Can a psychiatrist legally and safely prescribe medication to reduce pain and, if so, when? How can a psychiatrist avoid a negligence charge if the patient commits suicide after discharge?

This article offers answers to those questions.

Methadone prescription for pain blamed for overdose death

Richmond (VA) Circuit Court

The patient had been receiving psychiatric treatment for approximately 1 year and also sought care for chronic pain during that time. The psychiatrist prescribed a pain medication and advised the patient to find a physician specializing in pain management, which the patient did.

Later, the patient and her husband told the psychiatrist during an emergency visit that no other physician was willing to treat her pain and requested pain medication. The psychiatrist viewed this request as possible drug-seeking behavior but considered the incident a crisis. She gave the patient a 2-week prescription of methadone for both pain and withdrawal.

Five days later, the patient’s husband found her dead; her autopsy showed a high level of methadone and two other medications.

The plaintiff’s estate claimed that the psychiatrist was negligent and that the patient died from methadone intoxication. The defense argued that the prescription was appropriate, and that amitriptyline, which the patient also had been taking, caused the sudden cardiac arrest that led to her death.

• The jury found for the defense.
  

Dr. Grant’s observations

A physician can prescribe any medication for a legitimate purpose. When prescribing outside your psychiatric expertise—such as medication for this patient’s chronic pain—the following recommendations can help you prevent a negligence claim:

• Document your physical examination. Assess the physical and psychological aspects of a pain condition before treating it. Then document the condition and the rationale behind your treatment choice based on the medical assessment.

If you are uncomfortable examining and diagnosing a medical condition, avoid prescribing pain medication. Instead, refer the patient to a physician specializing in pain management.

• If prescribing pain medication, document the type, location, and severity of pain. Also document your discussion of pain management options with the patient, and ask about previous pain-reduction interventions.

• Assess type, quantity, and frequency of prescription drug use as well as illicit drug and alcohol use. Order urine and serum toxicology tests if you suspect or need to document substance abuse.

As in this case, refer patients with chronic pain to their primary care physicians or to another specialist for appropriate pain management. Pain reduction may require psychological and behavioral interventions (such as cognitivebehavioral therapy, relaxation therapy, hypnosis, biofeedback, stress management, educating patients and their families about pain management) as well as physical therapy, anesthetic treatments, or surgical evaluation.¹

• Assessing pain in the ER. A different level of chronic pain assessment may be necessary in the emergency room, and the law recognizes that resources—such as information from other providers—are limited in the ER.² In this case, the patient reported that no one was willing to treat her, and the psychiatrist feared she was seeking a prescription for illicit use. In such cases, consider contacting the patient’s previous pain specialist or hospitalizing the patient if you fear he or she will go into withdrawal.

Plaintiff: Premature discharge caused alcohol-related suicide by drowning

Lucas County (OH) Common Pleas Court

The patient, age 41, had a longstanding, treatment-refractory alcohol use disorder.

He was admitted to the hospital after he was dismissed from a halfway house; upon admission, his blood alcohol level was 0.41%.

When assessed by a psychiatrist several days later, the patient showed suicidal behavior. The psychiatrist evaluated him three additional times. After the final visit, the patient renounced suicide, and the psychiatrist decided that he had improved. The patient’s discharge was planned—with aftercare housing and outpatient program particiption arranged—and he left the hospital in a taxi.

Three days later, the patient was found dead in a creek. An autopsy showed that the patient died by drowning and that his blood alcohol level was 0.32%. The death was ruled a suicide secondary to excessive alcohol consumption.

The plaintiff—the patient’s estate —charged that the psychiatrist was negligent in discharging the patient from the hospital and claimed that lack of a post-discharge recovery plan made the suicide likely.

The defense argued that the patient’s history of suicide attempts was known and that a discharge plan—which included housing and participation in an outpatient program—was in place before he was discharged.

• The jury found for the defense.
  

Dr. Grant’s observations

Many factors associated with managed care—such as cost-containment policies that shorten hospital stays, shorter visits that limit opportunity to develop a therapeutic alliance with patients, and limited ability to communicate with patients—have increased the risk of malpractice suits alleging premature discharge of patients who later kill themselves.³

To avoid such a suit:⁴

• Document the patient’s risk factors for suicide as well as specific suicidal thoughts and methods expressed, extent of planning and action taken toward a suicide attempt, access to means, and response to prior therapeutic interventions.

• Explain in your notes why specific risk factors were ruled out. This supports the conclusion that you properly assessed the patient.

• Obtain a proper history of the patient’s current illness. Understanding how a patient’s substance use is affecting his mood may influence plans for care after discharge.

• Do not rely solely on a patient’s statements about suicidality. Document information from other sources (old records, previous providers, or family members) and note that you tried to contact collateral sources or get permission to talk with the patient’s family

• Arrange outpatient services that focus on substance addiction (for example, support groups such as Alcoholics Anonymous [see], and therapy with an addictions specialist). Schedule timely visits for therapy and medication management. A medical follow-up may be needed if health concerns are associated with a mental health issue. A patient may need to be placed in a sober house or residential facility if he cannot stay sober on his own.

Can a psychiatrist legally and safely prescribe medication to reduce pain and, if so, when? How can a psychiatrist avoid a negligence charge if the patient commits suicide after discharge?

This article offers answers to those questions.

Methadone prescription for pain blamed for overdose death

Richmond (VA) Circuit Court

The patient had been receiving psychiatric treatment for approximately 1 year and also sought care for chronic pain during that time. The psychiatrist prescribed a pain medication and advised the patient to find a physician specializing in pain management, which the patient did.

Later, the patient and her husband told the psychiatrist during an emergency visit that no other physician was willing to treat her pain and requested pain medication. The psychiatrist viewed this request as possible drug-seeking behavior but considered the incident a crisis. She gave the patient a 2-week prescription of methadone for both pain and withdrawal.

Five days later, the patient’s husband found her dead; her autopsy showed a high level of methadone and two other medications.

The plaintiff’s estate claimed that the psychiatrist was negligent and that the patient died from methadone intoxication. The defense argued that the prescription was appropriate, and that amitriptyline, which the patient also had been taking, caused the sudden cardiac arrest that led to her death.

• The jury found for the defense.
  

Dr. Grant’s observations

A physician can prescribe any medication for a legitimate purpose. When prescribing outside your psychiatric expertise—such as medication for this patient’s chronic pain—the following recommendations can help you prevent a negligence claim:

• Document your physical examination. Assess the physical and psychological aspects of a pain condition before treating it. Then document the condition and the rationale behind your treatment choice based on the medical assessment.

If you are uncomfortable examining and diagnosing a medical condition, avoid prescribing pain medication. Instead, refer the patient to a physician specializing in pain management.

• If prescribing pain medication, document the type, location, and severity of pain. Also document your discussion of pain management options with the patient, and ask about previous pain-reduction interventions.

• Assess type, quantity, and frequency of prescription drug use as well as illicit drug and alcohol use. Order urine and serum toxicology tests if you suspect or need to document substance abuse.

As in this case, refer patients with chronic pain to their primary care physicians or to another specialist for appropriate pain management. Pain reduction may require psychological and behavioral interventions (such as cognitivebehavioral therapy, relaxation therapy, hypnosis, biofeedback, stress management, educating patients and their families about pain management) as well as physical therapy, anesthetic treatments, or surgical evaluation.¹

• Assessing pain in the ER. A different level of chronic pain assessment may be necessary in the emergency room, and the law recognizes that resources—such as information from other providers—are limited in the ER.² In this case, the patient reported that no one was willing to treat her, and the psychiatrist feared she was seeking a prescription for illicit use. In such cases, consider contacting the patient’s previous pain specialist or hospitalizing the patient if you fear he or she will go into withdrawal.

Plaintiff: Premature discharge caused alcohol-related suicide by drowning

Lucas County (OH) Common Pleas Court

The patient, age 41, had a longstanding, treatment-refractory alcohol use disorder.

He was admitted to the hospital after he was dismissed from a halfway house; upon admission, his blood alcohol level was 0.41%.

When assessed by a psychiatrist several days later, the patient showed suicidal behavior. The psychiatrist evaluated him three additional times. After the final visit, the patient renounced suicide, and the psychiatrist decided that he had improved. The patient’s discharge was planned—with aftercare housing and outpatient program particiption arranged—and he left the hospital in a taxi.

Three days later, the patient was found dead in a creek. An autopsy showed that the patient died by drowning and that his blood alcohol level was 0.32%. The death was ruled a suicide secondary to excessive alcohol consumption.

The plaintiff—the patient’s estate —charged that the psychiatrist was negligent in discharging the patient from the hospital and claimed that lack of a post-discharge recovery plan made the suicide likely.

The defense argued that the patient’s history of suicide attempts was known and that a discharge plan—which included housing and participation in an outpatient program—was in place before he was discharged.

• The jury found for the defense.
  

Dr. Grant’s observations

Many factors associated with managed care—such as cost-containment policies that shorten hospital stays, shorter visits that limit opportunity to develop a therapeutic alliance with patients, and limited ability to communicate with patients—have increased the risk of malpractice suits alleging premature discharge of patients who later kill themselves.³

To avoid such a suit:⁴

• Document the patient’s risk factors for suicide as well as specific suicidal thoughts and methods expressed, extent of planning and action taken toward a suicide attempt, access to means, and response to prior therapeutic interventions.

• Explain in your notes why specific risk factors were ruled out. This supports the conclusion that you properly assessed the patient.

• Obtain a proper history of the patient’s current illness. Understanding how a patient’s substance use is affecting his mood may influence plans for care after discharge.

• Do not rely solely on a patient’s statements about suicidality. Document information from other sources (old records, previous providers, or family members) and note that you tried to contact collateral sources or get permission to talk with the patient’s family

• Arrange outpatient services that focus on substance addiction (for example, support groups such as Alcoholics Anonymous [see], and therapy with an addictions specialist). Schedule timely visits for therapy and medication management. A medical follow-up may be needed if health concerns are associated with a mental health issue. A patient may need to be placed in a sober house or residential facility if he cannot stay sober on his own.

Can a psychiatrist legally and safely prescribe medication to reduce pain and, if so, when? How can a psychiatrist avoid a negligence charge if the patient commits suicide after discharge?

This article offers answers to those questions.

Methadone prescription for pain blamed for overdose death

Richmond (VA) Circuit Court

The patient had been receiving psychiatric treatment for approximately 1 year and also sought care for chronic pain during that time. The psychiatrist prescribed a pain medication and advised the patient to find a physician specializing in pain management, which the patient did.

Later, the patient and her husband told the psychiatrist during an emergency visit that no other physician was willing to treat her pain and requested pain medication. The psychiatrist viewed this request as possible drug-seeking behavior but considered the incident a crisis. She gave the patient a 2-week prescription of methadone for both pain and withdrawal.

Five days later, the patient’s husband found her dead; her autopsy showed a high level of methadone and two other medications.

The plaintiff’s estate claimed that the psychiatrist was negligent and that the patient died from methadone intoxication. The defense argued that the prescription was appropriate, and that amitriptyline, which the patient also had been taking, caused the sudden cardiac arrest that led to her death.

• The jury found for the defense.
  

Dr. Grant’s observations

A physician can prescribe any medication for a legitimate purpose. When prescribing outside your psychiatric expertise—such as medication for this patient’s chronic pain—the following recommendations can help you prevent a negligence claim:

• Document your physical examination. Assess the physical and psychological aspects of a pain condition before treating it. Then document the condition and the rationale behind your treatment choice based on the medical assessment.

If you are uncomfortable examining and diagnosing a medical condition, avoid prescribing pain medication. Instead, refer the patient to a physician specializing in pain management.

• If prescribing pain medication, document the type, location, and severity of pain. Also document your discussion of pain management options with the patient, and ask about previous pain-reduction interventions.

• Assess type, quantity, and frequency of prescription drug use as well as illicit drug and alcohol use. Order urine and serum toxicology tests if you suspect or need to document substance abuse.

As in this case, refer patients with chronic pain to their primary care physicians or to another specialist for appropriate pain management. Pain reduction may require psychological and behavioral interventions (such as cognitivebehavioral therapy, relaxation therapy, hypnosis, biofeedback, stress management, educating patients and their families about pain management) as well as physical therapy, anesthetic treatments, or surgical evaluation.¹

• Assessing pain in the ER. A different level of chronic pain assessment may be necessary in the emergency room, and the law recognizes that resources—such as information from other providers—are limited in the ER.² In this case, the patient reported that no one was willing to treat her, and the psychiatrist feared she was seeking a prescription for illicit use. In such cases, consider contacting the patient’s previous pain specialist or hospitalizing the patient if you fear he or she will go into withdrawal.

Plaintiff: Premature discharge caused alcohol-related suicide by drowning

Lucas County (OH) Common Pleas Court

The patient, age 41, had a longstanding, treatment-refractory alcohol use disorder.

He was admitted to the hospital after he was dismissed from a halfway house; upon admission, his blood alcohol level was 0.41%.

When assessed by a psychiatrist several days later, the patient showed suicidal behavior. The psychiatrist evaluated him three additional times. After the final visit, the patient renounced suicide, and the psychiatrist decided that he had improved. The patient’s discharge was planned—with aftercare housing and outpatient program particiption arranged—and he left the hospital in a taxi.

