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CAR T cells target HER2 expression in advanced sarcomas
ATLANTA – Sarcomas of bone and soft tissues are considered to be “antigenically cold” tumors, with few identifiable mutations that may be susceptible to targeted therapies.
Some sarcoma subtypes such as osteosarcoma and rhabomyosarcoma, however, frequently express the human epidermal growth factor receptor 2 on tumor surfaces. Although HER2 expression in these tumors is at too low a level for HER2-targeted therapies such as trastuzumab (Herceptin), HER2 appears to be an opportunistic target for chimeric antigen receptor (CAR) T-cell therapy, according to Shoba Navai, MD, from Baylor College of Medicine, Houston.
In a video interview at the 2019 annual meeting of the American Association for Cancer Research, Dr. Navai describes her team’s early experience using a HER2-targeted CAR-T cell construct and preinfusion lymphodepletion in patients with advanced sarcomas.
Development of the CAR-T cell construct is supported by the Cancer Prevention & Research Institute of Texas, Stand Up to Cancer, the St. Baldrick’s Foundation, Cookies for Kids’ Cancer, Alex’s Lemonade Stand, and a grant from the National Institutes of Health. Dr. Navai reported having no disclosures.
ATLANTA – Sarcomas of bone and soft tissues are considered to be “antigenically cold” tumors, with few identifiable mutations that may be susceptible to targeted therapies.
Some sarcoma subtypes such as osteosarcoma and rhabomyosarcoma, however, frequently express the human epidermal growth factor receptor 2 on tumor surfaces. Although HER2 expression in these tumors is at too low a level for HER2-targeted therapies such as trastuzumab (Herceptin), HER2 appears to be an opportunistic target for chimeric antigen receptor (CAR) T-cell therapy, according to Shoba Navai, MD, from Baylor College of Medicine, Houston.
In a video interview at the 2019 annual meeting of the American Association for Cancer Research, Dr. Navai describes her team’s early experience using a HER2-targeted CAR-T cell construct and preinfusion lymphodepletion in patients with advanced sarcomas.
Development of the CAR-T cell construct is supported by the Cancer Prevention & Research Institute of Texas, Stand Up to Cancer, the St. Baldrick’s Foundation, Cookies for Kids’ Cancer, Alex’s Lemonade Stand, and a grant from the National Institutes of Health. Dr. Navai reported having no disclosures.
ATLANTA – Sarcomas of bone and soft tissues are considered to be “antigenically cold” tumors, with few identifiable mutations that may be susceptible to targeted therapies.
Some sarcoma subtypes such as osteosarcoma and rhabomyosarcoma, however, frequently express the human epidermal growth factor receptor 2 on tumor surfaces. Although HER2 expression in these tumors is at too low a level for HER2-targeted therapies such as trastuzumab (Herceptin), HER2 appears to be an opportunistic target for chimeric antigen receptor (CAR) T-cell therapy, according to Shoba Navai, MD, from Baylor College of Medicine, Houston.
In a video interview at the 2019 annual meeting of the American Association for Cancer Research, Dr. Navai describes her team’s early experience using a HER2-targeted CAR-T cell construct and preinfusion lymphodepletion in patients with advanced sarcomas.
Development of the CAR-T cell construct is supported by the Cancer Prevention & Research Institute of Texas, Stand Up to Cancer, the St. Baldrick’s Foundation, Cookies for Kids’ Cancer, Alex’s Lemonade Stand, and a grant from the National Institutes of Health. Dr. Navai reported having no disclosures.
REPORTING FROM AACR 2019
FDA approves Mavenclad for treatment of relapsing MS
including relapsing/remitting and active secondary progressive disease.
The drug’s manufacturer, EMD Serono, said in a press release that cladribine is the first short-course oral therapy for such patients, and its use is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. Cladribine is not recommended for use in patients with clinically isolated syndrome.
The agency’s decision is based on results from a clinical trial of 1,326 patients with relapsing MS who had experienced at least one relapse in the previous 12 months. Patients who received cladribine had significantly fewer relapses than did those who received placebo; the progression of disability was also significantly reduced in the cladribine group, compared with placebo, according to the FDA’s announcement.
The most common adverse events associated with cladribine include upper respiratory tract infections, headache, and decreased lymphocyte counts. In addition, the medication must be dispensed with a patient medication guide because the label includes a boxed warning for increased risk of malignancy and fetal harm. Other warnings include a risk for decreased lymphocyte count, hematologic toxicity and bone marrow suppression, and graft-versus-host-disease.
“We are committed to supporting the development of safe and effective treatments for patients with multiple sclerosis. The approval of Mavenclad represents an additional option for patients who have tried another treatment without success,” Billy Dunn, MD, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in the announcement.
The approved dose of cladribine is 3.5 mg/kg body weight over 2 years, administered as one treatment course of 1.75 mg/kg per year, each consisting of 2 treatment weeks. Additional courses of cladribine are not to be administered because retreatment with cladribine during years 3 and 4 may further increase the risk of malignancy. The safety and efficacy of reinitiating cladribine more than 2 years after completing two treatment courses has not been studied, according to EMD Serono.
Cladribine is approved in more than 50 other countries and was approved for use in the European Union in August 2017.
including relapsing/remitting and active secondary progressive disease.
The drug’s manufacturer, EMD Serono, said in a press release that cladribine is the first short-course oral therapy for such patients, and its use is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. Cladribine is not recommended for use in patients with clinically isolated syndrome.
The agency’s decision is based on results from a clinical trial of 1,326 patients with relapsing MS who had experienced at least one relapse in the previous 12 months. Patients who received cladribine had significantly fewer relapses than did those who received placebo; the progression of disability was also significantly reduced in the cladribine group, compared with placebo, according to the FDA’s announcement.
The most common adverse events associated with cladribine include upper respiratory tract infections, headache, and decreased lymphocyte counts. In addition, the medication must be dispensed with a patient medication guide because the label includes a boxed warning for increased risk of malignancy and fetal harm. Other warnings include a risk for decreased lymphocyte count, hematologic toxicity and bone marrow suppression, and graft-versus-host-disease.
“We are committed to supporting the development of safe and effective treatments for patients with multiple sclerosis. The approval of Mavenclad represents an additional option for patients who have tried another treatment without success,” Billy Dunn, MD, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in the announcement.
The approved dose of cladribine is 3.5 mg/kg body weight over 2 years, administered as one treatment course of 1.75 mg/kg per year, each consisting of 2 treatment weeks. Additional courses of cladribine are not to be administered because retreatment with cladribine during years 3 and 4 may further increase the risk of malignancy. The safety and efficacy of reinitiating cladribine more than 2 years after completing two treatment courses has not been studied, according to EMD Serono.
Cladribine is approved in more than 50 other countries and was approved for use in the European Union in August 2017.
including relapsing/remitting and active secondary progressive disease.
The drug’s manufacturer, EMD Serono, said in a press release that cladribine is the first short-course oral therapy for such patients, and its use is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. Cladribine is not recommended for use in patients with clinically isolated syndrome.
The agency’s decision is based on results from a clinical trial of 1,326 patients with relapsing MS who had experienced at least one relapse in the previous 12 months. Patients who received cladribine had significantly fewer relapses than did those who received placebo; the progression of disability was also significantly reduced in the cladribine group, compared with placebo, according to the FDA’s announcement.
The most common adverse events associated with cladribine include upper respiratory tract infections, headache, and decreased lymphocyte counts. In addition, the medication must be dispensed with a patient medication guide because the label includes a boxed warning for increased risk of malignancy and fetal harm. Other warnings include a risk for decreased lymphocyte count, hematologic toxicity and bone marrow suppression, and graft-versus-host-disease.
“We are committed to supporting the development of safe and effective treatments for patients with multiple sclerosis. The approval of Mavenclad represents an additional option for patients who have tried another treatment without success,” Billy Dunn, MD, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in the announcement.
The approved dose of cladribine is 3.5 mg/kg body weight over 2 years, administered as one treatment course of 1.75 mg/kg per year, each consisting of 2 treatment weeks. Additional courses of cladribine are not to be administered because retreatment with cladribine during years 3 and 4 may further increase the risk of malignancy. The safety and efficacy of reinitiating cladribine more than 2 years after completing two treatment courses has not been studied, according to EMD Serono.
Cladribine is approved in more than 50 other countries and was approved for use in the European Union in August 2017.
Fundamentals of Gene Therapy: Addressing Gaps in Physician Education
Click here to read supplement.
Gene therapy is a contemporary therapeutic intervention with recent positive results and regulatory approvals either completed or expected in the next several years for various conditions. In this supplement, learn more about:
- Basic principles of gene therapy
- In vivo vs ex vivo methods of gene transfer
- Vector types
- Clinical Considerations
About the Author
Click here to read supplement.
Click here to read supplement.
Gene therapy is a contemporary therapeutic intervention with recent positive results and regulatory approvals either completed or expected in the next several years for various conditions. In this supplement, learn more about:
- Basic principles of gene therapy
- In vivo vs ex vivo methods of gene transfer
- Vector types
- Clinical Considerations
About the Author
Click here to read supplement.
Click here to read supplement.
Gene therapy is a contemporary therapeutic intervention with recent positive results and regulatory approvals either completed or expected in the next several years for various conditions. In this supplement, learn more about:
- Basic principles of gene therapy
- In vivo vs ex vivo methods of gene transfer
- Vector types
- Clinical Considerations
About the Author
Click here to read supplement.
PA Specific Program Scheduled for VAM
The PA Section steering committee has been hard at work developing session programming for the 2019 Vascular Annual Meeting. Vascular PAs can look forward to a four-hour session on Thursday, June 13, completely dedicated to them. The program will focus on a variety of topics that include optimal team practice, vascular diagnostics, venous disease and wound management, an “Ask the Expert” portion and much more. Know a vascular PA who needs to become an SVS member? Encourage them to apply today.
The PA Section steering committee has been hard at work developing session programming for the 2019 Vascular Annual Meeting. Vascular PAs can look forward to a four-hour session on Thursday, June 13, completely dedicated to them. The program will focus on a variety of topics that include optimal team practice, vascular diagnostics, venous disease and wound management, an “Ask the Expert” portion and much more. Know a vascular PA who needs to become an SVS member? Encourage them to apply today.
The PA Section steering committee has been hard at work developing session programming for the 2019 Vascular Annual Meeting. Vascular PAs can look forward to a four-hour session on Thursday, June 13, completely dedicated to them. The program will focus on a variety of topics that include optimal team practice, vascular diagnostics, venous disease and wound management, an “Ask the Expert” portion and much more. Know a vascular PA who needs to become an SVS member? Encourage them to apply today.
SVSConnect – Save the Date!
The SVS is excited to announce that within your online community, SVSConnect, there will be an “Ask Us Anything” session at 2 p.m. CDT on April 8. Drs. Daniel McDevitt and William Shutze will be available in real time to answer questions about building relationships in a competitive environment. SVSConnect users will be able to chime in during the session to ask them anything. If you can’t make it to the live Q&A on April 8, all the questions and responses will be available in the SVSConnect library. More information will come soon.
