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Exercise can boost cognition after stroke
HOUSTON – Exercise seems to improve some of the cognitive difficulties that can manifest in stroke survivors, even if patients don’t hit the gym for a couple of years after the incident.
A meta-analysis of 14 randomized, controlled studies has determined that the combination of aerobic and weight-bearing exercises is most effective at boosting brain function. The studies showed a moderate, but consistent, effect of exercise in both the acute and chronic phase, Lauren Oberlin said at the International Stroke Conference sponsored by the American Heart Association.
“This is an important message for stroke survivors who have experienced cognitive deficits for a long time: These may not be permanent, and they can be modified with physical activity,” she said.
Long-term cognitive impairment is a very common problem after stroke, she said, occurring to some degree in up to 85% of survivors. The most commonly affected domains are executive function, attention, processing speed, and memory.
“These deficits can also be highly persistent, and remain in the years after a stroke,” Ms. Oberlin said. “And they represent a major health and economic burden. Stroke survivors with cognitive deficits are at an increased risk for long-term disability, functional decline, dependent living, hospitalization, and even mortality. Despite all this, there is an absence of effective treatments. There are no effective pharmaceutical treatments and cognitive rehabilitation training has not been widely successful.”
Exercise has not been as well-studied in stroke as it has in other neurological disorders, including Parkinson’s disease, multiple sclerosis, and more recently, Alzheimer’s disease. Physical activity has also been shown to help maintain and boost cognitive function and memory in healthy aging populations.
Ms. Oberlin and her colleagues conducted a meta-analysis of 14 randomized, controlled studies conducted during 2001-2016. The studies enrolled a total of 736 subjects. All of them randomized subjects to 3-6 months of an active exercise arm or a control arm that did not involve physical training.
The researchers assessed effect sizes by Hedges’ g, calculated separately for intervention and control conditions within each trial. The results were interpreted as follows:
• Small effect = 0.2
• Moderate effect = 0.5
• Large effect = 0.8
Only four of the studies demonstrated a statistically significant benefit between the active and control arms. Seven trended strongly toward the positive, but had wide confidence intervals that crossed the null. Three studies showed no significant benefit. The overall effects size was 0.56 (moderate).
Ms. Oberlin and her colleagues then parsed the data to examine the effect of when the program was initiated after the stroke, the program’s duration, and the type of exercise it studied.
Length of the intervention (less than 3 months and more than 3 months) was not significantly related to cognitive outcome. However, the combination of aerobic and strength training exerted a significantly greater effect size (0.45) than did aerobic training or weight training alone (0.2 and 0.34, respectively). Programs that started more than 3 months after the stroke were also more effective than were those started earlier in recovery (0.45 vs. 0.16).
Finally, in a subset of five studies, she evaluated whether particular cognitive domains benefited most from physical activity. Attention and processing speed improved the most (0.4). Changes in memory and executive function were not significant.
“I will say this was only five studies, so we may have been underpowered to see any effects on these other domains,” Ms. Oberlin said.
The mechanistic link between physical activity and improved cognition has not been fully elucidated in humans, she said. However, animal studies have identified a number of associations. “In rodent studies, we see that exercise improves blood flow to the brain, and promotes both neurogenesis and synaptogenesis. This has been confirmed in imaging studies of healthy older adults. Exercise was associated with increased structural connectivity, changes in functional connectivity, and increases in brain volume in some regions, including the hippocampus and prefrontal cortex.”
She also acknowledged that preaching exercise in clinic is much easier than actually getting patients into the gym. “Stroke survivors often have mobility limitations, and these studies were primarily conducted in subjects who did not have those issues and who could work out on a treadmill or exercise bike. How we can adapt these programs to patients with limited mobility is certainly a challenge.”
Ms. Oberlin had no financial disclosures.
[email protected]
On Twitter @alz_gal
HOUSTON – Exercise seems to improve some of the cognitive difficulties that can manifest in stroke survivors, even if patients don’t hit the gym for a couple of years after the incident.
A meta-analysis of 14 randomized, controlled studies has determined that the combination of aerobic and weight-bearing exercises is most effective at boosting brain function. The studies showed a moderate, but consistent, effect of exercise in both the acute and chronic phase, Lauren Oberlin said at the International Stroke Conference sponsored by the American Heart Association.
“This is an important message for stroke survivors who have experienced cognitive deficits for a long time: These may not be permanent, and they can be modified with physical activity,” she said.
Long-term cognitive impairment is a very common problem after stroke, she said, occurring to some degree in up to 85% of survivors. The most commonly affected domains are executive function, attention, processing speed, and memory.
“These deficits can also be highly persistent, and remain in the years after a stroke,” Ms. Oberlin said. “And they represent a major health and economic burden. Stroke survivors with cognitive deficits are at an increased risk for long-term disability, functional decline, dependent living, hospitalization, and even mortality. Despite all this, there is an absence of effective treatments. There are no effective pharmaceutical treatments and cognitive rehabilitation training has not been widely successful.”
Exercise has not been as well-studied in stroke as it has in other neurological disorders, including Parkinson’s disease, multiple sclerosis, and more recently, Alzheimer’s disease. Physical activity has also been shown to help maintain and boost cognitive function and memory in healthy aging populations.
Ms. Oberlin and her colleagues conducted a meta-analysis of 14 randomized, controlled studies conducted during 2001-2016. The studies enrolled a total of 736 subjects. All of them randomized subjects to 3-6 months of an active exercise arm or a control arm that did not involve physical training.
The researchers assessed effect sizes by Hedges’ g, calculated separately for intervention and control conditions within each trial. The results were interpreted as follows:
• Small effect = 0.2
• Moderate effect = 0.5
• Large effect = 0.8
Only four of the studies demonstrated a statistically significant benefit between the active and control arms. Seven trended strongly toward the positive, but had wide confidence intervals that crossed the null. Three studies showed no significant benefit. The overall effects size was 0.56 (moderate).
Ms. Oberlin and her colleagues then parsed the data to examine the effect of when the program was initiated after the stroke, the program’s duration, and the type of exercise it studied.
Length of the intervention (less than 3 months and more than 3 months) was not significantly related to cognitive outcome. However, the combination of aerobic and strength training exerted a significantly greater effect size (0.45) than did aerobic training or weight training alone (0.2 and 0.34, respectively). Programs that started more than 3 months after the stroke were also more effective than were those started earlier in recovery (0.45 vs. 0.16).
Finally, in a subset of five studies, she evaluated whether particular cognitive domains benefited most from physical activity. Attention and processing speed improved the most (0.4). Changes in memory and executive function were not significant.
“I will say this was only five studies, so we may have been underpowered to see any effects on these other domains,” Ms. Oberlin said.
The mechanistic link between physical activity and improved cognition has not been fully elucidated in humans, she said. However, animal studies have identified a number of associations. “In rodent studies, we see that exercise improves blood flow to the brain, and promotes both neurogenesis and synaptogenesis. This has been confirmed in imaging studies of healthy older adults. Exercise was associated with increased structural connectivity, changes in functional connectivity, and increases in brain volume in some regions, including the hippocampus and prefrontal cortex.”
She also acknowledged that preaching exercise in clinic is much easier than actually getting patients into the gym. “Stroke survivors often have mobility limitations, and these studies were primarily conducted in subjects who did not have those issues and who could work out on a treadmill or exercise bike. How we can adapt these programs to patients with limited mobility is certainly a challenge.”
