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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
TMS May Be a Good Alternative to ECT in Depression
DENVER — , according to results from a retrospective study of patients treated in the past 20 years.
“We always learn in our textbooks that after about two or three medication trials is when you can start exploring more serious treatment protocols, such as ECT or TMS, but a lot of these patients weren’t going forward with it, and I was curious about it. I figured that TMS, which is a less expensive, less scary procedure that patients would more likely be open to, that is also approved for treatment resistant depression, would be a good alternative to ECT,” said Anuttham Kandhadai, a third-year medical student at University of Texas Medical Branch at Galveston, who presented the study at the 2024 annual meeting of the American Academy of Neurology.
Study Findings Lead to More Questions
The researchers found lower rates of depressive episodes, suicidal attempts, and suicidal ideation among patients treated with TMS, but an important limitation was that the researchers did not know the severity of the depression in the two patient groups, according to Branch Coslett, MD, who attended the session and has performed research with TMS to treat aphasia in stroke patients. “I think it’s a very interesting study, and certainly something worth pursuing, but given that ECT is only used as a last resort, whereas TMS is often used as a second-line therapy, I think you’re really talking about very different populations that have had these treatments,” said Dr. Coslett.
Mr. Kandhadai recognized the limitations of the study and looks forward to expanding the research. “I’d love to explore cost effectiveness of the treatments. I’d love to explore patient familiarity and patient comfort with different treatments. And I’d also love to explore a more controlled study that can determine how severe someone’s depression is, and then be able to control for that and explore the outcomes based on the treatment protocol,” he said.
The ideal comparative study would be prospective, “but that will never be done. One Flew Over the Cuckoo’s Nest and similar sources of information have really poisoned the well,” said Dr. Coslett. However, he noted that advances have been made in ECT, and that targeting the right hemisphere produces fewer side effects: “The outcomes from unilateral right hemisphere stimulation are said to be every bit as good or maybe better, and you don’t get the confusion, you don’t get the memory loss, you don’t get all that sort of stuff that you’d expect when somebody has a prolonged, generalized tonic-clonic seizure.”
Still, people are naturally reluctant to undergo ECT. “I’ve seen it. It’s pretty barbaric. It’s better now and at my institution, people do get it, but they really, really have to be intractable,” he said.
Comparing Treatment Options
Mr. Kandhadai and his co-authors used the TriNetX database to identify patients with treatment-resistant major depressive disorder who received TMS or ECT in the past 20 years. There were 2,916 patients in both cohorts, who were matched by age, sex, ethnicity, mood and behavioral disorders, endocrine disorders, intellectual disabilities, cerebrovascular disease, and other nervous system disorders. The mean age at treatment was 48.2 years, 38.5% were male, and 3.1% were Black or African American.
Short-term outcomes favored TMS, including the frequency of disorientation (0.41% vs 2.81%), retrograde amnesia (0.34% vs 0.65%), and headache (4.36% vs 7.20%). Long-term outcomes from 1 month to 5 years post treatment were also better in the TMS group, including depressive episodes (44.99% vs 53.77%), suicide attempts (3.98% vs 6.86%), and suicidal ideation (12.38% vs 23.49%). Kaplan-Meier curve analysis between 1 month and 5 years showed a benefit to TMS in probability of not experiencing a depressive episode, and not experiencing suicidal ideation.
“ECT has been the gold standard of treatment resistant depression for a long time, and it deserves to be. I think it’s something you should offer your patients. Not everyone might be comfortable with it, and if they’re not, I think it’s important to not stop the conversation there, but to offer something like TMS because TMS is something that might be more accessible to patients. It might be more affordable, and it might be less scary,” said Mr. Kandhadai
Mr. Kandhadai and Dr. Coslett have no relevant financial disclosures.
DENVER — , according to results from a retrospective study of patients treated in the past 20 years.
“We always learn in our textbooks that after about two or three medication trials is when you can start exploring more serious treatment protocols, such as ECT or TMS, but a lot of these patients weren’t going forward with it, and I was curious about it. I figured that TMS, which is a less expensive, less scary procedure that patients would more likely be open to, that is also approved for treatment resistant depression, would be a good alternative to ECT,” said Anuttham Kandhadai, a third-year medical student at University of Texas Medical Branch at Galveston, who presented the study at the 2024 annual meeting of the American Academy of Neurology.
Study Findings Lead to More Questions
The researchers found lower rates of depressive episodes, suicidal attempts, and suicidal ideation among patients treated with TMS, but an important limitation was that the researchers did not know the severity of the depression in the two patient groups, according to Branch Coslett, MD, who attended the session and has performed research with TMS to treat aphasia in stroke patients. “I think it’s a very interesting study, and certainly something worth pursuing, but given that ECT is only used as a last resort, whereas TMS is often used as a second-line therapy, I think you’re really talking about very different populations that have had these treatments,” said Dr. Coslett.
Mr. Kandhadai recognized the limitations of the study and looks forward to expanding the research. “I’d love to explore cost effectiveness of the treatments. I’d love to explore patient familiarity and patient comfort with different treatments. And I’d also love to explore a more controlled study that can determine how severe someone’s depression is, and then be able to control for that and explore the outcomes based on the treatment protocol,” he said.
The ideal comparative study would be prospective, “but that will never be done. One Flew Over the Cuckoo’s Nest and similar sources of information have really poisoned the well,” said Dr. Coslett. However, he noted that advances have been made in ECT, and that targeting the right hemisphere produces fewer side effects: “The outcomes from unilateral right hemisphere stimulation are said to be every bit as good or maybe better, and you don’t get the confusion, you don’t get the memory loss, you don’t get all that sort of stuff that you’d expect when somebody has a prolonged, generalized tonic-clonic seizure.”
Still, people are naturally reluctant to undergo ECT. “I’ve seen it. It’s pretty barbaric. It’s better now and at my institution, people do get it, but they really, really have to be intractable,” he said.
Comparing Treatment Options
Mr. Kandhadai and his co-authors used the TriNetX database to identify patients with treatment-resistant major depressive disorder who received TMS or ECT in the past 20 years. There were 2,916 patients in both cohorts, who were matched by age, sex, ethnicity, mood and behavioral disorders, endocrine disorders, intellectual disabilities, cerebrovascular disease, and other nervous system disorders. The mean age at treatment was 48.2 years, 38.5% were male, and 3.1% were Black or African American.
Short-term outcomes favored TMS, including the frequency of disorientation (0.41% vs 2.81%), retrograde amnesia (0.34% vs 0.65%), and headache (4.36% vs 7.20%). Long-term outcomes from 1 month to 5 years post treatment were also better in the TMS group, including depressive episodes (44.99% vs 53.77%), suicide attempts (3.98% vs 6.86%), and suicidal ideation (12.38% vs 23.49%). Kaplan-Meier curve analysis between 1 month and 5 years showed a benefit to TMS in probability of not experiencing a depressive episode, and not experiencing suicidal ideation.
“ECT has been the gold standard of treatment resistant depression for a long time, and it deserves to be. I think it’s something you should offer your patients. Not everyone might be comfortable with it, and if they’re not, I think it’s important to not stop the conversation there, but to offer something like TMS because TMS is something that might be more accessible to patients. It might be more affordable, and it might be less scary,” said Mr. Kandhadai
Mr. Kandhadai and Dr. Coslett have no relevant financial disclosures.
DENVER — , according to results from a retrospective study of patients treated in the past 20 years.
“We always learn in our textbooks that after about two or three medication trials is when you can start exploring more serious treatment protocols, such as ECT or TMS, but a lot of these patients weren’t going forward with it, and I was curious about it. I figured that TMS, which is a less expensive, less scary procedure that patients would more likely be open to, that is also approved for treatment resistant depression, would be a good alternative to ECT,” said Anuttham Kandhadai, a third-year medical student at University of Texas Medical Branch at Galveston, who presented the study at the 2024 annual meeting of the American Academy of Neurology.
Study Findings Lead to More Questions
The researchers found lower rates of depressive episodes, suicidal attempts, and suicidal ideation among patients treated with TMS, but an important limitation was that the researchers did not know the severity of the depression in the two patient groups, according to Branch Coslett, MD, who attended the session and has performed research with TMS to treat aphasia in stroke patients. “I think it’s a very interesting study, and certainly something worth pursuing, but given that ECT is only used as a last resort, whereas TMS is often used as a second-line therapy, I think you’re really talking about very different populations that have had these treatments,” said Dr. Coslett.
Mr. Kandhadai recognized the limitations of the study and looks forward to expanding the research. “I’d love to explore cost effectiveness of the treatments. I’d love to explore patient familiarity and patient comfort with different treatments. And I’d also love to explore a more controlled study that can determine how severe someone’s depression is, and then be able to control for that and explore the outcomes based on the treatment protocol,” he said.
The ideal comparative study would be prospective, “but that will never be done. One Flew Over the Cuckoo’s Nest and similar sources of information have really poisoned the well,” said Dr. Coslett. However, he noted that advances have been made in ECT, and that targeting the right hemisphere produces fewer side effects: “The outcomes from unilateral right hemisphere stimulation are said to be every bit as good or maybe better, and you don’t get the confusion, you don’t get the memory loss, you don’t get all that sort of stuff that you’d expect when somebody has a prolonged, generalized tonic-clonic seizure.”
Still, people are naturally reluctant to undergo ECT. “I’ve seen it. It’s pretty barbaric. It’s better now and at my institution, people do get it, but they really, really have to be intractable,” he said.
Comparing Treatment Options
Mr. Kandhadai and his co-authors used the TriNetX database to identify patients with treatment-resistant major depressive disorder who received TMS or ECT in the past 20 years. There were 2,916 patients in both cohorts, who were matched by age, sex, ethnicity, mood and behavioral disorders, endocrine disorders, intellectual disabilities, cerebrovascular disease, and other nervous system disorders. The mean age at treatment was 48.2 years, 38.5% were male, and 3.1% were Black or African American.
Short-term outcomes favored TMS, including the frequency of disorientation (0.41% vs 2.81%), retrograde amnesia (0.34% vs 0.65%), and headache (4.36% vs 7.20%). Long-term outcomes from 1 month to 5 years post treatment were also better in the TMS group, including depressive episodes (44.99% vs 53.77%), suicide attempts (3.98% vs 6.86%), and suicidal ideation (12.38% vs 23.49%). Kaplan-Meier curve analysis between 1 month and 5 years showed a benefit to TMS in probability of not experiencing a depressive episode, and not experiencing suicidal ideation.
“ECT has been the gold standard of treatment resistant depression for a long time, and it deserves to be. I think it’s something you should offer your patients. Not everyone might be comfortable with it, and if they’re not, I think it’s important to not stop the conversation there, but to offer something like TMS because TMS is something that might be more accessible to patients. It might be more affordable, and it might be less scary,” said Mr. Kandhadai
Mr. Kandhadai and Dr. Coslett have no relevant financial disclosures.
FROM AAN 2024
More Cases of Acute Diverticulitis Treated Outside Hospital
BOSTON — Patients with acute colonic diverticulitis are more likely to be seen by primary care providers than by emergency physicians, representing a shift in the way clinicians detect and treat the condition.
Acute colonic diverticulitis affects roughly 180 per 100,000 people per year in the United States.
CT of the abdomen and pelvis may not be a first-line method to detect diverticulitis in the primary care setting as it has been in emergent care, according to Kaveh Sharzehi, MD, MS, associate professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland.
Indeed, clinical guidelines by multiple physician groups recommend that providers use a more individualized approach to detecting and treating the condition.
“There is still great value in proper and thorough physical history and some adjunct testing,” Dr. Sharzehi told attendees during a presentation on April 20 at the American College of Physicians Internal Medicine Meeting 2024. These two methods can detect the disease up to 65% of the time, Dr. Sharzehi added.
An initial evaluation of a patient with suspected acute diverticulitis should first assess the patient’s history of abdominal pain, fever, and leukocytosis, Dr. Sharzehi said.
A C-reactive protein level > 50 mg/L “almost doubles the odds of having diverticulitis,” Dr. Sharzehi said. Studies also suggest increased levels of procalcitonin and fecal calprotectin can indicate the presence of the condition.
The American Gastroenterological Association (AGA) and the American College of Physicians recommend abdominal CT if clinicians are uncertain of the diagnosis, and to evaluate potential complications in severe cases. Ultrasound and MRI can be useful alternatives, according to guidelines from the American Society of Colon and Rectal Surgeons.
The chances of developing diverticulitis increase with age. More than 60% of Americans aged 60 years or older have diverticulosis, a condition characterized by small pouches in the colon lining that can weaken the colon wall. Less than 5% of people with diverticulosis go on to develop diverticulitis.
“Aspirin and opioid use are also risk factors, likely from their effect on the colonic transit time and causing constipation that might contribute to diverticulitis, but that›s not very well understood,” Dr. Sharzehi said.
Medical management has shifted from predominantly inpatient to predominantly outpatient care, Dr. Sharzehi told attendees
“Unfortunately, there are not that many supportive guidelines for what diet a patient should have in the acute setting of diverticulitis,” he said.
Patients with a mild case may benefit from a clear liquid diet; for some patients, high-fiber diets, regular physical activity, and statins may protect against recurrence.
Current guidelines recommend against prescribing antibiotics for most cases because evidence suggests that diverticulitis is primarily an inflammatory process that can result in small tears in the diverticulum, rather than the disease being a complication of existing tears.
Patients should also not be treated with probiotics or 5-aminosalicylic acid agents, Dr. Sharzehi said.
“My practice is in the Pacific Northwest, where there’s a lot of belief in naturopathic remedies, so we get a lot of questions about supplements and probiotics in preventing diverticulitis,” he said. “We don’t think it does help, and this is unanimous among all the main [physician] societies.”
The AGA recommends referring patients for a colonoscopy within a year after diverticulitis symptoms have resided.
Severe or unresolved cases could require inpatient procedures such as percutaneous drainage or surgery. An estimated 15%-30% of patients admitted to hospital with acute diverticulitis require surgery, Dr. Sharzehi said.
Surgery may become an option for patients who have recurrent cases of the disease, even if not severe, Dr. Sharzehi said.
Dr. Sharzehi reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
BOSTON — Patients with acute colonic diverticulitis are more likely to be seen by primary care providers than by emergency physicians, representing a shift in the way clinicians detect and treat the condition.
Acute colonic diverticulitis affects roughly 180 per 100,000 people per year in the United States.
CT of the abdomen and pelvis may not be a first-line method to detect diverticulitis in the primary care setting as it has been in emergent care, according to Kaveh Sharzehi, MD, MS, associate professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland.
Indeed, clinical guidelines by multiple physician groups recommend that providers use a more individualized approach to detecting and treating the condition.
“There is still great value in proper and thorough physical history and some adjunct testing,” Dr. Sharzehi told attendees during a presentation on April 20 at the American College of Physicians Internal Medicine Meeting 2024. These two methods can detect the disease up to 65% of the time, Dr. Sharzehi added.
An initial evaluation of a patient with suspected acute diverticulitis should first assess the patient’s history of abdominal pain, fever, and leukocytosis, Dr. Sharzehi said.
A C-reactive protein level > 50 mg/L “almost doubles the odds of having diverticulitis,” Dr. Sharzehi said. Studies also suggest increased levels of procalcitonin and fecal calprotectin can indicate the presence of the condition.
The American Gastroenterological Association (AGA) and the American College of Physicians recommend abdominal CT if clinicians are uncertain of the diagnosis, and to evaluate potential complications in severe cases. Ultrasound and MRI can be useful alternatives, according to guidelines from the American Society of Colon and Rectal Surgeons.
The chances of developing diverticulitis increase with age. More than 60% of Americans aged 60 years or older have diverticulosis, a condition characterized by small pouches in the colon lining that can weaken the colon wall. Less than 5% of people with diverticulosis go on to develop diverticulitis.
“Aspirin and opioid use are also risk factors, likely from their effect on the colonic transit time and causing constipation that might contribute to diverticulitis, but that›s not very well understood,” Dr. Sharzehi said.
Medical management has shifted from predominantly inpatient to predominantly outpatient care, Dr. Sharzehi told attendees
“Unfortunately, there are not that many supportive guidelines for what diet a patient should have in the acute setting of diverticulitis,” he said.