Three days later, the patient was found dead in a creek. An autopsy showed that the patient died by drowning and that his blood alcohol level was 0.32%. The death was ruled a suicide secondary to excessive alcohol consumption.

The plaintiff—the patient’s estate —charged that the psychiatrist was negligent in discharging the patient from the hospital and claimed that lack of a post-discharge recovery plan made the suicide likely.

The defense argued that the patient’s history of suicide attempts was known and that a discharge plan—which included housing and participation in an outpatient program—was in place before he was discharged.

• The jury found for the defense.
  

Dr. Grant’s observations

Many factors associated with managed care—such as cost-containment policies that shorten hospital stays, shorter visits that limit opportunity to develop a therapeutic alliance with patients, and limited ability to communicate with patients—have increased the risk of malpractice suits alleging premature discharge of patients who later kill themselves.³

To avoid such a suit:⁴

• Document the patient’s risk factors for suicide as well as specific suicidal thoughts and methods expressed, extent of planning and action taken toward a suicide attempt, access to means, and response to prior therapeutic interventions.

• Explain in your notes why specific risk factors were ruled out. This supports the conclusion that you properly assessed the patient.

• Obtain a proper history of the patient’s current illness. Understanding how a patient’s substance use is affecting his mood may influence plans for care after discharge.

• Do not rely solely on a patient’s statements about suicidality. Document information from other sources (old records, previous providers, or family members) and note that you tried to contact collateral sources or get permission to talk with the patient’s family

• Arrange outpatient services that focus on substance addiction (for example, support groups such as Alcoholics Anonymous [see], and therapy with an addictions specialist). Schedule timely visits for therapy and medication management. A medical follow-up may be needed if health concerns are associated with a mental health issue. A patient may need to be placed in a sober house or residential facility if he cannot stay sober on his own.

Knowing what to look for can help you differentiate between pediatric bipolar disorder and attention-deficit/hyperactivity disorder (ADHD):

• Bipolar disorder is a problem with mood. Children with bipolar mania are elated and/or irritable and experience mood states that appear uncontrollable.
• ADHD is a problem with cognitive functioning, including attention, distractibility, and energy level.

Mood and cognitive symptoms may overlap,^1,2 but recognizing manic features is the key to distinguishing between these disorders—even when they co-occur.

We offer tips from our experience and a recent clinical trial to help you sort out the core symptoms that point to bipolar mania.

BIPOLAR CORE SYMPTOMS

Pediatric bipolar disorder is relatively rare, but children with it can experience substantial impairment and developmental delay. Intervening early with effective treatment³ can improve their quality of life, function, and prognosis.

Diagnostic criteria for type I bipolar disorder require at least one manic episode and are the same for all ages. Many clinicians and researchers have advocated adapting DSM-IV criteria for children, but we believe separate adult and pediatric criteria would confuse discussions about the same phenomena. We do agree that symptoms should be evaluated in a developmentally appropriate context, as mania can present differently across the ages (Table 1).

Mania in children and young adolescents tends to present with rapid cycling and a primarily irritable mood.⁴ Older adolescents and adults may present with more-distinct mood changes, with a primarily euphoric mood. Euphoric mania is less common in adults than previously thought. Forty percent to 60% of adults with bipolar disorder experience a chronic course, rather than more-discrete mood episodes.

A manic episode is an abnormally and persistently elevated (euphoria) or irritable mood that lasts at least 1 week. To satisfy DSM-IV-TR diagnostic criteria for a manic episode:

• patients with euphoria require three additional symptoms
• those who are irritable (and not euphoric) require another four symptoms.⁵

These symptoms must significantly impair several areas of functioning and not be caused by other mental or physical illness, including substance use or abuse. When depressive symptoms occur in the same week as mania, the mixed mania modifier is used.

Table 1

Diagnostic features of bipolar mania in adolescents vs adults

Disruptive and aggressive behavior are common and are what usually prompts parents to bring children to psychiatrists. These behaviors are not diagnostic of mania, however, and aggression has many other causes.

The threshold between a variant of normal and pathologic disruptive behavior can be difficult to establish and varies from culture to culture. Some families, for example, would allow a child to tell the parents what to do, whereas other families consider this a serious boundary violation.

Prolonged rages have been used as a proxy for mood swings. Although we agree that rages lasting >15 minutes and out-of-proportion to the circumstances may signal bipolar disorder, they are not diagnostic.

Other symptoms. Psychotic symptoms (hallucinations, delusions, disorganization) can occur in youths with bipolar disorder. Evaluation often reveals impaired social and cognitive development. Keep in mind that a child’s developmental level can affect symptom expression.

ADHD CORE SYMPTOMS

Children with ADHD often present with hyperactive, uncontrollable behaviors and academic failure. To meet DSM-IV-TR diagnostic criteria, they must show symptoms before age 7. Primary symptoms may be inattention, hyperactivity and impulsivity, or both.

ADHD is a disorder of attention and the cognitive skills related to attention, rather than a mood disorder. Children with ADHD show substantially impaired function in at least two settings (such as at home and in school), and—unlike bipolar disorder—their symptoms are persistent rather than episodic.

DIFFERENTIATING BY SYMPTOMS

When differentiating between ADHD and bipolar disorder in children, remain focused on both diagnoses’ core symptoms.

Euphoria, or elation, is a key distinguishing factor in bipolar disorder.⁶ Although all children are at times giddy or silly in appropriate environments—such as during slumber parties—consider a threshold of appropriateness when making a bipolar diagnosis. Families perceive the giddiness, inappropriate laughter, and elevated mood of children with mania as disturbing and inappropriate, not funny or endearing. They are often annoyed and concerned.

Children with primary ADHD do not show inappropriately elevated mood. In fact, their failures often make these children dysphoric.

Irritability is common in children with psychiatric illnesses. Manic youngsters can be very irritable most of the time. Families describe “walking on eggshells” because of these children’s touchiness. Unpredictable triggers set off explosive, prolonged tantrums that may be associated with aggression, and their mood swings are almost constant.

Children with ADHD can be irritable, but their irritability is less severe and intense than that seen in bipolar disorder. Stimulant medication “wear-off” can cause irritability in ADHD, so consider this possibility if symptoms occur mostly in the evening.

Grandiosity can be confusing to evaluate in children but is often a core symptom in bipolar disorder. All children sometimes say self-inflating things, but those with pathologic grandiosity cross the threshold into the dysfunctional belief that they are better, stronger, smarter, or more talented than others.

For example, a 7-year-old patient insisted he was the world’s best chess player and could beat anyone, including Russian chess masters. When the therapist asked him about chess, he did not know the names of the pieces or how they moved. Yet despite facing these contradictory facts, he continued to insist that he was the best.

Children with grandiosity may act inappropriately on their beliefs, such as by telling adults what to do or engaging in risky, daredevil acts with no concern for their safety or the law.

Children with ADHD are not usually grandiose. Instead, they often become demoralized and develop poor self-esteem from negative feedback about their behavior.

Decreased need for sleep is the hallmark symptom of mania that is absent in other psychiatric disorders. A true decreased need for sleep is only indicated in someone sleeping less than his or her usual cumulative hours each day, without fatigue or recuperative sleep.

Children with bipolar disorder may need 1 or more hours less sleep or deny needing sleep at all. Use age-appropriate amounts of sleep as a standard. A school age child usually averages 9 to 11 hours of sleep per night. If the patient is getting only 6 hours and is not tired, this would be a decreased need for sleep. A 24-hour sleep history can easily assess decreased need for sleep (Box).

Determine daytime fatigue by self-report or observation by parents or teachers. Then ascertain if there are periods of days with less fatigue. Many bipolar youth have a nearly continuous decreased need for sleep.

Children with ADHD often have difficulty settling at night, which delays their falling asleep. The sleep history will likely show that—once asleep—they sleep well for an appropriate amount of time or are fatigued during the day.

Box

Pressured speech, or the need to talk excessively, is a relatively straightforward symptom. Children experiencing mania often speak so quickly and excessively that others cannot understand or interrupt them. Flight of ideas and racing thoughts are reflected in their speech.

By contrast, rapid speech by children with ADHD is related to hyperactivity. They speak too fast and often become distracted from the topic.

Racing thoughts. Children with bipolar disorder may report that their thoughts come so quickly they cannot get them out fast enough. The idea that their thoughts “need a stop-sign” suggests racing thoughts, a core bipolar symptom. Their speech can be unintelligible, with rapid changes in thought patterns, flight of ideas, and sentence fragments. Children with ADHD are energetic and quick but do not report racing thoughts.

LESS-HELPFUL SYMPTOMS

Distractibility—a core symptom of both inattentive ADHD and manic episodes—does not help differentiate the two diagnoses. The high comorbidity of ADHD with bipolar disorder increases the likelihood that the child will be easily distracted.

Multi-tasking. Increased goal-directed activity is often associated with the high energy of children with mania. They have more energy than most people, are always on the go, and engage in multiple projects or activities that may be markedly creative or unrealistic. This increased energy—combined with other hallmark manic symptoms—can lead to high-risk behaviors.

Hyperactivity in ADHD can appear similar to agitation in bipolar disorder. In both disorders, children may engage in many tasks—not finishing any of them—or appear to move quickly from one task to another.

High-risk behaviors. Parents often report their children with bipolar disorder have tried to jump from moving vehicles, “fly” off of roofs, and jump their bicycles or skateboards over impossible distances. These children behave as if the laws of nature do not apply to them. Children with ADHD behave impulsively but are not always “daredevils.” Their activities appear more impulsive and feature high activity in inappropriate situations, rather than distinctly high-risk activities.

RESPONSE TO THERAPY

Our group⁷ showed that pediatric manic and ADHD symptoms respond differently to mood-stabilizer treatment (Table 2).

We first used open-label divalproex sodium to treat manic symptoms in 40 children ages 6 to 17 with bipolar I or II disorder and concurrent ADHD. Serum valproic acid levels averaged 82 μg/mL. Manic symptoms improved in 80% of patients, whereas ADHD symptoms improved in <10%. Most children’s symptoms still met severity criteria for ADHD.

In a subsequent double-blind, crossover trial, we compared the effects of mixed amphetamine salts (MAS) or placebo on ADHD symptoms in 30 children whose manic symptoms stabilized on divalproex. MAS showed a significant, independent effect on ADHD symptoms One patient’s manic symptoms recurred during stimulant therapy and subsided with MAS discontinuation.

In this trial, mania symptoms responded to divalproex, whereas ADHD symptoms did not. MAS treatment showed a specific effect on ADHD symptoms of inattention, impulsivity, and hyperactivity. The shared symptoms of mania and ADHD (impulsivity and hyperactivity) decreased with divalproex to some extent.

Table 2

Pediatric mania and ADHD
respond differently to mood-stabilizer therapy

WHEN MANIA/ADHD CO-OCCUR

ADHD and bipolar disorder symptoms overlap to a great extent, and the disorders can co-occur:

• Up to 20% of children diagnosed with ADHD also meet bipolar criteria.
• Two-thirds of children with bipolar disorder may also meet criteria for ADHD, with reports ranging from 29% to 98%.^1,2

When trying to differentiate ADHD and bipolar disorder in children, consider the core symptoms of each diagnosis (Table 3).

Table 3

Core symptoms: Pediatric bipolar disorder vs ADHD

Related resources

• Geller B, DelBello MP (eds). Bipolar disorder in childhood and early adolescence. New York: Guilford Press, 2003.
• Papolos DF, Papolos J. Bipolar child: The definitive and reassuring guide to childhood’s most misunderstood disorder. New York: Broadway Books, 2002.
• Fristad MA, Goldberg Arnold JS. Raising a moody child: How to cope with depression and bipolar disorder. New York: Guilford Press, 2003.
• Child and Adolescent Bipolar Foundation. Available at www.cabf.org. Accessed March 4, 2005.

Drug brand names

• Divalproex sodium • Depakote
• Mixed amphetamine salts • Adderall

Disclosures

Dr. Scheffer receives research support from and is a speaker for Abbott Laboratories.

Dr. Apps reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Knowing what to look for can help you differentiate between pediatric bipolar disorder and attention-deficit/hyperactivity disorder (ADHD):

• Bipolar disorder is a problem with mood. Children with bipolar mania are elated and/or irritable and experience mood states that appear uncontrollable.
• ADHD is a problem with cognitive functioning, including attention, distractibility, and energy level.

Mood and cognitive symptoms may overlap,^1,2 but recognizing manic features is the key to distinguishing between these disorders—even when they co-occur.

We offer tips from our experience and a recent clinical trial to help you sort out the core symptoms that point to bipolar mania.

BIPOLAR CORE SYMPTOMS

Pediatric bipolar disorder is relatively rare, but children with it can experience substantial impairment and developmental delay. Intervening early with effective treatment³ can improve their quality of life, function, and prognosis.

Diagnostic criteria for type I bipolar disorder require at least one manic episode and are the same for all ages. Many clinicians and researchers have advocated adapting DSM-IV criteria for children, but we believe separate adult and pediatric criteria would confuse discussions about the same phenomena. We do agree that symptoms should be evaluated in a developmentally appropriate context, as mania can present differently across the ages (Table 1).

