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Childhood-onset SLE rate doubles in children born in winter
SAN FRANCISCO – Simone Appenzeller, MD, PhD, reported at an international congress on systemic lupus erythematosus.
She presented a cross-sectional study of 760 consecutive SLE patients seen in a university lupus clinic and 700 healthy controls. Ninety-eight of the lupus patients had childhood-onset disease that began no later than age 16 years, while 662 had adult-onset SLE.
Southeastern Brazil, where the study was conducted, features a mostly subtropical climate with relatively mild winters. Because it is in the southern hemisphere, winter lasts from June 21 to September 21, while spring runs from September 22 to December 20.
Forty-six percent of subjects with childhood-onset SLE were born in winter, 17% in spring, another 17% in summer, and just over 19% in autumn, according to Dr. Appenzeller, a rheumatologist at the University of Campinas (Brazil).
In contrast, the occurrence of adult-onset SLE showed no variation by birth month or season.
The birth disparity between childhood- and adult-onset SLE was greatest in August, the depth of Brazilian winter, when 15.3% of all subjects with childhood-onset SLE were born, compared with 9% of adult-onset SLE patients and 8% of healthy controls.
The explanation for the increased likelihood of patients with childhood-onset SLE to be born in the winter months probably involves a gene-environment interaction, Dr. Appenzeller said. The most likely environmental factors are low seasonal maternal vitamin D levels and/or exposure to winter respiratory infections. The existence of a genetic component to the birth month disparity is suggested by another study by the Brazilian investigators in which they determined that the prevalence of SLE in both the first- and second-degree relatives of individuals with childhood-onset SLE was significantly higher than in patients with adult-onset disease.
Dr. Appenzeller reported having no financial conflicts regarding her study, funded by the Brazilian National Council for Scientific and Technological Development and other noncommercial research organizations.
SAN FRANCISCO – Simone Appenzeller, MD, PhD, reported at an international congress on systemic lupus erythematosus.
She presented a cross-sectional study of 760 consecutive SLE patients seen in a university lupus clinic and 700 healthy controls. Ninety-eight of the lupus patients had childhood-onset disease that began no later than age 16 years, while 662 had adult-onset SLE.
Southeastern Brazil, where the study was conducted, features a mostly subtropical climate with relatively mild winters. Because it is in the southern hemisphere, winter lasts from June 21 to September 21, while spring runs from September 22 to December 20.
Forty-six percent of subjects with childhood-onset SLE were born in winter, 17% in spring, another 17% in summer, and just over 19% in autumn, according to Dr. Appenzeller, a rheumatologist at the University of Campinas (Brazil).
In contrast, the occurrence of adult-onset SLE showed no variation by birth month or season.
The birth disparity between childhood- and adult-onset SLE was greatest in August, the depth of Brazilian winter, when 15.3% of all subjects with childhood-onset SLE were born, compared with 9% of adult-onset SLE patients and 8% of healthy controls.
The explanation for the increased likelihood of patients with childhood-onset SLE to be born in the winter months probably involves a gene-environment interaction, Dr. Appenzeller said. The most likely environmental factors are low seasonal maternal vitamin D levels and/or exposure to winter respiratory infections. The existence of a genetic component to the birth month disparity is suggested by another study by the Brazilian investigators in which they determined that the prevalence of SLE in both the first- and second-degree relatives of individuals with childhood-onset SLE was significantly higher than in patients with adult-onset disease.
Dr. Appenzeller reported having no financial conflicts regarding her study, funded by the Brazilian National Council for Scientific and Technological Development and other noncommercial research organizations.
SAN FRANCISCO – Simone Appenzeller, MD, PhD, reported at an international congress on systemic lupus erythematosus.
She presented a cross-sectional study of 760 consecutive SLE patients seen in a university lupus clinic and 700 healthy controls. Ninety-eight of the lupus patients had childhood-onset disease that began no later than age 16 years, while 662 had adult-onset SLE.
Southeastern Brazil, where the study was conducted, features a mostly subtropical climate with relatively mild winters. Because it is in the southern hemisphere, winter lasts from June 21 to September 21, while spring runs from September 22 to December 20.
Forty-six percent of subjects with childhood-onset SLE were born in winter, 17% in spring, another 17% in summer, and just over 19% in autumn, according to Dr. Appenzeller, a rheumatologist at the University of Campinas (Brazil).
In contrast, the occurrence of adult-onset SLE showed no variation by birth month or season.
The birth disparity between childhood- and adult-onset SLE was greatest in August, the depth of Brazilian winter, when 15.3% of all subjects with childhood-onset SLE were born, compared with 9% of adult-onset SLE patients and 8% of healthy controls.
The explanation for the increased likelihood of patients with childhood-onset SLE to be born in the winter months probably involves a gene-environment interaction, Dr. Appenzeller said. The most likely environmental factors are low seasonal maternal vitamin D levels and/or exposure to winter respiratory infections. The existence of a genetic component to the birth month disparity is suggested by another study by the Brazilian investigators in which they determined that the prevalence of SLE in both the first- and second-degree relatives of individuals with childhood-onset SLE was significantly higher than in patients with adult-onset disease.
Dr. Appenzeller reported having no financial conflicts regarding her study, funded by the Brazilian National Council for Scientific and Technological Development and other noncommercial research organizations.
REPORTING FROM LUPUS 2019
Think ‘fall prevention’ in SLE patients
SAN FRANCISCO – in a Dutch prospective longitudinal study, Irene E.M. Bultink, MD, PhD, reported at an international congress on systemic lupus erythematosus.
“I think we should focus on fall risk and fall events in lupus. I think that’s a neglected area,” according to Dr. Bultink, a rheumatologist at the University of Amsterdam.
Contrary to the conventional wisdom, in her study, cumulative corticosteroid dose, average daily dosage, and bone loss were not significantly related to fracture risk in these SLE patients. That’s because Dr. Bultink and her fellow rheumatologists took steps to mitigate steroid-induced bone loss.
“We know steroids are very important for bone loss in lupus, but we demonstrated in our long-term follow-up study that it’s very dose dependent. If you use steroids below 7.5 mg daily and you protect your patient with calcium and vitamin D and, if possible, with bisphosphonates, the bone loss is restricted. I think fracture risk in lupus is more related to fall risk and fall incidence than to bone loss and steroid use. That’s what we demonstrated in our study,” she said in an interview.
“Unfortunately, until now, no studies on fall risk and fall events in lupus have been published. It’s not investigated very well. I think that fall risk in lupus patients might be greatly increased, compared to healthy controls,” Dr. Bultink added.
The study included 145 Dutch SLE patients with a mean age of 41 years at baseline. Ninety percent were women; 69% were white. Bone mineral density measurements by dual x-ray bone densitometry and x-rays of the lumbar and thoracic spine were obtained at entry and again after a median of 5 years.
Forty-two incident fractures occurred during a median of 7.2 years of follow-up. This equated to an incidence rate of 2.2 peripheral and 2.0 vertebral fractures per 100 person-years, rates double those in the Dutch general population.
In a logistic regression analysis, white ethnicity was independently associated with a 13.2-fold increased risk of fractures overall. Postmenopausal status conferred a fourfold increased risk. Older age was another important determinant. And patients with a prior stroke were at 15.5-fold greater risk of peripheral fractures.
“The prior stroke subgroup is especially vulnerable. In an earlier population-based study using data from the U.K. we also demonstrated that fractures happened more frequently in SLE patients who had already suffered a stroke (Osteoporos Int. 2014 Apr;25[4]:1275-83). So those are patients who are at very high risk for falling and fractures. But I think there are many reasons why patients with SLE would have an elevated fall risk. They have fatigue. They have muscle weakness, which might be due to vitamin D deficiency or prednisone use or inactivity. And they often have balance problems due to neuropathy or medication,” the rheumatologist observed.
She reported having no financial conflicts regarding her study, carried out free of commercial support.
SAN FRANCISCO – in a Dutch prospective longitudinal study, Irene E.M. Bultink, MD, PhD, reported at an international congress on systemic lupus erythematosus.
“I think we should focus on fall risk and fall events in lupus. I think that’s a neglected area,” according to Dr. Bultink, a rheumatologist at the University of Amsterdam.
Contrary to the conventional wisdom, in her study, cumulative corticosteroid dose, average daily dosage, and bone loss were not significantly related to fracture risk in these SLE patients. That’s because Dr. Bultink and her fellow rheumatologists took steps to mitigate steroid-induced bone loss.
“We know steroids are very important for bone loss in lupus, but we demonstrated in our long-term follow-up study that it’s very dose dependent. If you use steroids below 7.5 mg daily and you protect your patient with calcium and vitamin D and, if possible, with bisphosphonates, the bone loss is restricted. I think fracture risk in lupus is more related to fall risk and fall incidence than to bone loss and steroid use. That’s what we demonstrated in our study,” she said in an interview.
“Unfortunately, until now, no studies on fall risk and fall events in lupus have been published. It’s not investigated very well. I think that fall risk in lupus patients might be greatly increased, compared to healthy controls,” Dr. Bultink added.
The study included 145 Dutch SLE patients with a mean age of 41 years at baseline. Ninety percent were women; 69% were white. Bone mineral density measurements by dual x-ray bone densitometry and x-rays of the lumbar and thoracic spine were obtained at entry and again after a median of 5 years.
Forty-two incident fractures occurred during a median of 7.2 years of follow-up. This equated to an incidence rate of 2.2 peripheral and 2.0 vertebral fractures per 100 person-years, rates double those in the Dutch general population.
In a logistic regression analysis, white ethnicity was independently associated with a 13.2-fold increased risk of fractures overall. Postmenopausal status conferred a fourfold increased risk. Older age was another important determinant. And patients with a prior stroke were at 15.5-fold greater risk of peripheral fractures.
“The prior stroke subgroup is especially vulnerable. In an earlier population-based study using data from the U.K. we also demonstrated that fractures happened more frequently in SLE patients who had already suffered a stroke (Osteoporos Int. 2014 Apr;25[4]:1275-83). So those are patients who are at very high risk for falling and fractures. But I think there are many reasons why patients with SLE would have an elevated fall risk. They have fatigue. They have muscle weakness, which might be due to vitamin D deficiency or prednisone use or inactivity. And they often have balance problems due to neuropathy or medication,” the rheumatologist observed.
She reported having no financial conflicts regarding her study, carried out free of commercial support.
SAN FRANCISCO – in a Dutch prospective longitudinal study, Irene E.M. Bultink, MD, PhD, reported at an international congress on systemic lupus erythematosus.
“I think we should focus on fall risk and fall events in lupus. I think that’s a neglected area,” according to Dr. Bultink, a rheumatologist at the University of Amsterdam.
Contrary to the conventional wisdom, in her study, cumulative corticosteroid dose, average daily dosage, and bone loss were not significantly related to fracture risk in these SLE patients. That’s because Dr. Bultink and her fellow rheumatologists took steps to mitigate steroid-induced bone loss.
“We know steroids are very important for bone loss in lupus, but we demonstrated in our long-term follow-up study that it’s very dose dependent. If you use steroids below 7.5 mg daily and you protect your patient with calcium and vitamin D and, if possible, with bisphosphonates, the bone loss is restricted. I think fracture risk in lupus is more related to fall risk and fall incidence than to bone loss and steroid use. That’s what we demonstrated in our study,” she said in an interview.
“Unfortunately, until now, no studies on fall risk and fall events in lupus have been published. It’s not investigated very well. I think that fall risk in lupus patients might be greatly increased, compared to healthy controls,” Dr. Bultink added.
The study included 145 Dutch SLE patients with a mean age of 41 years at baseline. Ninety percent were women; 69% were white. Bone mineral density measurements by dual x-ray bone densitometry and x-rays of the lumbar and thoracic spine were obtained at entry and again after a median of 5 years.
Forty-two incident fractures occurred during a median of 7.2 years of follow-up. This equated to an incidence rate of 2.2 peripheral and 2.0 vertebral fractures per 100 person-years, rates double those in the Dutch general population.
In a logistic regression analysis, white ethnicity was independently associated with a 13.2-fold increased risk of fractures overall. Postmenopausal status conferred a fourfold increased risk. Older age was another important determinant. And patients with a prior stroke were at 15.5-fold greater risk of peripheral fractures.
“The prior stroke subgroup is especially vulnerable. In an earlier population-based study using data from the U.K. we also demonstrated that fractures happened more frequently in SLE patients who had already suffered a stroke (Osteoporos Int. 2014 Apr;25[4]:1275-83). So those are patients who are at very high risk for falling and fractures. But I think there are many reasons why patients with SLE would have an elevated fall risk. They have fatigue. They have muscle weakness, which might be due to vitamin D deficiency or prednisone use or inactivity. And they often have balance problems due to neuropathy or medication,” the rheumatologist observed.
She reported having no financial conflicts regarding her study, carried out free of commercial support.
REPORTING FROM LUPUS 2019
Young lupus patients need more than medications
SAN FRANCISCO – – and therein lies the importance of introducing interventions beyond simply prescribing appropriate medications, Hermine I. Brunner, MD, asserted at an international congress on systemic lupus erythematosus.
Pilot studies conducted by her research group as well as others suggest that brief cognitive-behavioral interventions, web-based patient and caregiver education, and social media interactions significantly improve the fatigue and depression, poor quality of life, and lack of adherence to medication that are pervasive in young patients with SLE, according to Dr. Brunner, director of the division of rheumatology and professor of pediatrics at the University of Cincinnati and scientific director of the Pediatric Rheumatology Collaborative Study Group.