Ms. Oberlin had no financial disclosures.
[email protected]
On Twitter @alz_gal
HOUSTON – Exercise seems to improve some of the cognitive difficulties that can manifest in stroke survivors, even if patients don’t hit the gym for a couple of years after the incident.
A meta-analysis of 14 randomized, controlled studies has determined that the combination of aerobic and weight-bearing exercises is most effective at boosting brain function. The studies showed a moderate, but consistent, effect of exercise in both the acute and chronic phase, Lauren Oberlin said at the International Stroke Conference sponsored by the American Heart Association.
“This is an important message for stroke survivors who have experienced cognitive deficits for a long time: These may not be permanent, and they can be modified with physical activity,” she said.
Long-term cognitive impairment is a very common problem after stroke, she said, occurring to some degree in up to 85% of survivors. The most commonly affected domains are executive function, attention, processing speed, and memory.
“These deficits can also be highly persistent, and remain in the years after a stroke,” Ms. Oberlin said. “And they represent a major health and economic burden. Stroke survivors with cognitive deficits are at an increased risk for long-term disability, functional decline, dependent living, hospitalization, and even mortality. Despite all this, there is an absence of effective treatments. There are no effective pharmaceutical treatments and cognitive rehabilitation training has not been widely successful.”
Exercise has not been as well-studied in stroke as it has in other neurological disorders, including Parkinson’s disease, multiple sclerosis, and more recently, Alzheimer’s disease. Physical activity has also been shown to help maintain and boost cognitive function and memory in healthy aging populations.
Ms. Oberlin and her colleagues conducted a meta-analysis of 14 randomized, controlled studies conducted during 2001-2016. The studies enrolled a total of 736 subjects. All of them randomized subjects to 3-6 months of an active exercise arm or a control arm that did not involve physical training.
The researchers assessed effect sizes by Hedges’ g, calculated separately for intervention and control conditions within each trial. The results were interpreted as follows:
• Small effect = 0.2
• Moderate effect = 0.5
• Large effect = 0.8
Only four of the studies demonstrated a statistically significant benefit between the active and control arms. Seven trended strongly toward the positive, but had wide confidence intervals that crossed the null. Three studies showed no significant benefit. The overall effects size was 0.56 (moderate).
Ms. Oberlin and her colleagues then parsed the data to examine the effect of when the program was initiated after the stroke, the program’s duration, and the type of exercise it studied.
Length of the intervention (less than 3 months and more than 3 months) was not significantly related to cognitive outcome. However, the combination of aerobic and strength training exerted a significantly greater effect size (0.45) than did aerobic training or weight training alone (0.2 and 0.34, respectively). Programs that started more than 3 months after the stroke were also more effective than were those started earlier in recovery (0.45 vs. 0.16).
Finally, in a subset of five studies, she evaluated whether particular cognitive domains benefited most from physical activity. Attention and processing speed improved the most (0.4). Changes in memory and executive function were not significant.
“I will say this was only five studies, so we may have been underpowered to see any effects on these other domains,” Ms. Oberlin said.
The mechanistic link between physical activity and improved cognition has not been fully elucidated in humans, she said. However, animal studies have identified a number of associations. “In rodent studies, we see that exercise improves blood flow to the brain, and promotes both neurogenesis and synaptogenesis. This has been confirmed in imaging studies of healthy older adults. Exercise was associated with increased structural connectivity, changes in functional connectivity, and increases in brain volume in some regions, including the hippocampus and prefrontal cortex.”
She also acknowledged that preaching exercise in clinic is much easier than actually getting patients into the gym. “Stroke survivors often have mobility limitations, and these studies were primarily conducted in subjects who did not have those issues and who could work out on a treadmill or exercise bike. How we can adapt these programs to patients with limited mobility is certainly a challenge.”
Ms. Oberlin had no financial disclosures.
[email protected]
On Twitter @alz_gal
AT THE INTERNATIONAL STROKE CONFERENCE
Key clinical point:
Major finding: Overall, exercise after stroke exerted a moderate effect size of 0.56 on cognition.
Data source: The meta-analysis comprised 14 studies and 736 subjects.
Disclosures: Ms. Oberlin had no financial disclosures.
Inactivated hepatitis A vaccine shows promise in 5-year study
, a study has shown.
In October 2008, a team of investigators in China led by Zhilun Zhang of the Tianjin Center for Disease Control and Prevention, randomly assigned 332 children aged 18-60 months with prevaccination anti-HAV antibody titers of less than 20 mIU/mL to receive either one dose of inactivated hepatitis A vaccine or one dose of live, attenuated hepatitis A vaccine. Both groups were followed through December 2013, with assessments of anti-HAV antibody concentrations at years 1, 2, and 5 post vaccination. In all, 182 successfully completed the study, meeting all requirements, including providing serum samples at each time point.
Titer levels were 76.3% mIU/mL and 66.8mIU/mL for the inactivated and live vaccines at 5 years, respectively. No clinical hepatitis A case was reported.
The study appears online in Human Vaccines & Immunotherapeutics (doi: 10.1080/21645515.2016.1278329).
[email protected]
On Twitter @whitneymcknight
, a study has shown.
In October 2008, a team of investigators in China led by Zhilun Zhang of the Tianjin Center for Disease Control and Prevention, randomly assigned 332 children aged 18-60 months with prevaccination anti-HAV antibody titers of less than 20 mIU/mL to receive either one dose of inactivated hepatitis A vaccine or one dose of live, attenuated hepatitis A vaccine. Both groups were followed through December 2013, with assessments of anti-HAV antibody concentrations at years 1, 2, and 5 post vaccination. In all, 182 successfully completed the study, meeting all requirements, including providing serum samples at each time point.
Titer levels were 76.3% mIU/mL and 66.8mIU/mL for the inactivated and live vaccines at 5 years, respectively. No clinical hepatitis A case was reported.
The study appears online in Human Vaccines & Immunotherapeutics (doi: 10.1080/21645515.2016.1278329).
[email protected]
On Twitter @whitneymcknight
, a study has shown.
In October 2008, a team of investigators in China led by Zhilun Zhang of the Tianjin Center for Disease Control and Prevention, randomly assigned 332 children aged 18-60 months with prevaccination anti-HAV antibody titers of less than 20 mIU/mL to receive either one dose of inactivated hepatitis A vaccine or one dose of live, attenuated hepatitis A vaccine. Both groups were followed through December 2013, with assessments of anti-HAV antibody concentrations at years 1, 2, and 5 post vaccination. In all, 182 successfully completed the study, meeting all requirements, including providing serum samples at each time point.
Titer levels were 76.3% mIU/mL and 66.8mIU/mL for the inactivated and live vaccines at 5 years, respectively. No clinical hepatitis A case was reported.
The study appears online in Human Vaccines & Immunotherapeutics (doi: 10.1080/21645515.2016.1278329).
[email protected]
On Twitter @whitneymcknight
FROM HUMAN VACCINES & IMMUNOTHERAPEUTICS
Using Gel to Study Effects of Blasts on the Brain
A gel that mimics the texture and mass of the brain, developed by U.S. Army Research Laboratory scientists, may help reveal what happens to the brain during an explosion.
The researchers used pressure-sensitive nanomaterials. The fluorescence intensity of the gel increases or decreases with the amount of pressure applied. Based on how the nanoclusters fluoresce under each pressure, the researchers will be able to gauge what would happen in a “brain situation,” 1 of the researchers says in a Health.mil article. The researchers are planning to create a pressure scale to graph information about the effects of blast pressure from the changes in color.