Mania in children and young adolescents tends to present with rapid cycling and a primarily irritable mood.⁴ Older adolescents and adults may present with more-distinct mood changes, with a primarily euphoric mood. Euphoric mania is less common in adults than previously thought. Forty percent to 60% of adults with bipolar disorder experience a chronic course, rather than more-discrete mood episodes.

A manic episode is an abnormally and persistently elevated (euphoria) or irritable mood that lasts at least 1 week. To satisfy DSM-IV-TR diagnostic criteria for a manic episode:

• patients with euphoria require three additional symptoms
• those who are irritable (and not euphoric) require another four symptoms.⁵

These symptoms must significantly impair several areas of functioning and not be caused by other mental or physical illness, including substance use or abuse. When depressive symptoms occur in the same week as mania, the mixed mania modifier is used.

Table 1

Diagnostic features of bipolar mania in adolescents vs adults

Disruptive and aggressive behavior are common and are what usually prompts parents to bring children to psychiatrists. These behaviors are not diagnostic of mania, however, and aggression has many other causes.

The threshold between a variant of normal and pathologic disruptive behavior can be difficult to establish and varies from culture to culture. Some families, for example, would allow a child to tell the parents what to do, whereas other families consider this a serious boundary violation.

Prolonged rages have been used as a proxy for mood swings. Although we agree that rages lasting >15 minutes and out-of-proportion to the circumstances may signal bipolar disorder, they are not diagnostic.

Other symptoms. Psychotic symptoms (hallucinations, delusions, disorganization) can occur in youths with bipolar disorder. Evaluation often reveals impaired social and cognitive development. Keep in mind that a child’s developmental level can affect symptom expression.

ADHD CORE SYMPTOMS

Children with ADHD often present with hyperactive, uncontrollable behaviors and academic failure. To meet DSM-IV-TR diagnostic criteria, they must show symptoms before age 7. Primary symptoms may be inattention, hyperactivity and impulsivity, or both.

ADHD is a disorder of attention and the cognitive skills related to attention, rather than a mood disorder. Children with ADHD show substantially impaired function in at least two settings (such as at home and in school), and—unlike bipolar disorder—their symptoms are persistent rather than episodic.

DIFFERENTIATING BY SYMPTOMS

When differentiating between ADHD and bipolar disorder in children, remain focused on both diagnoses’ core symptoms.

Euphoria, or elation, is a key distinguishing factor in bipolar disorder.⁶ Although all children are at times giddy or silly in appropriate environments—such as during slumber parties—consider a threshold of appropriateness when making a bipolar diagnosis. Families perceive the giddiness, inappropriate laughter, and elevated mood of children with mania as disturbing and inappropriate, not funny or endearing. They are often annoyed and concerned.

Children with primary ADHD do not show inappropriately elevated mood. In fact, their failures often make these children dysphoric.

Irritability is common in children with psychiatric illnesses. Manic youngsters can be very irritable most of the time. Families describe “walking on eggshells” because of these children’s touchiness. Unpredictable triggers set off explosive, prolonged tantrums that may be associated with aggression, and their mood swings are almost constant.

Children with ADHD can be irritable, but their irritability is less severe and intense than that seen in bipolar disorder. Stimulant medication “wear-off” can cause irritability in ADHD, so consider this possibility if symptoms occur mostly in the evening.

Grandiosity can be confusing to evaluate in children but is often a core symptom in bipolar disorder. All children sometimes say self-inflating things, but those with pathologic grandiosity cross the threshold into the dysfunctional belief that they are better, stronger, smarter, or more talented than others.

For example, a 7-year-old patient insisted he was the world’s best chess player and could beat anyone, including Russian chess masters. When the therapist asked him about chess, he did not know the names of the pieces or how they moved. Yet despite facing these contradictory facts, he continued to insist that he was the best.

Children with grandiosity may act inappropriately on their beliefs, such as by telling adults what to do or engaging in risky, daredevil acts with no concern for their safety or the law.

Children with ADHD are not usually grandiose. Instead, they often become demoralized and develop poor self-esteem from negative feedback about their behavior.

Decreased need for sleep is the hallmark symptom of mania that is absent in other psychiatric disorders. A true decreased need for sleep is only indicated in someone sleeping less than his or her usual cumulative hours each day, without fatigue or recuperative sleep.

Children with bipolar disorder may need 1 or more hours less sleep or deny needing sleep at all. Use age-appropriate amounts of sleep as a standard. A school age child usually averages 9 to 11 hours of sleep per night. If the patient is getting only 6 hours and is not tired, this would be a decreased need for sleep. A 24-hour sleep history can easily assess decreased need for sleep (Box).

Determine daytime fatigue by self-report or observation by parents or teachers. Then ascertain if there are periods of days with less fatigue. Many bipolar youth have a nearly continuous decreased need for sleep.

Children with ADHD often have difficulty settling at night, which delays their falling asleep. The sleep history will likely show that—once asleep—they sleep well for an appropriate amount of time or are fatigued during the day.

Box

Pressured speech, or the need to talk excessively, is a relatively straightforward symptom. Children experiencing mania often speak so quickly and excessively that others cannot understand or interrupt them. Flight of ideas and racing thoughts are reflected in their speech.

By contrast, rapid speech by children with ADHD is related to hyperactivity. They speak too fast and often become distracted from the topic.

Racing thoughts. Children with bipolar disorder may report that their thoughts come so quickly they cannot get them out fast enough. The idea that their thoughts “need a stop-sign” suggests racing thoughts, a core bipolar symptom. Their speech can be unintelligible, with rapid changes in thought patterns, flight of ideas, and sentence fragments. Children with ADHD are energetic and quick but do not report racing thoughts.

LESS-HELPFUL SYMPTOMS

Distractibility—a core symptom of both inattentive ADHD and manic episodes—does not help differentiate the two diagnoses. The high comorbidity of ADHD with bipolar disorder increases the likelihood that the child will be easily distracted.

Multi-tasking. Increased goal-directed activity is often associated with the high energy of children with mania. They have more energy than most people, are always on the go, and engage in multiple projects or activities that may be markedly creative or unrealistic. This increased energy—combined with other hallmark manic symptoms—can lead to high-risk behaviors.

Hyperactivity in ADHD can appear similar to agitation in bipolar disorder. In both disorders, children may engage in many tasks—not finishing any of them—or appear to move quickly from one task to another.

High-risk behaviors. Parents often report their children with bipolar disorder have tried to jump from moving vehicles, “fly” off of roofs, and jump their bicycles or skateboards over impossible distances. These children behave as if the laws of nature do not apply to them. Children with ADHD behave impulsively but are not always “daredevils.” Their activities appear more impulsive and feature high activity in inappropriate situations, rather than distinctly high-risk activities.

RESPONSE TO THERAPY

Our group⁷ showed that pediatric manic and ADHD symptoms respond differently to mood-stabilizer treatment (Table 2).

We first used open-label divalproex sodium to treat manic symptoms in 40 children ages 6 to 17 with bipolar I or II disorder and concurrent ADHD. Serum valproic acid levels averaged 82 μg/mL. Manic symptoms improved in 80% of patients, whereas ADHD symptoms improved in <10%. Most children’s symptoms still met severity criteria for ADHD.

In a subsequent double-blind, crossover trial, we compared the effects of mixed amphetamine salts (MAS) or placebo on ADHD symptoms in 30 children whose manic symptoms stabilized on divalproex. MAS showed a significant, independent effect on ADHD symptoms One patient’s manic symptoms recurred during stimulant therapy and subsided with MAS discontinuation.

In this trial, mania symptoms responded to divalproex, whereas ADHD symptoms did not. MAS treatment showed a specific effect on ADHD symptoms of inattention, impulsivity, and hyperactivity. The shared symptoms of mania and ADHD (impulsivity and hyperactivity) decreased with divalproex to some extent.

Table 2

Pediatric mania and ADHD
respond differently to mood-stabilizer therapy

WHEN MANIA/ADHD CO-OCCUR

ADHD and bipolar disorder symptoms overlap to a great extent, and the disorders can co-occur:

• Up to 20% of children diagnosed with ADHD also meet bipolar criteria.
• Two-thirds of children with bipolar disorder may also meet criteria for ADHD, with reports ranging from 29% to 98%.^1,2

When trying to differentiate ADHD and bipolar disorder in children, consider the core symptoms of each diagnosis (Table 3).

Table 3

Core symptoms: Pediatric bipolar disorder vs ADHD

Related resources

• Geller B, DelBello MP (eds). Bipolar disorder in childhood and early adolescence. New York: Guilford Press, 2003.
• Papolos DF, Papolos J. Bipolar child: The definitive and reassuring guide to childhood’s most misunderstood disorder. New York: Broadway Books, 2002.
• Fristad MA, Goldberg Arnold JS. Raising a moody child: How to cope with depression and bipolar disorder. New York: Guilford Press, 2003.
• Child and Adolescent Bipolar Foundation. Available at www.cabf.org. Accessed March 4, 2005.

Drug brand names

• Divalproex sodium • Depakote
• Mixed amphetamine salts • Adderall

Disclosures

Dr. Scheffer receives research support from and is a speaker for Abbott Laboratories.

Dr. Apps reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Knowing what to look for can help you differentiate between pediatric bipolar disorder and attention-deficit/hyperactivity disorder (ADHD):

• Bipolar disorder is a problem with mood. Children with bipolar mania are elated and/or irritable and experience mood states that appear uncontrollable.
• ADHD is a problem with cognitive functioning, including attention, distractibility, and energy level.

Mood and cognitive symptoms may overlap,^1,2 but recognizing manic features is the key to distinguishing between these disorders—even when they co-occur.

We offer tips from our experience and a recent clinical trial to help you sort out the core symptoms that point to bipolar mania.

BIPOLAR CORE SYMPTOMS

Pediatric bipolar disorder is relatively rare, but children with it can experience substantial impairment and developmental delay. Intervening early with effective treatment³ can improve their quality of life, function, and prognosis.

Diagnostic criteria for type I bipolar disorder require at least one manic episode and are the same for all ages. Many clinicians and researchers have advocated adapting DSM-IV criteria for children, but we believe separate adult and pediatric criteria would confuse discussions about the same phenomena. We do agree that symptoms should be evaluated in a developmentally appropriate context, as mania can present differently across the ages (Table 1).

Mania in children and young adolescents tends to present with rapid cycling and a primarily irritable mood.⁴ Older adolescents and adults may present with more-distinct mood changes, with a primarily euphoric mood. Euphoric mania is less common in adults than previously thought. Forty percent to 60% of adults with bipolar disorder experience a chronic course, rather than more-discrete mood episodes.

A manic episode is an abnormally and persistently elevated (euphoria) or irritable mood that lasts at least 1 week. To satisfy DSM-IV-TR diagnostic criteria for a manic episode:

• patients with euphoria require three additional symptoms
• those who are irritable (and not euphoric) require another four symptoms.⁵

These symptoms must significantly impair several areas of functioning and not be caused by other mental or physical illness, including substance use or abuse. When depressive symptoms occur in the same week as mania, the mixed mania modifier is used.

Table 1

Diagnostic features of bipolar mania in adolescents vs adults

Disruptive and aggressive behavior are common and are what usually prompts parents to bring children to psychiatrists. These behaviors are not diagnostic of mania, however, and aggression has many other causes.

The threshold between a variant of normal and pathologic disruptive behavior can be difficult to establish and varies from culture to culture. Some families, for example, would allow a child to tell the parents what to do, whereas other families consider this a serious boundary violation.

Prolonged rages have been used as a proxy for mood swings. Although we agree that rages lasting >15 minutes and out-of-proportion to the circumstances may signal bipolar disorder, they are not diagnostic.

Other symptoms. Psychotic symptoms (hallucinations, delusions, disorganization) can occur in youths with bipolar disorder. Evaluation often reveals impaired social and cognitive development. Keep in mind that a child’s developmental level can affect symptom expression.

ADHD CORE SYMPTOMS

Children with ADHD often present with hyperactive, uncontrollable behaviors and academic failure. To meet DSM-IV-TR diagnostic criteria, they must show symptoms before age 7. Primary symptoms may be inattention, hyperactivity and impulsivity, or both.

ADHD is a disorder of attention and the cognitive skills related to attention, rather than a mood disorder. Children with ADHD show substantially impaired function in at least two settings (such as at home and in school), and—unlike bipolar disorder—their symptoms are persistent rather than episodic.

DIFFERENTIATING BY SYMPTOMS

When differentiating between ADHD and bipolar disorder in children, remain focused on both diagnoses’ core symptoms.

Euphoria, or elation, is a key distinguishing factor in bipolar disorder.⁶ Although all children are at times giddy or silly in appropriate environments—such as during slumber parties—consider a threshold of appropriateness when making a bipolar diagnosis. Families perceive the giddiness, inappropriate laughter, and elevated mood of children with mania as disturbing and inappropriate, not funny or endearing. They are often annoyed and concerned.

Children with primary ADHD do not show inappropriately elevated mood. In fact, their failures often make these children dysphoric.

Irritability is common in children with psychiatric illnesses. Manic youngsters can be very irritable most of the time. Families describe “walking on eggshells” because of these children’s touchiness. Unpredictable triggers set off explosive, prolonged tantrums that may be associated with aggression, and their mood swings are almost constant.