Patients with a mild case may benefit from a clear liquid diet; for some patients, high-fiber diets, regular physical activity, and statins may protect against recurrence.
Current guidelines recommend against prescribing antibiotics for most cases because evidence suggests that diverticulitis is primarily an inflammatory process that can result in small tears in the diverticulum, rather than the disease being a complication of existing tears.
Patients should also not be treated with probiotics or 5-aminosalicylic acid agents, Dr. Sharzehi said.
“My practice is in the Pacific Northwest, where there’s a lot of belief in naturopathic remedies, so we get a lot of questions about supplements and probiotics in preventing diverticulitis,” he said. “We don’t think it does help, and this is unanimous among all the main [physician] societies.”
The AGA recommends referring patients for a colonoscopy within a year after diverticulitis symptoms have resided.
Severe or unresolved cases could require inpatient procedures such as percutaneous drainage or surgery. An estimated 15%-30% of patients admitted to hospital with acute diverticulitis require surgery, Dr. Sharzehi said.
Surgery may become an option for patients who have recurrent cases of the disease, even if not severe, Dr. Sharzehi said.
Dr. Sharzehi reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
BOSTON — Patients with acute colonic diverticulitis are more likely to be seen by primary care providers than by emergency physicians, representing a shift in the way clinicians detect and treat the condition.
Acute colonic diverticulitis affects roughly 180 per 100,000 people per year in the United States.
CT of the abdomen and pelvis may not be a first-line method to detect diverticulitis in the primary care setting as it has been in emergent care, according to Kaveh Sharzehi, MD, MS, associate professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland.
Indeed, clinical guidelines by multiple physician groups recommend that providers use a more individualized approach to detecting and treating the condition.
“There is still great value in proper and thorough physical history and some adjunct testing,” Dr. Sharzehi told attendees during a presentation on April 20 at the American College of Physicians Internal Medicine Meeting 2024. These two methods can detect the disease up to 65% of the time, Dr. Sharzehi added.
An initial evaluation of a patient with suspected acute diverticulitis should first assess the patient’s history of abdominal pain, fever, and leukocytosis, Dr. Sharzehi said.
A C-reactive protein level > 50 mg/L “almost doubles the odds of having diverticulitis,” Dr. Sharzehi said. Studies also suggest increased levels of procalcitonin and fecal calprotectin can indicate the presence of the condition.
The American Gastroenterological Association (AGA) and the American College of Physicians recommend abdominal CT if clinicians are uncertain of the diagnosis, and to evaluate potential complications in severe cases. Ultrasound and MRI can be useful alternatives, according to guidelines from the American Society of Colon and Rectal Surgeons.
The chances of developing diverticulitis increase with age. More than 60% of Americans aged 60 years or older have diverticulosis, a condition characterized by small pouches in the colon lining that can weaken the colon wall. Less than 5% of people with diverticulosis go on to develop diverticulitis.
“Aspirin and opioid use are also risk factors, likely from their effect on the colonic transit time and causing constipation that might contribute to diverticulitis, but that›s not very well understood,” Dr. Sharzehi said.
Medical management has shifted from predominantly inpatient to predominantly outpatient care, Dr. Sharzehi told attendees
“Unfortunately, there are not that many supportive guidelines for what diet a patient should have in the acute setting of diverticulitis,” he said.
Patients with a mild case may benefit from a clear liquid diet; for some patients, high-fiber diets, regular physical activity, and statins may protect against recurrence.
Current guidelines recommend against prescribing antibiotics for most cases because evidence suggests that diverticulitis is primarily an inflammatory process that can result in small tears in the diverticulum, rather than the disease being a complication of existing tears.
Patients should also not be treated with probiotics or 5-aminosalicylic acid agents, Dr. Sharzehi said.
“My practice is in the Pacific Northwest, where there’s a lot of belief in naturopathic remedies, so we get a lot of questions about supplements and probiotics in preventing diverticulitis,” he said. “We don’t think it does help, and this is unanimous among all the main [physician] societies.”
The AGA recommends referring patients for a colonoscopy within a year after diverticulitis symptoms have resided.
Severe or unresolved cases could require inpatient procedures such as percutaneous drainage or surgery. An estimated 15%-30% of patients admitted to hospital with acute diverticulitis require surgery, Dr. Sharzehi said.
Surgery may become an option for patients who have recurrent cases of the disease, even if not severe, Dr. Sharzehi said.
Dr. Sharzehi reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
In the Story of the Rubella Virus as a Source of Granulomas, the Plot Is Still Thickening
SAN DIEGO — Approximately 10 years ago in France, high throughput .
Based on accumulating evidence, the Centers for Disease Control and Prevention (CDC) through collaborations with others also recognized this in pediatric patients with inborn errors of immunity, and it is now appropriate for clinicians to consider this etiology when no other infectious agents can be identified, according to Karolyn A. Wanat, MD, professor of dermatology, Medical College of Wisconsin, Milwaukee, who spoke about rubella as a trigger in granulomatous disease at the meeting. “This is a huge evolving area of interest,” said Dr. Wanat, who has been the first author or coauthor on several published papers, including a review article published earlier this year.
In the earliest cases, including those reported in 2014, the cutaneous granulomas presumed to be causally related to vaccine-derived rubella virus were found only in those with a primary immunodeficiency. This is no longer the case. In a collaboration among US clinics, granulomas that had persisted for years in immunocompetent adults were identified, according to Dr. Wanat, the first author of a report on these findings in four adults in 2022. In addition, it now appears that wild-type rubella virus, like vaccine-derived rubella virus, can be the source of the antigenic response that underlies the development of rubella-associated cutaneous granulomas.
The phenotype of these granulomas is comparable to granulomas associated with other infectious agents. On dermatopathology, these commonly feature a robust granulomatous inflammation with multinucleated giant cells and lymphocytic infiltrate. Necrosis and fibrosis are also common.
“These are the types of granulomas that we would be thinking infection. If tissue cultures are negative, we would probably repeat them,” she said, suggesting that suspicion of an infectious etiology would probably remain high even after multiple negative tests.
Of the cases accruing in the United States and elsewhere, most but not all have been linked to inborn errors of immunity. In a 2020 CDC review, the risk of granulomas caused by compromised immunity, such as defects in T cell function, was estimated to be in the range of 0.6% to 2.5%, Dr. Wanat said.
It is now known that primary immunodeficiency is not a prerequisite, but this should not change the perception that the rubella vaccine, which was introduced in 1979, is effective and safe, according to Dr. Wanat. The vaccine is associated with few serious adverse events and is so effective that rubella was eliminated from the United States in 2004 and from the Americas in 2015.
This makes cases of granuloma associated with wild-type rubella virus surprising, but they appear to be exceedingly rare. Whether caused by vaccine exposure or another source, the mechanism of latent development of cutaneous granulomas is consistent with other infectious sources, and is not well understood.
“Rubella is a sneaky virus that can persist in some immunoprivileged sites indefinitely,” Dr. Wanat said. These sites include the eyes, joints, and placenta.
Many initial cases of rubella-associated granulomas occurred on the arms, presumably where the vaccine was administered, despite long intervals between exposure and lesion growth. This interval is often measured in years.
With more cases, it is now understood that involvement of other organs does occur even if the skin is the most common site of antigenic response in patients with immunodeficiency. The liver and lymph nodes represent other tissues that have been affected. Even lesions in the brain have been seen on autopsy.
Based on the benefit-to-risk ratio of a highly effective and successful vaccine, however, the association with a risk of granulomas “should not raise questions” about the value of the vaccine itself, Dr. Wanat noted.
“The proportion of patients who develop these granulomas is very, very low. Yet, the vaccine provides life-long immunity,” she said.
The discovery of granulomas associated with wild type rubella infection was “shocking” based on the supposition that the rubella virus had been eliminated, but this is just one of the unexpected discoveries as the still-evolving science has traced the story of rubella-associated granulomas over the past 10 years.
Cases now include children and adults through advanced ages.
Shedding of the virus and risk of infection to others has been studied but so far, the risk — if it exists — is very low. The evidence includes the many patients who have lived with the granulomas for years, even decades, without any known spread to others.
As for ongoing work in this area, Dr. Wanat said that a histopathological case definition for rubella-associated granulomas is being developed, and she and other investigators are actively seeking new cases to better characterize the disease.
So far, optimal treatment is not well defined. A number of strategies have had limited success or are considered impractical for routine use. One example is a stem cell transplant. In a case Dr. Wanat cited, complete resolution of the skin lesions was achieved with a transplant.
“I am not suggesting that those with localized disease in the skin should undergo a transplant, but it does support the role of the immune system and the potential for a reboot to clear the skin,” she said.
Other therapies associated with benefit in at least some patients include tumor necrosis factor (TNF) inhibitors with dapsone and ribavirin. The risk of adverse events for the latter might again limit its use, Dr. Wanat said.
With awareness, the number of granulomas found to be associated with rubella virus is expected to grow. Dr. Wanat speculated that those areas of the country that not yet have documented a case will do so over time. For idiopathic cases of cutaneous granulomas, rubella should be kept in mind, she said.
Characterizing rubella-associated cutaneous granulomas as “a public health concern,” Dr. Wanat urged clinicians to consider this etiology in lesions that match the phenotype, particularly when other more common infectious agents cannot be identified.
Asked for his perspective, Jeffrey P. North, MD, managing director of the UCSF Dermatopathology, and professor of dermatology and pathology at the University of California, San Francisco, agreed that rubella should be considered as a source of granulomas with a suspected infectious etiology when a pathogen cannot be found.
“It is likely much more common than we know as it has only been recently described and testing for it is limited. I suspected there are a lot of undiagnosed patients suffering from this disease,” Dr. North said in an interview.
“One of the important points for clinicians to consider is that while this has been reported mostly in patients with some form of immunodeficiency, there have also been patients reported to have this condition with no immunodeficiency,” he added. Even though the association between rubella and granulomas was made 10 years ago, awareness is only now spreading, which means the frequency with which rubella leads to granulomas remains uncertain.
“I think we will start to get a better idea of how common this is as more people learn about and testing for it expands,” Dr. North said.
Dr. Wanat reports no potential conflicts of interest. Dr. North reports financial relationships with AdviNow and Kiniksa Pharmaceuticals.
SAN DIEGO — Approximately 10 years ago in France, high throughput .
Based on accumulating evidence, the Centers for Disease Control and Prevention (CDC) through collaborations with others also recognized this in pediatric patients with inborn errors of immunity, and it is now appropriate for clinicians to consider this etiology when no other infectious agents can be identified, according to Karolyn A. Wanat, MD, professor of dermatology, Medical College of Wisconsin, Milwaukee, who spoke about rubella as a trigger in granulomatous disease at the meeting. “This is a huge evolving area of interest,” said Dr. Wanat, who has been the first author or coauthor on several published papers, including a review article published earlier this year.
In the earliest cases, including those reported in 2014, the cutaneous granulomas presumed to be causally related to vaccine-derived rubella virus were found only in those with a primary immunodeficiency. This is no longer the case. In a collaboration among US clinics, granulomas that had persisted for years in immunocompetent adults were identified, according to Dr. Wanat, the first author of a report on these findings in four adults in 2022. In addition, it now appears that wild-type rubella virus, like vaccine-derived rubella virus, can be the source of the antigenic response that underlies the development of rubella-associated cutaneous granulomas.
The phenotype of these granulomas is comparable to granulomas associated with other infectious agents. On dermatopathology, these commonly feature a robust granulomatous inflammation with multinucleated giant cells and lymphocytic infiltrate. Necrosis and fibrosis are also common.
“These are the types of granulomas that we would be thinking infection. If tissue cultures are negative, we would probably repeat them,” she said, suggesting that suspicion of an infectious etiology would probably remain high even after multiple negative tests.
Of the cases accruing in the United States and elsewhere, most but not all have been linked to inborn errors of immunity. In a 2020 CDC review, the risk of granulomas caused by compromised immunity, such as defects in T cell function, was estimated to be in the range of 0.6% to 2.5%, Dr. Wanat said.
It is now known that primary immunodeficiency is not a prerequisite, but this should not change the perception that the rubella vaccine, which was introduced in 1979, is effective and safe, according to Dr. Wanat. The vaccine is associated with few serious adverse events and is so effective that rubella was eliminated from the United States in 2004 and from the Americas in 2015.
This makes cases of granuloma associated with wild-type rubella virus surprising, but they appear to be exceedingly rare. Whether caused by vaccine exposure or another source, the mechanism of latent development of cutaneous granulomas is consistent with other infectious sources, and is not well understood.
“Rubella is a sneaky virus that can persist in some immunoprivileged sites indefinitely,” Dr. Wanat said. These sites include the eyes, joints, and placenta.
Many initial cases of rubella-associated granulomas occurred on the arms, presumably where the vaccine was administered, despite long intervals between exposure and lesion growth. This interval is often measured in years.
With more cases, it is now understood that involvement of other organs does occur even if the skin is the most common site of antigenic response in patients with immunodeficiency. The liver and lymph nodes represent other tissues that have been affected. Even lesions in the brain have been seen on autopsy.
Based on the benefit-to-risk ratio of a highly effective and successful vaccine, however, the association with a risk of granulomas “should not raise questions” about the value of the vaccine itself, Dr. Wanat noted.
“The proportion of patients who develop these granulomas is very, very low. Yet, the vaccine provides life-long immunity,” she said.
The discovery of granulomas associated with wild type rubella infection was “shocking” based on the supposition that the rubella virus had been eliminated, but this is just one of the unexpected discoveries as the still-evolving science has traced the story of rubella-associated granulomas over the past 10 years.
Cases now include children and adults through advanced ages.
Shedding of the virus and risk of infection to others has been studied but so far, the risk — if it exists — is very low. The evidence includes the many patients who have lived with the granulomas for years, even decades, without any known spread to others.
As for ongoing work in this area, Dr. Wanat said that a histopathological case definition for rubella-associated granulomas is being developed, and she and other investigators are actively seeking new cases to better characterize the disease.
So far, optimal treatment is not well defined. A number of strategies have had limited success or are considered impractical for routine use. One example is a stem cell transplant. In a case Dr. Wanat cited, complete resolution of the skin lesions was achieved with a transplant.
“I am not suggesting that those with localized disease in the skin should undergo a transplant, but it does support the role of the immune system and the potential for a reboot to clear the skin,” she said.
Other therapies associated with benefit in at least some patients include tumor necrosis factor (TNF) inhibitors with dapsone and ribavirin. The risk of adverse events for the latter might again limit its use, Dr. Wanat said.
With awareness, the number of granulomas found to be associated with rubella virus is expected to grow. Dr. Wanat speculated that those areas of the country that not yet have documented a case will do so over time. For idiopathic cases of cutaneous granulomas, rubella should be kept in mind, she said.
Characterizing rubella-associated cutaneous granulomas as “a public health concern,” Dr. Wanat urged clinicians to consider this etiology in lesions that match the phenotype, particularly when other more common infectious agents cannot be identified.
Asked for his perspective, Jeffrey P. North, MD, managing director of the UCSF Dermatopathology, and professor of dermatology and pathology at the University of California, San Francisco, agreed that rubella should be considered as a source of granulomas with a suspected infectious etiology when a pathogen cannot be found.
“It is likely much more common than we know as it has only been recently described and testing for it is limited. I suspected there are a lot of undiagnosed patients suffering from this disease,” Dr. North said in an interview.
“One of the important points for clinicians to consider is that while this has been reported mostly in patients with some form of immunodeficiency, there have also been patients reported to have this condition with no immunodeficiency,” he added. Even though the association between rubella and granulomas was made 10 years ago, awareness is only now spreading, which means the frequency with which rubella leads to granulomas remains uncertain.
“I think we will start to get a better idea of how common this is as more people learn about and testing for it expands,” Dr. North said.
Dr. Wanat reports no potential conflicts of interest. Dr. North reports financial relationships with AdviNow and Kiniksa Pharmaceuticals.
SAN DIEGO — Approximately 10 years ago in France, high throughput .
