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Optimal management of GERD in IPF unknown
EXPERT ANALYSIS FROM CHEST 2016
LOS ANGELES – The optimal management of gastroesophageal reflux disease in patients with idiopathic pulmonary fibrosis has yet to be determined, according to Joyce S. Lee, MD.
“We need strong randomized clinical trial data to tell us whether or not medical or surgical treatment of GERD in IPF is indicated,” she said at the annual meeting of the American College of Chest Physicians.
Two proposed hypotheses explain the relationship between reflux and IPF. The first holds that reflux and microaspiration are involved in the pathogenesis of IPF. The second, favored by Dr. Lee, proposes that reflux and microaspiration impact the natural history, either through acute exacerbation, disease progression, or survival. Patients with IPF “have weakening of the lower esophageal sphincter, whether that’s due to the presence of a hiatal hernia, medications, or just aging of the tissue there,” she said. “We know how to diagnose reflux disease, but we don’t know how to diagnose microaspiration, which is defined as subclinical aspiration of small droplets of gastric contents. Reflux is a risk factor for the condition of microaspiration, but it is not a perfect surrogate. Not everybody with reflux will aspirate. There is a potential role for bronchoalveolar lavage pepsin and/or bile salt as a biomarker of microaspiration, but it is not validated or standardized in IPF yet.”
Reflux becomes pathologic when reflux of stomach contents causes troublesome symptoms and/or complications. “Troublesome” is defined as mild symptoms 2 or more days a week or moderate to severe symptoms more than 1 day a week. Dr. Lee said that chest physicians can diagnose GERD in their IPF patients the same way that gastroenterologists and primary care doctors do: with symptoms, barium swallow, 24-hour pH monitoring, impedance testing, and sometimes endoscopy. The 2015 IPF guidelines recommend that clinicians “use regular antacid treatment for patients with IPF (conditional recommendation, very low confidence in estimates of effect).” It does not extend to surgical treatment with fundoplication. (Am J Resp Crit Care Med. 2015 Jul 15;192[2]: e3-19).
In an effort to measure the relationship between antacid therapy and change in forced vital capacity, Dr. Lee and her associates evaluated IPF patients from placebo arms of the three Idiopathic Pulmonary Fibrosis Clinical Research Network randomized controlled trials. They found that, compared with patients who did not take antacid therapy at baseline, those who did experienced a slower decline in their forced vital capacity over time (Lancet Resp Med. 2013 Jul;1[5]:369-76). However, a more-recent analysis conducted by different investigators examined the placebo arms of three pirfenidone studies and found no significant effect of antacid therapy in IPF patients (Lancet Resp Med. 2016 May;4[5]:381-9). Dr. Lee said that both evaluations differed because they were secondary analyses of previously captured data. “There were also differences in the ways the trials obtained GERD history, medication indication, and dosing of the antacid therapy,” she said. “There were also differences in outcomes and different populations studied.”
Dr. Lee’s current approach to counseling IPF patients with GERD includes discussing lifestyle modifications and PPI therapy – either daily or twice a day dosing, depending on their symptoms. “Lifestyle modifications include weight loss, smoking cessation, raising the head of the bed 6-8 inches, and avoiding foods that cause acid reflux, including chocolate, alcohol, peppermint, and fatty or spicy foods, and avoiding large and late meals,” she said. “In terms of acid suppression therapy with H2 blockers and PPIs [proton pump inhibitors], symptom relief and healing of the esophagus occurs in 85%-90% of patients taking them correctly. This does not alter their risk of having microaspiration.” Laparoscopic antireflux therapy (fundoplication) is indicated only after the failure of medical therapy. “The goal is to correct any hernia and tighten the lower esophageal sphincter,” she said. “Efficacy and symptom relief is reported to be around 95%.”
An NIH-funded trial called Weighing Risks and Benefits of Laparoscopic Anti-Reflux Surgery in Patients with Idiopathic Fibrosis, is ongoing at six centers. Dr. Lee said that some results are expected within the next year. She reported having no financial disclosures.
EXPERT ANALYSIS FROM CHEST 2016
LOS ANGELES – The optimal management of gastroesophageal reflux disease in patients with idiopathic pulmonary fibrosis has yet to be determined, according to Joyce S. Lee, MD.
“We need strong randomized clinical trial data to tell us whether or not medical or surgical treatment of GERD in IPF is indicated,” she said at the annual meeting of the American College of Chest Physicians.
Two proposed hypotheses explain the relationship between reflux and IPF. The first holds that reflux and microaspiration are involved in the pathogenesis of IPF. The second, favored by Dr. Lee, proposes that reflux and microaspiration impact the natural history, either through acute exacerbation, disease progression, or survival. Patients with IPF “have weakening of the lower esophageal sphincter, whether that’s due to the presence of a hiatal hernia, medications, or just aging of the tissue there,” she said. “We know how to diagnose reflux disease, but we don’t know how to diagnose microaspiration, which is defined as subclinical aspiration of small droplets of gastric contents. Reflux is a risk factor for the condition of microaspiration, but it is not a perfect surrogate. Not everybody with reflux will aspirate. There is a potential role for bronchoalveolar lavage pepsin and/or bile salt as a biomarker of microaspiration, but it is not validated or standardized in IPF yet.”
Reflux becomes pathologic when reflux of stomach contents causes troublesome symptoms and/or complications. “Troublesome” is defined as mild symptoms 2 or more days a week or moderate to severe symptoms more than 1 day a week. Dr. Lee said that chest physicians can diagnose GERD in their IPF patients the same way that gastroenterologists and primary care doctors do: with symptoms, barium swallow, 24-hour pH monitoring, impedance testing, and sometimes endoscopy. The 2015 IPF guidelines recommend that clinicians “use regular antacid treatment for patients with IPF (conditional recommendation, very low confidence in estimates of effect).” It does not extend to surgical treatment with fundoplication. (Am J Resp Crit Care Med. 2015 Jul 15;192[2]: e3-19).
In an effort to measure the relationship between antacid therapy and change in forced vital capacity, Dr. Lee and her associates evaluated IPF patients from placebo arms of the three Idiopathic Pulmonary Fibrosis Clinical Research Network randomized controlled trials. They found that, compared with patients who did not take antacid therapy at baseline, those who did experienced a slower decline in their forced vital capacity over time (Lancet Resp Med. 2013 Jul;1[5]:369-76). However, a more-recent analysis conducted by different investigators examined the placebo arms of three pirfenidone studies and found no significant effect of antacid therapy in IPF patients (Lancet Resp Med. 2016 May;4[5]:381-9). Dr. Lee said that both evaluations differed because they were secondary analyses of previously captured data. “There were also differences in the ways the trials obtained GERD history, medication indication, and dosing of the antacid therapy,” she said. “There were also differences in outcomes and different populations studied.”
Dr. Lee’s current approach to counseling IPF patients with GERD includes discussing lifestyle modifications and PPI therapy – either daily or twice a day dosing, depending on their symptoms. “Lifestyle modifications include weight loss, smoking cessation, raising the head of the bed 6-8 inches, and avoiding foods that cause acid reflux, including chocolate, alcohol, peppermint, and fatty or spicy foods, and avoiding large and late meals,” she said. “In terms of acid suppression therapy with H2 blockers and PPIs [proton pump inhibitors], symptom relief and healing of the esophagus occurs in 85%-90% of patients taking them correctly. This does not alter their risk of having microaspiration.” Laparoscopic antireflux therapy (fundoplication) is indicated only after the failure of medical therapy. “The goal is to correct any hernia and tighten the lower esophageal sphincter,” she said. “Efficacy and symptom relief is reported to be around 95%.”
An NIH-funded trial called Weighing Risks and Benefits of Laparoscopic Anti-Reflux Surgery in Patients with Idiopathic Fibrosis, is ongoing at six centers. Dr. Lee said that some results are expected within the next year. She reported having no financial disclosures.
EXPERT ANALYSIS FROM CHEST 2016
LOS ANGELES – The optimal management of gastroesophageal reflux disease in patients with idiopathic pulmonary fibrosis has yet to be determined, according to Joyce S. Lee, MD.
“We need strong randomized clinical trial data to tell us whether or not medical or surgical treatment of GERD in IPF is indicated,” she said at the annual meeting of the American College of Chest Physicians.
Two proposed hypotheses explain the relationship between reflux and IPF. The first holds that reflux and microaspiration are involved in the pathogenesis of IPF. The second, favored by Dr. Lee, proposes that reflux and microaspiration impact the natural history, either through acute exacerbation, disease progression, or survival. Patients with IPF “have weakening of the lower esophageal sphincter, whether that’s due to the presence of a hiatal hernia, medications, or just aging of the tissue there,” she said. “We know how to diagnose reflux disease, but we don’t know how to diagnose microaspiration, which is defined as subclinical aspiration of small droplets of gastric contents. Reflux is a risk factor for the condition of microaspiration, but it is not a perfect surrogate. Not everybody with reflux will aspirate. There is a potential role for bronchoalveolar lavage pepsin and/or bile salt as a biomarker of microaspiration, but it is not validated or standardized in IPF yet.”
Reflux becomes pathologic when reflux of stomach contents causes troublesome symptoms and/or complications. “Troublesome” is defined as mild symptoms 2 or more days a week or moderate to severe symptoms more than 1 day a week. Dr. Lee said that chest physicians can diagnose GERD in their IPF patients the same way that gastroenterologists and primary care doctors do: with symptoms, barium swallow, 24-hour pH monitoring, impedance testing, and sometimes endoscopy. The 2015 IPF guidelines recommend that clinicians “use regular antacid treatment for patients with IPF (conditional recommendation, very low confidence in estimates of effect).” It does not extend to surgical treatment with fundoplication. (Am J Resp Crit Care Med. 2015 Jul 15;192[2]: e3-19).
In an effort to measure the relationship between antacid therapy and change in forced vital capacity, Dr. Lee and her associates evaluated IPF patients from placebo arms of the three Idiopathic Pulmonary Fibrosis Clinical Research Network randomized controlled trials. They found that, compared with patients who did not take antacid therapy at baseline, those who did experienced a slower decline in their forced vital capacity over time (Lancet Resp Med. 2013 Jul;1[5]:369-76). However, a more-recent analysis conducted by different investigators examined the placebo arms of three pirfenidone studies and found no significant effect of antacid therapy in IPF patients (Lancet Resp Med. 2016 May;4[5]:381-9). Dr. Lee said that both evaluations differed because they were secondary analyses of previously captured data. “There were also differences in the ways the trials obtained GERD history, medication indication, and dosing of the antacid therapy,” she said. “There were also differences in outcomes and different populations studied.”
Dr. Lee’s current approach to counseling IPF patients with GERD includes discussing lifestyle modifications and PPI therapy – either daily or twice a day dosing, depending on their symptoms. “Lifestyle modifications include weight loss, smoking cessation, raising the head of the bed 6-8 inches, and avoiding foods that cause acid reflux, including chocolate, alcohol, peppermint, and fatty or spicy foods, and avoiding large and late meals,” she said. “In terms of acid suppression therapy with H2 blockers and PPIs [proton pump inhibitors], symptom relief and healing of the esophagus occurs in 85%-90% of patients taking them correctly. This does not alter their risk of having microaspiration.” Laparoscopic antireflux therapy (fundoplication) is indicated only after the failure of medical therapy. “The goal is to correct any hernia and tighten the lower esophageal sphincter,” she said. “Efficacy and symptom relief is reported to be around 95%.”
An NIH-funded trial called Weighing Risks and Benefits of Laparoscopic Anti-Reflux Surgery in Patients with Idiopathic Fibrosis, is ongoing at six centers. Dr. Lee said that some results are expected within the next year. She reported having no financial disclosures.
Amantadine Hydrochloride Reduces Levodopa-Induced Dyskinesia in Patients With Parkinson’s Disease
PORTLAND, OR—Amantadine hydrochloride extended-release capsules, compared with placebo, result in a statistically significant and clinically meaningful improvement in levodopa-induced dyskinesia in patients with Parkinson’s disease, according to phase III trial results presented at the Fourth World Parkinson Congress. The drug also reduces daily off time and is generally well tolerated, researchers said.