“Don’t misunderstand: I don’t think we can treat lupus simply with a psychological intervention at the bedside. However, I think doctors would be well advised to offer both psychological interventions and medication when they see young lupus patients, because without the psychological intervention the patients may not feel sufficiently at ease to take their medication. They will not get the benefit of the medications you’ve prescribed,” she said.
Patients with SLE take an average of eight medications daily. Their medication adherence rate is comparable to that of patients with diabetes or many other chronic diseases: that is to say, lousy. When investigators at the University of Texas MD Anderson Cancer Center, Houston, utilized an electronic monitoring system to chart adherence to prescribed oral medications in adults with SLE, they found that over the course of 2 years of follow-up only one-fourth of them had an adherence rate of 80% or better, which is the standard definition of adherence (Lupus. 2012 Oct;21[11]:1158-65).
Treatment adherence is particularly problematic in adolescents and young adults with SLE. They often have great difficulty in mastering the self-management skills required to stay on top of their disease when they have so much else going on during what is a vulnerable and challenging period of development, even for healthy youths.
The texting intervention
Dr. Brunner and her colleagues at Cincinnati Children’s Hospital Medical Center recognized the scope of the nonadherence problem early on. Years ago they started sending text messaging reminders of pending clinic visits to their patients who had a poor track record of showing up for appointments.
“We texted patients 2 weeks before their scheduled visit, 1 week before, and then again the day before the visit,” she explained.
This simple intervention resulted in a 47% reduction in missed appointments, compared with a control group. Also, text recipients were more likely to cancel appointments instead of simply not showing up, an important benefit from a practice management and scheduling standpoint (J Rheumatol. 2012 Jan;39[1]:174-9). Disappointingly, however, the text messaging intervention had no impact on adherence to prescribed use of hydroxychloroquine. This led the investigators to conduct a deeper dive into the roots of the nonadherence problem in childhood-onset lupus.
Disease control, quality of life
Dr. Brunner and her coworkers conducted an in-depth assessment of health-related quality of life in 50 patients with childhood-onset SLE over the course of 6 months. The results were surprising.
“When we looked at the correlation between disease control and quality of life, actually there was none,” according to the pediatric rheumatologist.
Instead, the investigators found that young patients with persistently low quality of life despite objectively measured good disease control scored high for fatigue and depressive symptoms (Lupus. 2018 Jan;27[1]:124-33). This led Dr. Brunner and her coinvestigators to consider developing a practical behavioral intervention to address these potentially modifiable predictors of impaired health-related quality of life in their patient population.
The need for novel approaches was highlighted in focus groups conducted by the investigators, in which patients and their primary caregivers emphasized that current therapeutic strategies don’t adequately address key problems of living with lupus, especially the prominent fatigue, pain, and depressed mood that hamper daily function and personal relationships. Patients said they don’t feel an immediate benefit from taking their medications, so why bother? And parents expressed frustration about how difficult it is to get their teenagers to understand the consequences of nonadherence when they’re at an age when they don’t yet even grasp the concept of their own mortality (Lupus. 2019 Mar. doi: 10.1177/0961203319839478. These observations spurred the Cincinnati investigators to develop a modified cognitive-behavioral therapy (CBT) protocol, known as TEACH, which they believe is the first CBT intervention to specifically target psychological problems in young people with childhood-onset SLE.
The TEACH program
TEACH (Treatment and Education Approach for Childhood-Onset Lupus) is a six-session program that teaches patients and caregivers self-advocacy, relaxation techniques, how to improve sleep hygiene, the importance of engaging in planned pleasant activities, and why taking medications matters. The program content differs depending upon whether the patient is an adolescent or young adult.
Results of a recently published small feasibility study were highly encouraging, showing that 83% of people who enrolled in the program completed it. Posttreatment assessment showed that patients had a marked decrease in depressive symptoms as measured by both the Children’s Depression Inventory and the Beck Depression Inventory. They also showed a significant reduction in fatigue. However, while favorable trends in terms of reduced pain and anxiety symptoms were noted, they didn’t achieve statistical significance (Pediatr Rheumatol Online J. 2019 Feb 18. doi: 10.1186/s12969-019-0307-8). The next step in this project is a planned controlled randomized trial.
A web-based medication adherence program
Researchers at Pennsylvania State University took a different approach. They created a publicly available educational website, www.facinglupustogether.com, aimed at improving self-management skills – and especially medication adherence – in teens and young adults with SLE.
The website contains eight modules: Making the transition and taking charge of my medications, Learning about lupus, Learning about lupus medications, Managing symptoms of lupus, How do I handle lupus and my family, How do I handle lupus and my friends, Lupus and stress, and My personal goals and how I will achieve them. Each takes about 10 minutes to complete.
In a pilot study, 37 patients tackled one module per week and were randomized to respond to questions about the weekly topic either in a journal or by discussing the key points in an online social media forum with other young people with SLE. The idea was to create an intervention that capitalizes on the excellent social media skills possessed by today’s youth. And indeed, incorporation of social media proved to be a winning strategy. Medication adherence for hydroxychloroquine in the group randomized to social media participation jumped from 50% in the 3 months prior to starting the program to 92% in the first 3 months post completion, whereas medication adherence didn’t change significantly in the other study arm. The social media group also experienced significant improvements in self-efficacy, sense of community, acceptance of illness, optimism and control over the future, and other measures of empowerment. The control group did not show significant change in any of these domains (Pediatr Rheumatol Online J. 2018 Mar 14. doi: 10.1186/s12969-018-0232-2).
The TEACH study was sponsored by the National Institutes of Health. The web-based medication adherence program pilot study was supported by the Lupus Foundation of America. What the two approaches share in common is a conviction that, when it comes to addressing pain, fatigue, diminished quality of life, and poor medication adherence in young patients with SLE: “Our medication prescription alone doesn’t do it,” Dr. Brunner said.
She reported having no financial conflicts regarding her presentation.
SAN FRANCISCO – – and therein lies the importance of introducing interventions beyond simply prescribing appropriate medications, Hermine I. Brunner, MD, asserted at an international congress on systemic lupus erythematosus.
Pilot studies conducted by her research group as well as others suggest that brief cognitive-behavioral interventions, web-based patient and caregiver education, and social media interactions significantly improve the fatigue and depression, poor quality of life, and lack of adherence to medication that are pervasive in young patients with SLE, according to Dr. Brunner, director of the division of rheumatology and professor of pediatrics at the University of Cincinnati and scientific director of the Pediatric Rheumatology Collaborative Study Group.
“Don’t misunderstand: I don’t think we can treat lupus simply with a psychological intervention at the bedside. However, I think doctors would be well advised to offer both psychological interventions and medication when they see young lupus patients, because without the psychological intervention the patients may not feel sufficiently at ease to take their medication. They will not get the benefit of the medications you’ve prescribed,” she said.
Patients with SLE take an average of eight medications daily. Their medication adherence rate is comparable to that of patients with diabetes or many other chronic diseases: that is to say, lousy. When investigators at the University of Texas MD Anderson Cancer Center, Houston, utilized an electronic monitoring system to chart adherence to prescribed oral medications in adults with SLE, they found that over the course of 2 years of follow-up only one-fourth of them had an adherence rate of 80% or better, which is the standard definition of adherence (Lupus. 2012 Oct;21[11]:1158-65).
Treatment adherence is particularly problematic in adolescents and young adults with SLE. They often have great difficulty in mastering the self-management skills required to stay on top of their disease when they have so much else going on during what is a vulnerable and challenging period of development, even for healthy youths.
The texting intervention
Dr. Brunner and her colleagues at Cincinnati Children’s Hospital Medical Center recognized the scope of the nonadherence problem early on. Years ago they started sending text messaging reminders of pending clinic visits to their patients who had a poor track record of showing up for appointments.
“We texted patients 2 weeks before their scheduled visit, 1 week before, and then again the day before the visit,” she explained.
This simple intervention resulted in a 47% reduction in missed appointments, compared with a control group. Also, text recipients were more likely to cancel appointments instead of simply not showing up, an important benefit from a practice management and scheduling standpoint (J Rheumatol. 2012 Jan;39[1]:174-9). Disappointingly, however, the text messaging intervention had no impact on adherence to prescribed use of hydroxychloroquine. This led the investigators to conduct a deeper dive into the roots of the nonadherence problem in childhood-onset lupus.
Disease control, quality of life
Dr. Brunner and her coworkers conducted an in-depth assessment of health-related quality of life in 50 patients with childhood-onset SLE over the course of 6 months. The results were surprising.
“When we looked at the correlation between disease control and quality of life, actually there was none,” according to the pediatric rheumatologist.
Instead, the investigators found that young patients with persistently low quality of life despite objectively measured good disease control scored high for fatigue and depressive symptoms (Lupus. 2018 Jan;27[1]:124-33). This led Dr. Brunner and her coinvestigators to consider developing a practical behavioral intervention to address these potentially modifiable predictors of impaired health-related quality of life in their patient population.
The need for novel approaches was highlighted in focus groups conducted by the investigators, in which patients and their primary caregivers emphasized that current therapeutic strategies don’t adequately address key problems of living with lupus, especially the prominent fatigue, pain, and depressed mood that hamper daily function and personal relationships. Patients said they don’t feel an immediate benefit from taking their medications, so why bother? And parents expressed frustration about how difficult it is to get their teenagers to understand the consequences of nonadherence when they’re at an age when they don’t yet even grasp the concept of their own mortality (Lupus. 2019 Mar. doi: 10.1177/0961203319839478. These observations spurred the Cincinnati investigators to develop a modified cognitive-behavioral therapy (CBT) protocol, known as TEACH, which they believe is the first CBT intervention to specifically target psychological problems in young people with childhood-onset SLE.
The TEACH program
TEACH (Treatment and Education Approach for Childhood-Onset Lupus) is a six-session program that teaches patients and caregivers self-advocacy, relaxation techniques, how to improve sleep hygiene, the importance of engaging in planned pleasant activities, and why taking medications matters. The program content differs depending upon whether the patient is an adolescent or young adult.
Results of a recently published small feasibility study were highly encouraging, showing that 83% of people who enrolled in the program completed it. Posttreatment assessment showed that patients had a marked decrease in depressive symptoms as measured by both the Children’s Depression Inventory and the Beck Depression Inventory. They also showed a significant reduction in fatigue. However, while favorable trends in terms of reduced pain and anxiety symptoms were noted, they didn’t achieve statistical significance (Pediatr Rheumatol Online J. 2019 Feb 18. doi: 10.1186/s12969-019-0307-8). The next step in this project is a planned controlled randomized trial.
A web-based medication adherence program
Researchers at Pennsylvania State University took a different approach. They created a publicly available educational website, www.facinglupustogether.com, aimed at improving self-management skills – and especially medication adherence – in teens and young adults with SLE.
The website contains eight modules: Making the transition and taking charge of my medications, Learning about lupus, Learning about lupus medications, Managing symptoms of lupus, How do I handle lupus and my family, How do I handle lupus and my friends, Lupus and stress, and My personal goals and how I will achieve them. Each takes about 10 minutes to complete.
In a pilot study, 37 patients tackled one module per week and were randomized to respond to questions about the weekly topic either in a journal or by discussing the key points in an online social media forum with other young people with SLE. The idea was to create an intervention that capitalizes on the excellent social media skills possessed by today’s youth. And indeed, incorporation of social media proved to be a winning strategy. Medication adherence for hydroxychloroquine in the group randomized to social media participation jumped from 50% in the 3 months prior to starting the program to 92% in the first 3 months post completion, whereas medication adherence didn’t change significantly in the other study arm. The social media group also experienced significant improvements in self-efficacy, sense of community, acceptance of illness, optimism and control over the future, and other measures of empowerment. The control group did not show significant change in any of these domains (Pediatr Rheumatol Online J. 2018 Mar 14. doi: 10.1186/s12969-018-0232-2).
The TEACH study was sponsored by the National Institutes of Health. The web-based medication adherence program pilot study was supported by the Lupus Foundation of America. What the two approaches share in common is a conviction that, when it comes to addressing pain, fatigue, diminished quality of life, and poor medication adherence in young patients with SLE: “Our medication prescription alone doesn’t do it,” Dr. Brunner said.
She reported having no financial conflicts regarding her presentation.
SAN FRANCISCO – – and therein lies the importance of introducing interventions beyond simply prescribing appropriate medications, Hermine I. Brunner, MD, asserted at an international congress on systemic lupus erythematosus.
Pilot studies conducted by her research group as well as others suggest that brief cognitive-behavioral interventions, web-based patient and caregiver education, and social media interactions significantly improve the fatigue and depression, poor quality of life, and lack of adherence to medication that are pervasive in young patients with SLE, according to Dr. Brunner, director of the division of rheumatology and professor of pediatrics at the University of Cincinnati and scientific director of the Pediatric Rheumatology Collaborative Study Group.
“Don’t misunderstand: I don’t think we can treat lupus simply with a psychological intervention at the bedside. However, I think doctors would be well advised to offer both psychological interventions and medication when they see young lupus patients, because without the psychological intervention the patients may not feel sufficiently at ease to take their medication. They will not get the benefit of the medications you’ve prescribed,” she said.
