniaturization, a hallmark of androgenetic alopecia, they said. (Two patients had cicatricial alopecia, and two had features of both.)
“The predominant phenotypes of pCIA show prominent vellus hairs both clinically and histologically, suggesting that terminal hair follicles undergo miniaturization,” Dr. Bhoyrul and coauthors wrote. Among the 49 patients who completed 6 months or more of treatment, the median Sinclair grade improved from 4 to 3 in 21 patients who received topical minoxidil for a median duration of 17 months; from 4 to 2.5 in 18 patients who received LDOM for a median duration of 29 months; and from 5 to 3 in 10 patients who received LDOM combined with an antiandrogen, such as spironolactone, for a median of 33 months.
Almost three-quarters of the patients in the series received adjuvant hormone therapy, which is independently associated with hair loss, the authors noted. However, there was no statistically significant difference in the pattern or severity of alopecia between patients who were treated with endocrine therapy and those who weren’t.
Asked to comment on the study and on the care of patients with pCIA, Maria K. Hordinsky, MD, professor and chair of dermatology at the University of Minnesota, Minneapolis, and an expert in hair diseases, said the case series points to the value of biopsies in patients with pCIA.
“Some patients really do have a loss of hair follicles,” she said. “But if you do a biopsy and see this miniaturization of the hair follicles, then we have tools to stimulate the hair follicles to become more normal. ... These patients can be successfully treated.”
For patients who do not want to do a biopsy, a therapeutic trial is acceptable. “But knowing helps set expectations for people,” she said. “If the follicles are really small, it will take months [of therapy].”
In addition to topical minoxidil, which she said “is always a good tool,” and LDOM, which is “becoming very popular,” Dr. Hordinsky has used low-level laser light successfully. She cautioned against the use of spironolactone and other hair-growth promoting therapies with potentially significant hormonal impacts unless there is discussion between the dermatologist, oncologist, and patient.
The authors of the case series called in their conclusion for wider use of hair-protective strategies such as scalp hypothermia. But Dr. Hordinsky said that, in the United States, there are divergent opinions among oncologists and among cancer centers on the use of scalp cooling and whether or not it might lessen response to chemotherapy.
More research is needed, she noted, on chemotherapy-induced hair loss in patients of different races and ethnicities. Of the 100 patients in the case series, 91 were European; others were Afro Caribbean, Middle Eastern, and South Asian.
Dr. Bhoyrul is supported by the Geoffrey Dowling Fellowship from the British Association of Dermatologists. One coauthor disclosed serving as a principal investigator and/or scientific board member for various pharmaceutical companies, outside of the submitted study. There were no other disclosures reported. Dr. Hordinsky, the immediate past president of the American Hair Research Society and a section editor for hair diseases in UpToDate, had no relevant disclosures.
and treatment with minoxidil (sometimes with antiandrogen therapy) was associated with improved hair density, according to a recently published retrospective case series.
“An improvement in hair density was observed in most of the patients treated with topical minoxidil or LDOM [low-dose oral minoxidil], with a more favorable outcome seen with LDOM with or without antiandrogens,” reported Bevin Bhoyrul, MBBS, of Sinclair Dermatology in Melbourne and coauthors from the United Kingdom and Germany.
The findings, published in JAMA Dermatology, suggest that pCIA “may be at least partly reversible,” they wrote.
The investigators analyzed the clinicopathologic characteristics of pCIA in 100 patients presenting to the hair clinics, as well as the results of trichoscopy performed in 90 of the patients and biopsies in 18. The researchers also assessed the effectiveness of treatment in 49 of these patients who met their criteria of completing at least 6 months of therapy with minoxidil.
Almost all patients in their series – 92% – were treated with taxanes and had more severe alopecia than those who weren’t exposed to taxanes (a median Sinclair scale grade of 4 vs. 2). Defined as absent or incomplete hair regrowth 6 months or more after completion of chemotherapy, pCIA has been increasingly reported in the literature, the authors note.
Of the 100 patients, all but one of whom were women, 39 had globally-reduced hair density that also involved the occipital area (diffuse alopecia), and 55 patients had thinning of the centroparietal scalp hair in a female pattern hair loss (FPHL) distribution. Patients presented between November 2011 and February 2020 and had a mean age of 54. The Sinclair scale, which grades from 1 to 5, was used to assess the severity of hair loss in these patients.
Five female patients had bitemporal recession or balding of the crown in a male pattern hair loss (MPHL) distribution, and the one male patient had extensive baldness resembling Hamilton-Norwood type VII.
The vast majority of patients who had trichoscopy performed – 88% – had trichoscopic features that were “indistinguishable from those of androgenetic alopecia,” most commonly hair shaft diameter variability, increased vellus hairs, and predominant single-hair follicular units, the authors reported.
Of the 18 patients who had biopsies, 14 had androgenetic alopecia-like features with decreased terminal hairs, increased vellus hairs, and fibrous streamers. The reduced terminal-to-vellus ratio characterizes hair follicle miniaturization, a hallmark of androgenetic alopecia, they said. (Two patients had cicatricial alopecia, and two had features of both.)
“The predominant phenotypes of pCIA show prominent vellus hairs both clinically and histologically, suggesting that terminal hair follicles undergo miniaturization,” Dr. Bhoyrul and coauthors wrote. Among the 49 patients who completed 6 months or more of treatment, the median Sinclair grade improved from 4 to 3 in 21 patients who received topical minoxidil for a median duration of 17 months; from 4 to 2.5 in 18 patients who received LDOM for a median duration of 29 months; and from 5 to 3 in 10 patients who received LDOM combined with an antiandrogen, such as spironolactone, for a median of 33 months.
Almost three-quarters of the patients in the series received adjuvant hormone therapy, which is independently associated with hair loss, the authors noted. However, there was no statistically significant difference in the pattern or severity of alopecia between patients who were treated with endocrine therapy and those who weren’t.
Asked to comment on the study and on the care of patients with pCIA, Maria K. Hordinsky, MD, professor and chair of dermatology at the University of Minnesota, Minneapolis, and an expert in hair diseases, said the case series points to the value of biopsies in patients with pCIA.
“Some patients really do have a loss of hair follicles,” she said. “But if you do a biopsy and see this miniaturization of the hair follicles, then we have tools to stimulate the hair follicles to become more normal. ... These patients can be successfully treated.”
For patients who do not want to do a biopsy, a therapeutic trial is acceptable. “But knowing helps set expectations for people,” she said. “If the follicles are really small, it will take months [of therapy].”
In addition to topical minoxidil, which she said “is always a good tool,” and LDOM, which is “becoming very popular,” Dr. Hordinsky has used low-level laser light successfully. She cautioned against the use of spironolactone and other hair-growth promoting therapies with potentially significant hormonal impacts unless there is discussion between the dermatologist, oncologist, and patient.
The authors of the case series called in their conclusion for wider use of hair-protective strategies such as scalp hypothermia. But Dr. Hordinsky said that, in the United States, there are divergent opinions among oncologists and among cancer centers on the use of scalp cooling and whether or not it might lessen response to chemotherapy.
More research is needed, she noted, on chemotherapy-induced hair loss in patients of different races and ethnicities. Of the 100 patients in the case series, 91 were European; others were Afro Caribbean, Middle Eastern, and South Asian.