Amantadine hydrochloride extended-release capsules, known as ADS-5102, are being developed by Adamas Pharmaceuticals with the aim of improving the pharmacokinetic profile of immediate-release amantadine.
Rajesh Pahwa, MD, Professor of Neurology at University of Kansas Medical Center in Kansas City, and colleagues reported efficacy and safety results from the EASE LID 3 trial, one of three phase III trials of the drug.
EASE LID 3 was a randomized, double-blind, placebo-controlled study conducted at 39 sites in the United States and Europe. Seventy-seven patients with Parkinson’s disease were randomized to receive 340 mg of amantadine hydrochloride or placebo once daily at bedtime for the treatment of levodopa-induced dyskinesia. Participants had an average age of 64.8, 52% were men, and they had been diagnosed with Parkinson’s disease for an average of 10.6 years. They had received levodopa treatment for an average of 8.1 years. Patients’ mean duration of levodopa-induced dyskinesia was 3.9 years.
Treatment Improved Outcomes
The primary efficacy analysis compared the least square mean change from baseline to week 12 in Unified Dyskinesia Rating Scale total score in the ADS-5102 group with that in the placebo group. Key secondary efficacy analyses compared the least square mean change from baseline to week 12 in on time without troublesome dyskinesia and off time, as recorded in participants’ home diaries.
Thirty-eight patients were randomized to receive ADS-5102 and 39 patients were randomized to receive placebo. In the ADS-5102 group, the observed mean Unified Dyskinesia Rating Scale total score from baseline to week 12 decreased by 46%, compared with a 16% reduction in the placebo group. At 12 weeks, daily on time without troublesome dyskinesia increased by 4.0 hours in the ADS-5102 group and by 2.1 hours in the placebo group. Daily off time decreased by 0.5 hours in the ADS-5102 group and increased by 0.6 hours in the placebo group.
Adverse Events
Four patients, all in the ADS-5102 group, experienced serious adverse events. In one patient, the serious adverse event was considered related to the study drug (ie, constipation and urinary retention). The patient completed study treatment and did not discontinue participation in the trial.
Seven patients in the ADS-5102 group (19%) versus three patients in the placebo group (8%) discontinued treatment due to adverse events. In the ADS-5102 group, the most frequent adverse events (ie, they occurred in more than two patients) were dry mouth, nausea, decreased appetite, insomnia, orthostatic hypotension, constipation, fall, and hallucination.
“ADS-5102 resulted in statistically significant and clinically meaningful improvement in levodopa-induced dyskinesia, confirming results from earlier controlled clinical trials,” the researchers concluded.
Investigators are conducting an open-label safety study of ADS-5102 that includes patients from the phase III trials as well as patients with levodopa-induced dyskinesia who have undergone deep brain stimulation. Adamas also is investigating ADS-5102 for use in patients with multiple sclerosis with walking impairment.
—Jake Remaly
PORTLAND, OR—Amantadine hydrochloride extended-release capsules, compared with placebo, result in a statistically significant and clinically meaningful improvement in levodopa-induced dyskinesia in patients with Parkinson’s disease, according to phase III trial results presented at the Fourth World Parkinson Congress. The drug also reduces daily off time and is generally well tolerated, researchers said.
Amantadine hydrochloride extended-release capsules, known as ADS-5102, are being developed by Adamas Pharmaceuticals with the aim of improving the pharmacokinetic profile of immediate-release amantadine.
Rajesh Pahwa, MD, Professor of Neurology at University of Kansas Medical Center in Kansas City, and colleagues reported efficacy and safety results from the EASE LID 3 trial, one of three phase III trials of the drug.
EASE LID 3 was a randomized, double-blind, placebo-controlled study conducted at 39 sites in the United States and Europe. Seventy-seven patients with Parkinson’s disease were randomized to receive 340 mg of amantadine hydrochloride or placebo once daily at bedtime for the treatment of levodopa-induced dyskinesia. Participants had an average age of 64.8, 52% were men, and they had been diagnosed with Parkinson’s disease for an average of 10.6 years. They had received levodopa treatment for an average of 8.1 years. Patients’ mean duration of levodopa-induced dyskinesia was 3.9 years.
Treatment Improved Outcomes
The primary efficacy analysis compared the least square mean change from baseline to week 12 in Unified Dyskinesia Rating Scale total score in the ADS-5102 group with that in the placebo group. Key secondary efficacy analyses compared the least square mean change from baseline to week 12 in on time without troublesome dyskinesia and off time, as recorded in participants’ home diaries.
Thirty-eight patients were randomized to receive ADS-5102 and 39 patients were randomized to receive placebo. In the ADS-5102 group, the observed mean Unified Dyskinesia Rating Scale total score from baseline to week 12 decreased by 46%, compared with a 16% reduction in the placebo group. At 12 weeks, daily on time without troublesome dyskinesia increased by 4.0 hours in the ADS-5102 group and by 2.1 hours in the placebo group. Daily off time decreased by 0.5 hours in the ADS-5102 group and increased by 0.6 hours in the placebo group.
Adverse Events
Four patients, all in the ADS-5102 group, experienced serious adverse events. In one patient, the serious adverse event was considered related to the study drug (ie, constipation and urinary retention). The patient completed study treatment and did not discontinue participation in the trial.
Seven patients in the ADS-5102 group (19%) versus three patients in the placebo group (8%) discontinued treatment due to adverse events. In the ADS-5102 group, the most frequent adverse events (ie, they occurred in more than two patients) were dry mouth, nausea, decreased appetite, insomnia, orthostatic hypotension, constipation, fall, and hallucination.
“ADS-5102 resulted in statistically significant and clinically meaningful improvement in levodopa-induced dyskinesia, confirming results from earlier controlled clinical trials,” the researchers concluded.
Investigators are conducting an open-label safety study of ADS-5102 that includes patients from the phase III trials as well as patients with levodopa-induced dyskinesia who have undergone deep brain stimulation. Adamas also is investigating ADS-5102 for use in patients with multiple sclerosis with walking impairment.
—Jake Remaly
PORTLAND, OR—Amantadine hydrochloride extended-release capsules, compared with placebo, result in a statistically significant and clinically meaningful improvement in levodopa-induced dyskinesia in patients with Parkinson’s disease, according to phase III trial results presented at the Fourth World Parkinson Congress. The drug also reduces daily off time and is generally well tolerated, researchers said.
Amantadine hydrochloride extended-release capsules, known as ADS-5102, are being developed by Adamas Pharmaceuticals with the aim of improving the pharmacokinetic profile of immediate-release amantadine.
Rajesh Pahwa, MD, Professor of Neurology at University of Kansas Medical Center in Kansas City, and colleagues reported efficacy and safety results from the EASE LID 3 trial, one of three phase III trials of the drug.
EASE LID 3 was a randomized, double-blind, placebo-controlled study conducted at 39 sites in the United States and Europe. Seventy-seven patients with Parkinson’s disease were randomized to receive 340 mg of amantadine hydrochloride or placebo once daily at bedtime for the treatment of levodopa-induced dyskinesia. Participants had an average age of 64.8, 52% were men, and they had been diagnosed with Parkinson’s disease for an average of 10.6 years. They had received levodopa treatment for an average of 8.1 years. Patients’ mean duration of levodopa-induced dyskinesia was 3.9 years.
Treatment Improved Outcomes
The primary efficacy analysis compared the least square mean change from baseline to week 12 in Unified Dyskinesia Rating Scale total score in the ADS-5102 group with that in the placebo group. Key secondary efficacy analyses compared the least square mean change from baseline to week 12 in on time without troublesome dyskinesia and off time, as recorded in participants’ home diaries.
Thirty-eight patients were randomized to receive ADS-5102 and 39 patients were randomized to receive placebo. In the ADS-5102 group, the observed mean Unified Dyskinesia Rating Scale total score from baseline to week 12 decreased by 46%, compared with a 16% reduction in the placebo group. At 12 weeks, daily on time without troublesome dyskinesia increased by 4.0 hours in the ADS-5102 group and by 2.1 hours in the placebo group. Daily off time decreased by 0.5 hours in the ADS-5102 group and increased by 0.6 hours in the placebo group.
Adverse Events
Four patients, all in the ADS-5102 group, experienced serious adverse events. In one patient, the serious adverse event was considered related to the study drug (ie, constipation and urinary retention). The patient completed study treatment and did not discontinue participation in the trial.
Seven patients in the ADS-5102 group (19%) versus three patients in the placebo group (8%) discontinued treatment due to adverse events. In the ADS-5102 group, the most frequent adverse events (ie, they occurred in more than two patients) were dry mouth, nausea, decreased appetite, insomnia, orthostatic hypotension, constipation, fall, and hallucination.
“ADS-5102 resulted in statistically significant and clinically meaningful improvement in levodopa-induced dyskinesia, confirming results from earlier controlled clinical trials,” the researchers concluded.
Investigators are conducting an open-label safety study of ADS-5102 that includes patients from the phase III trials as well as patients with levodopa-induced dyskinesia who have undergone deep brain stimulation. Adamas also is investigating ADS-5102 for use in patients with multiple sclerosis with walking impairment.
—Jake Remaly
Ricardo Jorge, MD
High-Intensity Exercise May Be Feasible in Patients With Parkinson’s Disease
PORTLAND, OR—High-intensity exercise is feasible and safe in patients with Parkinson's disease, according to trial results presented at the Fourth World Parkinson Congress. An eight-week high-intensity exercise and fall-prevention boot camp was well attended, and participants tolerated high-intensity aerobic, strength, and balance training exercises, researchers said.
Most contemporary exercise programs for people with Parkinson's disease are low to moderate in intensity. Recent studies, however, suggest that older adults can safely tolerate high-intensity exercise programs and attain more meaningful benefits. "The optimal parameters of exercise for Parkinson's disease have not been thoroughly explored," said Merrill R. Landers, PT, DPT, PhD, OCS, Professor of Physical Therapy, and James Navalta, PhD, Associate Professor of Kinesiology, both at the University of Nevada in Las Vegas.
To test the feasibility and safety of a high-intensity exercise and fall-prevention boot camp in people with Parkinson's disease, Drs. Landers and Navalta conducted a phase II, pragmatic, randomized clinical trial.
Twenty-seven participants were included in the study. Fourteen patients were randomized to the high-intensity exercise program, and 13 patients were randomized to a low-intensity control program (ie, Fitness Counts Exercise Program). Physiotherapists supervised the exercise programs at community exercise gyms.
Patients had an average age of about 64 and disease duration of nearly five years. Nineteen men and eight women enrolled in the study. Most patients were Hoehn and Yahr stage 2.
The high-intensity boot camp sessions consisted of 30 minutes of aerobic exercise (70% of heart rate maximum), 30 minutes of strengthening (50% to 80% of one-repetition maximum), 15 minutes of balance training, and 15 minutes of active rest and stretching. The control sessions consisted of 15 minutes of aerobic exercise (60% of heart rate maximum), 15 minutes of strengthening (less than 50% of one-repetition maximum), 10 minutes of balance training, 10 minutes of rest, and 10 minutes of stretching. There was not a significant difference in the rate of injuries, falls, or exercise side effects between groups. Adverse events were similar in the two arms. Compared with low-intensity exercise, high-intensity exercise produced greater improvements in balance, physical activity, parkinsonian symptoms, endurance, fatigue, and bone health.
"These results warrant further investigation in a large-scale comparative effectiveness trial," the researchers concluded.
—Jake Remaly
PORTLAND, OR—High-intensity exercise is feasible and safe in patients with Parkinson's disease, according to trial results presented at the Fourth World Parkinson Congress. An eight-week high-intensity exercise and fall-prevention boot camp was well attended, and participants tolerated high-intensity aerobic, strength, and balance training exercises, researchers said.
Most contemporary exercise programs for people with Parkinson's disease are low to moderate in intensity. Recent studies, however, suggest that older adults can safely tolerate high-intensity exercise programs and attain more meaningful benefits. "The optimal parameters of exercise for Parkinson's disease have not been thoroughly explored," said Merrill R. Landers, PT, DPT, PhD, OCS, Professor of Physical Therapy, and James Navalta, PhD, Associate Professor of Kinesiology, both at the University of Nevada in Las Vegas.