Patients with SLE take an average of eight medications daily. Their medication adherence rate is comparable to that of patients with diabetes or many other chronic diseases: that is to say, lousy. When investigators at the University of Texas MD Anderson Cancer Center, Houston, utilized an electronic monitoring system to chart adherence to prescribed oral medications in adults with SLE, they found that over the course of 2 years of follow-up only one-fourth of them had an adherence rate of 80% or better, which is the standard definition of adherence (Lupus. 2012 Oct;21[11]:1158-65).
Treatment adherence is particularly problematic in adolescents and young adults with SLE. They often have great difficulty in mastering the self-management skills required to stay on top of their disease when they have so much else going on during what is a vulnerable and challenging period of development, even for healthy youths.
The texting intervention
Dr. Brunner and her colleagues at Cincinnati Children’s Hospital Medical Center recognized the scope of the nonadherence problem early on. Years ago they started sending text messaging reminders of pending clinic visits to their patients who had a poor track record of showing up for appointments.
“We texted patients 2 weeks before their scheduled visit, 1 week before, and then again the day before the visit,” she explained.
This simple intervention resulted in a 47% reduction in missed appointments, compared with a control group. Also, text recipients were more likely to cancel appointments instead of simply not showing up, an important benefit from a practice management and scheduling standpoint (J Rheumatol. 2012 Jan;39[1]:174-9). Disappointingly, however, the text messaging intervention had no impact on adherence to prescribed use of hydroxychloroquine. This led the investigators to conduct a deeper dive into the roots of the nonadherence problem in childhood-onset lupus.
Disease control, quality of life
Dr. Brunner and her coworkers conducted an in-depth assessment of health-related quality of life in 50 patients with childhood-onset SLE over the course of 6 months. The results were surprising.
“When we looked at the correlation between disease control and quality of life, actually there was none,” according to the pediatric rheumatologist.
Instead, the investigators found that young patients with persistently low quality of life despite objectively measured good disease control scored high for fatigue and depressive symptoms (Lupus. 2018 Jan;27[1]:124-33). This led Dr. Brunner and her coinvestigators to consider developing a practical behavioral intervention to address these potentially modifiable predictors of impaired health-related quality of life in their patient population.
The need for novel approaches was highlighted in focus groups conducted by the investigators, in which patients and their primary caregivers emphasized that current therapeutic strategies don’t adequately address key problems of living with lupus, especially the prominent fatigue, pain, and depressed mood that hamper daily function and personal relationships. Patients said they don’t feel an immediate benefit from taking their medications, so why bother? And parents expressed frustration about how difficult it is to get their teenagers to understand the consequences of nonadherence when they’re at an age when they don’t yet even grasp the concept of their own mortality (Lupus. 2019 Mar. doi: 10.1177/0961203319839478. These observations spurred the Cincinnati investigators to develop a modified cognitive-behavioral therapy (CBT) protocol, known as TEACH, which they believe is the first CBT intervention to specifically target psychological problems in young people with childhood-onset SLE.
The TEACH program
TEACH (Treatment and Education Approach for Childhood-Onset Lupus) is a six-session program that teaches patients and caregivers self-advocacy, relaxation techniques, how to improve sleep hygiene, the importance of engaging in planned pleasant activities, and why taking medications matters. The program content differs depending upon whether the patient is an adolescent or young adult.
Results of a recently published small feasibility study were highly encouraging, showing that 83% of people who enrolled in the program completed it. Posttreatment assessment showed that patients had a marked decrease in depressive symptoms as measured by both the Children’s Depression Inventory and the Beck Depression Inventory. They also showed a significant reduction in fatigue. However, while favorable trends in terms of reduced pain and anxiety symptoms were noted, they didn’t achieve statistical significance (Pediatr Rheumatol Online J. 2019 Feb 18. doi: 10.1186/s12969-019-0307-8). The next step in this project is a planned controlled randomized trial.
A web-based medication adherence program
Researchers at Pennsylvania State University took a different approach. They created a publicly available educational website, www.facinglupustogether.com, aimed at improving self-management skills – and especially medication adherence – in teens and young adults with SLE.
The website contains eight modules: Making the transition and taking charge of my medications, Learning about lupus, Learning about lupus medications, Managing symptoms of lupus, How do I handle lupus and my family, How do I handle lupus and my friends, Lupus and stress, and My personal goals and how I will achieve them. Each takes about 10 minutes to complete.
In a pilot study, 37 patients tackled one module per week and were randomized to respond to questions about the weekly topic either in a journal or by discussing the key points in an online social media forum with other young people with SLE. The idea was to create an intervention that capitalizes on the excellent social media skills possessed by today’s youth. And indeed, incorporation of social media proved to be a winning strategy. Medication adherence for hydroxychloroquine in the group randomized to social media participation jumped from 50% in the 3 months prior to starting the program to 92% in the first 3 months post completion, whereas medication adherence didn’t change significantly in the other study arm. The social media group also experienced significant improvements in self-efficacy, sense of community, acceptance of illness, optimism and control over the future, and other measures of empowerment. The control group did not show significant change in any of these domains (Pediatr Rheumatol Online J. 2018 Mar 14. doi: 10.1186/s12969-018-0232-2).
The TEACH study was sponsored by the National Institutes of Health. The web-based medication adherence program pilot study was supported by the Lupus Foundation of America. What the two approaches share in common is a conviction that, when it comes to addressing pain, fatigue, diminished quality of life, and poor medication adherence in young patients with SLE: “Our medication prescription alone doesn’t do it,” Dr. Brunner said.
She reported having no financial conflicts regarding her presentation.
REPORTING FROM LUPUS 2019
Here’s a top strategy for immunosuppressant discontinuation in SLE
SAN FRANCISCO – Long-term maintenance therapy with hydroxychloroquine initiated after patients with systemic lupus erythematosus (SLE) have discontinued immunosuppressant medication during remission greatly reduces their likelihood of disease flare, Margherita Zen, MD, reported at an international congress on systemic lupus erythematosus.
Dr. Zen, a rheumatologist at the University of Padova in Padua, Italy, presented a retrospective study of 319 SLE patients actively followed in the Padova Lupus Cohort. All of them were treated at some point with one or more immunosuppressants, most commonly mycophenolate, azathioprine, or methotrexate. Fifty-six percent of them never discontinued immunosuppressant therapy during long-term follow-up. Of the 139 patients who did, three-quarters of them were in remission at the time of discontinuation, while the remainder discontinued immunosuppressant medication because of intolerance or poor adherence.
The research question of greatest interest to Dr. Zen and her coinvestigators was whether withdrawal of immunosuppressant medication in lupus patients who have responded well and are in remission is a sound strategy or one fraught with an unacceptably high risk of flare.
“The benefits of drug tapering and discontinuation have been proven for glucocorticoids, but there is not enough evidence available for discontinuation of immunosuppressants,” she said.
The good news: 75% of patients who discontinued immunosuppressant therapy while in remission never experienced a flare during a mean 7.6 years of follow-up after discontinuation. And the median time to flare in those who did was 4.75 years. In contrast, more than two-thirds of patients who discontinued immunosuppressants while not in remission experienced an SLE flare, and the mean time to this event was a mere 8 months. In a Cox regression analysis, patients who discontinued their immunosuppressant medication because of intolerance or poor adherence were 6.9-fold more likely to flare during follow-up than were those who quit immunosuppressants while in remission.
Patients who’d been on methotrexate were significantly more likely to flare after discontinuing the drug than were those who’d been on other immunosuppressant medications. However, flare risk post immunosuppressants was unaffected by whether the medication was given for treatment of lupus nephritis, arthritis, neuropsychiatric involvement, vasculitis, hematologic manifestations of the disease, or skin involvement.
In a multivariate logistic regression analysis, by far the strongest independent protective factor against the occurrence of flare after immunosuppressant discontinuation was maintenance therapy with hydroxychloroquine; it was associated with a 76% reduction in flare risk. Put another way, patients not on maintenance antimalarial therapy after immunosuppressant discontinuation were at an adjusted 5.3-fold increased risk of flare. Combining hydroxychloroquine with low-dose prednisone didn’t provide any added benefit beyond the antimalarial alone in terms of protection against flares.
The other protective factor was duration of remission at the time of immunosuppressant discontinuation: the longer, the better. Patients who experienced a lupus flare had been in remission for an average of 28 months when they stopped taking their immunosuppressant medication. Those who remained flare free throughout follow-up had been in remission for an average of 46 months at discontinuation.
Reassuringly, median damage accrual as assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was similar in patients regardless of whether or not they discontinued immunosuppressant therapy.
Dr. Zen reported having no financial conflicts regarding this study, conducted free of commercial support.
SAN FRANCISCO – Long-term maintenance therapy with hydroxychloroquine initiated after patients with systemic lupus erythematosus (SLE) have discontinued immunosuppressant medication during remission greatly reduces their likelihood of disease flare, Margherita Zen, MD, reported at an international congress on systemic lupus erythematosus.
Dr. Zen, a rheumatologist at the University of Padova in Padua, Italy, presented a retrospective study of 319 SLE patients actively followed in the Padova Lupus Cohort. All of them were treated at some point with one or more immunosuppressants, most commonly mycophenolate, azathioprine, or methotrexate. Fifty-six percent of them never discontinued immunosuppressant therapy during long-term follow-up. Of the 139 patients who did, three-quarters of them were in remission at the time of discontinuation, while the remainder discontinued immunosuppressant medication because of intolerance or poor adherence.
The research question of greatest interest to Dr. Zen and her coinvestigators was whether withdrawal of immunosuppressant medication in lupus patients who have responded well and are in remission is a sound strategy or one fraught with an unacceptably high risk of flare.
“The benefits of drug tapering and discontinuation have been proven for glucocorticoids, but there is not enough evidence available for discontinuation of immunosuppressants,” she said.
The good news: 75% of patients who discontinued immunosuppressant therapy while in remission never experienced a flare during a mean 7.6 years of follow-up after discontinuation. And the median time to flare in those who did was 4.75 years. In contrast, more than two-thirds of patients who discontinued immunosuppressants while not in remission experienced an SLE flare, and the mean time to this event was a mere 8 months. In a Cox regression analysis, patients who discontinued their immunosuppressant medication because of intolerance or poor adherence were 6.9-fold more likely to flare during follow-up than were those who quit immunosuppressants while in remission.
Patients who’d been on methotrexate were significantly more likely to flare after discontinuing the drug than were those who’d been on other immunosuppressant medications. However, flare risk post immunosuppressants was unaffected by whether the medication was given for treatment of lupus nephritis, arthritis, neuropsychiatric involvement, vasculitis, hematologic manifestations of the disease, or skin involvement.
In a multivariate logistic regression analysis, by far the strongest independent protective factor against the occurrence of flare after immunosuppressant discontinuation was maintenance therapy with hydroxychloroquine; it was associated with a 76% reduction in flare risk. Put another way, patients not on maintenance antimalarial therapy after immunosuppressant discontinuation were at an adjusted 5.3-fold increased risk of flare. Combining hydroxychloroquine with low-dose prednisone didn’t provide any added benefit beyond the antimalarial alone in terms of protection against flares.
The other protective factor was duration of remission at the time of immunosuppressant discontinuation: the longer, the better. Patients who experienced a lupus flare had been in remission for an average of 28 months when they stopped taking their immunosuppressant medication. Those who remained flare free throughout follow-up had been in remission for an average of 46 months at discontinuation.
Reassuringly, median damage accrual as assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was similar in patients regardless of whether or not they discontinued immunosuppressant therapy.
Dr. Zen reported having no financial conflicts regarding this study, conducted free of commercial support.
SAN FRANCISCO – Long-term maintenance therapy with hydroxychloroquine initiated after patients with systemic lupus erythematosus (SLE) have discontinued immunosuppressant medication during remission greatly reduces their likelihood of disease flare, Margherita Zen, MD, reported at an international congress on systemic lupus erythematosus.
Dr. Zen, a rheumatologist at the University of Padova in Padua, Italy, presented a retrospective study of 319 SLE patients actively followed in the Padova Lupus Cohort. All of them were treated at some point with one or more immunosuppressants, most commonly mycophenolate, azathioprine, or methotrexate. Fifty-six percent of them never discontinued immunosuppressant therapy during long-term follow-up. Of the 139 patients who did, three-quarters of them were in remission at the time of discontinuation, while the remainder discontinued immunosuppressant medication because of intolerance or poor adherence.
The research question of greatest interest to Dr. Zen and her coinvestigators was whether withdrawal of immunosuppressant medication in lupus patients who have responded well and are in remission is a sound strategy or one fraught with an unacceptably high risk of flare.
“The benefits of drug tapering and discontinuation have been proven for glucocorticoids, but there is not enough evidence available for discontinuation of immunosuppressants,” she said.
The good news: 75% of patients who discontinued immunosuppressant therapy while in remission never experienced a flare during a mean 7.6 years of follow-up after discontinuation. And the median time to flare in those who did was 4.75 years. In contrast, more than two-thirds of patients who discontinued immunosuppressants while not in remission experienced an SLE flare, and the mean time to this event was a mere 8 months. In a Cox regression analysis, patients who discontinued their immunosuppressant medication because of intolerance or poor adherence were 6.9-fold more likely to flare during follow-up than were those who quit immunosuppressants while in remission.
Patients who’d been on methotrexate were significantly more likely to flare after discontinuing the drug than were those who’d been on other immunosuppressant medications. However, flare risk post immunosuppressants was unaffected by whether the medication was given for treatment of lupus nephritis, arthritis, neuropsychiatric involvement, vasculitis, hematologic manifestations of the disease, or skin involvement.