Dr. Bhoyrul is supported by the Geoffrey Dowling Fellowship from the British Association of Dermatologists. One coauthor disclosed serving as a principal investigator and/or scientific board member for various pharmaceutical companies, outside of the submitted study. There were no other disclosures reported. Dr. Hordinsky, the immediate past president of the American Hair Research Society and a section editor for hair diseases in UpToDate, had no relevant disclosures.
FROM JAMA DERMATOLOGY
Dr. Judy C. Washington shows URM physicians how to lead
For URM physicians, she also imparts a shared experience of being a minority in the field and helps prepare them for the challenges of facing racism or feeling marginalized or not equitably supported in academic life – and for making change.
While family medicine’s demographics have become more diverse over time, and more so than other specialties, they are not yet representative of the U.S. population. Within academia, male physicians who are Black or African American, or Hispanic or Latino, comprised about 4% and 5% of family medicine faculty, respectively, at the end of 2019, according to data from the Association of American Medical Colleges. For women, these numbers were about 9% and 4%, respectively. (Only those with an MD degree exclusively were included in the report.)
“When you have the privilege to serve in leadership, you have the responsibility to reach back and identify and help others who would not otherwise have the opportunity to be recognized,” Dr. Washington said.
Her mentorship work stems in large part from her long-time involvement and leadership roles in the Society of Teachers of Family Medicine (STFM) – roles she considers a pillar of her professional life. She currently serves as president of the STFM Foundation and is associate chief medical officer of the Atlantic Medical Group, a large multisite physician-led organization. She is also coordinator of women’s health for the Overlook Family Medicine Residency Program, which is affiliated with Atlantic Medical Group.
In Dr. Washington’s role as associate chief medical officer of Atlantic Medical Group in Summit, N.J., she focuses on physician engagement, satisfaction, and diversity. She also assists in areas such as population health. For the Overlook Family Medicine Residency Program also in Summit, she precepts residents in the obstetrics clinic and in the family medicine outpatient clinic.
Diana N. Carvajal, MD, MPH, one of Dr. Washington’s mentees, called her an “inspirational leader” for young academic faculty and said she is a familiar speaker at STFM meetings on topics of workforce diversity, equity, and leadership. She is “passionate” about mentorship, Dr. Carvajal said, and has understood “that URMs and women of color were not always getting [the mentorship they need to be successful].”
Guiding future leaders
Ivonne McLean, MD, assistant professor of family and community medicine at Icahn School of Medicine at Mount Sinai, New York, and an attending at a community health center in the Bronx, called Dr. Washington for advice a couple of years ago when she was considering her next career move.
“She took a genuine interest in me. She never said, this is what you should do. But the questions she asked and the examples she gave from her own life were incredibly helpful to me [in deciding to pursue a research fellowship] ... it was a pivotal conversation,” said Dr. McLean, associate director of a reproductive health fellowship and a research fellow in a New York State–funded program.
“From a lived experience angle, she also told me, here are some of the challenges you’ll have as a woman of color, and here are some of the ways you can approach that,” she said.
Dr. Carvajal, also a URM family physician, credits Dr. Washington’s mentorship with the development of a day-long workshop – held before the annual Society of Teachers of Family Medicine (STFM) meeting – on the low and declining rates of Black males in medicine. “We’d planned it as a presentation, and [she heard of it and] helped us expand it,” she said, calling Dr. Washington “warm, welcoming, and encouraging.
“That work and collaboration with her and the others she brought [into the process] have resulted in publications and more presentations and strategy building for diversifying the workforce,” said Dr. Carvajal, assistant professor, director of reproductive health education in family medicine, and codirector of the research section, all in the department of family and community medicine at the University of Maryland, Baltimore.
STFM involvement
Dr. Washington, who says that all or almost all of her mentees are now leaders in their academic institutions and communities, has been instrumental in developing STFM’s mentoring programming and in facilitating the organization’s multifaceted URM Initiative.
She has been active in STFM since the start of her academic career, and in 2009, while serving as assistant program director for the residency program in which she’d trained, she joined two other African American women, Monique Y. Davis-Smith, MD, and Joedrecka Brown-Speights, MD, in cochairing the society’s Group on Minority and Multicultural Health.
It was in this space, that Dr. Washington said she “heard people’s stories of being in major academic institutions and not feeling supported, not being given roadmaps to success, not getting assistance with publishing, or just kind of feeling like an outsider ... of not being pulled in.” Hispanic and African American females, in particular, “were feeling marginalized,” she said.
In 2018, having co-led development of the STFM Quality Mentoring Program for URM faculty, Dr. Washington was asked to join the STFM Foundation and subsequently led the STFM Foundation’s fundraising campaign for a new URM Initiative. She exceeded her goal, increasing support for URM participation in meetings and activities, and then participated in an STFM steering committee to create broader and longer-lasting support for URM faculty, community teachers, and medical students and residents going into academic family medicine.
Increasing the percentage of URM family medicine faculty in leadership positions – and raising awareness of structural barriers to achievement – is one of the current pillars of the URM Initiative.
Navigating the ‘minority tax’
As part of her mentoring, Dr. Washington helps URM physicians navigate the minority tax – a term referring to the uncompensated citizenship tasks that are more often assigned to Black and other URM physicians than to White physicians, and that take time away from scholarship, further perpetuating inequities.
“Some of our young faculty members find themselves thrust into being the diversity and inclusion leaders in their institutions at a level at which they feel little power and little buy-in from [leadership],” she noted.
A commentary written by Dr. Washington and several colleagues on the minority tax as it impacts women – and the need to build a “tax shelter” to make academic medicine a more just environment for URM women – was published earlier this year in the Journal of Women’s Health.
She also answers e-mails and fields phone calls from young URM faculty who are mulling career moves and facing other familiar challenges.
Physicians who are URM, and African American physicians in particular, tend to “get pulled into the [often underserved] communities, into the patient care and community service areas,” Dr. Washington explained. “But unless you convert these projects into scholarship and publications, and unless you serve on a national committee outside of your institution, you’re not going to be promoted.”
Dr. Washington helps junior faculty envision themselves 5-plus years down the road, find what she calls scholarly “passion projects,” and prepare themselves for their next steps.
She helps her mentees navigate other parts of the continuum of unconscious bias and racism as well, from microaggressions from colleagues to overt discrimination from patients.
“I spend countless minutes fielding texts and phone calls from those who need support,” she wrote in a blog post. “They are a constant reminder that I must continue to speak up when I get the opportunity to do so.”
A journey through family medicine, and through bias and racism
Dr. Washington’s early days in medicine included graduating from Meharry Medical College in 1983 and the Mountainside Family Practice Residency Program in 1990. Following 6 years of working in a private practice in rural Maryland, she moved to academia, spending 6 years at East Tennessee State University and 4 years at the UMDNJ–New Jersey Medical School in Newark as an assistant professor of family medicine.
As had happened in rural Maryland, bias and racism have too often lurked during her career as a physician.
“I grew up in Alabama so I was pretty much ready to deal with racism in the South,” Dr. Washington said. “What I was not ready for was coming to the Northeast and seeing that you’re marginalized because you’re not invited into the room. Or if you do go into spaces when you’re the only one, you often don’t feel as welcomed as you thought you might be.”