To test the feasibility and safety of a high-intensity exercise and fall-prevention boot camp in people with Parkinson's disease, Drs. Landers and Navalta conducted a phase II, pragmatic, randomized clinical trial.
Twenty-seven participants were included in the study. Fourteen patients were randomized to the high-intensity exercise program, and 13 patients were randomized to a low-intensity control program (ie, Fitness Counts Exercise Program). Physiotherapists supervised the exercise programs at community exercise gyms.
Patients had an average age of about 64 and disease duration of nearly five years. Nineteen men and eight women enrolled in the study. Most patients were Hoehn and Yahr stage 2.
The high-intensity boot camp sessions consisted of 30 minutes of aerobic exercise (70% of heart rate maximum), 30 minutes of strengthening (50% to 80% of one-repetition maximum), 15 minutes of balance training, and 15 minutes of active rest and stretching. The control sessions consisted of 15 minutes of aerobic exercise (60% of heart rate maximum), 15 minutes of strengthening (less than 50% of one-repetition maximum), 10 minutes of balance training, 10 minutes of rest, and 10 minutes of stretching. There was not a significant difference in the rate of injuries, falls, or exercise side effects between groups. Adverse events were similar in the two arms. Compared with low-intensity exercise, high-intensity exercise produced greater improvements in balance, physical activity, parkinsonian symptoms, endurance, fatigue, and bone health.
"These results warrant further investigation in a large-scale comparative effectiveness trial," the researchers concluded.
—Jake Remaly
PORTLAND, OR—High-intensity exercise is feasible and safe in patients with Parkinson's disease, according to trial results presented at the Fourth World Parkinson Congress. An eight-week high-intensity exercise and fall-prevention boot camp was well attended, and participants tolerated high-intensity aerobic, strength, and balance training exercises, researchers said.
Most contemporary exercise programs for people with Parkinson's disease are low to moderate in intensity. Recent studies, however, suggest that older adults can safely tolerate high-intensity exercise programs and attain more meaningful benefits. "The optimal parameters of exercise for Parkinson's disease have not been thoroughly explored," said Merrill R. Landers, PT, DPT, PhD, OCS, Professor of Physical Therapy, and James Navalta, PhD, Associate Professor of Kinesiology, both at the University of Nevada in Las Vegas.
To test the feasibility and safety of a high-intensity exercise and fall-prevention boot camp in people with Parkinson's disease, Drs. Landers and Navalta conducted a phase II, pragmatic, randomized clinical trial.
Twenty-seven participants were included in the study. Fourteen patients were randomized to the high-intensity exercise program, and 13 patients were randomized to a low-intensity control program (ie, Fitness Counts Exercise Program). Physiotherapists supervised the exercise programs at community exercise gyms.
Patients had an average age of about 64 and disease duration of nearly five years. Nineteen men and eight women enrolled in the study. Most patients were Hoehn and Yahr stage 2.
The high-intensity boot camp sessions consisted of 30 minutes of aerobic exercise (70% of heart rate maximum), 30 minutes of strengthening (50% to 80% of one-repetition maximum), 15 minutes of balance training, and 15 minutes of active rest and stretching. The control sessions consisted of 15 minutes of aerobic exercise (60% of heart rate maximum), 15 minutes of strengthening (less than 50% of one-repetition maximum), 10 minutes of balance training, 10 minutes of rest, and 10 minutes of stretching. There was not a significant difference in the rate of injuries, falls, or exercise side effects between groups. Adverse events were similar in the two arms. Compared with low-intensity exercise, high-intensity exercise produced greater improvements in balance, physical activity, parkinsonian symptoms, endurance, fatigue, and bone health.
"These results warrant further investigation in a large-scale comparative effectiveness trial," the researchers concluded.
—Jake Remaly
How Do Autonomic Symptoms Affect Patients With Early Parkinson’s Disease?
PORTLAND, OR—Autonomic symptoms are present in a majority of patients with early Parkinson's disease, and symptoms correlate with markers of disease severity and impaired quality of life, according to research presented at the Fourth World Parkinson Congress.
Although autonomic dysfunction is common in the later stages of Parkinson's disease, less is known about autonomic symptom presence and severity in early stages of Parkinson's disease. Naveed Malek, MD, Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, in Glasgow, and colleagues conducted a study to explore the prevalence, range, and severity of autonomic symptoms in a cohort of patients who had been diagnosed with Parkinson's disease in the preceding 3.5 years.
The researchers analyzed detailed patient-reported symptoms of autonomic dysfunction that were assessed in the multicenter United Kingdom Tracking Parkinson's study using the Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT).
The researchers assessed the relationship between baseline SCOPA-AUT score and baseline motor, nonmotor, and quality of life scores. The researchers adjusted for sex, age, and disease duration differences across groups.
A total of 1,738 patients (65.1% male, mean age 67.6) were included in the main analysis. Patients had a mean disease duration of 1.3 years and mean Movement Disorder Society Unified Parkinson's Disease Rating Scale motor score of 22.5. Hoehn and Yahr was stage 1 or 1.5 in 855 cases (49.2%), stage 2 or 2.5 in 783 cases (45.1%), and stage 3 or higher in 100 cases (5.8%).
Autonomic severity by SCOPA-AUT score increased significantly across the motor severity stages, from 10.7 for Hoehn and Yahr stages 1 and 1.5, to 12.7 for Hoehn and Yahr stages 2 and 2.5, and to 13.5 for Hoehn and Yahr stages 3 and higher. Urinary, bowel, and sexual dysfunctions were the most commonly reported autonomic symptoms. The results were between those previously reported in controls and in patients with Parkinson's disease at a mean duration of 10 years. Positive associations were present between autonomic severity and depression, sleep disturbance, and postural instability motor subtype.
"Our study highlights the extent to which we may expect to see autonomic features in early Parkinson's disease, and the relationship between autonomic features and diagnostic consideration, which is important in the balanced diagnostic judgment approach emphasized in recent consensus guidelines," Dr. Malek concluded.
—Jake Remaly
PORTLAND, OR—Autonomic symptoms are present in a majority of patients with early Parkinson's disease, and symptoms correlate with markers of disease severity and impaired quality of life, according to research presented at the Fourth World Parkinson Congress.
Although autonomic dysfunction is common in the later stages of Parkinson's disease, less is known about autonomic symptom presence and severity in early stages of Parkinson's disease. Naveed Malek, MD, Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, in Glasgow, and colleagues conducted a study to explore the prevalence, range, and severity of autonomic symptoms in a cohort of patients who had been diagnosed with Parkinson's disease in the preceding 3.5 years.
The researchers analyzed detailed patient-reported symptoms of autonomic dysfunction that were assessed in the multicenter United Kingdom Tracking Parkinson's study using the Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT).
The researchers assessed the relationship between baseline SCOPA-AUT score and baseline motor, nonmotor, and quality of life scores. The researchers adjusted for sex, age, and disease duration differences across groups.
A total of 1,738 patients (65.1% male, mean age 67.6) were included in the main analysis. Patients had a mean disease duration of 1.3 years and mean Movement Disorder Society Unified Parkinson's Disease Rating Scale motor score of 22.5. Hoehn and Yahr was stage 1 or 1.5 in 855 cases (49.2%), stage 2 or 2.5 in 783 cases (45.1%), and stage 3 or higher in 100 cases (5.8%).
Autonomic severity by SCOPA-AUT score increased significantly across the motor severity stages, from 10.7 for Hoehn and Yahr stages 1 and 1.5, to 12.7 for Hoehn and Yahr stages 2 and 2.5, and to 13.5 for Hoehn and Yahr stages 3 and higher. Urinary, bowel, and sexual dysfunctions were the most commonly reported autonomic symptoms. The results were between those previously reported in controls and in patients with Parkinson's disease at a mean duration of 10 years. Positive associations were present between autonomic severity and depression, sleep disturbance, and postural instability motor subtype.
"Our study highlights the extent to which we may expect to see autonomic features in early Parkinson's disease, and the relationship between autonomic features and diagnostic consideration, which is important in the balanced diagnostic judgment approach emphasized in recent consensus guidelines," Dr. Malek concluded.
—Jake Remaly
PORTLAND, OR—Autonomic symptoms are present in a majority of patients with early Parkinson's disease, and symptoms correlate with markers of disease severity and impaired quality of life, according to research presented at the Fourth World Parkinson Congress.
Although autonomic dysfunction is common in the later stages of Parkinson's disease, less is known about autonomic symptom presence and severity in early stages of Parkinson's disease. Naveed Malek, MD, Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, in Glasgow, and colleagues conducted a study to explore the prevalence, range, and severity of autonomic symptoms in a cohort of patients who had been diagnosed with Parkinson's disease in the preceding 3.5 years.
The researchers analyzed detailed patient-reported symptoms of autonomic dysfunction that were assessed in the multicenter United Kingdom Tracking Parkinson's study using the Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT).
The researchers assessed the relationship between baseline SCOPA-AUT score and baseline motor, nonmotor, and quality of life scores. The researchers adjusted for sex, age, and disease duration differences across groups.
A total of 1,738 patients (65.1% male, mean age 67.6) were included in the main analysis. Patients had a mean disease duration of 1.3 years and mean Movement Disorder Society Unified Parkinson's Disease Rating Scale motor score of 22.5. Hoehn and Yahr was stage 1 or 1.5 in 855 cases (49.2%), stage 2 or 2.5 in 783 cases (45.1%), and stage 3 or higher in 100 cases (5.8%).
Autonomic severity by SCOPA-AUT score increased significantly across the motor severity stages, from 10.7 for Hoehn and Yahr stages 1 and 1.5, to 12.7 for Hoehn and Yahr stages 2 and 2.5, and to 13.5 for Hoehn and Yahr stages 3 and higher. Urinary, bowel, and sexual dysfunctions were the most commonly reported autonomic symptoms. The results were between those previously reported in controls and in patients with Parkinson's disease at a mean duration of 10 years. Positive associations were present between autonomic severity and depression, sleep disturbance, and postural instability motor subtype.
"Our study highlights the extent to which we may expect to see autonomic features in early Parkinson's disease, and the relationship between autonomic features and diagnostic consideration, which is important in the balanced diagnostic judgment approach emphasized in recent consensus guidelines," Dr. Malek concluded.
—Jake Remaly
Common Genetic Variants Associated With Cognitive Impairment in Parkinson’s Disease
PORTLAND, OR—A large-scale analysis has identified several new putative susceptibility genes that may affect cognitive impairment in Parkinson's disease, researchers reported at the Fourth World Parkinson Congress.
Cognitive impairment is a common and disabling nonmotor feature of Parkinson's disease. Identifying genetic variants that influence cognitive deficits could clarify the pathophysiology of cognitive impairment, help identify potential therapies, and be useful when considering patient prognosis, said Ignacio F. Mata, PhD, Research Biologist at the Veterans Affairs Puget Sound Health Care System and Acting Assistant Professor of Neurology at the University of Washington in Seattle. Rate of cognitive decline in Parkinson's disease varies. "We are trying to understand why," Dr. Mata said.
Dr. Mata and colleagues conducted a genome-wide exploratory analysis of genetic risk factors for cognitive impairment in a multisite cohort. The investigators genotyped 1,105 patients from the Parkinson's Disease Cognitive Genetics Consortium for 249,336 variants using the NeuroX array, which includes variants that have been linked to neurologic diseases.
Participants completed tests of learning and memory (Hopkins Verbal Learning Test-Revised), working memory and executive function (Letter-Number Sequencing and Trail Making Test Parts A and B), language processing (semantic and phonemic verbal fluency), visuospatial abilities (Benton Judgment of Line Orientation), and global cognitive function (Montreal Cognitive Assessment).
The researchers used linear regression to test for associations between common variants and cognitive performance, with adjustment for important covariates (eg, age, sex, disease duration, and years of education). They analyzed rare variants using the optimal unified sequence kernel association test.
Participants' mean age was 68.8, 67.8% were male, and 17.5% had dementia. Mean disease duration was 8.4 years. Participants had 15.5 years of education on average.
The researchers identified 17 common genetic variants associated with cognitive performance. Three variants were associated with total recall, and two variants were associated with delayed recall on the revised Hopkins Verbal Learning Test. Five variants were associated with performance on the Trail Making Test, and seven variants were associated with performance on the Benton Judgment of Line Orientation test.