Based on accumulating evidence, the Centers for Disease Control and Prevention (CDC) through collaborations with others also recognized this in pediatric patients with inborn errors of immunity, and it is now appropriate for clinicians to consider this etiology when no other infectious agents can be identified, according to Karolyn A. Wanat, MD, professor of dermatology, Medical College of Wisconsin, Milwaukee, who spoke about rubella as a trigger in granulomatous disease at the meeting. “This is a huge evolving area of interest,” said Dr. Wanat, who has been the first author or coauthor on several published papers, including a review article published earlier this year.
In the earliest cases, including those reported in 2014, the cutaneous granulomas presumed to be causally related to vaccine-derived rubella virus were found only in those with a primary immunodeficiency. This is no longer the case. In a collaboration among US clinics, granulomas that had persisted for years in immunocompetent adults were identified, according to Dr. Wanat, the first author of a report on these findings in four adults in 2022. In addition, it now appears that wild-type rubella virus, like vaccine-derived rubella virus, can be the source of the antigenic response that underlies the development of rubella-associated cutaneous granulomas.
The phenotype of these granulomas is comparable to granulomas associated with other infectious agents. On dermatopathology, these commonly feature a robust granulomatous inflammation with multinucleated giant cells and lymphocytic infiltrate. Necrosis and fibrosis are also common.
“These are the types of granulomas that we would be thinking infection. If tissue cultures are negative, we would probably repeat them,” she said, suggesting that suspicion of an infectious etiology would probably remain high even after multiple negative tests.
Of the cases accruing in the United States and elsewhere, most but not all have been linked to inborn errors of immunity. In a 2020 CDC review, the risk of granulomas caused by compromised immunity, such as defects in T cell function, was estimated to be in the range of 0.6% to 2.5%, Dr. Wanat said.
It is now known that primary immunodeficiency is not a prerequisite, but this should not change the perception that the rubella vaccine, which was introduced in 1979, is effective and safe, according to Dr. Wanat. The vaccine is associated with few serious adverse events and is so effective that rubella was eliminated from the United States in 2004 and from the Americas in 2015.
This makes cases of granuloma associated with wild-type rubella virus surprising, but they appear to be exceedingly rare. Whether caused by vaccine exposure or another source, the mechanism of latent development of cutaneous granulomas is consistent with other infectious sources, and is not well understood.
“Rubella is a sneaky virus that can persist in some immunoprivileged sites indefinitely,” Dr. Wanat said. These sites include the eyes, joints, and placenta.
Many initial cases of rubella-associated granulomas occurred on the arms, presumably where the vaccine was administered, despite long intervals between exposure and lesion growth. This interval is often measured in years.
With more cases, it is now understood that involvement of other organs does occur even if the skin is the most common site of antigenic response in patients with immunodeficiency. The liver and lymph nodes represent other tissues that have been affected. Even lesions in the brain have been seen on autopsy.
Based on the benefit-to-risk ratio of a highly effective and successful vaccine, however, the association with a risk of granulomas “should not raise questions” about the value of the vaccine itself, Dr. Wanat noted.
“The proportion of patients who develop these granulomas is very, very low. Yet, the vaccine provides life-long immunity,” she said.
The discovery of granulomas associated with wild type rubella infection was “shocking” based on the supposition that the rubella virus had been eliminated, but this is just one of the unexpected discoveries as the still-evolving science has traced the story of rubella-associated granulomas over the past 10 years.
Cases now include children and adults through advanced ages.
Shedding of the virus and risk of infection to others has been studied but so far, the risk — if it exists — is very low. The evidence includes the many patients who have lived with the granulomas for years, even decades, without any known spread to others.
As for ongoing work in this area, Dr. Wanat said that a histopathological case definition for rubella-associated granulomas is being developed, and she and other investigators are actively seeking new cases to better characterize the disease.
So far, optimal treatment is not well defined. A number of strategies have had limited success or are considered impractical for routine use. One example is a stem cell transplant. In a case Dr. Wanat cited, complete resolution of the skin lesions was achieved with a transplant.
“I am not suggesting that those with localized disease in the skin should undergo a transplant, but it does support the role of the immune system and the potential for a reboot to clear the skin,” she said.
Other therapies associated with benefit in at least some patients include tumor necrosis factor (TNF) inhibitors with dapsone and ribavirin. The risk of adverse events for the latter might again limit its use, Dr. Wanat said.
With awareness, the number of granulomas found to be associated with rubella virus is expected to grow. Dr. Wanat speculated that those areas of the country that not yet have documented a case will do so over time. For idiopathic cases of cutaneous granulomas, rubella should be kept in mind, she said.
Characterizing rubella-associated cutaneous granulomas as “a public health concern,” Dr. Wanat urged clinicians to consider this etiology in lesions that match the phenotype, particularly when other more common infectious agents cannot be identified.
Asked for his perspective, Jeffrey P. North, MD, managing director of the UCSF Dermatopathology, and professor of dermatology and pathology at the University of California, San Francisco, agreed that rubella should be considered as a source of granulomas with a suspected infectious etiology when a pathogen cannot be found.
“It is likely much more common than we know as it has only been recently described and testing for it is limited. I suspected there are a lot of undiagnosed patients suffering from this disease,” Dr. North said in an interview.
“One of the important points for clinicians to consider is that while this has been reported mostly in patients with some form of immunodeficiency, there have also been patients reported to have this condition with no immunodeficiency,” he added. Even though the association between rubella and granulomas was made 10 years ago, awareness is only now spreading, which means the frequency with which rubella leads to granulomas remains uncertain.
“I think we will start to get a better idea of how common this is as more people learn about and testing for it expands,” Dr. North said.
Dr. Wanat reports no potential conflicts of interest. Dr. North reports financial relationships with AdviNow and Kiniksa Pharmaceuticals.
FROM AAD 2024
Major Gaps in Care and Management of Neurologic Diseases
DENVER –
Investigators led by Nikki Win, PhD, medical manager/team lead, OMNI Scientific Strategy and Collaborations, US Medical Affairs, Genentech/Roche, found that patients with Parkinson’s disease were referred to a specialist most often, followed by those with MS and those with AD.
The findings were presented at the 2024 annual meeting of the American Academy of Neurology (AAN).
National Neurologist Shortage
The national neurologist shortage, coupled with the growing incidence of Alzheimer’s disease, Parkinson’s disease, MS, and other conditions has led the AAN and other organizations to call for expanding the role of primary care physicians in the diagnosis and management of neurologic disorders, the leading global cause of disability.
“These neurological conditions are increasing in prevalence and there’s a limited number of neurologists, so we wanted to understand what this looks like in the US,” Dr. Win said.
“There is a need to understand the patient journey from primary care to neurology care, from presentation of a suspected neurological disorder to diagnosis, referral to a specialist, and the time elapsed before the specialist visit for Alzheimer’s disease, MS, and Parkinson’s disease in the US,” Dr. Win added.
Timely and accurate diagnoses of neurologic disorders can optimize treatment outcomes. Because many of these diseases are first detected during a visit with a primary care physician, it is important to understand the timeline from the initial visit to a specialist referral, the investigators noted.
Analyzing Trends in Specialist Referrals
Using claims data from the Optum Normative Health Information database, researchers identified 48,525 adults with Alzheimer’s disease, 26,431 with Parkinson’s disease, and 8169 with MS who received a diagnosis from a primary care physician between 2016 and 2021.
They examined the proportion, timing, and demographic factors associated with referrals from primary care clinicians or other healthcare providers to specialists including neurologists, neurosurgeons, psychiatrists, and geriatric medicine specialists.
Results showed that patients with Parkinson’s disease were referred to a specialist most often (53%), followed by those with MS (42%) and those with Alzheimer’s disease (27%).
Individuals with Alzheimer’s disease waited the longest for a specialist referral, with a median of 10 months between the time of referral and the first specialist visit compared with 5.7 months for patients with Parkinson’s disease and 2.6 months for MS patients.
“Some patients with common conditions like Alzheimer’s disease, MS, and Parkinson’s disease don’t see a neurologist, and when they do, it can take as long as 10 months,” said Dr. Win.
Using zip code heatmaps, researchers found that the proportion of referrals for all neurologic disorders was higher in the Midwest and Northeast, whereas patients in the South and West were less likely to receive a referral.
Referrals for Alzheimer’s disease were low nationwide, except for some areas of Michigan and New England. California had the lowest referral rate for MS, followed by regions in the South and Northeast. Patients with Parkinson’s disease living in the Midwest and Northeast were more likely than those in the West to receive a specialist referral.
Previous studies have reported regional shortages of neurologists, said Dr. Win. “Our data seem to correlate that in terms of the areas with lower referral patterns, but as to whether that is causative or correlative, we don’t know.”
Odds of referral were also influenced by demographic characteristics such as sex, age, race, and ethnicity, investigators found.
For example, there were fewer referrals with increasing age across all three neurologic disorders, and men were more likely than women to be referred for Alzheimer’s disease and Parkinson’s disease. Compared with White patients, Parkinson’s disease referrals were less likely among African American, Asian, and Hispanic patients and Alzheimer’s disease referrals were less common among Asian and Hispanic patients.
Insurance status also affected referrals. People with MS and Parkinson’s disease who had commercial insurance were referred more often than were those with Medicare Advantage, said Dr. Win.
She also noted, “Additional research is needed to understand how being referred or not being referred to a neurologist actually impacts patient treatment, care and outcomes.”
Neurology Challenges
Commenting on the research, Thomas Vidic, MD, a community neurologist in Elkhart, Indiana, and clinical professor of neurology at Indiana University School of Medicine at South Bend, said that he was surprised by the variation in wait times for patients.
This, he said, could reflect a study limitation or a higher comfort level among primary care doctors in treating dementia.
With respect to MS, Dr. Vidic said that he believes primary care physicians may not be uncertain about prescribing the approved medications for the disease because there are so many of them.
In addition, patients with Alzheimer’s disease are older and perhaps less accepting of being referred to a specialist that may be hours away.
The bottom line for Dr. Vidic, though, is the lack of specialists. “It comes back to the fact we’re not doing a good job of having community neurologists available to take care of these problems,” he said.
The issue of community neurologist shortages was underlined by the study’s findings about geographic gaps in specialist referrals across the country, he said.
Neurologists make up about 2% of the medical workforce and this has remained static for some time, Dr. Vidic noted. Meanwhile, people are living longer and developing more neurologic diseases.
Dr. Vidic also pointed to the lack of neurology training programs. “There has not been a significant change in the number of programs in the last 10-15 years,” he said.
Study funding was not disclosed. Dr. Win reports receiving personal compensation for serving as an employee of Genentech and has stock in Genentech. Dr. Vidic reports no relevant financial disclosures.
A version of this article appeared on Medscape.com.
DENVER –
Investigators led by Nikki Win, PhD, medical manager/team lead, OMNI Scientific Strategy and Collaborations, US Medical Affairs, Genentech/Roche, found that patients with Parkinson’s disease were referred to a specialist most often, followed by those with MS and those with AD.
The findings were presented at the 2024 annual meeting of the American Academy of Neurology (AAN).
National Neurologist Shortage
The national neurologist shortage, coupled with the growing incidence of Alzheimer’s disease, Parkinson’s disease, MS, and other conditions has led the AAN and other organizations to call for expanding the role of primary care physicians in the diagnosis and management of neurologic disorders, the leading global cause of disability.
“These neurological conditions are increasing in prevalence and there’s a limited number of neurologists, so we wanted to understand what this looks like in the US,” Dr. Win said.
“There is a need to understand the patient journey from primary care to neurology care, from presentation of a suspected neurological disorder to diagnosis, referral to a specialist, and the time elapsed before the specialist visit for Alzheimer’s disease, MS, and Parkinson’s disease in the US,” Dr. Win added.
Timely and accurate diagnoses of neurologic disorders can optimize treatment outcomes. Because many of these diseases are first detected during a visit with a primary care physician, it is important to understand the timeline from the initial visit to a specialist referral, the investigators noted.
Analyzing Trends in Specialist Referrals
Using claims data from the Optum Normative Health Information database, researchers identified 48,525 adults with Alzheimer’s disease, 26,431 with Parkinson’s disease, and 8169 with MS who received a diagnosis from a primary care physician between 2016 and 2021.
They examined the proportion, timing, and demographic factors associated with referrals from primary care clinicians or other healthcare providers to specialists including neurologists, neurosurgeons, psychiatrists, and geriatric medicine specialists.
Results showed that patients with Parkinson’s disease were referred to a specialist most often (53%), followed by those with MS (42%) and those with Alzheimer’s disease (27%).
Individuals with Alzheimer’s disease waited the longest for a specialist referral, with a median of 10 months between the time of referral and the first specialist visit compared with 5.7 months for patients with Parkinson’s disease and 2.6 months for MS patients.
“Some patients with common conditions like Alzheimer’s disease, MS, and Parkinson’s disease don’t see a neurologist, and when they do, it can take as long as 10 months,” said Dr. Win.
Using zip code heatmaps, researchers found that the proportion of referrals for all neurologic disorders was higher in the Midwest and Northeast, whereas patients in the South and West were less likely to receive a referral.
Referrals for Alzheimer’s disease were low nationwide, except for some areas of Michigan and New England. California had the lowest referral rate for MS, followed by regions in the South and Northeast. Patients with Parkinson’s disease living in the Midwest and Northeast were more likely than those in the West to receive a specialist referral.
Previous studies have reported regional shortages of neurologists, said Dr. Win. “Our data seem to correlate that in terms of the areas with lower referral patterns, but as to whether that is causative or correlative, we don’t know.”
Odds of referral were also influenced by demographic characteristics such as sex, age, race, and ethnicity, investigators found.
For example, there were fewer referrals with increasing age across all three neurologic disorders, and men were more likely than women to be referred for Alzheimer’s disease and Parkinson’s disease. Compared with White patients, Parkinson’s disease referrals were less likely among African American, Asian, and Hispanic patients and Alzheimer’s disease referrals were less common among Asian and Hispanic patients.
Insurance status also affected referrals. People with MS and Parkinson’s disease who had commercial insurance were referred more often than were those with Medicare Advantage, said Dr. Win.
She also noted, “Additional research is needed to understand how being referred or not being referred to a neurologist actually impacts patient treatment, care and outcomes.”
Neurology Challenges
Commenting on the research, Thomas Vidic, MD, a community neurologist in Elkhart, Indiana, and clinical professor of neurology at Indiana University School of Medicine at South Bend, said that he was surprised by the variation in wait times for patients.
This, he said, could reflect a study limitation or a higher comfort level among primary care doctors in treating dementia.
With respect to MS, Dr. Vidic said that he believes primary care physicians may not be uncertain about prescribing the approved medications for the disease because there are so many of them.
In addition, patients with Alzheimer’s disease are older and perhaps less accepting of being referred to a specialist that may be hours away.
The bottom line for Dr. Vidic, though, is the lack of specialists. “It comes back to the fact we’re not doing a good job of having community neurologists available to take care of these problems,” he said.
The issue of community neurologist shortages was underlined by the study’s findings about geographic gaps in specialist referrals across the country, he said.
Neurologists make up about 2% of the medical workforce and this has remained static for some time, Dr. Vidic noted. Meanwhile, people are living longer and developing more neurologic diseases.
Dr. Vidic also pointed to the lack of neurology training programs. “There has not been a significant change in the number of programs in the last 10-15 years,” he said.
Study funding was not disclosed. Dr. Win reports receiving personal compensation for serving as an employee of Genentech and has stock in Genentech. Dr. Vidic reports no relevant financial disclosures.
A version of this article appeared on Medscape.com.
DENVER –
Investigators led by Nikki Win, PhD, medical manager/team lead, OMNI Scientific Strategy and Collaborations, US Medical Affairs, Genentech/Roche, found that patients with Parkinson’s disease were referred to a specialist most often, followed by those with MS and those with AD.
The findings were presented at the 2024 annual meeting of the American Academy of Neurology (AAN).
National Neurologist Shortage
The national neurologist shortage, coupled with the growing incidence of Alzheimer’s disease, Parkinson’s disease, MS, and other conditions has led the AAN and other organizations to call for expanding the role of primary care physicians in the diagnosis and management of neurologic disorders, the leading global cause of disability.
“These neurological conditions are increasing in prevalence and there’s a limited number of neurologists, so we wanted to understand what this looks like in the US,” Dr. Win said.