Her ideas and contributions were too often dismissed, she wrote in a 2020 blog entry posted on her LinkedIn page. And during contract negotiations, “I was not aware of all the information that my White colleagues had. They had the advantage of inside information.”
Dr. Washington says that “it took a village” to make her who she is today: teachers in her segregated schools in Alabama, one of her college professors, her best friend in medical school – and STFM, “where the list [of her own mentors] is long.”
For URM physicians, she also imparts a shared experience of being a minority in the field and helps prepare them for the challenges of facing racism or feeling marginalized or not equitably supported in academic life – and for making change.
While family medicine’s demographics have become more diverse over time, and more so than other specialties, they are not yet representative of the U.S. population. Within academia, male physicians who are Black or African American, or Hispanic or Latino, comprised about 4% and 5% of family medicine faculty, respectively, at the end of 2019, according to data from the Association of American Medical Colleges. For women, these numbers were about 9% and 4%, respectively. (Only those with an MD degree exclusively were included in the report.)
“When you have the privilege to serve in leadership, you have the responsibility to reach back and identify and help others who would not otherwise have the opportunity to be recognized,” Dr. Washington said.
Her mentorship work stems in large part from her long-time involvement and leadership roles in the Society of Teachers of Family Medicine (STFM) – roles she considers a pillar of her professional life. She currently serves as president of the STFM Foundation and is associate chief medical officer of the Atlantic Medical Group, a large multisite physician-led organization. She is also coordinator of women’s health for the Overlook Family Medicine Residency Program, which is affiliated with Atlantic Medical Group.
In Dr. Washington’s role as associate chief medical officer of Atlantic Medical Group in Summit, N.J., she focuses on physician engagement, satisfaction, and diversity. She also assists in areas such as population health. For the Overlook Family Medicine Residency Program also in Summit, she precepts residents in the obstetrics clinic and in the family medicine outpatient clinic.
Diana N. Carvajal, MD, MPH, one of Dr. Washington’s mentees, called her an “inspirational leader” for young academic faculty and said she is a familiar speaker at STFM meetings on topics of workforce diversity, equity, and leadership. She is “passionate” about mentorship, Dr. Carvajal said, and has understood “that URMs and women of color were not always getting [the mentorship they need to be successful].”
Guiding future leaders
Ivonne McLean, MD, assistant professor of family and community medicine at Icahn School of Medicine at Mount Sinai, New York, and an attending at a community health center in the Bronx, called Dr. Washington for advice a couple of years ago when she was considering her next career move.
“She took a genuine interest in me. She never said, this is what you should do. But the questions she asked and the examples she gave from her own life were incredibly helpful to me [in deciding to pursue a research fellowship] ... it was a pivotal conversation,” said Dr. McLean, associate director of a reproductive health fellowship and a research fellow in a New York State–funded program.
“From a lived experience angle, she also told me, here are some of the challenges you’ll have as a woman of color, and here are some of the ways you can approach that,” she said.
Dr. Carvajal, also a URM family physician, credits Dr. Washington’s mentorship with the development of a day-long workshop – held before the annual Society of Teachers of Family Medicine (STFM) meeting – on the low and declining rates of Black males in medicine. “We’d planned it as a presentation, and [she heard of it and] helped us expand it,” she said, calling Dr. Washington “warm, welcoming, and encouraging.
“That work and collaboration with her and the others she brought [into the process] have resulted in publications and more presentations and strategy building for diversifying the workforce,” said Dr. Carvajal, assistant professor, director of reproductive health education in family medicine, and codirector of the research section, all in the department of family and community medicine at the University of Maryland, Baltimore.
STFM involvement
Dr. Washington, who says that all or almost all of her mentees are now leaders in their academic institutions and communities, has been instrumental in developing STFM’s mentoring programming and in facilitating the organization’s multifaceted URM Initiative.
She has been active in STFM since the start of her academic career, and in 2009, while serving as assistant program director for the residency program in which she’d trained, she joined two other African American women, Monique Y. Davis-Smith, MD, and Joedrecka Brown-Speights, MD, in cochairing the society’s Group on Minority and Multicultural Health.
It was in this space, that Dr. Washington said she “heard people’s stories of being in major academic institutions and not feeling supported, not being given roadmaps to success, not getting assistance with publishing, or just kind of feeling like an outsider ... of not being pulled in.” Hispanic and African American females, in particular, “were feeling marginalized,” she said.
In 2018, having co-led development of the STFM Quality Mentoring Program for URM faculty, Dr. Washington was asked to join the STFM Foundation and subsequently led the STFM Foundation’s fundraising campaign for a new URM Initiative. She exceeded her goal, increasing support for URM participation in meetings and activities, and then participated in an STFM steering committee to create broader and longer-lasting support for URM faculty, community teachers, and medical students and residents going into academic family medicine.
Increasing the percentage of URM family medicine faculty in leadership positions – and raising awareness of structural barriers to achievement – is one of the current pillars of the URM Initiative.
Navigating the ‘minority tax’
As part of her mentoring, Dr. Washington helps URM physicians navigate the minority tax – a term referring to the uncompensated citizenship tasks that are more often assigned to Black and other URM physicians than to White physicians, and that take time away from scholarship, further perpetuating inequities.
“Some of our young faculty members find themselves thrust into being the diversity and inclusion leaders in their institutions at a level at which they feel little power and little buy-in from [leadership],” she noted.
A commentary written by Dr. Washington and several colleagues on the minority tax as it impacts women – and the need to build a “tax shelter” to make academic medicine a more just environment for URM women – was published earlier this year in the Journal of Women’s Health.
She also answers e-mails and fields phone calls from young URM faculty who are mulling career moves and facing other familiar challenges.
Physicians who are URM, and African American physicians in particular, tend to “get pulled into the [often underserved] communities, into the patient care and community service areas,” Dr. Washington explained. “But unless you convert these projects into scholarship and publications, and unless you serve on a national committee outside of your institution, you’re not going to be promoted.”
Dr. Washington helps junior faculty envision themselves 5-plus years down the road, find what she calls scholarly “passion projects,” and prepare themselves for their next steps.
She helps her mentees navigate other parts of the continuum of unconscious bias and racism as well, from microaggressions from colleagues to overt discrimination from patients.
“I spend countless minutes fielding texts and phone calls from those who need support,” she wrote in a blog post. “They are a constant reminder that I must continue to speak up when I get the opportunity to do so.”
A journey through family medicine, and through bias and racism
Dr. Washington’s early days in medicine included graduating from Meharry Medical College in 1983 and the Mountainside Family Practice Residency Program in 1990. Following 6 years of working in a private practice in rural Maryland, she moved to academia, spending 6 years at East Tennessee State University and 4 years at the UMDNJ–New Jersey Medical School in Newark as an assistant professor of family medicine.
As had happened in rural Maryland, bias and racism have too often lurked during her career as a physician.
“I grew up in Alabama so I was pretty much ready to deal with racism in the South,” Dr. Washington said. “What I was not ready for was coming to the Northeast and seeing that you’re marginalized because you’re not invited into the room. Or if you do go into spaces when you’re the only one, you often don’t feel as welcomed as you thought you might be.”