The researchers aim to perform a similar analysis using longitudinal data. They also plan to see if these findings can be replicated in an independent cohort.
—Jake Remaly
PORTLAND, OR—A large-scale analysis has identified several new putative susceptibility genes that may affect cognitive impairment in Parkinson's disease, researchers reported at the Fourth World Parkinson Congress.
Cognitive impairment is a common and disabling nonmotor feature of Parkinson's disease. Identifying genetic variants that influence cognitive deficits could clarify the pathophysiology of cognitive impairment, help identify potential therapies, and be useful when considering patient prognosis, said Ignacio F. Mata, PhD, Research Biologist at the Veterans Affairs Puget Sound Health Care System and Acting Assistant Professor of Neurology at the University of Washington in Seattle. Rate of cognitive decline in Parkinson's disease varies. "We are trying to understand why," Dr. Mata said.
Dr. Mata and colleagues conducted a genome-wide exploratory analysis of genetic risk factors for cognitive impairment in a multisite cohort. The investigators genotyped 1,105 patients from the Parkinson's Disease Cognitive Genetics Consortium for 249,336 variants using the NeuroX array, which includes variants that have been linked to neurologic diseases.
Participants completed tests of learning and memory (Hopkins Verbal Learning Test-Revised), working memory and executive function (Letter-Number Sequencing and Trail Making Test Parts A and B), language processing (semantic and phonemic verbal fluency), visuospatial abilities (Benton Judgment of Line Orientation), and global cognitive function (Montreal Cognitive Assessment).
The researchers used linear regression to test for associations between common variants and cognitive performance, with adjustment for important covariates (eg, age, sex, disease duration, and years of education). They analyzed rare variants using the optimal unified sequence kernel association test.
Participants' mean age was 68.8, 67.8% were male, and 17.5% had dementia. Mean disease duration was 8.4 years. Participants had 15.5 years of education on average.
The researchers identified 17 common genetic variants associated with cognitive performance. Three variants were associated with total recall, and two variants were associated with delayed recall on the revised Hopkins Verbal Learning Test. Five variants were associated with performance on the Trail Making Test, and seven variants were associated with performance on the Benton Judgment of Line Orientation test.
The researchers aim to perform a similar analysis using longitudinal data. They also plan to see if these findings can be replicated in an independent cohort.
—Jake Remaly
PORTLAND, OR—A large-scale analysis has identified several new putative susceptibility genes that may affect cognitive impairment in Parkinson's disease, researchers reported at the Fourth World Parkinson Congress.
Cognitive impairment is a common and disabling nonmotor feature of Parkinson's disease. Identifying genetic variants that influence cognitive deficits could clarify the pathophysiology of cognitive impairment, help identify potential therapies, and be useful when considering patient prognosis, said Ignacio F. Mata, PhD, Research Biologist at the Veterans Affairs Puget Sound Health Care System and Acting Assistant Professor of Neurology at the University of Washington in Seattle. Rate of cognitive decline in Parkinson's disease varies. "We are trying to understand why," Dr. Mata said.
Dr. Mata and colleagues conducted a genome-wide exploratory analysis of genetic risk factors for cognitive impairment in a multisite cohort. The investigators genotyped 1,105 patients from the Parkinson's Disease Cognitive Genetics Consortium for 249,336 variants using the NeuroX array, which includes variants that have been linked to neurologic diseases.
Participants completed tests of learning and memory (Hopkins Verbal Learning Test-Revised), working memory and executive function (Letter-Number Sequencing and Trail Making Test Parts A and B), language processing (semantic and phonemic verbal fluency), visuospatial abilities (Benton Judgment of Line Orientation), and global cognitive function (Montreal Cognitive Assessment).
The researchers used linear regression to test for associations between common variants and cognitive performance, with adjustment for important covariates (eg, age, sex, disease duration, and years of education). They analyzed rare variants using the optimal unified sequence kernel association test.
Participants' mean age was 68.8, 67.8% were male, and 17.5% had dementia. Mean disease duration was 8.4 years. Participants had 15.5 years of education on average.
The researchers identified 17 common genetic variants associated with cognitive performance. Three variants were associated with total recall, and two variants were associated with delayed recall on the revised Hopkins Verbal Learning Test. Five variants were associated with performance on the Trail Making Test, and seven variants were associated with performance on the Benton Judgment of Line Orientation test.
The researchers aim to perform a similar analysis using longitudinal data. They also plan to see if these findings can be replicated in an independent cohort.
—Jake Remaly
New research on health-related behaviors of sexual minority youth
The Centers for Disease Control and Prevention released results from the first nationally representative study on health risk behaviors of gay, lesbian, and bisexual (GLB) high school students in August 2016.
These data were collected through the Youth Risk Behavior Survey (YRBS) questionnaire. The YRBS questionnaire was developed in 1990 as a way to monitor health-related behaviors that contribute to the leading causes of mortality and morbidity in youth and young adults. Areas covered by the survey include behaviors related to unintentional injuries and violence, tobacco use, alcohol and other drug use, sexual behaviors, dietary behaviors, and physical activity. Data are collected every 2 years through national, state, territorial, tribal government, and local school-based surveys of representative samples of 9th-12th grade students.
For the study, sexual minority youth were defined as those who identified as GLB; those who reported sexual contact with members of the same sex only; and those who reported sexual contact with members of both sexes. It is important to note that the YRBS is a school-based survey and does not include youth who do not attend school, for example, homeless and runaway youth.
Exploring and identifying disparities in health behaviors that affect sexual minorities can help us as providers to better target screenings for these health behaviors at the individual level. At the population level, it is important to continue to explore why these differences exist and to continue to develop interventions that help address these differences, while educating families and communities about how to support all of their youth. It is important to note that the majority of sexual minority youth live healthy live; however, this study shows that sexual minority youth do have a higher prevalence of certain health risk behaviors, likely leading to the health disparities we see in this population. Select findings of this study are summarized in the accompanying table.
Continued study is needed to understand the health disparities that occur in sexual minority populations. In October, the National Institutes of Health designated sexual and gender minorities as a specific health disparity population for NIH research. This term encompasses lesbian, gay, bisexual, and transgender individuals as well as any individuals whose sexual identity or gender identity does not align with traditional norms. This hopefully will lead to a growing body of evidence to help all of us learn about the spectrum of sexual and gender identity and better help sexual and gender minority youth reach their full potential.
For more information about the YRBS and the report on health related behaviors in sexual minority youth visit this link:
Selected questionnaire results
Sexual identity
• 88.8% of students identified as heterosexual.
• 6.0% identified as bisexual.
• 3.2% were not sure.
• 2.0% identified as gay or lesbian.
Sexual behaviors
• 48% had had sexual contact with the opposite sex only.
• 4.6% had sexual contact with both sexes.
• 1.7% had had sexual contact with the same sex only.
• 45.7% had no sexual contact.
Mental health
Percent of students who reported making a suicide plan in the 12 months preceding the survey:
• 11.9% of heterosexual students.
• 27.9% of students not sure of sexual identity.
• 38.2% of gay, lesbian, bisexual (GLB) students.
Percent of students who attempted suicide in the 12 months preceding the survey:
• 6.4% of heterosexual students.
• 13.7% of students not sure of sexual identity.
• 29.4% of GLB students.
Sexual Behaviors
First sex before the age of 13:
• 3.4% of heterosexual students.
• 8.8% of students not sure of their sexual identity.
• 7.3% of GLB students.
Drank alcohol or used drugs before last sex:
• 20.0% of heterosexual students.
• 44.5% of students not sure of their sexual identity.
• 22.4% of GLB students.
Tested for HIV:
• 9.3% of heterosexual students.
• 12.8% of students not sure of their sexual identity.
• 18.2% of GLB students.
Substance use
Currently smoking cigarettes daily:
• 1.9% of heterosexual students.
• 7.0% of students not sure of their sexual identity.
• 4.0% of GLB students.
Current alcohol use:
• 32.1% of heterosexual students.
• 34.6% of students not sure of their sexual identity.
• 40.5% of GLB students.
Current marijuana use:
• 20.7% of heterosexual students.
• 26.0% of students not sure of their sexual identity.
• 32.0% of GLB students.
Used hallucinogenic drugs (such as LSD, acid, PCP, angel dust, mescaline, or mushrooms):
• 5.5% of heterosexual students.
• 15.7% of students not sure of their sexual identity.
• 11.5% of GLB students.
Ever used heroin:
• 1.3% of heterosexual students.
• 9.3% of students not sure of their sexual identity.
• 6.0% of GLB students.
Ever took prescription drugs without a doctor’s prescription:
15.5% of heterosexual students.
24.3% of students not sure of their sexual identity.
27.5% of GLB students.
Physical Activity
Did not participate in at least 60 minutes of physical activity on at least 1 day in past week:
• 12.6% of heterosexual students.
• 27.0% of students not sure of their sexual identity.
• 25.7% of GLB students.
Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at the Ohio State University, both in Columbus.
The Centers for Disease Control and Prevention released results from the first nationally representative study on health risk behaviors of gay, lesbian, and bisexual (GLB) high school students in August 2016.
These data were collected through the Youth Risk Behavior Survey (YRBS) questionnaire. The YRBS questionnaire was developed in 1990 as a way to monitor health-related behaviors that contribute to the leading causes of mortality and morbidity in youth and young adults. Areas covered by the survey include behaviors related to unintentional injuries and violence, tobacco use, alcohol and other drug use, sexual behaviors, dietary behaviors, and physical activity. Data are collected every 2 years through national, state, territorial, tribal government, and local school-based surveys of representative samples of 9th-12th grade students.
For the study, sexual minority youth were defined as those who identified as GLB; those who reported sexual contact with members of the same sex only; and those who reported sexual contact with members of both sexes. It is important to note that the YRBS is a school-based survey and does not include youth who do not attend school, for example, homeless and runaway youth.
Exploring and identifying disparities in health behaviors that affect sexual minorities can help us as providers to better target screenings for these health behaviors at the individual level. At the population level, it is important to continue to explore why these differences exist and to continue to develop interventions that help address these differences, while educating families and communities about how to support all of their youth. It is important to note that the majority of sexual minority youth live healthy live; however, this study shows that sexual minority youth do have a higher prevalence of certain health risk behaviors, likely leading to the health disparities we see in this population. Select findings of this study are summarized in the accompanying table.
Continued study is needed to understand the health disparities that occur in sexual minority populations. In October, the National Institutes of Health designated sexual and gender minorities as a specific health disparity population for NIH research. This term encompasses lesbian, gay, bisexual, and transgender individuals as well as any individuals whose sexual identity or gender identity does not align with traditional norms. This hopefully will lead to a growing body of evidence to help all of us learn about the spectrum of sexual and gender identity and better help sexual and gender minority youth reach their full potential.
For more information about the YRBS and the report on health related behaviors in sexual minority youth visit this link:
Selected questionnaire results
Sexual identity
• 88.8% of students identified as heterosexual.
• 6.0% identified as bisexual.
• 3.2% were not sure.
• 2.0% identified as gay or lesbian.
Sexual behaviors
• 48% had had sexual contact with the opposite sex only.
• 4.6% had sexual contact with both sexes.
• 1.7% had had sexual contact with the same sex only.
• 45.7% had no sexual contact.
Mental health
Percent of students who reported making a suicide plan in the 12 months preceding the survey:
• 11.9% of heterosexual students.
• 27.9% of students not sure of sexual identity.
• 38.2% of gay, lesbian, bisexual (GLB) students.
Percent of students who attempted suicide in the 12 months preceding the survey:
• 6.4% of heterosexual students.
• 13.7% of students not sure of sexual identity.
• 29.4% of GLB students.
Sexual Behaviors
First sex before the age of 13:
• 3.4% of heterosexual students.
• 8.8% of students not sure of their sexual identity.
• 7.3% of GLB students.
Drank alcohol or used drugs before last sex:
• 20.0% of heterosexual students.
• 44.5% of students not sure of their sexual identity.
• 22.4% of GLB students.
Tested for HIV:
• 9.3% of heterosexual students.
• 12.8% of students not sure of their sexual identity.
• 18.2% of GLB students.
