Timothy F. Kirn

SAN DIEGO – Nancy Clark, a registered nurse, had been drug free and sober for 3 years when she tested positive for alcohol on the new ethyl glucuronide test, the same one used for many chemically dependent physicians who are entered into monitoring programs and are on probation.

She kept her job the first time, but then she tested positive again–and lost it.

So Ms. Clark bought a plane ticket. She flew almost 3,000 miles from Pennsylvania to San Diego to meet with the one person she thought might be able to help her and others in her situation: Dr. Greg Skipper.

“When I tested positive, I looked on the Internet, and everything I saw said this test was perfect,” said Ms. Clark of Fleetwood, Penn., at the meeting where she met with Dr. Skipper–the annual conference of the American Society of Addiction Medicine.

“I thought: How am I ever going to be able to protest this?” she said.

Recent evidence, however, suggests that while the test may be highly accurate and sensitive, it may also be fallible, said Dr. Skipper, who helped develop ethyl glucuronide (EtG) as a drug test to monitor whether a person has consumed alcohol.

In essence, the evidence suggests the test may be too good, in that it appears to pick up people who are exposed to alcohol in any number of ways without drinking it, said Dr. Skipper of Montgomery, Ala., director of that state's physician health program.

He says he knows of at least 60 people who claim that they have not touched a drink but have had positive results on the EtG test.

Consequently, some people who have not been drinking may lose their jobs, licenses, or even custody of their children. Still other people may be going back to jail.

For health care workers, washing hands with alcohol-containing sanitizers such as Purell might be the reason they are testing positive, Dr. Skipper said.

“We're getting data, and we're worried about what [they show],” Dr. Skipper said in an interview.

Ethyl glucuronide is a very specific metabolite of alcohol found in urine. It is considered a better test than a blood alcohol level, because it lasts much longer–about 5 days–depending on the amount ingested and individual variation.

Although it has been theorized that certain rare individuals could automatically ferment alcohol in their system, such as yeast in the bowel, it has been assumed that a positive test meant someone had to have taken a drink.

At the meeting, Dr. Michael R. Liepman presented an experiment on the EtG test that he conducted using 24 abstinent subjects.

One group of subjects washed their hands with Purell (62% alcohol) 15 times at 4-minute intervals in a small enclosed room where, presumably, they would be inhaling the fumes from the washing. Each of those subjects was accompanied by another subject who did not wash their hands but stood close enough for inhalation.

A third group washed their hands in an air-flow chamber to prevent inhalation, and a fourth group served as controls.

Three of the subjects who washed their hands and could inhale the sanitizer had positive EtG tests 30 minutes after washing, as did one of the subjects observing in the same room, said Dr. Liepman, director of addiction psychiatry and research at Michigan State University's Kalamazoo Center for Medical Studies.

That observer had a level of 350 ng/mL, while the cutoff used for a positive test in the experiment was 100 ng/mL, the same cutoff that is generally used out in the field.

None of the subjects who washed in the air-flow chamber had a positive test, though there were detectable levels.

Breathalyzer tests given to the subjects did not suggest any level of impairment.

The results confirmed that use of alcohol-containing hand wash can influence the EtG test, and the primary means appears to be inhalation, Dr. Liepman said.

“Recovering alcoholics, including those who are subject to urine monitoring, should avoid the use of alcohol-based hand sanitizer,” he said.

Dr. Liepman said he was motivated to perform the experiment because two nurses in his practice, both of whom were recovering opiate addicts and both of whom were pregnant, had tested positive for ethyl glucuronide and violated their recovery employment contracts, he said.

Both of the nurses were suspended for 1 month, just at the time they needed to be accumulating vacation hours so they could take time off for the birth of their babies.

Both denied drinking, neither tested positive for any other drugs, and both were doing well on the job.

One nurse measured 270 ng/mL on the EtG test, while the other measured 215 ng/mL, levels that might be considered fairly low for a substance abuser who has fallen off the wagon, since two drinks can produce a level of 23,000 ng/mL, Dr. Liepman said.

Both nurses reported washing their hands with sanitizer on the job upward of 30 times a day, a frequency that might explain why, among health care workers, so many of those who have been tripped up by the test have been nurses.

Dr. Skipper said that he does not want to see the test abandoned. He finds it frequently picks up monitored physicians whose alcohol use would not be detected otherwise, and even among those who deny drinking at first, 50%–80% later admit to it.

Random EtG testing surveys of physicians who are not supposed to be drinking in monitoring programs have found that around 7% will have a positive test result. It is important to catch those physicians to get them help, Dr. Skipper said.

Given the gathering evidence, however, the test needs to be used with some clinical judgment of the individual, he added.

“I am urging no use in administrative hearings and courts,” he said. “It is a clinical test.”

Moreover, if hand sanitizer can cause measurable EtG levels, then probably any product containing alcohol could, he noted. And products that contain alcohol are everywhere, ranging from the cold medicine NyQuil to asthma inhalers, topical testosterone, and bug spray.

In the laboratory, Dr. Skipper said he has found that two nonalcoholic beers will cause a level of 93 ng/mL and gargling with Listerine can trigger a level of 100 ng/mL.

“We have to expect that all recovering doctors are going to be using these products,” noted Dr. Michael M. Miller of Madison, Wis., president of the American Society of Addiction Medicine, who attended the session on ethyl glucuronide at which Dr. Liepman's study was presented.

The EtG test appears to be used widely by physician monitoring programs. In a survey of physician health programs conducted this year, 29 of 31 responding programs reported that they use the test, compared with 17 of 46 programs that reported using it in 2004, said Dr. Michael Sucher, who serves as medical director of the physician health program in Scottsdale, Ariz.

Some of those states use it routinely, others just for cause.

Michigan, which is one of the states that does not use the test, did use it previously but stopped because there were too many challenges to cases of positive test results.

Dr. Sucher agrees with Dr. Skipper that a positive test result should not be used as the sole basis of punitive action.

“We all learned in medical school that you don't treat a number or a test result,” he said at the meeting. “You have to have clinical correlation.”

Meanwhile, Ms. Clark, who came to the meeting with two other nurses and a pharmacist who also have had their licenses suspended because of EtG testing, has been out of work for 6 months.

She noted that, without the positive results on the second test, her 3-year probation period would have been over 2 months ago.

SAN DIEGO – Nancy Clark, a registered nurse, had been drug free and sober for 3 years when she tested positive for alcohol on the new ethyl glucuronide test, the same one used for many chemically dependent physicians who are entered into monitoring programs and are on probation.

She kept her job the first time, but then she tested positive again–and lost it.

So Ms. Clark bought a plane ticket. She flew almost 3,000 miles from Pennsylvania to San Diego to meet with the one person she thought might be able to help her and others in her situation: Dr. Greg Skipper.

“When I tested positive, I looked on the Internet, and everything I saw said this test was perfect,” said Ms. Clark of Fleetwood, Penn., at the meeting where she met with Dr. Skipper–the annual conference of the American Society of Addiction Medicine.

“I thought: How am I ever going to be able to protest this?” she said.

Recent evidence, however, suggests that while the test may be highly accurate and sensitive, it may also be fallible, said Dr. Skipper, who helped develop ethyl glucuronide (EtG) as a drug test to monitor whether a person has consumed alcohol.

In essence, the evidence suggests the test may be too good, in that it appears to pick up people who are exposed to alcohol in any number of ways without drinking it, said Dr. Skipper of Montgomery, Ala., director of that state's physician health program.

He says he knows of at least 60 people who claim that they have not touched a drink but have had positive results on the EtG test.

Consequently, some people who have not been drinking may lose their jobs, licenses, or even custody of their children. Still other people may be going back to jail.

For health care workers, washing hands with alcohol-containing sanitizers such as Purell might be the reason they are testing positive, Dr. Skipper said.

“We're getting data, and we're worried about what [they show],” Dr. Skipper said in an interview.

Ethyl glucuronide is a very specific metabolite of alcohol found in urine. It is considered a better test than a blood alcohol level, because it lasts much longer–about 5 days–depending on the amount ingested and individual variation.

Although it has been theorized that certain rare individuals could automatically ferment alcohol in their system, such as yeast in the bowel, it has been assumed that a positive test meant someone had to have taken a drink.

At the meeting, Dr. Michael R. Liepman presented an experiment on the EtG test that he conducted using 24 abstinent subjects.

One group of subjects washed their hands with Purell (62% alcohol) 15 times at 4-minute intervals in a small enclosed room where, presumably, they would be inhaling the fumes from the washing. Each of those subjects was accompanied by another subject who did not wash their hands but stood close enough for inhalation.

A third group washed their hands in an air-flow chamber to prevent inhalation, and a fourth group served as controls.

Three of the subjects who washed their hands and could inhale the sanitizer had positive EtG tests 30 minutes after washing, as did one of the subjects observing in the same room, said Dr. Liepman, director of addiction psychiatry and research at Michigan State University's Kalamazoo Center for Medical Studies.

That observer had a level of 350 ng/mL, while the cutoff used for a positive test in the experiment was 100 ng/mL, the same cutoff that is generally used out in the field.

None of the subjects who washed in the air-flow chamber had a positive test, though there were detectable levels.

Breathalyzer tests given to the subjects did not suggest any level of impairment.

The results confirmed that use of alcohol-containing hand wash can influence the EtG test, and the primary means appears to be inhalation, Dr. Liepman said.

“Recovering alcoholics, including those who are subject to urine monitoring, should avoid the use of alcohol-based hand sanitizer,” he said.

Dr. Liepman said he was motivated to perform the experiment because two nurses in his practice, both of whom were recovering opiate addicts and both of whom were pregnant, had tested positive for ethyl glucuronide and violated their recovery employment contracts, he said.

