Toxicology

HONOLULU -- Recent cocaine use raised the risk of death nearly threefold in a cohort of more than 1,000 patients who were hospitalized for an acute aneurysmal subarachnoid hemorrhage.

The significantly elevated risk of death was observed despite a lack of difference in severity of initial presentation and remained after exclusion of deaths due to rebleeding, which was higher in cocaine users, Dr. Neeraj Naval said at the International Stroke Conference. The study will also be presented at the annual meeting of the American Academy of Neurology in San Diego on March 19.

Patrice Wendling/IMNG Medical Media

"Patients with acute subarachnoid hemorrhage following cocaine use warrant very close monitoring," said Dr. Naval, director of Neurosciences Critical Care at Johns Hopkins Bayview Medical Center in Baltimore.

Although cocaine use and aneurysmal subarachnoid hemorrhage (SAH) is not controversial, data have been scattered on how cocaine affects presentation and outcomes, he observed. In the largest series prior to this, cocaine use had no significant effect on symptomatic vasospasm or neurologic outcome among 600 patients with SAH (World Neurosurg. 2010;73:357-60). An earlier study, however, showed a 2.8-fold higher risk of vasospasm and 3.3-fold higher risk of poor outcome among cocaine users with SAH (J. Neurosurg. 2003;99:271-5).

Dr. Naval and his colleagues reviewed 1,134 patients admitted to one of two Johns Hopkins University hospitals for ruptured brain aneurysm between 1991 and 2009. The cohort included 142 patients (12.5%) who had a history of cocaine use in the 72 hours prior to admission based on self-report or urine toxicology, and 992 with no cocaine use. Cocaine users were more likely to be younger (49 years vs. 53 years), but had similar rates of poor grade 4/5 Hunt & Hess scores (21% vs. 26%) and associated intraventricular hemorrhage (IVH, 56% vs. 51%). Their mean Glasgow Coma Scale scores at admission were also similar (15 in users vs. 14 in nonusers).

In all, 26% of cocaine users and 17% of nonusers died in the hospital (P = .01).

Significant independent predictors of in-hospital death were cocaine use (adjusted odds ratio 2.85), admission Hunt & Hess score (OR 2.33) and higher age (OR 1.03; all P less than .001), Dr. Naval said.

Cocaine users had higher rates of aneurysm re-rupture (7.7% vs. 2.7%; P = .004). Unfortunately, admission mean arterial pressure (MAP) data were unreliable from 1991 to 2005, but data available from 2006 to 2009 showed higher MAP in cocaine users, he said.

Cocaine users were more likely to have delayed cerebral ischemia (22% vs. 16%; P = .041), but the association was not statistically significant after correction for other confounding factors, including age and IVH. Delayed cerebral ischemia was defined as new clinical deterioration more than 48 hours post-SAH and more than 24 hours after surgical clipping or endovascular coiling, radiologic confirmation of cerebral infarction, and/or angiographic confirmation of vasospasm and/or clinical responsiveness (transient or sustained) to hemodynamic augmentation.

Dr. Naval suggested that it is controversial to include IVH in the model because data are available suggesting that cocaine use is independently associated with a higher rate of IVH in patients with intracerebral hemorrhage.

"If there really is a cause-effect relationship between cocaine use and IVH, one wonders whether using IVH in the multivariate analysis may mask the true impact of cocaine exposure on vasospasm-mediated cerebral infarction," he said.

The investigators did not demonstrate any difference between groups in functional outcomes at discharge or post discharge. Dr. Naval said this was not surprising given the significant difference in age between the groups, with younger patients much more likely to recover from neurological injury.

When asked during a discussion of the study to speculate on the mechanism of elevated mortality in cocaine users, Dr. Naval said subsequent analyses found no difference in rates of withdrawal of care between groups and no impact with frequency of cocaine use or delayed cerebral ischemia. Regional wall motion abnormalities have been identified in cocaine users, but electrocardiograms were not performed to tease out the impact of myocardial stunning on mortality.

In terms of its implications for management, a case could be made to use antifibrinolytic therapy in patients with SAH who are cocaine users because of the higher risk of rebleeding, but Dr. Naval said that a trial would be needed to evaluate this.

The conference was sponsored by the American Heart Association. Dr. Naval reported honoraria from EKR Therapeutics. His coauthors made no disclosures.

[email protected]

HONOLULU -- Recent cocaine use raised the risk of death nearly threefold in a cohort of more than 1,000 patients who were hospitalized for an acute aneurysmal subarachnoid hemorrhage.

The significantly elevated risk of death was observed despite a lack of difference in severity of initial presentation and remained after exclusion of deaths due to rebleeding, which was higher in cocaine users, Dr. Neeraj Naval said at the International Stroke Conference. The study will also be presented at the annual meeting of the American Academy of Neurology in San Diego on March 19.

Patrice Wendling/IMNG Medical Media

"Patients with acute subarachnoid hemorrhage following cocaine use warrant very close monitoring," said Dr. Naval, director of Neurosciences Critical Care at Johns Hopkins Bayview Medical Center in Baltimore.

Although cocaine use and aneurysmal subarachnoid hemorrhage (SAH) is not controversial, data have been scattered on how cocaine affects presentation and outcomes, he observed. In the largest series prior to this, cocaine use had no significant effect on symptomatic vasospasm or neurologic outcome among 600 patients with SAH (World Neurosurg. 2010;73:357-60). An earlier study, however, showed a 2.8-fold higher risk of vasospasm and 3.3-fold higher risk of poor outcome among cocaine users with SAH (J. Neurosurg. 2003;99:271-5).

Dr. Naval and his colleagues reviewed 1,134 patients admitted to one of two Johns Hopkins University hospitals for ruptured brain aneurysm between 1991 and 2009. The cohort included 142 patients (12.5%) who had a history of cocaine use in the 72 hours prior to admission based on self-report or urine toxicology, and 992 with no cocaine use. Cocaine users were more likely to be younger (49 years vs. 53 years), but had similar rates of poor grade 4/5 Hunt & Hess scores (21% vs. 26%) and associated intraventricular hemorrhage (IVH, 56% vs. 51%). Their mean Glasgow Coma Scale scores at admission were also similar (15 in users vs. 14 in nonusers).

In all, 26% of cocaine users and 17% of nonusers died in the hospital (P = .01).

Significant independent predictors of in-hospital death were cocaine use (adjusted odds ratio 2.85), admission Hunt & Hess score (OR 2.33) and higher age (OR 1.03; all P less than .001), Dr. Naval said.

Cocaine users had higher rates of aneurysm re-rupture (7.7% vs. 2.7%; P = .004). Unfortunately, admission mean arterial pressure (MAP) data were unreliable from 1991 to 2005, but data available from 2006 to 2009 showed higher MAP in cocaine users, he said.

Cocaine users were more likely to have delayed cerebral ischemia (22% vs. 16%; P = .041), but the association was not statistically significant after correction for other confounding factors, including age and IVH. Delayed cerebral ischemia was defined as new clinical deterioration more than 48 hours post-SAH and more than 24 hours after surgical clipping or endovascular coiling, radiologic confirmation of cerebral infarction, and/or angiographic confirmation of vasospasm and/or clinical responsiveness (transient or sustained) to hemodynamic augmentation.

Dr. Naval suggested that it is controversial to include IVH in the model because data are available suggesting that cocaine use is independently associated with a higher rate of IVH in patients with intracerebral hemorrhage.

"If there really is a cause-effect relationship between cocaine use and IVH, one wonders whether using IVH in the multivariate analysis may mask the true impact of cocaine exposure on vasospasm-mediated cerebral infarction," he said.

The investigators did not demonstrate any difference between groups in functional outcomes at discharge or post discharge. Dr. Naval said this was not surprising given the significant difference in age between the groups, with younger patients much more likely to recover from neurological injury.

When asked during a discussion of the study to speculate on the mechanism of elevated mortality in cocaine users, Dr. Naval said subsequent analyses found no difference in rates of withdrawal of care between groups and no impact with frequency of cocaine use or delayed cerebral ischemia. Regional wall motion abnormalities have been identified in cocaine users, but electrocardiograms were not performed to tease out the impact of myocardial stunning on mortality.

In terms of its implications for management, a case could be made to use antifibrinolytic therapy in patients with SAH who are cocaine users because of the higher risk of rebleeding, but Dr. Naval said that a trial would be needed to evaluate this.

The conference was sponsored by the American Heart Association. Dr. Naval reported honoraria from EKR Therapeutics. His coauthors made no disclosures.

[email protected]

HONOLULU -- Recent cocaine use raised the risk of death nearly threefold in a cohort of more than 1,000 patients who were hospitalized for an acute aneurysmal subarachnoid hemorrhage.

The significantly elevated risk of death was observed despite a lack of difference in severity of initial presentation and remained after exclusion of deaths due to rebleeding, which was higher in cocaine users, Dr. Neeraj Naval said at the International Stroke Conference. The study will also be presented at the annual meeting of the American Academy of Neurology in San Diego on March 19.

Patrice Wendling/IMNG Medical Media

"Patients with acute subarachnoid hemorrhage following cocaine use warrant very close monitoring," said Dr. Naval, director of Neurosciences Critical Care at Johns Hopkins Bayview Medical Center in Baltimore.

Although cocaine use and aneurysmal subarachnoid hemorrhage (SAH) is not controversial, data have been scattered on how cocaine affects presentation and outcomes, he observed. In the largest series prior to this, cocaine use had no significant effect on symptomatic vasospasm or neurologic outcome among 600 patients with SAH (World Neurosurg. 2010;73:357-60). An earlier study, however, showed a 2.8-fold higher risk of vasospasm and 3.3-fold higher risk of poor outcome among cocaine users with SAH (J. Neurosurg. 2003;99:271-5).

Dr. Naval and his colleagues reviewed 1,134 patients admitted to one of two Johns Hopkins University hospitals for ruptured brain aneurysm between 1991 and 2009. The cohort included 142 patients (12.5%) who had a history of cocaine use in the 72 hours prior to admission based on self-report or urine toxicology, and 992 with no cocaine use. Cocaine users were more likely to be younger (49 years vs. 53 years), but had similar rates of poor grade 4/5 Hunt & Hess scores (21% vs. 26%) and associated intraventricular hemorrhage (IVH, 56% vs. 51%). Their mean Glasgow Coma Scale scores at admission were also similar (15 in users vs. 14 in nonusers).

In all, 26% of cocaine users and 17% of nonusers died in the hospital (P = .01).

Significant independent predictors of in-hospital death were cocaine use (adjusted odds ratio 2.85), admission Hunt & Hess score (OR 2.33) and higher age (OR 1.03; all P less than .001), Dr. Naval said.

Cocaine users had higher rates of aneurysm re-rupture (7.7% vs. 2.7%; P = .004). Unfortunately, admission mean arterial pressure (MAP) data were unreliable from 1991 to 2005, but data available from 2006 to 2009 showed higher MAP in cocaine users, he said.

Cocaine users were more likely to have delayed cerebral ischemia (22% vs. 16%; P = .041), but the association was not statistically significant after correction for other confounding factors, including age and IVH. Delayed cerebral ischemia was defined as new clinical deterioration more than 48 hours post-SAH and more than 24 hours after surgical clipping or endovascular coiling, radiologic confirmation of cerebral infarction, and/or angiographic confirmation of vasospasm and/or clinical responsiveness (transient or sustained) to hemodynamic augmentation.