Substance use
Currently smoking cigarettes daily:
• 1.9% of heterosexual students.
• 7.0% of students not sure of their sexual identity.
• 4.0% of GLB students.
Current alcohol use:
• 32.1% of heterosexual students.
• 34.6% of students not sure of their sexual identity.
• 40.5% of GLB students.
Current marijuana use:
• 20.7% of heterosexual students.
• 26.0% of students not sure of their sexual identity.
• 32.0% of GLB students.
Used hallucinogenic drugs (such as LSD, acid, PCP, angel dust, mescaline, or mushrooms):
• 5.5% of heterosexual students.
• 15.7% of students not sure of their sexual identity.
• 11.5% of GLB students.
Ever used heroin:
• 1.3% of heterosexual students.
• 9.3% of students not sure of their sexual identity.
• 6.0% of GLB students.
Ever took prescription drugs without a doctor’s prescription:
15.5% of heterosexual students.
24.3% of students not sure of their sexual identity.
27.5% of GLB students.
Physical Activity
Did not participate in at least 60 minutes of physical activity on at least 1 day in past week:
• 12.6% of heterosexual students.
• 27.0% of students not sure of their sexual identity.
• 25.7% of GLB students.
Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at the Ohio State University, both in Columbus.
The Centers for Disease Control and Prevention released results from the first nationally representative study on health risk behaviors of gay, lesbian, and bisexual (GLB) high school students in August 2016.
These data were collected through the Youth Risk Behavior Survey (YRBS) questionnaire. The YRBS questionnaire was developed in 1990 as a way to monitor health-related behaviors that contribute to the leading causes of mortality and morbidity in youth and young adults. Areas covered by the survey include behaviors related to unintentional injuries and violence, tobacco use, alcohol and other drug use, sexual behaviors, dietary behaviors, and physical activity. Data are collected every 2 years through national, state, territorial, tribal government, and local school-based surveys of representative samples of 9th-12th grade students.
For the study, sexual minority youth were defined as those who identified as GLB; those who reported sexual contact with members of the same sex only; and those who reported sexual contact with members of both sexes. It is important to note that the YRBS is a school-based survey and does not include youth who do not attend school, for example, homeless and runaway youth.
Exploring and identifying disparities in health behaviors that affect sexual minorities can help us as providers to better target screenings for these health behaviors at the individual level. At the population level, it is important to continue to explore why these differences exist and to continue to develop interventions that help address these differences, while educating families and communities about how to support all of their youth. It is important to note that the majority of sexual minority youth live healthy live; however, this study shows that sexual minority youth do have a higher prevalence of certain health risk behaviors, likely leading to the health disparities we see in this population. Select findings of this study are summarized in the accompanying table.
Continued study is needed to understand the health disparities that occur in sexual minority populations. In October, the National Institutes of Health designated sexual and gender minorities as a specific health disparity population for NIH research. This term encompasses lesbian, gay, bisexual, and transgender individuals as well as any individuals whose sexual identity or gender identity does not align with traditional norms. This hopefully will lead to a growing body of evidence to help all of us learn about the spectrum of sexual and gender identity and better help sexual and gender minority youth reach their full potential.
For more information about the YRBS and the report on health related behaviors in sexual minority youth visit this link:
Selected questionnaire results
Sexual identity
• 88.8% of students identified as heterosexual.
• 6.0% identified as bisexual.
• 3.2% were not sure.
• 2.0% identified as gay or lesbian.
Sexual behaviors
• 48% had had sexual contact with the opposite sex only.
• 4.6% had sexual contact with both sexes.
• 1.7% had had sexual contact with the same sex only.
• 45.7% had no sexual contact.
Mental health
Percent of students who reported making a suicide plan in the 12 months preceding the survey:
• 11.9% of heterosexual students.
• 27.9% of students not sure of sexual identity.
• 38.2% of gay, lesbian, bisexual (GLB) students.
Percent of students who attempted suicide in the 12 months preceding the survey:
• 6.4% of heterosexual students.
• 13.7% of students not sure of sexual identity.
• 29.4% of GLB students.
Sexual Behaviors
First sex before the age of 13:
• 3.4% of heterosexual students.
• 8.8% of students not sure of their sexual identity.
• 7.3% of GLB students.
Drank alcohol or used drugs before last sex:
• 20.0% of heterosexual students.
• 44.5% of students not sure of their sexual identity.
• 22.4% of GLB students.
Tested for HIV:
• 9.3% of heterosexual students.
• 12.8% of students not sure of their sexual identity.
• 18.2% of GLB students.
Substance use
Currently smoking cigarettes daily:
• 1.9% of heterosexual students.
• 7.0% of students not sure of their sexual identity.
• 4.0% of GLB students.
Current alcohol use:
• 32.1% of heterosexual students.
• 34.6% of students not sure of their sexual identity.
• 40.5% of GLB students.
Current marijuana use:
• 20.7% of heterosexual students.
• 26.0% of students not sure of their sexual identity.
• 32.0% of GLB students.
Used hallucinogenic drugs (such as LSD, acid, PCP, angel dust, mescaline, or mushrooms):
• 5.5% of heterosexual students.
• 15.7% of students not sure of their sexual identity.
• 11.5% of GLB students.
Ever used heroin:
• 1.3% of heterosexual students.
• 9.3% of students not sure of their sexual identity.
• 6.0% of GLB students.
Ever took prescription drugs without a doctor’s prescription:
15.5% of heterosexual students.
24.3% of students not sure of their sexual identity.
27.5% of GLB students.
Physical Activity
Did not participate in at least 60 minutes of physical activity on at least 1 day in past week:
• 12.6% of heterosexual students.
• 27.0% of students not sure of their sexual identity.
• 25.7% of GLB students.
Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at the Ohio State University, both in Columbus.
Metabolic syndrome predicts cardiovascular events in HBV infection
Metabolic syndrome was associated with a fourfold rise in cardiovascular events among patients with chronic hepatitis B virus infection, according to a prospective cohort study published in Hepatology.
Over a median of 7.3 years of follow-up, 8% of patients with metabolic syndrome developed ischemic or hemorrhagic stroke, acute coronary syndrome, or congestive heart failure, or underwent revascularization, compared with 2% of patients without metabolic syndrome (P less than .0001), reported Jenny Yeuk-Ki Cheng, MD, and her associates at The Chinese University of Hong Kong.
But it was liver stiffness measure (LSM), not metabolic syndrome, that predicted hepatic events (hazard ratio, 1.6; 95% confidence interval, 1.0 to 2.5) and death (HR, 1.9; 95% CI, 1.1 to 3.2), the investigators reported (Hepatology. 2016 Sep 29. doi: 10.1002/hep.28778).
Their study included 1,466 patients with chronic HBV infection who averaged 46 years of age, with an average baseline LSM of 8.4 kPa (standard deviation, 6.3 kPa). A total of 188 patients (12.8%) had metabolic syndrome at baseline, defined as at least three of the following five factors: central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension, and type 2 diabetes mellitus or fasting hyperglycemia.
In all, 44 patients (3.0%) developed cardiovascular events during follow-up, while 93 (6.3%) developed cirrhotic events and hepatocellular carcinoma, and 70 (4.8%) died. Patients whose LSM exceeded 8.0 kPa at baseline had a significantly higher cumulative risk of hepatic events over the next 8 years than did patients with lower baseline LSM (12.3% versus 3%; P less than .001).
But high LSM “had no impact on cardiovascular events,” just as metabolic syndrome did not increase the risk of hepatic events or death, the investigators said. The study, the first to evaluate this group of clinical correlates in HBV-infected patients, highlights the need to monitor their metabolic risk factors over time, they concluded.
The researchers reported having no funding sources. Dr. Cheng had no relevant financial disclosures, although other coauthors reported multiple relationships with pharmaceutical and device firms.
Metabolic syndrome was associated with a fourfold rise in cardiovascular events among patients with chronic hepatitis B virus infection, according to a prospective cohort study published in Hepatology.
Over a median of 7.3 years of follow-up, 8% of patients with metabolic syndrome developed ischemic or hemorrhagic stroke, acute coronary syndrome, or congestive heart failure, or underwent revascularization, compared with 2% of patients without metabolic syndrome (P less than .0001), reported Jenny Yeuk-Ki Cheng, MD, and her associates at The Chinese University of Hong Kong.
But it was liver stiffness measure (LSM), not metabolic syndrome, that predicted hepatic events (hazard ratio, 1.6; 95% confidence interval, 1.0 to 2.5) and death (HR, 1.9; 95% CI, 1.1 to 3.2), the investigators reported (Hepatology. 2016 Sep 29. doi: 10.1002/hep.28778).
Their study included 1,466 patients with chronic HBV infection who averaged 46 years of age, with an average baseline LSM of 8.4 kPa (standard deviation, 6.3 kPa). A total of 188 patients (12.8%) had metabolic syndrome at baseline, defined as at least three of the following five factors: central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension, and type 2 diabetes mellitus or fasting hyperglycemia.
In all, 44 patients (3.0%) developed cardiovascular events during follow-up, while 93 (6.3%) developed cirrhotic events and hepatocellular carcinoma, and 70 (4.8%) died. Patients whose LSM exceeded 8.0 kPa at baseline had a significantly higher cumulative risk of hepatic events over the next 8 years than did patients with lower baseline LSM (12.3% versus 3%; P less than .001).
But high LSM “had no impact on cardiovascular events,” just as metabolic syndrome did not increase the risk of hepatic events or death, the investigators said. The study, the first to evaluate this group of clinical correlates in HBV-infected patients, highlights the need to monitor their metabolic risk factors over time, they concluded.
The researchers reported having no funding sources. Dr. Cheng had no relevant financial disclosures, although other coauthors reported multiple relationships with pharmaceutical and device firms.
Metabolic syndrome was associated with a fourfold rise in cardiovascular events among patients with chronic hepatitis B virus infection, according to a prospective cohort study published in Hepatology.
Over a median of 7.3 years of follow-up, 8% of patients with metabolic syndrome developed ischemic or hemorrhagic stroke, acute coronary syndrome, or congestive heart failure, or underwent revascularization, compared with 2% of patients without metabolic syndrome (P less than .0001), reported Jenny Yeuk-Ki Cheng, MD, and her associates at The Chinese University of Hong Kong.
But it was liver stiffness measure (LSM), not metabolic syndrome, that predicted hepatic events (hazard ratio, 1.6; 95% confidence interval, 1.0 to 2.5) and death (HR, 1.9; 95% CI, 1.1 to 3.2), the investigators reported (Hepatology. 2016 Sep 29. doi: 10.1002/hep.28778).
Their study included 1,466 patients with chronic HBV infection who averaged 46 years of age, with an average baseline LSM of 8.4 kPa (standard deviation, 6.3 kPa). A total of 188 patients (12.8%) had metabolic syndrome at baseline, defined as at least three of the following five factors: central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension, and type 2 diabetes mellitus or fasting hyperglycemia.
In all, 44 patients (3.0%) developed cardiovascular events during follow-up, while 93 (6.3%) developed cirrhotic events and hepatocellular carcinoma, and 70 (4.8%) died. Patients whose LSM exceeded 8.0 kPa at baseline had a significantly higher cumulative risk of hepatic events over the next 8 years than did patients with lower baseline LSM (12.3% versus 3%; P less than .001).
But high LSM “had no impact on cardiovascular events,” just as metabolic syndrome did not increase the risk of hepatic events or death, the investigators said. The study, the first to evaluate this group of clinical correlates in HBV-infected patients, highlights the need to monitor their metabolic risk factors over time, they concluded.
The researchers reported having no funding sources. Dr. Cheng had no relevant financial disclosures, although other coauthors reported multiple relationships with pharmaceutical and device firms.
Key clinical point: Metabolic syndrome significantly increases the risk of cardiovascular events in patients with chronic hepatitis B virus infection.
Major finding: In all, 8% of patients with metabolic syndrome had a cardiovascular event, compared with 2% of patients without metabolic syndrome (P less than .0001).
Data source: A single-center prospective cohort study of 1,466 patients with chronic hepatitis B virus infection.
Disclosures: The researchers reported having no funding sources. Dr. Cheng had no relevant financial disclosures, although other coauthors reported multiple relationships with pharmaceutical and device firms.