The SVS is excited to announce that within your online community, SVSConnect, there will be an “Ask Us Anything” session at 2 p.m. CDT on April 8. Drs. Daniel McDevitt and William Shutze will be available in real time to answer questions about building relationships in a competitive environment. SVSConnect users will be able to chime in during the session to ask them anything. If you can’t make it to the live Q&A on April 8, all the questions and responses will be available in the SVSConnect library. More information will come soon.
The SVS is excited to announce that within your online community, SVSConnect, there will be an “Ask Us Anything” session at 2 p.m. CDT on April 8. Drs. Daniel McDevitt and William Shutze will be available in real time to answer questions about building relationships in a competitive environment. SVSConnect users will be able to chime in during the session to ask them anything. If you can’t make it to the live Q&A on April 8, all the questions and responses will be available in the SVSConnect library. More information will come soon.
Reframing the conversation around the ‘gender-reveal’ ultrasound
How revealing fetal anatomy, not gender, is inclusive
Every ob.gyn. expects that the topic of gender will come up at some point in a patient’s pregnancy. “When will I find out the gender?” asks the 24-year-old at her first prenatal visit. “We want the gender to be a surprise!” exclaims the couple at their anatomy scan for their second in vitro fertilization pregnancy. “Do you know what you’re having?” asks the obstetrician anticipating an imminent delivery.
The topic of gender is in fact so ingrained in our practice that we don’t bat an eye when approached with questions about fetal gender. But what exactly are we talking about when we discuss the gender of an unborn baby?
As we established in our previous column, gender identity is an internal experience of gender that one feels to be a part of oneself. So, then, what does an ultrasound actually reveal? Objectively, ultrasound can show the provider the presence or absence of a hyperechoic anatomical structure between the fetal legs that may become a penis, a vagina, or an ambiguous form of genitalia. While ultrasound is an incredible tool for anatomical and other forms of antenatal testing, ultrasound cannot detect identity characteristics because identities are, by definition, socially and internally experienced without respect to anatomy.
The distinction between gender identity and sex assigned at birth in discussions of antenatal ultrasonography is more than just a simple problem of semantics or vocabulary. To describe a fetus as a boy or a girl based on the presence/absence of a projection between the fetal legs seen on ultrasound is to reinforce the idea that gender identity and sex assigned at birth are equivalent. This conflation also erases nonbinary, genderqueer, and many other groups that identify with genders other than “boy” or “girl.” To be clear, unborn fetuses do not have a gender identity. Studies have shown that children begin to self-label their gender as early as 18-24 months of age, and similarly those who grow up to inhabit gender-nonconforming identities usually already are starting to show signs of their nonconformity starting at age 2 years.1 Some of the deepest traumas that trans and gender-nonconforming people experience are rated to the enforcement of unwritten gender laws during early childhood that are applied based on the sex assigned at birth.
Obstetricians can help to break the cycle of inappropriate gender assignment by correctly using the terms “gender” and “sex assigned at birth.” One opportunity for addressing patients’ questions about fetal gender might be to avoid the term “gender” altogether when discussing fetal sex assigned at birth, emphasizing instead what fetal ultrasound is actually able to do: Give us information about the appearance of external genitalia to help predict what sex will be assigned at birth.2 We have used this strategy when performing anatomy scans, and our experience has been that patients often will make their own assumptions about what it means to see certain external genitalia on ultrasound between the fetal legs. Motivated providers who want to go the extra mile may use a patient’s exclamation about their understanding of the fetus’s gender as an opportunity to educate the patient on the distinction between gender and sex assigned at birth, but even just smiling and moving onto the next part of the scan is an appropriate way of maintaining an atmosphere of inclusion and respect.
One of the roots of gender-based violence and gender dysphoria later in life is the conflation of gender and sex assigned at birth. While there is an entire social and political framework that enforces and polices gender after birth, the obstetrician can take steps to break the cycle starting before the birth has even occurred. Obstetricians are tasked with the unique challenge of providing care for the mother-fetus dyad, and much of the work is in setting up the fetus for the best possible life. Our scope of inclusion should be sufficiently wide to account for nonanatomical variations that could develop later in life in the infants we deliver.
Dr. Bahng is a PGY-1 resident physician in the gynecology & obstetrics residency program at Emory University, Atlanta. Dr. Bahng identifies as nonbinary and uses they/them/their as their personal pronouns. Dr. Joyner is an assistant professor at Emory University and is the director of gynecologic services in the Gender Center at Grady Memorial Hospital in Atlanta. Dr. Joyner identifies as a cisgender female and uses she/hers/her as her personal pronouns. Dr. Bahng and Dr. Joyner reported no financial disclosures.
References
1. Horm Behav. 2013 Jul;64(2):288-97.
2. Obstet Gynecol Surv. 2009 Jan;64(1):50-7.
How revealing fetal anatomy, not gender, is inclusive
How revealing fetal anatomy, not gender, is inclusive
Every ob.gyn. expects that the topic of gender will come up at some point in a patient’s pregnancy. “When will I find out the gender?” asks the 24-year-old at her first prenatal visit. “We want the gender to be a surprise!” exclaims the couple at their anatomy scan for their second in vitro fertilization pregnancy. “Do you know what you’re having?” asks the obstetrician anticipating an imminent delivery.
The topic of gender is in fact so ingrained in our practice that we don’t bat an eye when approached with questions about fetal gender. But what exactly are we talking about when we discuss the gender of an unborn baby?
As we established in our previous column, gender identity is an internal experience of gender that one feels to be a part of oneself. So, then, what does an ultrasound actually reveal? Objectively, ultrasound can show the provider the presence or absence of a hyperechoic anatomical structure between the fetal legs that may become a penis, a vagina, or an ambiguous form of genitalia. While ultrasound is an incredible tool for anatomical and other forms of antenatal testing, ultrasound cannot detect identity characteristics because identities are, by definition, socially and internally experienced without respect to anatomy.
The distinction between gender identity and sex assigned at birth in discussions of antenatal ultrasonography is more than just a simple problem of semantics or vocabulary. To describe a fetus as a boy or a girl based on the presence/absence of a projection between the fetal legs seen on ultrasound is to reinforce the idea that gender identity and sex assigned at birth are equivalent. This conflation also erases nonbinary, genderqueer, and many other groups that identify with genders other than “boy” or “girl.” To be clear, unborn fetuses do not have a gender identity. Studies have shown that children begin to self-label their gender as early as 18-24 months of age, and similarly those who grow up to inhabit gender-nonconforming identities usually already are starting to show signs of their nonconformity starting at age 2 years.1 Some of the deepest traumas that trans and gender-nonconforming people experience are rated to the enforcement of unwritten gender laws during early childhood that are applied based on the sex assigned at birth.
Obstetricians can help to break the cycle of inappropriate gender assignment by correctly using the terms “gender” and “sex assigned at birth.” One opportunity for addressing patients’ questions about fetal gender might be to avoid the term “gender” altogether when discussing fetal sex assigned at birth, emphasizing instead what fetal ultrasound is actually able to do: Give us information about the appearance of external genitalia to help predict what sex will be assigned at birth.2 We have used this strategy when performing anatomy scans, and our experience has been that patients often will make their own assumptions about what it means to see certain external genitalia on ultrasound between the fetal legs. Motivated providers who want to go the extra mile may use a patient’s exclamation about their understanding of the fetus’s gender as an opportunity to educate the patient on the distinction between gender and sex assigned at birth, but even just smiling and moving onto the next part of the scan is an appropriate way of maintaining an atmosphere of inclusion and respect.
One of the roots of gender-based violence and gender dysphoria later in life is the conflation of gender and sex assigned at birth. While there is an entire social and political framework that enforces and polices gender after birth, the obstetrician can take steps to break the cycle starting before the birth has even occurred. Obstetricians are tasked with the unique challenge of providing care for the mother-fetus dyad, and much of the work is in setting up the fetus for the best possible life. Our scope of inclusion should be sufficiently wide to account for nonanatomical variations that could develop later in life in the infants we deliver.
Dr. Bahng is a PGY-1 resident physician in the gynecology & obstetrics residency program at Emory University, Atlanta. Dr. Bahng identifies as nonbinary and uses they/them/their as their personal pronouns. Dr. Joyner is an assistant professor at Emory University and is the director of gynecologic services in the Gender Center at Grady Memorial Hospital in Atlanta. Dr. Joyner identifies as a cisgender female and uses she/hers/her as her personal pronouns. Dr. Bahng and Dr. Joyner reported no financial disclosures.
References
1. Horm Behav. 2013 Jul;64(2):288-97.
2. Obstet Gynecol Surv. 2009 Jan;64(1):50-7.
Every ob.gyn. expects that the topic of gender will come up at some point in a patient’s pregnancy. “When will I find out the gender?” asks the 24-year-old at her first prenatal visit. “We want the gender to be a surprise!” exclaims the couple at their anatomy scan for their second in vitro fertilization pregnancy. “Do you know what you’re having?” asks the obstetrician anticipating an imminent delivery.
The topic of gender is in fact so ingrained in our practice that we don’t bat an eye when approached with questions about fetal gender. But what exactly are we talking about when we discuss the gender of an unborn baby?
As we established in our previous column, gender identity is an internal experience of gender that one feels to be a part of oneself. So, then, what does an ultrasound actually reveal? Objectively, ultrasound can show the provider the presence or absence of a hyperechoic anatomical structure between the fetal legs that may become a penis, a vagina, or an ambiguous form of genitalia. While ultrasound is an incredible tool for anatomical and other forms of antenatal testing, ultrasound cannot detect identity characteristics because identities are, by definition, socially and internally experienced without respect to anatomy.
The distinction between gender identity and sex assigned at birth in discussions of antenatal ultrasonography is more than just a simple problem of semantics or vocabulary. To describe a fetus as a boy or a girl based on the presence/absence of a projection between the fetal legs seen on ultrasound is to reinforce the idea that gender identity and sex assigned at birth are equivalent. This conflation also erases nonbinary, genderqueer, and many other groups that identify with genders other than “boy” or “girl.” To be clear, unborn fetuses do not have a gender identity. Studies have shown that children begin to self-label their gender as early as 18-24 months of age, and similarly those who grow up to inhabit gender-nonconforming identities usually already are starting to show signs of their nonconformity starting at age 2 years.1 Some of the deepest traumas that trans and gender-nonconforming people experience are rated to the enforcement of unwritten gender laws during early childhood that are applied based on the sex assigned at birth.
Obstetricians can help to break the cycle of inappropriate gender assignment by correctly using the terms “gender” and “sex assigned at birth.” One opportunity for addressing patients’ questions about fetal gender might be to avoid the term “gender” altogether when discussing fetal sex assigned at birth, emphasizing instead what fetal ultrasound is actually able to do: Give us information about the appearance of external genitalia to help predict what sex will be assigned at birth.2 We have used this strategy when performing anatomy scans, and our experience has been that patients often will make their own assumptions about what it means to see certain external genitalia on ultrasound between the fetal legs. Motivated providers who want to go the extra mile may use a patient’s exclamation about their understanding of the fetus’s gender as an opportunity to educate the patient on the distinction between gender and sex assigned at birth, but even just smiling and moving onto the next part of the scan is an appropriate way of maintaining an atmosphere of inclusion and respect.