In a multivariate logistic regression analysis, by far the strongest independent protective factor against the occurrence of flare after immunosuppressant discontinuation was maintenance therapy with hydroxychloroquine; it was associated with a 76% reduction in flare risk. Put another way, patients not on maintenance antimalarial therapy after immunosuppressant discontinuation were at an adjusted 5.3-fold increased risk of flare. Combining hydroxychloroquine with low-dose prednisone didn’t provide any added benefit beyond the antimalarial alone in terms of protection against flares.
The other protective factor was duration of remission at the time of immunosuppressant discontinuation: the longer, the better. Patients who experienced a lupus flare had been in remission for an average of 28 months when they stopped taking their immunosuppressant medication. Those who remained flare free throughout follow-up had been in remission for an average of 46 months at discontinuation.
Reassuringly, median damage accrual as assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was similar in patients regardless of whether or not they discontinued immunosuppressant therapy.
Dr. Zen reported having no financial conflicts regarding this study, conducted free of commercial support.
REPORTING FROM LUPUS 2019
ACE inhibitors may improve neuropsychiatric lupus
SAN FRANCISCO – The announcement of a first-ever multicenter randomized trial of ACE inhibitors for the treatment of cognitive impairment in systemic lupus erythematosus patients generated some of the biggest buzz at LUPUS 2019.
“The time has come to implement clinical trials in lupus to see if we can address what is one of the most distressing aspects of the disease to patients,” Betty Diamond, MD, said in announcing the planned trial at an international congress on systemic lupus erythematosus (SLE).
Neuropsychiatric lupus, characterized most often by cognitive impairment, affects 40%-90% of SLE patients, according to various epidemiologic studies. This confusion and memory loss has been shown to be independent of systemic disease activity.
“Cognitive impairment is a very common problem and a very insidious problem in lupus patients,” emphasized Dr. Diamond, professor and head of the Center for Autoimmune Musculoskeletal and Hematopoietic Diseases at the Feinstein Institute for Medical Research in Manhasset, New York.
Dr. Diamond was the recipient of the 2018 Lupus Insight Prize awarded by the Lupus Research Alliance, which is funding the multicenter randomized trial. For the study, roughly 70 SLE patients with cognitive impairment not associated with a focal brain lesion will be randomized to receive a centrally acting ACE inhibitor – captopril was the one she and her coinvestigators have used in their mouse model and preliminary clinical studies – or to a non–centrally acting ACE inhibitor, such as enalapril.
“The clinical trial compares an ACE inhibitor that crosses the blood-brain barrier with one that doesn’t. They both have the same renal protection and systemic anti-inflammatory effects,” explained Dr. Diamond, who is also professor of molecular medicine and of medicine at the Zucker School of Medicine at Hofstra/Northwell, East Garden City, N.Y.
In a recent publication (J Exp Med. 2018 Oct 1;215[10]:2554-66), Dr. Diamond and her coinvestigators presented much of the background work that underpins the upcoming randomized trial. Sixteen years ago, they discovered two anti-DNA antibodies that cross-react with the N-methyl-D-aspartate receptor (NMDAR) and enhance NMDAR signaling. They showed that while the NMDARs are critical in learning and memory, their prolonged stimulation results in a high degree of calcium influx, causing neuronal death. These anti-DNA/anti-NMDAR antibodies, known as DNRAbs, are present at elevated titers in 30%-40% of SLE patients, and in a higher proportion of those with neuropsychiatric lupus.
“Most importantly, DNRAbs are present in the cerebrospinal fluid of patients who have nonfocal CNS manifestations of lupus,” Dr. Diamond said.
She and her coworkers developed a mouse model of cognitive impairment in lupus and utilized it to identify a two-stage model of the pathogenesis of DNRAb-mediated neuropsychiatric lupus. First, a traumatic event such as an infection causes a temporary opening in the blood-brain barrier, allowing the DNRAbs to reach the brain. This results in acute excitotoxic neuronal death. This is followed by a second stage, which entails activation of microglia – known as the macrophages of the CNS – with resultant loss of neuronal dendritic arborization and complexity. In the mouse model, this causes a selective impairment in spatial memory that corresponds well to the spatial memory deficit the investigators documented in DNRAb-positive SLE patients, compared with healthy controls and DNRAb-negative lupus patients.
A key finding in this project, Dr. Diamond continued, was that activated microglia turn out to be critical for dendritic loss. If the microglia are deactivated, regrowth of the dendritic processes occurs. This raises a possibility that attendees at LUPUS 2019 found thrilling: Perhaps the cognitive impairment of neuropsychiatric SLE can be prevented and even reversed by suppressing microglial activation.
Promising work in the field of Alzheimer’s disease suggests that centrally acting ACE inhibitors can indeed suppress microglial activation and actually improve cognition. Dr. Diamond and her colleagues showed this also was the case in their mouse model. Moreover, in a small clinical study they used PET brain imaging to show that captopril reduced the increased glucose uptake and hippocampal hypermetabolism associated with DNRAb-positive neuropsychiatric lupus, an effect maintained through 18 months of follow-up.
“We think DNRAbs contribute to cognitive impairment in SLE patients, but we certainly wouldn’t say that antibodies are the only mechanism. Other investigators have shown that interferon can also do this, and that, like the antibodies, interferon acts through microglial activation. We think that this microglial activation is going to be a general paradigm in cognitive impairment in lupus and in other diseases, so microglia are a very good therapeutic target,” Dr. Diamond said.
The primary outcomes in the forthcoming randomized trial involve PET neuronal imaging. They investigators are hoping to see reduced hippocampal hypermetabolism and suppression of activated microglial cells.
“We’ll see if we’re actually hitting our target. We’re doing neuropsychologic testing, too, but we’re really concentrating on imaging outcomes, because those are objective and have many fewer variables to confound them,” according to Dr. Diamond.
Microglial activation is a current topic of intense research interest within the pharmaceutical industry, she added. If the imaging study is positive, she anticipates drug companies will quickly ramp up and conduct large clinical trials powered to show significant results in terms of neuropsychologic test scores and clinical outcomes.
Dr. Diamond reported having no financial conflicts regarding her work, which has been supported largely by the National Institutes of Health.
SAN FRANCISCO – The announcement of a first-ever multicenter randomized trial of ACE inhibitors for the treatment of cognitive impairment in systemic lupus erythematosus patients generated some of the biggest buzz at LUPUS 2019.
“The time has come to implement clinical trials in lupus to see if we can address what is one of the most distressing aspects of the disease to patients,” Betty Diamond, MD, said in announcing the planned trial at an international congress on systemic lupus erythematosus (SLE).
Neuropsychiatric lupus, characterized most often by cognitive impairment, affects 40%-90% of SLE patients, according to various epidemiologic studies. This confusion and memory loss has been shown to be independent of systemic disease activity.
“Cognitive impairment is a very common problem and a very insidious problem in lupus patients,” emphasized Dr. Diamond, professor and head of the Center for Autoimmune Musculoskeletal and Hematopoietic Diseases at the Feinstein Institute for Medical Research in Manhasset, New York.
Dr. Diamond was the recipient of the 2018 Lupus Insight Prize awarded by the Lupus Research Alliance, which is funding the multicenter randomized trial. For the study, roughly 70 SLE patients with cognitive impairment not associated with a focal brain lesion will be randomized to receive a centrally acting ACE inhibitor – captopril was the one she and her coinvestigators have used in their mouse model and preliminary clinical studies – or to a non–centrally acting ACE inhibitor, such as enalapril.
“The clinical trial compares an ACE inhibitor that crosses the blood-brain barrier with one that doesn’t. They both have the same renal protection and systemic anti-inflammatory effects,” explained Dr. Diamond, who is also professor of molecular medicine and of medicine at the Zucker School of Medicine at Hofstra/Northwell, East Garden City, N.Y.
In a recent publication (J Exp Med. 2018 Oct 1;215[10]:2554-66), Dr. Diamond and her coinvestigators presented much of the background work that underpins the upcoming randomized trial. Sixteen years ago, they discovered two anti-DNA antibodies that cross-react with the N-methyl-D-aspartate receptor (NMDAR) and enhance NMDAR signaling. They showed that while the NMDARs are critical in learning and memory, their prolonged stimulation results in a high degree of calcium influx, causing neuronal death. These anti-DNA/anti-NMDAR antibodies, known as DNRAbs, are present at elevated titers in 30%-40% of SLE patients, and in a higher proportion of those with neuropsychiatric lupus.
“Most importantly, DNRAbs are present in the cerebrospinal fluid of patients who have nonfocal CNS manifestations of lupus,” Dr. Diamond said.
She and her coworkers developed a mouse model of cognitive impairment in lupus and utilized it to identify a two-stage model of the pathogenesis of DNRAb-mediated neuropsychiatric lupus. First, a traumatic event such as an infection causes a temporary opening in the blood-brain barrier, allowing the DNRAbs to reach the brain. This results in acute excitotoxic neuronal death. This is followed by a second stage, which entails activation of microglia – known as the macrophages of the CNS – with resultant loss of neuronal dendritic arborization and complexity. In the mouse model, this causes a selective impairment in spatial memory that corresponds well to the spatial memory deficit the investigators documented in DNRAb-positive SLE patients, compared with healthy controls and DNRAb-negative lupus patients.
A key finding in this project, Dr. Diamond continued, was that activated microglia turn out to be critical for dendritic loss. If the microglia are deactivated, regrowth of the dendritic processes occurs. This raises a possibility that attendees at LUPUS 2019 found thrilling: Perhaps the cognitive impairment of neuropsychiatric SLE can be prevented and even reversed by suppressing microglial activation.
Promising work in the field of Alzheimer’s disease suggests that centrally acting ACE inhibitors can indeed suppress microglial activation and actually improve cognition. Dr. Diamond and her colleagues showed this also was the case in their mouse model. Moreover, in a small clinical study they used PET brain imaging to show that captopril reduced the increased glucose uptake and hippocampal hypermetabolism associated with DNRAb-positive neuropsychiatric lupus, an effect maintained through 18 months of follow-up.
“We think DNRAbs contribute to cognitive impairment in SLE patients, but we certainly wouldn’t say that antibodies are the only mechanism. Other investigators have shown that interferon can also do this, and that, like the antibodies, interferon acts through microglial activation. We think that this microglial activation is going to be a general paradigm in cognitive impairment in lupus and in other diseases, so microglia are a very good therapeutic target,” Dr. Diamond said.
The primary outcomes in the forthcoming randomized trial involve PET neuronal imaging. They investigators are hoping to see reduced hippocampal hypermetabolism and suppression of activated microglial cells.
“We’ll see if we’re actually hitting our target. We’re doing neuropsychologic testing, too, but we’re really concentrating on imaging outcomes, because those are objective and have many fewer variables to confound them,” according to Dr. Diamond.
Microglial activation is a current topic of intense research interest within the pharmaceutical industry, she added. If the imaging study is positive, she anticipates drug companies will quickly ramp up and conduct large clinical trials powered to show significant results in terms of neuropsychologic test scores and clinical outcomes.
Dr. Diamond reported having no financial conflicts regarding her work, which has been supported largely by the National Institutes of Health.
SAN FRANCISCO – The announcement of a first-ever multicenter randomized trial of ACE inhibitors for the treatment of cognitive impairment in systemic lupus erythematosus patients generated some of the biggest buzz at LUPUS 2019.
“The time has come to implement clinical trials in lupus to see if we can address what is one of the most distressing aspects of the disease to patients,” Betty Diamond, MD, said in announcing the planned trial at an international congress on systemic lupus erythematosus (SLE).
Neuropsychiatric lupus, characterized most often by cognitive impairment, affects 40%-90% of SLE patients, according to various epidemiologic studies. This confusion and memory loss has been shown to be independent of systemic disease activity.
“Cognitive impairment is a very common problem and a very insidious problem in lupus patients,” emphasized Dr. Diamond, professor and head of the Center for Autoimmune Musculoskeletal and Hematopoietic Diseases at the Feinstein Institute for Medical Research in Manhasset, New York.
Dr. Diamond was the recipient of the 2018 Lupus Insight Prize awarded by the Lupus Research Alliance, which is funding the multicenter randomized trial. For the study, roughly 70 SLE patients with cognitive impairment not associated with a focal brain lesion will be randomized to receive a centrally acting ACE inhibitor – captopril was the one she and her coinvestigators have used in their mouse model and preliminary clinical studies – or to a non–centrally acting ACE inhibitor, such as enalapril.
“The clinical trial compares an ACE inhibitor that crosses the blood-brain barrier with one that doesn’t. They both have the same renal protection and systemic anti-inflammatory effects,” explained Dr. Diamond, who is also professor of molecular medicine and of medicine at the Zucker School of Medicine at Hofstra/Northwell, East Garden City, N.Y.
In a recent publication (J Exp Med. 2018 Oct 1;215[10]:2554-66), Dr. Diamond and her coinvestigators presented much of the background work that underpins the upcoming randomized trial. Sixteen years ago, they discovered two anti-DNA antibodies that cross-react with the N-methyl-D-aspartate receptor (NMDAR) and enhance NMDAR signaling. They showed that while the NMDARs are critical in learning and memory, their prolonged stimulation results in a high degree of calcium influx, causing neuronal death. These anti-DNA/anti-NMDAR antibodies, known as DNRAbs, are present at elevated titers in 30%-40% of SLE patients, and in a higher proportion of those with neuropsychiatric lupus.