“There is a need to understand the patient journey from primary care to neurology care, from presentation of a suspected neurological disorder to diagnosis, referral to a specialist, and the time elapsed before the specialist visit for Alzheimer’s disease, MS, and Parkinson’s disease in the US,” Dr. Win added.
Timely and accurate diagnoses of neurologic disorders can optimize treatment outcomes. Because many of these diseases are first detected during a visit with a primary care physician, it is important to understand the timeline from the initial visit to a specialist referral, the investigators noted.
Analyzing Trends in Specialist Referrals
Using claims data from the Optum Normative Health Information database, researchers identified 48,525 adults with Alzheimer’s disease, 26,431 with Parkinson’s disease, and 8169 with MS who received a diagnosis from a primary care physician between 2016 and 2021.
They examined the proportion, timing, and demographic factors associated with referrals from primary care clinicians or other healthcare providers to specialists including neurologists, neurosurgeons, psychiatrists, and geriatric medicine specialists.
Results showed that patients with Parkinson’s disease were referred to a specialist most often (53%), followed by those with MS (42%) and those with Alzheimer’s disease (27%).
Individuals with Alzheimer’s disease waited the longest for a specialist referral, with a median of 10 months between the time of referral and the first specialist visit compared with 5.7 months for patients with Parkinson’s disease and 2.6 months for MS patients.
“Some patients with common conditions like Alzheimer’s disease, MS, and Parkinson’s disease don’t see a neurologist, and when they do, it can take as long as 10 months,” said Dr. Win.
Using zip code heatmaps, researchers found that the proportion of referrals for all neurologic disorders was higher in the Midwest and Northeast, whereas patients in the South and West were less likely to receive a referral.
Referrals for Alzheimer’s disease were low nationwide, except for some areas of Michigan and New England. California had the lowest referral rate for MS, followed by regions in the South and Northeast. Patients with Parkinson’s disease living in the Midwest and Northeast were more likely than those in the West to receive a specialist referral.
Previous studies have reported regional shortages of neurologists, said Dr. Win. “Our data seem to correlate that in terms of the areas with lower referral patterns, but as to whether that is causative or correlative, we don’t know.”
Odds of referral were also influenced by demographic characteristics such as sex, age, race, and ethnicity, investigators found.
For example, there were fewer referrals with increasing age across all three neurologic disorders, and men were more likely than women to be referred for Alzheimer’s disease and Parkinson’s disease. Compared with White patients, Parkinson’s disease referrals were less likely among African American, Asian, and Hispanic patients and Alzheimer’s disease referrals were less common among Asian and Hispanic patients.
Insurance status also affected referrals. People with MS and Parkinson’s disease who had commercial insurance were referred more often than were those with Medicare Advantage, said Dr. Win.
She also noted, “Additional research is needed to understand how being referred or not being referred to a neurologist actually impacts patient treatment, care and outcomes.”
Neurology Challenges
Commenting on the research, Thomas Vidic, MD, a community neurologist in Elkhart, Indiana, and clinical professor of neurology at Indiana University School of Medicine at South Bend, said that he was surprised by the variation in wait times for patients.
This, he said, could reflect a study limitation or a higher comfort level among primary care doctors in treating dementia.
With respect to MS, Dr. Vidic said that he believes primary care physicians may not be uncertain about prescribing the approved medications for the disease because there are so many of them.
In addition, patients with Alzheimer’s disease are older and perhaps less accepting of being referred to a specialist that may be hours away.
The bottom line for Dr. Vidic, though, is the lack of specialists. “It comes back to the fact we’re not doing a good job of having community neurologists available to take care of these problems,” he said.
The issue of community neurologist shortages was underlined by the study’s findings about geographic gaps in specialist referrals across the country, he said.
Neurologists make up about 2% of the medical workforce and this has remained static for some time, Dr. Vidic noted. Meanwhile, people are living longer and developing more neurologic diseases.
Dr. Vidic also pointed to the lack of neurology training programs. “There has not been a significant change in the number of programs in the last 10-15 years,” he said.
Study funding was not disclosed. Dr. Win reports receiving personal compensation for serving as an employee of Genentech and has stock in Genentech. Dr. Vidic reports no relevant financial disclosures.
A version of this article appeared on Medscape.com.
FROM AAN 2024
Updated Sjögren Disease Guideline Advises Doing ‘the Little Things Well’
LIVERPOOL, ENGLAND — An updated guideline from the British Society for Rheumatology (BSR) on the management of Sjögren disease asks rheumatologists and other clinicians caring for patients with the condition to “do the little things well” rather than overly focusing on rheumatologic treatments. The guideline’s new format provides recommendations for specific clinical questions and now also includes recommendations for managing the disease in children and adolescents.
“The original guideline was published in 2017, and things move on very rapidly,” consultant rheumatologist Elizabeth Price, MBBCh, PhD, said ahead of her presentation of the updated guideline at the annual meeting of the British Society for Rheumatology.
“We approached the update in a slightly different way,” said Dr. Price, who works at Great Western Hospital NHS Foundation Trust in Swindon, England. She was the chair of the new guideline’s working group and convenes the BSR’s Special Interest Group for Sjögren disease.
Previously, the approach was to look at the management of Sjögren disease affecting the eyes, mouth, salivary glands, and, in turn, systemic disease. “This time we posed questions that we felt needed to be asked, interrogated the literature, and then used that to come up with our recommendations,” Dr. Price said.
The answers to those questions were used to form the 19 recommendations that now make up the guideline. These cover four key areas on the management of Sjögren disease: confirming the diagnosis, treating the symptoms, managing systemic disease, and considering special situations such as planned pregnancy and comorbidities. There is also lifestyle advice and information about where to get good patient education.
What’s in a Name?
The BSR guideline on the management of adult and juvenile onset Sjögren disease is published in Rheumatology and is available via the BSR website, where it is accompanied by a short summary sheet.
The most notable change perhaps is the name the guideline now uses, Dr. Price said at BSR 2024. “We have been bold and called it Sjögren disease.” Previously, the guideline used the term primary Sjögren’s syndrome, but there has been a “move away from using eponymous syndromes and dropping s’s and apostrophes,” she explained.
Another significant change is that advice on managing Sjögren disease in children and adolescents is now included where appropriate, meaning that the British guideline is now the first to cover Sjögren disease “across the ages,” Dr. Price said.
A pediatric/adolescent rheumatologist joined the guideline working group, which already consisted of several adult rheumatologists, ophthalmologists, and a dentistry consultant. The group now comprises 22 members total, including a general practitioner, an oncologist, a renal physician, an occupational therapist, two patients with Sjögren disease, and a librarian.
Confirming the Diagnosis
The first questions asked to help form the new recommendations were around confirming a diagnosis of Sjögren disease, such as what is the diagnostic accuracy of antinuclear antibodies (ANAs), extractable nuclear antigens (ENAs), and other novel antigens in Sjögren disease? And what is the diagnostic accuracy of salivary gland ultrasound, imaging in general, and salivary gland or lacrimal gland biopsies?
The resulting recommendations advised not to measure ANAs in the absence of clinical indicators of Sjögren disease or any other connective tissue disease but to use it to screen if there was a clinical suspicion. And ENAs should be measured even if the ANAs were negative and there is a high index of suspicion.
In terms of imaging, ultrasound of the salivary glands was thought to be useful, but other imaging was not recommended for routine practice at the current time. Minor lip but not lacrimal gland biopsies were recommended if clinical and serologic features were not enough to make a diagnosis.
Lymphoma Worries
The 2017 version of the guideline did not include information about lymphoma, but this is the thing that most patients with Sjögren disease will worry about, Dr. Price said. “They all look it up on YouTube, they all come back and tell me that they are really worried they’ll develop it.”
The question that was therefore posed was whether there were any measurable biomarkers that could predict the development of lymphoma in adults and children. Seven predictors were found, the strongest being a low level of complement C4 alone or together with low levels of C3. Other predictors were salivary gland enlargement, lymphadenopathy, anti-Ro/La and rheumatoid factor autoantibodies, cryoglobulinemia, monoclonal gammopathy, and a high focus score.
All of these predictors put someone in a higher risk category for lymphoma. If two or fewer of those features are present, the lifetime risk is “probably below 2%,” Dr. Price said. However, if all seven are present, the lifetime risk is “approaching 100%.”
The recommendation made on the basis of these findings is that people with Sjögren disease need to be offered early further investigation if they present with any new salivary gland swelling or other symptoms that might suggest the development of lymphoma. In this regard, a labial salivary gland biopsy might provide additional prognostic information.
‘Do the Little Things Well’
“You have to do the little things well,” Dr. Price said. “Many of the patients [who] come to see me for a second opinion have not been prescribed the right eye drops, have not been given advice on dental care,” with their management taking “too much on the rheumatological treatments.”
Rheumatologists are of course not trained or expected to be experts in ophthalmology or dentistry, but “you need to look at their mouth and you do need to examine their eyes, and you do need to give them some advice,” Dr. Price advised.
Thankfully, that is where the updated guidelines should help, with a recommendation that people with Sjögren disease should use preservative-free eye drops every 2-3 hours.
“It’s vital you avoid preservatives, because preservatives flatten the corneal surface and reduce the surface area and can cause inflammation in their own right,” Dr. Price cautioned, adding that there are plenty of suitable eye drop formulations available.
In regard to helping with dry mouth symptoms, the recommendation is to use a saliva substitute for symptomatic relief. For vaginal dryness, the recommendation is to consider advising topical nonhormonal vaginal moisturizers plus estrogen creams or pessaries in peri- or postmenopausal women with significant vaginal dryness.
“Very important, however, is to maintain a neutral pH, an alkaline environment in the mouth because acid damages dental enamel,” Dr. Price said. Conversely, an acidic vaginal moisturizer is needed to treat vaginal dryness.
Dental hygiene is important. Regular brushing with a fluoride-based toothpaste is advised. The use of xylitol-containing products has been shown to reduce bacteria known to increase the risk for dental decay. Telling patients not to eat between meals is also simple but important advice.
“We do recommend that patients are assessed holistically,” Dr. Price said, noting that they should be offered access to cognitive-behavioral therapy and exercise therapies to help with the symptoms of fatigue and joint pain.
Watch Out for Comorbidities
Sjögren disease is associated with many comorbidities, some of which might be predicted from the age and demographics of the people who are normally affected.
“This is on the whole an older, female population, so you see a lot of osteoarthritis, gastroesophageal reflux, and hypertension,” Dr. Price said. “However, you may not be aware that 1 in 5 of these patients develop thyroid disease,” and there is a higher rate of celiac disease and primary biliary cholangitis than is seen in the general background population.
The recommendation, therefore, is to “be aware of and consider screening for commonly associated conditions, as guided by age and/or clinical presentation.” As such, it’s recommended that baseline and repeated investigations that look for signs of comorbidity are performed, such as thyroid function assessment and liver function tests, to name two.
Treatment Recommendations
As in the original guideline, the treatment of systemic disease is discussed, but the advice has been overhauled with the availability of new data.
The updated guidance notes that a trial of hydroxychloroquine for 6-12 months is the recommended treatment approach for people with fatigue and systemic symptoms.
Systemic steroids may be used in the short-term for specific indications but should not be offered routinely.
Conventional immunosuppressive or biologic drugs and immunoglobulins are not currently recommended outside of managing specific systemic complications.
In juvenile cases, the treatment of recurrent swollen parotid glands that are not due to infection or stone disease should include a short course of a nonsteroidal anti-inflammatory drug or a short course of oral steroids. This should be combined with massage followed by washouts with saline or steroids. In refractory cases, escalation to anti–B-cell–targeted therapies may be considered in select situations.
View on Updates
Patient advocate Bridget Crampton, who leads the helpline team at Sjögren’s UK (formerly the British Sjögren’s Syndrome Association), commented on the importance of the guidelines during a roundtable held by the BSR.
“I think it will help [patients] make better use of their own appointments. So, they’ll know what treatments might be offered. They’ll know what they want to talk about at their appointments,” she said.
Ms. Crampton, who has lived with Sjögren disease herself for the past 20 years, added: “I think it’s important for patients that we have guidelines like this. It means that all clinicians can easily access information. My hope is that it might standardize care across the UK a little bit more.”
No specific funding was received to create the guidelines, be that from any bodies in the public, commercial, or not-for-profit sectors. No conflicts of interests were expressed by any of the experts quoted in this article.
A version of this article appeared on Medscape.com.
LIVERPOOL, ENGLAND — An updated guideline from the British Society for Rheumatology (BSR) on the management of Sjögren disease asks rheumatologists and other clinicians caring for patients with the condition to “do the little things well” rather than overly focusing on rheumatologic treatments. The guideline’s new format provides recommendations for specific clinical questions and now also includes recommendations for managing the disease in children and adolescents.
“The original guideline was published in 2017, and things move on very rapidly,” consultant rheumatologist Elizabeth Price, MBBCh, PhD, said ahead of her presentation of the updated guideline at the annual meeting of the British Society for Rheumatology.
“We approached the update in a slightly different way,” said Dr. Price, who works at Great Western Hospital NHS Foundation Trust in Swindon, England. She was the chair of the new guideline’s working group and convenes the BSR’s Special Interest Group for Sjögren disease.
Previously, the approach was to look at the management of Sjögren disease affecting the eyes, mouth, salivary glands, and, in turn, systemic disease. “This time we posed questions that we felt needed to be asked, interrogated the literature, and then used that to come up with our recommendations,” Dr. Price said.
The answers to those questions were used to form the 19 recommendations that now make up the guideline. These cover four key areas on the management of Sjögren disease: confirming the diagnosis, treating the symptoms, managing systemic disease, and considering special situations such as planned pregnancy and comorbidities. There is also lifestyle advice and information about where to get good patient education.
What’s in a Name?
The BSR guideline on the management of adult and juvenile onset Sjögren disease is published in Rheumatology and is available via the BSR website, where it is accompanied by a short summary sheet.
The most notable change perhaps is the name the guideline now uses, Dr. Price said at BSR 2024. “We have been bold and called it Sjögren disease.” Previously, the guideline used the term primary Sjögren’s syndrome, but there has been a “move away from using eponymous syndromes and dropping s’s and apostrophes,” she explained.
Another significant change is that advice on managing Sjögren disease in children and adolescents is now included where appropriate, meaning that the British guideline is now the first to cover Sjögren disease “across the ages,” Dr. Price said.
A pediatric/adolescent rheumatologist joined the guideline working group, which already consisted of several adult rheumatologists, ophthalmologists, and a dentistry consultant. The group now comprises 22 members total, including a general practitioner, an oncologist, a renal physician, an occupational therapist, two patients with Sjögren disease, and a librarian.
Confirming the Diagnosis
The first questions asked to help form the new recommendations were around confirming a diagnosis of Sjögren disease, such as what is the diagnostic accuracy of antinuclear antibodies (ANAs), extractable nuclear antigens (ENAs), and other novel antigens in Sjögren disease? And what is the diagnostic accuracy of salivary gland ultrasound, imaging in general, and salivary gland or lacrimal gland biopsies?
The resulting recommendations advised not to measure ANAs in the absence of clinical indicators of Sjögren disease or any other connective tissue disease but to use it to screen if there was a clinical suspicion. And ENAs should be measured even if the ANAs were negative and there is a high index of suspicion.
In terms of imaging, ultrasound of the salivary glands was thought to be useful, but other imaging was not recommended for routine practice at the current time. Minor lip but not lacrimal gland biopsies were recommended if clinical and serologic features were not enough to make a diagnosis.
Lymphoma Worries
The 2017 version of the guideline did not include information about lymphoma, but this is the thing that most patients with Sjögren disease will worry about, Dr. Price said. “They all look it up on YouTube, they all come back and tell me that they are really worried they’ll develop it.”
The question that was therefore posed was whether there were any measurable biomarkers that could predict the development of lymphoma in adults and children. Seven predictors were found, the strongest being a low level of complement C4 alone or together with low levels of C3. Other predictors were salivary gland enlargement, lymphadenopathy, anti-Ro/La and rheumatoid factor autoantibodies, cryoglobulinemia, monoclonal gammopathy, and a high focus score.
All of these predictors put someone in a higher risk category for lymphoma. If two or fewer of those features are present, the lifetime risk is “probably below 2%,” Dr. Price said. However, if all seven are present, the lifetime risk is “approaching 100%.”