One of the roots of gender-based violence and gender dysphoria later in life is the conflation of gender and sex assigned at birth. While there is an entire social and political framework that enforces and polices gender after birth, the obstetrician can take steps to break the cycle starting before the birth has even occurred. Obstetricians are tasked with the unique challenge of providing care for the mother-fetus dyad, and much of the work is in setting up the fetus for the best possible life. Our scope of inclusion should be sufficiently wide to account for nonanatomical variations that could develop later in life in the infants we deliver.
Dr. Bahng is a PGY-1 resident physician in the gynecology & obstetrics residency program at Emory University, Atlanta. Dr. Bahng identifies as nonbinary and uses they/them/their as their personal pronouns. Dr. Joyner is an assistant professor at Emory University and is the director of gynecologic services in the Gender Center at Grady Memorial Hospital in Atlanta. Dr. Joyner identifies as a cisgender female and uses she/hers/her as her personal pronouns. Dr. Bahng and Dr. Joyner reported no financial disclosures.
References
1. Horm Behav. 2013 Jul;64(2):288-97.
2. Obstet Gynecol Surv. 2009 Jan;64(1):50-7.
Valproate, topiramate prescribed in young women despite known teratogenicity risks
results of a retrospective analysis suggest.
Topiramate, linked to increased risk of cleft palate and smaller-than-gestational-age newborns, was among the top three antiepileptic drugs (AEDs) prescribed to women 15-44 years of age in the population-based cohort study.
Valproate, linked to increases in both anatomic and behavioral teratogenicity, was less often prescribed, but nevertheless still prescribed in a considerable proportion of patients in the study, which looked at U.S. commercial, Medicare, and Medicaid claims data from 2009 to 2013.
Presence of comorbidities could be influencing whether or not a woman of childbearing age receives one of these AEDs, the investigators said. Specifically, they found valproate more often prescribed for women with epilepsy who also had mood or anxiety and dissociative disorder, while topiramate was more often prescribed in women with headaches or migraines.
Taken together, these findings suggest a lack of awareness of the teratogenic risks of valproate and topiramate, said the investigators, led by Hyunmi Kim, MD, PhD, MPH, of the department of neurology at Stanford (Calif.) University.
“To improve current practice, knowledge of the teratogenicity of certain AEDs should be disseminated to health care professionals and patients,” they wrote. The report is in JAMA Neurology.
The findings of Dr. Kim and her colleagues were based on data for 46,767 women of childbearing age: 8,003 incident (new) cases with a mean age of 27 years, and 38,764 prevalent cases with a mean age of 30 years.
Topiramate was the second- or third-most prescribed AED in the analyses, alongside levetiracetam and lamotrigine. In particular, topiramate prescriptions were found in incident cases receiving first-line monotherapy (15%), prevalent cases receiving first-line monotherapy (13%), and prevalent cases receiving polytherapy (29%).
Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy (5% and 10%, respectively), and came in fourth place among prevalent cases receiving polytherapy (22%).
The somewhat lower rate of valproate prescriptions tracks with other recent analyses showing that valproate use decreased among women of childbearing age following recommendations against its use during pregnancy, according to Dr. Kim and her coauthors.
However, topiramate is another story: “Although the magnitude of risk and range of adverse reproductive outcomes associated with topiramate use appear substantially less than those associated with valproate, some reduction in the use of topiramate in this population might be expected after evidence emerged in 2008 of its association with cleft palate,” they said in their report.
UCB Pharma sponsored this study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
SOURCE: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.
results of a retrospective analysis suggest.
Topiramate, linked to increased risk of cleft palate and smaller-than-gestational-age newborns, was among the top three antiepileptic drugs (AEDs) prescribed to women 15-44 years of age in the population-based cohort study.
Valproate, linked to increases in both anatomic and behavioral teratogenicity, was less often prescribed, but nevertheless still prescribed in a considerable proportion of patients in the study, which looked at U.S. commercial, Medicare, and Medicaid claims data from 2009 to 2013.
Presence of comorbidities could be influencing whether or not a woman of childbearing age receives one of these AEDs, the investigators said. Specifically, they found valproate more often prescribed for women with epilepsy who also had mood or anxiety and dissociative disorder, while topiramate was more often prescribed in women with headaches or migraines.
Taken together, these findings suggest a lack of awareness of the teratogenic risks of valproate and topiramate, said the investigators, led by Hyunmi Kim, MD, PhD, MPH, of the department of neurology at Stanford (Calif.) University.
“To improve current practice, knowledge of the teratogenicity of certain AEDs should be disseminated to health care professionals and patients,” they wrote. The report is in JAMA Neurology.
The findings of Dr. Kim and her colleagues were based on data for 46,767 women of childbearing age: 8,003 incident (new) cases with a mean age of 27 years, and 38,764 prevalent cases with a mean age of 30 years.
Topiramate was the second- or third-most prescribed AED in the analyses, alongside levetiracetam and lamotrigine. In particular, topiramate prescriptions were found in incident cases receiving first-line monotherapy (15%), prevalent cases receiving first-line monotherapy (13%), and prevalent cases receiving polytherapy (29%).
Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy (5% and 10%, respectively), and came in fourth place among prevalent cases receiving polytherapy (22%).
The somewhat lower rate of valproate prescriptions tracks with other recent analyses showing that valproate use decreased among women of childbearing age following recommendations against its use during pregnancy, according to Dr. Kim and her coauthors.
However, topiramate is another story: “Although the magnitude of risk and range of adverse reproductive outcomes associated with topiramate use appear substantially less than those associated with valproate, some reduction in the use of topiramate in this population might be expected after evidence emerged in 2008 of its association with cleft palate,” they said in their report.
UCB Pharma sponsored this study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
SOURCE: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.
results of a retrospective analysis suggest.
Topiramate, linked to increased risk of cleft palate and smaller-than-gestational-age newborns, was among the top three antiepileptic drugs (AEDs) prescribed to women 15-44 years of age in the population-based cohort study.
Valproate, linked to increases in both anatomic and behavioral teratogenicity, was less often prescribed, but nevertheless still prescribed in a considerable proportion of patients in the study, which looked at U.S. commercial, Medicare, and Medicaid claims data from 2009 to 2013.
Presence of comorbidities could be influencing whether or not a woman of childbearing age receives one of these AEDs, the investigators said. Specifically, they found valproate more often prescribed for women with epilepsy who also had mood or anxiety and dissociative disorder, while topiramate was more often prescribed in women with headaches or migraines.
Taken together, these findings suggest a lack of awareness of the teratogenic risks of valproate and topiramate, said the investigators, led by Hyunmi Kim, MD, PhD, MPH, of the department of neurology at Stanford (Calif.) University.
“To improve current practice, knowledge of the teratogenicity of certain AEDs should be disseminated to health care professionals and patients,” they wrote. The report is in JAMA Neurology.
The findings of Dr. Kim and her colleagues were based on data for 46,767 women of childbearing age: 8,003 incident (new) cases with a mean age of 27 years, and 38,764 prevalent cases with a mean age of 30 years.
Topiramate was the second- or third-most prescribed AED in the analyses, alongside levetiracetam and lamotrigine. In particular, topiramate prescriptions were found in incident cases receiving first-line monotherapy (15%), prevalent cases receiving first-line monotherapy (13%), and prevalent cases receiving polytherapy (29%).
Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy (5% and 10%, respectively), and came in fourth place among prevalent cases receiving polytherapy (22%).
The somewhat lower rate of valproate prescriptions tracks with other recent analyses showing that valproate use decreased among women of childbearing age following recommendations against its use during pregnancy, according to Dr. Kim and her coauthors.
However, topiramate is another story: “Although the magnitude of risk and range of adverse reproductive outcomes associated with topiramate use appear substantially less than those associated with valproate, some reduction in the use of topiramate in this population might be expected after evidence emerged in 2008 of its association with cleft palate,” they said in their report.
UCB Pharma sponsored this study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
SOURCE: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.
FROM JAMA NEUROLOGY
Key clinical point: Both valproate and topiramate are prescribed relatively often in women of childbearing age despite known teratogenic risks.
Major finding: Topiramate was the second- or third-most prescribed AED in the analyses. Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy.
Study details: Retrospective cohort study including nearly 47,000 women of childbearing age enrolled in claims databases between 2009 and 2013.
Disclosures: UCB Pharma sponsored the study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
Source: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.
Gene mutations may predispose women to alopecia subtype
in a study of women of African ancestry.
Central centrifugal cicatricial alopecia (CCCA) often runs in families, suggesting a possible genetic component, but specific genes have not been explored, wrote Liron Malki, of Tel Aviv Medical Center and his colleagues.
In a study published in the New England Journal of Medicine, the researchers used a genetic sequencing procedure to examine genes in 16 women with African ancestry with CCCA who served as a discovery set; they identified four heterozygous mutations in the PAD13 gene in 5 women, which included one splice site and three missense mutations. The PAD13 gene “is responsible for mediating the modification of proteins critical for normal hair shaft formation and shaping, such as trichohyalin, and may also play a role in interfollicular epidermal differentiation,” they wrote.
Mr. Malki and his associates then identified an additional 42 patients of African descent with CCCA and directly sequenced PADI3; they found 9 patients with genetic variations.
Overall, the researchers found six mutations in PAD13 that appeared in 14 of the 58 patients (24%) with CCCA.
In a post hoc analysis, the mutations were significantly more prevalent among CCCA patients, compared with 2,702 control women of African ancestry (P = .03 by the chi-square test and P = 0.04 by Fisher’s exact test after adjusting for relatedness of study participants).
The results were limited by several factors, including the small sample size and lack of data on individual hair grooming habits. However, the findings support data from previous studies indicating that PAD13 plays an important role in proper hair shaft formation, the researchers wrote.
“The different properties of hair among persons of African ancestry and those of European ancestry may explain, in part, the different clinical consequences of PADI3 mutations in CCCA and in the uncombable hair syndrome,” Mr. Malki and his associates wrote. “Alternatively, the distinct variants in PADI3 in each of the disorders may account for the difference in clinical outcomes.”
The study was supported in part by a grant to Eli Sprecher, MD, PhD, from the Ram Family Foundation and a grant to Dr. Sprecher and Regina C. Betz, MD, from the German-Israeli Foundation, a L’Oreal African Hair and Skin Research grant to Ncoza C. Dlova, a research grant from the Skin of Color Society to Amy McMichael, MD, and the Deutsche Forschungsgemeinschaft–funded Cluster of Excellence ImmunoSensation grant to Dr. Betz. Several other researchers – but not all – reported numerous financial disclosures from pharmaceutical and technology companies and universities and organizations.
SOURCE: Malki L et al. N Engl J Med. 2019 Feb 13. doi: 10.1056/NEJMoa1816614.
Central centrifugal cicatricial alopecia (CCCA) is characterized by hair loss with rapid, progressive, and permanent hair follicle destruction, Jouni Uitto, MD, PhD, wrote in an accompanying editorial.
The current study showed six distinct genetic mutations in PAD13, a gene that allows normal hair follicle development, in 14 of 58 women with CCCA. The researchers also found that genes involved in hair shaft formation were expressed differently in women with CCCA than in unaffected women. Dr. Uitto wrote. Thus, variants in other genes likely contribute to CCCA pathogenesis.