The laboratory has a working relationship with Japanese medical researchers who are also studying the effects of blast waves. The Japanese team will test the U.S. Army’s samples with a laser-induced shockwave and share the results of that experiment with the U.S. Army.
A gel that mimics the texture and mass of the brain, developed by U.S. Army Research Laboratory scientists, may help reveal what happens to the brain during an explosion.
The researchers used pressure-sensitive nanomaterials. The fluorescence intensity of the gel increases or decreases with the amount of pressure applied. Based on how the nanoclusters fluoresce under each pressure, the researchers will be able to gauge what would happen in a “brain situation,” 1 of the researchers says in a Health.mil article. The researchers are planning to create a pressure scale to graph information about the effects of blast pressure from the changes in color.
The laboratory has a working relationship with Japanese medical researchers who are also studying the effects of blast waves. The Japanese team will test the U.S. Army’s samples with a laser-induced shockwave and share the results of that experiment with the U.S. Army.
A gel that mimics the texture and mass of the brain, developed by U.S. Army Research Laboratory scientists, may help reveal what happens to the brain during an explosion.
The researchers used pressure-sensitive nanomaterials. The fluorescence intensity of the gel increases or decreases with the amount of pressure applied. Based on how the nanoclusters fluoresce under each pressure, the researchers will be able to gauge what would happen in a “brain situation,” 1 of the researchers says in a Health.mil article. The researchers are planning to create a pressure scale to graph information about the effects of blast pressure from the changes in color.
The laboratory has a working relationship with Japanese medical researchers who are also studying the effects of blast waves. The Japanese team will test the U.S. Army’s samples with a laser-induced shockwave and share the results of that experiment with the U.S. Army.
Blood in Urine, Rash on Trunk
Several days ago, a 14-year-old boy suddenly became ill with abdominal pain, fever, and arthralgia. Within 12 hours, a rash developed that covered most of his trunk, arms, and legs but spared his face, palms, and soles. It quickly flared bright red; some lesions were tender to touch. The patient’s legs and scrotum became edematous, and he lost his appetite. The patient developed diarrhea, and bright red blood was seen in his stools.
He was taken to the local emergency department, where examination revealed a fever of 101.5°F, an elevated white blood cell count, and a small amount of blood in his urine. Stool cultures were ordered, and the patient was placed on an unknown antibiotic.
The next day, he consulted his pediatrician, who referred him to dermatology.
EXAMINATION
Today, the patient is afebrile and in no acute distress. He still has a florid rash on his trunk, arms, and legs consisting of very evenly distributed, purpuric lesions that average 3 mm in diameter. A few are palpable, and none are blanchable. A punch biopsy is performed, and an entire lesion is obtained and submitted for pathologic examination.
What is the diagnosis?
The report showed leukocytoclastic vasculitis, in which activated lymphocytes attack the inner lining of blood vessels, causing them to leak blood into the surrounding interstitial spaces. Besides the extravasated red blood cells, nuclear dust (remnants of the attacking lymphocytes) is also seen.
These biopsy findings, in context with the patient’s history, help to confirm the diagnosis of Henoch-Schönlein purpura (HSP), an IgA-mediated disease that causes widespread vasculitis of small vessels throughout the body. Besides affecting the skin, this process can injure the gastrointestinal tract, joints, kidneys, and even lungs. As this case illustrates, it almost always presents with a palpable, purpuric, widespread rash, abdominal pain, fever, joint pain, and bloody stools.
HSP is seen primarily in children; in the US, 75% of cases occur in those ages 2 to 5. The most consistent presenting symptoms in this population include rash, abdominal pain, and joint pain. When fever is present, it is typically mild.
A variety factors can trigger HSP, including medications (eg, penicillin, NSAIDs, sulfa) and infection (with organisms such as mycoplasma, mononucleosis, strep, Legionella)—but many cases are simply idiopathic. History of upper respiratory infection, pharyngitis, or intestinal infection is found in 75% of young HSP patients. Antecedent vaccinations have also been reported as a potential trigger.
The diagnosis of HSP is primarily clinical, based on a combination of signs and symptoms and the exclusion of other items in the differential. Besides bloodwork to rule out end-organ (eg, renal) damage, a skin biopsy of the purpuric rash is necessary to establish the type of vasculitis.
Fortunately, most HSP patients recover uneventfully; the exception is the occasional patient with renal complications. The case patient successfully recovered following treatment with oral antibiotics (for presumed strep) and a three-week course of prednisone.
TAKE-HOME LEARNING POINTS
- A purpuric rash should prompt a punch biopsy to search for vasculitis.
- A widespread, palpable, purpuric rash accompanied by systemic symptoms of abdominal pain, arthralgia, fever, and malaise is suggestive of serious disease. In younger patients, Henoch-Schönlein purpura (HSP) should be a major suspect.
- Drugs, bugs, and vaccinations are all possible triggers for HSP.
- Once the diagnosis of HSP is made, monitoring for end-organ damage is essential.
Several days ago, a 14-year-old boy suddenly became ill with abdominal pain, fever, and arthralgia. Within 12 hours, a rash developed that covered most of his trunk, arms, and legs but spared his face, palms, and soles. It quickly flared bright red; some lesions were tender to touch. The patient’s legs and scrotum became edematous, and he lost his appetite. The patient developed diarrhea, and bright red blood was seen in his stools.
He was taken to the local emergency department, where examination revealed a fever of 101.5°F, an elevated white blood cell count, and a small amount of blood in his urine. Stool cultures were ordered, and the patient was placed on an unknown antibiotic.
The next day, he consulted his pediatrician, who referred him to dermatology.
EXAMINATION
Today, the patient is afebrile and in no acute distress. He still has a florid rash on his trunk, arms, and legs consisting of very evenly distributed, purpuric lesions that average 3 mm in diameter. A few are palpable, and none are blanchable. A punch biopsy is performed, and an entire lesion is obtained and submitted for pathologic examination.
What is the diagnosis?
The report showed leukocytoclastic vasculitis, in which activated lymphocytes attack the inner lining of blood vessels, causing them to leak blood into the surrounding interstitial spaces. Besides the extravasated red blood cells, nuclear dust (remnants of the attacking lymphocytes) is also seen.
These biopsy findings, in context with the patient’s history, help to confirm the diagnosis of Henoch-Schönlein purpura (HSP), an IgA-mediated disease that causes widespread vasculitis of small vessels throughout the body. Besides affecting the skin, this process can injure the gastrointestinal tract, joints, kidneys, and even lungs. As this case illustrates, it almost always presents with a palpable, purpuric, widespread rash, abdominal pain, fever, joint pain, and bloody stools.
HSP is seen primarily in children; in the US, 75% of cases occur in those ages 2 to 5. The most consistent presenting symptoms in this population include rash, abdominal pain, and joint pain. When fever is present, it is typically mild.
A variety factors can trigger HSP, including medications (eg, penicillin, NSAIDs, sulfa) and infection (with organisms such as mycoplasma, mononucleosis, strep, Legionella)—but many cases are simply idiopathic. History of upper respiratory infection, pharyngitis, or intestinal infection is found in 75% of young HSP patients. Antecedent vaccinations have also been reported as a potential trigger.