Children with ADHD can be irritable, but their irritability is less severe and intense than that seen in bipolar disorder. Stimulant medication “wear-off” can cause irritability in ADHD, so consider this possibility if symptoms occur mostly in the evening.

Grandiosity can be confusing to evaluate in children but is often a core symptom in bipolar disorder. All children sometimes say self-inflating things, but those with pathologic grandiosity cross the threshold into the dysfunctional belief that they are better, stronger, smarter, or more talented than others.

For example, a 7-year-old patient insisted he was the world’s best chess player and could beat anyone, including Russian chess masters. When the therapist asked him about chess, he did not know the names of the pieces or how they moved. Yet despite facing these contradictory facts, he continued to insist that he was the best.

Children with grandiosity may act inappropriately on their beliefs, such as by telling adults what to do or engaging in risky, daredevil acts with no concern for their safety or the law.

Children with ADHD are not usually grandiose. Instead, they often become demoralized and develop poor self-esteem from negative feedback about their behavior.

Decreased need for sleep is the hallmark symptom of mania that is absent in other psychiatric disorders. A true decreased need for sleep is only indicated in someone sleeping less than his or her usual cumulative hours each day, without fatigue or recuperative sleep.

Children with bipolar disorder may need 1 or more hours less sleep or deny needing sleep at all. Use age-appropriate amounts of sleep as a standard. A school age child usually averages 9 to 11 hours of sleep per night. If the patient is getting only 6 hours and is not tired, this would be a decreased need for sleep. A 24-hour sleep history can easily assess decreased need for sleep (Box).

Determine daytime fatigue by self-report or observation by parents or teachers. Then ascertain if there are periods of days with less fatigue. Many bipolar youth have a nearly continuous decreased need for sleep.

Children with ADHD often have difficulty settling at night, which delays their falling asleep. The sleep history will likely show that—once asleep—they sleep well for an appropriate amount of time or are fatigued during the day.

Box

Pressured speech, or the need to talk excessively, is a relatively straightforward symptom. Children experiencing mania often speak so quickly and excessively that others cannot understand or interrupt them. Flight of ideas and racing thoughts are reflected in their speech.

By contrast, rapid speech by children with ADHD is related to hyperactivity. They speak too fast and often become distracted from the topic.

Racing thoughts. Children with bipolar disorder may report that their thoughts come so quickly they cannot get them out fast enough. The idea that their thoughts “need a stop-sign” suggests racing thoughts, a core bipolar symptom. Their speech can be unintelligible, with rapid changes in thought patterns, flight of ideas, and sentence fragments. Children with ADHD are energetic and quick but do not report racing thoughts.

LESS-HELPFUL SYMPTOMS

Distractibility—a core symptom of both inattentive ADHD and manic episodes—does not help differentiate the two diagnoses. The high comorbidity of ADHD with bipolar disorder increases the likelihood that the child will be easily distracted.

Multi-tasking. Increased goal-directed activity is often associated with the high energy of children with mania. They have more energy than most people, are always on the go, and engage in multiple projects or activities that may be markedly creative or unrealistic. This increased energy—combined with other hallmark manic symptoms—can lead to high-risk behaviors.

Hyperactivity in ADHD can appear similar to agitation in bipolar disorder. In both disorders, children may engage in many tasks—not finishing any of them—or appear to move quickly from one task to another.

High-risk behaviors. Parents often report their children with bipolar disorder have tried to jump from moving vehicles, “fly” off of roofs, and jump their bicycles or skateboards over impossible distances. These children behave as if the laws of nature do not apply to them. Children with ADHD behave impulsively but are not always “daredevils.” Their activities appear more impulsive and feature high activity in inappropriate situations, rather than distinctly high-risk activities.

RESPONSE TO THERAPY

Our group⁷ showed that pediatric manic and ADHD symptoms respond differently to mood-stabilizer treatment (Table 2).

We first used open-label divalproex sodium to treat manic symptoms in 40 children ages 6 to 17 with bipolar I or II disorder and concurrent ADHD. Serum valproic acid levels averaged 82 μg/mL. Manic symptoms improved in 80% of patients, whereas ADHD symptoms improved in <10%. Most children’s symptoms still met severity criteria for ADHD.

In a subsequent double-blind, crossover trial, we compared the effects of mixed amphetamine salts (MAS) or placebo on ADHD symptoms in 30 children whose manic symptoms stabilized on divalproex. MAS showed a significant, independent effect on ADHD symptoms One patient’s manic symptoms recurred during stimulant therapy and subsided with MAS discontinuation.

In this trial, mania symptoms responded to divalproex, whereas ADHD symptoms did not. MAS treatment showed a specific effect on ADHD symptoms of inattention, impulsivity, and hyperactivity. The shared symptoms of mania and ADHD (impulsivity and hyperactivity) decreased with divalproex to some extent.

Table 2

Pediatric mania and ADHD
respond differently to mood-stabilizer therapy

WHEN MANIA/ADHD CO-OCCUR

ADHD and bipolar disorder symptoms overlap to a great extent, and the disorders can co-occur:

• Up to 20% of children diagnosed with ADHD also meet bipolar criteria.
• Two-thirds of children with bipolar disorder may also meet criteria for ADHD, with reports ranging from 29% to 98%.^1,2

When trying to differentiate ADHD and bipolar disorder in children, consider the core symptoms of each diagnosis (Table 3).

Table 3

Core symptoms: Pediatric bipolar disorder vs ADHD

Related resources

• Geller B, DelBello MP (eds). Bipolar disorder in childhood and early adolescence. New York: Guilford Press, 2003.
• Papolos DF, Papolos J. Bipolar child: The definitive and reassuring guide to childhood’s most misunderstood disorder. New York: Broadway Books, 2002.
• Fristad MA, Goldberg Arnold JS. Raising a moody child: How to cope with depression and bipolar disorder. New York: Guilford Press, 2003.
• Child and Adolescent Bipolar Foundation. Available at www.cabf.org. Accessed March 4, 2005.

Drug brand names

• Divalproex sodium • Depakote
• Mixed amphetamine salts • Adderall

Disclosures

Dr. Scheffer receives research support from and is a speaker for Abbott Laboratories.

Dr. Apps reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

NEW ORLEANS — Because of its myriad presentations on black skin, sarcoidosis can be called “the great imitator,” Rebat Halder, M.D., said at the annual meeting of the American Academy of Dermatology.

“The appearance on the skin can have many different morphologies,” said Dr. Halder, chair of the department of dermatology at Howard University, Washington.

“It can really fool you: The lesions can be macular, papular, ichthyosiform, nodular, ulcerative, vesicular, annular, or it can simply present as areas of hypopigmentation with no apparent inflammation.”

Sarcoidosis, characterized by noncaseating epithelioid granulomas that may affect any organ system, is uncommon in any group of patients. However, it is about 16 times more common in blacks than in whites, with an incidence of 35-65/100,000 among blacks. Black women in their fourth decade are most commonly affected, with an incidence of about 100/100,000, Dr. Halder said in an interview.

The etiology of sarcoidosis is unknown, although familial clustering has been observed.

For unknown reasons, sarcoidosis is often more aggressive and difficult to treat in blacks. They have a higher rate of relapse, are more likely to experience multiorgan involvement, and have a slightly higher mortality rate than whites.

About 90% of patients have lung involvement, usually fibrosis due to granulomatous lesions.

Skin lesions appear in about 35% of patients. Other affected organs are the eyes, liver, heart, central nervous system, and spleen.

Any suspicious lesions should be biopsied. Typically, histology will show characteristic noncaseating granulomas. Since so many patients have lung involvement, a chest x-ray is imperative, Dr. Halder said. “If you suspect a skin lesion is sarcoidosis, you must search for the disease elsewhere in the body.”

Papular sarcoidosis consists of red-brown papules usually occurring on the face, around the eyes, nose, mouth, and nape of neck.

The papules can be larger, or quite fine, with the skin assuming a sandpaperlike texture, Dr. Halder said.

Lupus pernio lesions are red or purple indurated plaques usually occurring around the nose. These lesions can affect the nasal cartilage or bone and upper respiratory system as well.

Plaquelike sarcoidosis can occur anywhere on the skin, but is most common on the back of the neck and on the arms and legs.

This condition is characterized by round or oval, red-brown to purple, infiltrated plaques.

Ulcerative sarcoidosis can be especially debilitating, especially when it occurs on the palms of the hands or soles of the feet.

These lesions are small but can become quite deep, Dr. Halder commented.

Vesicular sarcoidosis can occur anywhere on the skin and can easily be confused with other blistering diseases or with skin infections.

Hypopigmented sarcoidosis is especially difficult to recognize, he said. “This presents only as areas of the skin without pigment. You would have to consider sarcoidosis along with hypopigmented cutaneous T-cell lymphoma, vitiligo, or tinea versicolor. Again, biopsy is crucial to diagnosis.”

Treatment for skin lesions usually consists of topical or intralesional steroids.

Extensive or recalcitrant disease requires more aggressive treatment, which includes drugs such as oral steroids, methotrexate, allopurinol, thalidomide, or oral retinoids.

There has been some success with infliximab as well, Dr. Halder said.

Adjunctive phototherapy is useful for hypopigmented sarcoidosis, the investigator said.

NEW ORLEANS — Because of its myriad presentations on black skin, sarcoidosis can be called “the great imitator,” Rebat Halder, M.D., said at the annual meeting of the American Academy of Dermatology.

“The appearance on the skin can have many different morphologies,” said Dr. Halder, chair of the department of dermatology at Howard University, Washington.

“It can really fool you: The lesions can be macular, papular, ichthyosiform, nodular, ulcerative, vesicular, annular, or it can simply present as areas of hypopigmentation with no apparent inflammation.”

Sarcoidosis, characterized by noncaseating epithelioid granulomas that may affect any organ system, is uncommon in any group of patients. However, it is about 16 times more common in blacks than in whites, with an incidence of 35-65/100,000 among blacks. Black women in their fourth decade are most commonly affected, with an incidence of about 100/100,000, Dr. Halder said in an interview.

The etiology of sarcoidosis is unknown, although familial clustering has been observed.

For unknown reasons, sarcoidosis is often more aggressive and difficult to treat in blacks. They have a higher rate of relapse, are more likely to experience multiorgan involvement, and have a slightly higher mortality rate than whites.

About 90% of patients have lung involvement, usually fibrosis due to granulomatous lesions.

Skin lesions appear in about 35% of patients. Other affected organs are the eyes, liver, heart, central nervous system, and spleen.

Any suspicious lesions should be biopsied. Typically, histology will show characteristic noncaseating granulomas. Since so many patients have lung involvement, a chest x-ray is imperative, Dr. Halder said. “If you suspect a skin lesion is sarcoidosis, you must search for the disease elsewhere in the body.”

Papular sarcoidosis consists of red-brown papules usually occurring on the face, around the eyes, nose, mouth, and nape of neck.

The papules can be larger, or quite fine, with the skin assuming a sandpaperlike texture, Dr. Halder said.

Lupus pernio lesions are red or purple indurated plaques usually occurring around the nose. These lesions can affect the nasal cartilage or bone and upper respiratory system as well.

Plaquelike sarcoidosis can occur anywhere on the skin, but is most common on the back of the neck and on the arms and legs.

This condition is characterized by round or oval, red-brown to purple, infiltrated plaques.

Ulcerative sarcoidosis can be especially debilitating, especially when it occurs on the palms of the hands or soles of the feet.

These lesions are small but can become quite deep, Dr. Halder commented.

Vesicular sarcoidosis can occur anywhere on the skin and can easily be confused with other blistering diseases or with skin infections.

Hypopigmented sarcoidosis is especially difficult to recognize, he said. “This presents only as areas of the skin without pigment. You would have to consider sarcoidosis along with hypopigmented cutaneous T-cell lymphoma, vitiligo, or tinea versicolor. Again, biopsy is crucial to diagnosis.”

Treatment for skin lesions usually consists of topical or intralesional steroids.

Extensive or recalcitrant disease requires more aggressive treatment, which includes drugs such as oral steroids, methotrexate, allopurinol, thalidomide, or oral retinoids.

There has been some success with infliximab as well, Dr. Halder said.

Adjunctive phototherapy is useful for hypopigmented sarcoidosis, the investigator said.

NEW ORLEANS — Because of its myriad presentations on black skin, sarcoidosis can be called “the great imitator,” Rebat Halder, M.D., said at the annual meeting of the American Academy of Dermatology.

“The appearance on the skin can have many different morphologies,” said Dr. Halder, chair of the department of dermatology at Howard University, Washington.

“It can really fool you: The lesions can be macular, papular, ichthyosiform, nodular, ulcerative, vesicular, annular, or it can simply present as areas of hypopigmentation with no apparent inflammation.”

Sarcoidosis, characterized by noncaseating epithelioid granulomas that may affect any organ system, is uncommon in any group of patients. However, it is about 16 times more common in blacks than in whites, with an incidence of 35-65/100,000 among blacks. Black women in their fourth decade are most commonly affected, with an incidence of about 100/100,000, Dr. Halder said in an interview.

The etiology of sarcoidosis is unknown, although familial clustering has been observed.