Fatal measles complication occurs more often than realized
NEW ORLEANS – A fatal complication of measles known as subacute sclerosing panencephalitis (SSPE) can develop years after measles infection and appears to occur much more often than published reports suggest, according to a review of cases in California from 1998 to 2015.
The findings underscore the vital importance of herd immunity by vaccination, Kristen Wendorf, MD, reported at an annual scientific meeting on infectious diseases.
The incidence of postmeasles SSPE was previously thought be about 1 in 100,000, according to an IDWeek press release.
“There is no cure for SSPE, and the only way to prevent it is to vaccinate everyone against measles,” the release stated.
The cases in the current study were among children with a clinically compatible illness, and either measles IgG antibody detected in cerebrospinal fluid, a characteristic pattern on electroencephalography, typical histologic findings on brain biopsy, or medical record documentation of SSPE-related complications. They were identified based on death certificates, reports from the Centers for Diseases Control and Prevention, or through investigations for undiagnosed neurologic disease. Twelve of the 17 affected children had a clinical history of a febrile rash illness compatible with measles, and all 12 of those experienced illness before age 15 months and before measles vaccination.
Most (67%) were living in the United States when they had measles, Dr. Wendorf said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The median age at diagnosis of SSPE was 12 years, although the range was 3-35 years, and the mean latency period was 9.5 years. In many cases, long-standing cognitive or motor problems were experienced prior to diagnosis, she noted.
The findings suggest that SSPE is more common than previously recognized in unvaccinated children with measles during infancy, Dr. Wendorf said.
Protection of infants younger than 12-15 months of age – before the time when measles vaccine is routinely administered – and in those who can’t be vaccinated because of immune system disorders requires avoidance of travel to endemic areas. Parents also may consider early vaccination prior to such travel.
Further, clinicians should be aware of the risk of SSPE in patients with symptoms suggestive of the disease. This is true even among older patients in whom no specific history of measles infection is known, she said.
In the press release, coauthor James D. Cherry, MD, professor of pediatrics at the University of California, Los Angeles, further stressed the importance of protecting unvaccinated infants.
“Parents of infants who have not yet been vaccinated should avoid putting their children at risk. For example, they should postpone trips overseas – including to Europe – where measles is endemic and epidemic until after their baby has been vaccinated with two doses,” he said. “It’s just not worth the risk.”
The authors reported having no disclosures.
NEW ORLEANS – A fatal complication of measles known as subacute sclerosing panencephalitis (SSPE) can develop years after measles infection and appears to occur much more often than published reports suggest, according to a review of cases in California from 1998 to 2015.
The findings underscore the vital importance of herd immunity by vaccination, Kristen Wendorf, MD, reported at an annual scientific meeting on infectious diseases.
The incidence of postmeasles SSPE was previously thought be about 1 in 100,000, according to an IDWeek press release.
“There is no cure for SSPE, and the only way to prevent it is to vaccinate everyone against measles,” the release stated.
The cases in the current study were among children with a clinically compatible illness, and either measles IgG antibody detected in cerebrospinal fluid, a characteristic pattern on electroencephalography, typical histologic findings on brain biopsy, or medical record documentation of SSPE-related complications. They were identified based on death certificates, reports from the Centers for Diseases Control and Prevention, or through investigations for undiagnosed neurologic disease. Twelve of the 17 affected children had a clinical history of a febrile rash illness compatible with measles, and all 12 of those experienced illness before age 15 months and before measles vaccination.
Most (67%) were living in the United States when they had measles, Dr. Wendorf said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The median age at diagnosis of SSPE was 12 years, although the range was 3-35 years, and the mean latency period was 9.5 years. In many cases, long-standing cognitive or motor problems were experienced prior to diagnosis, she noted.
The findings suggest that SSPE is more common than previously recognized in unvaccinated children with measles during infancy, Dr. Wendorf said.
Protection of infants younger than 12-15 months of age – before the time when measles vaccine is routinely administered – and in those who can’t be vaccinated because of immune system disorders requires avoidance of travel to endemic areas. Parents also may consider early vaccination prior to such travel.
Further, clinicians should be aware of the risk of SSPE in patients with symptoms suggestive of the disease. This is true even among older patients in whom no specific history of measles infection is known, she said.
In the press release, coauthor James D. Cherry, MD, professor of pediatrics at the University of California, Los Angeles, further stressed the importance of protecting unvaccinated infants.
“Parents of infants who have not yet been vaccinated should avoid putting their children at risk. For example, they should postpone trips overseas – including to Europe – where measles is endemic and epidemic until after their baby has been vaccinated with two doses,” he said. “It’s just not worth the risk.”
The authors reported having no disclosures.
NEW ORLEANS – A fatal complication of measles known as subacute sclerosing panencephalitis (SSPE) can develop years after measles infection and appears to occur much more often than published reports suggest, according to a review of cases in California from 1998 to 2015.
The findings underscore the vital importance of herd immunity by vaccination, Kristen Wendorf, MD, reported at an annual scientific meeting on infectious diseases.
The incidence of postmeasles SSPE was previously thought be about 1 in 100,000, according to an IDWeek press release.
“There is no cure for SSPE, and the only way to prevent it is to vaccinate everyone against measles,” the release stated.
The cases in the current study were among children with a clinically compatible illness, and either measles IgG antibody detected in cerebrospinal fluid, a characteristic pattern on electroencephalography, typical histologic findings on brain biopsy, or medical record documentation of SSPE-related complications. They were identified based on death certificates, reports from the Centers for Diseases Control and Prevention, or through investigations for undiagnosed neurologic disease. Twelve of the 17 affected children had a clinical history of a febrile rash illness compatible with measles, and all 12 of those experienced illness before age 15 months and before measles vaccination.
Most (67%) were living in the United States when they had measles, Dr. Wendorf said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The median age at diagnosis of SSPE was 12 years, although the range was 3-35 years, and the mean latency period was 9.5 years. In many cases, long-standing cognitive or motor problems were experienced prior to diagnosis, she noted.
The findings suggest that SSPE is more common than previously recognized in unvaccinated children with measles during infancy, Dr. Wendorf said.
Protection of infants younger than 12-15 months of age – before the time when measles vaccine is routinely administered – and in those who can’t be vaccinated because of immune system disorders requires avoidance of travel to endemic areas. Parents also may consider early vaccination prior to such travel.
Further, clinicians should be aware of the risk of SSPE in patients with symptoms suggestive of the disease. This is true even among older patients in whom no specific history of measles infection is known, she said.
In the press release, coauthor James D. Cherry, MD, professor of pediatrics at the University of California, Los Angeles, further stressed the importance of protecting unvaccinated infants.
“Parents of infants who have not yet been vaccinated should avoid putting their children at risk. For example, they should postpone trips overseas – including to Europe – where measles is endemic and epidemic until after their baby has been vaccinated with two doses,” he said. “It’s just not worth the risk.”
The authors reported having no disclosures.
AT IDWEEK 2016
Key clinical point:
Major finding: The incidence of SSPE among measles cases was 1 in 1,367 children under age 5 years and 1 in 609 children under age 12 months at the time of measles disease.
Data source: A review of records and 17 cases of SSPE.
Disclosures: The authors reported having no disclosures.
Idiopathic Livedo Racemosa Presenting With Splenomegaly and Diffuse Lymphadenopathy
Sneddon syndrome (SS) was first described in 1965 in patients with persistent livedo racemosa and neurological events.1 Because the other manifestations of SS are nonspecific (eg, hypertension, cardiac valvulopathy, arterial and venous occlusion), the diagnosis often is delayed. Many patients who experience prodromal neurologic symptoms such as headaches, depression, anxiety, dizziness, and neuropathy often present to a physician prior to developing ischemic brain manifestations2 but seldom receive the correct diagnosis. Onset of cerebral occlusive events typically occurs in patients younger than 45 years and may present as a transient ischemic attack, stroke, or intracranial hemorrhage.3 The disease is more prevalent in females than males (2:1 ratio). The exact pathogenesis of SS is still unknown, and although it has been thought of as a separate entity from systemic lupus erythematosus and other antiphospholipid disorders, it has been postulated that an immunological dysfunction damages vessel walls leading to thrombosis.
Cutaneous findings associated with SS involve small- to medium-sized dermal-subdermal arteries. Histopathology in some patients demonstrates proliferation of the endothelium and fibrin deposits with subsequent obliteration of involved arteries.4 In many patients including our patient, histopathologic examination of involved skin fails to show specific abnormalities.1 Zelger et al5 reported the sequence of histopathologic skin events in a series of antiphospholipid-negative SS patients. The authors reported that only small arteries at the dermis-subcutis junction were involved and a progression of endothelial dysfunction was observed. The authors believed there were several nonspecific stages prior to fibrin occlusion of involved arteries.5 Stage I involved loosening of endothelial cells with nonspecific perivascular lymphocytic infiltration with perivascular inflammation and lymphocytic infiltration representing the prime mover of the disease.5,6 This stage is thought to be short lived, thus the reason why it has gone undetected for many years in SS patients. Stages II to IV progress through fibrin deposition and occlusion.5 Histological features of stages I to II have not been reported because of late diagnosis of SS. Stage I patients typically present with an average duration of symptoms of 6 months with few neurologic symptoms, the most common being paresthesia of the legs.5
Case Report
A 37-year-old woman with epigastric tenderness on the left side and splenomegaly seen on computed tomography was referred by a hematologist for evaluation of a reticular rash on the left side of the flank of 9 months’ duration with a presumed diagnosis of focal melanoderma. Her medical history was remarkable for a congenital ventricular septal defect and coarctation of the aorta, as well as endometriosis, myalgia, and joint stiffness that had all developed over the last year. Her medical history also was remarkable for nephrolithiasis, irritable bowel syndrome, and chronic sinusitis, as well as psychiatric depression and anxiety disorders. She recently had been diagnosed with moderate hypertension and had experienced difficulty getting pregnant for the last several years with 3 consecutive miscarriages in the first trimester. Neurologic symptoms included neuropathy involving the feet, intermittent paresthesia of the legs, and a history of chronic migraine headaches for several months.
Dermatologic examination revealed a slightly overweight woman with a 25×30-cm dusky, erythematous, irregular, netlike pattern on the left side of the upper and lower trunk (Figure 1). Extensive livedo racemosa was not altered by changes in temperature and had been unchanged for more than 9 months. There were no signs of pruritus or ulcerations, and areas of livedo racemosa were slightly tender to palpation.
We performed 2 sets of three 4-mm biopsies. The first set targeted areas within the violaceous pattern, while the second set targeted areas of normal tissue between the mottled areas. All 6 specimens demonstrated superficial perivascular lymphocytic infiltrate with no evidence of vasculitis or connective tissue disease. The vessels showed no microthrombi or surrounding fibrosis. No eosinophils were identified within the epidermis. There was no evidence of increased dermal mucin. Both the superficial and deep vascular plexuses were unremarkable and showed no evidence of damage to the walls (Figure 2).
To rule out other possible causes of livedo racemosa, complete blood cell count, comprehensive metabolic panel, coagulation profile, lipase test, urinalysis, serologic testing, and immunologic workup were performed. Lipase was within reference range. The complete blood cell count revealed mild anemia, while the rest of the values were within reference range. An immunologic workup included Sjögren syndrome antigen A, Sjögren syndrome antigen B, anticardiolipin antibodies, and antinuclear antibody, which were all negative. Family history was remarkable for first-degree relatives with systemic lupus erythematosus and Crohn disease.
Computed tomography revealed enlargement of the spleen, as well as periaortic, portacaval, and porta hepatis lymphadenopathy. Based on the laboratory findings and clinical presentation as well as the patient’s medical history, the diagnosis of exclusion was idiopathic livedo racemosa with unknown progression to full-blown SS. The patient did not meet the current diagnostic criteria for SS, and her immunologic studies failed to confirm any present antibodies, but involvement of the reticuloendothelial system pointed to production of antibodies that were not yet detectable on laboratory testing.