The diagnosis of HSP is primarily clinical, based on a combination of signs and symptoms and the exclusion of other items in the differential. Besides bloodwork to rule out end-organ (eg, renal) damage, a skin biopsy of the purpuric rash is necessary to establish the type of vasculitis.
Fortunately, most HSP patients recover uneventfully; the exception is the occasional patient with renal complications. The case patient successfully recovered following treatment with oral antibiotics (for presumed strep) and a three-week course of prednisone.
TAKE-HOME LEARNING POINTS
- A purpuric rash should prompt a punch biopsy to search for vasculitis.
- A widespread, palpable, purpuric rash accompanied by systemic symptoms of abdominal pain, arthralgia, fever, and malaise is suggestive of serious disease. In younger patients, Henoch-Schönlein purpura (HSP) should be a major suspect.
- Drugs, bugs, and vaccinations are all possible triggers for HSP.
- Once the diagnosis of HSP is made, monitoring for end-organ damage is essential.
Several days ago, a 14-year-old boy suddenly became ill with abdominal pain, fever, and arthralgia. Within 12 hours, a rash developed that covered most of his trunk, arms, and legs but spared his face, palms, and soles. It quickly flared bright red; some lesions were tender to touch. The patient’s legs and scrotum became edematous, and he lost his appetite. The patient developed diarrhea, and bright red blood was seen in his stools.
He was taken to the local emergency department, where examination revealed a fever of 101.5°F, an elevated white blood cell count, and a small amount of blood in his urine. Stool cultures were ordered, and the patient was placed on an unknown antibiotic.
The next day, he consulted his pediatrician, who referred him to dermatology.
EXAMINATION
Today, the patient is afebrile and in no acute distress. He still has a florid rash on his trunk, arms, and legs consisting of very evenly distributed, purpuric lesions that average 3 mm in diameter. A few are palpable, and none are blanchable. A punch biopsy is performed, and an entire lesion is obtained and submitted for pathologic examination.
What is the diagnosis?
The report showed leukocytoclastic vasculitis, in which activated lymphocytes attack the inner lining of blood vessels, causing them to leak blood into the surrounding interstitial spaces. Besides the extravasated red blood cells, nuclear dust (remnants of the attacking lymphocytes) is also seen.
These biopsy findings, in context with the patient’s history, help to confirm the diagnosis of Henoch-Schönlein purpura (HSP), an IgA-mediated disease that causes widespread vasculitis of small vessels throughout the body. Besides affecting the skin, this process can injure the gastrointestinal tract, joints, kidneys, and even lungs. As this case illustrates, it almost always presents with a palpable, purpuric, widespread rash, abdominal pain, fever, joint pain, and bloody stools.
HSP is seen primarily in children; in the US, 75% of cases occur in those ages 2 to 5. The most consistent presenting symptoms in this population include rash, abdominal pain, and joint pain. When fever is present, it is typically mild.
A variety factors can trigger HSP, including medications (eg, penicillin, NSAIDs, sulfa) and infection (with organisms such as mycoplasma, mononucleosis, strep, Legionella)—but many cases are simply idiopathic. History of upper respiratory infection, pharyngitis, or intestinal infection is found in 75% of young HSP patients. Antecedent vaccinations have also been reported as a potential trigger.
The diagnosis of HSP is primarily clinical, based on a combination of signs and symptoms and the exclusion of other items in the differential. Besides bloodwork to rule out end-organ (eg, renal) damage, a skin biopsy of the purpuric rash is necessary to establish the type of vasculitis.
Fortunately, most HSP patients recover uneventfully; the exception is the occasional patient with renal complications. The case patient successfully recovered following treatment with oral antibiotics (for presumed strep) and a three-week course of prednisone.
TAKE-HOME LEARNING POINTS
- A purpuric rash should prompt a punch biopsy to search for vasculitis.
- A widespread, palpable, purpuric rash accompanied by systemic symptoms of abdominal pain, arthralgia, fever, and malaise is suggestive of serious disease. In younger patients, Henoch-Schönlein purpura (HSP) should be a major suspect.
- Drugs, bugs, and vaccinations are all possible triggers for HSP.
- Once the diagnosis of HSP is made, monitoring for end-organ damage is essential.
Dark line across nose
The FP recognized the dark line on the patient’s face as a hyperpigmented horizontal nasal crease based on the fact that she had the atopic triad and repeatedly wiped her nose in an upward motion (an “allergic salute”) whenever her nose felt itchy. There is no specific treatment for a hyperpigmented horizontal nose crease, except to help control the allergic rhinitis. It also helps to control any atopic dermatitis, which can lead to pruritus.
The patient was happy to know the cause of the condition and did not request treatment for the cosmetic aspect of it. For patients who want treatment, a good place to start is with an over-the-counter 3% hydroquinone bleaching agent, along with 1% hydrocortisone cream. (These can both be applied twice daily.)
The FP in this case also recommended sun protection and sun avoidance to avoid further darkening of the hyperpigmented crease.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Finklea L. Atopic dermatitis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:584-590.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
The FP recognized the dark line on the patient’s face as a hyperpigmented horizontal nasal crease based on the fact that she had the atopic triad and repeatedly wiped her nose in an upward motion (an “allergic salute”) whenever her nose felt itchy. There is no specific treatment for a hyperpigmented horizontal nose crease, except to help control the allergic rhinitis. It also helps to control any atopic dermatitis, which can lead to pruritus.
The patient was happy to know the cause of the condition and did not request treatment for the cosmetic aspect of it. For patients who want treatment, a good place to start is with an over-the-counter 3% hydroquinone bleaching agent, along with 1% hydrocortisone cream. (These can both be applied twice daily.)
The FP in this case also recommended sun protection and sun avoidance to avoid further darkening of the hyperpigmented crease.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Finklea L. Atopic dermatitis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:584-590.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
The FP recognized the dark line on the patient’s face as a hyperpigmented horizontal nasal crease based on the fact that she had the atopic triad and repeatedly wiped her nose in an upward motion (an “allergic salute”) whenever her nose felt itchy. There is no specific treatment for a hyperpigmented horizontal nose crease, except to help control the allergic rhinitis. It also helps to control any atopic dermatitis, which can lead to pruritus.
The patient was happy to know the cause of the condition and did not request treatment for the cosmetic aspect of it. For patients who want treatment, a good place to start is with an over-the-counter 3% hydroquinone bleaching agent, along with 1% hydrocortisone cream. (These can both be applied twice daily.)
The FP in this case also recommended sun protection and sun avoidance to avoid further darkening of the hyperpigmented crease.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Finklea L. Atopic dermatitis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:584-590.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
Neuromyelitis Optica Spectrum Disorders: Critical Role of Complement-Dependent Cytotoxicity
Critical Role of Complement-Dependent Cytotoxicity
The complement system was once thought to have a fairly limited role in the immune system, recognizing and eliminating pathogens. Now, however, complement proteins are known to have a much broader role in immunity, and dysregulation of the complement system has been shown to affect the pathogenesis and clinical picture of several autoimmune diseases. This supplement discusses the role of complement-dependent cytotoxicity in the pathophysiology of neuromyelitis optica spectrum disorders.
Click here to read the supplement
US/UNB-NMO/17/0002c
The complement system was once thought to have a fairly limited role in the immune system, recognizing and eliminating pathogens. Now, however, complement proteins are known to have a much broader role in immunity, and dysregulation of the complement system has been shown to affect the pathogenesis and clinical picture of several autoimmune diseases. This supplement discusses the role of complement-dependent cytotoxicity in the pathophysiology of neuromyelitis optica spectrum disorders.