Both of the nurses were suspended for 1 month, just at the time they needed to be accumulating vacation hours so they could take time off for the birth of their babies.

Both denied drinking, neither tested positive for any other drugs, and both were doing well on the job.

One nurse measured 270 ng/mL on the EtG test, while the other measured 215 ng/mL, levels that might be considered fairly low for a substance abuser who has fallen off the wagon, since two drinks can produce a level of 23,000 ng/mL, Dr. Liepman said.

Both nurses reported washing their hands with sanitizer on the job upward of 30 times a day, a frequency that might explain why, among health care workers, so many of those who have been tripped up by the test have been nurses.

Dr. Skipper said that he does not want to see the test abandoned. He finds it frequently picks up monitored physicians whose alcohol use would not be detected otherwise, and even among those who deny drinking at first, 50%–80% later admit to it.

Random EtG testing surveys of physicians who are not supposed to be drinking in monitoring programs have found that around 7% will have a positive test result. It is important to catch those physicians to get them help, Dr. Skipper said.

Given the gathering evidence, however, the test needs to be used with some clinical judgment of the individual, he added.

“I am urging no use in administrative hearings and courts,” he said. “It is a clinical test.”

Moreover, if hand sanitizer can cause measurable EtG levels, then probably any product containing alcohol could, he noted. And products that contain alcohol are everywhere, ranging from the cold medicine NyQuil to asthma inhalers, topical testosterone, and bug spray.

In the laboratory, Dr. Skipper said he has found that two nonalcoholic beers will cause a level of 93 ng/mL and gargling with Listerine can trigger a level of 100 ng/mL.

“We have to expect that all recovering doctors are going to be using these products,” noted Dr. Michael M. Miller of Madison, Wis., president of the American Society of Addiction Medicine, who attended the session on ethyl glucuronide at which Dr. Liepman's study was presented.

The EtG test appears to be used widely by physician monitoring programs. In a survey of physician health programs conducted this year, 29 of 31 responding programs reported that they use the test, compared with 17 of 46 programs that reported using it in 2004, said Dr. Michael Sucher, who serves as medical director of the physician health program in Scottsdale, Ariz.

Some of those states use it routinely, others just for cause.

Michigan, which is one of the states that does not use the test, did use it previously but stopped because there were too many challenges to cases of positive test results.

Dr. Sucher agrees with Dr. Skipper that a positive test result should not be used as the sole basis of punitive action.

“We all learned in medical school that you don't treat a number or a test result,” he said at the meeting. “You have to have clinical correlation.”

Meanwhile, Ms. Clark, who came to the meeting with two other nurses and a pharmacist who also have had their licenses suspended because of EtG testing, has been out of work for 6 months.

She noted that, without the positive results on the second test, her 3-year probation period would have been over 2 months ago.

SAN DIEGO – Nancy Clark, a registered nurse, had been drug free and sober for 3 years when she tested positive for alcohol on the new ethyl glucuronide test, the same one used for many chemically dependent physicians who are entered into monitoring programs and are on probation.

She kept her job the first time, but then she tested positive again–and lost it.

So Ms. Clark bought a plane ticket. She flew almost 3,000 miles from Pennsylvania to San Diego to meet with the one person she thought might be able to help her and others in her situation: Dr. Greg Skipper.

“When I tested positive, I looked on the Internet, and everything I saw said this test was perfect,” said Ms. Clark of Fleetwood, Penn., at the meeting where she met with Dr. Skipper–the annual conference of the American Society of Addiction Medicine.

“I thought: How am I ever going to be able to protest this?” she said.

Recent evidence, however, suggests that while the test may be highly accurate and sensitive, it may also be fallible, said Dr. Skipper, who helped develop ethyl glucuronide (EtG) as a drug test to monitor whether a person has consumed alcohol.

In essence, the evidence suggests the test may be too good, in that it appears to pick up people who are exposed to alcohol in any number of ways without drinking it, said Dr. Skipper of Montgomery, Ala., director of that state's physician health program.

He says he knows of at least 60 people who claim that they have not touched a drink but have had positive results on the EtG test.

Consequently, some people who have not been drinking may lose their jobs, licenses, or even custody of their children. Still other people may be going back to jail.

For health care workers, washing hands with alcohol-containing sanitizers such as Purell might be the reason they are testing positive, Dr. Skipper said.

“We're getting data, and we're worried about what [they show],” Dr. Skipper said in an interview.

Ethyl glucuronide is a very specific metabolite of alcohol found in urine. It is considered a better test than a blood alcohol level, because it lasts much longer–about 5 days–depending on the amount ingested and individual variation.

Although it has been theorized that certain rare individuals could automatically ferment alcohol in their system, such as yeast in the bowel, it has been assumed that a positive test meant someone had to have taken a drink.

At the meeting, Dr. Michael R. Liepman presented an experiment on the EtG test that he conducted using 24 abstinent subjects.

One group of subjects washed their hands with Purell (62% alcohol) 15 times at 4-minute intervals in a small enclosed room where, presumably, they would be inhaling the fumes from the washing. Each of those subjects was accompanied by another subject who did not wash their hands but stood close enough for inhalation.

A third group washed their hands in an air-flow chamber to prevent inhalation, and a fourth group served as controls.

Three of the subjects who washed their hands and could inhale the sanitizer had positive EtG tests 30 minutes after washing, as did one of the subjects observing in the same room, said Dr. Liepman, director of addiction psychiatry and research at Michigan State University's Kalamazoo Center for Medical Studies.

That observer had a level of 350 ng/mL, while the cutoff used for a positive test in the experiment was 100 ng/mL, the same cutoff that is generally used out in the field.

None of the subjects who washed in the air-flow chamber had a positive test, though there were detectable levels.

Breathalyzer tests given to the subjects did not suggest any level of impairment.

The results confirmed that use of alcohol-containing hand wash can influence the EtG test, and the primary means appears to be inhalation, Dr. Liepman said.

“Recovering alcoholics, including those who are subject to urine monitoring, should avoid the use of alcohol-based hand sanitizer,” he said.

Dr. Liepman said he was motivated to perform the experiment because two nurses in his practice, both of whom were recovering opiate addicts and both of whom were pregnant, had tested positive for ethyl glucuronide and violated their recovery employment contracts, he said.

Both of the nurses were suspended for 1 month, just at the time they needed to be accumulating vacation hours so they could take time off for the birth of their babies.

Both denied drinking, neither tested positive for any other drugs, and both were doing well on the job.

One nurse measured 270 ng/mL on the EtG test, while the other measured 215 ng/mL, levels that might be considered fairly low for a substance abuser who has fallen off the wagon, since two drinks can produce a level of 23,000 ng/mL, Dr. Liepman said.

Both nurses reported washing their hands with sanitizer on the job upward of 30 times a day, a frequency that might explain why, among health care workers, so many of those who have been tripped up by the test have been nurses.

Dr. Skipper said that he does not want to see the test abandoned. He finds it frequently picks up monitored physicians whose alcohol use would not be detected otherwise, and even among those who deny drinking at first, 50%–80% later admit to it.

Random EtG testing surveys of physicians who are not supposed to be drinking in monitoring programs have found that around 7% will have a positive test result. It is important to catch those physicians to get them help, Dr. Skipper said.

Given the gathering evidence, however, the test needs to be used with some clinical judgment of the individual, he added.

“I am urging no use in administrative hearings and courts,” he said. “It is a clinical test.”

Moreover, if hand sanitizer can cause measurable EtG levels, then probably any product containing alcohol could, he noted. And products that contain alcohol are everywhere, ranging from the cold medicine NyQuil to asthma inhalers, topical testosterone, and bug spray.

In the laboratory, Dr. Skipper said he has found that two nonalcoholic beers will cause a level of 93 ng/mL and gargling with Listerine can trigger a level of 100 ng/mL.

“We have to expect that all recovering doctors are going to be using these products,” noted Dr. Michael M. Miller of Madison, Wis., president of the American Society of Addiction Medicine, who attended the session on ethyl glucuronide at which Dr. Liepman's study was presented.

The EtG test appears to be used widely by physician monitoring programs. In a survey of physician health programs conducted this year, 29 of 31 responding programs reported that they use the test, compared with 17 of 46 programs that reported using it in 2004, said Dr. Michael Sucher, who serves as medical director of the physician health program in Scottsdale, Ariz.

Some of those states use it routinely, others just for cause.

Michigan, which is one of the states that does not use the test, did use it previously but stopped because there were too many challenges to cases of positive test results.

Dr. Sucher agrees with Dr. Skipper that a positive test result should not be used as the sole basis of punitive action.

“We all learned in medical school that you don't treat a number or a test result,” he said at the meeting. “You have to have clinical correlation.”

Meanwhile, Ms. Clark, who came to the meeting with two other nurses and a pharmacist who also have had their licenses suspended because of EtG testing, has been out of work for 6 months.

She noted that, without the positive results on the second test, her 3-year probation period would have been over 2 months ago.

ATLANTA – Current data on sexually abusive adolescents who molest others are consistent with those of previous studies, which showed that they tend to have been molested before the age of 9 years, two researchers said at a meeting of the National Adolescent Perpetration Network.

Among girls who were abused and became abusers, a common characteristic is that they were abused by a woman, reported Dr. Gene G. Abel and Nora Harlow of the Child Molestation Research & Prevention Institute, Atlanta.

Perhaps one of the most important findings of the latest investigation for males who have been abused and become abusers is that they report knowing almost nothing about sex before their molestation, Ms. Harlow said at the conference.

That finding suggests that early sex education might have an impact on reducing sex offenses, she said.