The recommendation made on the basis of these findings is that people with Sjögren disease need to be offered early further investigation if they present with any new salivary gland swelling or other symptoms that might suggest the development of lymphoma. In this regard, a labial salivary gland biopsy might provide additional prognostic information.
‘Do the Little Things Well’
“You have to do the little things well,” Dr. Price said. “Many of the patients [who] come to see me for a second opinion have not been prescribed the right eye drops, have not been given advice on dental care,” with their management taking “too much on the rheumatological treatments.”
Rheumatologists are of course not trained or expected to be experts in ophthalmology or dentistry, but “you need to look at their mouth and you do need to examine their eyes, and you do need to give them some advice,” Dr. Price advised.
Thankfully, that is where the updated guidelines should help, with a recommendation that people with Sjögren disease should use preservative-free eye drops every 2-3 hours.
“It’s vital you avoid preservatives, because preservatives flatten the corneal surface and reduce the surface area and can cause inflammation in their own right,” Dr. Price cautioned, adding that there are plenty of suitable eye drop formulations available.
In regard to helping with dry mouth symptoms, the recommendation is to use a saliva substitute for symptomatic relief. For vaginal dryness, the recommendation is to consider advising topical nonhormonal vaginal moisturizers plus estrogen creams or pessaries in peri- or postmenopausal women with significant vaginal dryness.
“Very important, however, is to maintain a neutral pH, an alkaline environment in the mouth because acid damages dental enamel,” Dr. Price said. Conversely, an acidic vaginal moisturizer is needed to treat vaginal dryness.
Dental hygiene is important. Regular brushing with a fluoride-based toothpaste is advised. The use of xylitol-containing products has been shown to reduce bacteria known to increase the risk for dental decay. Telling patients not to eat between meals is also simple but important advice.
“We do recommend that patients are assessed holistically,” Dr. Price said, noting that they should be offered access to cognitive-behavioral therapy and exercise therapies to help with the symptoms of fatigue and joint pain.
Watch Out for Comorbidities
Sjögren disease is associated with many comorbidities, some of which might be predicted from the age and demographics of the people who are normally affected.
“This is on the whole an older, female population, so you see a lot of osteoarthritis, gastroesophageal reflux, and hypertension,” Dr. Price said. “However, you may not be aware that 1 in 5 of these patients develop thyroid disease,” and there is a higher rate of celiac disease and primary biliary cholangitis than is seen in the general background population.
The recommendation, therefore, is to “be aware of and consider screening for commonly associated conditions, as guided by age and/or clinical presentation.” As such, it’s recommended that baseline and repeated investigations that look for signs of comorbidity are performed, such as thyroid function assessment and liver function tests, to name two.
Treatment Recommendations
As in the original guideline, the treatment of systemic disease is discussed, but the advice has been overhauled with the availability of new data.
The updated guidance notes that a trial of hydroxychloroquine for 6-12 months is the recommended treatment approach for people with fatigue and systemic symptoms.
Systemic steroids may be used in the short-term for specific indications but should not be offered routinely.
Conventional immunosuppressive or biologic drugs and immunoglobulins are not currently recommended outside of managing specific systemic complications.
In juvenile cases, the treatment of recurrent swollen parotid glands that are not due to infection or stone disease should include a short course of a nonsteroidal anti-inflammatory drug or a short course of oral steroids. This should be combined with massage followed by washouts with saline or steroids. In refractory cases, escalation to anti–B-cell–targeted therapies may be considered in select situations.
View on Updates
Patient advocate Bridget Crampton, who leads the helpline team at Sjögren’s UK (formerly the British Sjögren’s Syndrome Association), commented on the importance of the guidelines during a roundtable held by the BSR.
“I think it will help [patients] make better use of their own appointments. So, they’ll know what treatments might be offered. They’ll know what they want to talk about at their appointments,” she said.
Ms. Crampton, who has lived with Sjögren disease herself for the past 20 years, added: “I think it’s important for patients that we have guidelines like this. It means that all clinicians can easily access information. My hope is that it might standardize care across the UK a little bit more.”
No specific funding was received to create the guidelines, be that from any bodies in the public, commercial, or not-for-profit sectors. No conflicts of interests were expressed by any of the experts quoted in this article.
A version of this article appeared on Medscape.com.
LIVERPOOL, ENGLAND — An updated guideline from the British Society for Rheumatology (BSR) on the management of Sjögren disease asks rheumatologists and other clinicians caring for patients with the condition to “do the little things well” rather than overly focusing on rheumatologic treatments. The guideline’s new format provides recommendations for specific clinical questions and now also includes recommendations for managing the disease in children and adolescents.
“The original guideline was published in 2017, and things move on very rapidly,” consultant rheumatologist Elizabeth Price, MBBCh, PhD, said ahead of her presentation of the updated guideline at the annual meeting of the British Society for Rheumatology.
“We approached the update in a slightly different way,” said Dr. Price, who works at Great Western Hospital NHS Foundation Trust in Swindon, England. She was the chair of the new guideline’s working group and convenes the BSR’s Special Interest Group for Sjögren disease.
Previously, the approach was to look at the management of Sjögren disease affecting the eyes, mouth, salivary glands, and, in turn, systemic disease. “This time we posed questions that we felt needed to be asked, interrogated the literature, and then used that to come up with our recommendations,” Dr. Price said.
The answers to those questions were used to form the 19 recommendations that now make up the guideline. These cover four key areas on the management of Sjögren disease: confirming the diagnosis, treating the symptoms, managing systemic disease, and considering special situations such as planned pregnancy and comorbidities. There is also lifestyle advice and information about where to get good patient education.
What’s in a Name?
The BSR guideline on the management of adult and juvenile onset Sjögren disease is published in Rheumatology and is available via the BSR website, where it is accompanied by a short summary sheet.
The most notable change perhaps is the name the guideline now uses, Dr. Price said at BSR 2024. “We have been bold and called it Sjögren disease.” Previously, the guideline used the term primary Sjögren’s syndrome, but there has been a “move away from using eponymous syndromes and dropping s’s and apostrophes,” she explained.
Another significant change is that advice on managing Sjögren disease in children and adolescents is now included where appropriate, meaning that the British guideline is now the first to cover Sjögren disease “across the ages,” Dr. Price said.
A pediatric/adolescent rheumatologist joined the guideline working group, which already consisted of several adult rheumatologists, ophthalmologists, and a dentistry consultant. The group now comprises 22 members total, including a general practitioner, an oncologist, a renal physician, an occupational therapist, two patients with Sjögren disease, and a librarian.
Confirming the Diagnosis
The first questions asked to help form the new recommendations were around confirming a diagnosis of Sjögren disease, such as what is the diagnostic accuracy of antinuclear antibodies (ANAs), extractable nuclear antigens (ENAs), and other novel antigens in Sjögren disease? And what is the diagnostic accuracy of salivary gland ultrasound, imaging in general, and salivary gland or lacrimal gland biopsies?
The resulting recommendations advised not to measure ANAs in the absence of clinical indicators of Sjögren disease or any other connective tissue disease but to use it to screen if there was a clinical suspicion. And ENAs should be measured even if the ANAs were negative and there is a high index of suspicion.
In terms of imaging, ultrasound of the salivary glands was thought to be useful, but other imaging was not recommended for routine practice at the current time. Minor lip but not lacrimal gland biopsies were recommended if clinical and serologic features were not enough to make a diagnosis.
Lymphoma Worries
The 2017 version of the guideline did not include information about lymphoma, but this is the thing that most patients with Sjögren disease will worry about, Dr. Price said. “They all look it up on YouTube, they all come back and tell me that they are really worried they’ll develop it.”
The question that was therefore posed was whether there were any measurable biomarkers that could predict the development of lymphoma in adults and children. Seven predictors were found, the strongest being a low level of complement C4 alone or together with low levels of C3. Other predictors were salivary gland enlargement, lymphadenopathy, anti-Ro/La and rheumatoid factor autoantibodies, cryoglobulinemia, monoclonal gammopathy, and a high focus score.
All of these predictors put someone in a higher risk category for lymphoma. If two or fewer of those features are present, the lifetime risk is “probably below 2%,” Dr. Price said. However, if all seven are present, the lifetime risk is “approaching 100%.”
The recommendation made on the basis of these findings is that people with Sjögren disease need to be offered early further investigation if they present with any new salivary gland swelling or other symptoms that might suggest the development of lymphoma. In this regard, a labial salivary gland biopsy might provide additional prognostic information.
‘Do the Little Things Well’
“You have to do the little things well,” Dr. Price said. “Many of the patients [who] come to see me for a second opinion have not been prescribed the right eye drops, have not been given advice on dental care,” with their management taking “too much on the rheumatological treatments.”
Rheumatologists are of course not trained or expected to be experts in ophthalmology or dentistry, but “you need to look at their mouth and you do need to examine their eyes, and you do need to give them some advice,” Dr. Price advised.
Thankfully, that is where the updated guidelines should help, with a recommendation that people with Sjögren disease should use preservative-free eye drops every 2-3 hours.
“It’s vital you avoid preservatives, because preservatives flatten the corneal surface and reduce the surface area and can cause inflammation in their own right,” Dr. Price cautioned, adding that there are plenty of suitable eye drop formulations available.
In regard to helping with dry mouth symptoms, the recommendation is to use a saliva substitute for symptomatic relief. For vaginal dryness, the recommendation is to consider advising topical nonhormonal vaginal moisturizers plus estrogen creams or pessaries in peri- or postmenopausal women with significant vaginal dryness.
“Very important, however, is to maintain a neutral pH, an alkaline environment in the mouth because acid damages dental enamel,” Dr. Price said. Conversely, an acidic vaginal moisturizer is needed to treat vaginal dryness.
Dental hygiene is important. Regular brushing with a fluoride-based toothpaste is advised. The use of xylitol-containing products has been shown to reduce bacteria known to increase the risk for dental decay. Telling patients not to eat between meals is also simple but important advice.
“We do recommend that patients are assessed holistically,” Dr. Price said, noting that they should be offered access to cognitive-behavioral therapy and exercise therapies to help with the symptoms of fatigue and joint pain.
Watch Out for Comorbidities
Sjögren disease is associated with many comorbidities, some of which might be predicted from the age and demographics of the people who are normally affected.
“This is on the whole an older, female population, so you see a lot of osteoarthritis, gastroesophageal reflux, and hypertension,” Dr. Price said. “However, you may not be aware that 1 in 5 of these patients develop thyroid disease,” and there is a higher rate of celiac disease and primary biliary cholangitis than is seen in the general background population.
The recommendation, therefore, is to “be aware of and consider screening for commonly associated conditions, as guided by age and/or clinical presentation.” As such, it’s recommended that baseline and repeated investigations that look for signs of comorbidity are performed, such as thyroid function assessment and liver function tests, to name two.
Treatment Recommendations
As in the original guideline, the treatment of systemic disease is discussed, but the advice has been overhauled with the availability of new data.
The updated guidance notes that a trial of hydroxychloroquine for 6-12 months is the recommended treatment approach for people with fatigue and systemic symptoms.
Systemic steroids may be used in the short-term for specific indications but should not be offered routinely.
Conventional immunosuppressive or biologic drugs and immunoglobulins are not currently recommended outside of managing specific systemic complications.
In juvenile cases, the treatment of recurrent swollen parotid glands that are not due to infection or stone disease should include a short course of a nonsteroidal anti-inflammatory drug or a short course of oral steroids. This should be combined with massage followed by washouts with saline or steroids. In refractory cases, escalation to anti–B-cell–targeted therapies may be considered in select situations.
View on Updates
Patient advocate Bridget Crampton, who leads the helpline team at Sjögren’s UK (formerly the British Sjögren’s Syndrome Association), commented on the importance of the guidelines during a roundtable held by the BSR.
“I think it will help [patients] make better use of their own appointments. So, they’ll know what treatments might be offered. They’ll know what they want to talk about at their appointments,” she said.
Ms. Crampton, who has lived with Sjögren disease herself for the past 20 years, added: “I think it’s important for patients that we have guidelines like this. It means that all clinicians can easily access information. My hope is that it might standardize care across the UK a little bit more.”
No specific funding was received to create the guidelines, be that from any bodies in the public, commercial, or not-for-profit sectors. No conflicts of interests were expressed by any of the experts quoted in this article.
A version of this article appeared on Medscape.com.
FROM BSR 2024
Complement Inhibitor Scores Impressive Data in CIDP
DENVER — , with good results in treatment-refractory and treatment-naive patients, according to results from a phase 2 clinical trial.
‘Impressive’ Results
The results were impressive, especially given that riliprubart outperformed IVIG, according to Frank Tennigkeit, PhD, senior director of pediatric development rare diseases at UCB Biosciences, who attended the session at the 2024 annual meeting of the American Academy of Neurology, where the study was presented. “There are few trials on CIDP, and the standard data are IVIG data.
“This is really amazing, especially in refractory patients. I turned to my neighbor [during the presentation] and said, ‘I’ve never seen CIDP data that good in my life. It works in all kinds of different patient populations, and also on the refractory ones. That’s what you want. That’s where the need is. And you saw a consistent effect and a strong effect on top of standard of care,” said Dr. Tennigkeit.
“It’s impressive. The only problem with CIDP is that it’s very difficult to compare treatments, because everyone has a different outcome. This was an open-label study, so there’s always a confounding bias. The proof of the pudding is going to be in a phase 3 blinded, randomized trial, but what I really admire about them, and I thought was very gutsy, is that they’re going head-to-head versus IVIG. I haven’t seen anyone who’s done that yet [in CIDP],” said Shalom Patole, MD, an internist and telehealth consultant in India, who also attended the session.
An Open-Label Phase 2 Study
The study had a somewhat unique design, according to Richard Lewis, MD, who presented the results. It was an open-label design that examined three subpopulations: 25 who had objective response to treatments (standard of care [SOC]–treated, mean age, 58.2 years; 80% male), 18 refractory patients who had been off treatment for up to 12 weeks (SOC-refractory, mean age, 63.9 years; 61% male), and 12 patients who had not been treated at all for at least 6 months or were treatment-naive (SOC-naive, mean age, 59.1 years; 67% male).
At 24 weeks, “if you looked at the treated group, 88% of those patients improved to remain stable, and only 12% relapsed. Most significantly, these patients who had responded to their IVIG, who were supposedly doing pretty well, 44% of those actually got better, so they improved from what would have been a pretty good baseline. The refractory patients, despite flunking the other treatments, 50% actually passed or improved with the treatment, so a significant response rate in a group that was not responding so well,” said Dr. Lewis, who is a neurologist at Cedars Sinai Medical Center.
The researchers also found that treatment with riliprubart led to inhibition of complement activity and a trend in reduction in neurofilament light chain levels by week 24 in all three groups.
Treatment-emergent adverse events occurred in 60% of the SOC-treated group, 72% of the SOC-refractory group, and 75% of the SOC-naive group, though grade 3 or higher events were rare (4%, 17%, and 8%, respectively). There was one death in the SOC-treated group and one in the SOC-refractory group. Both patients were elderly and had comorbid conditions.
Challenging the Current Standard of Care
The data have led to two additional phase 3 trials, one in refractory patients (Mobilize), and another for patients treated with IVIG who have residual disability (Vitalize). Sanofi is also planning a phase 3, placebo-controlled trial with one arm that will compare the antibody to IVIG, “which is a pretty ambitious trial design,” admitted Dr. Lewis.
Such a strategy is risky, but it could represent a big payoff for Sanofi if the phase 3 studies replicate the phase 2 studies. “No one would be using IVIG anymore if you beat IVIG by 50%. That will be the standard. If you do the trial [versus IVIG], you have a higher risk, but if you win it, you will win big,” said Dr. Tennigkeit.
The study was funded by Sanofi. Dr. Lewis has financial relationships with CSL Behring, Grifols, Pfizer, Sanofi, Argenx, Pharnext, Roche, Johnson & Johnson, Takeda, Boehringer Ingelheim, Nuvig, Dianthus, Janssen, Medscape, Alexion, Alnylam, and Novartis. Dr. Tennigkeit is an employee of UCB Biosciences. Dr. Patole has no relevant financial disclosures.