“Most importantly, DNRAbs are present in the cerebrospinal fluid of patients who have nonfocal CNS manifestations of lupus,” Dr. Diamond said.
She and her coworkers developed a mouse model of cognitive impairment in lupus and utilized it to identify a two-stage model of the pathogenesis of DNRAb-mediated neuropsychiatric lupus. First, a traumatic event such as an infection causes a temporary opening in the blood-brain barrier, allowing the DNRAbs to reach the brain. This results in acute excitotoxic neuronal death. This is followed by a second stage, which entails activation of microglia – known as the macrophages of the CNS – with resultant loss of neuronal dendritic arborization and complexity. In the mouse model, this causes a selective impairment in spatial memory that corresponds well to the spatial memory deficit the investigators documented in DNRAb-positive SLE patients, compared with healthy controls and DNRAb-negative lupus patients.
A key finding in this project, Dr. Diamond continued, was that activated microglia turn out to be critical for dendritic loss. If the microglia are deactivated, regrowth of the dendritic processes occurs. This raises a possibility that attendees at LUPUS 2019 found thrilling: Perhaps the cognitive impairment of neuropsychiatric SLE can be prevented and even reversed by suppressing microglial activation.
Promising work in the field of Alzheimer’s disease suggests that centrally acting ACE inhibitors can indeed suppress microglial activation and actually improve cognition. Dr. Diamond and her colleagues showed this also was the case in their mouse model. Moreover, in a small clinical study they used PET brain imaging to show that captopril reduced the increased glucose uptake and hippocampal hypermetabolism associated with DNRAb-positive neuropsychiatric lupus, an effect maintained through 18 months of follow-up.
“We think DNRAbs contribute to cognitive impairment in SLE patients, but we certainly wouldn’t say that antibodies are the only mechanism. Other investigators have shown that interferon can also do this, and that, like the antibodies, interferon acts through microglial activation. We think that this microglial activation is going to be a general paradigm in cognitive impairment in lupus and in other diseases, so microglia are a very good therapeutic target,” Dr. Diamond said.
The primary outcomes in the forthcoming randomized trial involve PET neuronal imaging. They investigators are hoping to see reduced hippocampal hypermetabolism and suppression of activated microglial cells.
“We’ll see if we’re actually hitting our target. We’re doing neuropsychologic testing, too, but we’re really concentrating on imaging outcomes, because those are objective and have many fewer variables to confound them,” according to Dr. Diamond.
Microglial activation is a current topic of intense research interest within the pharmaceutical industry, she added. If the imaging study is positive, she anticipates drug companies will quickly ramp up and conduct large clinical trials powered to show significant results in terms of neuropsychologic test scores and clinical outcomes.
Dr. Diamond reported having no financial conflicts regarding her work, which has been supported largely by the National Institutes of Health.
REPORTING FROM LUPUS 2019
Key clinical point: ACE inhibitor therapy may prevent and/or improve neuropsychiatric lupus.
Major finding: The first-ever multicenter randomized trial of ACE inhibitor therapy for neuropsychiatric SLE will soon get underway.
Study details: The planned – and funded – trial will include roughly 70 patients with neuropsychiatric lupus.
Disclosures: The presenter reported having no financial conflicts regarding her work, which has been supported largely by the National Institutes of Health.
Atmospheric fluctuations tied to lupus flares
SAN FRANCISCO – , according to investigators from Johns Hopkins University, Baltimore.
The work helps solve a longstanding mystery in systemic lupus erythematosus (SLE): why symptoms seem to come and go with the seasons.
Johns Hopkins University research previously has shown that renal flares are more common in the winter; double-stranded DNA antibodies more common in late fall; and rashes more likely in late spring.
However, “the exact reasons of why the seasonality was there remained a big question,” said lead investigator George Stojan, MD, an assistant professor of rheumatology and the codirector of the Hopkins Lupus Center.
To get a handle on the matter, Dr. Stojan and his team reviewed 1,628 patients treated at the university during 1999-2017. Using Environmental Protection Agency data, they examined atmospheric conditions within 350 km of Baltimore in the 10 days leading up to lupus visits for flares; the researchers adjusted for age, sex, income, ethnicity, rural versus urban residence, and how close patients lived to highways and airports.
“We [found] specific, strong associations between atmospheric variables and fine particulate matter concentrations ... and organ-specific lupus flares,” Dr. Stojan said. He explained why that matters in a video interview at an international congress on SLE.
In short, rash was directly associated with concentrations of ozone and inhalable, fine particulate matter less than 2.5 mcm in diameter (PM 2.5). Joint flares were associated with PM 2.5, ozone, resultant wind, and humidity.
Renal flares were inversely associated with temperature, and directly associated with wind and humidity. Pulmonary flares and serositis were associated with PM 2.5, and both hematologic and neurologic flares with wind and temperature.
The analysis was based on a per-unit basis. For example, each mcg/m3 increase in PM 2.5 increased the odds of a pulmonary flare about 4% (odds ratio, 1.042, P = .026). The other findings were mostly of smaller magnitude, but still statistically significant.
The National Institutes of Health funded the research. Dr. Stojan had no disclosures.
SOURCE: Stojan G et al. LUPUS 2019, Abstract M31.
SAN FRANCISCO – , according to investigators from Johns Hopkins University, Baltimore.
The work helps solve a longstanding mystery in systemic lupus erythematosus (SLE): why symptoms seem to come and go with the seasons.
Johns Hopkins University research previously has shown that renal flares are more common in the winter; double-stranded DNA antibodies more common in late fall; and rashes more likely in late spring.
However, “the exact reasons of why the seasonality was there remained a big question,” said lead investigator George Stojan, MD, an assistant professor of rheumatology and the codirector of the Hopkins Lupus Center.
To get a handle on the matter, Dr. Stojan and his team reviewed 1,628 patients treated at the university during 1999-2017. Using Environmental Protection Agency data, they examined atmospheric conditions within 350 km of Baltimore in the 10 days leading up to lupus visits for flares; the researchers adjusted for age, sex, income, ethnicity, rural versus urban residence, and how close patients lived to highways and airports.
“We [found] specific, strong associations between atmospheric variables and fine particulate matter concentrations ... and organ-specific lupus flares,” Dr. Stojan said. He explained why that matters in a video interview at an international congress on SLE.
In short, rash was directly associated with concentrations of ozone and inhalable, fine particulate matter less than 2.5 mcm in diameter (PM 2.5). Joint flares were associated with PM 2.5, ozone, resultant wind, and humidity.
Renal flares were inversely associated with temperature, and directly associated with wind and humidity. Pulmonary flares and serositis were associated with PM 2.5, and both hematologic and neurologic flares with wind and temperature.
The analysis was based on a per-unit basis. For example, each mcg/m3 increase in PM 2.5 increased the odds of a pulmonary flare about 4% (odds ratio, 1.042, P = .026). The other findings were mostly of smaller magnitude, but still statistically significant.
The National Institutes of Health funded the research. Dr. Stojan had no disclosures.
SOURCE: Stojan G et al. LUPUS 2019, Abstract M31.
SAN FRANCISCO – , according to investigators from Johns Hopkins University, Baltimore.
The work helps solve a longstanding mystery in systemic lupus erythematosus (SLE): why symptoms seem to come and go with the seasons.
Johns Hopkins University research previously has shown that renal flares are more common in the winter; double-stranded DNA antibodies more common in late fall; and rashes more likely in late spring.
However, “the exact reasons of why the seasonality was there remained a big question,” said lead investigator George Stojan, MD, an assistant professor of rheumatology and the codirector of the Hopkins Lupus Center.
To get a handle on the matter, Dr. Stojan and his team reviewed 1,628 patients treated at the university during 1999-2017. Using Environmental Protection Agency data, they examined atmospheric conditions within 350 km of Baltimore in the 10 days leading up to lupus visits for flares; the researchers adjusted for age, sex, income, ethnicity, rural versus urban residence, and how close patients lived to highways and airports.
“We [found] specific, strong associations between atmospheric variables and fine particulate matter concentrations ... and organ-specific lupus flares,” Dr. Stojan said. He explained why that matters in a video interview at an international congress on SLE.
In short, rash was directly associated with concentrations of ozone and inhalable, fine particulate matter less than 2.5 mcm in diameter (PM 2.5). Joint flares were associated with PM 2.5, ozone, resultant wind, and humidity.
Renal flares were inversely associated with temperature, and directly associated with wind and humidity. Pulmonary flares and serositis were associated with PM 2.5, and both hematologic and neurologic flares with wind and temperature.
The analysis was based on a per-unit basis. For example, each mcg/m3 increase in PM 2.5 increased the odds of a pulmonary flare about 4% (odds ratio, 1.042, P = .026). The other findings were mostly of smaller magnitude, but still statistically significant.
The National Institutes of Health funded the research. Dr. Stojan had no disclosures.
SOURCE: Stojan G et al. LUPUS 2019, Abstract M31.
REPORTING FROM LUPUS 2019
Expert gives tips on timing, managing lupus pregnancies
SAN FRANCISCO – Not that many years ago, women with systemic lupus erythematosus were told not to get pregnant. It was just one more lupus heartbreak.
Times have changed, according to Lisa Sammaritano, MD, a lupus specialist and associate professor of clinical medicine at Weill Cornell Medical College, New York.
While lupus certainly complicates pregnancy, it by no means rules it out these days. With careful management, the dream of motherhood can become a reality for many women. Dr. Sammaritano shared her insights about timing and treatment at an international congress on systemic lupus erythematosus.
It’s important that the disease is under control as much as possible; that means that timing – and contraception – are key. Antiphospholipid antibodies, common in lupus, complicate matters, but there are workarounds, she said.
SAN FRANCISCO – Not that many years ago, women with systemic lupus erythematosus were told not to get pregnant. It was just one more lupus heartbreak.
Times have changed, according to Lisa Sammaritano, MD, a lupus specialist and associate professor of clinical medicine at Weill Cornell Medical College, New York.
While lupus certainly complicates pregnancy, it by no means rules it out these days. With careful management, the dream of motherhood can become a reality for many women. Dr. Sammaritano shared her insights about timing and treatment at an international congress on systemic lupus erythematosus.
It’s important that the disease is under control as much as possible; that means that timing – and contraception – are key. Antiphospholipid antibodies, common in lupus, complicate matters, but there are workarounds, she said.
SAN FRANCISCO – Not that many years ago, women with systemic lupus erythematosus were told not to get pregnant. It was just one more lupus heartbreak.
Times have changed, according to Lisa Sammaritano, MD, a lupus specialist and associate professor of clinical medicine at Weill Cornell Medical College, New York.
While lupus certainly complicates pregnancy, it by no means rules it out these days. With careful management, the dream of motherhood can become a reality for many women. Dr. Sammaritano shared her insights about timing and treatment at an international congress on systemic lupus erythematosus.
It’s important that the disease is under control as much as possible; that means that timing – and contraception – are key. Antiphospholipid antibodies, common in lupus, complicate matters, but there are workarounds, she said.
AT LUPUS 2019
ECHO Rheum widens rheumatology best practice care
according to the results of a qualitative and quantitative study.
Over a 9-year period, ECHO (Extension for Community Healthcare Outcomes) Rheum educated 2,230 primary care clinicians, the majority of whom were physicians (53%) or nurse practitioners (22%), and helped increase the clinicians’ confidence in managing rheumatic conditions locally while still having access to specialist guidance.
Participants in ECHO Rheum accrued a total of 1,958 CME credits between them, and 21 of 30 (70%) clinicians who participated in 2-day miniresidencies obtained online certification from the American College of Rheumatology.
“ECHO Rheum and programs like it have the potential to positively impact the national shortage of rheumatologic care for underserved patients,” Arthur Bankhurst, MD, and his associates from the University of New Mexico, Albuquerque wrote in Arthritis Care & Research. “Empowering the health care workforce by disseminating knowledge of best practice diagnosis and treatment has the potential to reduce suboptimal rheumatologic care and expand access for those suffering from rheumatologic conditions regardless of economic status or location.”
ECHO Rheum is part of the larger Project ECHO (Extension for Community Healthcare Outcomes), a program developed at UNM by gastroenterologist Sanjeev Arora, MD. Dr. Arora came up with the idea for the ECHO model in 2003 to try to improve access to best practice care for patients with hepatitis C. The potential of the model to translate across medical specialties was soon seen, however, and today, there are more than 40 teleECHO programs operating in New Mexico that also involve more than 400 community clinic sites. The ECHO model is also being used nationally, operating in more than 30 states, and globally in 31 countries.
According to information available via the Project ECHO website, “the ECHO model is not traditional ‘telemedicine’ where the specialist assumes care of the patient, but is instead telementoring, a guided practice model where the participating clinician retains responsibility for managing the patient.” The aim is to use medical education and care management to empower “clinicians everywhere to provide better care to more people, right where they live.”
The rheumatology arm of Project ECHO started in 2006 and follows the four main principles of the ECHO model: Using technology to leverage scarce resources, such as by facilitating regular educational sessions between central expert “hubs” at specialist centers and “spokes” at community practices; sharing best practice information to help reduce disparities in the quality of care; presenting and discussion around case histories; and evaluating and monitoring outcomes.
To demonstrate the effectiveness of ECHO Rheum, the team at UNM evaluated data on participants who had attended weekly teleconferencing sessions, lectures, grand rounds, and miniresidency training between June 2006 and June 2014.