Click here to read the supplement
US/UNB-NMO/17/0002c
The complement system was once thought to have a fairly limited role in the immune system, recognizing and eliminating pathogens. Now, however, complement proteins are known to have a much broader role in immunity, and dysregulation of the complement system has been shown to affect the pathogenesis and clinical picture of several autoimmune diseases. This supplement discusses the role of complement-dependent cytotoxicity in the pathophysiology of neuromyelitis optica spectrum disorders.
Click here to read the supplement
US/UNB-NMO/17/0002c
Critical Role of Complement-Dependent Cytotoxicity
Critical Role of Complement-Dependent Cytotoxicity
Multiple myeloma: Lenalidomide approved as maintenance therapy after auto-HSCT
The Food and Drug Administration has approved the use of lenalidomide (Revlimid) for maintenance therapy following autologous hematopoietic stem cell transplant in patients with multiple myeloma.
The expanded indication, announced Feb. 22, makes the immunomodulatory agent the first and only approved treatment for post autologous hematopoietic stem cell transplant (auto-HSCT) maintenance. It was initially approved in 2006 for use in combination with dexamethasone in patients with multiple myeloma who have received at least one prior therapy, and that indication was expanded in 2015 to include those with newly diagnosed multiple myeloma.
According to Celgene, the maker of Revlimid, the latest approval was based on data showing that lenalidomide maintenance therapy delays disease progression following auto-HSCT. Updated phase III randomized controlled trial data from two studies including more than 1,000 patients demonstrated median progression-free survival (PFS) advantages with lenalidomide maintenance vs. no maintenance. In one study – the U.S.-based CALGB 1001014 – median PFS was 5.7 vs. 1.9 years for a difference of 3.8 years (hazard ratio, 0.38). In the second study – the European IFM 2005-02 – median PFS was 3.9 vs. 2 years, for a difference of 1.9 years (HR, 0.53).
In both studies lenalidomide was given as a 10-mg daily oral dose (increased to 15 mg daily after 3 months if tolerated) until disease progression or unacceptable toxicity after auto-HSCT.
Lenalidomide, a derivative of thalidomide, can cause fetal harm and is contraindicated in women who are pregnant. It is available only through a restricted distribution program.
The most frequently reported adverse reactions in the two studies were neutropenia, thrombocytopenia, leukopenia, anemia, upper respiratory tract infection, bronchitis, nasopharyngitis, cough, gastroenteritis, diarrhea, rash, fatigue, muscle spasm, and pyrexia. The most frequently reported grade 3 or 4 reactions occurring in more than 20% of patients in the lenalidomide arms included neutropenia, thrombocytopenia, and leukopenia.
“Autologous stem cell transplant after induction therapy is part of the continuum of care for transplant-eligible multiple myeloma patients. However, most patients will still see their disease recur or progress after this treatment,” Philip McCarthy, MD, of the Roswell Park Cancer Institute in Buffalo, N.Y., said in a Celgene press statement. “Lenalidomide maintenance therapy ... can be considered a standard of care for these patients.”
The Food and Drug Administration has approved the use of lenalidomide (Revlimid) for maintenance therapy following autologous hematopoietic stem cell transplant in patients with multiple myeloma.
The expanded indication, announced Feb. 22, makes the immunomodulatory agent the first and only approved treatment for post autologous hematopoietic stem cell transplant (auto-HSCT) maintenance. It was initially approved in 2006 for use in combination with dexamethasone in patients with multiple myeloma who have received at least one prior therapy, and that indication was expanded in 2015 to include those with newly diagnosed multiple myeloma.
According to Celgene, the maker of Revlimid, the latest approval was based on data showing that lenalidomide maintenance therapy delays disease progression following auto-HSCT. Updated phase III randomized controlled trial data from two studies including more than 1,000 patients demonstrated median progression-free survival (PFS) advantages with lenalidomide maintenance vs. no maintenance. In one study – the U.S.-based CALGB 1001014 – median PFS was 5.7 vs. 1.9 years for a difference of 3.8 years (hazard ratio, 0.38). In the second study – the European IFM 2005-02 – median PFS was 3.9 vs. 2 years, for a difference of 1.9 years (HR, 0.53).
In both studies lenalidomide was given as a 10-mg daily oral dose (increased to 15 mg daily after 3 months if tolerated) until disease progression or unacceptable toxicity after auto-HSCT.
Lenalidomide, a derivative of thalidomide, can cause fetal harm and is contraindicated in women who are pregnant. It is available only through a restricted distribution program.
The most frequently reported adverse reactions in the two studies were neutropenia, thrombocytopenia, leukopenia, anemia, upper respiratory tract infection, bronchitis, nasopharyngitis, cough, gastroenteritis, diarrhea, rash, fatigue, muscle spasm, and pyrexia. The most frequently reported grade 3 or 4 reactions occurring in more than 20% of patients in the lenalidomide arms included neutropenia, thrombocytopenia, and leukopenia.
“Autologous stem cell transplant after induction therapy is part of the continuum of care for transplant-eligible multiple myeloma patients. However, most patients will still see their disease recur or progress after this treatment,” Philip McCarthy, MD, of the Roswell Park Cancer Institute in Buffalo, N.Y., said in a Celgene press statement. “Lenalidomide maintenance therapy ... can be considered a standard of care for these patients.”
The Food and Drug Administration has approved the use of lenalidomide (Revlimid) for maintenance therapy following autologous hematopoietic stem cell transplant in patients with multiple myeloma.
The expanded indication, announced Feb. 22, makes the immunomodulatory agent the first and only approved treatment for post autologous hematopoietic stem cell transplant (auto-HSCT) maintenance. It was initially approved in 2006 for use in combination with dexamethasone in patients with multiple myeloma who have received at least one prior therapy, and that indication was expanded in 2015 to include those with newly diagnosed multiple myeloma.
According to Celgene, the maker of Revlimid, the latest approval was based on data showing that lenalidomide maintenance therapy delays disease progression following auto-HSCT. Updated phase III randomized controlled trial data from two studies including more than 1,000 patients demonstrated median progression-free survival (PFS) advantages with lenalidomide maintenance vs. no maintenance. In one study – the U.S.-based CALGB 1001014 – median PFS was 5.7 vs. 1.9 years for a difference of 3.8 years (hazard ratio, 0.38). In the second study – the European IFM 2005-02 – median PFS was 3.9 vs. 2 years, for a difference of 1.9 years (HR, 0.53).
In both studies lenalidomide was given as a 10-mg daily oral dose (increased to 15 mg daily after 3 months if tolerated) until disease progression or unacceptable toxicity after auto-HSCT.
Lenalidomide, a derivative of thalidomide, can cause fetal harm and is contraindicated in women who are pregnant. It is available only through a restricted distribution program.
The most frequently reported adverse reactions in the two studies were neutropenia, thrombocytopenia, leukopenia, anemia, upper respiratory tract infection, bronchitis, nasopharyngitis, cough, gastroenteritis, diarrhea, rash, fatigue, muscle spasm, and pyrexia. The most frequently reported grade 3 or 4 reactions occurring in more than 20% of patients in the lenalidomide arms included neutropenia, thrombocytopenia, and leukopenia.