Dr. Naval suggested that it is controversial to include IVH in the model because data are available suggesting that cocaine use is independently associated with a higher rate of IVH in patients with intracerebral hemorrhage.

"If there really is a cause-effect relationship between cocaine use and IVH, one wonders whether using IVH in the multivariate analysis may mask the true impact of cocaine exposure on vasospasm-mediated cerebral infarction," he said.

The investigators did not demonstrate any difference between groups in functional outcomes at discharge or post discharge. Dr. Naval said this was not surprising given the significant difference in age between the groups, with younger patients much more likely to recover from neurological injury.

When asked during a discussion of the study to speculate on the mechanism of elevated mortality in cocaine users, Dr. Naval said subsequent analyses found no difference in rates of withdrawal of care between groups and no impact with frequency of cocaine use or delayed cerebral ischemia. Regional wall motion abnormalities have been identified in cocaine users, but electrocardiograms were not performed to tease out the impact of myocardial stunning on mortality.

In terms of its implications for management, a case could be made to use antifibrinolytic therapy in patients with SAH who are cocaine users because of the higher risk of rebleeding, but Dr. Naval said that a trial would be needed to evaluate this.

The conference was sponsored by the American Heart Association. Dr. Naval reported honoraria from EKR Therapeutics. His coauthors made no disclosures.

[email protected]

Boston emergency department physicians are now reporting impaired motorists for possible driver’s license revocation.

Over a 16-month period, 31% of admitted drivers were impaired. Of these, 17 were considered medically unqualified to drive, and 86 needed further medical evaluation.

"The vast majority of patients believe they’ll be reported [to authorities] if they arrive at the hospital impaired or under the influence, but that is not the case in Massachusetts, or in most other states from what we’ve found," according to trauma surgeon Eric Mahoney, who helped develop the reporting protocol.

Many health care personnel resist such reporting because they fear a lawsuit or retaliation. The Massachusetts Safe Driving Law of 2010 has changed the landscape by expanding the ability of health care providers and law enforcement to report drivers whom the health care providers believe are unfit to drive because of cognitive or functional impairment. The reports are sent to the Registry of Motor Vehicles (RMV), not the police.

"This has never been meant to be punitive," noted Dr. Mahoney of the department of trauma and emergency services at Boston Medical Center.

The intent has always been to get impaired drivers to visit their physicians to adjust their medication if needed, reevaluate their medical condition, or, if impairment results from substance abuse, counsel them. It’s been shown that the more contact patients have with health care, the more successful they will be at managing their health problems, he said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma (EAST).

The protocol may also reduce motor vehicle crashes by having recidivists held accountable for their actions.

"In our state, the acquittal rate is close to 90% for first-time DUI offenders, so we know the current system in place really isn’t working," according to study coauthor Lisa Allee, Boston Medical Center’s injury prevention coordinator. "So our goal is to reduce recidivism and get people the help they need," she said.

Dr. Mahoney and his colleagues used the Massachusetts RMV definition of impaired driving and vetted HIPPA compliance through the hospital’s legal department. A physician can request that the RMV medical advisory board seek medical evaluation of a driver when the physician has a good faith belief of impairment based on personal observation, physical examinations, or laboratory studies. The request cannot be based on driver age or previous diagnosis.

When the accident involves substance abuse, reporting is limited to instances of a "violent/high risk" to the public such as driving in the wrong direction of traffic, speed exceeding 55 mph, having a child or loaded firearm in the car, or fleeing from police

In the 16-month study period, 363 motor vehicle–crash drivers were admitted to the ED, of which 114 (31%) were impaired and 90% met the "dangerousness" requirement, Dr. Mahoney reported. Their average age was 42 years, 60% were white, 23% were black, 8% were Hispanic, and 41% had private commercial insurance.

Of those reported as being impaired, 18% were incapacitated by a medical condition, 78% were impaired because of substance use, and 3% were incapacitated by both.

Syncope and seizure were the most common medical conditions causing impairment (50% and 25%), followed by about 5% each of narcolepsy, brain lesion, respiratory failure, dizziness, dementia, normal pressure hydrocephalus, and cerebrovascular accident.

Alcohol was the most common substance causing impairment, present in more than 80% of cases, followed by a benzodiazepine, cocaine, and other prescriptions, he said.

"Impairment is common in drivers admitted to the trauma center, and 90% are violent, dangerous to the public," Dr. Mahoney said. "We need to encourage and empower others to report."

Courtesy Wikimedia Commons/Huhu Uet/Creative Commons License

The topic of impaired drivers was on the radar of other EAST investigators. Dr. Felicia Ivascu of the Beaumont Health System in Royal Oak, Mich., reported that 11% of the 541 crash victims treated from 2008 to 2010 at their level I trauma center were legally intoxicated. Moreover, data available on 52 of these drivers revealed these patients cost the hospital $5.2 million in total charges, which accounts for 12% of all charges for drivers.

Michigan is one of 12 states to have no-fault automobile insurance, and the only one that provides unlimited medical benefits. Because of the high costs, House Bill 5588 was recently introduced to remove no-fault benefits if a person is found driving while intoxicated or impaired at the time of the accident, regardless of responsibility.

The dilemma, however, is that passage of the bill would reduce net revenue, and "this will lead to a large financial burden for hospitals that treat intoxicated drivers, requiring them to either absorb this cost or pass it on to Medicaid," the authors wrote.

Dr. Mahoney, Dr. Ivascu, and their coauthors reported no relevant financial disclosures.

[email protected]

Boston emergency department physicians are now reporting impaired motorists for possible driver’s license revocation.

Over a 16-month period, 31% of admitted drivers were impaired. Of these, 17 were considered medically unqualified to drive, and 86 needed further medical evaluation.

"The vast majority of patients believe they’ll be reported [to authorities] if they arrive at the hospital impaired or under the influence, but that is not the case in Massachusetts, or in most other states from what we’ve found," according to trauma surgeon Eric Mahoney, who helped develop the reporting protocol.

Many health care personnel resist such reporting because they fear a lawsuit or retaliation. The Massachusetts Safe Driving Law of 2010 has changed the landscape by expanding the ability of health care providers and law enforcement to report drivers whom the health care providers believe are unfit to drive because of cognitive or functional impairment. The reports are sent to the Registry of Motor Vehicles (RMV), not the police.

"This has never been meant to be punitive," noted Dr. Mahoney of the department of trauma and emergency services at Boston Medical Center.

The intent has always been to get impaired drivers to visit their physicians to adjust their medication if needed, reevaluate their medical condition, or, if impairment results from substance abuse, counsel them. It’s been shown that the more contact patients have with health care, the more successful they will be at managing their health problems, he said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma (EAST).

The protocol may also reduce motor vehicle crashes by having recidivists held accountable for their actions.

"In our state, the acquittal rate is close to 90% for first-time DUI offenders, so we know the current system in place really isn’t working," according to study coauthor Lisa Allee, Boston Medical Center’s injury prevention coordinator. "So our goal is to reduce recidivism and get people the help they need," she said.

Dr. Mahoney and his colleagues used the Massachusetts RMV definition of impaired driving and vetted HIPPA compliance through the hospital’s legal department. A physician can request that the RMV medical advisory board seek medical evaluation of a driver when the physician has a good faith belief of impairment based on personal observation, physical examinations, or laboratory studies. The request cannot be based on driver age or previous diagnosis.

When the accident involves substance abuse, reporting is limited to instances of a "violent/high risk" to the public such as driving in the wrong direction of traffic, speed exceeding 55 mph, having a child or loaded firearm in the car, or fleeing from police

In the 16-month study period, 363 motor vehicle–crash drivers were admitted to the ED, of which 114 (31%) were impaired and 90% met the "dangerousness" requirement, Dr. Mahoney reported. Their average age was 42 years, 60% were white, 23% were black, 8% were Hispanic, and 41% had private commercial insurance.

Of those reported as being impaired, 18% were incapacitated by a medical condition, 78% were impaired because of substance use, and 3% were incapacitated by both.

Syncope and seizure were the most common medical conditions causing impairment (50% and 25%), followed by about 5% each of narcolepsy, brain lesion, respiratory failure, dizziness, dementia, normal pressure hydrocephalus, and cerebrovascular accident.

Alcohol was the most common substance causing impairment, present in more than 80% of cases, followed by a benzodiazepine, cocaine, and other prescriptions, he said.

"Impairment is common in drivers admitted to the trauma center, and 90% are violent, dangerous to the public," Dr. Mahoney said. "We need to encourage and empower others to report."

Courtesy Wikimedia Commons/Huhu Uet/Creative Commons License

The topic of impaired drivers was on the radar of other EAST investigators. Dr. Felicia Ivascu of the Beaumont Health System in Royal Oak, Mich., reported that 11% of the 541 crash victims treated from 2008 to 2010 at their level I trauma center were legally intoxicated. Moreover, data available on 52 of these drivers revealed these patients cost the hospital $5.2 million in total charges, which accounts for 12% of all charges for drivers.

Michigan is one of 12 states to have no-fault automobile insurance, and the only one that provides unlimited medical benefits. Because of the high costs, House Bill 5588 was recently introduced to remove no-fault benefits if a person is found driving while intoxicated or impaired at the time of the accident, regardless of responsibility.

The dilemma, however, is that passage of the bill would reduce net revenue, and "this will lead to a large financial burden for hospitals that treat intoxicated drivers, requiring them to either absorb this cost or pass it on to Medicaid," the authors wrote.

Dr. Mahoney, Dr. Ivascu, and their coauthors reported no relevant financial disclosures.

[email protected]

Boston emergency department physicians are now reporting impaired motorists for possible driver’s license revocation.

Over a 16-month period, 31% of admitted drivers were impaired. Of these, 17 were considered medically unqualified to drive, and 86 needed further medical evaluation.

"The vast majority of patients believe they’ll be reported [to authorities] if they arrive at the hospital impaired or under the influence, but that is not the case in Massachusetts, or in most other states from what we’ve found," according to trauma surgeon Eric Mahoney, who helped develop the reporting protocol.

Many health care personnel resist such reporting because they fear a lawsuit or retaliation. The Massachusetts Safe Driving Law of 2010 has changed the landscape by expanding the ability of health care providers and law enforcement to report drivers whom the health care providers believe are unfit to drive because of cognitive or functional impairment. The reports are sent to the Registry of Motor Vehicles (RMV), not the police.

"This has never been meant to be punitive," noted Dr. Mahoney of the department of trauma and emergency services at Boston Medical Center.

The intent has always been to get impaired drivers to visit their physicians to adjust their medication if needed, reevaluate their medical condition, or, if impairment results from substance abuse, counsel them. It’s been shown that the more contact patients have with health care, the more successful they will be at managing their health problems, he said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma (EAST).

The protocol may also reduce motor vehicle crashes by having recidivists held accountable for their actions.

"In our state, the acquittal rate is close to 90% for first-time DUI offenders, so we know the current system in place really isn’t working," according to study coauthor Lisa Allee, Boston Medical Center’s injury prevention coordinator. "So our goal is to reduce recidivism and get people the help they need," she said.