Comment
More than 50 years after the first case of SS was diagnosed, better laboratory workup is available and more information is known about the pathophysiology. Sneddon syndrome is a rare disorder, affecting only approximately 4 patients per million each year worldwide. Seronegative antiphospholipid antibody syndrome (SNAPS) describes patients with clinical presentations of antiphospholipid syndrome (APS) without detectable serological markers.7 Antiphospholipid-negative SS, which was seen in our patient, would be categorized under SNAPS. A PubMed search of articles indexed for MEDLINE using the terms livedo racemosa, Sneddon syndrome, and SNAPS and splenomegaly revealed there currently are no known cases of SNAPS that have been reported with splenomegaly and lymphadenopathy. Our patient presented with the following clinical features of SS: livedo racemosa, history of miscarriage, psychiatric disturbances, and hypertension. Surprisingly, biopsies from affected skin did not show any fibrin deposition or microthrombi but did reveal perivascular lymphocytic infiltrations. Magnetic resonance imaging did not show any pathological lesions or vascular changes.
Sneddon syndrome and APS share a common pathway to occlusive arteriolopathy for which 4 stages have been described by Zelger et al.5 Stage I involves a nonspecific Langerhans cell infiltrate with polymorphonuclear leukocytes. The tunica media and elastic lamina usually are unaltered at this early stage, while the surrounding connective tissue may appear edematous.5 This early stage of histopathology has not been evaluated in SS patients, primarily because of delay of diagnosis. Late stages III and IV will show fibrin deposition and shrinkage of affected vessels.7
A PubMed search using the terms Sneddon syndrome, lymphadenopathy and livedo racemosa, and Sneddon syndrome and lymphadenopathy revealed that splenomegaly and lymphadenopathy have not been reported in patients with SS. In patients with antiphospholipid-negative SS, one can assume that antibodies to other phospholipids not tested must exist because of striking similarities between APS and antiphospholipid-negative SS.8 Although our patient did not test positive for any of these antibodies, she did present with lymphadenopathy and splenic enlargement, leading us to believe that involvement of the reticuloendothelial system may be a feature of SS that has not been previously reported. Further studies are required to name specific antigens responsible for clinical manifestations in SS.
Currently, no single diagnostic test for SS exists, thus delaying both diagnosis and initiation of treatment. Histopathologic examination may be helpful, but in many cases it is nonspecific, as are serologic markers. Neuroradiological confirmation of involvement usually is the confirmatory feature in many patients with late-stage diagnosis.2 A diagnostic schematic for SS, which was first described by Daoud et al,2 illustrates classification of symptoms and aids in diagnosis. A working diagnosis of idiopathic livedo racemosa is made after ruling out other causes of SS in a patient with nonspecific biopsy findings and negative magnetic resonance imaging results with prodromal symptoms. The prognosis for such patients progressing to full SS is unknown with or without management using anticoagulant therapy.
Conclusion
Early diagnosis of livedo racemosa and SS is essential, as prevention of cerebrovascular accidents, myocardial infarction, and other thromboembolic diseases can be minimized by attacking risk factors such as smoking, taking oral contraceptive pills, becoming pregnant,9 and by initiating either antiplatelet or anticoagulation treatments. These treatments have been shown to delay the development of neurovascular damage and early-onset dementia. We present this case to demonstrate the variability of early-presenting symptoms in idiopathic livedo racemosa. Recognizing some of the early manifestations can lead to early diagnosis and initiation of treatment.
- Sneddon IB. Cerebro-vascular lesions and livedo reticularis. Br J Dermatol. 1965;77:180-185.
- Daoud MS, Wilmoth GJ, Su WP, et al. Sneddon syndrome. Semin Dermatol. 1995;14:166-172.
- Besnier R, Francès C, Ankri A, et al. Factor V Leiden mutation in Sneddon syndrome. Lupus. 2003;12:406-408.
- K aragülle AT, Karadağ D, Erden A, et al. Sneddon’s syndrome: MR imaging findings. Eur Radiol. 2002;12:144-146.
- Zelg er B, Sepp N, Schmid KW, et al. Life-history of cutaneous vascular-lesions in Sneddon’s syndrome. Hum Pathol. 1992;23:668-675.
- Ayoub N, Esposito G, Barete S, et al. Protein Z deficiency in antiphospholipid-negative Sneddon’s syndrome. Stroke. 2004;35:1329-1332.
- Duva l A, Darnige L, Glowacki F, et al. Livedo, dementia, thrombocytopenia, and endotheliitis without antiphospholipid antibodies: seronegative antiphospholipid-like syndrome. J Am Acad Dermatol. 2009;61:1076-1078.
- Kala shnikova LA, Nasonov EL, Kushekbaeva AE, et al. Anticardiolipin antibodies in Sneddon’s syndrome. Neurology. 1990;40:464-467.
- Wohl rab J, Fischer M, Wolter M, et al. Diagnostic impact and sensitivity of skin biopsies in Sneddon’s syndrome. a report of 15 cases. Br J Dermatol. 2001;145:285-288.
Sneddon syndrome (SS) was first described in 1965 in patients with persistent livedo racemosa and neurological events.1 Because the other manifestations of SS are nonspecific (eg, hypertension, cardiac valvulopathy, arterial and venous occlusion), the diagnosis often is delayed. Many patients who experience prodromal neurologic symptoms such as headaches, depression, anxiety, dizziness, and neuropathy often present to a physician prior to developing ischemic brain manifestations2 but seldom receive the correct diagnosis. Onset of cerebral occlusive events typically occurs in patients younger than 45 years and may present as a transient ischemic attack, stroke, or intracranial hemorrhage.3 The disease is more prevalent in females than males (2:1 ratio). The exact pathogenesis of SS is still unknown, and although it has been thought of as a separate entity from systemic lupus erythematosus and other antiphospholipid disorders, it has been postulated that an immunological dysfunction damages vessel walls leading to thrombosis.
Cutaneous findings associated with SS involve small- to medium-sized dermal-subdermal arteries. Histopathology in some patients demonstrates proliferation of the endothelium and fibrin deposits with subsequent obliteration of involved arteries.4 In many patients including our patient, histopathologic examination of involved skin fails to show specific abnormalities.1 Zelger et al5 reported the sequence of histopathologic skin events in a series of antiphospholipid-negative SS patients. The authors reported that only small arteries at the dermis-subcutis junction were involved and a progression of endothelial dysfunction was observed. The authors believed there were several nonspecific stages prior to fibrin occlusion of involved arteries.5 Stage I involved loosening of endothelial cells with nonspecific perivascular lymphocytic infiltration with perivascular inflammation and lymphocytic infiltration representing the prime mover of the disease.5,6 This stage is thought to be short lived, thus the reason why it has gone undetected for many years in SS patients. Stages II to IV progress through fibrin deposition and occlusion.5 Histological features of stages I to II have not been reported because of late diagnosis of SS. Stage I patients typically present with an average duration of symptoms of 6 months with few neurologic symptoms, the most common being paresthesia of the legs.5
Case Report
A 37-year-old woman with epigastric tenderness on the left side and splenomegaly seen on computed tomography was referred by a hematologist for evaluation of a reticular rash on the left side of the flank of 9 months’ duration with a presumed diagnosis of focal melanoderma. Her medical history was remarkable for a congenital ventricular septal defect and coarctation of the aorta, as well as endometriosis, myalgia, and joint stiffness that had all developed over the last year. Her medical history also was remarkable for nephrolithiasis, irritable bowel syndrome, and chronic sinusitis, as well as psychiatric depression and anxiety disorders. She recently had been diagnosed with moderate hypertension and had experienced difficulty getting pregnant for the last several years with 3 consecutive miscarriages in the first trimester. Neurologic symptoms included neuropathy involving the feet, intermittent paresthesia of the legs, and a history of chronic migraine headaches for several months.
Dermatologic examination revealed a slightly overweight woman with a 25×30-cm dusky, erythematous, irregular, netlike pattern on the left side of the upper and lower trunk (Figure 1). Extensive livedo racemosa was not altered by changes in temperature and had been unchanged for more than 9 months. There were no signs of pruritus or ulcerations, and areas of livedo racemosa were slightly tender to palpation.
We performed 2 sets of three 4-mm biopsies. The first set targeted areas within the violaceous pattern, while the second set targeted areas of normal tissue between the mottled areas. All 6 specimens demonstrated superficial perivascular lymphocytic infiltrate with no evidence of vasculitis or connective tissue disease. The vessels showed no microthrombi or surrounding fibrosis. No eosinophils were identified within the epidermis. There was no evidence of increased dermal mucin. Both the superficial and deep vascular plexuses were unremarkable and showed no evidence of damage to the walls (Figure 2).
To rule out other possible causes of livedo racemosa, complete blood cell count, comprehensive metabolic panel, coagulation profile, lipase test, urinalysis, serologic testing, and immunologic workup were performed. Lipase was within reference range. The complete blood cell count revealed mild anemia, while the rest of the values were within reference range. An immunologic workup included Sjögren syndrome antigen A, Sjögren syndrome antigen B, anticardiolipin antibodies, and antinuclear antibody, which were all negative. Family history was remarkable for first-degree relatives with systemic lupus erythematosus and Crohn disease.
Computed tomography revealed enlargement of the spleen, as well as periaortic, portacaval, and porta hepatis lymphadenopathy. Based on the laboratory findings and clinical presentation as well as the patient’s medical history, the diagnosis of exclusion was idiopathic livedo racemosa with unknown progression to full-blown SS. The patient did not meet the current diagnostic criteria for SS, and her immunologic studies failed to confirm any present antibodies, but involvement of the reticuloendothelial system pointed to production of antibodies that were not yet detectable on laboratory testing.
Comment
More than 50 years after the first case of SS was diagnosed, better laboratory workup is available and more information is known about the pathophysiology. Sneddon syndrome is a rare disorder, affecting only approximately 4 patients per million each year worldwide. Seronegative antiphospholipid antibody syndrome (SNAPS) describes patients with clinical presentations of antiphospholipid syndrome (APS) without detectable serological markers.7 Antiphospholipid-negative SS, which was seen in our patient, would be categorized under SNAPS. A PubMed search of articles indexed for MEDLINE using the terms livedo racemosa, Sneddon syndrome, and SNAPS and splenomegaly revealed there currently are no known cases of SNAPS that have been reported with splenomegaly and lymphadenopathy. Our patient presented with the following clinical features of SS: livedo racemosa, history of miscarriage, psychiatric disturbances, and hypertension. Surprisingly, biopsies from affected skin did not show any fibrin deposition or microthrombi but did reveal perivascular lymphocytic infiltrations. Magnetic resonance imaging did not show any pathological lesions or vascular changes.
Sneddon syndrome and APS share a common pathway to occlusive arteriolopathy for which 4 stages have been described by Zelger et al.5 Stage I involves a nonspecific Langerhans cell infiltrate with polymorphonuclear leukocytes. The tunica media and elastic lamina usually are unaltered at this early stage, while the surrounding connective tissue may appear edematous.5 This early stage of histopathology has not been evaluated in SS patients, primarily because of delay of diagnosis. Late stages III and IV will show fibrin deposition and shrinkage of affected vessels.7
A PubMed search using the terms Sneddon syndrome, lymphadenopathy and livedo racemosa, and Sneddon syndrome and lymphadenopathy revealed that splenomegaly and lymphadenopathy have not been reported in patients with SS. In patients with antiphospholipid-negative SS, one can assume that antibodies to other phospholipids not tested must exist because of striking similarities between APS and antiphospholipid-negative SS.8 Although our patient did not test positive for any of these antibodies, she did present with lymphadenopathy and splenic enlargement, leading us to believe that involvement of the reticuloendothelial system may be a feature of SS that has not been previously reported. Further studies are required to name specific antigens responsible for clinical manifestations in SS.
Currently, no single diagnostic test for SS exists, thus delaying both diagnosis and initiation of treatment. Histopathologic examination may be helpful, but in many cases it is nonspecific, as are serologic markers. Neuroradiological confirmation of involvement usually is the confirmatory feature in many patients with late-stage diagnosis.2 A diagnostic schematic for SS, which was first described by Daoud et al,2 illustrates classification of symptoms and aids in diagnosis. A working diagnosis of idiopathic livedo racemosa is made after ruling out other causes of SS in a patient with nonspecific biopsy findings and negative magnetic resonance imaging results with prodromal symptoms. The prognosis for such patients progressing to full SS is unknown with or without management using anticoagulant therapy.