Her ideas and contributions were too often dismissed, she wrote in a 2020 blog entry posted on her LinkedIn page. And during contract negotiations, “I was not aware of all the information that my White colleagues had. They had the advantage of inside information.”
Dr. Washington says that “it took a village” to make her who she is today: teachers in her segregated schools in Alabama, one of her college professors, her best friend in medical school – and STFM, “where the list [of her own mentors] is long.”
For URM physicians, she also imparts a shared experience of being a minority in the field and helps prepare them for the challenges of facing racism or feeling marginalized or not equitably supported in academic life – and for making change.
While family medicine’s demographics have become more diverse over time, and more so than other specialties, they are not yet representative of the U.S. population. Within academia, male physicians who are Black or African American, or Hispanic or Latino, comprised about 4% and 5% of family medicine faculty, respectively, at the end of 2019, according to data from the Association of American Medical Colleges. For women, these numbers were about 9% and 4%, respectively. (Only those with an MD degree exclusively were included in the report.)
“When you have the privilege to serve in leadership, you have the responsibility to reach back and identify and help others who would not otherwise have the opportunity to be recognized,” Dr. Washington said.
Her mentorship work stems in large part from her long-time involvement and leadership roles in the Society of Teachers of Family Medicine (STFM) – roles she considers a pillar of her professional life. She currently serves as president of the STFM Foundation and is associate chief medical officer of the Atlantic Medical Group, a large multisite physician-led organization. She is also coordinator of women’s health for the Overlook Family Medicine Residency Program, which is affiliated with Atlantic Medical Group.
In Dr. Washington’s role as associate chief medical officer of Atlantic Medical Group in Summit, N.J., she focuses on physician engagement, satisfaction, and diversity. She also assists in areas such as population health. For the Overlook Family Medicine Residency Program also in Summit, she precepts residents in the obstetrics clinic and in the family medicine outpatient clinic.
Diana N. Carvajal, MD, MPH, one of Dr. Washington’s mentees, called her an “inspirational leader” for young academic faculty and said she is a familiar speaker at STFM meetings on topics of workforce diversity, equity, and leadership. She is “passionate” about mentorship, Dr. Carvajal said, and has understood “that URMs and women of color were not always getting [the mentorship they need to be successful].”
Guiding future leaders
Ivonne McLean, MD, assistant professor of family and community medicine at Icahn School of Medicine at Mount Sinai, New York, and an attending at a community health center in the Bronx, called Dr. Washington for advice a couple of years ago when she was considering her next career move.
“She took a genuine interest in me. She never said, this is what you should do. But the questions she asked and the examples she gave from her own life were incredibly helpful to me [in deciding to pursue a research fellowship] ... it was a pivotal conversation,” said Dr. McLean, associate director of a reproductive health fellowship and a research fellow in a New York State–funded program.
“From a lived experience angle, she also told me, here are some of the challenges you’ll have as a woman of color, and here are some of the ways you can approach that,” she said.
Dr. Carvajal, also a URM family physician, credits Dr. Washington’s mentorship with the development of a day-long workshop – held before the annual Society of Teachers of Family Medicine (STFM) meeting – on the low and declining rates of Black males in medicine. “We’d planned it as a presentation, and [she heard of it and] helped us expand it,” she said, calling Dr. Washington “warm, welcoming, and encouraging.
“That work and collaboration with her and the others she brought [into the process] have resulted in publications and more presentations and strategy building for diversifying the workforce,” said Dr. Carvajal, assistant professor, director of reproductive health education in family medicine, and codirector of the research section, all in the department of family and community medicine at the University of Maryland, Baltimore.
STFM involvement
Dr. Washington, who says that all or almost all of her mentees are now leaders in their academic institutions and communities, has been instrumental in developing STFM’s mentoring programming and in facilitating the organization’s multifaceted URM Initiative.
She has been active in STFM since the start of her academic career, and in 2009, while serving as assistant program director for the residency program in which she’d trained, she joined two other African American women, Monique Y. Davis-Smith, MD, and Joedrecka Brown-Speights, MD, in cochairing the society’s Group on Minority and Multicultural Health.
It was in this space, that Dr. Washington said she “heard people’s stories of being in major academic institutions and not feeling supported, not being given roadmaps to success, not getting assistance with publishing, or just kind of feeling like an outsider ... of not being pulled in.” Hispanic and African American females, in particular, “were feeling marginalized,” she said.
In 2018, having co-led development of the STFM Quality Mentoring Program for URM faculty, Dr. Washington was asked to join the STFM Foundation and subsequently led the STFM Foundation’s fundraising campaign for a new URM Initiative. She exceeded her goal, increasing support for URM participation in meetings and activities, and then participated in an STFM steering committee to create broader and longer-lasting support for URM faculty, community teachers, and medical students and residents going into academic family medicine.
Increasing the percentage of URM family medicine faculty in leadership positions – and raising awareness of structural barriers to achievement – is one of the current pillars of the URM Initiative.
Navigating the ‘minority tax’
As part of her mentoring, Dr. Washington helps URM physicians navigate the minority tax – a term referring to the uncompensated citizenship tasks that are more often assigned to Black and other URM physicians than to White physicians, and that take time away from scholarship, further perpetuating inequities.
“Some of our young faculty members find themselves thrust into being the diversity and inclusion leaders in their institutions at a level at which they feel little power and little buy-in from [leadership],” she noted.
A commentary written by Dr. Washington and several colleagues on the minority tax as it impacts women – and the need to build a “tax shelter” to make academic medicine a more just environment for URM women – was published earlier this year in the Journal of Women’s Health.
She also answers e-mails and fields phone calls from young URM faculty who are mulling career moves and facing other familiar challenges.
Physicians who are URM, and African American physicians in particular, tend to “get pulled into the [often underserved] communities, into the patient care and community service areas,” Dr. Washington explained. “But unless you convert these projects into scholarship and publications, and unless you serve on a national committee outside of your institution, you’re not going to be promoted.”
Dr. Washington helps junior faculty envision themselves 5-plus years down the road, find what she calls scholarly “passion projects,” and prepare themselves for their next steps.
She helps her mentees navigate other parts of the continuum of unconscious bias and racism as well, from microaggressions from colleagues to overt discrimination from patients.
“I spend countless minutes fielding texts and phone calls from those who need support,” she wrote in a blog post. “They are a constant reminder that I must continue to speak up when I get the opportunity to do so.”
A journey through family medicine, and through bias and racism
Dr. Washington’s early days in medicine included graduating from Meharry Medical College in 1983 and the Mountainside Family Practice Residency Program in 1990. Following 6 years of working in a private practice in rural Maryland, she moved to academia, spending 6 years at East Tennessee State University and 4 years at the UMDNJ–New Jersey Medical School in Newark as an assistant professor of family medicine.
As had happened in rural Maryland, bias and racism have too often lurked during her career as a physician.
“I grew up in Alabama so I was pretty much ready to deal with racism in the South,” Dr. Washington said. “What I was not ready for was coming to the Northeast and seeing that you’re marginalized because you’re not invited into the room. Or if you do go into spaces when you’re the only one, you often don’t feel as welcomed as you thought you might be.”