“The observations by Malki et al. suggest that PADI3 mutations predispose persons to CCCA, which is then clinically manifested when hairstyling practices damage the hair. Thus, in the familial setting, such practices should be discouraged in both symptomatic and asymptomatic family members.” he wrote.
Dr. Uitto also noted that uncombable hair syndrome, a rare disorder not associated with alopecia or scarring, also has been associated with mutations in PAD13. However, uncombable hair syndrome is most common in children, who usually outgrow the condition, and it appears not to be inherited. “The mutations in PADI3 in these two conditions are distinct, which suggests different pathogenic consequences of specific PADI3 variants on hair development.”
The PAD13 mutations may predispose women to CCCA, but the data do not support screening asymptomatic women, Dr. Uitto wrote.
“The presence of variants in PADI3 in both CCCA and uncombable hair syndrome suggests that this gene has a pleiotropic effect on the determination of hair texture, and the finding holds implications for future development of therapy, such as the restoration of PADI3 activity,” he concluded.
Dr. Uitto is affiliated with the department of dermatology and cutaneous biology at Jefferson Medical College, Philadelphia. This is a summary of his editorial accompanying the article by Malki et al. (New Engl J Med. 2019 Feb 13. doi: 10.1056/NEJMe1900042). He reported no relevant financial disclosures.
Central centrifugal cicatricial alopecia (CCCA) is characterized by hair loss with rapid, progressive, and permanent hair follicle destruction, Jouni Uitto, MD, PhD, wrote in an accompanying editorial.
The current study showed six distinct genetic mutations in PAD13, a gene that allows normal hair follicle development, in 14 of 58 women with CCCA. The researchers also found that genes involved in hair shaft formation were expressed differently in women with CCCA than in unaffected women. Dr. Uitto wrote. Thus, variants in other genes likely contribute to CCCA pathogenesis.
“The observations by Malki et al. suggest that PADI3 mutations predispose persons to CCCA, which is then clinically manifested when hairstyling practices damage the hair. Thus, in the familial setting, such practices should be discouraged in both symptomatic and asymptomatic family members.” he wrote.
Dr. Uitto also noted that uncombable hair syndrome, a rare disorder not associated with alopecia or scarring, also has been associated with mutations in PAD13. However, uncombable hair syndrome is most common in children, who usually outgrow the condition, and it appears not to be inherited. “The mutations in PADI3 in these two conditions are distinct, which suggests different pathogenic consequences of specific PADI3 variants on hair development.”
The PAD13 mutations may predispose women to CCCA, but the data do not support screening asymptomatic women, Dr. Uitto wrote.
“The presence of variants in PADI3 in both CCCA and uncombable hair syndrome suggests that this gene has a pleiotropic effect on the determination of hair texture, and the finding holds implications for future development of therapy, such as the restoration of PADI3 activity,” he concluded.
Dr. Uitto is affiliated with the department of dermatology and cutaneous biology at Jefferson Medical College, Philadelphia. This is a summary of his editorial accompanying the article by Malki et al. (New Engl J Med. 2019 Feb 13. doi: 10.1056/NEJMe1900042). He reported no relevant financial disclosures.
Central centrifugal cicatricial alopecia (CCCA) is characterized by hair loss with rapid, progressive, and permanent hair follicle destruction, Jouni Uitto, MD, PhD, wrote in an accompanying editorial.
The current study showed six distinct genetic mutations in PAD13, a gene that allows normal hair follicle development, in 14 of 58 women with CCCA. The researchers also found that genes involved in hair shaft formation were expressed differently in women with CCCA than in unaffected women. Dr. Uitto wrote. Thus, variants in other genes likely contribute to CCCA pathogenesis.
“The observations by Malki et al. suggest that PADI3 mutations predispose persons to CCCA, which is then clinically manifested when hairstyling practices damage the hair. Thus, in the familial setting, such practices should be discouraged in both symptomatic and asymptomatic family members.” he wrote.
Dr. Uitto also noted that uncombable hair syndrome, a rare disorder not associated with alopecia or scarring, also has been associated with mutations in PAD13. However, uncombable hair syndrome is most common in children, who usually outgrow the condition, and it appears not to be inherited. “The mutations in PADI3 in these two conditions are distinct, which suggests different pathogenic consequences of specific PADI3 variants on hair development.”
The PAD13 mutations may predispose women to CCCA, but the data do not support screening asymptomatic women, Dr. Uitto wrote.
“The presence of variants in PADI3 in both CCCA and uncombable hair syndrome suggests that this gene has a pleiotropic effect on the determination of hair texture, and the finding holds implications for future development of therapy, such as the restoration of PADI3 activity,” he concluded.
Dr. Uitto is affiliated with the department of dermatology and cutaneous biology at Jefferson Medical College, Philadelphia. This is a summary of his editorial accompanying the article by Malki et al. (New Engl J Med. 2019 Feb 13. doi: 10.1056/NEJMe1900042). He reported no relevant financial disclosures.
in a study of women of African ancestry.
Central centrifugal cicatricial alopecia (CCCA) often runs in families, suggesting a possible genetic component, but specific genes have not been explored, wrote Liron Malki, of Tel Aviv Medical Center and his colleagues.
In a study published in the New England Journal of Medicine, the researchers used a genetic sequencing procedure to examine genes in 16 women with African ancestry with CCCA who served as a discovery set; they identified four heterozygous mutations in the PAD13 gene in 5 women, which included one splice site and three missense mutations. The PAD13 gene “is responsible for mediating the modification of proteins critical for normal hair shaft formation and shaping, such as trichohyalin, and may also play a role in interfollicular epidermal differentiation,” they wrote.
Mr. Malki and his associates then identified an additional 42 patients of African descent with CCCA and directly sequenced PADI3; they found 9 patients with genetic variations.
Overall, the researchers found six mutations in PAD13 that appeared in 14 of the 58 patients (24%) with CCCA.
In a post hoc analysis, the mutations were significantly more prevalent among CCCA patients, compared with 2,702 control women of African ancestry (P = .03 by the chi-square test and P = 0.04 by Fisher’s exact test after adjusting for relatedness of study participants).
The results were limited by several factors, including the small sample size and lack of data on individual hair grooming habits. However, the findings support data from previous studies indicating that PAD13 plays an important role in proper hair shaft formation, the researchers wrote.
“The different properties of hair among persons of African ancestry and those of European ancestry may explain, in part, the different clinical consequences of PADI3 mutations in CCCA and in the uncombable hair syndrome,” Mr. Malki and his associates wrote. “Alternatively, the distinct variants in PADI3 in each of the disorders may account for the difference in clinical outcomes.”
The study was supported in part by a grant to Eli Sprecher, MD, PhD, from the Ram Family Foundation and a grant to Dr. Sprecher and Regina C. Betz, MD, from the German-Israeli Foundation, a L’Oreal African Hair and Skin Research grant to Ncoza C. Dlova, a research grant from the Skin of Color Society to Amy McMichael, MD, and the Deutsche Forschungsgemeinschaft–funded Cluster of Excellence ImmunoSensation grant to Dr. Betz. Several other researchers – but not all – reported numerous financial disclosures from pharmaceutical and technology companies and universities and organizations.
SOURCE: Malki L et al. N Engl J Med. 2019 Feb 13. doi: 10.1056/NEJMoa1816614.
in a study of women of African ancestry.
Central centrifugal cicatricial alopecia (CCCA) often runs in families, suggesting a possible genetic component, but specific genes have not been explored, wrote Liron Malki, of Tel Aviv Medical Center and his colleagues.
In a study published in the New England Journal of Medicine, the researchers used a genetic sequencing procedure to examine genes in 16 women with African ancestry with CCCA who served as a discovery set; they identified four heterozygous mutations in the PAD13 gene in 5 women, which included one splice site and three missense mutations. The PAD13 gene “is responsible for mediating the modification of proteins critical for normal hair shaft formation and shaping, such as trichohyalin, and may also play a role in interfollicular epidermal differentiation,” they wrote.
Mr. Malki and his associates then identified an additional 42 patients of African descent with CCCA and directly sequenced PADI3; they found 9 patients with genetic variations.
Overall, the researchers found six mutations in PAD13 that appeared in 14 of the 58 patients (24%) with CCCA.
In a post hoc analysis, the mutations were significantly more prevalent among CCCA patients, compared with 2,702 control women of African ancestry (P = .03 by the chi-square test and P = 0.04 by Fisher’s exact test after adjusting for relatedness of study participants).
The results were limited by several factors, including the small sample size and lack of data on individual hair grooming habits. However, the findings support data from previous studies indicating that PAD13 plays an important role in proper hair shaft formation, the researchers wrote.
“The different properties of hair among persons of African ancestry and those of European ancestry may explain, in part, the different clinical consequences of PADI3 mutations in CCCA and in the uncombable hair syndrome,” Mr. Malki and his associates wrote. “Alternatively, the distinct variants in PADI3 in each of the disorders may account for the difference in clinical outcomes.”
The study was supported in part by a grant to Eli Sprecher, MD, PhD, from the Ram Family Foundation and a grant to Dr. Sprecher and Regina C. Betz, MD, from the German-Israeli Foundation, a L’Oreal African Hair and Skin Research grant to Ncoza C. Dlova, a research grant from the Skin of Color Society to Amy McMichael, MD, and the Deutsche Forschungsgemeinschaft–funded Cluster of Excellence ImmunoSensation grant to Dr. Betz. Several other researchers – but not all – reported numerous financial disclosures from pharmaceutical and technology companies and universities and organizations.
SOURCE: Malki L et al. N Engl J Med. 2019 Feb 13. doi: 10.1056/NEJMoa1816614.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Women with central centrifugal cicatricial alopecia (CCCA) were more likely to have a mutation of the PAD13 gene than unaffected women.
Major finding: Researchers identified six mutations in PAD13 that appeared in 24% of 58 women with CCCA.
Study details: The data come from 58 adult women with African ancestry who had a diagnosis of CCCA.
Disclosures: The study was supported in part by a grant to Eli Sprecher, MD, PhD, from the Ram Family Foundation and a grant to Dr. Sprecher and Regina C. Betz, MD, from the German-Israeli Foundation, a L’Oreal African Hair and Skin Research grant to Ncoza C. Dlova, a research grant from the Skin of Color Society to Amy McMichael, MD, and the Deutsche Forschungsgemeinschaft–funded Cluster of Excellence ImmunoSensation grant to Dr. Betz. Several other researchers – but not all – reported numerous financial disclosures from pharmaceutical and technology companies and universities and organizations.
Source: Malki L et al. N Engl J Med. 2019 Feb 13. doi: 10.1056/NEJMoa1816614.
Psoriatic Arthritis Journal Scan: March 2019
A systematic review of herpes zoster incidence and consensus recommendations on vaccination in adult patients on systemic therapy for psoriasis or psoriatic arthritis: From the Medical Board of the National Psoriasis Foundation.
Baumrin E, Van Voorhees A, Garg A, Feldman SR, Merola JF. J Am Acad Dermatol. 2019 Mar 15
A systematic literature search was performed of HZ in patients with PsO/PsA. HZ vaccination guidelines were reviewed and the medical board of the National Psoriasis Foundation made consensus recommendations in PsO/PsA patients based on graded evidence. HZ risk depends on disease severity and treatment class. Recombinant zoster vaccine should be given to all PsO/PsA patients >50 years old and younger patients at increased risk.