Conclusion
Early diagnosis of livedo racemosa and SS is essential, as prevention of cerebrovascular accidents, myocardial infarction, and other thromboembolic diseases can be minimized by attacking risk factors such as smoking, taking oral contraceptive pills, becoming pregnant,9 and by initiating either antiplatelet or anticoagulation treatments. These treatments have been shown to delay the development of neurovascular damage and early-onset dementia. We present this case to demonstrate the variability of early-presenting symptoms in idiopathic livedo racemosa. Recognizing some of the early manifestations can lead to early diagnosis and initiation of treatment.
Sneddon syndrome (SS) was first described in 1965 in patients with persistent livedo racemosa and neurological events.1 Because the other manifestations of SS are nonspecific (eg, hypertension, cardiac valvulopathy, arterial and venous occlusion), the diagnosis often is delayed. Many patients who experience prodromal neurologic symptoms such as headaches, depression, anxiety, dizziness, and neuropathy often present to a physician prior to developing ischemic brain manifestations2 but seldom receive the correct diagnosis. Onset of cerebral occlusive events typically occurs in patients younger than 45 years and may present as a transient ischemic attack, stroke, or intracranial hemorrhage.3 The disease is more prevalent in females than males (2:1 ratio). The exact pathogenesis of SS is still unknown, and although it has been thought of as a separate entity from systemic lupus erythematosus and other antiphospholipid disorders, it has been postulated that an immunological dysfunction damages vessel walls leading to thrombosis.
Cutaneous findings associated with SS involve small- to medium-sized dermal-subdermal arteries. Histopathology in some patients demonstrates proliferation of the endothelium and fibrin deposits with subsequent obliteration of involved arteries.4 In many patients including our patient, histopathologic examination of involved skin fails to show specific abnormalities.1 Zelger et al5 reported the sequence of histopathologic skin events in a series of antiphospholipid-negative SS patients. The authors reported that only small arteries at the dermis-subcutis junction were involved and a progression of endothelial dysfunction was observed. The authors believed there were several nonspecific stages prior to fibrin occlusion of involved arteries.5 Stage I involved loosening of endothelial cells with nonspecific perivascular lymphocytic infiltration with perivascular inflammation and lymphocytic infiltration representing the prime mover of the disease.5,6 This stage is thought to be short lived, thus the reason why it has gone undetected for many years in SS patients. Stages II to IV progress through fibrin deposition and occlusion.5 Histological features of stages I to II have not been reported because of late diagnosis of SS. Stage I patients typically present with an average duration of symptoms of 6 months with few neurologic symptoms, the most common being paresthesia of the legs.5
Case Report
A 37-year-old woman with epigastric tenderness on the left side and splenomegaly seen on computed tomography was referred by a hematologist for evaluation of a reticular rash on the left side of the flank of 9 months’ duration with a presumed diagnosis of focal melanoderma. Her medical history was remarkable for a congenital ventricular septal defect and coarctation of the aorta, as well as endometriosis, myalgia, and joint stiffness that had all developed over the last year. Her medical history also was remarkable for nephrolithiasis, irritable bowel syndrome, and chronic sinusitis, as well as psychiatric depression and anxiety disorders. She recently had been diagnosed with moderate hypertension and had experienced difficulty getting pregnant for the last several years with 3 consecutive miscarriages in the first trimester. Neurologic symptoms included neuropathy involving the feet, intermittent paresthesia of the legs, and a history of chronic migraine headaches for several months.
Dermatologic examination revealed a slightly overweight woman with a 25×30-cm dusky, erythematous, irregular, netlike pattern on the left side of the upper and lower trunk (Figure 1). Extensive livedo racemosa was not altered by changes in temperature and had been unchanged for more than 9 months. There were no signs of pruritus or ulcerations, and areas of livedo racemosa were slightly tender to palpation.
We performed 2 sets of three 4-mm biopsies. The first set targeted areas within the violaceous pattern, while the second set targeted areas of normal tissue between the mottled areas. All 6 specimens demonstrated superficial perivascular lymphocytic infiltrate with no evidence of vasculitis or connective tissue disease. The vessels showed no microthrombi or surrounding fibrosis. No eosinophils were identified within the epidermis. There was no evidence of increased dermal mucin. Both the superficial and deep vascular plexuses were unremarkable and showed no evidence of damage to the walls (Figure 2).
To rule out other possible causes of livedo racemosa, complete blood cell count, comprehensive metabolic panel, coagulation profile, lipase test, urinalysis, serologic testing, and immunologic workup were performed. Lipase was within reference range. The complete blood cell count revealed mild anemia, while the rest of the values were within reference range. An immunologic workup included Sjögren syndrome antigen A, Sjögren syndrome antigen B, anticardiolipin antibodies, and antinuclear antibody, which were all negative. Family history was remarkable for first-degree relatives with systemic lupus erythematosus and Crohn disease.
Computed tomography revealed enlargement of the spleen, as well as periaortic, portacaval, and porta hepatis lymphadenopathy. Based on the laboratory findings and clinical presentation as well as the patient’s medical history, the diagnosis of exclusion was idiopathic livedo racemosa with unknown progression to full-blown SS. The patient did not meet the current diagnostic criteria for SS, and her immunologic studies failed to confirm any present antibodies, but involvement of the reticuloendothelial system pointed to production of antibodies that were not yet detectable on laboratory testing.
Comment
More than 50 years after the first case of SS was diagnosed, better laboratory workup is available and more information is known about the pathophysiology. Sneddon syndrome is a rare disorder, affecting only approximately 4 patients per million each year worldwide. Seronegative antiphospholipid antibody syndrome (SNAPS) describes patients with clinical presentations of antiphospholipid syndrome (APS) without detectable serological markers.7 Antiphospholipid-negative SS, which was seen in our patient, would be categorized under SNAPS. A PubMed search of articles indexed for MEDLINE using the terms livedo racemosa, Sneddon syndrome, and SNAPS and splenomegaly revealed there currently are no known cases of SNAPS that have been reported with splenomegaly and lymphadenopathy. Our patient presented with the following clinical features of SS: livedo racemosa, history of miscarriage, psychiatric disturbances, and hypertension. Surprisingly, biopsies from affected skin did not show any fibrin deposition or microthrombi but did reveal perivascular lymphocytic infiltrations. Magnetic resonance imaging did not show any pathological lesions or vascular changes.
Sneddon syndrome and APS share a common pathway to occlusive arteriolopathy for which 4 stages have been described by Zelger et al.5 Stage I involves a nonspecific Langerhans cell infiltrate with polymorphonuclear leukocytes. The tunica media and elastic lamina usually are unaltered at this early stage, while the surrounding connective tissue may appear edematous.5 This early stage of histopathology has not been evaluated in SS patients, primarily because of delay of diagnosis. Late stages III and IV will show fibrin deposition and shrinkage of affected vessels.7
A PubMed search using the terms Sneddon syndrome, lymphadenopathy and livedo racemosa, and Sneddon syndrome and lymphadenopathy revealed that splenomegaly and lymphadenopathy have not been reported in patients with SS. In patients with antiphospholipid-negative SS, one can assume that antibodies to other phospholipids not tested must exist because of striking similarities between APS and antiphospholipid-negative SS.8 Although our patient did not test positive for any of these antibodies, she did present with lymphadenopathy and splenic enlargement, leading us to believe that involvement of the reticuloendothelial system may be a feature of SS that has not been previously reported. Further studies are required to name specific antigens responsible for clinical manifestations in SS.
Currently, no single diagnostic test for SS exists, thus delaying both diagnosis and initiation of treatment. Histopathologic examination may be helpful, but in many cases it is nonspecific, as are serologic markers. Neuroradiological confirmation of involvement usually is the confirmatory feature in many patients with late-stage diagnosis.2 A diagnostic schematic for SS, which was first described by Daoud et al,2 illustrates classification of symptoms and aids in diagnosis. A working diagnosis of idiopathic livedo racemosa is made after ruling out other causes of SS in a patient with nonspecific biopsy findings and negative magnetic resonance imaging results with prodromal symptoms. The prognosis for such patients progressing to full SS is unknown with or without management using anticoagulant therapy.
Conclusion
Early diagnosis of livedo racemosa and SS is essential, as prevention of cerebrovascular accidents, myocardial infarction, and other thromboembolic diseases can be minimized by attacking risk factors such as smoking, taking oral contraceptive pills, becoming pregnant,9 and by initiating either antiplatelet or anticoagulation treatments. These treatments have been shown to delay the development of neurovascular damage and early-onset dementia. We present this case to demonstrate the variability of early-presenting symptoms in idiopathic livedo racemosa. Recognizing some of the early manifestations can lead to early diagnosis and initiation of treatment.
- Sneddon IB. Cerebro-vascular lesions and livedo reticularis. Br J Dermatol. 1965;77:180-185.
- Daoud MS, Wilmoth GJ, Su WP, et al. Sneddon syndrome. Semin Dermatol. 1995;14:166-172.
- Besnier R, Francès C, Ankri A, et al. Factor V Leiden mutation in Sneddon syndrome. Lupus. 2003;12:406-408.
- K aragülle AT, Karadağ D, Erden A, et al. Sneddon’s syndrome: MR imaging findings. Eur Radiol. 2002;12:144-146.
- Zelg er B, Sepp N, Schmid KW, et al. Life-history of cutaneous vascular-lesions in Sneddon’s syndrome. Hum Pathol. 1992;23:668-675.
- Ayoub N, Esposito G, Barete S, et al. Protein Z deficiency in antiphospholipid-negative Sneddon’s syndrome. Stroke. 2004;35:1329-1332.
- Duva l A, Darnige L, Glowacki F, et al. Livedo, dementia, thrombocytopenia, and endotheliitis without antiphospholipid antibodies: seronegative antiphospholipid-like syndrome. J Am Acad Dermatol. 2009;61:1076-1078.
- Kala shnikova LA, Nasonov EL, Kushekbaeva AE, et al. Anticardiolipin antibodies in Sneddon’s syndrome. Neurology. 1990;40:464-467.
- Wohl rab J, Fischer M, Wolter M, et al. Diagnostic impact and sensitivity of skin biopsies in Sneddon’s syndrome. a report of 15 cases. Br J Dermatol. 2001;145:285-288.
- Sneddon IB. Cerebro-vascular lesions and livedo reticularis. Br J Dermatol. 1965;77:180-185.
- Daoud MS, Wilmoth GJ, Su WP, et al. Sneddon syndrome. Semin Dermatol. 1995;14:166-172.
- Besnier R, Francès C, Ankri A, et al. Factor V Leiden mutation in Sneddon syndrome. Lupus. 2003;12:406-408.
- K aragülle AT, Karadağ D, Erden A, et al. Sneddon’s syndrome: MR imaging findings. Eur Radiol. 2002;12:144-146.
- Zelg er B, Sepp N, Schmid KW, et al. Life-history of cutaneous vascular-lesions in Sneddon’s syndrome. Hum Pathol. 1992;23:668-675.
- Ayoub N, Esposito G, Barete S, et al. Protein Z deficiency in antiphospholipid-negative Sneddon’s syndrome. Stroke. 2004;35:1329-1332.
- Duva l A, Darnige L, Glowacki F, et al. Livedo, dementia, thrombocytopenia, and endotheliitis without antiphospholipid antibodies: seronegative antiphospholipid-like syndrome. J Am Acad Dermatol. 2009;61:1076-1078.
- Kala shnikova LA, Nasonov EL, Kushekbaeva AE, et al. Anticardiolipin antibodies in Sneddon’s syndrome. Neurology. 1990;40:464-467.
- Wohl rab J, Fischer M, Wolter M, et al. Diagnostic impact and sensitivity of skin biopsies in Sneddon’s syndrome. a report of 15 cases. Br J Dermatol. 2001;145:285-288.
Practice Points
- The classic physical diagnostic finding of Sneddon syndrome (SS) is livedo racemosa.
- Early identification and treatment of SS can prevent serious morbidity due to stroke, myocardial infarction, and other thrombotic events.
- Preventive care in SS should include antiplatelet therapy or anticoagulants and smoking cessation along with avoidance of birth control pills.