For unknown reasons, sarcoidosis is often more aggressive and difficult to treat in blacks. They have a higher rate of relapse, are more likely to experience multiorgan involvement, and have a slightly higher mortality rate than whites.

About 90% of patients have lung involvement, usually fibrosis due to granulomatous lesions.

Skin lesions appear in about 35% of patients. Other affected organs are the eyes, liver, heart, central nervous system, and spleen.

Any suspicious lesions should be biopsied. Typically, histology will show characteristic noncaseating granulomas. Since so many patients have lung involvement, a chest x-ray is imperative, Dr. Halder said. “If you suspect a skin lesion is sarcoidosis, you must search for the disease elsewhere in the body.”

Papular sarcoidosis consists of red-brown papules usually occurring on the face, around the eyes, nose, mouth, and nape of neck.

The papules can be larger, or quite fine, with the skin assuming a sandpaperlike texture, Dr. Halder said.

Lupus pernio lesions are red or purple indurated plaques usually occurring around the nose. These lesions can affect the nasal cartilage or bone and upper respiratory system as well.

Plaquelike sarcoidosis can occur anywhere on the skin, but is most common on the back of the neck and on the arms and legs.

This condition is characterized by round or oval, red-brown to purple, infiltrated plaques.

Ulcerative sarcoidosis can be especially debilitating, especially when it occurs on the palms of the hands or soles of the feet.

These lesions are small but can become quite deep, Dr. Halder commented.

Vesicular sarcoidosis can occur anywhere on the skin and can easily be confused with other blistering diseases or with skin infections.

Hypopigmented sarcoidosis is especially difficult to recognize, he said. “This presents only as areas of the skin without pigment. You would have to consider sarcoidosis along with hypopigmented cutaneous T-cell lymphoma, vitiligo, or tinea versicolor. Again, biopsy is crucial to diagnosis.”

Treatment for skin lesions usually consists of topical or intralesional steroids.

Extensive or recalcitrant disease requires more aggressive treatment, which includes drugs such as oral steroids, methotrexate, allopurinol, thalidomide, or oral retinoids.

There has been some success with infliximab as well, Dr. Halder said.

Adjunctive phototherapy is useful for hypopigmented sarcoidosis, the investigator said.

LONDON — Significant weight loss is possible in obese patients with systemic lupus erythematosus being treated with corticosteroids, Siaw Ing Yeo, M.D., said at the Sixth European Lupus Meeting.

This was demonstrated in a study that compared simple calorie restriction with a low-glycemic-index diet. In this type of diet, patients avoid refined carbohydrates, consuming only low-glycemic-index complex carbohydrates—those that have little immediate effect on blood glucose—and higher amounts of protein and fat.

The study randomly assigned 23 women aged 18-65 years whose body mass index was 25 or greater and who were on a stable dose of prednisolone of 5-20 mg/day to one of the two diets for 6 weeks.

There were significant weight reductions in both groups, with a mean weight loss of 2.44 kg in the low-calorie group and a mean of 4 kg in the low-glycemic-index group, Dr. Yeo said in a poster session at the meeting, sponsored by the British Society for Rheumatology.

Fasting LDL, HDL, triglycerides, glucose, insulin, C-reactive protein, fibrinogen, and homocysteine levels did not alter significantly on either diet. Fasting urate levels showed a trend toward improvement in the low-calorie group and remained unchanged in the low-glycemic-index diet, said Dr. Yeo of the lupus research unit at the Rayne Institute, St. Thomas' Hospital, London.

Constipation was reported by 50% of patients in the low-glycemic-index group, while increased bowel frequency and bloating were reported by 25% of those in the low-calorie group.

A surprising additional finding was that patients in both groups reported significant improvements on the fatigue severity score. Finally, neither diet was associated with a disease flare, she said.

LONDON — Significant weight loss is possible in obese patients with systemic lupus erythematosus being treated with corticosteroids, Siaw Ing Yeo, M.D., said at the Sixth European Lupus Meeting.

This was demonstrated in a study that compared simple calorie restriction with a low-glycemic-index diet. In this type of diet, patients avoid refined carbohydrates, consuming only low-glycemic-index complex carbohydrates—those that have little immediate effect on blood glucose—and higher amounts of protein and fat.

The study randomly assigned 23 women aged 18-65 years whose body mass index was 25 or greater and who were on a stable dose of prednisolone of 5-20 mg/day to one of the two diets for 6 weeks.

There were significant weight reductions in both groups, with a mean weight loss of 2.44 kg in the low-calorie group and a mean of 4 kg in the low-glycemic-index group, Dr. Yeo said in a poster session at the meeting, sponsored by the British Society for Rheumatology.

Fasting LDL, HDL, triglycerides, glucose, insulin, C-reactive protein, fibrinogen, and homocysteine levels did not alter significantly on either diet. Fasting urate levels showed a trend toward improvement in the low-calorie group and remained unchanged in the low-glycemic-index diet, said Dr. Yeo of the lupus research unit at the Rayne Institute, St. Thomas' Hospital, London.

Constipation was reported by 50% of patients in the low-glycemic-index group, while increased bowel frequency and bloating were reported by 25% of those in the low-calorie group.

A surprising additional finding was that patients in both groups reported significant improvements on the fatigue severity score. Finally, neither diet was associated with a disease flare, she said.

LONDON — Significant weight loss is possible in obese patients with systemic lupus erythematosus being treated with corticosteroids, Siaw Ing Yeo, M.D., said at the Sixth European Lupus Meeting.

This was demonstrated in a study that compared simple calorie restriction with a low-glycemic-index diet. In this type of diet, patients avoid refined carbohydrates, consuming only low-glycemic-index complex carbohydrates—those that have little immediate effect on blood glucose—and higher amounts of protein and fat.

The study randomly assigned 23 women aged 18-65 years whose body mass index was 25 or greater and who were on a stable dose of prednisolone of 5-20 mg/day to one of the two diets for 6 weeks.

There were significant weight reductions in both groups, with a mean weight loss of 2.44 kg in the low-calorie group and a mean of 4 kg in the low-glycemic-index group, Dr. Yeo said in a poster session at the meeting, sponsored by the British Society for Rheumatology.

Fasting LDL, HDL, triglycerides, glucose, insulin, C-reactive protein, fibrinogen, and homocysteine levels did not alter significantly on either diet. Fasting urate levels showed a trend toward improvement in the low-calorie group and remained unchanged in the low-glycemic-index diet, said Dr. Yeo of the lupus research unit at the Rayne Institute, St. Thomas' Hospital, London.

Constipation was reported by 50% of patients in the low-glycemic-index group, while increased bowel frequency and bloating were reported by 25% of those in the low-calorie group.

A surprising additional finding was that patients in both groups reported significant improvements on the fatigue severity score. Finally, neither diet was associated with a disease flare, she said.

LONDON — Incorporating a broader range of activities into lupus disability assessments would provide a more accurate measurement of the disease burden and could help identify patients at risk for depression, Patricia Katz, Ph.D., said at the Sixth European Lupus Meeting.

Disability has traditionally been measured by assessing difficulty in managing activities associated with self-care, independent living, and productive roles such as work. But studies of patients with other chronic conditions such as rheumatoid arthritis have shown that other activities associated with quality of life also can have significant impact.

“We have tried to expand the assessment of disability by incorporating a wide range of activities and also by incorporating the concept of personal value. The reason for including this concept is that certain activities may be more meaningful to some patients than to others, and the meaning or value attached to those activities is likely to affect the impact of the disability,” said Dr. Katz of University of California, San Francisco.

These Valued Life Activities (VLA) and their relationship to overall disability and depression were evaluated in a group of 912 adults with systemic lupus erythematosus.

Activities were subdivided into three groups: obligatory, committed, and discretionary.

Obligatory activities were those necessary for survival and self-sufficiency, including personal care, sleeping, walking, and using local transportation.

Committed activities were those associated with principal productive roles and household management, such as paid work, housework, food preparation, household repairs, yard maintenance, shopping and errands, and child or elder care.

Discretionary activities were pursuits, including socializing with friends and relatives; entertainment away from home; hobbies and other leisure activities; sports and physical recreation; public service; and religious, club, and education activities.

Patients were asked to rate the amount of difficulty they experienced in each of these activities, and their disability was rated on a scale of 0 (none) to 3 (unable).

Mean difficulty ratings were calculated separately for all items and then by activity group. Depression was defined as a score of 16 or greater on the Center for Epidemiologic Studies Depression (CES-D) scale.

Multiple regression analysis was used to test whether VLA disability was associated with depression, and analyses controlled for demographic characteristics, symptoms, and other health conditions.

Overall, patients were unable to perform an average of 1.6 VLA activities because of their lupus, and the overall difficulty rating was 0.81, Dr. Katz said at the meeting, sponsored by the British Society for Rheumatology.

Difficulty ratings were lower for obligatory activities (0.56) than for committed activities (0.87) or discretionary activities (0.81). Patients were unable to perform more discretionary activities (8.3%) than committed activities (6.1%) or obligatory activities (1.8%).

A total of 44% of patients had CESD scores suggestive of probable depression. Each VLA a person was unable to do significantly increased the risk of depression, and a 1-point increase in the difficulty rating increased the odds of depression more than threefold, she said.

“Only disability in discretionary activities was consistently significantly associated with depression, yet these activities are rarely included in traditional disability assessments,” she said.

LONDON — Incorporating a broader range of activities into lupus disability assessments would provide a more accurate measurement of the disease burden and could help identify patients at risk for depression, Patricia Katz, Ph.D., said at the Sixth European Lupus Meeting.

Disability has traditionally been measured by assessing difficulty in managing activities associated with self-care, independent living, and productive roles such as work. But studies of patients with other chronic conditions such as rheumatoid arthritis have shown that other activities associated with quality of life also can have significant impact.

“We have tried to expand the assessment of disability by incorporating a wide range of activities and also by incorporating the concept of personal value. The reason for including this concept is that certain activities may be more meaningful to some patients than to others, and the meaning or value attached to those activities is likely to affect the impact of the disability,” said Dr. Katz of University of California, San Francisco.

These Valued Life Activities (VLA) and their relationship to overall disability and depression were evaluated in a group of 912 adults with systemic lupus erythematosus.

Activities were subdivided into three groups: obligatory, committed, and discretionary.

Obligatory activities were those necessary for survival and self-sufficiency, including personal care, sleeping, walking, and using local transportation.

Committed activities were those associated with principal productive roles and household management, such as paid work, housework, food preparation, household repairs, yard maintenance, shopping and errands, and child or elder care.

Discretionary activities were pursuits, including socializing with friends and relatives; entertainment away from home; hobbies and other leisure activities; sports and physical recreation; public service; and religious, club, and education activities.

Patients were asked to rate the amount of difficulty they experienced in each of these activities, and their disability was rated on a scale of 0 (none) to 3 (unable).

Mean difficulty ratings were calculated separately for all items and then by activity group. Depression was defined as a score of 16 or greater on the Center for Epidemiologic Studies Depression (CES-D) scale.

Multiple regression analysis was used to test whether VLA disability was associated with depression, and analyses controlled for demographic characteristics, symptoms, and other health conditions.

Overall, patients were unable to perform an average of 1.6 VLA activities because of their lupus, and the overall difficulty rating was 0.81, Dr. Katz said at the meeting, sponsored by the British Society for Rheumatology.

Difficulty ratings were lower for obligatory activities (0.56) than for committed activities (0.87) or discretionary activities (0.81). Patients were unable to perform more discretionary activities (8.3%) than committed activities (6.1%) or obligatory activities (1.8%).

A total of 44% of patients had CESD scores suggestive of probable depression. Each VLA a person was unable to do significantly increased the risk of depression, and a 1-point increase in the difficulty rating increased the odds of depression more than threefold, she said.

“Only disability in discretionary activities was consistently significantly associated with depression, yet these activities are rarely included in traditional disability assessments,” she said.

LONDON — Incorporating a broader range of activities into lupus disability assessments would provide a more accurate measurement of the disease burden and could help identify patients at risk for depression, Patricia Katz, Ph.D., said at the Sixth European Lupus Meeting.

Disability has traditionally been measured by assessing difficulty in managing activities associated with self-care, independent living, and productive roles such as work. But studies of patients with other chronic conditions such as rheumatoid arthritis have shown that other activities associated with quality of life also can have significant impact.

“We have tried to expand the assessment of disability by incorporating a wide range of activities and also by incorporating the concept of personal value. The reason for including this concept is that certain activities may be more meaningful to some patients than to others, and the meaning or value attached to those activities is likely to affect the impact of the disability,” said Dr. Katz of University of California, San Francisco.

These Valued Life Activities (VLA) and their relationship to overall disability and depression were evaluated in a group of 912 adults with systemic lupus erythematosus.

Activities were subdivided into three groups: obligatory, committed, and discretionary.

Obligatory activities were those necessary for survival and self-sufficiency, including personal care, sleeping, walking, and using local transportation.

Committed activities were those associated with principal productive roles and household management, such as paid work, housework, food preparation, household repairs, yard maintenance, shopping and errands, and child or elder care.

Discretionary activities were pursuits, including socializing with friends and relatives; entertainment away from home; hobbies and other leisure activities; sports and physical recreation; public service; and religious, club, and education activities.