Ultrasonographic and Clinical Assessment of Peripheral Enthesitis in Patients with Psoriatic Arthritis, Psoriasis, and Fibromyalgia Syndrome: The ULISSE Study.
Macchioni P, Salvarani C, Possemato N, et al. J Rheumatol. 2019 Mar 15.
The ULISSE study indicated that enthesitis is a common feature in patients with PsA, those with psoriasis, and in those with FMS if only clinical examination is used. US entheseal assessment showed findings more consistent with the 3 disorders.
The development of a modified Psoriatic Arthritis Disease Activity Score (mPASDAS) using SF-12 as a measure of quality of life.
Perruccio AV, Got M, Li S, Ye Y, Gladman DD, Chandran V. Arthritis Care Res (Hoboken). 2019 Mar 15.
The Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite measure of psoriatic arthritis (PsA) disease activity. The length of its patient-reported components raises concern about questionnaire burden. The PASDAS includes the SF-36 measure. The study investigated the agreement between PASDAS and a modified PASDAS (mPASDAS) which substituted the SF-36 with the shortened SF-12.
The Impact of Intermittent Fasting (Ramadan Fasting) on Psoriatic Arthritis Disease Activity, Enthesitis, and Dactylitis: A Multicentre Study.
Adawi M, Damiani G, Bragazzi NL, et al. Nutrients. 2019 Mar 12;11(3).
Fasting was found to be a predictor of a decrease in PsA disease activity scores (DAPSA, BASDAI, LEI, DSS) even after adjustment for weight loss. IL-17 therapy was found to be an independent predictor of decreases in LEI after fasting.
Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition.
Scher JU, Ogdie A, Merola JF, Ritchlin C. Nat Rev Rheumatol. 2019 Mar;15(3):153-166.
The events responsible for progression to PsA are currently unclear. Genetic and clinical–demographic risk factors (most notably familial aggregation and psoriasis sub-phenotypes) provide relevant insights into the variables that promote transition.
A systematic review of herpes zoster incidence and consensus recommendations on vaccination in adult patients on systemic therapy for psoriasis or psoriatic arthritis: From the Medical Board of the National Psoriasis Foundation.
Baumrin E, Van Voorhees A, Garg A, Feldman SR, Merola JF. J Am Acad Dermatol. 2019 Mar 15
A systematic literature search was performed of HZ in patients with PsO/PsA. HZ vaccination guidelines were reviewed and the medical board of the National Psoriasis Foundation made consensus recommendations in PsO/PsA patients based on graded evidence. HZ risk depends on disease severity and treatment class. Recombinant zoster vaccine should be given to all PsO/PsA patients >50 years old and younger patients at increased risk.
Ultrasonographic and Clinical Assessment of Peripheral Enthesitis in Patients with Psoriatic Arthritis, Psoriasis, and Fibromyalgia Syndrome: The ULISSE Study.
Macchioni P, Salvarani C, Possemato N, et al. J Rheumatol. 2019 Mar 15.
The ULISSE study indicated that enthesitis is a common feature in patients with PsA, those with psoriasis, and in those with FMS if only clinical examination is used. US entheseal assessment showed findings more consistent with the 3 disorders.
The development of a modified Psoriatic Arthritis Disease Activity Score (mPASDAS) using SF-12 as a measure of quality of life.
Perruccio AV, Got M, Li S, Ye Y, Gladman DD, Chandran V. Arthritis Care Res (Hoboken). 2019 Mar 15.
The Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite measure of psoriatic arthritis (PsA) disease activity. The length of its patient-reported components raises concern about questionnaire burden. The PASDAS includes the SF-36 measure. The study investigated the agreement between PASDAS and a modified PASDAS (mPASDAS) which substituted the SF-36 with the shortened SF-12.
The Impact of Intermittent Fasting (Ramadan Fasting) on Psoriatic Arthritis Disease Activity, Enthesitis, and Dactylitis: A Multicentre Study.
Adawi M, Damiani G, Bragazzi NL, et al. Nutrients. 2019 Mar 12;11(3).
Fasting was found to be a predictor of a decrease in PsA disease activity scores (DAPSA, BASDAI, LEI, DSS) even after adjustment for weight loss. IL-17 therapy was found to be an independent predictor of decreases in LEI after fasting.
Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition.
Scher JU, Ogdie A, Merola JF, Ritchlin C. Nat Rev Rheumatol. 2019 Mar;15(3):153-166.
The events responsible for progression to PsA are currently unclear. Genetic and clinical–demographic risk factors (most notably familial aggregation and psoriasis sub-phenotypes) provide relevant insights into the variables that promote transition.
A systematic review of herpes zoster incidence and consensus recommendations on vaccination in adult patients on systemic therapy for psoriasis or psoriatic arthritis: From the Medical Board of the National Psoriasis Foundation.
Baumrin E, Van Voorhees A, Garg A, Feldman SR, Merola JF. J Am Acad Dermatol. 2019 Mar 15
A systematic literature search was performed of HZ in patients with PsO/PsA. HZ vaccination guidelines were reviewed and the medical board of the National Psoriasis Foundation made consensus recommendations in PsO/PsA patients based on graded evidence. HZ risk depends on disease severity and treatment class. Recombinant zoster vaccine should be given to all PsO/PsA patients >50 years old and younger patients at increased risk.
Ultrasonographic and Clinical Assessment of Peripheral Enthesitis in Patients with Psoriatic Arthritis, Psoriasis, and Fibromyalgia Syndrome: The ULISSE Study.
Macchioni P, Salvarani C, Possemato N, et al. J Rheumatol. 2019 Mar 15.
The ULISSE study indicated that enthesitis is a common feature in patients with PsA, those with psoriasis, and in those with FMS if only clinical examination is used. US entheseal assessment showed findings more consistent with the 3 disorders.
The development of a modified Psoriatic Arthritis Disease Activity Score (mPASDAS) using SF-12 as a measure of quality of life.
Perruccio AV, Got M, Li S, Ye Y, Gladman DD, Chandran V. Arthritis Care Res (Hoboken). 2019 Mar 15.
The Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite measure of psoriatic arthritis (PsA) disease activity. The length of its patient-reported components raises concern about questionnaire burden. The PASDAS includes the SF-36 measure. The study investigated the agreement between PASDAS and a modified PASDAS (mPASDAS) which substituted the SF-36 with the shortened SF-12.
The Impact of Intermittent Fasting (Ramadan Fasting) on Psoriatic Arthritis Disease Activity, Enthesitis, and Dactylitis: A Multicentre Study.
Adawi M, Damiani G, Bragazzi NL, et al. Nutrients. 2019 Mar 12;11(3).
Fasting was found to be a predictor of a decrease in PsA disease activity scores (DAPSA, BASDAI, LEI, DSS) even after adjustment for weight loss. IL-17 therapy was found to be an independent predictor of decreases in LEI after fasting.
Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition.
Scher JU, Ogdie A, Merola JF, Ritchlin C. Nat Rev Rheumatol. 2019 Mar;15(3):153-166.
The events responsible for progression to PsA are currently unclear. Genetic and clinical–demographic risk factors (most notably familial aggregation and psoriasis sub-phenotypes) provide relevant insights into the variables that promote transition.
Spontaneous coronary artery dissection: An often unrecognized cause of acute coronary syndrome
A 12-lead electrocardiogram (Figure 1) showed ST-segment elevation of more than 2 mm in leads V2, V3, V4, and V5, with no reciprocal changes.
Based on the classic angiographic appearance and the absence of atherosclerotic disease in other coronary arteries, type 2 spontaneous coronary artery dissection (SCAD) was diagnosed.
CORONARY ARTERY WALL SEPARATION
SCAD is defined as a nontraumatic, noniatrogenic intramural hemorrhage leading to separation of the coronary arterial wall and the formation of a false lumen. The separation can occur between any of the coronary artery wall layers and may or may not involve an intimal tear. The bleeding may result in an intramural hematoma and possible narrowing of the arterial lumen. Depending on the severity of narrowing, blood supply to the myocardium could be compromised, resulting in symptoms of ischemia.1
SCAD usually involves a single coronary artery, although multiple coronary artery involvement has been reported.2
CASE CONTINUED: MANAGEMENT
The patient recovered completely and was discharged home with plans to return for outpatient imaging for fibromuscular dysplasia.
SCAD: RARE OR JUST RARELY RECOGNIZED?
SCAD appears to be a rare cause of acute coronary syndrome, but it is likely underdiagnosed and is becoming increasingly recognized worldwide. Typically, it affects women younger than 50, with women in general outnumbering men 9 to 1.3 Overall, SCAD causes up to 4% of acute myocardial infarctions, but in women age 50 or younger, it is responsible for 24% to 35% of acute myocardial infarctions, and the proportion is even higher in pregnant women.4
Not just pregnancy-associated
SCAD was previously thought to be mainly idiopathic and mostly affecting women peripartum. Current understanding paints a different picture: pregnancy-associated SCAD does not account for the majority of cases. That said, SCAD is the most common cause of myocardial infarction peripartum, with the third trimester and early postpartum period being the times of highest risk.5 SCAD development at those times is believed to be related to hormonal changes causing weakening of coronary artery walls.6
Weakening of the coronary artery wall also may occur in the setting of fibromuscular dysplasia, connective tissue disease, recurrent pregnancies, systemic inflammatory disease, hormonal therapy, and other disease states that cause arteriopathy. Exposure to a stressor in a patient with underlying risk factors can lead to either an intimal tear or rupture of the vasa vasorum, with subsequent formation of intramural hemorrhage and eventually SCAD.7 Stressors can be emotional or physical and can include labor and delivery, intense physical exercise, the Valsalva maneuver, and drug abuse.8
Presentation is variable
SCAD presentation depends on the degree of flow limitation and extent of the dissection. Presentation can range from asymptomatic to sudden cardiac death and can include signs and symptoms of acute coronary syndrome caused by ST-segment elevation or non-ST-segment elevation myocardial infarction.
DIAGNOSIS BY ANGIOGRAPHY
SCAD can be diagnosed by coronary angiography. There are 3 angiographic types:
Type 1 (about 25% of SCAD cases) has typical contrast dye staining of the arterial wall and multiple radiolucent luminal abnormalities, with or without dye hang-up.
Type 2 (about 70%) has diffuse, smooth narrowing of the coronary artery, with the left anterior descending artery the most frequently affected.8
Type 3 (about 5%) mimics atherosclerosis, with focal or tubular stenosis.9
Types 1 and 2 are usually easy to recognize. To diagnose type 2, intravenous nitroglycerin should first be administered to rule out coronary spasm.
Type 3 SCAD is more challenging to diagnose because its appearance on angiography is similar to that of atherosclerosis. For equivocal findings in any type, but especially in type 3, intravascular ultrasonography or optical coherence tomography can help.10 Optical coherence tomography is preferred because of superior image resolution, although ultrasonography offers better tissue penetration.11
MANAGE MOST CASES CONSERVATIVELY
Management algorithms for SCAD are available.8,12
The initial and most critical step is to make the correct diagnosis. Although the presentation of acute coronary syndrome caused by SCAD is often identical to that of atherosclerosis, the conditions have different pathophysiologies and thus require different management. Theoretically, systemic anticoagulation may worsen an intramural hemorrhage.