“Autologous stem cell transplant after induction therapy is part of the continuum of care for transplant-eligible multiple myeloma patients. However, most patients will still see their disease recur or progress after this treatment,” Philip McCarthy, MD, of the Roswell Park Cancer Institute in Buffalo, N.Y., said in a Celgene press statement. “Lenalidomide maintenance therapy ... can be considered a standard of care for these patients.”
Annual nailfold videocapillaroscopy found prognostic in systemic sclerosis
Annual nailfold videocapillaroscopy can be used to predict disease progression in systemic sclerosis, according to a report in Seminars in Arthritis & Rheumatism.
Early and diffuse alterations in the microvasculature are a key feature of systemic sclerosis, and nailfold videocapillaroscopy can detect morphologic changes that reflect such alterations, including capillary loss, neoangiogenesis, giant capillaries, microhemorrhages, and the presence of avascular areas. The technique already has an established role in diagnosing systemic sclerosis, said Jérôme Avouac, MD, of the rheumatology department at Cochin Hospital, Paris, and his associates.
Two contiguous fields extending over 1 mm in the middle of each nailfold, corresponding to the distal row of capillaries, were assessed for four features: the number of capillaries, the presence of giant capillaries, microhemorrhages, and neoangiogenesis (defined as meandering, ramified, branching, bushy, bizarre capillaries and those with more than two crossings). A total of 72 patients (51%) showed significant progression of at least one of these features during follow-up.
A progressive loss of capillaries over time strongly predicted overall disease progression (hazard ratio, 4.35). Other significant predictors of overall disease progression included the development of new ischemic digital ulcers (HR, 5.33), progression of lung involvement (HR, 18.53), progression of skin fibrosis (HR, 4.22), and worsening of the Medsger severity score (HR, 5.26). In addition, the presence of neoangiogenesis at baseline, but not the progression of neoangiogenesis over time, also predicted overall disease progression (HR, 2.53), the development of new ischemic digital ulcers (HR, 2.60), progression of lung involvement (HR, 7.38), and worsening of the Medsger severity score (HR, 2.72), Dr. Avouac and his associates said (Semin Arthritis Rheum. 2017 Feb 10. doi: 10.1016/j.semarthrit.2017.02.006).
These findings demonstrate that serial videocapillaroscopy, which they described as a simple, safe, noninvasive, and inexpensive imaging technique, can be used in routine follow-up of systemic sclerosis to improve risk assessment, the investigators said.
The authors reported no financial support for this study and reported having no relevant financial disclosures.
Annual nailfold videocapillaroscopy can be used to predict disease progression in systemic sclerosis, according to a report in Seminars in Arthritis & Rheumatism.
Early and diffuse alterations in the microvasculature are a key feature of systemic sclerosis, and nailfold videocapillaroscopy can detect morphologic changes that reflect such alterations, including capillary loss, neoangiogenesis, giant capillaries, microhemorrhages, and the presence of avascular areas. The technique already has an established role in diagnosing systemic sclerosis, said Jérôme Avouac, MD, of the rheumatology department at Cochin Hospital, Paris, and his associates.
Two contiguous fields extending over 1 mm in the middle of each nailfold, corresponding to the distal row of capillaries, were assessed for four features: the number of capillaries, the presence of giant capillaries, microhemorrhages, and neoangiogenesis (defined as meandering, ramified, branching, bushy, bizarre capillaries and those with more than two crossings). A total of 72 patients (51%) showed significant progression of at least one of these features during follow-up.
A progressive loss of capillaries over time strongly predicted overall disease progression (hazard ratio, 4.35). Other significant predictors of overall disease progression included the development of new ischemic digital ulcers (HR, 5.33), progression of lung involvement (HR, 18.53), progression of skin fibrosis (HR, 4.22), and worsening of the Medsger severity score (HR, 5.26). In addition, the presence of neoangiogenesis at baseline, but not the progression of neoangiogenesis over time, also predicted overall disease progression (HR, 2.53), the development of new ischemic digital ulcers (HR, 2.60), progression of lung involvement (HR, 7.38), and worsening of the Medsger severity score (HR, 2.72), Dr. Avouac and his associates said (Semin Arthritis Rheum. 2017 Feb 10. doi: 10.1016/j.semarthrit.2017.02.006).
These findings demonstrate that serial videocapillaroscopy, which they described as a simple, safe, noninvasive, and inexpensive imaging technique, can be used in routine follow-up of systemic sclerosis to improve risk assessment, the investigators said.
The authors reported no financial support for this study and reported having no relevant financial disclosures.
Annual nailfold videocapillaroscopy can be used to predict disease progression in systemic sclerosis, according to a report in Seminars in Arthritis & Rheumatism.
Early and diffuse alterations in the microvasculature are a key feature of systemic sclerosis, and nailfold videocapillaroscopy can detect morphologic changes that reflect such alterations, including capillary loss, neoangiogenesis, giant capillaries, microhemorrhages, and the presence of avascular areas. The technique already has an established role in diagnosing systemic sclerosis, said Jérôme Avouac, MD, of the rheumatology department at Cochin Hospital, Paris, and his associates.
Two contiguous fields extending over 1 mm in the middle of each nailfold, corresponding to the distal row of capillaries, were assessed for four features: the number of capillaries, the presence of giant capillaries, microhemorrhages, and neoangiogenesis (defined as meandering, ramified, branching, bushy, bizarre capillaries and those with more than two crossings). A total of 72 patients (51%) showed significant progression of at least one of these features during follow-up.
A progressive loss of capillaries over time strongly predicted overall disease progression (hazard ratio, 4.35). Other significant predictors of overall disease progression included the development of new ischemic digital ulcers (HR, 5.33), progression of lung involvement (HR, 18.53), progression of skin fibrosis (HR, 4.22), and worsening of the Medsger severity score (HR, 5.26). In addition, the presence of neoangiogenesis at baseline, but not the progression of neoangiogenesis over time, also predicted overall disease progression (HR, 2.53), the development of new ischemic digital ulcers (HR, 2.60), progression of lung involvement (HR, 7.38), and worsening of the Medsger severity score (HR, 2.72), Dr. Avouac and his associates said (Semin Arthritis Rheum. 2017 Feb 10. doi: 10.1016/j.semarthrit.2017.02.006).
These findings demonstrate that serial videocapillaroscopy, which they described as a simple, safe, noninvasive, and inexpensive imaging technique, can be used in routine follow-up of systemic sclerosis to improve risk assessment, the investigators said.
The authors reported no financial support for this study and reported having no relevant financial disclosures.
Key clinical point: Annual nailfold videocapillaroscopy can be used to predict disease progression in systemic sclerosis.
Major finding: A progressive loss of capillaries over time strongly predicted overall disease progression (HR, 4.35).
Data source: A prospective single-center observational cohort study involving 140 patients followed for up to 5 years.
Disclosures: The authors reported no financial support for this study and reported having no relevant financial disclosures.
ACIP approves minor changes to pediatric hepatitis B vaccine recommendations
Approval to changes of current recommendations for hepatitis B vaccinations for children were voted on by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).
The 14-member panel voted to approve changes to existing language, which states that infants who are HBsAg negative with anti-HBs levels of less than 10 mIU/mL should be revaccinated with a second three-dose series and retested within 2 months of the series’ final dose. The approved proposal will change that language to state that these infants should receive only one dose, not the entire series of three. However, if anti-HBs levels remain lower than 10 mIU/mL after the one dose, the remaining two vaccinations should be administered, along with testing within 2 months of the final dose.