Patients were asked to rate the amount of difficulty they experienced in each of these activities, and their disability was rated on a scale of 0 (none) to 3 (unable).

Mean difficulty ratings were calculated separately for all items and then by activity group. Depression was defined as a score of 16 or greater on the Center for Epidemiologic Studies Depression (CES-D) scale.

Multiple regression analysis was used to test whether VLA disability was associated with depression, and analyses controlled for demographic characteristics, symptoms, and other health conditions.

Overall, patients were unable to perform an average of 1.6 VLA activities because of their lupus, and the overall difficulty rating was 0.81, Dr. Katz said at the meeting, sponsored by the British Society for Rheumatology.

Difficulty ratings were lower for obligatory activities (0.56) than for committed activities (0.87) or discretionary activities (0.81). Patients were unable to perform more discretionary activities (8.3%) than committed activities (6.1%) or obligatory activities (1.8%).

A total of 44% of patients had CESD scores suggestive of probable depression. Each VLA a person was unable to do significantly increased the risk of depression, and a 1-point increase in the difficulty rating increased the odds of depression more than threefold, she said.

“Only disability in discretionary activities was consistently significantly associated with depression, yet these activities are rarely included in traditional disability assessments,” she said.

CHICAGO — Mycophenolate mofetil may be eclipsing cyclophosphamide as the standard-of-care induction therapy for lupus nephritis, Jill P. Buyon, M.D., reported at a symposium sponsored by the American College of Rheumatology.

Although the role of mycophenolate mofetil (MMF) in maintenance therapy still needs to be defined, the immunosuppressive agent has generated a lot of excitement, she said.

“In patients who don't have rapidly escalating renal insufficiency and whose creatinines are less than 2, there is little question at this point in time that I would suggest MMF over IV Cytoxan [cyclophosphamide],” she said. “I think it's better tolerated.”

She cited results from the largest open-label, controlled study, led by Ellen M. Ginzler, M.D., of the State University of New York Downstate Medical Center, Brooklyn. In that investigation, Dr. Ginzler and colleagues randomly assigned 140 patients with class III, VI, or V lupus nephritis to MMF, starting at 1 g/day and escalating to 3 g, as tolerated, or to intravenous cyclophosphamide, dosed according to National Institutes of Health protocols. The treatment period was 24 weeks.

In all, 16 of the 71 patients initially assigned to the MMF group achieved complete remission of their nephritis, defined as normal serum creatinine level, inactive urine sediment, and proteinuria less than or equal to 500 mg/24 hours. By comparison, 4 of the 69 patients initially assigned to the cyclophosphamide group achieved this primary end point (Arthritis Rheum. 2003;48[9 suppl.]:S647[abstract 1690]).

MMF was well tolerated and appeared better accepted by participants than cyclophosphamide.

“This study has really changed the way I manage patients,” said Dr. Buyon, of the Hospital for Joint Diseases and professor of medicine at New York University. “I certainly call this to my patients' attention, and many, many patients prefer using MMF.”

Dr. Buyon starts patients on MMF 500 mg twice daily, titrating to a target dose of 3 g/day. Some patients may not be able to achieve the target dose because of GI intolerance.

All patients started on MMF also receive prednisone at approximately 60 mg daily, which is reduced over the course of 2-3 months to between 5 mg/day and 10 mg/day.

Dr. Buyon added that she also switches patients induced with cyclophosphamide to MMF if they are doing well at 6 months.

CHICAGO — Mycophenolate mofetil may be eclipsing cyclophosphamide as the standard-of-care induction therapy for lupus nephritis, Jill P. Buyon, M.D., reported at a symposium sponsored by the American College of Rheumatology.

Although the role of mycophenolate mofetil (MMF) in maintenance therapy still needs to be defined, the immunosuppressive agent has generated a lot of excitement, she said.

“In patients who don't have rapidly escalating renal insufficiency and whose creatinines are less than 2, there is little question at this point in time that I would suggest MMF over IV Cytoxan [cyclophosphamide],” she said. “I think it's better tolerated.”

She cited results from the largest open-label, controlled study, led by Ellen M. Ginzler, M.D., of the State University of New York Downstate Medical Center, Brooklyn. In that investigation, Dr. Ginzler and colleagues randomly assigned 140 patients with class III, VI, or V lupus nephritis to MMF, starting at 1 g/day and escalating to 3 g, as tolerated, or to intravenous cyclophosphamide, dosed according to National Institutes of Health protocols. The treatment period was 24 weeks.

In all, 16 of the 71 patients initially assigned to the MMF group achieved complete remission of their nephritis, defined as normal serum creatinine level, inactive urine sediment, and proteinuria less than or equal to 500 mg/24 hours. By comparison, 4 of the 69 patients initially assigned to the cyclophosphamide group achieved this primary end point (Arthritis Rheum. 2003;48[9 suppl.]:S647[abstract 1690]).

MMF was well tolerated and appeared better accepted by participants than cyclophosphamide.

“This study has really changed the way I manage patients,” said Dr. Buyon, of the Hospital for Joint Diseases and professor of medicine at New York University. “I certainly call this to my patients' attention, and many, many patients prefer using MMF.”

Dr. Buyon starts patients on MMF 500 mg twice daily, titrating to a target dose of 3 g/day. Some patients may not be able to achieve the target dose because of GI intolerance.

All patients started on MMF also receive prednisone at approximately 60 mg daily, which is reduced over the course of 2-3 months to between 5 mg/day and 10 mg/day.

Dr. Buyon added that she also switches patients induced with cyclophosphamide to MMF if they are doing well at 6 months.

CHICAGO — Mycophenolate mofetil may be eclipsing cyclophosphamide as the standard-of-care induction therapy for lupus nephritis, Jill P. Buyon, M.D., reported at a symposium sponsored by the American College of Rheumatology.

Although the role of mycophenolate mofetil (MMF) in maintenance therapy still needs to be defined, the immunosuppressive agent has generated a lot of excitement, she said.

“In patients who don't have rapidly escalating renal insufficiency and whose creatinines are less than 2, there is little question at this point in time that I would suggest MMF over IV Cytoxan [cyclophosphamide],” she said. “I think it's better tolerated.”

She cited results from the largest open-label, controlled study, led by Ellen M. Ginzler, M.D., of the State University of New York Downstate Medical Center, Brooklyn. In that investigation, Dr. Ginzler and colleagues randomly assigned 140 patients with class III, VI, or V lupus nephritis to MMF, starting at 1 g/day and escalating to 3 g, as tolerated, or to intravenous cyclophosphamide, dosed according to National Institutes of Health protocols. The treatment period was 24 weeks.

In all, 16 of the 71 patients initially assigned to the MMF group achieved complete remission of their nephritis, defined as normal serum creatinine level, inactive urine sediment, and proteinuria less than or equal to 500 mg/24 hours. By comparison, 4 of the 69 patients initially assigned to the cyclophosphamide group achieved this primary end point (Arthritis Rheum. 2003;48[9 suppl.]:S647[abstract 1690]).

MMF was well tolerated and appeared better accepted by participants than cyclophosphamide.

“This study has really changed the way I manage patients,” said Dr. Buyon, of the Hospital for Joint Diseases and professor of medicine at New York University. “I certainly call this to my patients' attention, and many, many patients prefer using MMF.”

Dr. Buyon starts patients on MMF 500 mg twice daily, titrating to a target dose of 3 g/day. Some patients may not be able to achieve the target dose because of GI intolerance.

All patients started on MMF also receive prednisone at approximately 60 mg daily, which is reduced over the course of 2-3 months to between 5 mg/day and 10 mg/day.

Dr. Buyon added that she also switches patients induced with cyclophosphamide to MMF if they are doing well at 6 months.

NEW YORK — New revelations about the complex cellular processes underlying scleroderma suggest that manipulating the immune system with thalidomide may offer a new means of targeting the disease, Stephen J. Oliver, M.D., said at a rheumatology meeting sponsored by New York University.

Scleroderma begins with inflammation and the production of cytokines, including transforming growth factor (TGF)-β and interleukin (IL)-4, both of which are profibrogenic and activate the fibroblast.

Once the fibroblast becomes activated, it produces its own TGF-β and other cytokines, such as connective tissue growth factor. This leads to further proliferation of fibroblasts and the production of collagen, Dr. Oliver explained.

“At this point, immunosuppression could theoretically act to shut off the production of cytokines and other exogenous activators of the fibroblast. But immune suppression has not been as effective in scleroderma as we would have liked it to be and, in fact, in many cases it hasn't been effective at all.” Early studies targeted TGF-β. However, this cytokine has multiple functions aside from its profibrogenic actions, “so blocking TGF-β systemically might not be such a great idea,” said Dr. Oliver of New York University, New York.

An alternative approach now being studied involves immune manipulation with thalidomide. In scleroderma, the T helper (Th)2 type of immune response is predominant, and laboratory investigations have revealed that thalidomide stimulates a Th1-type cellular response, causing increased production of interferon (IFN)-γ, IL-2, and IL-12 and enhancing the T-cell expression of the CD40 ligand.

Its potential applicability in scleroderma was suggested by the observation that this autoimmune disease shares many clinical features with graft-versus-host disease—a condition that sometimes responds to thalidomide.

In the first open-label study of the drug in scleroderma, 8 of 11 patients completed 12 weeks of treatment. The initial dosage was 50 mg/day; this was gradually increased to 400 mg/day, which is the maximum dosage used for the treatment of erythema nodosum leprosum.

Pruritus and dry skin were reported by seven of the eight patients, but there were no serious adverse events, such as the induction of renal disease, Dr. Oliver said.

Among the changes seen in patients in this preliminary study were increases in CD8 cells within the skin; this could offset the increased levels of CD4 cells that are associated with fibrosis of the skin, he said. Increases also were seen in tumor necrosis factor-α and IL-12. Moreover, there was a “striking clinical effect” in the healing of digital ulcers in four of five patients (Clin. Immunol. 2000;97:109-20).

Recruitment for a double-blind, placebo-controlled trial is under way. Dr. Oliver noted that he had no potential conflicts of interest.

Clinicians with patients who may be candidates for the New York University Scleroderma Trial can contact Dr. Oliver at 212-263-3874.

NEW YORK — New revelations about the complex cellular processes underlying scleroderma suggest that manipulating the immune system with thalidomide may offer a new means of targeting the disease, Stephen J. Oliver, M.D., said at a rheumatology meeting sponsored by New York University.

Scleroderma begins with inflammation and the production of cytokines, including transforming growth factor (TGF)-β and interleukin (IL)-4, both of which are profibrogenic and activate the fibroblast.

Once the fibroblast becomes activated, it produces its own TGF-β and other cytokines, such as connective tissue growth factor. This leads to further proliferation of fibroblasts and the production of collagen, Dr. Oliver explained.

“At this point, immunosuppression could theoretically act to shut off the production of cytokines and other exogenous activators of the fibroblast. But immune suppression has not been as effective in scleroderma as we would have liked it to be and, in fact, in many cases it hasn't been effective at all.” Early studies targeted TGF-β. However, this cytokine has multiple functions aside from its profibrogenic actions, “so blocking TGF-β systemically might not be such a great idea,” said Dr. Oliver of New York University, New York.

An alternative approach now being studied involves immune manipulation with thalidomide. In scleroderma, the T helper (Th)2 type of immune response is predominant, and laboratory investigations have revealed that thalidomide stimulates a Th1-type cellular response, causing increased production of interferon (IFN)-γ, IL-2, and IL-12 and enhancing the T-cell expression of the CD40 ligand.

Its potential applicability in scleroderma was suggested by the observation that this autoimmune disease shares many clinical features with graft-versus-host disease—a condition that sometimes responds to thalidomide.

In the first open-label study of the drug in scleroderma, 8 of 11 patients completed 12 weeks of treatment. The initial dosage was 50 mg/day; this was gradually increased to 400 mg/day, which is the maximum dosage used for the treatment of erythema nodosum leprosum.

Pruritus and dry skin were reported by seven of the eight patients, but there were no serious adverse events, such as the induction of renal disease, Dr. Oliver said.

Among the changes seen in patients in this preliminary study were increases in CD8 cells within the skin; this could offset the increased levels of CD4 cells that are associated with fibrosis of the skin, he said. Increases also were seen in tumor necrosis factor-α and IL-12. Moreover, there was a “striking clinical effect” in the healing of digital ulcers in four of five patients (Clin. Immunol. 2000;97:109-20).

Recruitment for a double-blind, placebo-controlled trial is under way. Dr. Oliver noted that he had no potential conflicts of interest.

Clinicians with patients who may be candidates for the New York University Scleroderma Trial can contact Dr. Oliver at 212-263-3874.

NEW YORK — New revelations about the complex cellular processes underlying scleroderma suggest that manipulating the immune system with thalidomide may offer a new means of targeting the disease, Stephen J. Oliver, M.D., said at a rheumatology meeting sponsored by New York University.

Scleroderma begins with inflammation and the production of cytokines, including transforming growth factor (TGF)-β and interleukin (IL)-4, both of which are profibrogenic and activate the fibroblast.

Once the fibroblast becomes activated, it produces its own TGF-β and other cytokines, such as connective tissue growth factor. This leads to further proliferation of fibroblasts and the production of collagen, Dr. Oliver explained.