First-line therapy for most patients with SCAD is conservative management and close inpatient monitoring for 3 to 5 days.13 More aggressive management is indicated for any of the following:
- Left main or severe proximal 2-vessel dissection
- Hemodynamic instability
- Ongoing ischemic symptoms.
In a prospective cohort of 168 patients, 134 (80%) were initially treated conservatively; of those, in-hospital myocardial infarction recurred in 4.5%, a major cardiac event occurred within 2 years in 17%, and SCAD recurred in 13%.8
Observational data on patients with SCAD who had repeat angiography weeks to months after the initial event has shown that lesions heal in 70% to 97% of patients.12
WHEN TO CONSIDER AGGRESSIVE MANAGEMENT
Under the circumstances listed above, revascularization with PCI or coronary artery bypass grafting (CABG) should be considered, with choice of procedure determined by feasibility, technical considerations, and local expertise.
The American Heart Association recommendations are as follows12:
- For left main or severe proximal 2-vessel dissection in clinically stable patients, consider CABG
- For active ischemia or hemodynamic instability, consider PCI if feasible or perform urgent CABG.
A few series have shown that the prognosis with conservative management or CABG is better than with PCI.8,13,14 The success rate for revascularization with PCI is only about 60% because of challenges including risk of inducing iatrogenic dissection, passing the wire into the false lumen and worsening a dissection, and propagating an intramural hematoma with stenting and further compromising coronary blood flow. In addition, dissection tends to extend into distal arteries that are difficult to stent. There is also the risk of stent malapposition after resorption of the intramural hematoma, causing late stent thrombosis.7
SCREEN FOR OTHER VASCULAR PROBLEMS
Imaging of the renal, iliac, and cerebral vasculature is recommended for all patients with SCAD.12 Screening for fibromuscular dysplasia can be done with angiography, computed tomographic angiography (CTA), or magnetic resonance angiography (MRA).12
Multifocal fibromuscular dysplasia in extracoronary arteries occurs with SCAD in 25% to 86% of cases. In a single-center series of 115 patients with confirmed SCAD who underwent CTA from 2010 to 2014, extracoronary vascular abnormalities were found in 66%, with fibromuscular dysplasia being the most common type (45%).15 In another single-center study, 327 patients with SCAD were prospectively followed from 2012 to 2016 with screening for cerebrovascular, renal, and iliac fibromuscular dysplasia using CTA or catheter angiography. Fibromuscular dysplasia was found in 63%, and intracranial aneurysm was found in 14% of patients with fibromuscular dysplasia.9
SCAD can also be associated with connective tissue disorders such as Ehlers-Danlos syndrome type IV and Marfan syndrome.16,17
LONG-TERM MANAGEMENT
Patients with SCAD should start long-term aspirin and 1 year of clopidogrel. Statins are indicated for patients with hyperlipidemia8,18 but otherwise offer no clear benefit for SCAD alone. If there are no contraindications, a beta-adrenergic blocker should be considered, especially if left ventricular dysfunction or arrhythmias are present. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers should also be considered with concomitant left ventricular dysfunction. Antianginal therapy can be used for post-SCAD chest pain syndromes.12
Repeat angiography is recommended only to evaluate recurrent symptoms, to confirm an unclear initial diagnosis, to assess for atherosclerosis-related stenosis, or to evaluate high-risk anatomy, eg, involvement of the left main coronary artery.12
Genetic testing is reserved for patients with a high clinical suspicion of connective tissue disease or systemic arteriopathy.19
- Garcia NA, Khan AN, Boppana RC, Smith HL. Spontaneous coronary artery dissection: a case series and literature review. J Community Hosp Intern Med Perspect 2014; 4(4). doi:10.3402/jchimp.v4.25261
- Lempereur M, Gin K, Saw J. Multivessel spontaneous coronary artery dissection mimicking atherosclerosis. JACC Cardiovasc Interv 2014; 7(7):e87–e88. doi:10.1016/j.jcin.2013.12.207
- Mahmoud AN, Taduru SS, Mentias A, et al. Trends of incidence, clinical presentation, and in-hospital mortality among women with acute myocardial infarction with or without spontaneous coronary artery dissection: a population-based analysis. JACC Cardiovasc Interv 2018; 11(1):80–90. doi:10.1016/j.jcin.2017.08.016
- Saw J. Pregnancy-associated spontaneous coronary artery dissection represents an exceptionally high-risk spontaneous coronary artery dissection cohort. Circ Cardiovasc Interv 2017; 10(3)pii:e005119. doi:10.1161/CIRCINTERVENTIONS.117.005119
- Elkayam U, Jalnapurkar S, Barakkat MN, et al. Pregnancy-associated acute myocardial infarction: a review of contemporary experience in 150 cases between 2006 and 2011. Circulation 2014; 129(16):1695–1702. doi:10.1161/CIRCULATIONAHA.113.002054
- Vijayaraghavan R, Verma S, Gupta N, Saw J. Pregnancy-related spontaneous coronary artery dissection. Circulation 2014; 130(21):1915–1920. doi:10.1161/CIRCULATIONAHA.114.011422
- Saw J, Mancini GBJ, Humphries KH. Contemporary review on spontaneous coronary artery dissection. J Am Coll Cardiol 2016; 68(3):297–312. doi:10.1016/j.jacc.2016.05.034
- Saw J, Aymong E, Sedlak T, et al. Spontaneous coronary artery dissection: association with predisposing arteriopathies and precipitating stressors and cardiovascular outcomes. Circ Cardiovasc Interv 2014; 7(5):645–655. doi:10.1161/CIRCINTERVENTIONS.114.001760
- Saw J, Humphries K ,Aymong E, et al. Spontaneous coronary artery dissection: clinical outcomes and risk of recurrence. J Am Coll Cardiol 2017; 70(9):1148–1158. doi:10.1016/j.jacc.2017.06.053
- Alfonso F, Bastante T, Cuesta J, Rodríguez D, Benedicto A, Rivero F. Spontaneous coronary artery dissection: novel insights on diagnosis and management. Cardiovasc Diagn Ther 2015; 5(2):133–140. doi:10.3978/j.issn.2223-3652.2015.03.05
- Kern MJ, Meier B. Evaluation of the culprit plaque and the physiological significance of coronary atherosclerotic narrowings. Circulation 2001; 103(25):3142–3149. pmid:11425782
- Hayes SN, Kim ESH, Saw J, et al; American Heart Association Council on Peripheral Vascular Disease; Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Genomic and Precision Medicine; and Stroke Council. Spontaneous coronary artery dissection: current state of the science: a scientific statement from the American Heart Association. Circulation 2018; 137(19):e523–e557. doi:10.1161/CIR.0000000000000564
- Tweet MS, Eleid MF, Best PJ, et al. Spontaneous coronary artery dissection: revascularization versus conservative therapy. Circ Cardiovasc Interv 2014; 7(6):777–786. doi:10.1161/CIRCINTERVENTIONS.114.001659
- Tweet MS, Hayes SN, Pitta SR, et al. Clinical features, management, and prognosis of spontaneous coronary artery dissection. Circulation 2012; 126(5):579–588. doi:10.1161/CIRCULATIONAHA.112.105718
- Prasad M, Tweet MS, Hayes SN, et al. Prevalence of extracoronary vascular abnormalities and fibromuscular dysplasia in patients with spontaneous coronary artery dissection. Am J Cardiol 2015; 115(12):1672–1677. doi:10.1016/j.amjcard.2015.03.011
- Adès LC, Waltham RD, Chiodo AA, Bateman JF. Myocardial infarction resulting from coronary artery dissection in an adolescent with Ehlers-Danlos syndrome type IV due to a type III collagen mutation. Br Heart J 1995; 74(2):112–116. pmid:7546986
- Judge DP, Dietz HC. Marfan’s syndrome. Lancet 2005; 366(9501):1965–1976. doi:10.1016/S0140-6736(05)67789-6
- Saw J. Spontaneous coronary artery dissection. Can J Cardiol 2013; 29(9):1027–1033. doi:10.1016/j.cjca.2012.12.018
- Poloskey SL, Kim ES, Sanghani R, et al. Low yield of genetic testing for known vascular connective tissue disorders in patients with fibromuscular dysplasia. Vasc Med 2012; 17(6):371–378. doi:10.1177/1358863X12459650
A 12-lead electrocardiogram (Figure 1) showed ST-segment elevation of more than 2 mm in leads V2, V3, V4, and V5, with no reciprocal changes.
Based on the classic angiographic appearance and the absence of atherosclerotic disease in other coronary arteries, type 2 spontaneous coronary artery dissection (SCAD) was diagnosed.
CORONARY ARTERY WALL SEPARATION
SCAD is defined as a nontraumatic, noniatrogenic intramural hemorrhage leading to separation of the coronary arterial wall and the formation of a false lumen. The separation can occur between any of the coronary artery wall layers and may or may not involve an intimal tear. The bleeding may result in an intramural hematoma and possible narrowing of the arterial lumen. Depending on the severity of narrowing, blood supply to the myocardium could be compromised, resulting in symptoms of ischemia.1
SCAD usually involves a single coronary artery, although multiple coronary artery involvement has been reported.2
CASE CONTINUED: MANAGEMENT
The patient recovered completely and was discharged home with plans to return for outpatient imaging for fibromuscular dysplasia.
SCAD: RARE OR JUST RARELY RECOGNIZED?
SCAD appears to be a rare cause of acute coronary syndrome, but it is likely underdiagnosed and is becoming increasingly recognized worldwide. Typically, it affects women younger than 50, with women in general outnumbering men 9 to 1.3 Overall, SCAD causes up to 4% of acute myocardial infarctions, but in women age 50 or younger, it is responsible for 24% to 35% of acute myocardial infarctions, and the proportion is even higher in pregnant women.4
Not just pregnancy-associated
SCAD was previously thought to be mainly idiopathic and mostly affecting women peripartum. Current understanding paints a different picture: pregnancy-associated SCAD does not account for the majority of cases. That said, SCAD is the most common cause of myocardial infarction peripartum, with the third trimester and early postpartum period being the times of highest risk.5 SCAD development at those times is believed to be related to hormonal changes causing weakening of coronary artery walls.6
Weakening of the coronary artery wall also may occur in the setting of fibromuscular dysplasia, connective tissue disease, recurrent pregnancies, systemic inflammatory disease, hormonal therapy, and other disease states that cause arteriopathy. Exposure to a stressor in a patient with underlying risk factors can lead to either an intimal tear or rupture of the vasa vasorum, with subsequent formation of intramural hemorrhage and eventually SCAD.7 Stressors can be emotional or physical and can include labor and delivery, intense physical exercise, the Valsalva maneuver, and drug abuse.8
Presentation is variable
SCAD presentation depends on the degree of flow limitation and extent of the dissection. Presentation can range from asymptomatic to sudden cardiac death and can include signs and symptoms of acute coronary syndrome caused by ST-segment elevation or non-ST-segment elevation myocardial infarction.