The research presented by Dr. Abel and Ms. Harlow was an investigation of more than 10,000 adolescents who took the Abel Assessment for Sexual Interest for Boys and Girls, a test designed by Dr. Abel, a past president of the Society of Behavioral Medicine. The test, administered at more than 500 sites, can be administered for a variety of reasons, including self-referral. Most often, it was administered after referral by law enforcement or a mental health professional because of known or alleged sexual misconduct of some sort.

Of the more than 10,000 adolescents in the study, 5,678 had sexually abused younger children. Analysis of the 2,811 boys in the study who had been child victims of sexual abuse revealed that 2,034 had abused others. Among the 390 sexually abused adolescent females, 187 had abused others.

Because the research had been put together only recently before the conference, Dr. Abel said, the researchers did not have much information on the characteristics of the sexually abused adolescents who had not abused anyone, such as why they had taken the test.

However, the researchers did present the molestation factors that were significantly associated with becoming an abuser (P value less than .06) and their rank of importance.

Some of those attending the conference were bothered by the lack of detail.

“I think a lot of it probably is useful,” but it is difficult to judge without information on who constituted the comparison group and little information on the strength of association, said Michael H. Miner, Ph.D., a psychologist with the Center for Sexual Health at the University of Minnesota, Minneapolis, in an interview.

Ms. Harlow said many of the factors identified by their analysis seemed to reflect that it was the “inner experience” of the molestation that appeared to be a determining factor.

For example, those who had abused others tended to still be tormented by the experience, had experienced sexual arousal, and, for the males at least, had tended to be molested by someone they looked up to, she noted.

Dr. Abel said it is not surprising that the children reported experiencing arousal, because abusers generally want the child to be compliant and to believe that the child is enjoying the experience. As a result, the abusers work hard to stimulate the child.

Ms. Harlow said she was “stunned” to find that so many of the females who became abusers reported that they had been molested by a woman.

She also said that the fact that the second most associated factor among the boys was that they were completely uninformed about sex before their abuse suggested that sex information, given early to children as a social norm, could be beneficial.

Among the other findings from the survey are:

▸ The number of times the child was molested correlated significantly with the number of victims they abused. Among the male abusers who were not molested themselves, the average number of victims they had was three, but it was eight for those who had been molested 50 times or more. The pattern was the same for females.

“In other words, it is a marker,” Ms. Harlow said. “If you see a child who has been abused a lot, pay attention to that child.”

▸ The data from 16,000 adult males who also have taken the test show that 70% of adult men who molest boys score as being heterosexual on the Kinsey Scale.

That is the exact percentage of men in the general population who score as heterosexual on the Kinsey Scale, Dr. Abel said.

▸ Of the adolescent boys who were abused, 55% were abused by an older boy, 40% by a man, 27% by an older girl, and 14% by a woman. (The percentages add up to more than 100% because some had multiple abusers.)

Of the adolescent females who were abused, 66% were abused by a man, 63% by an older boy, 20% by an older girl, and 13% by a woman.

Past Experiences Of Abusive

For males, factors significantly associated with abuse of others were:

I was less than 9 years old when sexually abused.

I knew nothing about sex before I was sexually abused.

I wish the molestation did not bother me so much.

I was abused by my idol.

Sometimes I got a strong sexual feeling between my legs when I was being sexually abused.

I was touched by a boy more than 3 years older than me.

I took baths or showers with my sexual abuser.

The abuser put their tongue in my mouth.

The abuser was a relative living in my house.

I was molested by more than one person.

For females, significant factors were:

I was less than 9 years old when sexually abused.

I was touched by a woman.

Sometimes when my girlfriend or boyfriend rubs my chest, I have flashbacks of when I was abused.

Sometimes I got a strong sexual feeling between my legs when I was being sexually abused.

ATLANTA – Current data on sexually abusive adolescents who molest others are consistent with those of previous studies, which showed that they tend to have been molested before the age of 9 years, two researchers said at a meeting of the National Adolescent Perpetration Network.

Among girls who were abused and became abusers, a common characteristic is that they were abused by a woman, reported Dr. Gene G. Abel and Nora Harlow of the Child Molestation Research & Prevention Institute, Atlanta.

Perhaps one of the most important findings of the latest investigation for males who have been abused and become abusers is that they report knowing almost nothing about sex before their molestation, Ms. Harlow said at the conference.

That finding suggests that early sex education might have an impact on reducing sex offenses, she said.

The research presented by Dr. Abel and Ms. Harlow was an investigation of more than 10,000 adolescents who took the Abel Assessment for Sexual Interest for Boys and Girls, a test designed by Dr. Abel, a past president of the Society of Behavioral Medicine. The test, administered at more than 500 sites, can be administered for a variety of reasons, including self-referral. Most often, it was administered after referral by law enforcement or a mental health professional because of known or alleged sexual misconduct of some sort.

Of the more than 10,000 adolescents in the study, 5,678 had sexually abused younger children. Analysis of the 2,811 boys in the study who had been child victims of sexual abuse revealed that 2,034 had abused others. Among the 390 sexually abused adolescent females, 187 had abused others.

Because the research had been put together only recently before the conference, Dr. Abel said, the researchers did not have much information on the characteristics of the sexually abused adolescents who had not abused anyone, such as why they had taken the test.

However, the researchers did present the molestation factors that were significantly associated with becoming an abuser (P value less than .06) and their rank of importance.

Some of those attending the conference were bothered by the lack of detail.

“I think a lot of it probably is useful,” but it is difficult to judge without information on who constituted the comparison group and little information on the strength of association, said Michael H. Miner, Ph.D., a psychologist with the Center for Sexual Health at the University of Minnesota, Minneapolis, in an interview.

Ms. Harlow said many of the factors identified by their analysis seemed to reflect that it was the “inner experience” of the molestation that appeared to be a determining factor.

For example, those who had abused others tended to still be tormented by the experience, had experienced sexual arousal, and, for the males at least, had tended to be molested by someone they looked up to, she noted.

Dr. Abel said it is not surprising that the children reported experiencing arousal, because abusers generally want the child to be compliant and to believe that the child is enjoying the experience. As a result, the abusers work hard to stimulate the child.

Ms. Harlow said she was “stunned” to find that so many of the females who became abusers reported that they had been molested by a woman.

She also said that the fact that the second most associated factor among the boys was that they were completely uninformed about sex before their abuse suggested that sex information, given early to children as a social norm, could be beneficial.

Among the other findings from the survey are:

▸ The number of times the child was molested correlated significantly with the number of victims they abused. Among the male abusers who were not molested themselves, the average number of victims they had was three, but it was eight for those who had been molested 50 times or more. The pattern was the same for females.

“In other words, it is a marker,” Ms. Harlow said. “If you see a child who has been abused a lot, pay attention to that child.”

▸ The data from 16,000 adult males who also have taken the test show that 70% of adult men who molest boys score as being heterosexual on the Kinsey Scale.

That is the exact percentage of men in the general population who score as heterosexual on the Kinsey Scale, Dr. Abel said.

▸ Of the adolescent boys who were abused, 55% were abused by an older boy, 40% by a man, 27% by an older girl, and 14% by a woman. (The percentages add up to more than 100% because some had multiple abusers.)

Of the adolescent females who were abused, 66% were abused by a man, 63% by an older boy, 20% by an older girl, and 13% by a woman.

Past Experiences Of Abusive

For males, factors significantly associated with abuse of others were:

I was less than 9 years old when sexually abused.

I knew nothing about sex before I was sexually abused.

I wish the molestation did not bother me so much.

I was abused by my idol.

Sometimes I got a strong sexual feeling between my legs when I was being sexually abused.

I was touched by a boy more than 3 years older than me.

I took baths or showers with my sexual abuser.

The abuser put their tongue in my mouth.

The abuser was a relative living in my house.

I was molested by more than one person.

For females, significant factors were:

I was less than 9 years old when sexually abused.

I was touched by a woman.

Sometimes when my girlfriend or boyfriend rubs my chest, I have flashbacks of when I was abused.

Sometimes I got a strong sexual feeling between my legs when I was being sexually abused.

ATLANTA – Current data on sexually abusive adolescents who molest others are consistent with those of previous studies, which showed that they tend to have been molested before the age of 9 years, two researchers said at a meeting of the National Adolescent Perpetration Network.

Among girls who were abused and became abusers, a common characteristic is that they were abused by a woman, reported Dr. Gene G. Abel and Nora Harlow of the Child Molestation Research & Prevention Institute, Atlanta.

Perhaps one of the most important findings of the latest investigation for males who have been abused and become abusers is that they report knowing almost nothing about sex before their molestation, Ms. Harlow said at the conference.

That finding suggests that early sex education might have an impact on reducing sex offenses, she said.

The research presented by Dr. Abel and Ms. Harlow was an investigation of more than 10,000 adolescents who took the Abel Assessment for Sexual Interest for Boys and Girls, a test designed by Dr. Abel, a past president of the Society of Behavioral Medicine. The test, administered at more than 500 sites, can be administered for a variety of reasons, including self-referral. Most often, it was administered after referral by law enforcement or a mental health professional because of known or alleged sexual misconduct of some sort.

Of the more than 10,000 adolescents in the study, 5,678 had sexually abused younger children. Analysis of the 2,811 boys in the study who had been child victims of sexual abuse revealed that 2,034 had abused others. Among the 390 sexually abused adolescent females, 187 had abused others.

Because the research had been put together only recently before the conference, Dr. Abel said, the researchers did not have much information on the characteristics of the sexually abused adolescents who had not abused anyone, such as why they had taken the test.

However, the researchers did present the molestation factors that were significantly associated with becoming an abuser (P value less than .06) and their rank of importance.

Some of those attending the conference were bothered by the lack of detail.