The other change, a relatively minor one, affects the wording of the recommendations regarding the Vaccines for Children program. In addition to incorporating a language change similar to the aforementioned one – the only difference being that now, the recommendations will explicitly mention postvaccination serologic testing within 2 months of series completion – under the minimum dosing intervals for interrupted vaccination schedules, the second bullet has been modified to say “final dose” instead of “third dose,” as it currently does.
“[This is] to address potential confusion related to different schedules when single-antigen or combination vaccines are used,” explained Jeanne Santoli, MD, of the CDC’s National Center for Immunization and Respiratory Diseases, adding that “the eligible groups are unchanged, schedule and intervals are unchanged, [so] the purpose is to clarify related to dosing intervals and revaccination.”
Both votes were approved of nearly unanimously, with 13 committee members voting to approve while 1 – José R. Romero, MD, who holds the Horace C. Cabe Endowed Chair in Pediatric Infectious Diseases at the University of Arkansas in Little Rock – abstained because of potential conflicts of interest.
Approval by ACIP does not automatically mean that these changes will go into effect; they must first be approved by CDC director Tom Frieden, MD. However, the CDC generally follows ACIP guidance.
Approval to changes of current recommendations for hepatitis B vaccinations for children were voted on by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).
The 14-member panel voted to approve changes to existing language, which states that infants who are HBsAg negative with anti-HBs levels of less than 10 mIU/mL should be revaccinated with a second three-dose series and retested within 2 months of the series’ final dose. The approved proposal will change that language to state that these infants should receive only one dose, not the entire series of three. However, if anti-HBs levels remain lower than 10 mIU/mL after the one dose, the remaining two vaccinations should be administered, along with testing within 2 months of the final dose.
The other change, a relatively minor one, affects the wording of the recommendations regarding the Vaccines for Children program. In addition to incorporating a language change similar to the aforementioned one – the only difference being that now, the recommendations will explicitly mention postvaccination serologic testing within 2 months of series completion – under the minimum dosing intervals for interrupted vaccination schedules, the second bullet has been modified to say “final dose” instead of “third dose,” as it currently does.
“[This is] to address potential confusion related to different schedules when single-antigen or combination vaccines are used,” explained Jeanne Santoli, MD, of the CDC’s National Center for Immunization and Respiratory Diseases, adding that “the eligible groups are unchanged, schedule and intervals are unchanged, [so] the purpose is to clarify related to dosing intervals and revaccination.”
Both votes were approved of nearly unanimously, with 13 committee members voting to approve while 1 – José R. Romero, MD, who holds the Horace C. Cabe Endowed Chair in Pediatric Infectious Diseases at the University of Arkansas in Little Rock – abstained because of potential conflicts of interest.
Approval by ACIP does not automatically mean that these changes will go into effect; they must first be approved by CDC director Tom Frieden, MD. However, the CDC generally follows ACIP guidance.
Approval to changes of current recommendations for hepatitis B vaccinations for children were voted on by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).
The 14-member panel voted to approve changes to existing language, which states that infants who are HBsAg negative with anti-HBs levels of less than 10 mIU/mL should be revaccinated with a second three-dose series and retested within 2 months of the series’ final dose. The approved proposal will change that language to state that these infants should receive only one dose, not the entire series of three. However, if anti-HBs levels remain lower than 10 mIU/mL after the one dose, the remaining two vaccinations should be administered, along with testing within 2 months of the final dose.
The other change, a relatively minor one, affects the wording of the recommendations regarding the Vaccines for Children program. In addition to incorporating a language change similar to the aforementioned one – the only difference being that now, the recommendations will explicitly mention postvaccination serologic testing within 2 months of series completion – under the minimum dosing intervals for interrupted vaccination schedules, the second bullet has been modified to say “final dose” instead of “third dose,” as it currently does.
“[This is] to address potential confusion related to different schedules when single-antigen or combination vaccines are used,” explained Jeanne Santoli, MD, of the CDC’s National Center for Immunization and Respiratory Diseases, adding that “the eligible groups are unchanged, schedule and intervals are unchanged, [so] the purpose is to clarify related to dosing intervals and revaccination.”
Both votes were approved of nearly unanimously, with 13 committee members voting to approve while 1 – José R. Romero, MD, who holds the Horace C. Cabe Endowed Chair in Pediatric Infectious Diseases at the University of Arkansas in Little Rock – abstained because of potential conflicts of interest.
Approval by ACIP does not automatically mean that these changes will go into effect; they must first be approved by CDC director Tom Frieden, MD. However, the CDC generally follows ACIP guidance.
Lanadelumab reduced hereditary angioedema attacks by 88%-100%
Lanadelumab, a monoclonal antibody that inhibits kallikrein, reduced attacks of hereditary angioedema with C1 inhibitor deficiency by 88%-100% in a small, phase I trial.
Hereditary angioedema with C1 inhibitor deficiency is a rare disorder characterized by unpredictable, recurrent, and potentially life-threatening episodes of subcutaneous or submucosal swelling, typically affecting the hands and feet, abdomen, face, larynx, or genitourinary tract. It is caused by a deficiency or dysfunction of the C1 inhibitor, which regulates the complement, coagulation, and kallikrein-kinin cascades.
They performed a multicenter, double-blind, randomized study to assess the safety and adverse-effect profile of four doses of this new agent or placebo in 37 adults (aged 18-71 years, mean age, 39.9 years) who received two injections, 2 weeks apart, and were followed for 6 weeks. Given their histories, all the study participants had “a reasonable probability of having one or more attacks” during the study period, the researchers noted.
Four participants received a 30-mg dose, 4 received a 100-mg dose, 5 received a 300-mg dose, 11 received a 400-mg dose, and 13 received placebo.
There were no serious adverse events, no deaths, and no discontinuations of the study medication because of an adverse effect. One patient each developed severe adverse events: pain at the injection site that lasted for 1 minute and headache plus night sweats.
Pharmacodynamic assessments showed that lanadelumab inhibited kallikrein in a linear, dose-dependent manner, and the two higher doses reduced levels of cleaved high-molecular-weight kininogen to those reported in healthy control subjects. At the same time, the two higher doses decreased the number of attacks by 88% and 100%, respectively, compared with placebo.
All the patients in the 300-mg group and 9 of the 11 in the 400-mg group had no attacks during the study period, the investigators said.
These findings “provide proof of concept that lanadelumab has the potential to correct the pathophysiological abnormality underlying attacks of angioedema and may be a new therapeutic option for hereditary angioedema with C1 inhibitor deficiency,” Dr. Banerji and her associates said.
The HELP Study, a phase III trial assessing the safety and efficacy of 6 months of lanadelumab treatment, is now underway, they added.
The trial was sponsored by Dyax, which also participated in the study design, data collection and interpretation, and writing of the results. Dr. Banerji reported ties to Alnylam Pharmaceuticals, CSL Behring, Dyax, and Shire; her associates reported ties to numerous industry sources.
This preliminary study suggests that a new agent, in injections that would be convenient and widely accessible, could provide an unprecedented level of protection against angioedema.
If these findings are confirmed, and if lanadelumab is affordable, it could transform the way hereditary angioedema is managed and the life prospects for affected families.
Moreover, kallikrein is implicated in other forms of bradykinin-mediated angioedema, such as that associated with ACE inhibitors, and plays a key role in the generation of inflammation and pain. So, the sustained inhibition of kallikrein potentially could be beneficial for a much wider range of disorders.