Dr. Mahoney and his colleagues used the Massachusetts RMV definition of impaired driving and vetted HIPPA compliance through the hospital’s legal department. A physician can request that the RMV medical advisory board seek medical evaluation of a driver when the physician has a good faith belief of impairment based on personal observation, physical examinations, or laboratory studies. The request cannot be based on driver age or previous diagnosis.

When the accident involves substance abuse, reporting is limited to instances of a "violent/high risk" to the public such as driving in the wrong direction of traffic, speed exceeding 55 mph, having a child or loaded firearm in the car, or fleeing from police

In the 16-month study period, 363 motor vehicle–crash drivers were admitted to the ED, of which 114 (31%) were impaired and 90% met the "dangerousness" requirement, Dr. Mahoney reported. Their average age was 42 years, 60% were white, 23% were black, 8% were Hispanic, and 41% had private commercial insurance.

Of those reported as being impaired, 18% were incapacitated by a medical condition, 78% were impaired because of substance use, and 3% were incapacitated by both.

Syncope and seizure were the most common medical conditions causing impairment (50% and 25%), followed by about 5% each of narcolepsy, brain lesion, respiratory failure, dizziness, dementia, normal pressure hydrocephalus, and cerebrovascular accident.

Alcohol was the most common substance causing impairment, present in more than 80% of cases, followed by a benzodiazepine, cocaine, and other prescriptions, he said.

"Impairment is common in drivers admitted to the trauma center, and 90% are violent, dangerous to the public," Dr. Mahoney said. "We need to encourage and empower others to report."

Courtesy Wikimedia Commons/Huhu Uet/Creative Commons License

The topic of impaired drivers was on the radar of other EAST investigators. Dr. Felicia Ivascu of the Beaumont Health System in Royal Oak, Mich., reported that 11% of the 541 crash victims treated from 2008 to 2010 at their level I trauma center were legally intoxicated. Moreover, data available on 52 of these drivers revealed these patients cost the hospital $5.2 million in total charges, which accounts for 12% of all charges for drivers.

Michigan is one of 12 states to have no-fault automobile insurance, and the only one that provides unlimited medical benefits. Because of the high costs, House Bill 5588 was recently introduced to remove no-fault benefits if a person is found driving while intoxicated or impaired at the time of the accident, regardless of responsibility.

The dilemma, however, is that passage of the bill would reduce net revenue, and "this will lead to a large financial burden for hospitals that treat intoxicated drivers, requiring them to either absorb this cost or pass it on to Medicaid," the authors wrote.

Dr. Mahoney, Dr. Ivascu, and their coauthors reported no relevant financial disclosures.

[email protected]

Sixteen cases of acute kidney injury following the use of synthetic cannabinoids were identified in the United States in 2012, according to a report from the Centers for Disease Control and Prevention.

The cases, which occurred in six states and were unrelated in all but two incidents, underscore the importance of awareness on the part of health care providers about renal and other unexpected toxicities from the use of synthetic cannabinoid (SC) compounds, the CDC said in the Feb. 15 issue of the Morbidity and Mortality Weekly Report.

Courtesy DEA

This is particularly true given the increasing use of SCs, also known as synthetic marijuana, "spice," or "K2, and in light of prior reports of toxicities associated with SC.

The initial four cases of acute kidney injury (AKI) following recent SC use were reported in Wyoming in March 2012, and an additional 12 cases were subsequently identified, including 6 in Oregon, 2 in New York, 2 in Oklahoma, and 1 each in Rhode Island and Kansas (MMWR 2013;62:93-8).

The patients – 15 adolescent or adult males aged 15-33 years, and one 15-year-old female – all visited emergency departments complaining of nausea and vomiting within days or hours of SC use; 12 also reported abdominal, flank, and/or back pain, and none had preexisting renal dysfunction or used medications associated with renal problems. All were hospitalized.

"The highest serum creatinine concentrations (creatinine peak) among the 16 patients ranged from 3.3 to 21.0 mg/dL (median: 6.7 mg/dL; normal 0.6-1.3 mg/dL) and occurred 1-6 days after symptom onset (median: 3 days)," according to the report.

Urinalysis results were variable, demonstrating proteinuria in eight patients, casts in five patients, white blood cells in nine patients, and red blood cells in eight patients. Renal ultrasonography in 12 patients showed that 9 had a nonspecific increase in renal cortical echogenicity. None had hydronephrosis.

Renal biopsy in eight patients demonstrated acute tubular injury in six cases, and features of acute interstitial nephritis in three.

Most patients experienced kidney function recovery within 3 days of creatinine peak, but five required hemodialysis, and four received corticosteroids.

Toxicologic analysis of the implicated SC product and clinical specimens were possible in seven cases, and two products were linked with the first three cases. These products contained 3-(1-naphthoyl) indole, a precursor to several aminoalkylindole synthetic cannabinoids, and one also contained AM 2201, a potent SC previously linked to human disease and death, but not to AKI.

With one exception, other product samples and/or blood or urine specimens from patients contained XLR-11 (a previously undescribed fluorinated-derivative of the known SC compound UR-144) either alone or in combination with an N-pentanoic acid metabolite of XLR-11 or UR-144.

These reports of AKI following SC use are concerning given the worldwide distribution of SC products, which are "packaged in colorful wrappers designed to appeal to teens, young adults, and first-time drug users," according to an editorial note in the report, which also states that SCs often are packaged with disingenuous labels claiming the products are not for human consumption, although it is widely known that they are smoked like marijuana.

Despite federal and state regulations prohibiting SC sale and distribution, illicit use continues, and reports of illness are increasing.

"The increasing use of synthetic cannabinoids in adolescents is particularly concerning because these substances can contain multiple active and inactive substances with a variety of short-term and potentially unknown long-term effects," Dr. Joanna S. Cohen said in an interview.

In a case study published last year, Dr. Cohen, of the departments of pediatrics and emergency medicine at George Washington University, Washington, noted the increasing use of SCs among adolescents, the potential dangers of SCs with respect to the developing brain, and the need for providers to become familiar with the presenting signs and symptoms of SC-related intoxication (Pediatrics 2012;129:e1064-7).

According to the MMWR report, SCs are related to the active ingredient in marijuana (delta-9-tetrahydrocannabinol), but are up to three times more likely to be associated with sympathomimetic effects such as tachycardia and hypertension, and about five times more likely to be associated with hallucinations.

An increase in seizure occurrence also has been reported with SC use.

"Given the rapidity with which new SC compounds enter the marketplace and their increasing use in the past 3 years, outbreaks of unexpected toxicity associated with their use are likely to increase," the CDC said.

Furthermore, no antidote currently exists; management of SC toxicity is symptomatic and supportive. All patients in this report of 16 cases of AKI recovered creatinine clearance during their hospital stay, but a risk for long-term kidney sequelae is possible. Findings from recent studies suggest the risk for chronic and end-stage renal disease is increased among patients who experience AKI, regardless of etiology and initial recovery.

The CDC recommends that physicians caring for adolescents and young adults with unexplained AKI inquire about SC use. Cases of suspected SC poisoning should be reported to the appropriate state health department, and to a regional poison center by calling 800-222-1222.

The authors reported on disclosures.

Sixteen cases of acute kidney injury following the use of synthetic cannabinoids were identified in the United States in 2012, according to a report from the Centers for Disease Control and Prevention.

The cases, which occurred in six states and were unrelated in all but two incidents, underscore the importance of awareness on the part of health care providers about renal and other unexpected toxicities from the use of synthetic cannabinoid (SC) compounds, the CDC said in the Feb. 15 issue of the Morbidity and Mortality Weekly Report.

Courtesy DEA

This is particularly true given the increasing use of SCs, also known as synthetic marijuana, "spice," or "K2, and in light of prior reports of toxicities associated with SC.

The initial four cases of acute kidney injury (AKI) following recent SC use were reported in Wyoming in March 2012, and an additional 12 cases were subsequently identified, including 6 in Oregon, 2 in New York, 2 in Oklahoma, and 1 each in Rhode Island and Kansas (MMWR 2013;62:93-8).

The patients – 15 adolescent or adult males aged 15-33 years, and one 15-year-old female – all visited emergency departments complaining of nausea and vomiting within days or hours of SC use; 12 also reported abdominal, flank, and/or back pain, and none had preexisting renal dysfunction or used medications associated with renal problems. All were hospitalized.

"The highest serum creatinine concentrations (creatinine peak) among the 16 patients ranged from 3.3 to 21.0 mg/dL (median: 6.7 mg/dL; normal 0.6-1.3 mg/dL) and occurred 1-6 days after symptom onset (median: 3 days)," according to the report.

Urinalysis results were variable, demonstrating proteinuria in eight patients, casts in five patients, white blood cells in nine patients, and red blood cells in eight patients. Renal ultrasonography in 12 patients showed that 9 had a nonspecific increase in renal cortical echogenicity. None had hydronephrosis.

Renal biopsy in eight patients demonstrated acute tubular injury in six cases, and features of acute interstitial nephritis in three.

Most patients experienced kidney function recovery within 3 days of creatinine peak, but five required hemodialysis, and four received corticosteroids.

Toxicologic analysis of the implicated SC product and clinical specimens were possible in seven cases, and two products were linked with the first three cases. These products contained 3-(1-naphthoyl) indole, a precursor to several aminoalkylindole synthetic cannabinoids, and one also contained AM 2201, a potent SC previously linked to human disease and death, but not to AKI.

With one exception, other product samples and/or blood or urine specimens from patients contained XLR-11 (a previously undescribed fluorinated-derivative of the known SC compound UR-144) either alone or in combination with an N-pentanoic acid metabolite of XLR-11 or UR-144.

These reports of AKI following SC use are concerning given the worldwide distribution of SC products, which are "packaged in colorful wrappers designed to appeal to teens, young adults, and first-time drug users," according to an editorial note in the report, which also states that SCs often are packaged with disingenuous labels claiming the products are not for human consumption, although it is widely known that they are smoked like marijuana.

Despite federal and state regulations prohibiting SC sale and distribution, illicit use continues, and reports of illness are increasing.

"The increasing use of synthetic cannabinoids in adolescents is particularly concerning because these substances can contain multiple active and inactive substances with a variety of short-term and potentially unknown long-term effects," Dr. Joanna S. Cohen said in an interview.

In a case study published last year, Dr. Cohen, of the departments of pediatrics and emergency medicine at George Washington University, Washington, noted the increasing use of SCs among adolescents, the potential dangers of SCs with respect to the developing brain, and the need for providers to become familiar with the presenting signs and symptoms of SC-related intoxication (Pediatrics 2012;129:e1064-7).

According to the MMWR report, SCs are related to the active ingredient in marijuana (delta-9-tetrahydrocannabinol), but are up to three times more likely to be associated with sympathomimetic effects such as tachycardia and hypertension, and about five times more likely to be associated with hallucinations.

An increase in seizure occurrence also has been reported with SC use.

"Given the rapidity with which new SC compounds enter the marketplace and their increasing use in the past 3 years, outbreaks of unexpected toxicity associated with their use are likely to increase," the CDC said.

Furthermore, no antidote currently exists; management of SC toxicity is symptomatic and supportive. All patients in this report of 16 cases of AKI recovered creatinine clearance during their hospital stay, but a risk for long-term kidney sequelae is possible. Findings from recent studies suggest the risk for chronic and end-stage renal disease is increased among patients who experience AKI, regardless of etiology and initial recovery.