“I think a lot of it probably is useful,” but it is difficult to judge without information on who constituted the comparison group and little information on the strength of association, said Michael H. Miner, Ph.D., a psychologist with the Center for Sexual Health at the University of Minnesota, Minneapolis, in an interview.

Ms. Harlow said many of the factors identified by their analysis seemed to reflect that it was the “inner experience” of the molestation that appeared to be a determining factor.

For example, those who had abused others tended to still be tormented by the experience, had experienced sexual arousal, and, for the males at least, had tended to be molested by someone they looked up to, she noted.

Dr. Abel said it is not surprising that the children reported experiencing arousal, because abusers generally want the child to be compliant and to believe that the child is enjoying the experience. As a result, the abusers work hard to stimulate the child.

Ms. Harlow said she was “stunned” to find that so many of the females who became abusers reported that they had been molested by a woman.

She also said that the fact that the second most associated factor among the boys was that they were completely uninformed about sex before their abuse suggested that sex information, given early to children as a social norm, could be beneficial.

Among the other findings from the survey are:

▸ The number of times the child was molested correlated significantly with the number of victims they abused. Among the male abusers who were not molested themselves, the average number of victims they had was three, but it was eight for those who had been molested 50 times or more. The pattern was the same for females.

“In other words, it is a marker,” Ms. Harlow said. “If you see a child who has been abused a lot, pay attention to that child.”

▸ The data from 16,000 adult males who also have taken the test show that 70% of adult men who molest boys score as being heterosexual on the Kinsey Scale.

That is the exact percentage of men in the general population who score as heterosexual on the Kinsey Scale, Dr. Abel said.

▸ Of the adolescent boys who were abused, 55% were abused by an older boy, 40% by a man, 27% by an older girl, and 14% by a woman. (The percentages add up to more than 100% because some had multiple abusers.)

Of the adolescent females who were abused, 66% were abused by a man, 63% by an older boy, 20% by an older girl, and 13% by a woman.

Past Experiences Of Abusive

For males, factors significantly associated with abuse of others were:

I was less than 9 years old when sexually abused.

I knew nothing about sex before I was sexually abused.

I wish the molestation did not bother me so much.

I was abused by my idol.

Sometimes I got a strong sexual feeling between my legs when I was being sexually abused.

I was touched by a boy more than 3 years older than me.

I took baths or showers with my sexual abuser.

The abuser put their tongue in my mouth.

The abuser was a relative living in my house.

I was molested by more than one person.

For females, significant factors were:

I was less than 9 years old when sexually abused.

I was touched by a woman.

Sometimes when my girlfriend or boyfriend rubs my chest, I have flashbacks of when I was abused.

Sometimes I got a strong sexual feeling between my legs when I was being sexually abused.

SNOWMASS, COLO. — Lupus treatment should not be discontinued in anticipation of a pregnancy, Dr. W. Joseph McCune said at a symposium sponsored by the American College of Rheumatology.

Terminating drug treatment results in flares, and it is now clear that “there is really nothing worse for a lupus pregnancy than a flare, either immediately before the pregnancy or during the pregnancy,” said Dr. McCune, director of rheumatology outpatient services at the University of Michigan, Ann Arbor.

The use of hydroxychloroquine during pregnancy in lupus patients is receiving increased interest from specialists, he said.

Instead of cessation of therapy, many physicians are trying to continue their patients on a corticosteroid (when necessary) and hydroxychloroquine, with informed consent and disclosure that the drug is known to cross the placenta.

Hydroxychloroquine is a drug that is not the most potent agent for resolving manifestations of lupus, but one that is very good at preventing serious disease developments and flares, Dr. McCune said.

Antimalarials have a number of potentially beneficial side effects, such as improving glucose tolerance, noted Dr. McCune, who previously reviewed and reported on evidence suggesting that antimalarials positively affect both cholesterol levels and thrombosis in lupus patients with increased cardiovascular risk.

There have been no apparent adverse fetal effects, and “in general, the experience has been that there have been no difficulties using this drug,” in reports of some 300 lupus patients treated with hydroxychloroquine during pregnancy, he said.

SNOWMASS, COLO. — Lupus treatment should not be discontinued in anticipation of a pregnancy, Dr. W. Joseph McCune said at a symposium sponsored by the American College of Rheumatology.

Terminating drug treatment results in flares, and it is now clear that “there is really nothing worse for a lupus pregnancy than a flare, either immediately before the pregnancy or during the pregnancy,” said Dr. McCune, director of rheumatology outpatient services at the University of Michigan, Ann Arbor.

The use of hydroxychloroquine during pregnancy in lupus patients is receiving increased interest from specialists, he said.

Instead of cessation of therapy, many physicians are trying to continue their patients on a corticosteroid (when necessary) and hydroxychloroquine, with informed consent and disclosure that the drug is known to cross the placenta.

Hydroxychloroquine is a drug that is not the most potent agent for resolving manifestations of lupus, but one that is very good at preventing serious disease developments and flares, Dr. McCune said.

Antimalarials have a number of potentially beneficial side effects, such as improving glucose tolerance, noted Dr. McCune, who previously reviewed and reported on evidence suggesting that antimalarials positively affect both cholesterol levels and thrombosis in lupus patients with increased cardiovascular risk.

There have been no apparent adverse fetal effects, and “in general, the experience has been that there have been no difficulties using this drug,” in reports of some 300 lupus patients treated with hydroxychloroquine during pregnancy, he said.

SNOWMASS, COLO. — Lupus treatment should not be discontinued in anticipation of a pregnancy, Dr. W. Joseph McCune said at a symposium sponsored by the American College of Rheumatology.

Terminating drug treatment results in flares, and it is now clear that “there is really nothing worse for a lupus pregnancy than a flare, either immediately before the pregnancy or during the pregnancy,” said Dr. McCune, director of rheumatology outpatient services at the University of Michigan, Ann Arbor.

The use of hydroxychloroquine during pregnancy in lupus patients is receiving increased interest from specialists, he said.

Instead of cessation of therapy, many physicians are trying to continue their patients on a corticosteroid (when necessary) and hydroxychloroquine, with informed consent and disclosure that the drug is known to cross the placenta.

Hydroxychloroquine is a drug that is not the most potent agent for resolving manifestations of lupus, but one that is very good at preventing serious disease developments and flares, Dr. McCune said.

Antimalarials have a number of potentially beneficial side effects, such as improving glucose tolerance, noted Dr. McCune, who previously reviewed and reported on evidence suggesting that antimalarials positively affect both cholesterol levels and thrombosis in lupus patients with increased cardiovascular risk.

There have been no apparent adverse fetal effects, and “in general, the experience has been that there have been no difficulties using this drug,” in reports of some 300 lupus patients treated with hydroxychloroquine during pregnancy, he said.

SNOWMASS, COLO. — Only the absence of “trio” families prevents major breakthroughs in finding genetic mutations for rheumatoid arthritis, even using the present technology, said Dr. Peter K. Gregersen at a symposium sponsored by the American College of Rheumatology.

Trio families, consisting of the patient and both parents, “are very hard to find, because RA is a late-onset disease,” explained Dr. Gregersen, the principal investigator of the North American Rheumatoid Arthritis Consortium, the world's largest effort to identify the genes associated with the development of rheumatoid arthritis. “But [studying trio families] is an extremely powerful way of doing association mapping.”

In searching for genes associated with complex diseases such as rheumatoid arthritis, the approach is to survey the entire genome of many individuals and their siblings with single nucleotide polymorphism markers (SNPs) to find regions of the DNA where particular SNPs are shared more frequently among affected siblings than nonaffected siblings.

This process requires enormous numbers of individuals, especially since rates of RA vary among different populations. Dr. Gergersen's consortium currently has about 1,000 sibling pairs, representing almost 800 families and 200 trio families. It has taken a few years to recruit them, and he estimates that they will need “several thousand,” said Dr. Gregersen, of North Shore University Hospital, Manhasset, N.Y.

Once the shared SNPs are found, the researchers can plot those SNP regions on the human genome map to try to identify likely candidate genes and refine the search.

A gene found by Dr. Gregersen's group with this method is the PTPN22 allele. The gene encodes a tyrosine phosphatase inhibitory to T cells, and it appears also to be involved in Graves' disease, systemic lupus, and type 1 diabetes.

Just in the last couple of years, the technology for this kind of work has all come together: the human genome map, the catalog of SNPs, and a fiber-optic technology for rapidly sorting through SNPs. And the cost of genotyping has dropped dramatically, from about $1 per SNP to “a couple of pennies,” Dr. Gregersen said.

But much more work needs to be done to hunt out other candidate genes. Neither the HLA-DRB1 allele, identified back in the 1970s, nor the PTPN22 allele accounts for all of the relative risk for rheumatoid arthritis, which has a heritability of about 60%.

The PTPN22 polymorphism is found in 28% of rheumatoid arthritis patients, versus 17% of the general population.

More than 300 other possible candidate gene regions have been identified already, and others probably exist.

But the sheer volume of the material that needs to be sorted through for this work means that even when the probability of chance associations is extremely low, they will occur often, Dr. Gregersen said.

The use of trio families, where the genotype of an affected individual can be compared with a parent who would have transferred the DNA of interest with the parent who did not, can greatly speed and improve the process.

The work will also elucidate the pharmacogenetics of response to arthritis drugs, an area of research about which there has been a lot of talk, but not much clinical translation so far, Dr. Gregersen said.

Physicians who have an adult patient with a confirmed diagnosis of RA, two living parents, and an interest in participating should have the patient call 800-382-4827.