“At this point, immunosuppression could theoretically act to shut off the production of cytokines and other exogenous activators of the fibroblast. But immune suppression has not been as effective in scleroderma as we would have liked it to be and, in fact, in many cases it hasn't been effective at all.” Early studies targeted TGF-β. However, this cytokine has multiple functions aside from its profibrogenic actions, “so blocking TGF-β systemically might not be such a great idea,” said Dr. Oliver of New York University, New York.

An alternative approach now being studied involves immune manipulation with thalidomide. In scleroderma, the T helper (Th)2 type of immune response is predominant, and laboratory investigations have revealed that thalidomide stimulates a Th1-type cellular response, causing increased production of interferon (IFN)-γ, IL-2, and IL-12 and enhancing the T-cell expression of the CD40 ligand.

Its potential applicability in scleroderma was suggested by the observation that this autoimmune disease shares many clinical features with graft-versus-host disease—a condition that sometimes responds to thalidomide.

In the first open-label study of the drug in scleroderma, 8 of 11 patients completed 12 weeks of treatment. The initial dosage was 50 mg/day; this was gradually increased to 400 mg/day, which is the maximum dosage used for the treatment of erythema nodosum leprosum.

Pruritus and dry skin were reported by seven of the eight patients, but there were no serious adverse events, such as the induction of renal disease, Dr. Oliver said.

Among the changes seen in patients in this preliminary study were increases in CD8 cells within the skin; this could offset the increased levels of CD4 cells that are associated with fibrosis of the skin, he said. Increases also were seen in tumor necrosis factor-α and IL-12. Moreover, there was a “striking clinical effect” in the healing of digital ulcers in four of five patients (Clin. Immunol. 2000;97:109-20).

Recruitment for a double-blind, placebo-controlled trial is under way. Dr. Oliver noted that he had no potential conflicts of interest.

Clinicians with patients who may be candidates for the New York University Scleroderma Trial can contact Dr. Oliver at 212-263-3874.

LONDON — The prognosis for patients with lupus nephritis who undergo renal transplantation today is good, with a low risk of recurrent renal flare and a decrease in lupus disease activity, Jo H. Berden, M.D., said at the Sixth European Lupus Meeting.

Uncertainty has existed as to whether outcomes among patients with systemic lupus erythematosus (SLE) would be equivalent to those seen among patients whose end-stage renal disease derives from another cause; studies have shown conflicting results and have been limited by confounding factors.

But a more comprehensive review of the European and U.S. experience has found no differences in graft or patient survival between lupus and nonlupus transplant recipients, said Dr. Berden of Radboud University, Nijmegen, the Netherlands.

An analysis based on European data for the years 1984 through 1992 provided by the Eurotransplant International Foundation, Leiden, the Netherlands, found no differences in either patient or graft survival when 165 lupus patients were compared with 20,000 nonlupus controls, Dr. Berden said at the meeting sponsored by the British Society for Rheumatology.

A larger analysis of data from the United States Renal Data System included 772 cadaveric transplants for lupus nephritis and 32,644 cadaveric transplants for other causes. This review also analyzed data from 390 lupus patients whose transplants had been from living donors and from 10,512 nonlupus patients whose transplants had been from living donors.

In an unadjusted analysis, patient survival was better in the lupus group, but graft survival was worse. Once adjustments were made for important confounding factors such as age and gender, however, there were no differences (Kidney Int. 2000;57:2136-43).

Nonlupus patients requiring renal transplantation tend to be male and older than the predominantly female lupus patients with this requirement.

Following transplantation, the incidence of renal flare in lupus patients is reported to be 2%-4% if clinical criteria are used and slightly higher if histologic criteria are used. This is a rather low incidence of recurrence, compared with that for other diseases, the nephrologist said.

Renal transplantation also confers nonrenal benefits to SLE patients. “In the Dutch Working Party on SLE, we found that most patients had severe disease before dialysis, intermediate disease during dialysis, and no extrarenal disease at all after transplantation. Apparently immune suppression that failed to control the disease initially was able to do so post transplantation,” he said.

The immunosuppressive regimen used for lupus patients after transplantation should take into account the heightened risk for cardiovascular disease in these patients, Dr. Berden cautioned. Among the immunosuppressant drugs, some, particularly cyclosporine, increase blood pressure. Sirolimus and cyclosporine raise cholesterol levels; tacrolimus and prednisone can induce or aggravate diabetes. In contrast, mycophenolate mofetil and azathioprine have little if any effect on blood pressure, cholesterol, or glucose levels. The long-term maintenance phase of immune suppression should therefore include one of these two less atherogenic agents, he said.

Experience also has taught that a careful evaluation before transplantation is essential for achieving the best outcome. “We screen all our candidates … for the presence of coronary abnormalities, even if there are no clinical symptoms,” he said. Because the exercise electrocardiogram is not sufficiently sensitive, a thallium scan or stress echocardiogram is recommended. “Until recently, we also did coronary angiography and if abnormalities were seen, revascularization was done,” he said. But recently a randomized clinical trial found no benefit for elective revascularization in asymptomatic patients awaiting major vascular surgery (N. Engl. J. Med. 2004;351:2795-804). “Therefore, there now is a question mark as to whether we should always advise revascularization,” he said.

Antiphospholipid antibodies, which are present in approximately one-third of lupus patients, present another unresolved issue. These antibodies signals an increased risk for acute graft thrombosis, so it remains unclear whether prolonged anticoagulation is needed following transplantation because there have been no randomized trials addressing this issue.

As with any patient approaching end-stage renal failure, “we should always consider preemptive living transplantation because the results are much better,” he said.

LONDON — The prognosis for patients with lupus nephritis who undergo renal transplantation today is good, with a low risk of recurrent renal flare and a decrease in lupus disease activity, Jo H. Berden, M.D., said at the Sixth European Lupus Meeting.

Uncertainty has existed as to whether outcomes among patients with systemic lupus erythematosus (SLE) would be equivalent to those seen among patients whose end-stage renal disease derives from another cause; studies have shown conflicting results and have been limited by confounding factors.

But a more comprehensive review of the European and U.S. experience has found no differences in graft or patient survival between lupus and nonlupus transplant recipients, said Dr. Berden of Radboud University, Nijmegen, the Netherlands.

An analysis based on European data for the years 1984 through 1992 provided by the Eurotransplant International Foundation, Leiden, the Netherlands, found no differences in either patient or graft survival when 165 lupus patients were compared with 20,000 nonlupus controls, Dr. Berden said at the meeting sponsored by the British Society for Rheumatology.

A larger analysis of data from the United States Renal Data System included 772 cadaveric transplants for lupus nephritis and 32,644 cadaveric transplants for other causes. This review also analyzed data from 390 lupus patients whose transplants had been from living donors and from 10,512 nonlupus patients whose transplants had been from living donors.

In an unadjusted analysis, patient survival was better in the lupus group, but graft survival was worse. Once adjustments were made for important confounding factors such as age and gender, however, there were no differences (Kidney Int. 2000;57:2136-43).

Nonlupus patients requiring renal transplantation tend to be male and older than the predominantly female lupus patients with this requirement.

Following transplantation, the incidence of renal flare in lupus patients is reported to be 2%-4% if clinical criteria are used and slightly higher if histologic criteria are used. This is a rather low incidence of recurrence, compared with that for other diseases, the nephrologist said.

Renal transplantation also confers nonrenal benefits to SLE patients. “In the Dutch Working Party on SLE, we found that most patients had severe disease before dialysis, intermediate disease during dialysis, and no extrarenal disease at all after transplantation. Apparently immune suppression that failed to control the disease initially was able to do so post transplantation,” he said.

The immunosuppressive regimen used for lupus patients after transplantation should take into account the heightened risk for cardiovascular disease in these patients, Dr. Berden cautioned. Among the immunosuppressant drugs, some, particularly cyclosporine, increase blood pressure. Sirolimus and cyclosporine raise cholesterol levels; tacrolimus and prednisone can induce or aggravate diabetes. In contrast, mycophenolate mofetil and azathioprine have little if any effect on blood pressure, cholesterol, or glucose levels. The long-term maintenance phase of immune suppression should therefore include one of these two less atherogenic agents, he said.

Experience also has taught that a careful evaluation before transplantation is essential for achieving the best outcome. “We screen all our candidates … for the presence of coronary abnormalities, even if there are no clinical symptoms,” he said. Because the exercise electrocardiogram is not sufficiently sensitive, a thallium scan or stress echocardiogram is recommended. “Until recently, we also did coronary angiography and if abnormalities were seen, revascularization was done,” he said. But recently a randomized clinical trial found no benefit for elective revascularization in asymptomatic patients awaiting major vascular surgery (N. Engl. J. Med. 2004;351:2795-804). “Therefore, there now is a question mark as to whether we should always advise revascularization,” he said.

Antiphospholipid antibodies, which are present in approximately one-third of lupus patients, present another unresolved issue. These antibodies signals an increased risk for acute graft thrombosis, so it remains unclear whether prolonged anticoagulation is needed following transplantation because there have been no randomized trials addressing this issue.

As with any patient approaching end-stage renal failure, “we should always consider preemptive living transplantation because the results are much better,” he said.

LONDON — The prognosis for patients with lupus nephritis who undergo renal transplantation today is good, with a low risk of recurrent renal flare and a decrease in lupus disease activity, Jo H. Berden, M.D., said at the Sixth European Lupus Meeting.

Uncertainty has existed as to whether outcomes among patients with systemic lupus erythematosus (SLE) would be equivalent to those seen among patients whose end-stage renal disease derives from another cause; studies have shown conflicting results and have been limited by confounding factors.

But a more comprehensive review of the European and U.S. experience has found no differences in graft or patient survival between lupus and nonlupus transplant recipients, said Dr. Berden of Radboud University, Nijmegen, the Netherlands.

An analysis based on European data for the years 1984 through 1992 provided by the Eurotransplant International Foundation, Leiden, the Netherlands, found no differences in either patient or graft survival when 165 lupus patients were compared with 20,000 nonlupus controls, Dr. Berden said at the meeting sponsored by the British Society for Rheumatology.

A larger analysis of data from the United States Renal Data System included 772 cadaveric transplants for lupus nephritis and 32,644 cadaveric transplants for other causes. This review also analyzed data from 390 lupus patients whose transplants had been from living donors and from 10,512 nonlupus patients whose transplants had been from living donors.

In an unadjusted analysis, patient survival was better in the lupus group, but graft survival was worse. Once adjustments were made for important confounding factors such as age and gender, however, there were no differences (Kidney Int. 2000;57:2136-43).

Nonlupus patients requiring renal transplantation tend to be male and older than the predominantly female lupus patients with this requirement.

Following transplantation, the incidence of renal flare in lupus patients is reported to be 2%-4% if clinical criteria are used and slightly higher if histologic criteria are used. This is a rather low incidence of recurrence, compared with that for other diseases, the nephrologist said.

Renal transplantation also confers nonrenal benefits to SLE patients. “In the Dutch Working Party on SLE, we found that most patients had severe disease before dialysis, intermediate disease during dialysis, and no extrarenal disease at all after transplantation. Apparently immune suppression that failed to control the disease initially was able to do so post transplantation,” he said.

The immunosuppressive regimen used for lupus patients after transplantation should take into account the heightened risk for cardiovascular disease in these patients, Dr. Berden cautioned. Among the immunosuppressant drugs, some, particularly cyclosporine, increase blood pressure. Sirolimus and cyclosporine raise cholesterol levels; tacrolimus and prednisone can induce or aggravate diabetes. In contrast, mycophenolate mofetil and azathioprine have little if any effect on blood pressure, cholesterol, or glucose levels. The long-term maintenance phase of immune suppression should therefore include one of these two less atherogenic agents, he said.

Experience also has taught that a careful evaluation before transplantation is essential for achieving the best outcome. “We screen all our candidates … for the presence of coronary abnormalities, even if there are no clinical symptoms,” he said. Because the exercise electrocardiogram is not sufficiently sensitive, a thallium scan or stress echocardiogram is recommended. “Until recently, we also did coronary angiography and if abnormalities were seen, revascularization was done,” he said. But recently a randomized clinical trial found no benefit for elective revascularization in asymptomatic patients awaiting major vascular surgery (N. Engl. J. Med. 2004;351:2795-804). “Therefore, there now is a question mark as to whether we should always advise revascularization,” he said.

Antiphospholipid antibodies, which are present in approximately one-third of lupus patients, present another unresolved issue. These antibodies signals an increased risk for acute graft thrombosis, so it remains unclear whether prolonged anticoagulation is needed following transplantation because there have been no randomized trials addressing this issue.

As with any patient approaching end-stage renal failure, “we should always consider preemptive living transplantation because the results are much better,” he said.

High-dose aspirin is just as effective as warfarin in treating intracranial arterial stenosis, and appears much safer, Marc Chimowitz, M.B., and colleagues have reported.

“The common practice of administering warfarin rather than aspirin for symptomatic intracranial arterial stenosis is not supported by the results of this trial,” said Dr. Chimowitz of Emory University, Atlanta.