Her ideas and contributions were too often dismissed, she wrote in a 2020 blog entry posted on her LinkedIn page. And during contract negotiations, “I was not aware of all the information that my White colleagues had. They had the advantage of inside information.”
Dr. Washington says that “it took a village” to make her who she is today: teachers in her segregated schools in Alabama, one of her college professors, her best friend in medical school – and STFM, “where the list [of her own mentors] is long.”
Western diet promoted skin, joint inflammation in preclinical study
A short-term Western diet facilitated the development of interleukin (IL)-23-mediated psoriasis-like skin and joint inflammation and caused shifts in the intestinal microbiota in a murine model – , say the investigators and other experts who reviewed the findings.
The mice did not become obese during the short duration of the multilayered study, which suggests that a Western diet (high sugar, moderate fat) can be impactful independent of obesity, Samuel T. Hwang, MD, PhD, professor and chair of dermatology at the University of California, Davis, and senior author of the study, said in an interview. The study was published in the Journal of Investigative Dermatology.
In an accompanying commentary, Renuka R. Nayak, MD, PhD, of the department of rheumatology at the University of California, San Francisco, wrote that the findings “add to the mounting evidence suggesting that diet has a prominent role in the treatment of psoriasis and [psoriatic arthritis] and raise the possibility that the microbiome may contribute to disease severity”.
Mice were fed a Western diet (WD) or conventional chow diet for 6 weeks and then injected with IL-23 minicircle (MC) DNA to induce systemic IL-23 overexpression – or a control minicircle DNA injection – and continued on these diets for another 4 weeks.
The mice in the WD/IL-23 MC DNA group developed erythema and scaling and increased epidermal thickness in the ears; such changes were “remarkably milder” or nonexistent in the other groups. Skin and joint immune cell populations, such as gamma delta T cells, neutrophils, and T helper type 17 cytokines were elevated in WD-fed mice, as were other markers of IL-23-mediated joint inflammation.
Recent research has suggested that the gut microbiota is dysbiotic in patients with psoriasis, and this new study found that WD-fed mice had less microbial diversity than that of mice fed a conventional diet. After IL-23 MC delivery, WD-fed reduced microbial diversity and pronounced dysbiosis.
“When we combined the Western diet and IL-23, we saw some very different microbes in abundance. The whole landscape changed,” Dr. Hwang said in the interview.
The data “suggest that WD and overexpression of IL-23 may contribute to gut microbiota dysbiosis in a synergistic and complex manner,” he and his coinvestigators wrote.
Treatment with broad-spectrum antibiotics suppressed IL-23-mediated skin and joint inflammation in the WD-fed mice – and moderately affected skin inflammation in conventionally-fed mice as well – which affirmed the role of dysbiosis.
And “notably,” in another layer of the study, mice that switched diets from a WD to a conventional diet had reduced skin and joint inflammation and increased diversity of gut microbiota. (Mice that were fed a WD for 6 weeks and given the IL-23 MC DNA were randomized to continue this diet for another 4 weeks or switch to a conventional diet.)
Commenting on the new research, Wilson Liao, MD, professor and vice chair of research in the department of dermatology at the University of California, San Francisco, said it “provides evidence” that diet can affect not only psoriasis, but psoriatic arthritis (PsA) as well, “through altering the ratio of good to bad bacteria in the gut.”
Going forward, better understanding “which specific gut bacteria and bacterial products lead to increased psoriatic inflammation, and the immunologic mechanism by which this occurs” will be important and could lead to novel treatments for psoriasis and PsA, said Dr. Liao, director of the UCSF Psoriasis and Skin Treatment Center.
Next on his research agenda, Dr. Hwang said, is the question of “how microbiota in the gut are actually able to influence inflammation at very distant sites in the joints and the skin.
“We want to understand the metabolic mechanisms,” he said, noting that “we invariably talk about cytokines, but there are other substances, like certain bile acids that are metabolized through the gut microbiome,” which may play a role.
The findings also offer a basis for treatment experiments in humans – of diet, probiotic therapy, or selective antibiotic modulation, for instance, Dr. Hwang said.
And in the meantime, the findings should encourage patients who are interested in making dietary changes, such as reducing sugar intake. “There’s wide interest – patients will ask, is there something I can change to make this better?” Dr. Hwang said. “Before, we could say it might be logical, but now we have some evidence. The message now is [high-sugar, moderate-fat] diets, apart from their ability to stimulate obesity, probably have some effects.”
Dietary change may not replace the need for other psoriasis treatments, he said, “but I think there’s good reason to believe that if you do change your diet, your treatment will be better than it would be without that dietary change,” he said.
In their discussion, Dr. Hwang and coauthors note that WD with IL-23 overexpression also decreased the mRNA expression of barrier-forming tight junction proteins, thus increasing intestinal permeability. This finding may be relevant, they wrote, because “leaky gut has been proposed as a pathogenic link between unhealthy diet, gut dysbiosis, and enhanced immune response,” and has been observed in a number of autoimmune diseases, including psoriasis.
Dr. Hwang, lead author Zhenrui Shi, MD, PhD, and coauthors reported no conflicts of interest. Their study was supported by the National Psoriasis Foundation, as well as the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Cancer Institute.
A short-term Western diet facilitated the development of interleukin (IL)-23-mediated psoriasis-like skin and joint inflammation and caused shifts in the intestinal microbiota in a murine model – , say the investigators and other experts who reviewed the findings.
The mice did not become obese during the short duration of the multilayered study, which suggests that a Western diet (high sugar, moderate fat) can be impactful independent of obesity, Samuel T. Hwang, MD, PhD, professor and chair of dermatology at the University of California, Davis, and senior author of the study, said in an interview. The study was published in the Journal of Investigative Dermatology.
In an accompanying commentary, Renuka R. Nayak, MD, PhD, of the department of rheumatology at the University of California, San Francisco, wrote that the findings “add to the mounting evidence suggesting that diet has a prominent role in the treatment of psoriasis and [psoriatic arthritis] and raise the possibility that the microbiome may contribute to disease severity”.
Mice were fed a Western diet (WD) or conventional chow diet for 6 weeks and then injected with IL-23 minicircle (MC) DNA to induce systemic IL-23 overexpression – or a control minicircle DNA injection – and continued on these diets for another 4 weeks.
The mice in the WD/IL-23 MC DNA group developed erythema and scaling and increased epidermal thickness in the ears; such changes were “remarkably milder” or nonexistent in the other groups. Skin and joint immune cell populations, such as gamma delta T cells, neutrophils, and T helper type 17 cytokines were elevated in WD-fed mice, as were other markers of IL-23-mediated joint inflammation.
Recent research has suggested that the gut microbiota is dysbiotic in patients with psoriasis, and this new study found that WD-fed mice had less microbial diversity than that of mice fed a conventional diet. After IL-23 MC delivery, WD-fed reduced microbial diversity and pronounced dysbiosis.
“When we combined the Western diet and IL-23, we saw some very different microbes in abundance. The whole landscape changed,” Dr. Hwang said in the interview.
The data “suggest that WD and overexpression of IL-23 may contribute to gut microbiota dysbiosis in a synergistic and complex manner,” he and his coinvestigators wrote.
Treatment with broad-spectrum antibiotics suppressed IL-23-mediated skin and joint inflammation in the WD-fed mice – and moderately affected skin inflammation in conventionally-fed mice as well – which affirmed the role of dysbiosis.