The results demonstrated that “participation in ECHO Rheum provides clinicians in underresourced areas access to best practice knowledge and training in rheumatology,” Dr. Bankhurst and his coauthors observed.
Increased knowledge and confidence in managing rheumatic conditions among primary care physicians could help to reduce the ever-widening gap between the demand and supply of appropriate care. Indeed, while the projected population of adults with rheumatic disease is expected to grow to almost 67 million adults in the next 20 years, there is expected to be a shortfall of 4,700 full-time rheumatologists by 2030.
“Regular participation in teleECHO sessions creates a community of practice among rural clinicians,” the UNM team stated. Every week, participants were invited to attend a 90-minute virtual teleconference, either by video or telephone, that consisted of a brief evidence-based lecture by a subject matter expert and presentation of deidentified case histories submitted by the participants. Participants were able to obtain CME credits at no cost and learn how to use ACR-recommended disease activity measures, such as the Disease Activity Score in 28 joints.
Over the 9-year study period, 1,173 cases were presented, the majority of which (85%) reflected the three most common diagnoses seen in rheumatologic practice, namely RA (n = 715), fibromyalgia (n = 241), and systemic lupus erythematosus (n = 54). As might be expected, female cases were presented more often than male cases, as were cases involving patients aged 40-60 years, compared with other age groups.
“ECHO Rheum saw an increase in participation in 2010, when the ACR certification was offered at no cost, suggesting that ACR certification was an incentive for participation,” Dr. Bankhurst and his team observed.
In 2012, however, there was a drop-off in participation, which may have been caused by the end of funding for ACR certification or clinicians becoming “more confident in their abilities to diagnose and initiate treatment appropriately.” Clinical responsibilities may also have prevented clinicians from attending the weekly sessions.
“Although our formal collaboration with the ACR concluded when funds for this initiative came to an end, ECHO Rheum encourages clinicians to obtain certification in rheumatology and provides them with information about opportunities to offset the cost,” Dr. Bankhurst and his colleagues wrote.
Despite a decline in attendance at the weekly teleECHO sessions during the evaluation period, the UNM team believes that its continued use holds value for primary care practice. Since 2014, a further four clinicians have obtained ACR grant funding for certification and a number of the certified participants return to contribute to the weekly teleECHO sessions.
“This continued use of ECHO Rheum as a readily available resource for case presentations and acquisition of new learning about developments in treatment and medication demonstrates the long-term viability of the community of practice created by the program,” the team suggested.
“I think programs like this are going to be very important in addressing the physician shortage in rheumatology,” said Chad Deal, MD, in an interview.
Dr. Deal, who was not involved in the study, noted that such programs may work particularly well in underserved areas such as New Mexico, as shown in this study, as well as other states, such as in Alaska, North Dakota, and South Dakota. Essentially, “places where people are having to drive forever to get to a rheumatologist.”
“I like what they’ve done,” Dr. Deal said. It can make clinicians “feel much more comfortable with diagnosing and even treating inflammatory arthritis. I think that’s really important.”
It would be difficult to have harder outcomes measures, observed Dr. Deal, head of the Center for Osteoporosis and Metabolic Bone Disease and vice chair for quality and outcomes in the department of rheumatology at the Cleveland Clinic. “The goal is obviously early diagnosis and treatment of rheumatoid arthritis, let’s say, and improved outcomes, and that’s really difficult to show in any kind of program like this.”
Dr. Deal added that “maintaining any kind of program like this is difficult; physicians get busy, and like the authors note, sometimes clinicians get to a point where they are comfortable, and they don’t need it as much.”
Perhaps, these programs don’t need to run forever, he suggested. Perhaps a 1- or 2-year program may be sufficient for one group before moving on to focus on a different group of physicians.
Dr. Bankhurst and other authors of the study reported having no conflicts of interest. The work was funded by the Robert Wood Johnson Foundation, the New Mexico legislature, and the New Mexico Department of Health. Dr. Deal reported no conflicts of interest in relation to his comments.
SOURCE: Bankhurst A et al. Arthritis Care Res. 2019 Mar 30. doi: 10.1002/acr.23889.
Although there is controversy regarding a potential physician shortage in the United States, the incontrovertible fact that the number of rheumatologists is declining and the daily experience of difficulty and delay in access to rheumatologists would argue that there surely is a problem. Moreover, the variability in distribution has resulted in many smaller regions of the country having no or few practicing adult rheumatologists. While addressing rheumatologist physician shortage and distribution may be important avenues to pursue, there are many barriers to overcoming the evident lack of access. Thus, changes in the delivery of rheumatologic care are urgently needed, and increasing our ability to use primary care physicians and midlevel practitioners is one immediate avenue to address this problem.
What remains to be done, as the authors themselves note, is measurement of patient and population-level outcomes. It is clear that the demand for rheumatologic services will continue to grow, and disparities in the regional distribution of rheumatologists in the United States will exacerbate the growing limits to access. The use of the ECHO model in this study to facilitate primary care practitioners and other providers in the management of common musculoskeletal conditions, especially in underserved areas, clearly deserves further study.
Calvin R. Brown Jr., MD, is a professor of medicine in the division of rheumatology at Northwestern University, Chicago. He is the director of the rheumatology training program there.
Although there is controversy regarding a potential physician shortage in the United States, the incontrovertible fact that the number of rheumatologists is declining and the daily experience of difficulty and delay in access to rheumatologists would argue that there surely is a problem. Moreover, the variability in distribution has resulted in many smaller regions of the country having no or few practicing adult rheumatologists. While addressing rheumatologist physician shortage and distribution may be important avenues to pursue, there are many barriers to overcoming the evident lack of access. Thus, changes in the delivery of rheumatologic care are urgently needed, and increasing our ability to use primary care physicians and midlevel practitioners is one immediate avenue to address this problem.
What remains to be done, as the authors themselves note, is measurement of patient and population-level outcomes. It is clear that the demand for rheumatologic services will continue to grow, and disparities in the regional distribution of rheumatologists in the United States will exacerbate the growing limits to access. The use of the ECHO model in this study to facilitate primary care practitioners and other providers in the management of common musculoskeletal conditions, especially in underserved areas, clearly deserves further study.
Calvin R. Brown Jr., MD, is a professor of medicine in the division of rheumatology at Northwestern University, Chicago. He is the director of the rheumatology training program there.
Although there is controversy regarding a potential physician shortage in the United States, the incontrovertible fact that the number of rheumatologists is declining and the daily experience of difficulty and delay in access to rheumatologists would argue that there surely is a problem. Moreover, the variability in distribution has resulted in many smaller regions of the country having no or few practicing adult rheumatologists. While addressing rheumatologist physician shortage and distribution may be important avenues to pursue, there are many barriers to overcoming the evident lack of access. Thus, changes in the delivery of rheumatologic care are urgently needed, and increasing our ability to use primary care physicians and midlevel practitioners is one immediate avenue to address this problem.
What remains to be done, as the authors themselves note, is measurement of patient and population-level outcomes. It is clear that the demand for rheumatologic services will continue to grow, and disparities in the regional distribution of rheumatologists in the United States will exacerbate the growing limits to access. The use of the ECHO model in this study to facilitate primary care practitioners and other providers in the management of common musculoskeletal conditions, especially in underserved areas, clearly deserves further study.
Calvin R. Brown Jr., MD, is a professor of medicine in the division of rheumatology at Northwestern University, Chicago. He is the director of the rheumatology training program there.
according to the results of a qualitative and quantitative study.
Over a 9-year period, ECHO (Extension for Community Healthcare Outcomes) Rheum educated 2,230 primary care clinicians, the majority of whom were physicians (53%) or nurse practitioners (22%), and helped increase the clinicians’ confidence in managing rheumatic conditions locally while still having access to specialist guidance.
Participants in ECHO Rheum accrued a total of 1,958 CME credits between them, and 21 of 30 (70%) clinicians who participated in 2-day miniresidencies obtained online certification from the American College of Rheumatology.
“ECHO Rheum and programs like it have the potential to positively impact the national shortage of rheumatologic care for underserved patients,” Arthur Bankhurst, MD, and his associates from the University of New Mexico, Albuquerque wrote in Arthritis Care & Research. “Empowering the health care workforce by disseminating knowledge of best practice diagnosis and treatment has the potential to reduce suboptimal rheumatologic care and expand access for those suffering from rheumatologic conditions regardless of economic status or location.”
ECHO Rheum is part of the larger Project ECHO (Extension for Community Healthcare Outcomes), a program developed at UNM by gastroenterologist Sanjeev Arora, MD. Dr. Arora came up with the idea for the ECHO model in 2003 to try to improve access to best practice care for patients with hepatitis C. The potential of the model to translate across medical specialties was soon seen, however, and today, there are more than 40 teleECHO programs operating in New Mexico that also involve more than 400 community clinic sites. The ECHO model is also being used nationally, operating in more than 30 states, and globally in 31 countries.
According to information available via the Project ECHO website, “the ECHO model is not traditional ‘telemedicine’ where the specialist assumes care of the patient, but is instead telementoring, a guided practice model where the participating clinician retains responsibility for managing the patient.” The aim is to use medical education and care management to empower “clinicians everywhere to provide better care to more people, right where they live.”
The rheumatology arm of Project ECHO started in 2006 and follows the four main principles of the ECHO model: Using technology to leverage scarce resources, such as by facilitating regular educational sessions between central expert “hubs” at specialist centers and “spokes” at community practices; sharing best practice information to help reduce disparities in the quality of care; presenting and discussion around case histories; and evaluating and monitoring outcomes.
To demonstrate the effectiveness of ECHO Rheum, the team at UNM evaluated data on participants who had attended weekly teleconferencing sessions, lectures, grand rounds, and miniresidency training between June 2006 and June 2014.
The results demonstrated that “participation in ECHO Rheum provides clinicians in underresourced areas access to best practice knowledge and training in rheumatology,” Dr. Bankhurst and his coauthors observed.
Increased knowledge and confidence in managing rheumatic conditions among primary care physicians could help to reduce the ever-widening gap between the demand and supply of appropriate care. Indeed, while the projected population of adults with rheumatic disease is expected to grow to almost 67 million adults in the next 20 years, there is expected to be a shortfall of 4,700 full-time rheumatologists by 2030.
“Regular participation in teleECHO sessions creates a community of practice among rural clinicians,” the UNM team stated. Every week, participants were invited to attend a 90-minute virtual teleconference, either by video or telephone, that consisted of a brief evidence-based lecture by a subject matter expert and presentation of deidentified case histories submitted by the participants. Participants were able to obtain CME credits at no cost and learn how to use ACR-recommended disease activity measures, such as the Disease Activity Score in 28 joints.
Over the 9-year study period, 1,173 cases were presented, the majority of which (85%) reflected the three most common diagnoses seen in rheumatologic practice, namely RA (n = 715), fibromyalgia (n = 241), and systemic lupus erythematosus (n = 54). As might be expected, female cases were presented more often than male cases, as were cases involving patients aged 40-60 years, compared with other age groups.
“ECHO Rheum saw an increase in participation in 2010, when the ACR certification was offered at no cost, suggesting that ACR certification was an incentive for participation,” Dr. Bankhurst and his team observed.
In 2012, however, there was a drop-off in participation, which may have been caused by the end of funding for ACR certification or clinicians becoming “more confident in their abilities to diagnose and initiate treatment appropriately.” Clinical responsibilities may also have prevented clinicians from attending the weekly sessions.
“Although our formal collaboration with the ACR concluded when funds for this initiative came to an end, ECHO Rheum encourages clinicians to obtain certification in rheumatology and provides them with information about opportunities to offset the cost,” Dr. Bankhurst and his colleagues wrote.
Despite a decline in attendance at the weekly teleECHO sessions during the evaluation period, the UNM team believes that its continued use holds value for primary care practice. Since 2014, a further four clinicians have obtained ACR grant funding for certification and a number of the certified participants return to contribute to the weekly teleECHO sessions.
“This continued use of ECHO Rheum as a readily available resource for case presentations and acquisition of new learning about developments in treatment and medication demonstrates the long-term viability of the community of practice created by the program,” the team suggested.
“I think programs like this are going to be very important in addressing the physician shortage in rheumatology,” said Chad Deal, MD, in an interview.
Dr. Deal, who was not involved in the study, noted that such programs may work particularly well in underserved areas such as New Mexico, as shown in this study, as well as other states, such as in Alaska, North Dakota, and South Dakota. Essentially, “places where people are having to drive forever to get to a rheumatologist.”
“I like what they’ve done,” Dr. Deal said. It can make clinicians “feel much more comfortable with diagnosing and even treating inflammatory arthritis. I think that’s really important.”
It would be difficult to have harder outcomes measures, observed Dr. Deal, head of the Center for Osteoporosis and Metabolic Bone Disease and vice chair for quality and outcomes in the department of rheumatology at the Cleveland Clinic. “The goal is obviously early diagnosis and treatment of rheumatoid arthritis, let’s say, and improved outcomes, and that’s really difficult to show in any kind of program like this.”
Dr. Deal added that “maintaining any kind of program like this is difficult; physicians get busy, and like the authors note, sometimes clinicians get to a point where they are comfortable, and they don’t need it as much.”
Perhaps, these programs don’t need to run forever, he suggested. Perhaps a 1- or 2-year program may be sufficient for one group before moving on to focus on a different group of physicians.
Dr. Bankhurst and other authors of the study reported having no conflicts of interest. The work was funded by the Robert Wood Johnson Foundation, the New Mexico legislature, and the New Mexico Department of Health. Dr. Deal reported no conflicts of interest in relation to his comments.