The CDC recommends that physicians caring for adolescents and young adults with unexplained AKI inquire about SC use. Cases of suspected SC poisoning should be reported to the appropriate state health department, and to a regional poison center by calling 800-222-1222.

The authors reported on disclosures.

Sixteen cases of acute kidney injury following the use of synthetic cannabinoids were identified in the United States in 2012, according to a report from the Centers for Disease Control and Prevention.

The cases, which occurred in six states and were unrelated in all but two incidents, underscore the importance of awareness on the part of health care providers about renal and other unexpected toxicities from the use of synthetic cannabinoid (SC) compounds, the CDC said in the Feb. 15 issue of the Morbidity and Mortality Weekly Report.

Courtesy DEA

This is particularly true given the increasing use of SCs, also known as synthetic marijuana, "spice," or "K2, and in light of prior reports of toxicities associated with SC.

The initial four cases of acute kidney injury (AKI) following recent SC use were reported in Wyoming in March 2012, and an additional 12 cases were subsequently identified, including 6 in Oregon, 2 in New York, 2 in Oklahoma, and 1 each in Rhode Island and Kansas (MMWR 2013;62:93-8).

The patients – 15 adolescent or adult males aged 15-33 years, and one 15-year-old female – all visited emergency departments complaining of nausea and vomiting within days or hours of SC use; 12 also reported abdominal, flank, and/or back pain, and none had preexisting renal dysfunction or used medications associated with renal problems. All were hospitalized.

"The highest serum creatinine concentrations (creatinine peak) among the 16 patients ranged from 3.3 to 21.0 mg/dL (median: 6.7 mg/dL; normal 0.6-1.3 mg/dL) and occurred 1-6 days after symptom onset (median: 3 days)," according to the report.

Urinalysis results were variable, demonstrating proteinuria in eight patients, casts in five patients, white blood cells in nine patients, and red blood cells in eight patients. Renal ultrasonography in 12 patients showed that 9 had a nonspecific increase in renal cortical echogenicity. None had hydronephrosis.

Renal biopsy in eight patients demonstrated acute tubular injury in six cases, and features of acute interstitial nephritis in three.

Most patients experienced kidney function recovery within 3 days of creatinine peak, but five required hemodialysis, and four received corticosteroids.

Toxicologic analysis of the implicated SC product and clinical specimens were possible in seven cases, and two products were linked with the first three cases. These products contained 3-(1-naphthoyl) indole, a precursor to several aminoalkylindole synthetic cannabinoids, and one also contained AM 2201, a potent SC previously linked to human disease and death, but not to AKI.

With one exception, other product samples and/or blood or urine specimens from patients contained XLR-11 (a previously undescribed fluorinated-derivative of the known SC compound UR-144) either alone or in combination with an N-pentanoic acid metabolite of XLR-11 or UR-144.

These reports of AKI following SC use are concerning given the worldwide distribution of SC products, which are "packaged in colorful wrappers designed to appeal to teens, young adults, and first-time drug users," according to an editorial note in the report, which also states that SCs often are packaged with disingenuous labels claiming the products are not for human consumption, although it is widely known that they are smoked like marijuana.

Despite federal and state regulations prohibiting SC sale and distribution, illicit use continues, and reports of illness are increasing.

"The increasing use of synthetic cannabinoids in adolescents is particularly concerning because these substances can contain multiple active and inactive substances with a variety of short-term and potentially unknown long-term effects," Dr. Joanna S. Cohen said in an interview.

In a case study published last year, Dr. Cohen, of the departments of pediatrics and emergency medicine at George Washington University, Washington, noted the increasing use of SCs among adolescents, the potential dangers of SCs with respect to the developing brain, and the need for providers to become familiar with the presenting signs and symptoms of SC-related intoxication (Pediatrics 2012;129:e1064-7).

According to the MMWR report, SCs are related to the active ingredient in marijuana (delta-9-tetrahydrocannabinol), but are up to three times more likely to be associated with sympathomimetic effects such as tachycardia and hypertension, and about five times more likely to be associated with hallucinations.

An increase in seizure occurrence also has been reported with SC use.

"Given the rapidity with which new SC compounds enter the marketplace and their increasing use in the past 3 years, outbreaks of unexpected toxicity associated with their use are likely to increase," the CDC said.

Furthermore, no antidote currently exists; management of SC toxicity is symptomatic and supportive. All patients in this report of 16 cases of AKI recovered creatinine clearance during their hospital stay, but a risk for long-term kidney sequelae is possible. Findings from recent studies suggest the risk for chronic and end-stage renal disease is increased among patients who experience AKI, regardless of etiology and initial recovery.

The CDC recommends that physicians caring for adolescents and young adults with unexplained AKI inquire about SC use. Cases of suspected SC poisoning should be reported to the appropriate state health department, and to a regional poison center by calling 800-222-1222.

The authors reported on disclosures.

PRAGUE  – Low-dose thalidomide for refractory cutaneous lupus erythematosus is best used together with hydroxychloroquine or another antimalarial agent rather than as monotherapy, Dr. Victoria P. Werth asserted at the annual congress of the European Academy of Dermatology and Venereology.

When prescribing thalidomide for a patient with refractory cutaneous lupus erythematosus (CLE), many physicians discontinue antimalarial therapy, reasoning that since the patient wasn’t responsive to monotherapy, there’s no point in continued exposure to the potential risks. But that’s probably a mistake. Combination therapy acting through different mechanisms may boost the likelihood of a good response; plus, the antiplatelet action of hydroxychloroquine or another antimalarial agent will help counteract thalidomide’s prothrombotic effects, said Dr. Werth, professor of dermatology at the University of Pennsylvania, Philadelphia.

Thalidomide is unquestionably an effective therapy in patients with refractory CLE. But it’s also a drug with big problems, including perhaps an increased stroke risk, as highlighted in a recent Spanish study, she noted.

The Spanish study included 60 consecutive patients with refractory CLE who were treated with thalidomide at 100 mg/day and followed for up to 8 years. One dropped out due to side effects. Fifty-eight of the remaining 59 experienced significant clinical improvement, including 49 (85%) with a complete response as defined by a CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) activity score of 0.

Relapse occurred in most patients, usually about 5 months after thalidomide dose reduction or withdrawal. Patients with subacute CLE were 30-fold more likely to remain in remission after drug discontinuation; those with discoid LE were at increased risk for relapse (Br. J. Dermatol. 2012;166:616-23).

Of particular concern to Dr. Werth was the finding that two patients had a stroke while on the drug. Neither had antiphospholipid antibodies, and one was quite young to have had a stroke, although both were heavy smokers.

Prescribing a drug such as thalidomide that promotes a hypercoagulable state to patients with refractory CLE is problematic because they often already have multiple risk factors for thrombosis. For one thing, treatment-refractory CLE patients tend to be smokers. Many of them are women on oral contraceptives. And there is an increased prevalence of antiphospholipid antibodies in patients with CLE, according to Dr. Werth.

Neuropathy is another major issue with thalidomide. In the Spanish study, 11 of 60 patients (18%) developed paresthesias; nerve conduction studies confirmed sensory polyneuropathy in 5 of the 11. Fortunately, the neurologic symptoms resolved in an average of 12 months after drug withdrawal.

Of course, thalidomide is a notorious teratogen. It can also cause premature ovarian failure, although this is usually reversible upon drug discontinuation.

"Obviously we need better therapies than thalidomide," Dr. Werth concluded.

Toward that end, interest is growing in thalidomide analogues as a novel potential therapy for refractory CLE. These analogues are up to 50,000 times more active than thalidomide, and are potentially less neurotoxic. One of them, lenalidomide (Revlimid), is marketed as a treatment for multiple myeloma and myelodysplastic syndrome. Others are in the development pipeline.

Several small observational studies have recently reported favorable results with lenalidomide in patients with refractory CLE. For example, investigators at Vall d’Hebron University Hospital in Barcelona reported on 15 patients treated open label with lenalidomide at 5-10 mg/day, with a follow-up of 15 months. One patient dropped out early due to side effects, but the other 14 saw clinical improvement within the first 2 weeks. Twelve patients, or 86%, achieved a CLASI score of 0. However, 9 of 12 complete responders experienced clinical relapse, usually 2-8 weeks after the drug was tapered and discontinued. Side effects were mild and infrequent, with no thrombosis or polyneuropathy (Arthritis Res. Ther. 2012;14:R265).

In another series, 4 of 5 lenalidomide-treated patients showed significant skin improvement, although one eventually developed symptoms of SLE (J. Am. Acad. Dermatol. 2012;66:571-82).

Based upon these and other promising reports, Celgene, which markets lenalidomide, recently launched the first-ever phase II study of a thalidomide analogue for the treatment of CLE.

Dr. Werth reported having no financial conflicts.

PRAGUE  – Low-dose thalidomide for refractory cutaneous lupus erythematosus is best used together with hydroxychloroquine or another antimalarial agent rather than as monotherapy, Dr. Victoria P. Werth asserted at the annual congress of the European Academy of Dermatology and Venereology.

When prescribing thalidomide for a patient with refractory cutaneous lupus erythematosus (CLE), many physicians discontinue antimalarial therapy, reasoning that since the patient wasn’t responsive to monotherapy, there’s no point in continued exposure to the potential risks. But that’s probably a mistake. Combination therapy acting through different mechanisms may boost the likelihood of a good response; plus, the antiplatelet action of hydroxychloroquine or another antimalarial agent will help counteract thalidomide’s prothrombotic effects, said Dr. Werth, professor of dermatology at the University of Pennsylvania, Philadelphia.

Thalidomide is unquestionably an effective therapy in patients with refractory CLE. But it’s also a drug with big problems, including perhaps an increased stroke risk, as highlighted in a recent Spanish study, she noted.

The Spanish study included 60 consecutive patients with refractory CLE who were treated with thalidomide at 100 mg/day and followed for up to 8 years. One dropped out due to side effects. Fifty-eight of the remaining 59 experienced significant clinical improvement, including 49 (85%) with a complete response as defined by a CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) activity score of 0.

Relapse occurred in most patients, usually about 5 months after thalidomide dose reduction or withdrawal. Patients with subacute CLE were 30-fold more likely to remain in remission after drug discontinuation; those with discoid LE were at increased risk for relapse (Br. J. Dermatol. 2012;166:616-23).

Of particular concern to Dr. Werth was the finding that two patients had a stroke while on the drug. Neither had antiphospholipid antibodies, and one was quite young to have had a stroke, although both were heavy smokers.

Prescribing a drug such as thalidomide that promotes a hypercoagulable state to patients with refractory CLE is problematic because they often already have multiple risk factors for thrombosis. For one thing, treatment-refractory CLE patients tend to be smokers. Many of them are women on oral contraceptives. And there is an increased prevalence of antiphospholipid antibodies in patients with CLE, according to Dr. Werth.

Neuropathy is another major issue with thalidomide. In the Spanish study, 11 of 60 patients (18%) developed paresthesias; nerve conduction studies confirmed sensory polyneuropathy in 5 of the 11. Fortunately, the neurologic symptoms resolved in an average of 12 months after drug withdrawal.

Of course, thalidomide is a notorious teratogen. It can also cause premature ovarian failure, although this is usually reversible upon drug discontinuation.

"Obviously we need better therapies than thalidomide," Dr. Werth concluded.