DENVER — , with good results in treatment-refractory and treatment-naive patients, according to results from a phase 2 clinical trial.
‘Impressive’ Results
The results were impressive, especially given that riliprubart outperformed IVIG, according to Frank Tennigkeit, PhD, senior director of pediatric development rare diseases at UCB Biosciences, who attended the session at the 2024 annual meeting of the American Academy of Neurology, where the study was presented. “There are few trials on CIDP, and the standard data are IVIG data.
“This is really amazing, especially in refractory patients. I turned to my neighbor [during the presentation] and said, ‘I’ve never seen CIDP data that good in my life. It works in all kinds of different patient populations, and also on the refractory ones. That’s what you want. That’s where the need is. And you saw a consistent effect and a strong effect on top of standard of care,” said Dr. Tennigkeit.
“It’s impressive. The only problem with CIDP is that it’s very difficult to compare treatments, because everyone has a different outcome. This was an open-label study, so there’s always a confounding bias. The proof of the pudding is going to be in a phase 3 blinded, randomized trial, but what I really admire about them, and I thought was very gutsy, is that they’re going head-to-head versus IVIG. I haven’t seen anyone who’s done that yet [in CIDP],” said Shalom Patole, MD, an internist and telehealth consultant in India, who also attended the session.
An Open-Label Phase 2 Study
The study had a somewhat unique design, according to Richard Lewis, MD, who presented the results. It was an open-label design that examined three subpopulations: 25 who had objective response to treatments (standard of care [SOC]–treated, mean age, 58.2 years; 80% male), 18 refractory patients who had been off treatment for up to 12 weeks (SOC-refractory, mean age, 63.9 years; 61% male), and 12 patients who had not been treated at all for at least 6 months or were treatment-naive (SOC-naive, mean age, 59.1 years; 67% male).
At 24 weeks, “if you looked at the treated group, 88% of those patients improved to remain stable, and only 12% relapsed. Most significantly, these patients who had responded to their IVIG, who were supposedly doing pretty well, 44% of those actually got better, so they improved from what would have been a pretty good baseline. The refractory patients, despite flunking the other treatments, 50% actually passed or improved with the treatment, so a significant response rate in a group that was not responding so well,” said Dr. Lewis, who is a neurologist at Cedars Sinai Medical Center.
The researchers also found that treatment with riliprubart led to inhibition of complement activity and a trend in reduction in neurofilament light chain levels by week 24 in all three groups.
Treatment-emergent adverse events occurred in 60% of the SOC-treated group, 72% of the SOC-refractory group, and 75% of the SOC-naive group, though grade 3 or higher events were rare (4%, 17%, and 8%, respectively). There was one death in the SOC-treated group and one in the SOC-refractory group. Both patients were elderly and had comorbid conditions.
Challenging the Current Standard of Care
The data have led to two additional phase 3 trials, one in refractory patients (Mobilize), and another for patients treated with IVIG who have residual disability (Vitalize). Sanofi is also planning a phase 3, placebo-controlled trial with one arm that will compare the antibody to IVIG, “which is a pretty ambitious trial design,” admitted Dr. Lewis.
Such a strategy is risky, but it could represent a big payoff for Sanofi if the phase 3 studies replicate the phase 2 studies. “No one would be using IVIG anymore if you beat IVIG by 50%. That will be the standard. If you do the trial [versus IVIG], you have a higher risk, but if you win it, you will win big,” said Dr. Tennigkeit.
The study was funded by Sanofi. Dr. Lewis has financial relationships with CSL Behring, Grifols, Pfizer, Sanofi, Argenx, Pharnext, Roche, Johnson & Johnson, Takeda, Boehringer Ingelheim, Nuvig, Dianthus, Janssen, Medscape, Alexion, Alnylam, and Novartis. Dr. Tennigkeit is an employee of UCB Biosciences. Dr. Patole has no relevant financial disclosures.
DENVER — , with good results in treatment-refractory and treatment-naive patients, according to results from a phase 2 clinical trial.
‘Impressive’ Results
The results were impressive, especially given that riliprubart outperformed IVIG, according to Frank Tennigkeit, PhD, senior director of pediatric development rare diseases at UCB Biosciences, who attended the session at the 2024 annual meeting of the American Academy of Neurology, where the study was presented. “There are few trials on CIDP, and the standard data are IVIG data.
“This is really amazing, especially in refractory patients. I turned to my neighbor [during the presentation] and said, ‘I’ve never seen CIDP data that good in my life. It works in all kinds of different patient populations, and also on the refractory ones. That’s what you want. That’s where the need is. And you saw a consistent effect and a strong effect on top of standard of care,” said Dr. Tennigkeit.
“It’s impressive. The only problem with CIDP is that it’s very difficult to compare treatments, because everyone has a different outcome. This was an open-label study, so there’s always a confounding bias. The proof of the pudding is going to be in a phase 3 blinded, randomized trial, but what I really admire about them, and I thought was very gutsy, is that they’re going head-to-head versus IVIG. I haven’t seen anyone who’s done that yet [in CIDP],” said Shalom Patole, MD, an internist and telehealth consultant in India, who also attended the session.
An Open-Label Phase 2 Study
The study had a somewhat unique design, according to Richard Lewis, MD, who presented the results. It was an open-label design that examined three subpopulations: 25 who had objective response to treatments (standard of care [SOC]–treated, mean age, 58.2 years; 80% male), 18 refractory patients who had been off treatment for up to 12 weeks (SOC-refractory, mean age, 63.9 years; 61% male), and 12 patients who had not been treated at all for at least 6 months or were treatment-naive (SOC-naive, mean age, 59.1 years; 67% male).
At 24 weeks, “if you looked at the treated group, 88% of those patients improved to remain stable, and only 12% relapsed. Most significantly, these patients who had responded to their IVIG, who were supposedly doing pretty well, 44% of those actually got better, so they improved from what would have been a pretty good baseline. The refractory patients, despite flunking the other treatments, 50% actually passed or improved with the treatment, so a significant response rate in a group that was not responding so well,” said Dr. Lewis, who is a neurologist at Cedars Sinai Medical Center.
The researchers also found that treatment with riliprubart led to inhibition of complement activity and a trend in reduction in neurofilament light chain levels by week 24 in all three groups.
Treatment-emergent adverse events occurred in 60% of the SOC-treated group, 72% of the SOC-refractory group, and 75% of the SOC-naive group, though grade 3 or higher events were rare (4%, 17%, and 8%, respectively). There was one death in the SOC-treated group and one in the SOC-refractory group. Both patients were elderly and had comorbid conditions.
Challenging the Current Standard of Care
The data have led to two additional phase 3 trials, one in refractory patients (Mobilize), and another for patients treated with IVIG who have residual disability (Vitalize). Sanofi is also planning a phase 3, placebo-controlled trial with one arm that will compare the antibody to IVIG, “which is a pretty ambitious trial design,” admitted Dr. Lewis.
Such a strategy is risky, but it could represent a big payoff for Sanofi if the phase 3 studies replicate the phase 2 studies. “No one would be using IVIG anymore if you beat IVIG by 50%. That will be the standard. If you do the trial [versus IVIG], you have a higher risk, but if you win it, you will win big,” said Dr. Tennigkeit.
The study was funded by Sanofi. Dr. Lewis has financial relationships with CSL Behring, Grifols, Pfizer, Sanofi, Argenx, Pharnext, Roche, Johnson & Johnson, Takeda, Boehringer Ingelheim, Nuvig, Dianthus, Janssen, Medscape, Alexion, Alnylam, and Novartis. Dr. Tennigkeit is an employee of UCB Biosciences. Dr. Patole has no relevant financial disclosures.
FROM AAN 2024
Will Changing the Term Obesity Reduce Stigma?
ASUNCIÓN, PARAGUAY — The Lancet Diabetes & Endocrinology’s Commission for the Definition and Diagnosis of Clinical Obesity will soon publish criteria for distinguishing between clinical obesity and other preclinical phases. The criteria are intended to limit the negative connotations and misunderstandings associated with the word obesity and to clearly convey the idea that it is a disease and not just a condition that increases the risk for other pathologies.
One of the two Latin American experts on the 60-member commission, Ricardo Cohen, MD, PhD, coordinator of the Obesity and Diabetes Center at the Oswaldo Cruz German Hospital in São Paulo, Brazil, discussed this effort with this news organization.
The proposal being finalized would acknowledge a preclinical stage of obesity characterized by alterations in cells or tissues that lead to changes in organ structure, but not function. This stage can be measured by body mass index (BMI) or waist circumference.
The clinical stage occurs when “obesity already affects [the function of] organs, tissues, and functions like mobility. Here, it is a disease per se. And an active disease requires treatment,” said Dr. Cohen. The health risks associated with excess adiposity have already materialized and can be objectively documented through specific signs and symptoms.
Various experts from Latin America who participated in the XV Congress of the Latin American Obesity Societies (FLASO) and II Paraguayan Obesity Congress expressed to this news organization their reservations about the proposed name change and its practical effects. They highlighted the pros and cons of various terminologies that had been considered in recent years.
“Stigma undoubtedly exists. There’s also no doubt that this stigma and daily pressure on a person’s self-esteem influence behavior and condition a poor future clinical outcome because they promote denial of the disease. Healthcare professionals can make these mistakes. But I’m not sure that changing the name of a known disease will make a difference,” said Rafael Figueredo Grijalba, MD, president of FLASO and director of the Nutrition program at the Faculty of Health Sciences of the Nuestra Señora de la Asunción Catholic University in Paraguay.
Spotlight on Adiposity
An alternative term for obesity proposed in 2016 by what is now the American Association of Clinical Endocrinology and by the American College of Endocrinology is “adiposity-based chronic disease (ABCD).” This designation “is on the right track,” said Violeta Jiménez, MD, internal medicine and endocrinology specialist at the Clinical Hospital of the National University of Asunción and the Comprehensive Diabetes Care Network of the Paraguay Social Security Institute.
The word obese is perceived as an insult, and the health impact of obesity is related to the quantity, distribution, and function of adipose tissue, said Dr. Jiménez. The BMI, the most used parameter in practice to determine overweight and obesity, “does not predict excess adiposity or determine a disease here and now, just as waist circumference does not confirm the condition.”
Will the public be attracted to ABCD? What disease do these initials refer to, asked Dr. Jiménez. “What I like about the term ABCD is that it is not solely based on weight. It brings up the issue that a person who may not have obesity by BMI has adiposity and therefore has a disease brewing inside them.”
“Any obesity denomination is useful as long as the impact of comorbidities is taken into account, as well as the fact that it is not an aesthetic problem and treatment will be escalated aiming to benefit not only weight loss but also comorbidities,” said Paul Camperos Sánchez, MD, internal medicine and endocrinology specialist and head of research at La Trinidad Teaching Medical Center in Caracas, Venezuela, and former president of the Venezuelan Association for the Study of Obesity.
Dr. Camperos Sánchez added that the classification of overweight and obesity into grades on the basis of BMI, which is recognized by the World Health Organization, “is the most known and for me remains the most comfortable. I will accept any other approach, but in my clinical practice, I continue to do it this way.”
Fundamentally, knowledge can reduce social stigma and even prejudice from the medical community itself. “We must be respectful and compassionate and understand well what we are treating and the best way to approach each patient with realistic expectations. Evaluate whether, in addition to medication or intensive lifestyle changes, behavioral interventions or physiotherapy are required. If you don’t manage it well and find it challenging, perhaps that’s why we see so much stigmatization or humiliation of the patient. And that has nothing to do with the name [of the disease],” said Dr. Camperos Sánchez.
‘Biological Injustices’
Julio Montero, MD, nutritionist, president of the Argentine Society of Obesity and Eating Disorders, and former president of FLASO, told this news organization that the topic of nomenclatures “provides a lot of grounds for debate,” but he prefers the term “clinical obesity” because it has a medical meaning, is appropriate for statistical purposes, better conveys the concept of obesity as a disease, and distinguishes patients who have high weight or a spherical figure but may be free of weight-dependent conditions.
“Clinical obesity suggests that it is a person with high weight who has health problems and life expectancy issues related to excessive corpulence (weight-fat). The addition of the adjective clinical suggests that the patient has been evaluated by phenotype, fat distribution, hypertension, blood glucose, triglycerides, apnea, cardiac dilation, and mechanical problems, and based on that analysis, the diagnosis has been made,” said Dr. Montero.
Other positive aspects of the designation include not assuming that comorbidities are a direct consequence of adipose tissue accumulation because “lean mass often increases in patients with obesity, and diet and sedentary lifestyle also have an influence” nor does the term exclude people with central obesity. On the other hand, it does not propose a specific weight or fat that defines the disease, just like BMI does (which defines obesity but not its clinical consequences).
Regarding the proposed term ABCD, Montero pointed out that it focuses the diagnosis on the concept that adipose fat and adipocyte function are protagonists of the disease in question, even though there are chronic metabolic diseases like gout, porphyrias, and type 1 diabetes that do not depend on adiposity.
“ABCD also involves some degree of biological injustice, since femorogluteal adiposity (aside from aesthetic problems and excluding possible mechanical effects) is normal and healthy during pregnancy, lactation, growth, or situations of food scarcity risk, among others. Besides, it is an expression that is difficult to interpret for the untrained professional and even more so for communication to the population,” Dr. Montero concluded.
Dr. Cohen, Dr. Figueredo Grijalba, Dr. Jiménez, Dr. Camperos Sánchez, and Dr. Montero declared no relevant financial conflicts of interest.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
ASUNCIÓN, PARAGUAY — The Lancet Diabetes & Endocrinology’s Commission for the Definition and Diagnosis of Clinical Obesity will soon publish criteria for distinguishing between clinical obesity and other preclinical phases. The criteria are intended to limit the negative connotations and misunderstandings associated with the word obesity and to clearly convey the idea that it is a disease and not just a condition that increases the risk for other pathologies.
One of the two Latin American experts on the 60-member commission, Ricardo Cohen, MD, PhD, coordinator of the Obesity and Diabetes Center at the Oswaldo Cruz German Hospital in São Paulo, Brazil, discussed this effort with this news organization.
The proposal being finalized would acknowledge a preclinical stage of obesity characterized by alterations in cells or tissues that lead to changes in organ structure, but not function. This stage can be measured by body mass index (BMI) or waist circumference.
The clinical stage occurs when “obesity already affects [the function of] organs, tissues, and functions like mobility. Here, it is a disease per se. And an active disease requires treatment,” said Dr. Cohen. The health risks associated with excess adiposity have already materialized and can be objectively documented through specific signs and symptoms.
Various experts from Latin America who participated in the XV Congress of the Latin American Obesity Societies (FLASO) and II Paraguayan Obesity Congress expressed to this news organization their reservations about the proposed name change and its practical effects. They highlighted the pros and cons of various terminologies that had been considered in recent years.
“Stigma undoubtedly exists. There’s also no doubt that this stigma and daily pressure on a person’s self-esteem influence behavior and condition a poor future clinical outcome because they promote denial of the disease. Healthcare professionals can make these mistakes. But I’m not sure that changing the name of a known disease will make a difference,” said Rafael Figueredo Grijalba, MD, president of FLASO and director of the Nutrition program at the Faculty of Health Sciences of the Nuestra Señora de la Asunción Catholic University in Paraguay.
Spotlight on Adiposity
An alternative term for obesity proposed in 2016 by what is now the American Association of Clinical Endocrinology and by the American College of Endocrinology is “adiposity-based chronic disease (ABCD).” This designation “is on the right track,” said Violeta Jiménez, MD, internal medicine and endocrinology specialist at the Clinical Hospital of the National University of Asunción and the Comprehensive Diabetes Care Network of the Paraguay Social Security Institute.
The word obese is perceived as an insult, and the health impact of obesity is related to the quantity, distribution, and function of adipose tissue, said Dr. Jiménez. The BMI, the most used parameter in practice to determine overweight and obesity, “does not predict excess adiposity or determine a disease here and now, just as waist circumference does not confirm the condition.”
Will the public be attracted to ABCD? What disease do these initials refer to, asked Dr. Jiménez. “What I like about the term ABCD is that it is not solely based on weight. It brings up the issue that a person who may not have obesity by BMI has adiposity and therefore has a disease brewing inside them.”