DIAGNOSIS BY ANGIOGRAPHY
SCAD can be diagnosed by coronary angiography. There are 3 angiographic types:
Type 1 (about 25% of SCAD cases) has typical contrast dye staining of the arterial wall and multiple radiolucent luminal abnormalities, with or without dye hang-up.
Type 2 (about 70%) has diffuse, smooth narrowing of the coronary artery, with the left anterior descending artery the most frequently affected.8
Type 3 (about 5%) mimics atherosclerosis, with focal or tubular stenosis.9
Types 1 and 2 are usually easy to recognize. To diagnose type 2, intravenous nitroglycerin should first be administered to rule out coronary spasm.
Type 3 SCAD is more challenging to diagnose because its appearance on angiography is similar to that of atherosclerosis. For equivocal findings in any type, but especially in type 3, intravascular ultrasonography or optical coherence tomography can help.10 Optical coherence tomography is preferred because of superior image resolution, although ultrasonography offers better tissue penetration.11
MANAGE MOST CASES CONSERVATIVELY
Management algorithms for SCAD are available.8,12
The initial and most critical step is to make the correct diagnosis. Although the presentation of acute coronary syndrome caused by SCAD is often identical to that of atherosclerosis, the conditions have different pathophysiologies and thus require different management. Theoretically, systemic anticoagulation may worsen an intramural hemorrhage.
First-line therapy for most patients with SCAD is conservative management and close inpatient monitoring for 3 to 5 days.13 More aggressive management is indicated for any of the following:
- Left main or severe proximal 2-vessel dissection
- Hemodynamic instability
- Ongoing ischemic symptoms.
In a prospective cohort of 168 patients, 134 (80%) were initially treated conservatively; of those, in-hospital myocardial infarction recurred in 4.5%, a major cardiac event occurred within 2 years in 17%, and SCAD recurred in 13%.8
Observational data on patients with SCAD who had repeat angiography weeks to months after the initial event has shown that lesions heal in 70% to 97% of patients.12
WHEN TO CONSIDER AGGRESSIVE MANAGEMENT
Under the circumstances listed above, revascularization with PCI or coronary artery bypass grafting (CABG) should be considered, with choice of procedure determined by feasibility, technical considerations, and local expertise.
The American Heart Association recommendations are as follows12:
- For left main or severe proximal 2-vessel dissection in clinically stable patients, consider CABG
- For active ischemia or hemodynamic instability, consider PCI if feasible or perform urgent CABG.
A few series have shown that the prognosis with conservative management or CABG is better than with PCI.8,13,14 The success rate for revascularization with PCI is only about 60% because of challenges including risk of inducing iatrogenic dissection, passing the wire into the false lumen and worsening a dissection, and propagating an intramural hematoma with stenting and further compromising coronary blood flow. In addition, dissection tends to extend into distal arteries that are difficult to stent. There is also the risk of stent malapposition after resorption of the intramural hematoma, causing late stent thrombosis.7
SCREEN FOR OTHER VASCULAR PROBLEMS
Imaging of the renal, iliac, and cerebral vasculature is recommended for all patients with SCAD.12 Screening for fibromuscular dysplasia can be done with angiography, computed tomographic angiography (CTA), or magnetic resonance angiography (MRA).12
Multifocal fibromuscular dysplasia in extracoronary arteries occurs with SCAD in 25% to 86% of cases. In a single-center series of 115 patients with confirmed SCAD who underwent CTA from 2010 to 2014, extracoronary vascular abnormalities were found in 66%, with fibromuscular dysplasia being the most common type (45%).15 In another single-center study, 327 patients with SCAD were prospectively followed from 2012 to 2016 with screening for cerebrovascular, renal, and iliac fibromuscular dysplasia using CTA or catheter angiography. Fibromuscular dysplasia was found in 63%, and intracranial aneurysm was found in 14% of patients with fibromuscular dysplasia.9
SCAD can also be associated with connective tissue disorders such as Ehlers-Danlos syndrome type IV and Marfan syndrome.16,17
LONG-TERM MANAGEMENT
Patients with SCAD should start long-term aspirin and 1 year of clopidogrel. Statins are indicated for patients with hyperlipidemia8,18 but otherwise offer no clear benefit for SCAD alone. If there are no contraindications, a beta-adrenergic blocker should be considered, especially if left ventricular dysfunction or arrhythmias are present. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers should also be considered with concomitant left ventricular dysfunction. Antianginal therapy can be used for post-SCAD chest pain syndromes.12
Repeat angiography is recommended only to evaluate recurrent symptoms, to confirm an unclear initial diagnosis, to assess for atherosclerosis-related stenosis, or to evaluate high-risk anatomy, eg, involvement of the left main coronary artery.12
Genetic testing is reserved for patients with a high clinical suspicion of connective tissue disease or systemic arteriopathy.19
A 12-lead electrocardiogram (Figure 1) showed ST-segment elevation of more than 2 mm in leads V2, V3, V4, and V5, with no reciprocal changes.
Based on the classic angiographic appearance and the absence of atherosclerotic disease in other coronary arteries, type 2 spontaneous coronary artery dissection (SCAD) was diagnosed.
CORONARY ARTERY WALL SEPARATION
SCAD is defined as a nontraumatic, noniatrogenic intramural hemorrhage leading to separation of the coronary arterial wall and the formation of a false lumen. The separation can occur between any of the coronary artery wall layers and may or may not involve an intimal tear. The bleeding may result in an intramural hematoma and possible narrowing of the arterial lumen. Depending on the severity of narrowing, blood supply to the myocardium could be compromised, resulting in symptoms of ischemia.1
SCAD usually involves a single coronary artery, although multiple coronary artery involvement has been reported.2
CASE CONTINUED: MANAGEMENT
The patient recovered completely and was discharged home with plans to return for outpatient imaging for fibromuscular dysplasia.
SCAD: RARE OR JUST RARELY RECOGNIZED?
SCAD appears to be a rare cause of acute coronary syndrome, but it is likely underdiagnosed and is becoming increasingly recognized worldwide. Typically, it affects women younger than 50, with women in general outnumbering men 9 to 1.3 Overall, SCAD causes up to 4% of acute myocardial infarctions, but in women age 50 or younger, it is responsible for 24% to 35% of acute myocardial infarctions, and the proportion is even higher in pregnant women.4
Not just pregnancy-associated
SCAD was previously thought to be mainly idiopathic and mostly affecting women peripartum. Current understanding paints a different picture: pregnancy-associated SCAD does not account for the majority of cases. That said, SCAD is the most common cause of myocardial infarction peripartum, with the third trimester and early postpartum period being the times of highest risk.5 SCAD development at those times is believed to be related to hormonal changes causing weakening of coronary artery walls.6
Weakening of the coronary artery wall also may occur in the setting of fibromuscular dysplasia, connective tissue disease, recurrent pregnancies, systemic inflammatory disease, hormonal therapy, and other disease states that cause arteriopathy. Exposure to a stressor in a patient with underlying risk factors can lead to either an intimal tear or rupture of the vasa vasorum, with subsequent formation of intramural hemorrhage and eventually SCAD.7 Stressors can be emotional or physical and can include labor and delivery, intense physical exercise, the Valsalva maneuver, and drug abuse.8
Presentation is variable
SCAD presentation depends on the degree of flow limitation and extent of the dissection. Presentation can range from asymptomatic to sudden cardiac death and can include signs and symptoms of acute coronary syndrome caused by ST-segment elevation or non-ST-segment elevation myocardial infarction.
DIAGNOSIS BY ANGIOGRAPHY
SCAD can be diagnosed by coronary angiography. There are 3 angiographic types:
Type 1 (about 25% of SCAD cases) has typical contrast dye staining of the arterial wall and multiple radiolucent luminal abnormalities, with or without dye hang-up.
Type 2 (about 70%) has diffuse, smooth narrowing of the coronary artery, with the left anterior descending artery the most frequently affected.8
Type 3 (about 5%) mimics atherosclerosis, with focal or tubular stenosis.9
Types 1 and 2 are usually easy to recognize. To diagnose type 2, intravenous nitroglycerin should first be administered to rule out coronary spasm.
Type 3 SCAD is more challenging to diagnose because its appearance on angiography is similar to that of atherosclerosis. For equivocal findings in any type, but especially in type 3, intravascular ultrasonography or optical coherence tomography can help.10 Optical coherence tomography is preferred because of superior image resolution, although ultrasonography offers better tissue penetration.11
MANAGE MOST CASES CONSERVATIVELY
Management algorithms for SCAD are available.8,12
The initial and most critical step is to make the correct diagnosis. Although the presentation of acute coronary syndrome caused by SCAD is often identical to that of atherosclerosis, the conditions have different pathophysiologies and thus require different management. Theoretically, systemic anticoagulation may worsen an intramural hemorrhage.
First-line therapy for most patients with SCAD is conservative management and close inpatient monitoring for 3 to 5 days.13 More aggressive management is indicated for any of the following:
- Left main or severe proximal 2-vessel dissection
- Hemodynamic instability
- Ongoing ischemic symptoms.
In a prospective cohort of 168 patients, 134 (80%) were initially treated conservatively; of those, in-hospital myocardial infarction recurred in 4.5%, a major cardiac event occurred within 2 years in 17%, and SCAD recurred in 13%.8
Observational data on patients with SCAD who had repeat angiography weeks to months after the initial event has shown that lesions heal in 70% to 97% of patients.12
WHEN TO CONSIDER AGGRESSIVE MANAGEMENT
Under the circumstances listed above, revascularization with PCI or coronary artery bypass grafting (CABG) should be considered, with choice of procedure determined by feasibility, technical considerations, and local expertise.
The American Heart Association recommendations are as follows12:
- For left main or severe proximal 2-vessel dissection in clinically stable patients, consider CABG
- For active ischemia or hemodynamic instability, consider PCI if feasible or perform urgent CABG.