The rheumatologists who assist are compensated $150 for their time for each patient. They need to confirm the subject's RA diagnosis on a checklist, and draw a blood specimen for overnight delivery. They will also be paid an additional $50 for each blood sample they draw from a parent. For parents not local to the rheumatologist, a phlebotomy service is available, arranged and paid for by the consortium.

SNOWMASS, COLO. — Only the absence of “trio” families prevents major breakthroughs in finding genetic mutations for rheumatoid arthritis, even using the present technology, said Dr. Peter K. Gregersen at a symposium sponsored by the American College of Rheumatology.

Trio families, consisting of the patient and both parents, “are very hard to find, because RA is a late-onset disease,” explained Dr. Gregersen, the principal investigator of the North American Rheumatoid Arthritis Consortium, the world's largest effort to identify the genes associated with the development of rheumatoid arthritis. “But [studying trio families] is an extremely powerful way of doing association mapping.”

In searching for genes associated with complex diseases such as rheumatoid arthritis, the approach is to survey the entire genome of many individuals and their siblings with single nucleotide polymorphism markers (SNPs) to find regions of the DNA where particular SNPs are shared more frequently among affected siblings than nonaffected siblings.

This process requires enormous numbers of individuals, especially since rates of RA vary among different populations. Dr. Gergersen's consortium currently has about 1,000 sibling pairs, representing almost 800 families and 200 trio families. It has taken a few years to recruit them, and he estimates that they will need “several thousand,” said Dr. Gregersen, of North Shore University Hospital, Manhasset, N.Y.

Once the shared SNPs are found, the researchers can plot those SNP regions on the human genome map to try to identify likely candidate genes and refine the search.

A gene found by Dr. Gregersen's group with this method is the PTPN22 allele. The gene encodes a tyrosine phosphatase inhibitory to T cells, and it appears also to be involved in Graves' disease, systemic lupus, and type 1 diabetes.

Just in the last couple of years, the technology for this kind of work has all come together: the human genome map, the catalog of SNPs, and a fiber-optic technology for rapidly sorting through SNPs. And the cost of genotyping has dropped dramatically, from about $1 per SNP to “a couple of pennies,” Dr. Gregersen said.

But much more work needs to be done to hunt out other candidate genes. Neither the HLA-DRB1 allele, identified back in the 1970s, nor the PTPN22 allele accounts for all of the relative risk for rheumatoid arthritis, which has a heritability of about 60%.

The PTPN22 polymorphism is found in 28% of rheumatoid arthritis patients, versus 17% of the general population.

More than 300 other possible candidate gene regions have been identified already, and others probably exist.

But the sheer volume of the material that needs to be sorted through for this work means that even when the probability of chance associations is extremely low, they will occur often, Dr. Gregersen said.

The use of trio families, where the genotype of an affected individual can be compared with a parent who would have transferred the DNA of interest with the parent who did not, can greatly speed and improve the process.

The work will also elucidate the pharmacogenetics of response to arthritis drugs, an area of research about which there has been a lot of talk, but not much clinical translation so far, Dr. Gregersen said.

Physicians who have an adult patient with a confirmed diagnosis of RA, two living parents, and an interest in participating should have the patient call 800-382-4827.

The rheumatologists who assist are compensated $150 for their time for each patient. They need to confirm the subject's RA diagnosis on a checklist, and draw a blood specimen for overnight delivery. They will also be paid an additional $50 for each blood sample they draw from a parent. For parents not local to the rheumatologist, a phlebotomy service is available, arranged and paid for by the consortium.

SNOWMASS, COLO. — Only the absence of “trio” families prevents major breakthroughs in finding genetic mutations for rheumatoid arthritis, even using the present technology, said Dr. Peter K. Gregersen at a symposium sponsored by the American College of Rheumatology.

Trio families, consisting of the patient and both parents, “are very hard to find, because RA is a late-onset disease,” explained Dr. Gregersen, the principal investigator of the North American Rheumatoid Arthritis Consortium, the world's largest effort to identify the genes associated with the development of rheumatoid arthritis. “But [studying trio families] is an extremely powerful way of doing association mapping.”

In searching for genes associated with complex diseases such as rheumatoid arthritis, the approach is to survey the entire genome of many individuals and their siblings with single nucleotide polymorphism markers (SNPs) to find regions of the DNA where particular SNPs are shared more frequently among affected siblings than nonaffected siblings.

This process requires enormous numbers of individuals, especially since rates of RA vary among different populations. Dr. Gergersen's consortium currently has about 1,000 sibling pairs, representing almost 800 families and 200 trio families. It has taken a few years to recruit them, and he estimates that they will need “several thousand,” said Dr. Gregersen, of North Shore University Hospital, Manhasset, N.Y.

Once the shared SNPs are found, the researchers can plot those SNP regions on the human genome map to try to identify likely candidate genes and refine the search.

A gene found by Dr. Gregersen's group with this method is the PTPN22 allele. The gene encodes a tyrosine phosphatase inhibitory to T cells, and it appears also to be involved in Graves' disease, systemic lupus, and type 1 diabetes.

Just in the last couple of years, the technology for this kind of work has all come together: the human genome map, the catalog of SNPs, and a fiber-optic technology for rapidly sorting through SNPs. And the cost of genotyping has dropped dramatically, from about $1 per SNP to “a couple of pennies,” Dr. Gregersen said.

But much more work needs to be done to hunt out other candidate genes. Neither the HLA-DRB1 allele, identified back in the 1970s, nor the PTPN22 allele accounts for all of the relative risk for rheumatoid arthritis, which has a heritability of about 60%.

The PTPN22 polymorphism is found in 28% of rheumatoid arthritis patients, versus 17% of the general population.

More than 300 other possible candidate gene regions have been identified already, and others probably exist.

But the sheer volume of the material that needs to be sorted through for this work means that even when the probability of chance associations is extremely low, they will occur often, Dr. Gregersen said.

The use of trio families, where the genotype of an affected individual can be compared with a parent who would have transferred the DNA of interest with the parent who did not, can greatly speed and improve the process.

The work will also elucidate the pharmacogenetics of response to arthritis drugs, an area of research about which there has been a lot of talk, but not much clinical translation so far, Dr. Gregersen said.

Physicians who have an adult patient with a confirmed diagnosis of RA, two living parents, and an interest in participating should have the patient call 800-382-4827.

The rheumatologists who assist are compensated $150 for their time for each patient. They need to confirm the subject's RA diagnosis on a checklist, and draw a blood specimen for overnight delivery. They will also be paid an additional $50 for each blood sample they draw from a parent. For parents not local to the rheumatologist, a phlebotomy service is available, arranged and paid for by the consortium.

SNOWMASS, COLO. — Mycophenolate mofetil and rituximab are expected to join the lupus armamentarium, promising to be particularly useful for lupus nephritis, Dr. Susan M. Manzi predicted at a symposium sponsored by the American College of Rheumatology.

“Those are two we are putting our money on,” said Dr. Manzi, codirector of the Lupus Center of Excellence at the University of Pittsburgh.

Advancement in lupus treatment has not kept pace with breakthroughs in rheumatoid arthritis (RA) therapy, in general, Dr. Manzi said. The tumor necrosis factor inhibitors that are so effective in RA do not appear to have much benefit in lupus, although ongoing experiments continue to assess the effectiveness of very short-term use of these biologic agents in lupus.

And because of the failure of some promising novel agents—notably the still-controversial anti-CD40 ligand—physicians have gotten the impression that advances in lupus treatment have been few and far between.

But that would be a misperception, Dr. Manzi said.

A recently published study compared mycophenolate mofetil (CellCept) with an IV cyclophosphamide regimen in a total of 140 patients, Dr. Manzi said.

Full remissions were more common in patients treated with mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor with anti-inflammatory action that is approved for prevention of transplant rejection. Specifically, 22% of the patients on mycophenolate mofetil versus 6% of those on IV cyclophosphamide met the American College of Rheumatology criteria for complete remission (N. Eng. J. Med. 2005;353:2219–28). Patients in both treatment groups showed a significant lessening of their lupus nephritis, and all the patients benefited.

The main advantage seen with mycophenolate mofetil was that it was much better tolerated than IV cyclophosphamide, Dr. Manzi said. Diarrhea was more common in patients on mycophenolate mofetil; all other minor side effects occurred more frequently with cyclophosphamide therapy. Severe infections, such as pneumonia and sepsis, occurred in 1 of 71 patients treated with mycophenolate mofetil, but in 6 of 69 patients treated with cyclophosphamide.

Two patients died during cyclophosphamide therapy, and two others developed irreversible amenorrhea.

One question unanswered by the study was what happens later, Dr. Manzi said. The study drugs were given for 24 weeks, and the patients were assessed at 12 and 24 weeks. It has been suggested that the full beneficial effect of cyclophosphamide occurs after 24 weeks.

However, findings from a previous study that also compared the two agents in lupus nephritis and followed the patients for a full year showed that similar percentages of patients (about 80%) on each agent had achieved full remission of their nephritis at the end of the study. That study was considered somewhat less definitive than the new one, at least in this country, because it used oral cyclophosphamide, a practice not common in the United States.

Based on the new study, Dr. Manzi suggested that appropriate patients for mycophenolate mofetil treatment are going to be those without rapidly progressing glomerulonephritis, who were excluded from the study, for whom there might be a risk of infection during the treatment, and, maybe more importantly, women of childbearing age.

At Dr. Manzi's center, mycophenolate mofetil is already being used as a maintenance treatment after short courses of cyclophosphamide.

Rituximab (Rituxan) has been used to treat lupus nephritis in a handful of open-label trials, in a total of about 100 patients. The results are “impressive,” Dr. Manzi said. The agent's sole indication is for cancer, specifically B-cell non-Hodgkin's lymphoma.