“Any obesity denomination is useful as long as the impact of comorbidities is taken into account, as well as the fact that it is not an aesthetic problem and treatment will be escalated aiming to benefit not only weight loss but also comorbidities,” said Paul Camperos Sánchez, MD, internal medicine and endocrinology specialist and head of research at La Trinidad Teaching Medical Center in Caracas, Venezuela, and former president of the Venezuelan Association for the Study of Obesity.
Dr. Camperos Sánchez added that the classification of overweight and obesity into grades on the basis of BMI, which is recognized by the World Health Organization, “is the most known and for me remains the most comfortable. I will accept any other approach, but in my clinical practice, I continue to do it this way.”
Fundamentally, knowledge can reduce social stigma and even prejudice from the medical community itself. “We must be respectful and compassionate and understand well what we are treating and the best way to approach each patient with realistic expectations. Evaluate whether, in addition to medication or intensive lifestyle changes, behavioral interventions or physiotherapy are required. If you don’t manage it well and find it challenging, perhaps that’s why we see so much stigmatization or humiliation of the patient. And that has nothing to do with the name [of the disease],” said Dr. Camperos Sánchez.
‘Biological Injustices’
Julio Montero, MD, nutritionist, president of the Argentine Society of Obesity and Eating Disorders, and former president of FLASO, told this news organization that the topic of nomenclatures “provides a lot of grounds for debate,” but he prefers the term “clinical obesity” because it has a medical meaning, is appropriate for statistical purposes, better conveys the concept of obesity as a disease, and distinguishes patients who have high weight or a spherical figure but may be free of weight-dependent conditions.
“Clinical obesity suggests that it is a person with high weight who has health problems and life expectancy issues related to excessive corpulence (weight-fat). The addition of the adjective clinical suggests that the patient has been evaluated by phenotype, fat distribution, hypertension, blood glucose, triglycerides, apnea, cardiac dilation, and mechanical problems, and based on that analysis, the diagnosis has been made,” said Dr. Montero.
Other positive aspects of the designation include not assuming that comorbidities are a direct consequence of adipose tissue accumulation because “lean mass often increases in patients with obesity, and diet and sedentary lifestyle also have an influence” nor does the term exclude people with central obesity. On the other hand, it does not propose a specific weight or fat that defines the disease, just like BMI does (which defines obesity but not its clinical consequences).
Regarding the proposed term ABCD, Montero pointed out that it focuses the diagnosis on the concept that adipose fat and adipocyte function are protagonists of the disease in question, even though there are chronic metabolic diseases like gout, porphyrias, and type 1 diabetes that do not depend on adiposity.
“ABCD also involves some degree of biological injustice, since femorogluteal adiposity (aside from aesthetic problems and excluding possible mechanical effects) is normal and healthy during pregnancy, lactation, growth, or situations of food scarcity risk, among others. Besides, it is an expression that is difficult to interpret for the untrained professional and even more so for communication to the population,” Dr. Montero concluded.
Dr. Cohen, Dr. Figueredo Grijalba, Dr. Jiménez, Dr. Camperos Sánchez, and Dr. Montero declared no relevant financial conflicts of interest.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
ASUNCIÓN, PARAGUAY — The Lancet Diabetes & Endocrinology’s Commission for the Definition and Diagnosis of Clinical Obesity will soon publish criteria for distinguishing between clinical obesity and other preclinical phases. The criteria are intended to limit the negative connotations and misunderstandings associated with the word obesity and to clearly convey the idea that it is a disease and not just a condition that increases the risk for other pathologies.
One of the two Latin American experts on the 60-member commission, Ricardo Cohen, MD, PhD, coordinator of the Obesity and Diabetes Center at the Oswaldo Cruz German Hospital in São Paulo, Brazil, discussed this effort with this news organization.
The proposal being finalized would acknowledge a preclinical stage of obesity characterized by alterations in cells or tissues that lead to changes in organ structure, but not function. This stage can be measured by body mass index (BMI) or waist circumference.
The clinical stage occurs when “obesity already affects [the function of] organs, tissues, and functions like mobility. Here, it is a disease per se. And an active disease requires treatment,” said Dr. Cohen. The health risks associated with excess adiposity have already materialized and can be objectively documented through specific signs and symptoms.
Various experts from Latin America who participated in the XV Congress of the Latin American Obesity Societies (FLASO) and II Paraguayan Obesity Congress expressed to this news organization their reservations about the proposed name change and its practical effects. They highlighted the pros and cons of various terminologies that had been considered in recent years.
“Stigma undoubtedly exists. There’s also no doubt that this stigma and daily pressure on a person’s self-esteem influence behavior and condition a poor future clinical outcome because they promote denial of the disease. Healthcare professionals can make these mistakes. But I’m not sure that changing the name of a known disease will make a difference,” said Rafael Figueredo Grijalba, MD, president of FLASO and director of the Nutrition program at the Faculty of Health Sciences of the Nuestra Señora de la Asunción Catholic University in Paraguay.
Spotlight on Adiposity
An alternative term for obesity proposed in 2016 by what is now the American Association of Clinical Endocrinology and by the American College of Endocrinology is “adiposity-based chronic disease (ABCD).” This designation “is on the right track,” said Violeta Jiménez, MD, internal medicine and endocrinology specialist at the Clinical Hospital of the National University of Asunción and the Comprehensive Diabetes Care Network of the Paraguay Social Security Institute.
The word obese is perceived as an insult, and the health impact of obesity is related to the quantity, distribution, and function of adipose tissue, said Dr. Jiménez. The BMI, the most used parameter in practice to determine overweight and obesity, “does not predict excess adiposity or determine a disease here and now, just as waist circumference does not confirm the condition.”
Will the public be attracted to ABCD? What disease do these initials refer to, asked Dr. Jiménez. “What I like about the term ABCD is that it is not solely based on weight. It brings up the issue that a person who may not have obesity by BMI has adiposity and therefore has a disease brewing inside them.”
“Any obesity denomination is useful as long as the impact of comorbidities is taken into account, as well as the fact that it is not an aesthetic problem and treatment will be escalated aiming to benefit not only weight loss but also comorbidities,” said Paul Camperos Sánchez, MD, internal medicine and endocrinology specialist and head of research at La Trinidad Teaching Medical Center in Caracas, Venezuela, and former president of the Venezuelan Association for the Study of Obesity.
Dr. Camperos Sánchez added that the classification of overweight and obesity into grades on the basis of BMI, which is recognized by the World Health Organization, “is the most known and for me remains the most comfortable. I will accept any other approach, but in my clinical practice, I continue to do it this way.”
Fundamentally, knowledge can reduce social stigma and even prejudice from the medical community itself. “We must be respectful and compassionate and understand well what we are treating and the best way to approach each patient with realistic expectations. Evaluate whether, in addition to medication or intensive lifestyle changes, behavioral interventions or physiotherapy are required. If you don’t manage it well and find it challenging, perhaps that’s why we see so much stigmatization or humiliation of the patient. And that has nothing to do with the name [of the disease],” said Dr. Camperos Sánchez.
‘Biological Injustices’
Julio Montero, MD, nutritionist, president of the Argentine Society of Obesity and Eating Disorders, and former president of FLASO, told this news organization that the topic of nomenclatures “provides a lot of grounds for debate,” but he prefers the term “clinical obesity” because it has a medical meaning, is appropriate for statistical purposes, better conveys the concept of obesity as a disease, and distinguishes patients who have high weight or a spherical figure but may be free of weight-dependent conditions.
“Clinical obesity suggests that it is a person with high weight who has health problems and life expectancy issues related to excessive corpulence (weight-fat). The addition of the adjective clinical suggests that the patient has been evaluated by phenotype, fat distribution, hypertension, blood glucose, triglycerides, apnea, cardiac dilation, and mechanical problems, and based on that analysis, the diagnosis has been made,” said Dr. Montero.
Other positive aspects of the designation include not assuming that comorbidities are a direct consequence of adipose tissue accumulation because “lean mass often increases in patients with obesity, and diet and sedentary lifestyle also have an influence” nor does the term exclude people with central obesity. On the other hand, it does not propose a specific weight or fat that defines the disease, just like BMI does (which defines obesity but not its clinical consequences).
Regarding the proposed term ABCD, Montero pointed out that it focuses the diagnosis on the concept that adipose fat and adipocyte function are protagonists of the disease in question, even though there are chronic metabolic diseases like gout, porphyrias, and type 1 diabetes that do not depend on adiposity.
“ABCD also involves some degree of biological injustice, since femorogluteal adiposity (aside from aesthetic problems and excluding possible mechanical effects) is normal and healthy during pregnancy, lactation, growth, or situations of food scarcity risk, among others. Besides, it is an expression that is difficult to interpret for the untrained professional and even more so for communication to the population,” Dr. Montero concluded.
Dr. Cohen, Dr. Figueredo Grijalba, Dr. Jiménez, Dr. Camperos Sánchez, and Dr. Montero declared no relevant financial conflicts of interest.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Gene Therapy for Dystrophic EB: Extension Study Results Reported
and no new safety signals were identified.
The results were presented by Amy S. Paller, MD, during a late-breaking session at the annual meeting of the American Academy of Dermatology.
In May 2023, beremagene geperpavec, marketed as Vyjuvek (formerly known as B-VEC) was approved by the US Food and Drug Administration (FDA) for the treatment of wounds in patients 6 months of age and older with DEB, a rare genetic blistering disorder caused by COL7A1 gene variants. The therapy uses a nonreplicating herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure. It is designed to be used repetitively, to heal a single wound, or on more than one wound.
In the pivotal study of patients with DEB, the gene therapy, delivered in a topical gel, was administered once a week for 6 months to one wound and placebo was applied to another wound for each participant. The proportion of wounds treated with beremagene geperpavec that healed was significantly higher than among placebo-treated wounds at 3 and 6 months (68% vs. 23% at 3 months, P = .003) and 65% vs. 26% at 6 months (P = .012), with no serious adverse events related to treatment.
The prospective, open label, uncontrolled extension study included 24 patients from the phase 3 study and 23 treatment-naive patients from five US sites. Their mean age was 16 years (range, 6 months to 46 years).
Of the 47 patients, 29 (62%) were on treatment for more than 1 year (the longest was about 2 years), and the mean duration of treatment was 475 days; 5 patients withdrew from the study for reasons not related to treatment.
Their types of adverse events (AEs) were similar to those seen in the phase 3 study and were consistent with what would be expected in patients with DEB, said Dr. Paller, professor and chair of dermatology, Northwestern University, Chicago. One patient experienced two wound hemorrhages that were possibly related to treatment, but there were no treatment-related AEs, no deaths or treatment discontinuations because of an AE, and no serious AEs thought to be related to treatment.
Wounds that were evaluated in the phase 3 study showed “a high durability of closure with continued treatment,” according to Dr. Paller. There were enough data on 19 of the 24 patients who had been in the phase 3 trial to evaluate wound closure, defined as “complete wound closure based on comparison to the exact wound area selected at baseline” at the beginning of the phase 3 study.
In the extension study, wound closure rates were almost 90% at baseline, 84.2% at 3 months, 61.1% at 6 months, 82.4% at 9 months, and 62.5% at 12 months, which was comparable to the rates observed in the third (86.4%) and sixth (73.7%) months of the phase 3 study, Dr. Paller said.
Patient-reported outcomes indicated that quality of life and satisfaction with treatment were preserved with continued treatment.The extension study was terminated in July 2023, after FDA approval, when patients could be transitioned to the commercially available treatment.Dr. Paller disclosed being an investigator (funds to institution) for multiple pharmaceutical companies, including the manufacturer of beremagene geperpavec, Krystal Biotech, which funded the study.
and no new safety signals were identified.
The results were presented by Amy S. Paller, MD, during a late-breaking session at the annual meeting of the American Academy of Dermatology.
In May 2023, beremagene geperpavec, marketed as Vyjuvek (formerly known as B-VEC) was approved by the US Food and Drug Administration (FDA) for the treatment of wounds in patients 6 months of age and older with DEB, a rare genetic blistering disorder caused by COL7A1 gene variants. The therapy uses a nonreplicating herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure. It is designed to be used repetitively, to heal a single wound, or on more than one wound.
In the pivotal study of patients with DEB, the gene therapy, delivered in a topical gel, was administered once a week for 6 months to one wound and placebo was applied to another wound for each participant. The proportion of wounds treated with beremagene geperpavec that healed was significantly higher than among placebo-treated wounds at 3 and 6 months (68% vs. 23% at 3 months, P = .003) and 65% vs. 26% at 6 months (P = .012), with no serious adverse events related to treatment.
The prospective, open label, uncontrolled extension study included 24 patients from the phase 3 study and 23 treatment-naive patients from five US sites. Their mean age was 16 years (range, 6 months to 46 years).
Of the 47 patients, 29 (62%) were on treatment for more than 1 year (the longest was about 2 years), and the mean duration of treatment was 475 days; 5 patients withdrew from the study for reasons not related to treatment.
Their types of adverse events (AEs) were similar to those seen in the phase 3 study and were consistent with what would be expected in patients with DEB, said Dr. Paller, professor and chair of dermatology, Northwestern University, Chicago. One patient experienced two wound hemorrhages that were possibly related to treatment, but there were no treatment-related AEs, no deaths or treatment discontinuations because of an AE, and no serious AEs thought to be related to treatment.
Wounds that were evaluated in the phase 3 study showed “a high durability of closure with continued treatment,” according to Dr. Paller. There were enough data on 19 of the 24 patients who had been in the phase 3 trial to evaluate wound closure, defined as “complete wound closure based on comparison to the exact wound area selected at baseline” at the beginning of the phase 3 study.
In the extension study, wound closure rates were almost 90% at baseline, 84.2% at 3 months, 61.1% at 6 months, 82.4% at 9 months, and 62.5% at 12 months, which was comparable to the rates observed in the third (86.4%) and sixth (73.7%) months of the phase 3 study, Dr. Paller said.
Patient-reported outcomes indicated that quality of life and satisfaction with treatment were preserved with continued treatment.The extension study was terminated in July 2023, after FDA approval, when patients could be transitioned to the commercially available treatment.Dr. Paller disclosed being an investigator (funds to institution) for multiple pharmaceutical companies, including the manufacturer of beremagene geperpavec, Krystal Biotech, which funded the study.
and no new safety signals were identified.
The results were presented by Amy S. Paller, MD, during a late-breaking session at the annual meeting of the American Academy of Dermatology.
In May 2023, beremagene geperpavec, marketed as Vyjuvek (formerly known as B-VEC) was approved by the US Food and Drug Administration (FDA) for the treatment of wounds in patients 6 months of age and older with DEB, a rare genetic blistering disorder caused by COL7A1 gene variants. The therapy uses a nonreplicating herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure. It is designed to be used repetitively, to heal a single wound, or on more than one wound.
In the pivotal study of patients with DEB, the gene therapy, delivered in a topical gel, was administered once a week for 6 months to one wound and placebo was applied to another wound for each participant. The proportion of wounds treated with beremagene geperpavec that healed was significantly higher than among placebo-treated wounds at 3 and 6 months (68% vs. 23% at 3 months, P = .003) and 65% vs. 26% at 6 months (P = .012), with no serious adverse events related to treatment.
The prospective, open label, uncontrolled extension study included 24 patients from the phase 3 study and 23 treatment-naive patients from five US sites. Their mean age was 16 years (range, 6 months to 46 years).
Of the 47 patients, 29 (62%) were on treatment for more than 1 year (the longest was about 2 years), and the mean duration of treatment was 475 days; 5 patients withdrew from the study for reasons not related to treatment.
Their types of adverse events (AEs) were similar to those seen in the phase 3 study and were consistent with what would be expected in patients with DEB, said Dr. Paller, professor and chair of dermatology, Northwestern University, Chicago. One patient experienced two wound hemorrhages that were possibly related to treatment, but there were no treatment-related AEs, no deaths or treatment discontinuations because of an AE, and no serious AEs thought to be related to treatment.
Wounds that were evaluated in the phase 3 study showed “a high durability of closure with continued treatment,” according to Dr. Paller. There were enough data on 19 of the 24 patients who had been in the phase 3 trial to evaluate wound closure, defined as “complete wound closure based on comparison to the exact wound area selected at baseline” at the beginning of the phase 3 study.