SOURCE: Bankhurst A et al. Arthritis Care Res. 2019 Mar 30. doi: 10.1002/acr.23889.
according to the results of a qualitative and quantitative study.
Over a 9-year period, ECHO (Extension for Community Healthcare Outcomes) Rheum educated 2,230 primary care clinicians, the majority of whom were physicians (53%) or nurse practitioners (22%), and helped increase the clinicians’ confidence in managing rheumatic conditions locally while still having access to specialist guidance.
Participants in ECHO Rheum accrued a total of 1,958 CME credits between them, and 21 of 30 (70%) clinicians who participated in 2-day miniresidencies obtained online certification from the American College of Rheumatology.
“ECHO Rheum and programs like it have the potential to positively impact the national shortage of rheumatologic care for underserved patients,” Arthur Bankhurst, MD, and his associates from the University of New Mexico, Albuquerque wrote in Arthritis Care & Research. “Empowering the health care workforce by disseminating knowledge of best practice diagnosis and treatment has the potential to reduce suboptimal rheumatologic care and expand access for those suffering from rheumatologic conditions regardless of economic status or location.”
ECHO Rheum is part of the larger Project ECHO (Extension for Community Healthcare Outcomes), a program developed at UNM by gastroenterologist Sanjeev Arora, MD. Dr. Arora came up with the idea for the ECHO model in 2003 to try to improve access to best practice care for patients with hepatitis C. The potential of the model to translate across medical specialties was soon seen, however, and today, there are more than 40 teleECHO programs operating in New Mexico that also involve more than 400 community clinic sites. The ECHO model is also being used nationally, operating in more than 30 states, and globally in 31 countries.
According to information available via the Project ECHO website, “the ECHO model is not traditional ‘telemedicine’ where the specialist assumes care of the patient, but is instead telementoring, a guided practice model where the participating clinician retains responsibility for managing the patient.” The aim is to use medical education and care management to empower “clinicians everywhere to provide better care to more people, right where they live.”
The rheumatology arm of Project ECHO started in 2006 and follows the four main principles of the ECHO model: Using technology to leverage scarce resources, such as by facilitating regular educational sessions between central expert “hubs” at specialist centers and “spokes” at community practices; sharing best practice information to help reduce disparities in the quality of care; presenting and discussion around case histories; and evaluating and monitoring outcomes.
To demonstrate the effectiveness of ECHO Rheum, the team at UNM evaluated data on participants who had attended weekly teleconferencing sessions, lectures, grand rounds, and miniresidency training between June 2006 and June 2014.
The results demonstrated that “participation in ECHO Rheum provides clinicians in underresourced areas access to best practice knowledge and training in rheumatology,” Dr. Bankhurst and his coauthors observed.
Increased knowledge and confidence in managing rheumatic conditions among primary care physicians could help to reduce the ever-widening gap between the demand and supply of appropriate care. Indeed, while the projected population of adults with rheumatic disease is expected to grow to almost 67 million adults in the next 20 years, there is expected to be a shortfall of 4,700 full-time rheumatologists by 2030.
“Regular participation in teleECHO sessions creates a community of practice among rural clinicians,” the UNM team stated. Every week, participants were invited to attend a 90-minute virtual teleconference, either by video or telephone, that consisted of a brief evidence-based lecture by a subject matter expert and presentation of deidentified case histories submitted by the participants. Participants were able to obtain CME credits at no cost and learn how to use ACR-recommended disease activity measures, such as the Disease Activity Score in 28 joints.
Over the 9-year study period, 1,173 cases were presented, the majority of which (85%) reflected the three most common diagnoses seen in rheumatologic practice, namely RA (n = 715), fibromyalgia (n = 241), and systemic lupus erythematosus (n = 54). As might be expected, female cases were presented more often than male cases, as were cases involving patients aged 40-60 years, compared with other age groups.
“ECHO Rheum saw an increase in participation in 2010, when the ACR certification was offered at no cost, suggesting that ACR certification was an incentive for participation,” Dr. Bankhurst and his team observed.
In 2012, however, there was a drop-off in participation, which may have been caused by the end of funding for ACR certification or clinicians becoming “more confident in their abilities to diagnose and initiate treatment appropriately.” Clinical responsibilities may also have prevented clinicians from attending the weekly sessions.
“Although our formal collaboration with the ACR concluded when funds for this initiative came to an end, ECHO Rheum encourages clinicians to obtain certification in rheumatology and provides them with information about opportunities to offset the cost,” Dr. Bankhurst and his colleagues wrote.
Despite a decline in attendance at the weekly teleECHO sessions during the evaluation period, the UNM team believes that its continued use holds value for primary care practice. Since 2014, a further four clinicians have obtained ACR grant funding for certification and a number of the certified participants return to contribute to the weekly teleECHO sessions.
“This continued use of ECHO Rheum as a readily available resource for case presentations and acquisition of new learning about developments in treatment and medication demonstrates the long-term viability of the community of practice created by the program,” the team suggested.
“I think programs like this are going to be very important in addressing the physician shortage in rheumatology,” said Chad Deal, MD, in an interview.
Dr. Deal, who was not involved in the study, noted that such programs may work particularly well in underserved areas such as New Mexico, as shown in this study, as well as other states, such as in Alaska, North Dakota, and South Dakota. Essentially, “places where people are having to drive forever to get to a rheumatologist.”
“I like what they’ve done,” Dr. Deal said. It can make clinicians “feel much more comfortable with diagnosing and even treating inflammatory arthritis. I think that’s really important.”
It would be difficult to have harder outcomes measures, observed Dr. Deal, head of the Center for Osteoporosis and Metabolic Bone Disease and vice chair for quality and outcomes in the department of rheumatology at the Cleveland Clinic. “The goal is obviously early diagnosis and treatment of rheumatoid arthritis, let’s say, and improved outcomes, and that’s really difficult to show in any kind of program like this.”
Dr. Deal added that “maintaining any kind of program like this is difficult; physicians get busy, and like the authors note, sometimes clinicians get to a point where they are comfortable, and they don’t need it as much.”
Perhaps, these programs don’t need to run forever, he suggested. Perhaps a 1- or 2-year program may be sufficient for one group before moving on to focus on a different group of physicians.
Dr. Bankhurst and other authors of the study reported having no conflicts of interest. The work was funded by the Robert Wood Johnson Foundation, the New Mexico legislature, and the New Mexico Department of Health. Dr. Deal reported no conflicts of interest in relation to his comments.
SOURCE: Bankhurst A et al. Arthritis Care Res. 2019 Mar 30. doi: 10.1002/acr.23889.
FROM Arthritis care & research
Key clinical point: Primary care clinician confidence in managing rheumatic conditions can be increased by the ECHO Rheum program.
Major finding: Over a 9-year period, 2,230 primary care clinicians were educated via the program, with 21 of 30 (70%) participants obtaining American College of Rheumatology online accreditation.
Study details: A qualitative study looking at the success of a telementoring and medical education program in New Mexico between June 2006 and June 2014.
Disclosures: Dr. Bankhurst and other authors of the study reported having no conflicts of interest. The work was funded by the Robert Wood Johnson Foundation, the New Mexico legislature, and the New Mexico Department of Health. Dr. Deal reported no conflicts of interest in relation to his comments.
Source: Bankhurst A et al. Arthritis Care Res. 2019 Mar 30. doi: 10.1002/acr.23889.
EULAR takes SLE guidance to the next level
The goal was “to update the EULAR recommendations for the management of systemic lupus erythematosus [SLE], based on literature review and expert consensus,” said authors led by Antonis Fanouriakis, MD, PhD, of the rheumatology and clinical immunology unit at Attikon University Hospital, Athens.
The team accomplished their aim in 33 recommendations – about twice as many as in 2008 – covering goals of therapy, treatment, specific manifestations, and comorbidities (Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089).
A lot has changed in the past 11 years, and the new guidelines reflect that. Biologics, for instance, were barely mentioned in 2008, except as a topic for future research. The new document makes a strong recommendation for add-on belimumab (Benlysta) to be considered in persistently active or flaring extrarenal disease, and rituximab (Rituxan) for organ-threatening, refractory disease.
The group now also makes a strong recommendation for hydroxychloroquine (Plaquenil) for all lupus patients, barring contraindications, at a dose not exceeding 5 mg per kg real body weight, with ophthalmologic screening performed at baseline, after 5 years, and yearly thereafter. It also calls for routine antiphospholipid antibody testing.
Calcineurin inhibitors weren’t mentioned at all in 2008, but they show up in the new document with a moderate recommendation as first-line topical options for skin disease, along with glucocorticoids. The authors also made a moderate recommendation for diagnostic kidney biopsy, calling it “essential” to catch renal involvement early; EULAR was less certain in 2008. Also new in 2019, and barely mentioned in 2008, there’s an entire section on hematologic manifestations, as well as advice on thalidomide for cutaneous disease.
For hematologic disease, the group makes a weak recommendation for pulsed intravenous methylprednisolone and/or intravenous immunoglobulin, with mycophenolate, azathioprine, or cyclosporine for maintenance. Cyclophosphamide, along with rituximab, are options for severe hematologic cases.
Cardiovascular disease, like biologics, was mentioned mostly in 2008 as a topic for future research; the new guidelines contain an entire section on the issue. There’s a strong recommendation for regular assessment of traditional and disease-related risk factors, including persistently active disease; increased disease duration; medium or high titers of antiphospholipid antibodies; renal involvement; and chronic glucocorticoid use. High-risk people, the document notes, “may be candidates for preventative strategies as in the general population,” including low-dose aspirin and statins.
The new guidance is also more certain about mycophenolate for renal disease, with a strong recommendation for use as an induction and maintenance agent, with azathioprine the other strong candidate for maintenance. EULAR also made a weak recommendation for mycophenolate with low-dose calcineurin inhibitors in severe nephrotic syndrome, in some circumstances.
For antiphospholipid antibody carriers, EULAR noted that a recent randomized, open-label trial comparing rivaroxaban against warfarin “was prematurely terminated due to an excess of thromboembolic events in the rivaroxaban arm. Thus, in patients with SLE-antiphospholipid syndrome, “use of novel oral anticoagulants for secondary prevention should be avoided.”
The group notes that management should aim at “remission of disease symptoms and signs, prevention of damage accrual, and minimization of drug side effects, as well as improvement of quality of life.” To that end, it said newly defined low disease-activity states, such as an SLE Disease Activity Index score of 3 or less on antimalarials, are useful to guide treatment, and have comparable rates of remission and flare prevention.
SOURCE: Fanouriakis A et al. Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089
The goal was “to update the EULAR recommendations for the management of systemic lupus erythematosus [SLE], based on literature review and expert consensus,” said authors led by Antonis Fanouriakis, MD, PhD, of the rheumatology and clinical immunology unit at Attikon University Hospital, Athens.
The team accomplished their aim in 33 recommendations – about twice as many as in 2008 – covering goals of therapy, treatment, specific manifestations, and comorbidities (Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089).
A lot has changed in the past 11 years, and the new guidelines reflect that. Biologics, for instance, were barely mentioned in 2008, except as a topic for future research. The new document makes a strong recommendation for add-on belimumab (Benlysta) to be considered in persistently active or flaring extrarenal disease, and rituximab (Rituxan) for organ-threatening, refractory disease.
The group now also makes a strong recommendation for hydroxychloroquine (Plaquenil) for all lupus patients, barring contraindications, at a dose not exceeding 5 mg per kg real body weight, with ophthalmologic screening performed at baseline, after 5 years, and yearly thereafter. It also calls for routine antiphospholipid antibody testing.
Calcineurin inhibitors weren’t mentioned at all in 2008, but they show up in the new document with a moderate recommendation as first-line topical options for skin disease, along with glucocorticoids. The authors also made a moderate recommendation for diagnostic kidney biopsy, calling it “essential” to catch renal involvement early; EULAR was less certain in 2008. Also new in 2019, and barely mentioned in 2008, there’s an entire section on hematologic manifestations, as well as advice on thalidomide for cutaneous disease.
For hematologic disease, the group makes a weak recommendation for pulsed intravenous methylprednisolone and/or intravenous immunoglobulin, with mycophenolate, azathioprine, or cyclosporine for maintenance. Cyclophosphamide, along with rituximab, are options for severe hematologic cases.
Cardiovascular disease, like biologics, was mentioned mostly in 2008 as a topic for future research; the new guidelines contain an entire section on the issue. There’s a strong recommendation for regular assessment of traditional and disease-related risk factors, including persistently active disease; increased disease duration; medium or high titers of antiphospholipid antibodies; renal involvement; and chronic glucocorticoid use. High-risk people, the document notes, “may be candidates for preventative strategies as in the general population,” including low-dose aspirin and statins.
The new guidance is also more certain about mycophenolate for renal disease, with a strong recommendation for use as an induction and maintenance agent, with azathioprine the other strong candidate for maintenance. EULAR also made a weak recommendation for mycophenolate with low-dose calcineurin inhibitors in severe nephrotic syndrome, in some circumstances.
For antiphospholipid antibody carriers, EULAR noted that a recent randomized, open-label trial comparing rivaroxaban against warfarin “was prematurely terminated due to an excess of thromboembolic events in the rivaroxaban arm. Thus, in patients with SLE-antiphospholipid syndrome, “use of novel oral anticoagulants for secondary prevention should be avoided.”