Two different regimens have been used with the B-cell-depleting agent, one in which treatment is given every 4 weeks, as for non-Hodgkin's lymphoma, and another in which rituximab is given the first day, followed by intravenous cyclophosphamide, followed by tapering prednisone. And, overall 80% of patients treated have had partial remission at 4–6 months, with over 50% achieving long-term remission lasting longer than 12 months.

As with the mycophenolate mofetil, the major advantages of rituximab are tolerability and safety, Dr. Manzi said. Bcause of its widespread use in cancer therapy, safety data are plentiful.

“This drug has a lot of potential,” she said. “We certainly are using it off-label now in patients with refractory nephritis—it's just a matter of wrestling with insurance companies to get [the reimbursement] approved.”

The major advantages of the two drugs are tolerability and safety. DR. MANZI

SNOWMASS, COLO. — Mycophenolate mofetil and rituximab are expected to join the lupus armamentarium, promising to be particularly useful for lupus nephritis, Dr. Susan M. Manzi predicted at a symposium sponsored by the American College of Rheumatology.

“Those are two we are putting our money on,” said Dr. Manzi, codirector of the Lupus Center of Excellence at the University of Pittsburgh.

Advancement in lupus treatment has not kept pace with breakthroughs in rheumatoid arthritis (RA) therapy, in general, Dr. Manzi said. The tumor necrosis factor inhibitors that are so effective in RA do not appear to have much benefit in lupus, although ongoing experiments continue to assess the effectiveness of very short-term use of these biologic agents in lupus.

And because of the failure of some promising novel agents—notably the still-controversial anti-CD40 ligand—physicians have gotten the impression that advances in lupus treatment have been few and far between.

But that would be a misperception, Dr. Manzi said.

A recently published study compared mycophenolate mofetil (CellCept) with an IV cyclophosphamide regimen in a total of 140 patients, Dr. Manzi said.

Full remissions were more common in patients treated with mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor with anti-inflammatory action that is approved for prevention of transplant rejection. Specifically, 22% of the patients on mycophenolate mofetil versus 6% of those on IV cyclophosphamide met the American College of Rheumatology criteria for complete remission (N. Eng. J. Med. 2005;353:2219–28). Patients in both treatment groups showed a significant lessening of their lupus nephritis, and all the patients benefited.

The main advantage seen with mycophenolate mofetil was that it was much better tolerated than IV cyclophosphamide, Dr. Manzi said. Diarrhea was more common in patients on mycophenolate mofetil; all other minor side effects occurred more frequently with cyclophosphamide therapy. Severe infections, such as pneumonia and sepsis, occurred in 1 of 71 patients treated with mycophenolate mofetil, but in 6 of 69 patients treated with cyclophosphamide.

Two patients died during cyclophosphamide therapy, and two others developed irreversible amenorrhea.

One question unanswered by the study was what happens later, Dr. Manzi said. The study drugs were given for 24 weeks, and the patients were assessed at 12 and 24 weeks. It has been suggested that the full beneficial effect of cyclophosphamide occurs after 24 weeks.

However, findings from a previous study that also compared the two agents in lupus nephritis and followed the patients for a full year showed that similar percentages of patients (about 80%) on each agent had achieved full remission of their nephritis at the end of the study. That study was considered somewhat less definitive than the new one, at least in this country, because it used oral cyclophosphamide, a practice not common in the United States.

Based on the new study, Dr. Manzi suggested that appropriate patients for mycophenolate mofetil treatment are going to be those without rapidly progressing glomerulonephritis, who were excluded from the study, for whom there might be a risk of infection during the treatment, and, maybe more importantly, women of childbearing age.

At Dr. Manzi's center, mycophenolate mofetil is already being used as a maintenance treatment after short courses of cyclophosphamide.

Rituximab (Rituxan) has been used to treat lupus nephritis in a handful of open-label trials, in a total of about 100 patients. The results are “impressive,” Dr. Manzi said. The agent's sole indication is for cancer, specifically B-cell non-Hodgkin's lymphoma.

Two different regimens have been used with the B-cell-depleting agent, one in which treatment is given every 4 weeks, as for non-Hodgkin's lymphoma, and another in which rituximab is given the first day, followed by intravenous cyclophosphamide, followed by tapering prednisone. And, overall 80% of patients treated have had partial remission at 4–6 months, with over 50% achieving long-term remission lasting longer than 12 months.

As with the mycophenolate mofetil, the major advantages of rituximab are tolerability and safety, Dr. Manzi said. Bcause of its widespread use in cancer therapy, safety data are plentiful.

“This drug has a lot of potential,” she said. “We certainly are using it off-label now in patients with refractory nephritis—it's just a matter of wrestling with insurance companies to get [the reimbursement] approved.”

The major advantages of the two drugs are tolerability and safety. DR. MANZI

SNOWMASS, COLO. — Mycophenolate mofetil and rituximab are expected to join the lupus armamentarium, promising to be particularly useful for lupus nephritis, Dr. Susan M. Manzi predicted at a symposium sponsored by the American College of Rheumatology.

“Those are two we are putting our money on,” said Dr. Manzi, codirector of the Lupus Center of Excellence at the University of Pittsburgh.

Advancement in lupus treatment has not kept pace with breakthroughs in rheumatoid arthritis (RA) therapy, in general, Dr. Manzi said. The tumor necrosis factor inhibitors that are so effective in RA do not appear to have much benefit in lupus, although ongoing experiments continue to assess the effectiveness of very short-term use of these biologic agents in lupus.

And because of the failure of some promising novel agents—notably the still-controversial anti-CD40 ligand—physicians have gotten the impression that advances in lupus treatment have been few and far between.

But that would be a misperception, Dr. Manzi said.

A recently published study compared mycophenolate mofetil (CellCept) with an IV cyclophosphamide regimen in a total of 140 patients, Dr. Manzi said.

Full remissions were more common in patients treated with mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor with anti-inflammatory action that is approved for prevention of transplant rejection. Specifically, 22% of the patients on mycophenolate mofetil versus 6% of those on IV cyclophosphamide met the American College of Rheumatology criteria for complete remission (N. Eng. J. Med. 2005;353:2219–28). Patients in both treatment groups showed a significant lessening of their lupus nephritis, and all the patients benefited.

The main advantage seen with mycophenolate mofetil was that it was much better tolerated than IV cyclophosphamide, Dr. Manzi said. Diarrhea was more common in patients on mycophenolate mofetil; all other minor side effects occurred more frequently with cyclophosphamide therapy. Severe infections, such as pneumonia and sepsis, occurred in 1 of 71 patients treated with mycophenolate mofetil, but in 6 of 69 patients treated with cyclophosphamide.

Two patients died during cyclophosphamide therapy, and two others developed irreversible amenorrhea.

One question unanswered by the study was what happens later, Dr. Manzi said. The study drugs were given for 24 weeks, and the patients were assessed at 12 and 24 weeks. It has been suggested that the full beneficial effect of cyclophosphamide occurs after 24 weeks.

However, findings from a previous study that also compared the two agents in lupus nephritis and followed the patients for a full year showed that similar percentages of patients (about 80%) on each agent had achieved full remission of their nephritis at the end of the study. That study was considered somewhat less definitive than the new one, at least in this country, because it used oral cyclophosphamide, a practice not common in the United States.

Based on the new study, Dr. Manzi suggested that appropriate patients for mycophenolate mofetil treatment are going to be those without rapidly progressing glomerulonephritis, who were excluded from the study, for whom there might be a risk of infection during the treatment, and, maybe more importantly, women of childbearing age.

At Dr. Manzi's center, mycophenolate mofetil is already being used as a maintenance treatment after short courses of cyclophosphamide.

Rituximab (Rituxan) has been used to treat lupus nephritis in a handful of open-label trials, in a total of about 100 patients. The results are “impressive,” Dr. Manzi said. The agent's sole indication is for cancer, specifically B-cell non-Hodgkin's lymphoma.

Two different regimens have been used with the B-cell-depleting agent, one in which treatment is given every 4 weeks, as for non-Hodgkin's lymphoma, and another in which rituximab is given the first day, followed by intravenous cyclophosphamide, followed by tapering prednisone. And, overall 80% of patients treated have had partial remission at 4–6 months, with over 50% achieving long-term remission lasting longer than 12 months.

As with the mycophenolate mofetil, the major advantages of rituximab are tolerability and safety, Dr. Manzi said. Bcause of its widespread use in cancer therapy, safety data are plentiful.

“This drug has a lot of potential,” she said. “We certainly are using it off-label now in patients with refractory nephritis—it's just a matter of wrestling with insurance companies to get [the reimbursement] approved.”

The major advantages of the two drugs are tolerability and safety. DR. MANZI

SNOWMASS, COLO. — Lupus treatment should not be discontinued in anticipation of a pregnancy, Dr. W. Joseph McCune said at a symposium sponsored by the American College of Rheumatology.

Terminating drug treatment results in flares, and it is now clear that “there is really nothing worse for a lupus pregnancy than a flare, either immediately before the pregnancy or during the pregnancy,” said Dr. McCune, director of rheumatology outpatient services at the University of Michigan, Ann Arbor.

The use of hydroxychloroquine during pregnancy in lupus patients is receiving increased interest from specialists, he said.

Instead of cessation of therapy, many physicians are trying to continue their patients on a corticosteroid (when necessary) and hydroxychloroquine, with informed consent and disclosure that the drug is known to cross the placenta.

Hydroxychloroquine is a drug that is not the most potent agent for resolving manifestations of lupus, but one that is very good at preventing serious disease developments and flares, Dr. McCune said.