Toward that end, interest is growing in thalidomide analogues as a novel potential therapy for refractory CLE. These analogues are up to 50,000 times more active than thalidomide, and are potentially less neurotoxic. One of them, lenalidomide (Revlimid), is marketed as a treatment for multiple myeloma and myelodysplastic syndrome. Others are in the development pipeline.

Several small observational studies have recently reported favorable results with lenalidomide in patients with refractory CLE. For example, investigators at Vall d’Hebron University Hospital in Barcelona reported on 15 patients treated open label with lenalidomide at 5-10 mg/day, with a follow-up of 15 months. One patient dropped out early due to side effects, but the other 14 saw clinical improvement within the first 2 weeks. Twelve patients, or 86%, achieved a CLASI score of 0. However, 9 of 12 complete responders experienced clinical relapse, usually 2-8 weeks after the drug was tapered and discontinued. Side effects were mild and infrequent, with no thrombosis or polyneuropathy (Arthritis Res. Ther. 2012;14:R265).

In another series, 4 of 5 lenalidomide-treated patients showed significant skin improvement, although one eventually developed symptoms of SLE (J. Am. Acad. Dermatol. 2012;66:571-82).

Based upon these and other promising reports, Celgene, which markets lenalidomide, recently launched the first-ever phase II study of a thalidomide analogue for the treatment of CLE.

Dr. Werth reported having no financial conflicts.

PRAGUE  – Low-dose thalidomide for refractory cutaneous lupus erythematosus is best used together with hydroxychloroquine or another antimalarial agent rather than as monotherapy, Dr. Victoria P. Werth asserted at the annual congress of the European Academy of Dermatology and Venereology.

When prescribing thalidomide for a patient with refractory cutaneous lupus erythematosus (CLE), many physicians discontinue antimalarial therapy, reasoning that since the patient wasn’t responsive to monotherapy, there’s no point in continued exposure to the potential risks. But that’s probably a mistake. Combination therapy acting through different mechanisms may boost the likelihood of a good response; plus, the antiplatelet action of hydroxychloroquine or another antimalarial agent will help counteract thalidomide’s prothrombotic effects, said Dr. Werth, professor of dermatology at the University of Pennsylvania, Philadelphia.

Thalidomide is unquestionably an effective therapy in patients with refractory CLE. But it’s also a drug with big problems, including perhaps an increased stroke risk, as highlighted in a recent Spanish study, she noted.

The Spanish study included 60 consecutive patients with refractory CLE who were treated with thalidomide at 100 mg/day and followed for up to 8 years. One dropped out due to side effects. Fifty-eight of the remaining 59 experienced significant clinical improvement, including 49 (85%) with a complete response as defined by a CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) activity score of 0.

Relapse occurred in most patients, usually about 5 months after thalidomide dose reduction or withdrawal. Patients with subacute CLE were 30-fold more likely to remain in remission after drug discontinuation; those with discoid LE were at increased risk for relapse (Br. J. Dermatol. 2012;166:616-23).

Of particular concern to Dr. Werth was the finding that two patients had a stroke while on the drug. Neither had antiphospholipid antibodies, and one was quite young to have had a stroke, although both were heavy smokers.

Prescribing a drug such as thalidomide that promotes a hypercoagulable state to patients with refractory CLE is problematic because they often already have multiple risk factors for thrombosis. For one thing, treatment-refractory CLE patients tend to be smokers. Many of them are women on oral contraceptives. And there is an increased prevalence of antiphospholipid antibodies in patients with CLE, according to Dr. Werth.

Neuropathy is another major issue with thalidomide. In the Spanish study, 11 of 60 patients (18%) developed paresthesias; nerve conduction studies confirmed sensory polyneuropathy in 5 of the 11. Fortunately, the neurologic symptoms resolved in an average of 12 months after drug withdrawal.

Of course, thalidomide is a notorious teratogen. It can also cause premature ovarian failure, although this is usually reversible upon drug discontinuation.

"Obviously we need better therapies than thalidomide," Dr. Werth concluded.

Toward that end, interest is growing in thalidomide analogues as a novel potential therapy for refractory CLE. These analogues are up to 50,000 times more active than thalidomide, and are potentially less neurotoxic. One of them, lenalidomide (Revlimid), is marketed as a treatment for multiple myeloma and myelodysplastic syndrome. Others are in the development pipeline.

Several small observational studies have recently reported favorable results with lenalidomide in patients with refractory CLE. For example, investigators at Vall d’Hebron University Hospital in Barcelona reported on 15 patients treated open label with lenalidomide at 5-10 mg/day, with a follow-up of 15 months. One patient dropped out early due to side effects, but the other 14 saw clinical improvement within the first 2 weeks. Twelve patients, or 86%, achieved a CLASI score of 0. However, 9 of 12 complete responders experienced clinical relapse, usually 2-8 weeks after the drug was tapered and discontinued. Side effects were mild and infrequent, with no thrombosis or polyneuropathy (Arthritis Res. Ther. 2012;14:R265).

In another series, 4 of 5 lenalidomide-treated patients showed significant skin improvement, although one eventually developed symptoms of SLE (J. Am. Acad. Dermatol. 2012;66:571-82).

Based upon these and other promising reports, Celgene, which markets lenalidomide, recently launched the first-ever phase II study of a thalidomide analogue for the treatment of CLE.

Dr. Werth reported having no financial conflicts.

DENVER – Most rashes and other skin conditions are not worrisome, but a few are signs of potentially fatal infections or disease processes.

Recognizing and knowing how best to treat these "death rashes" literally make the difference between life and death, Dr. Heather Murphy-Lavoie said at the annual meeting of the American College of Emergency Physicians.

Courtesy Dr. Heather Murphy-Lavoie

"You don’t want to miss it. You want to make the diagnosis early and use specific interventions that reduce morbidity and mortality," said Dr. Murphy-Lavoie of Louisiana State University, New Orleans.

She co-created a free app for iPhones and iPads colloquially called "EM Rashes" to help emergency physicians who might be puzzled by a patient with an undifferentiated rash. The app user picks from a selection of rash types, then answers a series of simple questions, such as, "Is the patient febrile?" The app then uses an algorithm to narrow the differential diagnoses, discuss possible causes and findings, and list treatments.

Dr. Murphy-Lavoie offered the following pearls for physicians who are thinking about rashes.

Petechiae and fever? Worry! Only about 50% of people with Rocky Mountain spotted fever will recall a tick bite, so you have to be suspecting it if you’re in an appropriate geographic area. Patients get febrile and toxic. The rash starts out on the wrist and ankle as a maculopapular rash and then spreads and becomes petechial.

"The tip-off is that it spreads to the palms and the soles," she said. "It’s a vasculitis, so it’s a palpable petechiae."

Rocky Mountain spotted fever is a bit of a misnomer, because the disease occurs largely in central and eastern states like North Carolina, Georgia, Tennessee, and Arkansas.

"This is a clinical diagnosis," she said. Don’t wait the 4-5 days it takes to get serology results from a laboratory to decide on treatment. Up to 15% of people with Rocky Mountain spotted fever may develop permanent neurologic deficits. Treatment with doxycycline reduces the risk of death from 30% to 5%. In pregnant women consider chloramphenicol instead of doxycycline, she suggested.

Palpable petechiae, vasculitis could mean infection. A patient with fever, mental status changes, vasculitis, and palpable petechiae should scare you, Dr. Murphy-Lavoie said. This could be meningococcemia, which carries a 3%-50% mortality rate depending on the promptness of treatment. Over the last 10 years in the United States, the mortality has hovered around 13%, she said.

Courtesy Dr. Heather Murphy-Lavoie

Ceftriaxone is the drug of choice. "Because of diagnostic uncertainty, any time you have a suspected case of bacterial meningitis, you’re going to add on vancomycin to cover resistant Streptococcus," and dexamethasone has been shown to decrease neurologic sequelae, she said. People exposed to a patient with this disease should get prophylactic therapy

Palpable petechiae also are a feature of many types of bacteremia. Petechiae are the most common skin manifestation of bacterial endocarditis, but it’s only present in 20%-40% of cases. When you suspect bacterial endocarditis, get three sets of blood cultures because nailing down the type of bacteria will inform the long-term treatment strategy. Treat initially with broad-spectrum IV antibiotics such as vancomycin and gentamicin to cover methicillin-resistant Staphylococcus aureus (MRSA).

"If you have a S. aureus–related endocarditis, your mortality is almost double that of a streptococcal endocarditis, so you really, really have to make sure that you’re covering for MRSA," she said.

Nonpalpable petechiae = thrombocytopenia. "If petechiae are not palpable, it’s thrombocytopenia unless proven otherwise," Dr. Murphy-Lavoie said.

A febrile, tachycardic woman came to her emergency room complaining of a rash on both legs comprising diffuse, nonpalpable petechiae. She appeared generally ill, had no past medical or medication history of note, and had a very low platelet count. "You should be scared to death if you get this patient in your ER," because she had thrombotic thrombocytopenia purpura (TTP).

More than 90% of patients will die if TTP is not treated with plasmapheresis (also called exchange transfusion), which reduces the mortality risk to 10%. If this treatment is not available at your institution, transfer the patient, she said. Manage the patient in the ICU, and treat the underlying cause of the TTP. Do not give platelets to patients with TTP, which will trigger increased end-organ damage, she warned.

Hemorrhagic bullae? Ominous! "Nothing good causes hemorrhagic bullae," Dr. Murphy-Lavoie said.

Anything that can cause disseminated intravascular coagulation can cause purpura fulminans, which may present with hemorrhagic bullae, rapid hemorrhagic skin necrosis, ecchymosis, purpura, fever, shock, multiorgan failure, and bleeding from multiple sites.

Lab results will show thrombocytopenia, hemolytic anemia, increases in prothrombin time and partial thromboplastin time, and an increase in fibrin degradation products. As the disease progresses, the fibrinogen level falls.

Treatment starts off similar to treating TTP, with an emergent consultation with hematology/oncology, ICU admission, and treatment of the underlying illness. Add supporting vitamin K and folate. "Then it gets tricky," she said. "You’re going to need to balance how much of their problem is from bleeding and not enough coagulation factors and platelets, and how much is from overactivation of the fibrinolytic system and bleeding, and whether or not you need heparin to treat their thrombus. You really don’t want to be doing this in your emergency department."

Hemorrhagic bullae also are a classic presentation of necrotizing fasciitis, along with pain out of proportion for typical cellulitis, systemic toxicity, crepitus, and rapid spread along fascial planes. Not all cases of necrotizing fasciitis will have hemorrhagic bullae, but worry if you see this, she said.

Treat with strategic debridement and broad-spectrum antibiotics. Studies have shown that adding hyperbaric oxygen therapy decreases mortality risk. It’s not worth transferring someone with necrotizing fasciitis to someplace hours away in order to get hyperbaric oxygen, but if this is available, "please use it," she urged. In the literature, mortality rates with necrotizing fasciitis range from 0% to 75%. "Guess which ones had 0% mortality patients who got hyperbaric oxygen."

Consider steroids for bullous rash with mucosal involvement. A woman came to Dr. Murphy-Lavoie’s emergency department complaining of a rash and pain with swallowing. She appeared moderately toxic, was tachycardic, had a bullous rash, and had dry mucous membranes but with oral lesions. Diagnosis: pemphigus vulgaris, which will involve mucosal surfaces 70% of the time.