Hilary J. Longhurst, MD, is at Barts Health National Health Service Trust, London. She reported having ties to BioCryst, CSL Behring, and Shire. Dr. Longhurst made these remarks in an editorial accompanying Dr. Banerji’s report (N Engl J Med. 2017 Feb 23;376[8]:788-9).
This preliminary study suggests that a new agent, in injections that would be convenient and widely accessible, could provide an unprecedented level of protection against angioedema.
If these findings are confirmed, and if lanadelumab is affordable, it could transform the way hereditary angioedema is managed and the life prospects for affected families.
Moreover, kallikrein is implicated in other forms of bradykinin-mediated angioedema, such as that associated with ACE inhibitors, and plays a key role in the generation of inflammation and pain. So, the sustained inhibition of kallikrein potentially could be beneficial for a much wider range of disorders.
Hilary J. Longhurst, MD, is at Barts Health National Health Service Trust, London. She reported having ties to BioCryst, CSL Behring, and Shire. Dr. Longhurst made these remarks in an editorial accompanying Dr. Banerji’s report (N Engl J Med. 2017 Feb 23;376[8]:788-9).
This preliminary study suggests that a new agent, in injections that would be convenient and widely accessible, could provide an unprecedented level of protection against angioedema.
If these findings are confirmed, and if lanadelumab is affordable, it could transform the way hereditary angioedema is managed and the life prospects for affected families.
Moreover, kallikrein is implicated in other forms of bradykinin-mediated angioedema, such as that associated with ACE inhibitors, and plays a key role in the generation of inflammation and pain. So, the sustained inhibition of kallikrein potentially could be beneficial for a much wider range of disorders.
Hilary J. Longhurst, MD, is at Barts Health National Health Service Trust, London. She reported having ties to BioCryst, CSL Behring, and Shire. Dr. Longhurst made these remarks in an editorial accompanying Dr. Banerji’s report (N Engl J Med. 2017 Feb 23;376[8]:788-9).
Lanadelumab, a monoclonal antibody that inhibits kallikrein, reduced attacks of hereditary angioedema with C1 inhibitor deficiency by 88%-100% in a small, phase I trial.
Hereditary angioedema with C1 inhibitor deficiency is a rare disorder characterized by unpredictable, recurrent, and potentially life-threatening episodes of subcutaneous or submucosal swelling, typically affecting the hands and feet, abdomen, face, larynx, or genitourinary tract. It is caused by a deficiency or dysfunction of the C1 inhibitor, which regulates the complement, coagulation, and kallikrein-kinin cascades.
They performed a multicenter, double-blind, randomized study to assess the safety and adverse-effect profile of four doses of this new agent or placebo in 37 adults (aged 18-71 years, mean age, 39.9 years) who received two injections, 2 weeks apart, and were followed for 6 weeks. Given their histories, all the study participants had “a reasonable probability of having one or more attacks” during the study period, the researchers noted.
Four participants received a 30-mg dose, 4 received a 100-mg dose, 5 received a 300-mg dose, 11 received a 400-mg dose, and 13 received placebo.
There were no serious adverse events, no deaths, and no discontinuations of the study medication because of an adverse effect. One patient each developed severe adverse events: pain at the injection site that lasted for 1 minute and headache plus night sweats.
Pharmacodynamic assessments showed that lanadelumab inhibited kallikrein in a linear, dose-dependent manner, and the two higher doses reduced levels of cleaved high-molecular-weight kininogen to those reported in healthy control subjects. At the same time, the two higher doses decreased the number of attacks by 88% and 100%, respectively, compared with placebo.
All the patients in the 300-mg group and 9 of the 11 in the 400-mg group had no attacks during the study period, the investigators said.
These findings “provide proof of concept that lanadelumab has the potential to correct the pathophysiological abnormality underlying attacks of angioedema and may be a new therapeutic option for hereditary angioedema with C1 inhibitor deficiency,” Dr. Banerji and her associates said.
The HELP Study, a phase III trial assessing the safety and efficacy of 6 months of lanadelumab treatment, is now underway, they added.
The trial was sponsored by Dyax, which also participated in the study design, data collection and interpretation, and writing of the results. Dr. Banerji reported ties to Alnylam Pharmaceuticals, CSL Behring, Dyax, and Shire; her associates reported ties to numerous industry sources.
Lanadelumab, a monoclonal antibody that inhibits kallikrein, reduced attacks of hereditary angioedema with C1 inhibitor deficiency by 88%-100% in a small, phase I trial.
Hereditary angioedema with C1 inhibitor deficiency is a rare disorder characterized by unpredictable, recurrent, and potentially life-threatening episodes of subcutaneous or submucosal swelling, typically affecting the hands and feet, abdomen, face, larynx, or genitourinary tract. It is caused by a deficiency or dysfunction of the C1 inhibitor, which regulates the complement, coagulation, and kallikrein-kinin cascades.
They performed a multicenter, double-blind, randomized study to assess the safety and adverse-effect profile of four doses of this new agent or placebo in 37 adults (aged 18-71 years, mean age, 39.9 years) who received two injections, 2 weeks apart, and were followed for 6 weeks. Given their histories, all the study participants had “a reasonable probability of having one or more attacks” during the study period, the researchers noted.
Four participants received a 30-mg dose, 4 received a 100-mg dose, 5 received a 300-mg dose, 11 received a 400-mg dose, and 13 received placebo.
There were no serious adverse events, no deaths, and no discontinuations of the study medication because of an adverse effect. One patient each developed severe adverse events: pain at the injection site that lasted for 1 minute and headache plus night sweats.
Pharmacodynamic assessments showed that lanadelumab inhibited kallikrein in a linear, dose-dependent manner, and the two higher doses reduced levels of cleaved high-molecular-weight kininogen to those reported in healthy control subjects. At the same time, the two higher doses decreased the number of attacks by 88% and 100%, respectively, compared with placebo.
All the patients in the 300-mg group and 9 of the 11 in the 400-mg group had no attacks during the study period, the investigators said.
These findings “provide proof of concept that lanadelumab has the potential to correct the pathophysiological abnormality underlying attacks of angioedema and may be a new therapeutic option for hereditary angioedema with C1 inhibitor deficiency,” Dr. Banerji and her associates said.
The HELP Study, a phase III trial assessing the safety and efficacy of 6 months of lanadelumab treatment, is now underway, they added.
The trial was sponsored by Dyax, which also participated in the study design, data collection and interpretation, and writing of the results. Dr. Banerji reported ties to Alnylam Pharmaceuticals, CSL Behring, Dyax, and Shire; her associates reported ties to numerous industry sources.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Lanadelumab, a monoclonal antibody that inhibits kallikrein, reduced attacks of hereditary angioedema with C1 inhibitor deficiency by 88%-100%.
Major finding: All the patients in the 300-mg group and 9 of the 11 in the 400-mg group had no angioedema attacks during the study period.
Data source: A multicenter, randomized, double-blind, placebo-controlled phase Ib trial involving 37 adults who had hereditary angioedema with C1 inhibitor deficiency.
Disclosures: The trial was sponsored by Dyax, which also participated in the study design, data collection and interpretation, and writing the results. Dr. Banerji reported ties to Alnylam Pharmaceuticals, CSL Behring, Dyax, and Shire; her associates reported ties to numerous industry sources.