Antimalarials have a number of potentially beneficial side effects, such as improving glucose tolerance, noted Dr. McCune, who previously reviewed and reported on evidence suggesting that antimalarials positively affect both cholesterol levels and thrombosis in lupus patients who have increased cardiovascular risk.

There have been no apparent, adverse, fetal effects, and “in general, the experience has been that there have been no difficulties using this drug,” in recent reports of approximately 300 lupus patients treated with hydroxychloroquine during pregnancy, Dr. McCune said.

The reports come from various series as well as a blinded, placebo-controlled clinical trial.

In the 20-patient clinical trial, none of the 10 treated patients developed toxemia of pregnancy, while 3 of the 10 patients in the placebo group did.

Moreover, the infants of the treated mothers had a greater average delivery age and had a better average Apgar score. The hydroxychloroquine-treated mothers used less prednisone (Lupus 2001;10:401–4).

SNOWMASS, COLO. — Lupus treatment should not be discontinued in anticipation of a pregnancy, Dr. W. Joseph McCune said at a symposium sponsored by the American College of Rheumatology.

Terminating drug treatment results in flares, and it is now clear that “there is really nothing worse for a lupus pregnancy than a flare, either immediately before the pregnancy or during the pregnancy,” said Dr. McCune, director of rheumatology outpatient services at the University of Michigan, Ann Arbor.

The use of hydroxychloroquine during pregnancy in lupus patients is receiving increased interest from specialists, he said.

Instead of cessation of therapy, many physicians are trying to continue their patients on a corticosteroid (when necessary) and hydroxychloroquine, with informed consent and disclosure that the drug is known to cross the placenta.

Hydroxychloroquine is a drug that is not the most potent agent for resolving manifestations of lupus, but one that is very good at preventing serious disease developments and flares, Dr. McCune said.

Antimalarials have a number of potentially beneficial side effects, such as improving glucose tolerance, noted Dr. McCune, who previously reviewed and reported on evidence suggesting that antimalarials positively affect both cholesterol levels and thrombosis in lupus patients who have increased cardiovascular risk.

There have been no apparent, adverse, fetal effects, and “in general, the experience has been that there have been no difficulties using this drug,” in recent reports of approximately 300 lupus patients treated with hydroxychloroquine during pregnancy, Dr. McCune said.

The reports come from various series as well as a blinded, placebo-controlled clinical trial.

In the 20-patient clinical trial, none of the 10 treated patients developed toxemia of pregnancy, while 3 of the 10 patients in the placebo group did.

Moreover, the infants of the treated mothers had a greater average delivery age and had a better average Apgar score. The hydroxychloroquine-treated mothers used less prednisone (Lupus 2001;10:401–4).

SNOWMASS, COLO. — Lupus treatment should not be discontinued in anticipation of a pregnancy, Dr. W. Joseph McCune said at a symposium sponsored by the American College of Rheumatology.

Terminating drug treatment results in flares, and it is now clear that “there is really nothing worse for a lupus pregnancy than a flare, either immediately before the pregnancy or during the pregnancy,” said Dr. McCune, director of rheumatology outpatient services at the University of Michigan, Ann Arbor.

The use of hydroxychloroquine during pregnancy in lupus patients is receiving increased interest from specialists, he said.

Instead of cessation of therapy, many physicians are trying to continue their patients on a corticosteroid (when necessary) and hydroxychloroquine, with informed consent and disclosure that the drug is known to cross the placenta.

Hydroxychloroquine is a drug that is not the most potent agent for resolving manifestations of lupus, but one that is very good at preventing serious disease developments and flares, Dr. McCune said.

Antimalarials have a number of potentially beneficial side effects, such as improving glucose tolerance, noted Dr. McCune, who previously reviewed and reported on evidence suggesting that antimalarials positively affect both cholesterol levels and thrombosis in lupus patients who have increased cardiovascular risk.

There have been no apparent, adverse, fetal effects, and “in general, the experience has been that there have been no difficulties using this drug,” in recent reports of approximately 300 lupus patients treated with hydroxychloroquine during pregnancy, Dr. McCune said.

The reports come from various series as well as a blinded, placebo-controlled clinical trial.

In the 20-patient clinical trial, none of the 10 treated patients developed toxemia of pregnancy, while 3 of the 10 patients in the placebo group did.

Moreover, the infants of the treated mothers had a greater average delivery age and had a better average Apgar score. The hydroxychloroquine-treated mothers used less prednisone (Lupus 2001;10:401–4).

SNOWMASS, COLO. — The current evidence suggests it is a very small group of individuals with low bone density who should be treated with parathyroid hormone, Dr. Lenore Buckley said at a symposium sponsored by the American College of Rheumatology.

Probably the only patients who are proper candidates for parathyroid hormone (PTH) therapy, according to a recent cost-effectiveness analysis, are those patients who have an extremely low T score, below −3.5, and who are at least 70 years old or have had a vertebral fracture, said Dr. Buckley, a professor of internal medicine at Virginia Commonwealth University, Richmond.

The cost-effectiveness analysis to which she referred considered the case of a postmenopausal woman with osteoporosis and compared four different treatment strategies: calcium and vitamin D supplementation, 5 years of treatment with alendronate, 2 years of PTH therapy, and 2 years of PTH followed by 5 years of alendronate.

The analysis said that vitamin D supplementation and the alendronate treatment fell within the cost range that is considered economical. The 5 years of alendronate treatment cost $15,800 per quality-adjusted life year gained. The 2 years of PTH therapy alone was not as effective as the alendronate alone regimen, and cost more. And the combined PTH followed by alendronate regimen cost $157,500 per quality-adjusted life year gained, which is considered well outside the range of cost effectiveness.

It was only when the risk of fracture became very high that the combined regimen began to become cost effective.

Those findings appear to be practical and to reflect what recent research indicates about PTH treatment, Dr. Buckley said.

PTH does seem to produce greater increases in bone density than bisphosphonates, and in patients who are at high risk of fracture, the hormone appears to reduce the rate of fracture by approximately 65% over 2 years, she said. But PTH also costs about $7,000 a year, and patients have a hard time with the required daily injections.

A number of recent studies have looked at combining PTH with bisphosphonates as a way to either improve on the density gains or make treatment easier.

Those studies have found that it is possible to get some additional benefit when PTH is used cyclically (3-month cycles) with continuous bisphosphonate treatment and that there may be some benefit in using PTH in patients who do not seem to be responding to bisphosphonate treatment.

But, in general, combining the two appears to dampen the gains in density that are achieved with PTH alone, probably because it is not possible to fully uncouple bone resorption, which is prevented with bisphosphonate treatment, from bone formation, which is stimulated by PTH, Dr. Buckley said.

She said that given the length of activity of bisphosphonates, it probably would take a patient about 1 year off bisphosphonate treatment to be ready to reap the full benefit of PTH.

However, the present evidence suggests it's possible to consolidate gains achieved with PTH treatment by following it with a bisphosphonate; a year of PTH followed by a year of alendronate can produce a 12% increase in bone mineral density in the lumbar spine.

SNOWMASS, COLO. — The current evidence suggests it is a very small group of individuals with low bone density who should be treated with parathyroid hormone, Dr. Lenore Buckley said at a symposium sponsored by the American College of Rheumatology.

Probably the only patients who are proper candidates for parathyroid hormone (PTH) therapy, according to a recent cost-effectiveness analysis, are those patients who have an extremely low T score, below −3.5, and who are at least 70 years old or have had a vertebral fracture, said Dr. Buckley, a professor of internal medicine at Virginia Commonwealth University, Richmond.

The cost-effectiveness analysis to which she referred considered the case of a postmenopausal woman with osteoporosis and compared four different treatment strategies: calcium and vitamin D supplementation, 5 years of treatment with alendronate, 2 years of PTH therapy, and 2 years of PTH followed by 5 years of alendronate.

The analysis said that vitamin D supplementation and the alendronate treatment fell within the cost range that is considered economical. The 5 years of alendronate treatment cost $15,800 per quality-adjusted life year gained. The 2 years of PTH therapy alone was not as effective as the alendronate alone regimen, and cost more. And the combined PTH followed by alendronate regimen cost $157,500 per quality-adjusted life year gained, which is considered well outside the range of cost effectiveness.

It was only when the risk of fracture became very high that the combined regimen began to become cost effective.

Those findings appear to be practical and to reflect what recent research indicates about PTH treatment, Dr. Buckley said.

PTH does seem to produce greater increases in bone density than bisphosphonates, and in patients who are at high risk of fracture, the hormone appears to reduce the rate of fracture by approximately 65% over 2 years, she said. But PTH also costs about $7,000 a year, and patients have a hard time with the required daily injections.

A number of recent studies have looked at combining PTH with bisphosphonates as a way to either improve on the density gains or make treatment easier.

Those studies have found that it is possible to get some additional benefit when PTH is used cyclically (3-month cycles) with continuous bisphosphonate treatment and that there may be some benefit in using PTH in patients who do not seem to be responding to bisphosphonate treatment.

But, in general, combining the two appears to dampen the gains in density that are achieved with PTH alone, probably because it is not possible to fully uncouple bone resorption, which is prevented with bisphosphonate treatment, from bone formation, which is stimulated by PTH, Dr. Buckley said.

She said that given the length of activity of bisphosphonates, it probably would take a patient about 1 year off bisphosphonate treatment to be ready to reap the full benefit of PTH.

However, the present evidence suggests it's possible to consolidate gains achieved with PTH treatment by following it with a bisphosphonate; a year of PTH followed by a year of alendronate can produce a 12% increase in bone mineral density in the lumbar spine.

SNOWMASS, COLO. — The current evidence suggests it is a very small group of individuals with low bone density who should be treated with parathyroid hormone, Dr. Lenore Buckley said at a symposium sponsored by the American College of Rheumatology.