Enrollment in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial ended early because of the high rate of serious adverse events in the warfarin patients. In addition to being safer for patients, the researchers said, aspirin therapy did not require constant monitoring of international normalized ratios (INRs) and treatment of warfarin-associated bleeding. Aspirin also is much cheaper, they noted (N. Engl. J. Med. 2005;352:1305-16).

Ralph Sacco, M.D., an investigator in the Northern Manhattan Stroke Study, noted in an interview that the WASID trial's findings add to existing data to dispel beliefs about the benefit of warfarin for certain stroke populations.

The conclusion that warfarin provides no survival benefit over aspirin, but confers added risk, is more expensive, and requires intensive monitoring, should reshape its risk/benefit profile for some patients, said Dr. Sacco, professor of neurology and epidemiology at Columbia University, New York.

Dr. Chimowitz and his associates reported on the trial's final analysis that included 569 patients with symptomatic intracranial arterial stenosis who were randomized to either warfarin 5 mg daily or aspirin 650 mg twice daily.

The patients' mean age was about 63 years; about 61% were men. All had a history of either stroke or transient ischemic attack caused by 50%-90% stenosis of a major intracranial artery. The mean follow-up was 1.8 years.

The primary outcome—stroke, brain hemorrhage, or death from vascular causes other than stroke—occurred in 22% (62) of the aspirin patients and 21.8% (63) of the warfarin patients. Myocardial infarction or sudden death occurred significantly more often in the warfarin group than in the aspirin group (7.3% vs. 2.9%).

The overall rate of death was significantly higher in the warfarin group than in the aspirin group: 5.9% (17) vs. 4.3% (12). However, chance probably accounted for some of the deaths that were higher in the warfarin group, especially the six cancers. Major hemorrhages occurred significantly more often in the warfarin group (8.3% vs 3.2%).

Dr. Sacco noted that warfarin is “clearly indicated” for cardioembolic stroke. “This has been made clear in multiple studies, which were actually so positive that they were the springboard for these other studies looking at warfarin in different populations.”

High-dose aspirin is just as effective as warfarin in treating intracranial arterial stenosis, and appears much safer, Marc Chimowitz, M.B., and colleagues have reported.

“The common practice of administering warfarin rather than aspirin for symptomatic intracranial arterial stenosis is not supported by the results of this trial,” said Dr. Chimowitz of Emory University, Atlanta.

Enrollment in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial ended early because of the high rate of serious adverse events in the warfarin patients. In addition to being safer for patients, the researchers said, aspirin therapy did not require constant monitoring of international normalized ratios (INRs) and treatment of warfarin-associated bleeding. Aspirin also is much cheaper, they noted (N. Engl. J. Med. 2005;352:1305-16).

Ralph Sacco, M.D., an investigator in the Northern Manhattan Stroke Study, noted in an interview that the WASID trial's findings add to existing data to dispel beliefs about the benefit of warfarin for certain stroke populations.

The conclusion that warfarin provides no survival benefit over aspirin, but confers added risk, is more expensive, and requires intensive monitoring, should reshape its risk/benefit profile for some patients, said Dr. Sacco, professor of neurology and epidemiology at Columbia University, New York.

Dr. Chimowitz and his associates reported on the trial's final analysis that included 569 patients with symptomatic intracranial arterial stenosis who were randomized to either warfarin 5 mg daily or aspirin 650 mg twice daily.

The patients' mean age was about 63 years; about 61% were men. All had a history of either stroke or transient ischemic attack caused by 50%-90% stenosis of a major intracranial artery. The mean follow-up was 1.8 years.

The primary outcome—stroke, brain hemorrhage, or death from vascular causes other than stroke—occurred in 22% (62) of the aspirin patients and 21.8% (63) of the warfarin patients. Myocardial infarction or sudden death occurred significantly more often in the warfarin group than in the aspirin group (7.3% vs. 2.9%).

The overall rate of death was significantly higher in the warfarin group than in the aspirin group: 5.9% (17) vs. 4.3% (12). However, chance probably accounted for some of the deaths that were higher in the warfarin group, especially the six cancers. Major hemorrhages occurred significantly more often in the warfarin group (8.3% vs 3.2%).

Dr. Sacco noted that warfarin is “clearly indicated” for cardioembolic stroke. “This has been made clear in multiple studies, which were actually so positive that they were the springboard for these other studies looking at warfarin in different populations.”

High-dose aspirin is just as effective as warfarin in treating intracranial arterial stenosis, and appears much safer, Marc Chimowitz, M.B., and colleagues have reported.

“The common practice of administering warfarin rather than aspirin for symptomatic intracranial arterial stenosis is not supported by the results of this trial,” said Dr. Chimowitz of Emory University, Atlanta.

Enrollment in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial ended early because of the high rate of serious adverse events in the warfarin patients. In addition to being safer for patients, the researchers said, aspirin therapy did not require constant monitoring of international normalized ratios (INRs) and treatment of warfarin-associated bleeding. Aspirin also is much cheaper, they noted (N. Engl. J. Med. 2005;352:1305-16).

Ralph Sacco, M.D., an investigator in the Northern Manhattan Stroke Study, noted in an interview that the WASID trial's findings add to existing data to dispel beliefs about the benefit of warfarin for certain stroke populations.

The conclusion that warfarin provides no survival benefit over aspirin, but confers added risk, is more expensive, and requires intensive monitoring, should reshape its risk/benefit profile for some patients, said Dr. Sacco, professor of neurology and epidemiology at Columbia University, New York.

Dr. Chimowitz and his associates reported on the trial's final analysis that included 569 patients with symptomatic intracranial arterial stenosis who were randomized to either warfarin 5 mg daily or aspirin 650 mg twice daily.

The patients' mean age was about 63 years; about 61% were men. All had a history of either stroke or transient ischemic attack caused by 50%-90% stenosis of a major intracranial artery. The mean follow-up was 1.8 years.

The primary outcome—stroke, brain hemorrhage, or death from vascular causes other than stroke—occurred in 22% (62) of the aspirin patients and 21.8% (63) of the warfarin patients. Myocardial infarction or sudden death occurred significantly more often in the warfarin group than in the aspirin group (7.3% vs. 2.9%).

The overall rate of death was significantly higher in the warfarin group than in the aspirin group: 5.9% (17) vs. 4.3% (12). However, chance probably accounted for some of the deaths that were higher in the warfarin group, especially the six cancers. Major hemorrhages occurred significantly more often in the warfarin group (8.3% vs 3.2%).

Dr. Sacco noted that warfarin is “clearly indicated” for cardioembolic stroke. “This has been made clear in multiple studies, which were actually so positive that they were the springboard for these other studies looking at warfarin in different populations.”

NEW ORLEANS — A lower-than-usual intravenous dose of tissue plasminogen activator may still be effective for treating patients with acute stroke, according to a review of 83 patients.

“A low dose of 0.6 mg/kg was safe and effective,” Marilyn M. Rymer, M.D., and associates reported in a poster at the 30th International Stroke Conference.

The usual dose of intravenous tissue plasminogen activator (TPA) is 0.9 mg/kg, based on the regimen's safety and efficacy in the original thrombolytic therapy trial by the National Institute of Neurological Disorders and Stroke (NINDS) and reported in 1995, according to Dr. Rymer, medical director of the stroke center at Saint Luke's Hospital in Kansas City, Mo., and colleagues.

The idea of treating patients initially with a 0.6-mg/kg IV dose began with the Interventional Management of Stroke (IMS) trial, which reserved a 0.3-mg/kg dose for subsequent intraarterial delivery. Hospitals in the Mid America Brain and Stroke Institute (MABSI) regional network now routinely use the 0.6-mg/kg dose of intravenous TPA, and then send the patient by ambulance to a hospital or a referral center for further evaluation, Dr. Rymer and her associates reported in a poster at a conference sponsored by the American Stroke Association.

Dr. Rymer and her colleagues identified 83 patients who received the 0.6-mg/kg dose only in the MABSI database, as well as another 50 patients who received a 0.6-mg/kg dose initially that was later followed by intraarterial treatment with 0.3 mg/kg of TPA to assess in-hospital mortality and patients' NIH Stroke Scale (NIHSS) score at discharge. This analysis used a discharge NIHSS of 4 or less and 2 or less as criteria for good outcomes.

The in-hospital mortality rates were 6% in the 83 patients treated with 0.6 mg/kg of TPA only and 12% in all 133 patients in the MABSI database. The 90-day mortality rates were 17% in the original NINDS trial and 16% in the IMS trial.

At hospital discharge, 71% of the patients who received just the 0.6-mg/kg dose had an NIHSS of 4 or less, and 63% had a score of 2 or less. In the entire MABSI group, 62% had discharge scores of 4 or less and 48% had scores of 2 or less. In the NINDS and IMS studies, NIHSS were measured 90 days after treatment; 31% and 28% of patients, respectively, had scores of 1 or 0 at that time, the investigators reported.

NEW ORLEANS — A lower-than-usual intravenous dose of tissue plasminogen activator may still be effective for treating patients with acute stroke, according to a review of 83 patients.

“A low dose of 0.6 mg/kg was safe and effective,” Marilyn M. Rymer, M.D., and associates reported in a poster at the 30th International Stroke Conference.

The usual dose of intravenous tissue plasminogen activator (TPA) is 0.9 mg/kg, based on the regimen's safety and efficacy in the original thrombolytic therapy trial by the National Institute of Neurological Disorders and Stroke (NINDS) and reported in 1995, according to Dr. Rymer, medical director of the stroke center at Saint Luke's Hospital in Kansas City, Mo., and colleagues.

The idea of treating patients initially with a 0.6-mg/kg IV dose began with the Interventional Management of Stroke (IMS) trial, which reserved a 0.3-mg/kg dose for subsequent intraarterial delivery. Hospitals in the Mid America Brain and Stroke Institute (MABSI) regional network now routinely use the 0.6-mg/kg dose of intravenous TPA, and then send the patient by ambulance to a hospital or a referral center for further evaluation, Dr. Rymer and her associates reported in a poster at a conference sponsored by the American Stroke Association.

Dr. Rymer and her colleagues identified 83 patients who received the 0.6-mg/kg dose only in the MABSI database, as well as another 50 patients who received a 0.6-mg/kg dose initially that was later followed by intraarterial treatment with 0.3 mg/kg of TPA to assess in-hospital mortality and patients' NIH Stroke Scale (NIHSS) score at discharge. This analysis used a discharge NIHSS of 4 or less and 2 or less as criteria for good outcomes.

The in-hospital mortality rates were 6% in the 83 patients treated with 0.6 mg/kg of TPA only and 12% in all 133 patients in the MABSI database. The 90-day mortality rates were 17% in the original NINDS trial and 16% in the IMS trial.

At hospital discharge, 71% of the patients who received just the 0.6-mg/kg dose had an NIHSS of 4 or less, and 63% had a score of 2 or less. In the entire MABSI group, 62% had discharge scores of 4 or less and 48% had scores of 2 or less. In the NINDS and IMS studies, NIHSS were measured 90 days after treatment; 31% and 28% of patients, respectively, had scores of 1 or 0 at that time, the investigators reported.

NEW ORLEANS — A lower-than-usual intravenous dose of tissue plasminogen activator may still be effective for treating patients with acute stroke, according to a review of 83 patients.

“A low dose of 0.6 mg/kg was safe and effective,” Marilyn M. Rymer, M.D., and associates reported in a poster at the 30th International Stroke Conference.

The usual dose of intravenous tissue plasminogen activator (TPA) is 0.9 mg/kg, based on the regimen's safety and efficacy in the original thrombolytic therapy trial by the National Institute of Neurological Disorders and Stroke (NINDS) and reported in 1995, according to Dr. Rymer, medical director of the stroke center at Saint Luke's Hospital in Kansas City, Mo., and colleagues.

The idea of treating patients initially with a 0.6-mg/kg IV dose began with the Interventional Management of Stroke (IMS) trial, which reserved a 0.3-mg/kg dose for subsequent intraarterial delivery. Hospitals in the Mid America Brain and Stroke Institute (MABSI) regional network now routinely use the 0.6-mg/kg dose of intravenous TPA, and then send the patient by ambulance to a hospital or a referral center for further evaluation, Dr. Rymer and her associates reported in a poster at a conference sponsored by the American Stroke Association.

Dr. Rymer and her colleagues identified 83 patients who received the 0.6-mg/kg dose only in the MABSI database, as well as another 50 patients who received a 0.6-mg/kg dose initially that was later followed by intraarterial treatment with 0.3 mg/kg of TPA to assess in-hospital mortality and patients' NIH Stroke Scale (NIHSS) score at discharge. This analysis used a discharge NIHSS of 4 or less and 2 or less as criteria for good outcomes.

The in-hospital mortality rates were 6% in the 83 patients treated with 0.6 mg/kg of TPA only and 12% in all 133 patients in the MABSI database. The 90-day mortality rates were 17% in the original NINDS trial and 16% in the IMS trial.

At hospital discharge, 71% of the patients who received just the 0.6-mg/kg dose had an NIHSS of 4 or less, and 63% had a score of 2 or less. In the entire MABSI group, 62% had discharge scores of 4 or less and 48% had scores of 2 or less. In the NINDS and IMS studies, NIHSS were measured 90 days after treatment; 31% and 28% of patients, respectively, had scores of 1 or 0 at that time, the investigators reported.