The bullae may coalesce, and there may be a positive Nikolsky sign (sloughing of full-thickness skin with lateral pressure) and a positive Asboe-Hansen sign (light lateral pressure on the blister edge spreads the blister into adjacent clinically normal skin).

The biggest favor that emergency physicians can do for these patients is to start them on steroids. Before the advent of steroid therapy for pemphigus vulgaris, 50%-90% of patients died, compared with 4%-15% who are treated with steroids. Also provide local wound care to prevent secondary infection. Pemphigus vulgaris is associated with autoimmune diseases, and long-term management with immunosuppressive drugs probably will be handled by a rheumatologist, she said.

Dr. Murphy-Lavoie reported having no financial disclosures. She codeveloped the free app "EM Rashes."

DENVER – Most rashes and other skin conditions are not worrisome, but a few are signs of potentially fatal infections or disease processes.

Recognizing and knowing how best to treat these "death rashes" literally make the difference between life and death, Dr. Heather Murphy-Lavoie said at the annual meeting of the American College of Emergency Physicians.

Courtesy Dr. Heather Murphy-Lavoie

"You don’t want to miss it. You want to make the diagnosis early and use specific interventions that reduce morbidity and mortality," said Dr. Murphy-Lavoie of Louisiana State University, New Orleans.

She co-created a free app for iPhones and iPads colloquially called "EM Rashes" to help emergency physicians who might be puzzled by a patient with an undifferentiated rash. The app user picks from a selection of rash types, then answers a series of simple questions, such as, "Is the patient febrile?" The app then uses an algorithm to narrow the differential diagnoses, discuss possible causes and findings, and list treatments.

Dr. Murphy-Lavoie offered the following pearls for physicians who are thinking about rashes.

Petechiae and fever? Worry! Only about 50% of people with Rocky Mountain spotted fever will recall a tick bite, so you have to be suspecting it if you’re in an appropriate geographic area. Patients get febrile and toxic. The rash starts out on the wrist and ankle as a maculopapular rash and then spreads and becomes petechial.

"The tip-off is that it spreads to the palms and the soles," she said. "It’s a vasculitis, so it’s a palpable petechiae."

Rocky Mountain spotted fever is a bit of a misnomer, because the disease occurs largely in central and eastern states like North Carolina, Georgia, Tennessee, and Arkansas.

"This is a clinical diagnosis," she said. Don’t wait the 4-5 days it takes to get serology results from a laboratory to decide on treatment. Up to 15% of people with Rocky Mountain spotted fever may develop permanent neurologic deficits. Treatment with doxycycline reduces the risk of death from 30% to 5%. In pregnant women consider chloramphenicol instead of doxycycline, she suggested.

Palpable petechiae, vasculitis could mean infection. A patient with fever, mental status changes, vasculitis, and palpable petechiae should scare you, Dr. Murphy-Lavoie said. This could be meningococcemia, which carries a 3%-50% mortality rate depending on the promptness of treatment. Over the last 10 years in the United States, the mortality has hovered around 13%, she said.

Courtesy Dr. Heather Murphy-Lavoie

Ceftriaxone is the drug of choice. "Because of diagnostic uncertainty, any time you have a suspected case of bacterial meningitis, you’re going to add on vancomycin to cover resistant Streptococcus," and dexamethasone has been shown to decrease neurologic sequelae, she said. People exposed to a patient with this disease should get prophylactic therapy

Palpable petechiae also are a feature of many types of bacteremia. Petechiae are the most common skin manifestation of bacterial endocarditis, but it’s only present in 20%-40% of cases. When you suspect bacterial endocarditis, get three sets of blood cultures because nailing down the type of bacteria will inform the long-term treatment strategy. Treat initially with broad-spectrum IV antibiotics such as vancomycin and gentamicin to cover methicillin-resistant Staphylococcus aureus (MRSA).

"If you have a S. aureus–related endocarditis, your mortality is almost double that of a streptococcal endocarditis, so you really, really have to make sure that you’re covering for MRSA," she said.

Nonpalpable petechiae = thrombocytopenia. "If petechiae are not palpable, it’s thrombocytopenia unless proven otherwise," Dr. Murphy-Lavoie said.

A febrile, tachycardic woman came to her emergency room complaining of a rash on both legs comprising diffuse, nonpalpable petechiae. She appeared generally ill, had no past medical or medication history of note, and had a very low platelet count. "You should be scared to death if you get this patient in your ER," because she had thrombotic thrombocytopenia purpura (TTP).

More than 90% of patients will die if TTP is not treated with plasmapheresis (also called exchange transfusion), which reduces the mortality risk to 10%. If this treatment is not available at your institution, transfer the patient, she said. Manage the patient in the ICU, and treat the underlying cause of the TTP. Do not give platelets to patients with TTP, which will trigger increased end-organ damage, she warned.

Hemorrhagic bullae? Ominous! "Nothing good causes hemorrhagic bullae," Dr. Murphy-Lavoie said.

Anything that can cause disseminated intravascular coagulation can cause purpura fulminans, which may present with hemorrhagic bullae, rapid hemorrhagic skin necrosis, ecchymosis, purpura, fever, shock, multiorgan failure, and bleeding from multiple sites.

Lab results will show thrombocytopenia, hemolytic anemia, increases in prothrombin time and partial thromboplastin time, and an increase in fibrin degradation products. As the disease progresses, the fibrinogen level falls.

Treatment starts off similar to treating TTP, with an emergent consultation with hematology/oncology, ICU admission, and treatment of the underlying illness. Add supporting vitamin K and folate. "Then it gets tricky," she said. "You’re going to need to balance how much of their problem is from bleeding and not enough coagulation factors and platelets, and how much is from overactivation of the fibrinolytic system and bleeding, and whether or not you need heparin to treat their thrombus. You really don’t want to be doing this in your emergency department."

Hemorrhagic bullae also are a classic presentation of necrotizing fasciitis, along with pain out of proportion for typical cellulitis, systemic toxicity, crepitus, and rapid spread along fascial planes. Not all cases of necrotizing fasciitis will have hemorrhagic bullae, but worry if you see this, she said.

Treat with strategic debridement and broad-spectrum antibiotics. Studies have shown that adding hyperbaric oxygen therapy decreases mortality risk. It’s not worth transferring someone with necrotizing fasciitis to someplace hours away in order to get hyperbaric oxygen, but if this is available, "please use it," she urged. In the literature, mortality rates with necrotizing fasciitis range from 0% to 75%. "Guess which ones had 0% mortality patients who got hyperbaric oxygen."

Consider steroids for bullous rash with mucosal involvement. A woman came to Dr. Murphy-Lavoie’s emergency department complaining of a rash and pain with swallowing. She appeared moderately toxic, was tachycardic, had a bullous rash, and had dry mucous membranes but with oral lesions. Diagnosis: pemphigus vulgaris, which will involve mucosal surfaces 70% of the time.

The bullae may coalesce, and there may be a positive Nikolsky sign (sloughing of full-thickness skin with lateral pressure) and a positive Asboe-Hansen sign (light lateral pressure on the blister edge spreads the blister into adjacent clinically normal skin).

The biggest favor that emergency physicians can do for these patients is to start them on steroids. Before the advent of steroid therapy for pemphigus vulgaris, 50%-90% of patients died, compared with 4%-15% who are treated with steroids. Also provide local wound care to prevent secondary infection. Pemphigus vulgaris is associated with autoimmune diseases, and long-term management with immunosuppressive drugs probably will be handled by a rheumatologist, she said.

Dr. Murphy-Lavoie reported having no financial disclosures. She codeveloped the free app "EM Rashes."

DENVER – Most rashes and other skin conditions are not worrisome, but a few are signs of potentially fatal infections or disease processes.

Recognizing and knowing how best to treat these "death rashes" literally make the difference between life and death, Dr. Heather Murphy-Lavoie said at the annual meeting of the American College of Emergency Physicians.

Courtesy Dr. Heather Murphy-Lavoie

"You don’t want to miss it. You want to make the diagnosis early and use specific interventions that reduce morbidity and mortality," said Dr. Murphy-Lavoie of Louisiana State University, New Orleans.

She co-created a free app for iPhones and iPads colloquially called "EM Rashes" to help emergency physicians who might be puzzled by a patient with an undifferentiated rash. The app user picks from a selection of rash types, then answers a series of simple questions, such as, "Is the patient febrile?" The app then uses an algorithm to narrow the differential diagnoses, discuss possible causes and findings, and list treatments.

Dr. Murphy-Lavoie offered the following pearls for physicians who are thinking about rashes.

Petechiae and fever? Worry! Only about 50% of people with Rocky Mountain spotted fever will recall a tick bite, so you have to be suspecting it if you’re in an appropriate geographic area. Patients get febrile and toxic. The rash starts out on the wrist and ankle as a maculopapular rash and then spreads and becomes petechial.

"The tip-off is that it spreads to the palms and the soles," she said. "It’s a vasculitis, so it’s a palpable petechiae."

Rocky Mountain spotted fever is a bit of a misnomer, because the disease occurs largely in central and eastern states like North Carolina, Georgia, Tennessee, and Arkansas.

"This is a clinical diagnosis," she said. Don’t wait the 4-5 days it takes to get serology results from a laboratory to decide on treatment. Up to 15% of people with Rocky Mountain spotted fever may develop permanent neurologic deficits. Treatment with doxycycline reduces the risk of death from 30% to 5%. In pregnant women consider chloramphenicol instead of doxycycline, she suggested.

Palpable petechiae, vasculitis could mean infection. A patient with fever, mental status changes, vasculitis, and palpable petechiae should scare you, Dr. Murphy-Lavoie said. This could be meningococcemia, which carries a 3%-50% mortality rate depending on the promptness of treatment. Over the last 10 years in the United States, the mortality has hovered around 13%, she said.

Courtesy Dr. Heather Murphy-Lavoie

Ceftriaxone is the drug of choice. "Because of diagnostic uncertainty, any time you have a suspected case of bacterial meningitis, you’re going to add on vancomycin to cover resistant Streptococcus," and dexamethasone has been shown to decrease neurologic sequelae, she said. People exposed to a patient with this disease should get prophylactic therapy

Palpable petechiae also are a feature of many types of bacteremia. Petechiae are the most common skin manifestation of bacterial endocarditis, but it’s only present in 20%-40% of cases. When you suspect bacterial endocarditis, get three sets of blood cultures because nailing down the type of bacteria will inform the long-term treatment strategy. Treat initially with broad-spectrum IV antibiotics such as vancomycin and gentamicin to cover methicillin-resistant Staphylococcus aureus (MRSA).

"If you have a S. aureus–related endocarditis, your mortality is almost double that of a streptococcal endocarditis, so you really, really have to make sure that you’re covering for MRSA," she said.

Nonpalpable petechiae = thrombocytopenia. "If petechiae are not palpable, it’s thrombocytopenia unless proven otherwise," Dr. Murphy-Lavoie said.

A febrile, tachycardic woman came to her emergency room complaining of a rash on both legs comprising diffuse, nonpalpable petechiae. She appeared generally ill, had no past medical or medication history of note, and had a very low platelet count. "You should be scared to death if you get this patient in your ER," because she had thrombotic thrombocytopenia purpura (TTP).

More than 90% of patients will die if TTP is not treated with plasmapheresis (also called exchange transfusion), which reduces the mortality risk to 10%. If this treatment is not available at your institution, transfer the patient, she said. Manage the patient in the ICU, and treat the underlying cause of the TTP. Do not give platelets to patients with TTP, which will trigger increased end-organ damage, she warned.