And “notably,” in another layer of the study, mice that switched diets from a WD to a conventional diet had reduced skin and joint inflammation and increased diversity of gut microbiota. (Mice that were fed a WD for 6 weeks and given the IL-23 MC DNA were randomized to continue this diet for another 4 weeks or switch to a conventional diet.)
Commenting on the new research, Wilson Liao, MD, professor and vice chair of research in the department of dermatology at the University of California, San Francisco, said it “provides evidence” that diet can affect not only psoriasis, but psoriatic arthritis (PsA) as well, “through altering the ratio of good to bad bacteria in the gut.”
Going forward, better understanding “which specific gut bacteria and bacterial products lead to increased psoriatic inflammation, and the immunologic mechanism by which this occurs” will be important and could lead to novel treatments for psoriasis and PsA, said Dr. Liao, director of the UCSF Psoriasis and Skin Treatment Center.
Next on his research agenda, Dr. Hwang said, is the question of “how microbiota in the gut are actually able to influence inflammation at very distant sites in the joints and the skin.
“We want to understand the metabolic mechanisms,” he said, noting that “we invariably talk about cytokines, but there are other substances, like certain bile acids that are metabolized through the gut microbiome,” which may play a role.
The findings also offer a basis for treatment experiments in humans – of diet, probiotic therapy, or selective antibiotic modulation, for instance, Dr. Hwang said.
And in the meantime, the findings should encourage patients who are interested in making dietary changes, such as reducing sugar intake. “There’s wide interest – patients will ask, is there something I can change to make this better?” Dr. Hwang said. “Before, we could say it might be logical, but now we have some evidence. The message now is [high-sugar, moderate-fat] diets, apart from their ability to stimulate obesity, probably have some effects.”
Dietary change may not replace the need for other psoriasis treatments, he said, “but I think there’s good reason to believe that if you do change your diet, your treatment will be better than it would be without that dietary change,” he said.
In their discussion, Dr. Hwang and coauthors note that WD with IL-23 overexpression also decreased the mRNA expression of barrier-forming tight junction proteins, thus increasing intestinal permeability. This finding may be relevant, they wrote, because “leaky gut has been proposed as a pathogenic link between unhealthy diet, gut dysbiosis, and enhanced immune response,” and has been observed in a number of autoimmune diseases, including psoriasis.
Dr. Hwang, lead author Zhenrui Shi, MD, PhD, and coauthors reported no conflicts of interest. Their study was supported by the National Psoriasis Foundation, as well as the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Cancer Institute.
A short-term Western diet facilitated the development of interleukin (IL)-23-mediated psoriasis-like skin and joint inflammation and caused shifts in the intestinal microbiota in a murine model – , say the investigators and other experts who reviewed the findings.
The mice did not become obese during the short duration of the multilayered study, which suggests that a Western diet (high sugar, moderate fat) can be impactful independent of obesity, Samuel T. Hwang, MD, PhD, professor and chair of dermatology at the University of California, Davis, and senior author of the study, said in an interview. The study was published in the Journal of Investigative Dermatology.
In an accompanying commentary, Renuka R. Nayak, MD, PhD, of the department of rheumatology at the University of California, San Francisco, wrote that the findings “add to the mounting evidence suggesting that diet has a prominent role in the treatment of psoriasis and [psoriatic arthritis] and raise the possibility that the microbiome may contribute to disease severity”.
Mice were fed a Western diet (WD) or conventional chow diet for 6 weeks and then injected with IL-23 minicircle (MC) DNA to induce systemic IL-23 overexpression – or a control minicircle DNA injection – and continued on these diets for another 4 weeks.
The mice in the WD/IL-23 MC DNA group developed erythema and scaling and increased epidermal thickness in the ears; such changes were “remarkably milder” or nonexistent in the other groups. Skin and joint immune cell populations, such as gamma delta T cells, neutrophils, and T helper type 17 cytokines were elevated in WD-fed mice, as were other markers of IL-23-mediated joint inflammation.
Recent research has suggested that the gut microbiota is dysbiotic in patients with psoriasis, and this new study found that WD-fed mice had less microbial diversity than that of mice fed a conventional diet. After IL-23 MC delivery, WD-fed reduced microbial diversity and pronounced dysbiosis.
“When we combined the Western diet and IL-23, we saw some very different microbes in abundance. The whole landscape changed,” Dr. Hwang said in the interview.
The data “suggest that WD and overexpression of IL-23 may contribute to gut microbiota dysbiosis in a synergistic and complex manner,” he and his coinvestigators wrote.
Treatment with broad-spectrum antibiotics suppressed IL-23-mediated skin and joint inflammation in the WD-fed mice – and moderately affected skin inflammation in conventionally-fed mice as well – which affirmed the role of dysbiosis.
And “notably,” in another layer of the study, mice that switched diets from a WD to a conventional diet had reduced skin and joint inflammation and increased diversity of gut microbiota. (Mice that were fed a WD for 6 weeks and given the IL-23 MC DNA were randomized to continue this diet for another 4 weeks or switch to a conventional diet.)
Commenting on the new research, Wilson Liao, MD, professor and vice chair of research in the department of dermatology at the University of California, San Francisco, said it “provides evidence” that diet can affect not only psoriasis, but psoriatic arthritis (PsA) as well, “through altering the ratio of good to bad bacteria in the gut.”
Going forward, better understanding “which specific gut bacteria and bacterial products lead to increased psoriatic inflammation, and the immunologic mechanism by which this occurs” will be important and could lead to novel treatments for psoriasis and PsA, said Dr. Liao, director of the UCSF Psoriasis and Skin Treatment Center.
Next on his research agenda, Dr. Hwang said, is the question of “how microbiota in the gut are actually able to influence inflammation at very distant sites in the joints and the skin.
“We want to understand the metabolic mechanisms,” he said, noting that “we invariably talk about cytokines, but there are other substances, like certain bile acids that are metabolized through the gut microbiome,” which may play a role.
The findings also offer a basis for treatment experiments in humans – of diet, probiotic therapy, or selective antibiotic modulation, for instance, Dr. Hwang said.
And in the meantime, the findings should encourage patients who are interested in making dietary changes, such as reducing sugar intake. “There’s wide interest – patients will ask, is there something I can change to make this better?” Dr. Hwang said. “Before, we could say it might be logical, but now we have some evidence. The message now is [high-sugar, moderate-fat] diets, apart from their ability to stimulate obesity, probably have some effects.”
Dietary change may not replace the need for other psoriasis treatments, he said, “but I think there’s good reason to believe that if you do change your diet, your treatment will be better than it would be without that dietary change,” he said.
In their discussion, Dr. Hwang and coauthors note that WD with IL-23 overexpression also decreased the mRNA expression of barrier-forming tight junction proteins, thus increasing intestinal permeability. This finding may be relevant, they wrote, because “leaky gut has been proposed as a pathogenic link between unhealthy diet, gut dysbiosis, and enhanced immune response,” and has been observed in a number of autoimmune diseases, including psoriasis.
Dr. Hwang, lead author Zhenrui Shi, MD, PhD, and coauthors reported no conflicts of interest. Their study was supported by the National Psoriasis Foundation, as well as the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Cancer Institute.