In the extension study, wound closure rates were almost 90% at baseline, 84.2% at 3 months, 61.1% at 6 months, 82.4% at 9 months, and 62.5% at 12 months, which was comparable to the rates observed in the third (86.4%) and sixth (73.7%) months of the phase 3 study, Dr. Paller said.
Patient-reported outcomes indicated that quality of life and satisfaction with treatment were preserved with continued treatment.The extension study was terminated in July 2023, after FDA approval, when patients could be transitioned to the commercially available treatment.Dr. Paller disclosed being an investigator (funds to institution) for multiple pharmaceutical companies, including the manufacturer of beremagene geperpavec, Krystal Biotech, which funded the study.
FROM AAD 2024
Positive Phase 2 Results Reported for TYK2 Inhibitor for Patients With Moderate to Severe Psoriasis
, in a phase 2 study presented during a late breaker presentation at the annual meeting of the American Academy of Dermatology.
ESK-001 is a highly-selective TYK2 inhibitor that “reduces signaling through several cytokine receptors including receptors for interleukin (IL)-12, IL-23, and interferon (IFN)-alpha,” according to Alumis, the company developing ESK-001.
The STRIDE trial enrolled 228 adults (mean age, 48 years) with a mean PASI score of 17.8 at baseline, randomized to one of five doses of ESK-001, or placebo. Nearly 70% of those enrolled were men, 82.5% were White, nearly 6% were Asian, and about 4% were Black.
The proportion of patients achieving at least a PASI-75 at 12 weeks, the primary endpoint, ranged from 19.4% among those on the lower dose (10 mg a day) to 56.4% among those on 20 mg twice a day and those on 40 mg once a day, and 64.1% among those on 40 mg twice a day, the highest dose evaluated, compared with 0% of those on placebo.
In addition, 38.5% and 15.4% of those on the highest dose achieved a PASI 90 and PASI 100, respectively, at 12 weeks, according to results presented at the meeting by Kim A. Papp, MD.
Improvements in static Physician’s Global Assessment (sPGA) scores, a secondary endpoint, at 12 weeks were also observed; including 59% of those on the highest dose (40 mg twice a day) achieving an sPGA of 0/1 at 12 weeks, according to Dr. Papp, president of Probity Medical Research, in Waterloo, Ontario, and a study investigator.
Treatment was “generally safe and well tolerated” at all doses, and most treatment-emergent adverse events were “mild to moderate” and self-limited, he said.
The most frequent treatment emergent adverse events included headache and nasopharyngitis (also reported in the placebo group), and upper respiratory tract infections. No cases of treatment-related serious adverse events were reported, and there were no cases of MACE (major adverse cardiovascular events), serious infections, thromboses related to treatment, or lab or ECG findings of concern.
In an ongoing open label extension study, 165 patients on 40 mg once a day and those on 40 mg twice a day are continuing to be evaluated, and at week 16, have continued to show significant efficacy, with a favorable risk-benefit profile to date, according to Dr. Papp.
ESK-001 is also being evaluated in a phase 2b study of patients with systemic lupus erythematosus, and a phase 2 proof-of-concept study of patients with non-infectious uveitis, according to Alumis.
In addition to being an investigator for Alumis, Dr. Papp disclosed serving as an adviser, consultant, investigator, and/or speaker for multiple other pharmaceutical companies.
, in a phase 2 study presented during a late breaker presentation at the annual meeting of the American Academy of Dermatology.
ESK-001 is a highly-selective TYK2 inhibitor that “reduces signaling through several cytokine receptors including receptors for interleukin (IL)-12, IL-23, and interferon (IFN)-alpha,” according to Alumis, the company developing ESK-001.
The STRIDE trial enrolled 228 adults (mean age, 48 years) with a mean PASI score of 17.8 at baseline, randomized to one of five doses of ESK-001, or placebo. Nearly 70% of those enrolled were men, 82.5% were White, nearly 6% were Asian, and about 4% were Black.
The proportion of patients achieving at least a PASI-75 at 12 weeks, the primary endpoint, ranged from 19.4% among those on the lower dose (10 mg a day) to 56.4% among those on 20 mg twice a day and those on 40 mg once a day, and 64.1% among those on 40 mg twice a day, the highest dose evaluated, compared with 0% of those on placebo.
In addition, 38.5% and 15.4% of those on the highest dose achieved a PASI 90 and PASI 100, respectively, at 12 weeks, according to results presented at the meeting by Kim A. Papp, MD.
Improvements in static Physician’s Global Assessment (sPGA) scores, a secondary endpoint, at 12 weeks were also observed; including 59% of those on the highest dose (40 mg twice a day) achieving an sPGA of 0/1 at 12 weeks, according to Dr. Papp, president of Probity Medical Research, in Waterloo, Ontario, and a study investigator.
Treatment was “generally safe and well tolerated” at all doses, and most treatment-emergent adverse events were “mild to moderate” and self-limited, he said.
The most frequent treatment emergent adverse events included headache and nasopharyngitis (also reported in the placebo group), and upper respiratory tract infections. No cases of treatment-related serious adverse events were reported, and there were no cases of MACE (major adverse cardiovascular events), serious infections, thromboses related to treatment, or lab or ECG findings of concern.
In an ongoing open label extension study, 165 patients on 40 mg once a day and those on 40 mg twice a day are continuing to be evaluated, and at week 16, have continued to show significant efficacy, with a favorable risk-benefit profile to date, according to Dr. Papp.
ESK-001 is also being evaluated in a phase 2b study of patients with systemic lupus erythematosus, and a phase 2 proof-of-concept study of patients with non-infectious uveitis, according to Alumis.
In addition to being an investigator for Alumis, Dr. Papp disclosed serving as an adviser, consultant, investigator, and/or speaker for multiple other pharmaceutical companies.
, in a phase 2 study presented during a late breaker presentation at the annual meeting of the American Academy of Dermatology.
ESK-001 is a highly-selective TYK2 inhibitor that “reduces signaling through several cytokine receptors including receptors for interleukin (IL)-12, IL-23, and interferon (IFN)-alpha,” according to Alumis, the company developing ESK-001.
The STRIDE trial enrolled 228 adults (mean age, 48 years) with a mean PASI score of 17.8 at baseline, randomized to one of five doses of ESK-001, or placebo. Nearly 70% of those enrolled were men, 82.5% were White, nearly 6% were Asian, and about 4% were Black.
The proportion of patients achieving at least a PASI-75 at 12 weeks, the primary endpoint, ranged from 19.4% among those on the lower dose (10 mg a day) to 56.4% among those on 20 mg twice a day and those on 40 mg once a day, and 64.1% among those on 40 mg twice a day, the highest dose evaluated, compared with 0% of those on placebo.
In addition, 38.5% and 15.4% of those on the highest dose achieved a PASI 90 and PASI 100, respectively, at 12 weeks, according to results presented at the meeting by Kim A. Papp, MD.
Improvements in static Physician’s Global Assessment (sPGA) scores, a secondary endpoint, at 12 weeks were also observed; including 59% of those on the highest dose (40 mg twice a day) achieving an sPGA of 0/1 at 12 weeks, according to Dr. Papp, president of Probity Medical Research, in Waterloo, Ontario, and a study investigator.
Treatment was “generally safe and well tolerated” at all doses, and most treatment-emergent adverse events were “mild to moderate” and self-limited, he said.
The most frequent treatment emergent adverse events included headache and nasopharyngitis (also reported in the placebo group), and upper respiratory tract infections. No cases of treatment-related serious adverse events were reported, and there were no cases of MACE (major adverse cardiovascular events), serious infections, thromboses related to treatment, or lab or ECG findings of concern.
In an ongoing open label extension study, 165 patients on 40 mg once a day and those on 40 mg twice a day are continuing to be evaluated, and at week 16, have continued to show significant efficacy, with a favorable risk-benefit profile to date, according to Dr. Papp.
ESK-001 is also being evaluated in a phase 2b study of patients with systemic lupus erythematosus, and a phase 2 proof-of-concept study of patients with non-infectious uveitis, according to Alumis.
In addition to being an investigator for Alumis, Dr. Papp disclosed serving as an adviser, consultant, investigator, and/or speaker for multiple other pharmaceutical companies.
FROM AAD 2024
Three Conditions for Which Cannabis Appears to Help
The utility of cannabinoids to treat most medical conditions remains uncertain at best, but for at least three indications the data lean in favor of effectiveness, Ellie Grossman, MD, MPH, told attendees recently at the 2024 American College of Physicians Internal Medicine meeting.
Those are neuropathic pain, chemotherapy-induced nausea or vomiting, and spasticity in people with multiple sclerosis, said Dr. Grossman, an instructor at Harvard Medical School in Boston and medical director for primary care/behavioral health integration at Cambridge Health Alliance in Somerville, Massachusetts.
Dearth of Research Persists
Research is sorely lacking and of low quality in the field for many reasons, Dr. Grossman said. Most of the products tested come from outside the United States and often are synthetic and taken orally — which does not match the real-world use when patients go to dispensaries for cannabis derived directly from plants (or the plant product itself). And studies often rely on self-report.
Chronic pain is by far the top reason patients say they use medical cannabis, Dr. Grossman said. A Cochrane review of 16 studies found only that the potential benefits of cannabis may outweigh the potential harms for chronic neuropathic pain.
No Evidence in OUD
Dr. Grossman said she is frequently asked if cannabis can help people quit taking opioids. The answer seems to be no. A study published earlier this year in states with legalized medical or recreational cannabis found no difference between rates of opioid overdose compared with states with no such laws. “It seems like it doesn’t do anything to help us with our opioid problem,” she said.
Nor does high-quality evidence exist showing use of cannabis can improve sleep, she said. A 2022 systematic review found fewer than half of studies showed the substance useful for sleep outcomes. “Where studies were positives, it was in people who had chronic pain,” Dr. Grossman noted. Research indicates cannabis may have substantial benefit for chronic pain compared with placebo.
Potential Harms
If the medical benefits of cannabis are murky, the evidence for its potential harms, at least in the short term, are clearer, according to Dr. Grossman. A simplified guideline for prescribing medical cannabinoids in primary care includes sedation, feeling high, dizziness, speech disorders, muscle twitching, hypotension, and several other conditions among the potential hazards of the drug.
But the potential for long-term harm is uncertain. “All the evidence comes from people who have been using it for recreational reasons,” where there may be co-use of tobacco, self-reported outcomes, and recall bias, she said. The characteristics of people using cannabis recreationally often differ from those using it medicinally.
Use With Other Controlled Substances
Dr. Grossman said clinicians should consider whether the co-use of cannabis and other controlled substances, such as benzodiazepines, opioids, or Adderall, raises the potential risks associated with those drugs. “Ultimately it comes down to talking to your patients,” she said. If a toxicity screen shows the presence of controlled substances, ask about their experience with the drugs they are using and let them know your main concern is their safety.
Dr. Grossman reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
The utility of cannabinoids to treat most medical conditions remains uncertain at best, but for at least three indications the data lean in favor of effectiveness, Ellie Grossman, MD, MPH, told attendees recently at the 2024 American College of Physicians Internal Medicine meeting.
Those are neuropathic pain, chemotherapy-induced nausea or vomiting, and spasticity in people with multiple sclerosis, said Dr. Grossman, an instructor at Harvard Medical School in Boston and medical director for primary care/behavioral health integration at Cambridge Health Alliance in Somerville, Massachusetts.
Dearth of Research Persists
Research is sorely lacking and of low quality in the field for many reasons, Dr. Grossman said. Most of the products tested come from outside the United States and often are synthetic and taken orally — which does not match the real-world use when patients go to dispensaries for cannabis derived directly from plants (or the plant product itself). And studies often rely on self-report.
Chronic pain is by far the top reason patients say they use medical cannabis, Dr. Grossman said. A Cochrane review of 16 studies found only that the potential benefits of cannabis may outweigh the potential harms for chronic neuropathic pain.
No Evidence in OUD
Dr. Grossman said she is frequently asked if cannabis can help people quit taking opioids. The answer seems to be no. A study published earlier this year in states with legalized medical or recreational cannabis found no difference between rates of opioid overdose compared with states with no such laws. “It seems like it doesn’t do anything to help us with our opioid problem,” she said.
Nor does high-quality evidence exist showing use of cannabis can improve sleep, she said. A 2022 systematic review found fewer than half of studies showed the substance useful for sleep outcomes. “Where studies were positives, it was in people who had chronic pain,” Dr. Grossman noted. Research indicates cannabis may have substantial benefit for chronic pain compared with placebo.
Potential Harms
If the medical benefits of cannabis are murky, the evidence for its potential harms, at least in the short term, are clearer, according to Dr. Grossman. A simplified guideline for prescribing medical cannabinoids in primary care includes sedation, feeling high, dizziness, speech disorders, muscle twitching, hypotension, and several other conditions among the potential hazards of the drug.
But the potential for long-term harm is uncertain. “All the evidence comes from people who have been using it for recreational reasons,” where there may be co-use of tobacco, self-reported outcomes, and recall bias, she said. The characteristics of people using cannabis recreationally often differ from those using it medicinally.
Use With Other Controlled Substances
Dr. Grossman said clinicians should consider whether the co-use of cannabis and other controlled substances, such as benzodiazepines, opioids, or Adderall, raises the potential risks associated with those drugs. “Ultimately it comes down to talking to your patients,” she said. If a toxicity screen shows the presence of controlled substances, ask about their experience with the drugs they are using and let them know your main concern is their safety.
Dr. Grossman reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
The utility of cannabinoids to treat most medical conditions remains uncertain at best, but for at least three indications the data lean in favor of effectiveness, Ellie Grossman, MD, MPH, told attendees recently at the 2024 American College of Physicians Internal Medicine meeting.
Those are neuropathic pain, chemotherapy-induced nausea or vomiting, and spasticity in people with multiple sclerosis, said Dr. Grossman, an instructor at Harvard Medical School in Boston and medical director for primary care/behavioral health integration at Cambridge Health Alliance in Somerville, Massachusetts.
Dearth of Research Persists
Research is sorely lacking and of low quality in the field for many reasons, Dr. Grossman said. Most of the products tested come from outside the United States and often are synthetic and taken orally — which does not match the real-world use when patients go to dispensaries for cannabis derived directly from plants (or the plant product itself). And studies often rely on self-report.
Chronic pain is by far the top reason patients say they use medical cannabis, Dr. Grossman said. A Cochrane review of 16 studies found only that the potential benefits of cannabis may outweigh the potential harms for chronic neuropathic pain.
No Evidence in OUD
Dr. Grossman said she is frequently asked if cannabis can help people quit taking opioids. The answer seems to be no. A study published earlier this year in states with legalized medical or recreational cannabis found no difference between rates of opioid overdose compared with states with no such laws. “It seems like it doesn’t do anything to help us with our opioid problem,” she said.
Nor does high-quality evidence exist showing use of cannabis can improve sleep, she said. A 2022 systematic review found fewer than half of studies showed the substance useful for sleep outcomes. “Where studies were positives, it was in people who had chronic pain,” Dr. Grossman noted. Research indicates cannabis may have substantial benefit for chronic pain compared with placebo.
Potential Harms
If the medical benefits of cannabis are murky, the evidence for its potential harms, at least in the short term, are clearer, according to Dr. Grossman. A simplified guideline for prescribing medical cannabinoids in primary care includes sedation, feeling high, dizziness, speech disorders, muscle twitching, hypotension, and several other conditions among the potential hazards of the drug.
But the potential for long-term harm is uncertain. “All the evidence comes from people who have been using it for recreational reasons,” where there may be co-use of tobacco, self-reported outcomes, and recall bias, she said. The characteristics of people using cannabis recreationally often differ from those using it medicinally.
Use With Other Controlled Substances
Dr. Grossman said clinicians should consider whether the co-use of cannabis and other controlled substances, such as benzodiazepines, opioids, or Adderall, raises the potential risks associated with those drugs. “Ultimately it comes down to talking to your patients,” she said. If a toxicity screen shows the presence of controlled substances, ask about their experience with the drugs they are using and let them know your main concern is their safety.
Dr. Grossman reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.