Hemorrhagic bullae? Ominous! "Nothing good causes hemorrhagic bullae," Dr. Murphy-Lavoie said.

Anything that can cause disseminated intravascular coagulation can cause purpura fulminans, which may present with hemorrhagic bullae, rapid hemorrhagic skin necrosis, ecchymosis, purpura, fever, shock, multiorgan failure, and bleeding from multiple sites.

Lab results will show thrombocytopenia, hemolytic anemia, increases in prothrombin time and partial thromboplastin time, and an increase in fibrin degradation products. As the disease progresses, the fibrinogen level falls.

Treatment starts off similar to treating TTP, with an emergent consultation with hematology/oncology, ICU admission, and treatment of the underlying illness. Add supporting vitamin K and folate. "Then it gets tricky," she said. "You’re going to need to balance how much of their problem is from bleeding and not enough coagulation factors and platelets, and how much is from overactivation of the fibrinolytic system and bleeding, and whether or not you need heparin to treat their thrombus. You really don’t want to be doing this in your emergency department."

Hemorrhagic bullae also are a classic presentation of necrotizing fasciitis, along with pain out of proportion for typical cellulitis, systemic toxicity, crepitus, and rapid spread along fascial planes. Not all cases of necrotizing fasciitis will have hemorrhagic bullae, but worry if you see this, she said.

Treat with strategic debridement and broad-spectrum antibiotics. Studies have shown that adding hyperbaric oxygen therapy decreases mortality risk. It’s not worth transferring someone with necrotizing fasciitis to someplace hours away in order to get hyperbaric oxygen, but if this is available, "please use it," she urged. In the literature, mortality rates with necrotizing fasciitis range from 0% to 75%. "Guess which ones had 0% mortality patients who got hyperbaric oxygen."

Consider steroids for bullous rash with mucosal involvement. A woman came to Dr. Murphy-Lavoie’s emergency department complaining of a rash and pain with swallowing. She appeared moderately toxic, was tachycardic, had a bullous rash, and had dry mucous membranes but with oral lesions. Diagnosis: pemphigus vulgaris, which will involve mucosal surfaces 70% of the time.

The bullae may coalesce, and there may be a positive Nikolsky sign (sloughing of full-thickness skin with lateral pressure) and a positive Asboe-Hansen sign (light lateral pressure on the blister edge spreads the blister into adjacent clinically normal skin).

The biggest favor that emergency physicians can do for these patients is to start them on steroids. Before the advent of steroid therapy for pemphigus vulgaris, 50%-90% of patients died, compared with 4%-15% who are treated with steroids. Also provide local wound care to prevent secondary infection. Pemphigus vulgaris is associated with autoimmune diseases, and long-term management with immunosuppressive drugs probably will be handled by a rheumatologist, she said.

Dr. Murphy-Lavoie reported having no financial disclosures. She codeveloped the free app "EM Rashes."

The outbreak of fungal meningitis caused by contaminated methylprednisolone has topped 200 patients and is likely to include more, according to a review article on the subject published online in the New England Journal of Medicine. The article was written in an attempt to answer some of the "numerous questions have been raised by physicians, patients who received injections from the implicated lots, and the public."

Despite the fact that the first case reported found the mold Aspergillus fumigatus as the cause of the meningitis, this organism was not been detected in any of the subsequent 200-plus cases and is no longer considered as the basis for appropriate treatment. Instead, the fungal plant pathogen, Exserohilum rostratum, has been cultured or identified using polymerase chain reaction assay from cerebrospinal fluid in at least 25 patients and was detected in at least one unopened vial from the implicated lot of methylprednisolone, according to Dr. Carol A. Kaufman of the Veterans Affairs Ann Arbor (Mich.) Healthcare System, and her colleagues from Alabama and Texas.

E. rostratum is a "black mold" containing melanin in its cell wall. It is rarely infectious to humans and is usually restricted to mild diseases, such as allergic sinusitis, keratitis, and localized soft-tissue infection. In tissues, E. rostratum has the same appearance of irregular, beaded hyphae as seen in many other dematiaceous fungi, and unlike the rarely septate, ribbonlike hyphae of Mucorales fungi or the acutely branching, hyaline hyphae of aspergillus species.

Recommendations for treating this rare infection are based on small case series, individual case reports, and personal experience, according to the authors of the review article (N. Engl. J. Med. 2012 [doi:10.10156/NEJMra1212617]). The Centers for Disease Control and Prevention is providing information on the outbreak with daily updates, along with appropriate diagnostic testing and treatment details on its website, according to the authors.

Initially, when the causative agent was not known and the only detected microorganism was A. fumigatus, high doses of both liposomal amphotericin B and voriconazole were recommended. Once the primary pathogen was determined to be the black mold, however, monotherapy with voriconazole was recommended, except for the sickest patients or those who had substantial side-effects to the drug. For these, amphotericin B could still play a role, the said.

Although exserohilum species are susceptible to available antifungals, for some strains, the minimal inhibitor concentration for the usually recommended agents, including voriconazole, is increased. Thus, susceptibility testing is advised, they added.

Because of the potential toxic effects of voriconazole, especially in the large doses recommended, and the host of drug-drug interactions in which it is involved, prophylactic use is not recommended, the authors said. They noted that side effects included visual hallucinations, which have been noted in patients treated during the outbreak. Other side effects can include photopsia, nausea, and hepatic enzyme elevation.

"Without objective evidence of infection in the cerebrospinal fluid, treatment is not recommended. However, patients who have symptoms should be monitored closely, and if there is even subtle progression of symptoms, a repeat lumbar puncture should be performed immediately. If the number of white cells has increased [reaching 5 mm³or more], then empirical antifungal treatment should be initiated immediately," the authors stated.

"It is encouraging to note that clinically apparent disease has developed in only a small percentage of exposed patients. Management recommendations will almost assuredly change as more information becomes available regarding the pathogenesis of these infections," they concluded.

Dr. Kaufman and the other authors reported having no relevant disclosures for their review paper.

The outbreak of fungal meningitis caused by contaminated methylprednisolone has topped 200 patients and is likely to include more, according to a review article on the subject published online in the New England Journal of Medicine. The article was written in an attempt to answer some of the "numerous questions have been raised by physicians, patients who received injections from the implicated lots, and the public."

Despite the fact that the first case reported found the mold Aspergillus fumigatus as the cause of the meningitis, this organism was not been detected in any of the subsequent 200-plus cases and is no longer considered as the basis for appropriate treatment. Instead, the fungal plant pathogen, Exserohilum rostratum, has been cultured or identified using polymerase chain reaction assay from cerebrospinal fluid in at least 25 patients and was detected in at least one unopened vial from the implicated lot of methylprednisolone, according to Dr. Carol A. Kaufman of the Veterans Affairs Ann Arbor (Mich.) Healthcare System, and her colleagues from Alabama and Texas.

E. rostratum is a "black mold" containing melanin in its cell wall. It is rarely infectious to humans and is usually restricted to mild diseases, such as allergic sinusitis, keratitis, and localized soft-tissue infection. In tissues, E. rostratum has the same appearance of irregular, beaded hyphae as seen in many other dematiaceous fungi, and unlike the rarely septate, ribbonlike hyphae of Mucorales fungi or the acutely branching, hyaline hyphae of aspergillus species.

Recommendations for treating this rare infection are based on small case series, individual case reports, and personal experience, according to the authors of the review article (N. Engl. J. Med. 2012 [doi:10.10156/NEJMra1212617]). The Centers for Disease Control and Prevention is providing information on the outbreak with daily updates, along with appropriate diagnostic testing and treatment details on its website, according to the authors.

Initially, when the causative agent was not known and the only detected microorganism was A. fumigatus, high doses of both liposomal amphotericin B and voriconazole were recommended. Once the primary pathogen was determined to be the black mold, however, monotherapy with voriconazole was recommended, except for the sickest patients or those who had substantial side-effects to the drug. For these, amphotericin B could still play a role, the said.

Although exserohilum species are susceptible to available antifungals, for some strains, the minimal inhibitor concentration for the usually recommended agents, including voriconazole, is increased. Thus, susceptibility testing is advised, they added.

Because of the potential toxic effects of voriconazole, especially in the large doses recommended, and the host of drug-drug interactions in which it is involved, prophylactic use is not recommended, the authors said. They noted that side effects included visual hallucinations, which have been noted in patients treated during the outbreak. Other side effects can include photopsia, nausea, and hepatic enzyme elevation.

"Without objective evidence of infection in the cerebrospinal fluid, treatment is not recommended. However, patients who have symptoms should be monitored closely, and if there is even subtle progression of symptoms, a repeat lumbar puncture should be performed immediately. If the number of white cells has increased [reaching 5 mm³or more], then empirical antifungal treatment should be initiated immediately," the authors stated.

"It is encouraging to note that clinically apparent disease has developed in only a small percentage of exposed patients. Management recommendations will almost assuredly change as more information becomes available regarding the pathogenesis of these infections," they concluded.

Dr. Kaufman and the other authors reported having no relevant disclosures for their review paper.

The outbreak of fungal meningitis caused by contaminated methylprednisolone has topped 200 patients and is likely to include more, according to a review article on the subject published online in the New England Journal of Medicine. The article was written in an attempt to answer some of the "numerous questions have been raised by physicians, patients who received injections from the implicated lots, and the public."

Despite the fact that the first case reported found the mold Aspergillus fumigatus as the cause of the meningitis, this organism was not been detected in any of the subsequent 200-plus cases and is no longer considered as the basis for appropriate treatment. Instead, the fungal plant pathogen, Exserohilum rostratum, has been cultured or identified using polymerase chain reaction assay from cerebrospinal fluid in at least 25 patients and was detected in at least one unopened vial from the implicated lot of methylprednisolone, according to Dr. Carol A. Kaufman of the Veterans Affairs Ann Arbor (Mich.) Healthcare System, and her colleagues from Alabama and Texas.

E. rostratum is a "black mold" containing melanin in its cell wall. It is rarely infectious to humans and is usually restricted to mild diseases, such as allergic sinusitis, keratitis, and localized soft-tissue infection. In tissues, E. rostratum has the same appearance of irregular, beaded hyphae as seen in many other dematiaceous fungi, and unlike the rarely septate, ribbonlike hyphae of Mucorales fungi or the acutely branching, hyaline hyphae of aspergillus species.

Recommendations for treating this rare infection are based on small case series, individual case reports, and personal experience, according to the authors of the review article (N. Engl. J. Med. 2012 [doi:10.10156/NEJMra1212617]). The Centers for Disease Control and Prevention is providing information on the outbreak with daily updates, along with appropriate diagnostic testing and treatment details on its website, according to the authors.

Initially, when the causative agent was not known and the only detected microorganism was A. fumigatus, high doses of both liposomal amphotericin B and voriconazole were recommended. Once the primary pathogen was determined to be the black mold, however, monotherapy with voriconazole was recommended, except for the sickest patients or those who had substantial side-effects to the drug. For these, amphotericin B could still play a role, the said.

Although exserohilum species are susceptible to available antifungals, for some strains, the minimal inhibitor concentration for the usually recommended agents, including voriconazole, is increased. Thus, susceptibility testing is advised, they added.