FROM THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
Study estimates carbon footprint reduction of virtual isotretinoin visits
: A reduction of 5,137 kg of greenhouse gas emissions in carbon dioxide equivalents.
In what they say is “one of the first studies to evaluate the environmental impact of any aspect of dermatology,” the authors of the retrospective cross-sectional study identified patients who had virtual visits for isotretinoin management between March 25 and May 29, 2020, – the period during which all such visits were conducted virtually in keeping with hospital recommendations to minimize the spread of COVID-19.
The investigators, from the department of dermatology and the department of civil and environmental engineering at West Virginia University, Morgantown, then counted the number of virtual visits that occurred during this period and through Dec. 1, 2020, (175 virtual visits), calculated the distance patients would have traveled round-trip had these visits been in-person, and converted miles saved into the environmental impact using U.S. Environmental Protection Agency and Federal Highway Administration data and relevant EPA standards.
Most patients had elected to continue virtual visits after May 29, the point at which patients were given the option to return to the WVUH clinic. (Patients who initiated treatment during the 2-month identification period were not included.)
The investigators determined that virtual management of isotretinoin saved a median of 37.8 miles per visit during the study period of March 25 to Dec. 1, and estimated that the virtual visits reduced total travel by 14,450 miles. For the analysis, patients were assumed to use light-duty vehicles.
In addition to calculating the reduction in emissions during the study period (5,137 kg of CO2equivalents) they used patient census data from 2019 to 2020 and data from the study period to project the mileage – and the associated emissions – that would be saved annually if all in-person visits for isotretinoin management occurred virtually.
Their calculation for a projected emissions reduction with 1 year of all-virtual isotretinoin management was 49,400 kg of greenhouse gas emissions in CO2equivalents. This is the emission load released when 24,690 kg of coal are burned or 6.3 million smartphones are charged, the researchers wrote.
“Considering that more than 1,000,000 prescriptions of isotretinoin are authorized annually in the United States, the environmental impact could be magnified if virtual delivery of isotretinoin care is adopted on a national scale,” they commented.“Given the serious consequences of global climate change, analysis of the environmental impact of all fields of medicine, including dermatology, is warranted,” they added.
The reduced greenhouse gas emissions are “definitely [being taken] into consideration for future decisions about virtual visits” in the department of dermatology, said Zachary Zinn, MD, residency director and associate professor in the department of dermatology at West Virginia University, Morgantown, who is the senior author of the study. “The main benefit of virtual care in my opinion,” he said in an interview, “is the potential to reduce our carbon footprint.”
Justin Lee, MD, an intern at WVU and the study’s first author, said that the research team was motivated to think about how they “could reduce the negative environmental impact of practicing dermatology” after they read a paper about the environmental impact of endoscopy, written by a gastroenterologist.
In the study, no pregnancies occurred and monthly tests were performed, but “formal assessment of pregnancy risk with virtual isotretinoin management would be warranted,” Dr. Lee and coauthors wrote, noting too that, while no differences were seen with respect to isotretinoin side effects, these were not formally analyzed.
Dr. Zinn said that he and colleagues at WVUH are currently conducting clinical trials to assess the quality and efficacy of virtual care for patients with acne, atopic dermatitis, and psoriasis. Delivering care virtually “will be easier to do if there are data supporting [its] quality and efficacy,” he said. Rosacea is another condition that may be amendable to virtual care, he noted.
Meanwhile, he said, isotretinoin management is “well suited” for virtual visits. When initiating isotretinoin treatment, Dr. Zinn now “proactively inquires” if patients would like to pursue their follow-up visits virtually. “I’ll note that it will save the time and decrease the burden of travel, including the financial cost as well as the environmental cost of travel,” he said, estimating that about half of their management visits are currently virtual.
Asked about the study, Misha Rosenbach, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia, said the reduced carbon footprint calculated by the researchers and its downstream health benefits “should be taken into consideration by [dermatology] departments, insurers and policymakers” when making decisions about teledermatology.
While environmental impact is “not something I think most institutions are considering for virtual versus in-person care, they should be. And some are,” said Dr. Rosenbach, a founder and cochair of the American Academy of Dermatology Expert Resource Group for Climate Change and Environmental Issues.
Limitations of the study include the generalizability of the results. The impact of virtual isotretinoin management “may be less in predominantly urban areas” than it is in predominately rural West Virginia, the study authors note. And in the case of West Virginia, travel to a local laboratory and pharmacy offsets some of the environmental benefits for the virtual care, they noted. Such travel wasn’t accounted for in the study, but it was found to be a fraction of travel to the WVU hospital clinic. (Patients traveled a median of 5.8 miles to a lab 2.4 times from March 25 to Dec. 1, 2020.)
Dr. Lee will start his dermatology residency at WVU next year. The study was funded by a grant from the U.S. National Science Foundation. The authors have no relevant conflicts of interest, according to Dr. Lee.
: A reduction of 5,137 kg of greenhouse gas emissions in carbon dioxide equivalents.
In what they say is “one of the first studies to evaluate the environmental impact of any aspect of dermatology,” the authors of the retrospective cross-sectional study identified patients who had virtual visits for isotretinoin management between March 25 and May 29, 2020, – the period during which all such visits were conducted virtually in keeping with hospital recommendations to minimize the spread of COVID-19.
The investigators, from the department of dermatology and the department of civil and environmental engineering at West Virginia University, Morgantown, then counted the number of virtual visits that occurred during this period and through Dec. 1, 2020, (175 virtual visits), calculated the distance patients would have traveled round-trip had these visits been in-person, and converted miles saved into the environmental impact using U.S. Environmental Protection Agency and Federal Highway Administration data and relevant EPA standards.
Most patients had elected to continue virtual visits after May 29, the point at which patients were given the option to return to the WVUH clinic. (Patients who initiated treatment during the 2-month identification period were not included.)
The investigators determined that virtual management of isotretinoin saved a median of 37.8 miles per visit during the study period of March 25 to Dec. 1, and estimated that the virtual visits reduced total travel by 14,450 miles. For the analysis, patients were assumed to use light-duty vehicles.
In addition to calculating the reduction in emissions during the study period (5,137 kg of CO2equivalents) they used patient census data from 2019 to 2020 and data from the study period to project the mileage – and the associated emissions – that would be saved annually if all in-person visits for isotretinoin management occurred virtually.
Their calculation for a projected emissions reduction with 1 year of all-virtual isotretinoin management was 49,400 kg of greenhouse gas emissions in CO2equivalents. This is the emission load released when 24,690 kg of coal are burned or 6.3 million smartphones are charged, the researchers wrote.
“Considering that more than 1,000,000 prescriptions of isotretinoin are authorized annually in the United States, the environmental impact could be magnified if virtual delivery of isotretinoin care is adopted on a national scale,” they commented.“Given the serious consequences of global climate change, analysis of the environmental impact of all fields of medicine, including dermatology, is warranted,” they added.
The reduced greenhouse gas emissions are “definitely [being taken] into consideration for future decisions about virtual visits” in the department of dermatology, said Zachary Zinn, MD, residency director and associate professor in the department of dermatology at West Virginia University, Morgantown, who is the senior author of the study. “The main benefit of virtual care in my opinion,” he said in an interview, “is the potential to reduce our carbon footprint.”