The group notes that management should aim at “remission of disease symptoms and signs, prevention of damage accrual, and minimization of drug side effects, as well as improvement of quality of life.” To that end, it said newly defined low disease-activity states, such as an SLE Disease Activity Index score of 3 or less on antimalarials, are useful to guide treatment, and have comparable rates of remission and flare prevention.
SOURCE: Fanouriakis A et al. Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089
The goal was “to update the EULAR recommendations for the management of systemic lupus erythematosus [SLE], based on literature review and expert consensus,” said authors led by Antonis Fanouriakis, MD, PhD, of the rheumatology and clinical immunology unit at Attikon University Hospital, Athens.
The team accomplished their aim in 33 recommendations – about twice as many as in 2008 – covering goals of therapy, treatment, specific manifestations, and comorbidities (Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089).
A lot has changed in the past 11 years, and the new guidelines reflect that. Biologics, for instance, were barely mentioned in 2008, except as a topic for future research. The new document makes a strong recommendation for add-on belimumab (Benlysta) to be considered in persistently active or flaring extrarenal disease, and rituximab (Rituxan) for organ-threatening, refractory disease.
The group now also makes a strong recommendation for hydroxychloroquine (Plaquenil) for all lupus patients, barring contraindications, at a dose not exceeding 5 mg per kg real body weight, with ophthalmologic screening performed at baseline, after 5 years, and yearly thereafter. It also calls for routine antiphospholipid antibody testing.
Calcineurin inhibitors weren’t mentioned at all in 2008, but they show up in the new document with a moderate recommendation as first-line topical options for skin disease, along with glucocorticoids. The authors also made a moderate recommendation for diagnostic kidney biopsy, calling it “essential” to catch renal involvement early; EULAR was less certain in 2008. Also new in 2019, and barely mentioned in 2008, there’s an entire section on hematologic manifestations, as well as advice on thalidomide for cutaneous disease.
For hematologic disease, the group makes a weak recommendation for pulsed intravenous methylprednisolone and/or intravenous immunoglobulin, with mycophenolate, azathioprine, or cyclosporine for maintenance. Cyclophosphamide, along with rituximab, are options for severe hematologic cases.
Cardiovascular disease, like biologics, was mentioned mostly in 2008 as a topic for future research; the new guidelines contain an entire section on the issue. There’s a strong recommendation for regular assessment of traditional and disease-related risk factors, including persistently active disease; increased disease duration; medium or high titers of antiphospholipid antibodies; renal involvement; and chronic glucocorticoid use. High-risk people, the document notes, “may be candidates for preventative strategies as in the general population,” including low-dose aspirin and statins.
The new guidance is also more certain about mycophenolate for renal disease, with a strong recommendation for use as an induction and maintenance agent, with azathioprine the other strong candidate for maintenance. EULAR also made a weak recommendation for mycophenolate with low-dose calcineurin inhibitors in severe nephrotic syndrome, in some circumstances.
For antiphospholipid antibody carriers, EULAR noted that a recent randomized, open-label trial comparing rivaroxaban against warfarin “was prematurely terminated due to an excess of thromboembolic events in the rivaroxaban arm. Thus, in patients with SLE-antiphospholipid syndrome, “use of novel oral anticoagulants for secondary prevention should be avoided.”
The group notes that management should aim at “remission of disease symptoms and signs, prevention of damage accrual, and minimization of drug side effects, as well as improvement of quality of life.” To that end, it said newly defined low disease-activity states, such as an SLE Disease Activity Index score of 3 or less on antimalarials, are useful to guide treatment, and have comparable rates of remission and flare prevention.
SOURCE: Fanouriakis A et al. Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089
FROM ANNALS OF THE RHEUMATIC DISEASES
Bronchiolitis is a feared complication of connective tissue disease
MAUI, HAWAII – who develop shortness of breath and cough or a precipitous drop in their forced expiratory volume on pulmonary function testing, Aryeh Fischer, MD, said at the 2019 Rheumatology Winter Clinical Symposium.
“This is an underappreciated – and I think among the most potentially devastating – of the lung diseases we as rheumatologists will encounter in our patients,” said Dr. Fischer, a rheumatologist at the University of Colorado at Denver, Aurora, with a special interest in autoimmune lung disease.
“If you’re seeing patients with rheumatoid arthritis, SLE, or Sjögren’s and they’ve got bad asthma they can’t get under control, you’ve got to think about bronchiolitis because I can tell you your lung doc quite often is not thinking about this,” he added.
Bronchiolitis involves inflammation, narrowing, or obliteration of the small airways. The diagnosis is often missed because of the false sense of reassurance provided by the normal chest x-ray and regular CT findings, which are a feature of the disease.
“This is really important: You have to get a high-resolution CT that includes expiratory images, because that’s the only way you’re going to be able to tell if your patient has small airways disease,” he explained. “You must, must, must do an expiratory CT.”
A normal expiratory CT image should be gray, since the lungs are empty. Air is black on CT, so large areas of black intermixed with gray on an expiratory CT – a finding known as mosaicism – indicate air trapping due to small airways disease, Dr. Fischer noted.
Surgical lung biopsy will yield a pathologic report documenting isolated constrictive, follicular, and/or lymphocytic bronchiolitis. However, the terminology can be confusing: What pathologists describe as constrictive bronchiolitis is called obliterative by pulmonologists and radiologists.
Pulmonary function testing shows an obstructive defect. The diffusing capacity of the lungs for carbon monoxide (DLCO) is fairly normal, the forced expiratory volume in 1 second (FEV1) is sharply reduced, and the forced vital capacity (FVC) is near normal, with a resultant abnormally low FEV1/FVC ratio. A patient with bronchiolitis may or may not have a response to bronchodilators.
“I tell you, I’ve seen a bunch of these patients. They typically have a precipitous drop in their FEV1 and then stay stable at a very low level of lung function without much opportunity for improvement,” Dr. Fischer said. “Stability equals success in these patients. It’s really unusual to see much improvement.”
In theory, patients with follicular or lymphocytic bronchiolitis have an ongoing inflammatory process that should be amenable to rheumatologic ministrations. But there is no convincing evidence of treatment efficacy to date. And in obliterative bronchiolitis, marked by airway scarring, there is no reason to think anti-inflammatory therapies should be helpful. Anecdotally, Dr. Fischer said, he has seen immunosuppression help patients with obliterative bronchiolitis.
“Actually, the only proven therapy is lung transplantation,” he said.
He recommended that his fellow rheumatologists periodically use office spirometry to check the FEV1 in their patients with rheumatoid arthritis, Sjögren’s, or SLE, the forms of connective tissue disease most often associated with bronchiolitis. Compared with all the other testing rheumatologists routinely order in their patients, having them blow into a tube is a simple enough matter.
“We really don’t have anything to impact the natural history, but I like the notion of not being surprised. What are you going to do with that [abnormal] FEV1 data? I have no idea. But maybe it’s better to know earlier,” he said.
Dr. Fischer reported having no financial conflicts of interest regarding his presentation.
MAUI, HAWAII – who develop shortness of breath and cough or a precipitous drop in their forced expiratory volume on pulmonary function testing, Aryeh Fischer, MD, said at the 2019 Rheumatology Winter Clinical Symposium.
“This is an underappreciated – and I think among the most potentially devastating – of the lung diseases we as rheumatologists will encounter in our patients,” said Dr. Fischer, a rheumatologist at the University of Colorado at Denver, Aurora, with a special interest in autoimmune lung disease.
“If you’re seeing patients with rheumatoid arthritis, SLE, or Sjögren’s and they’ve got bad asthma they can’t get under control, you’ve got to think about bronchiolitis because I can tell you your lung doc quite often is not thinking about this,” he added.
Bronchiolitis involves inflammation, narrowing, or obliteration of the small airways. The diagnosis is often missed because of the false sense of reassurance provided by the normal chest x-ray and regular CT findings, which are a feature of the disease.
“This is really important: You have to get a high-resolution CT that includes expiratory images, because that’s the only way you’re going to be able to tell if your patient has small airways disease,” he explained. “You must, must, must do an expiratory CT.”
A normal expiratory CT image should be gray, since the lungs are empty. Air is black on CT, so large areas of black intermixed with gray on an expiratory CT – a finding known as mosaicism – indicate air trapping due to small airways disease, Dr. Fischer noted.
Surgical lung biopsy will yield a pathologic report documenting isolated constrictive, follicular, and/or lymphocytic bronchiolitis. However, the terminology can be confusing: What pathologists describe as constrictive bronchiolitis is called obliterative by pulmonologists and radiologists.
Pulmonary function testing shows an obstructive defect. The diffusing capacity of the lungs for carbon monoxide (DLCO) is fairly normal, the forced expiratory volume in 1 second (FEV1) is sharply reduced, and the forced vital capacity (FVC) is near normal, with a resultant abnormally low FEV1/FVC ratio. A patient with bronchiolitis may or may not have a response to bronchodilators.
“I tell you, I’ve seen a bunch of these patients. They typically have a precipitous drop in their FEV1 and then stay stable at a very low level of lung function without much opportunity for improvement,” Dr. Fischer said. “Stability equals success in these patients. It’s really unusual to see much improvement.”
In theory, patients with follicular or lymphocytic bronchiolitis have an ongoing inflammatory process that should be amenable to rheumatologic ministrations. But there is no convincing evidence of treatment efficacy to date. And in obliterative bronchiolitis, marked by airway scarring, there is no reason to think anti-inflammatory therapies should be helpful. Anecdotally, Dr. Fischer said, he has seen immunosuppression help patients with obliterative bronchiolitis.
“Actually, the only proven therapy is lung transplantation,” he said.
He recommended that his fellow rheumatologists periodically use office spirometry to check the FEV1 in their patients with rheumatoid arthritis, Sjögren’s, or SLE, the forms of connective tissue disease most often associated with bronchiolitis. Compared with all the other testing rheumatologists routinely order in their patients, having them blow into a tube is a simple enough matter.
“We really don’t have anything to impact the natural history, but I like the notion of not being surprised. What are you going to do with that [abnormal] FEV1 data? I have no idea. But maybe it’s better to know earlier,” he said.
Dr. Fischer reported having no financial conflicts of interest regarding his presentation.
MAUI, HAWAII – who develop shortness of breath and cough or a precipitous drop in their forced expiratory volume on pulmonary function testing, Aryeh Fischer, MD, said at the 2019 Rheumatology Winter Clinical Symposium.
“This is an underappreciated – and I think among the most potentially devastating – of the lung diseases we as rheumatologists will encounter in our patients,” said Dr. Fischer, a rheumatologist at the University of Colorado at Denver, Aurora, with a special interest in autoimmune lung disease.
“If you’re seeing patients with rheumatoid arthritis, SLE, or Sjögren’s and they’ve got bad asthma they can’t get under control, you’ve got to think about bronchiolitis because I can tell you your lung doc quite often is not thinking about this,” he added.
Bronchiolitis involves inflammation, narrowing, or obliteration of the small airways. The diagnosis is often missed because of the false sense of reassurance provided by the normal chest x-ray and regular CT findings, which are a feature of the disease.
“This is really important: You have to get a high-resolution CT that includes expiratory images, because that’s the only way you’re going to be able to tell if your patient has small airways disease,” he explained. “You must, must, must do an expiratory CT.”
A normal expiratory CT image should be gray, since the lungs are empty. Air is black on CT, so large areas of black intermixed with gray on an expiratory CT – a finding known as mosaicism – indicate air trapping due to small airways disease, Dr. Fischer noted.
Surgical lung biopsy will yield a pathologic report documenting isolated constrictive, follicular, and/or lymphocytic bronchiolitis. However, the terminology can be confusing: What pathologists describe as constrictive bronchiolitis is called obliterative by pulmonologists and radiologists.
Pulmonary function testing shows an obstructive defect. The diffusing capacity of the lungs for carbon monoxide (DLCO) is fairly normal, the forced expiratory volume in 1 second (FEV1) is sharply reduced, and the forced vital capacity (FVC) is near normal, with a resultant abnormally low FEV1/FVC ratio. A patient with bronchiolitis may or may not have a response to bronchodilators.
“I tell you, I’ve seen a bunch of these patients. They typically have a precipitous drop in their FEV1 and then stay stable at a very low level of lung function without much opportunity for improvement,” Dr. Fischer said. “Stability equals success in these patients. It’s really unusual to see much improvement.”
In theory, patients with follicular or lymphocytic bronchiolitis have an ongoing inflammatory process that should be amenable to rheumatologic ministrations. But there is no convincing evidence of treatment efficacy to date. And in obliterative bronchiolitis, marked by airway scarring, there is no reason to think anti-inflammatory therapies should be helpful. Anecdotally, Dr. Fischer said, he has seen immunosuppression help patients with obliterative bronchiolitis.
“Actually, the only proven therapy is lung transplantation,” he said.
He recommended that his fellow rheumatologists periodically use office spirometry to check the FEV1 in their patients with rheumatoid arthritis, Sjögren’s, or SLE, the forms of connective tissue disease most often associated with bronchiolitis. Compared with all the other testing rheumatologists routinely order in their patients, having them blow into a tube is a simple enough matter.
“We really don’t have anything to impact the natural history, but I like the notion of not being surprised. What are you going to do with that [abnormal] FEV1 data? I have no idea. But maybe it’s better to know earlier,” he said.
Dr. Fischer reported having no financial conflicts of interest regarding his presentation.
REPORTING FROM RWCS 2019