Because of the potential toxic effects of voriconazole, especially in the large doses recommended, and the host of drug-drug interactions in which it is involved, prophylactic use is not recommended, the authors said. They noted that side effects included visual hallucinations, which have been noted in patients treated during the outbreak. Other side effects can include photopsia, nausea, and hepatic enzyme elevation.

"Without objective evidence of infection in the cerebrospinal fluid, treatment is not recommended. However, patients who have symptoms should be monitored closely, and if there is even subtle progression of symptoms, a repeat lumbar puncture should be performed immediately. If the number of white cells has increased [reaching 5 mm³or more], then empirical antifungal treatment should be initiated immediately," the authors stated.

"It is encouraging to note that clinically apparent disease has developed in only a small percentage of exposed patients. Management recommendations will almost assuredly change as more information becomes available regarding the pathogenesis of these infections," they concluded.

Dr. Kaufman and the other authors reported having no relevant disclosures for their review paper.

WASHINGTON – Nationwide efforts to curb prescription drug abuse might be paying off, as fewer Americans reported nonmedical use of such drugs – pain relievers in particular – according to a government survey.

The most significant decline was seen among 18- to 25-year-olds, a 14% decline from 2 million users in 2010 to 1.7 million in 2011. The decline is particularly exciting, because this is a cohort where most substances are abused and a lot mental health disorders occur, said Dr. H. Westley Clark, director of the Substance Abuse and Mental Health Services Administration’s Center for Behavioral Health Statistics and Quality, which plans and manages the annual National Survey on Drug Use and Health. There was no significant change in the overall rate of past-month illicit drug use, which was estimated to be around 8.7% in 2011, compared with 8.9% during the previous year.

The government survey, released by SAMHSA and conducted since 1971, is based on statistical estimates from 67,500 face-to-face interviews with Americans aged 12 years or older.

Over the past 30 years, overall drug use among Americans has declined by 30%, said R. Gil Kerlikowske, director of the White House Office of National Drug Control Policy. He added that the Obama administration has spent more than $31 billion in drug education and treatment programs over the last 3 years.

"We have repeatedly affirmed that we’re not waging a war on drugs," Mr. Kerlikowske said. The administration is taking a holistic approach, instead, he said. "We understand that addiction is disease. It’s not a moral failing. It can be treated, and recovery is possible."

The SAMHSA survey showed that in 2011, nearly 9% of Americans older than 12 years of age reported using an illicit drug, including marijuana, cocaine, heroin, hallucinogens, inhalants, or prescription drugs used nonmedically.

Of the four categories of prescription drugs – pain relievers, tranquilizers, stimulants, and sedatives – the past-month use of pain relievers reported by people aged 12 years or older showed the sharpest decline from 2010, dropping from 2.0% to 1.7%. That was followed by a 0.2% decline in tranquilizers, which were the second most commonly used prescription drugs. The misuse rates for stimulants (0.4%) and sedatives (0.1%) did not change.

More than half of Americans reported being current alcohol drinkers, and more than a quarter said they used tobacco products.

Among the tobacco users, the prevalence of smoking among pregnant women is on the rise (17.6%), the survey showed, slowly creeping up to the ranges reported in 2002-2003 (18%), after reaching a low of 15.2% in 2008-2009.

Marijuana remains the most commonly used illicit drug. The number of users increased from 14.5 million in 2007 (5.8% of Americans) to 18.1 million in 2011 (7.0%).

Meanwhile, the rate of illicit drug use among adults between aged 50-59 years has been increasing since 2002, from 2.7% to 6.3% in 2011. The trend is partly because baby boomers are entering this age group and their "lifetime rate of illicit drug use has been higher than those of older cohorts," authors write in the 150-page report.

2012 National Drug Use Survey

The survey did not include data on synthetic drugs such as bath salts and synthetic marijuana, which have become a concern for state and federal officials only in recent years. Dr. Clark said officials are closely monitoring the states and hope that passage of state and federal bans on chemicals used to make the drugs would curb their spread.

Dr. Clark stressed the importance of physician education, whether it’s through mentoring programs or continuing medical education, as he attributed the decline in prescription drug abuse rates partly to the efforts in the physician community.

"Physicians need to be educated about prescription drug abuse; they need to educate their patients; and they should tell their patients what they should do with prescription drugs that they don’t finish," he said.

More than half of those who reported abusing prescription pain medication said that they had received the drugs from a friend or relative for free. Only 4% reported having received the drugs from a dealer or stranger.

WASHINGTON – Nationwide efforts to curb prescription drug abuse might be paying off, as fewer Americans reported nonmedical use of such drugs – pain relievers in particular – according to a government survey.

The most significant decline was seen among 18- to 25-year-olds, a 14% decline from 2 million users in 2010 to 1.7 million in 2011. The decline is particularly exciting, because this is a cohort where most substances are abused and a lot mental health disorders occur, said Dr. H. Westley Clark, director of the Substance Abuse and Mental Health Services Administration’s Center for Behavioral Health Statistics and Quality, which plans and manages the annual National Survey on Drug Use and Health. There was no significant change in the overall rate of past-month illicit drug use, which was estimated to be around 8.7% in 2011, compared with 8.9% during the previous year.

The government survey, released by SAMHSA and conducted since 1971, is based on statistical estimates from 67,500 face-to-face interviews with Americans aged 12 years or older.

Over the past 30 years, overall drug use among Americans has declined by 30%, said R. Gil Kerlikowske, director of the White House Office of National Drug Control Policy. He added that the Obama administration has spent more than $31 billion in drug education and treatment programs over the last 3 years.

"We have repeatedly affirmed that we’re not waging a war on drugs," Mr. Kerlikowske said. The administration is taking a holistic approach, instead, he said. "We understand that addiction is disease. It’s not a moral failing. It can be treated, and recovery is possible."

The SAMHSA survey showed that in 2011, nearly 9% of Americans older than 12 years of age reported using an illicit drug, including marijuana, cocaine, heroin, hallucinogens, inhalants, or prescription drugs used nonmedically.

Of the four categories of prescription drugs – pain relievers, tranquilizers, stimulants, and sedatives – the past-month use of pain relievers reported by people aged 12 years or older showed the sharpest decline from 2010, dropping from 2.0% to 1.7%. That was followed by a 0.2% decline in tranquilizers, which were the second most commonly used prescription drugs. The misuse rates for stimulants (0.4%) and sedatives (0.1%) did not change.

More than half of Americans reported being current alcohol drinkers, and more than a quarter said they used tobacco products.

Among the tobacco users, the prevalence of smoking among pregnant women is on the rise (17.6%), the survey showed, slowly creeping up to the ranges reported in 2002-2003 (18%), after reaching a low of 15.2% in 2008-2009.

Marijuana remains the most commonly used illicit drug. The number of users increased from 14.5 million in 2007 (5.8% of Americans) to 18.1 million in 2011 (7.0%).

Meanwhile, the rate of illicit drug use among adults between aged 50-59 years has been increasing since 2002, from 2.7% to 6.3% in 2011. The trend is partly because baby boomers are entering this age group and their "lifetime rate of illicit drug use has been higher than those of older cohorts," authors write in the 150-page report.

2012 National Drug Use Survey

The survey did not include data on synthetic drugs such as bath salts and synthetic marijuana, which have become a concern for state and federal officials only in recent years. Dr. Clark said officials are closely monitoring the states and hope that passage of state and federal bans on chemicals used to make the drugs would curb their spread.

Dr. Clark stressed the importance of physician education, whether it’s through mentoring programs or continuing medical education, as he attributed the decline in prescription drug abuse rates partly to the efforts in the physician community.

"Physicians need to be educated about prescription drug abuse; they need to educate their patients; and they should tell their patients what they should do with prescription drugs that they don’t finish," he said.

More than half of those who reported abusing prescription pain medication said that they had received the drugs from a friend or relative for free. Only 4% reported having received the drugs from a dealer or stranger.

WASHINGTON – Nationwide efforts to curb prescription drug abuse might be paying off, as fewer Americans reported nonmedical use of such drugs – pain relievers in particular – according to a government survey.

The most significant decline was seen among 18- to 25-year-olds, a 14% decline from 2 million users in 2010 to 1.7 million in 2011. The decline is particularly exciting, because this is a cohort where most substances are abused and a lot mental health disorders occur, said Dr. H. Westley Clark, director of the Substance Abuse and Mental Health Services Administration’s Center for Behavioral Health Statistics and Quality, which plans and manages the annual National Survey on Drug Use and Health. There was no significant change in the overall rate of past-month illicit drug use, which was estimated to be around 8.7% in 2011, compared with 8.9% during the previous year.

The government survey, released by SAMHSA and conducted since 1971, is based on statistical estimates from 67,500 face-to-face interviews with Americans aged 12 years or older.

Over the past 30 years, overall drug use among Americans has declined by 30%, said R. Gil Kerlikowske, director of the White House Office of National Drug Control Policy. He added that the Obama administration has spent more than $31 billion in drug education and treatment programs over the last 3 years.

"We have repeatedly affirmed that we’re not waging a war on drugs," Mr. Kerlikowske said. The administration is taking a holistic approach, instead, he said. "We understand that addiction is disease. It’s not a moral failing. It can be treated, and recovery is possible."

The SAMHSA survey showed that in 2011, nearly 9% of Americans older than 12 years of age reported using an illicit drug, including marijuana, cocaine, heroin, hallucinogens, inhalants, or prescription drugs used nonmedically.

Of the four categories of prescription drugs – pain relievers, tranquilizers, stimulants, and sedatives – the past-month use of pain relievers reported by people aged 12 years or older showed the sharpest decline from 2010, dropping from 2.0% to 1.7%. That was followed by a 0.2% decline in tranquilizers, which were the second most commonly used prescription drugs. The misuse rates for stimulants (0.4%) and sedatives (0.1%) did not change.

More than half of Americans reported being current alcohol drinkers, and more than a quarter said they used tobacco products.

Among the tobacco users, the prevalence of smoking among pregnant women is on the rise (17.6%), the survey showed, slowly creeping up to the ranges reported in 2002-2003 (18%), after reaching a low of 15.2% in 2008-2009.

Marijuana remains the most commonly used illicit drug. The number of users increased from 14.5 million in 2007 (5.8% of Americans) to 18.1 million in 2011 (7.0%).

Meanwhile, the rate of illicit drug use among adults between aged 50-59 years has been increasing since 2002, from 2.7% to 6.3% in 2011. The trend is partly because baby boomers are entering this age group and their "lifetime rate of illicit drug use has been higher than those of older cohorts," authors write in the 150-page report.

2012 National Drug Use Survey

The survey did not include data on synthetic drugs such as bath salts and synthetic marijuana, which have become a concern for state and federal officials only in recent years. Dr. Clark said officials are closely monitoring the states and hope that passage of state and federal bans on chemicals used to make the drugs would curb their spread.

Dr. Clark stressed the importance of physician education, whether it’s through mentoring programs or continuing medical education, as he attributed the decline in prescription drug abuse rates partly to the efforts in the physician community.

"Physicians need to be educated about prescription drug abuse; they need to educate their patients; and they should tell their patients what they should do with prescription drugs that they don’t finish," he said.

More than half of those who reported abusing prescription pain medication said that they had received the drugs from a friend or relative for free. Only 4% reported having received the drugs from a dealer or stranger.