Justin Lee, MD, an intern at WVU and the study’s first author, said that the research team was motivated to think about how they “could reduce the negative environmental impact of practicing dermatology” after they read a paper about the environmental impact of endoscopy, written by a gastroenterologist.
In the study, no pregnancies occurred and monthly tests were performed, but “formal assessment of pregnancy risk with virtual isotretinoin management would be warranted,” Dr. Lee and coauthors wrote, noting too that, while no differences were seen with respect to isotretinoin side effects, these were not formally analyzed.
Dr. Zinn said that he and colleagues at WVUH are currently conducting clinical trials to assess the quality and efficacy of virtual care for patients with acne, atopic dermatitis, and psoriasis. Delivering care virtually “will be easier to do if there are data supporting [its] quality and efficacy,” he said. Rosacea is another condition that may be amendable to virtual care, he noted.
Meanwhile, he said, isotretinoin management is “well suited” for virtual visits. When initiating isotretinoin treatment, Dr. Zinn now “proactively inquires” if patients would like to pursue their follow-up visits virtually. “I’ll note that it will save the time and decrease the burden of travel, including the financial cost as well as the environmental cost of travel,” he said, estimating that about half of their management visits are currently virtual.
Asked about the study, Misha Rosenbach, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia, said the reduced carbon footprint calculated by the researchers and its downstream health benefits “should be taken into consideration by [dermatology] departments, insurers and policymakers” when making decisions about teledermatology.
While environmental impact is “not something I think most institutions are considering for virtual versus in-person care, they should be. And some are,” said Dr. Rosenbach, a founder and cochair of the American Academy of Dermatology Expert Resource Group for Climate Change and Environmental Issues.
Limitations of the study include the generalizability of the results. The impact of virtual isotretinoin management “may be less in predominantly urban areas” than it is in predominately rural West Virginia, the study authors note. And in the case of West Virginia, travel to a local laboratory and pharmacy offsets some of the environmental benefits for the virtual care, they noted. Such travel wasn’t accounted for in the study, but it was found to be a fraction of travel to the WVU hospital clinic. (Patients traveled a median of 5.8 miles to a lab 2.4 times from March 25 to Dec. 1, 2020.)
Dr. Lee will start his dermatology residency at WVU next year. The study was funded by a grant from the U.S. National Science Foundation. The authors have no relevant conflicts of interest, according to Dr. Lee.
: A reduction of 5,137 kg of greenhouse gas emissions in carbon dioxide equivalents.
In what they say is “one of the first studies to evaluate the environmental impact of any aspect of dermatology,” the authors of the retrospective cross-sectional study identified patients who had virtual visits for isotretinoin management between March 25 and May 29, 2020, – the period during which all such visits were conducted virtually in keeping with hospital recommendations to minimize the spread of COVID-19.
The investigators, from the department of dermatology and the department of civil and environmental engineering at West Virginia University, Morgantown, then counted the number of virtual visits that occurred during this period and through Dec. 1, 2020, (175 virtual visits), calculated the distance patients would have traveled round-trip had these visits been in-person, and converted miles saved into the environmental impact using U.S. Environmental Protection Agency and Federal Highway Administration data and relevant EPA standards.
Most patients had elected to continue virtual visits after May 29, the point at which patients were given the option to return to the WVUH clinic. (Patients who initiated treatment during the 2-month identification period were not included.)
The investigators determined that virtual management of isotretinoin saved a median of 37.8 miles per visit during the study period of March 25 to Dec. 1, and estimated that the virtual visits reduced total travel by 14,450 miles. For the analysis, patients were assumed to use light-duty vehicles.
In addition to calculating the reduction in emissions during the study period (5,137 kg of CO2equivalents) they used patient census data from 2019 to 2020 and data from the study period to project the mileage – and the associated emissions – that would be saved annually if all in-person visits for isotretinoin management occurred virtually.
Their calculation for a projected emissions reduction with 1 year of all-virtual isotretinoin management was 49,400 kg of greenhouse gas emissions in CO2equivalents. This is the emission load released when 24,690 kg of coal are burned or 6.3 million smartphones are charged, the researchers wrote.
“Considering that more than 1,000,000 prescriptions of isotretinoin are authorized annually in the United States, the environmental impact could be magnified if virtual delivery of isotretinoin care is adopted on a national scale,” they commented.“Given the serious consequences of global climate change, analysis of the environmental impact of all fields of medicine, including dermatology, is warranted,” they added.
The reduced greenhouse gas emissions are “definitely [being taken] into consideration for future decisions about virtual visits” in the department of dermatology, said Zachary Zinn, MD, residency director and associate professor in the department of dermatology at West Virginia University, Morgantown, who is the senior author of the study. “The main benefit of virtual care in my opinion,” he said in an interview, “is the potential to reduce our carbon footprint.”
Justin Lee, MD, an intern at WVU and the study’s first author, said that the research team was motivated to think about how they “could reduce the negative environmental impact of practicing dermatology” after they read a paper about the environmental impact of endoscopy, written by a gastroenterologist.
In the study, no pregnancies occurred and monthly tests were performed, but “formal assessment of pregnancy risk with virtual isotretinoin management would be warranted,” Dr. Lee and coauthors wrote, noting too that, while no differences were seen with respect to isotretinoin side effects, these were not formally analyzed.
Dr. Zinn said that he and colleagues at WVUH are currently conducting clinical trials to assess the quality and efficacy of virtual care for patients with acne, atopic dermatitis, and psoriasis. Delivering care virtually “will be easier to do if there are data supporting [its] quality and efficacy,” he said. Rosacea is another condition that may be amendable to virtual care, he noted.
Meanwhile, he said, isotretinoin management is “well suited” for virtual visits. When initiating isotretinoin treatment, Dr. Zinn now “proactively inquires” if patients would like to pursue their follow-up visits virtually. “I’ll note that it will save the time and decrease the burden of travel, including the financial cost as well as the environmental cost of travel,” he said, estimating that about half of their management visits are currently virtual.
Asked about the study, Misha Rosenbach, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia, said the reduced carbon footprint calculated by the researchers and its downstream health benefits “should be taken into consideration by [dermatology] departments, insurers and policymakers” when making decisions about teledermatology.
While environmental impact is “not something I think most institutions are considering for virtual versus in-person care, they should be. And some are,” said Dr. Rosenbach, a founder and cochair of the American Academy of Dermatology Expert Resource Group for Climate Change and Environmental Issues.
Limitations of the study include the generalizability of the results. The impact of virtual isotretinoin management “may be less in predominantly urban areas” than it is in predominately rural West Virginia, the study authors note. And in the case of West Virginia, travel to a local laboratory and pharmacy offsets some of the environmental benefits for the virtual care, they noted. Such travel wasn’t accounted for in the study, but it was found to be a fraction of travel to the WVU hospital clinic. (Patients traveled a median of 5.8 miles to a lab 2.4 times from March 25 to Dec. 1, 2020.)
Dr. Lee will start his dermatology residency at WVU next year. The study was funded by a grant from the U.S. National Science Foundation. The authors have no relevant conflicts of interest, according to Dr. Lee.
FROM PEDIATRIC DERMATOLOGY