A few series have shown that the prognosis with conservative management or CABG is better than with PCI.8,13,14 The success rate for revascularization with PCI is only about 60% because of challenges including risk of inducing iatrogenic dissection, passing the wire into the false lumen and worsening a dissection, and propagating an intramural hematoma with stenting and further compromising coronary blood flow. In addition, dissection tends to extend into distal arteries that are difficult to stent. There is also the risk of stent malapposition after resorption of the intramural hematoma, causing late stent thrombosis.7
SCREEN FOR OTHER VASCULAR PROBLEMS
Imaging of the renal, iliac, and cerebral vasculature is recommended for all patients with SCAD.12 Screening for fibromuscular dysplasia can be done with angiography, computed tomographic angiography (CTA), or magnetic resonance angiography (MRA).12
Multifocal fibromuscular dysplasia in extracoronary arteries occurs with SCAD in 25% to 86% of cases. In a single-center series of 115 patients with confirmed SCAD who underwent CTA from 2010 to 2014, extracoronary vascular abnormalities were found in 66%, with fibromuscular dysplasia being the most common type (45%).15 In another single-center study, 327 patients with SCAD were prospectively followed from 2012 to 2016 with screening for cerebrovascular, renal, and iliac fibromuscular dysplasia using CTA or catheter angiography. Fibromuscular dysplasia was found in 63%, and intracranial aneurysm was found in 14% of patients with fibromuscular dysplasia.9
SCAD can also be associated with connective tissue disorders such as Ehlers-Danlos syndrome type IV and Marfan syndrome.16,17
LONG-TERM MANAGEMENT
Patients with SCAD should start long-term aspirin and 1 year of clopidogrel. Statins are indicated for patients with hyperlipidemia8,18 but otherwise offer no clear benefit for SCAD alone. If there are no contraindications, a beta-adrenergic blocker should be considered, especially if left ventricular dysfunction or arrhythmias are present. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers should also be considered with concomitant left ventricular dysfunction. Antianginal therapy can be used for post-SCAD chest pain syndromes.12
Repeat angiography is recommended only to evaluate recurrent symptoms, to confirm an unclear initial diagnosis, to assess for atherosclerosis-related stenosis, or to evaluate high-risk anatomy, eg, involvement of the left main coronary artery.12
Genetic testing is reserved for patients with a high clinical suspicion of connective tissue disease or systemic arteriopathy.19
- Garcia NA, Khan AN, Boppana RC, Smith HL. Spontaneous coronary artery dissection: a case series and literature review. J Community Hosp Intern Med Perspect 2014; 4(4). doi:10.3402/jchimp.v4.25261
- Lempereur M, Gin K, Saw J. Multivessel spontaneous coronary artery dissection mimicking atherosclerosis. JACC Cardiovasc Interv 2014; 7(7):e87–e88. doi:10.1016/j.jcin.2013.12.207
- Mahmoud AN, Taduru SS, Mentias A, et al. Trends of incidence, clinical presentation, and in-hospital mortality among women with acute myocardial infarction with or without spontaneous coronary artery dissection: a population-based analysis. JACC Cardiovasc Interv 2018; 11(1):80–90. doi:10.1016/j.jcin.2017.08.016
- Saw J. Pregnancy-associated spontaneous coronary artery dissection represents an exceptionally high-risk spontaneous coronary artery dissection cohort. Circ Cardiovasc Interv 2017; 10(3)pii:e005119. doi:10.1161/CIRCINTERVENTIONS.117.005119
- Elkayam U, Jalnapurkar S, Barakkat MN, et al. Pregnancy-associated acute myocardial infarction: a review of contemporary experience in 150 cases between 2006 and 2011. Circulation 2014; 129(16):1695–1702. doi:10.1161/CIRCULATIONAHA.113.002054
- Vijayaraghavan R, Verma S, Gupta N, Saw J. Pregnancy-related spontaneous coronary artery dissection. Circulation 2014; 130(21):1915–1920. doi:10.1161/CIRCULATIONAHA.114.011422
- Saw J, Mancini GBJ, Humphries KH. Contemporary review on spontaneous coronary artery dissection. J Am Coll Cardiol 2016; 68(3):297–312. doi:10.1016/j.jacc.2016.05.034
- Saw J, Aymong E, Sedlak T, et al. Spontaneous coronary artery dissection: association with predisposing arteriopathies and precipitating stressors and cardiovascular outcomes. Circ Cardiovasc Interv 2014; 7(5):645–655. doi:10.1161/CIRCINTERVENTIONS.114.001760
- Saw J, Humphries K ,Aymong E, et al. Spontaneous coronary artery dissection: clinical outcomes and risk of recurrence. J Am Coll Cardiol 2017; 70(9):1148–1158. doi:10.1016/j.jacc.2017.06.053
- Alfonso F, Bastante T, Cuesta J, Rodríguez D, Benedicto A, Rivero F. Spontaneous coronary artery dissection: novel insights on diagnosis and management. Cardiovasc Diagn Ther 2015; 5(2):133–140. doi:10.3978/j.issn.2223-3652.2015.03.05
- Kern MJ, Meier B. Evaluation of the culprit plaque and the physiological significance of coronary atherosclerotic narrowings. Circulation 2001; 103(25):3142–3149. pmid:11425782
- Hayes SN, Kim ESH, Saw J, et al; American Heart Association Council on Peripheral Vascular Disease; Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Genomic and Precision Medicine; and Stroke Council. Spontaneous coronary artery dissection: current state of the science: a scientific statement from the American Heart Association. Circulation 2018; 137(19):e523–e557. doi:10.1161/CIR.0000000000000564
- Tweet MS, Eleid MF, Best PJ, et al. Spontaneous coronary artery dissection: revascularization versus conservative therapy. Circ Cardiovasc Interv 2014; 7(6):777–786. doi:10.1161/CIRCINTERVENTIONS.114.001659
- Tweet MS, Hayes SN, Pitta SR, et al. Clinical features, management, and prognosis of spontaneous coronary artery dissection. Circulation 2012; 126(5):579–588. doi:10.1161/CIRCULATIONAHA.112.105718
- Prasad M, Tweet MS, Hayes SN, et al. Prevalence of extracoronary vascular abnormalities and fibromuscular dysplasia in patients with spontaneous coronary artery dissection. Am J Cardiol 2015; 115(12):1672–1677. doi:10.1016/j.amjcard.2015.03.011
- Adès LC, Waltham RD, Chiodo AA, Bateman JF. Myocardial infarction resulting from coronary artery dissection in an adolescent with Ehlers-Danlos syndrome type IV due to a type III collagen mutation. Br Heart J 1995; 74(2):112–116. pmid:7546986
- Judge DP, Dietz HC. Marfan’s syndrome. Lancet 2005; 366(9501):1965–1976. doi:10.1016/S0140-6736(05)67789-6
- Saw J. Spontaneous coronary artery dissection. Can J Cardiol 2013; 29(9):1027–1033. doi:10.1016/j.cjca.2012.12.018
- Poloskey SL, Kim ES, Sanghani R, et al. Low yield of genetic testing for known vascular connective tissue disorders in patients with fibromuscular dysplasia. Vasc Med 2012; 17(6):371–378. doi:10.1177/1358863X12459650
- Garcia NA, Khan AN, Boppana RC, Smith HL. Spontaneous coronary artery dissection: a case series and literature review. J Community Hosp Intern Med Perspect 2014; 4(4). doi:10.3402/jchimp.v4.25261
- Lempereur M, Gin K, Saw J. Multivessel spontaneous coronary artery dissection mimicking atherosclerosis. JACC Cardiovasc Interv 2014; 7(7):e87–e88. doi:10.1016/j.jcin.2013.12.207
- Mahmoud AN, Taduru SS, Mentias A, et al. Trends of incidence, clinical presentation, and in-hospital mortality among women with acute myocardial infarction with or without spontaneous coronary artery dissection: a population-based analysis. JACC Cardiovasc Interv 2018; 11(1):80–90. doi:10.1016/j.jcin.2017.08.016
- Saw J. Pregnancy-associated spontaneous coronary artery dissection represents an exceptionally high-risk spontaneous coronary artery dissection cohort. Circ Cardiovasc Interv 2017; 10(3)pii:e005119. doi:10.1161/CIRCINTERVENTIONS.117.005119
- Elkayam U, Jalnapurkar S, Barakkat MN, et al. Pregnancy-associated acute myocardial infarction: a review of contemporary experience in 150 cases between 2006 and 2011. Circulation 2014; 129(16):1695–1702. doi:10.1161/CIRCULATIONAHA.113.002054
- Vijayaraghavan R, Verma S, Gupta N, Saw J. Pregnancy-related spontaneous coronary artery dissection. Circulation 2014; 130(21):1915–1920. doi:10.1161/CIRCULATIONAHA.114.011422
- Saw J, Mancini GBJ, Humphries KH. Contemporary review on spontaneous coronary artery dissection. J Am Coll Cardiol 2016; 68(3):297–312. doi:10.1016/j.jacc.2016.05.034
- Saw J, Aymong E, Sedlak T, et al. Spontaneous coronary artery dissection: association with predisposing arteriopathies and precipitating stressors and cardiovascular outcomes. Circ Cardiovasc Interv 2014; 7(5):645–655. doi:10.1161/CIRCINTERVENTIONS.114.001760
- Saw J, Humphries K ,Aymong E, et al. Spontaneous coronary artery dissection: clinical outcomes and risk of recurrence. J Am Coll Cardiol 2017; 70(9):1148–1158. doi:10.1016/j.jacc.2017.06.053
- Alfonso F, Bastante T, Cuesta J, Rodríguez D, Benedicto A, Rivero F. Spontaneous coronary artery dissection: novel insights on diagnosis and management. Cardiovasc Diagn Ther 2015; 5(2):133–140. doi:10.3978/j.issn.2223-3652.2015.03.05
- Kern MJ, Meier B. Evaluation of the culprit plaque and the physiological significance of coronary atherosclerotic narrowings. Circulation 2001; 103(25):3142–3149. pmid:11425782
- Hayes SN, Kim ESH, Saw J, et al; American Heart Association Council on Peripheral Vascular Disease; Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Genomic and Precision Medicine; and Stroke Council. Spontaneous coronary artery dissection: current state of the science: a scientific statement from the American Heart Association. Circulation 2018; 137(19):e523–e557. doi:10.1161/CIR.0000000000000564
- Tweet MS, Eleid MF, Best PJ, et al. Spontaneous coronary artery dissection: revascularization versus conservative therapy. Circ Cardiovasc Interv 2014; 7(6):777–786. doi:10.1161/CIRCINTERVENTIONS.114.001659
- Tweet MS, Hayes SN, Pitta SR, et al. Clinical features, management, and prognosis of spontaneous coronary artery dissection. Circulation 2012; 126(5):579–588. doi:10.1161/CIRCULATIONAHA.112.105718
- Prasad M, Tweet MS, Hayes SN, et al. Prevalence of extracoronary vascular abnormalities and fibromuscular dysplasia in patients with spontaneous coronary artery dissection. Am J Cardiol 2015; 115(12):1672–1677. doi:10.1016/j.amjcard.2015.03.011
- Adès LC, Waltham RD, Chiodo AA, Bateman JF. Myocardial infarction resulting from coronary artery dissection in an adolescent with Ehlers-Danlos syndrome type IV due to a type III collagen mutation. Br Heart J 1995; 74(2):112–116. pmid:7546986
- Judge DP, Dietz HC. Marfan’s syndrome. Lancet 2005; 366(9501):1965–1976. doi:10.1016/S0140-6736(05)67789-6
- Saw J. Spontaneous coronary artery dissection. Can J Cardiol 2013; 29(9):1027–1033. doi:10.1016/j.cjca.2012.12.018
- Poloskey SL, Kim ES, Sanghani R, et al. Low yield of genetic testing for known vascular connective tissue disorders in patients with fibromuscular dysplasia. Vasc Med 2012; 17(6):371–378. doi:10.1177/1358863X12459650
KEY POINTS
- SCAD often presents with symptoms of acute coronary syndrome but can be asymptomatic or cause sudden death.
- Management is generally conservative, but a left main or severe proximal 2-vessel dissection, hemodynamic instability, or ongoing ischemic symptoms may warrant revascularization.
- All patients with SCAD should be screened for other vascular problems, especially fibromuscular dysplasia.
- Long-term aspirin therapy and 1 year of clopidogrel are recommended after an episode of SCAD.