Probably the only patients who are proper candidates for parathyroid hormone (PTH) therapy, according to a recent cost-effectiveness analysis, are those patients who have an extremely low T score, below −3.5, and who are at least 70 years old or have had a vertebral fracture, said Dr. Buckley, a professor of internal medicine at Virginia Commonwealth University, Richmond.

The cost-effectiveness analysis to which she referred considered the case of a postmenopausal woman with osteoporosis and compared four different treatment strategies: calcium and vitamin D supplementation, 5 years of treatment with alendronate, 2 years of PTH therapy, and 2 years of PTH followed by 5 years of alendronate.

The analysis said that vitamin D supplementation and the alendronate treatment fell within the cost range that is considered economical. The 5 years of alendronate treatment cost $15,800 per quality-adjusted life year gained. The 2 years of PTH therapy alone was not as effective as the alendronate alone regimen, and cost more. And the combined PTH followed by alendronate regimen cost $157,500 per quality-adjusted life year gained, which is considered well outside the range of cost effectiveness.

It was only when the risk of fracture became very high that the combined regimen began to become cost effective.

Those findings appear to be practical and to reflect what recent research indicates about PTH treatment, Dr. Buckley said.

PTH does seem to produce greater increases in bone density than bisphosphonates, and in patients who are at high risk of fracture, the hormone appears to reduce the rate of fracture by approximately 65% over 2 years, she said. But PTH also costs about $7,000 a year, and patients have a hard time with the required daily injections.

A number of recent studies have looked at combining PTH with bisphosphonates as a way to either improve on the density gains or make treatment easier.

Those studies have found that it is possible to get some additional benefit when PTH is used cyclically (3-month cycles) with continuous bisphosphonate treatment and that there may be some benefit in using PTH in patients who do not seem to be responding to bisphosphonate treatment.

But, in general, combining the two appears to dampen the gains in density that are achieved with PTH alone, probably because it is not possible to fully uncouple bone resorption, which is prevented with bisphosphonate treatment, from bone formation, which is stimulated by PTH, Dr. Buckley said.

She said that given the length of activity of bisphosphonates, it probably would take a patient about 1 year off bisphosphonate treatment to be ready to reap the full benefit of PTH.

However, the present evidence suggests it's possible to consolidate gains achieved with PTH treatment by following it with a bisphosphonate; a year of PTH followed by a year of alendronate can produce a 12% increase in bone mineral density in the lumbar spine.

SNOWMASS, COLO. — Glucocorticoid steroid use appears to limit height gains in children with idiopathic nephrotic syndrome, but do not necessarily reduce bone density, Dr. Lenore Buckley said at a symposium sponsored by the American College of Rheumatology.

“The issue of what glucocorticoids do to bone mass in children is an area where we are only just beginning to get some data,” said Dr. Buckley, of the Medical College of Virginia, Richmond.

One cross-sectional study looked at 60 children with isolated idiopathic nephrotic syndrome being treated with glucocorticoids, and compared them with 195 matched controls, mean age 9–10 years. Children treated with glucocorticoids were found to lose height but not necessarily bone density (N. Engl. J. Med. 2004;351:868–75).

In the group treated with glucocorticoids, 26 study participants were black, and 39 control group participants were black, according to the study data.

Previous studies have found that children lose bone mineral density when treated with glucocorticoids. But those studies looked at children with systemic illnesses, such as juvenile rheumatoid arthritis and inflammatory bowel disease, so it is not clear whether their low density was due to their treatment with glucocorticoids or to their systemic condition.

The mean height z score of the children in the control group was positive (0.35), whereas the mean height z score of the glucocorticoid treated children was negative (- 0.17), the study found.

At the lumbar spine, the same bone mineral density per unit area was found in both the control and glucocorticoid treated groups, however.

“For what bone [both groups] have, the density is the same, but [the glucocorticoid group doesn't] have as much bone because they don't grow as much,” Dr. Buckley said. The bone density for the treatment group could be due to the glucocorticoid, which causes weight gain, and weight stimulates bone density growth.

The mean body mass index z score for children with nephrotic syndrome was 1.24, while the score for controls was 0.34. There was also a higher percentage of obese children in the nephrotic syndrome group, compared with the control group (38% vs. 16%, respectively), the study found.

A more detailed look at the children's bone density found that those with nephrotic syndrome had slightly lower trabecular bone density (mean z score - 0.27, vs. 0), but much greater cortical bone density (mean z score 0.87, vs. 0). This situation also suggests that while there may be a process interfering with bone accumulation, there is also some compensation due to weight gain, Dr. Buckley said.

Children with nephrotic syndrome go on and off glucocorticoid treatment, which could allow for some periods of recovery, so these findings may not extrapolate to children treated chronically, Dr. Buckley noted.

“What it tells us is that in the short run, these kids are not at risk for fracture—they have pretty good density,” she said. “But what it doesn't tell us is the risk of fracture in the future.”

Adults not taking glucocorticoids whose rate was one standard deviation below the mean as a child have a four times higher risk of fracture, studies show.

The evidence also shows that adult patients who take glucocorticoids lose bone mineral density early and quickly, and their risk of fracture goes up rapidly. However, over time, it has been found that the loss stabilizes, and when glucocorticoids are stopped there is some recovery, though it is not clear how much recovery and whether patients fracture risk returns to the level it was before glucocorticoid use.

In adults, “we think now that there probably is almost no safe dose of glucocorticoids that couldn't possibly lead to some decrease in bone mass,” said Dr. Buckley.

'In the short run, these kids are not at risk of fracture—they have pretty good density.' DR. BUCKLEY

SNOWMASS, COLO. — Glucocorticoid steroid use appears to limit height gains in children with idiopathic nephrotic syndrome, but do not necessarily reduce bone density, Dr. Lenore Buckley said at a symposium sponsored by the American College of Rheumatology.

“The issue of what glucocorticoids do to bone mass in children is an area where we are only just beginning to get some data,” said Dr. Buckley, of the Medical College of Virginia, Richmond.

One cross-sectional study looked at 60 children with isolated idiopathic nephrotic syndrome being treated with glucocorticoids, and compared them with 195 matched controls, mean age 9–10 years. Children treated with glucocorticoids were found to lose height but not necessarily bone density (N. Engl. J. Med. 2004;351:868–75).

In the group treated with glucocorticoids, 26 study participants were black, and 39 control group participants were black, according to the study data.

Previous studies have found that children lose bone mineral density when treated with glucocorticoids. But those studies looked at children with systemic illnesses, such as juvenile rheumatoid arthritis and inflammatory bowel disease, so it is not clear whether their low density was due to their treatment with glucocorticoids or to their systemic condition.

The mean height z score of the children in the control group was positive (0.35), whereas the mean height z score of the glucocorticoid treated children was negative (- 0.17), the study found.

At the lumbar spine, the same bone mineral density per unit area was found in both the control and glucocorticoid treated groups, however.

“For what bone [both groups] have, the density is the same, but [the glucocorticoid group doesn't] have as much bone because they don't grow as much,” Dr. Buckley said. The bone density for the treatment group could be due to the glucocorticoid, which causes weight gain, and weight stimulates bone density growth.

The mean body mass index z score for children with nephrotic syndrome was 1.24, while the score for controls was 0.34. There was also a higher percentage of obese children in the nephrotic syndrome group, compared with the control group (38% vs. 16%, respectively), the study found.

A more detailed look at the children's bone density found that those with nephrotic syndrome had slightly lower trabecular bone density (mean z score - 0.27, vs. 0), but much greater cortical bone density (mean z score 0.87, vs. 0). This situation also suggests that while there may be a process interfering with bone accumulation, there is also some compensation due to weight gain, Dr. Buckley said.

Children with nephrotic syndrome go on and off glucocorticoid treatment, which could allow for some periods of recovery, so these findings may not extrapolate to children treated chronically, Dr. Buckley noted.

“What it tells us is that in the short run, these kids are not at risk for fracture—they have pretty good density,” she said. “But what it doesn't tell us is the risk of fracture in the future.”

Adults not taking glucocorticoids whose rate was one standard deviation below the mean as a child have a four times higher risk of fracture, studies show.

The evidence also shows that adult patients who take glucocorticoids lose bone mineral density early and quickly, and their risk of fracture goes up rapidly. However, over time, it has been found that the loss stabilizes, and when glucocorticoids are stopped there is some recovery, though it is not clear how much recovery and whether patients fracture risk returns to the level it was before glucocorticoid use.

In adults, “we think now that there probably is almost no safe dose of glucocorticoids that couldn't possibly lead to some decrease in bone mass,” said Dr. Buckley.

'In the short run, these kids are not at risk of fracture—they have pretty good density.' DR. BUCKLEY

SNOWMASS, COLO. — Glucocorticoid steroid use appears to limit height gains in children with idiopathic nephrotic syndrome, but do not necessarily reduce bone density, Dr. Lenore Buckley said at a symposium sponsored by the American College of Rheumatology.

“The issue of what glucocorticoids do to bone mass in children is an area where we are only just beginning to get some data,” said Dr. Buckley, of the Medical College of Virginia, Richmond.

One cross-sectional study looked at 60 children with isolated idiopathic nephrotic syndrome being treated with glucocorticoids, and compared them with 195 matched controls, mean age 9–10 years. Children treated with glucocorticoids were found to lose height but not necessarily bone density (N. Engl. J. Med. 2004;351:868–75).

In the group treated with glucocorticoids, 26 study participants were black, and 39 control group participants were black, according to the study data.

Previous studies have found that children lose bone mineral density when treated with glucocorticoids. But those studies looked at children with systemic illnesses, such as juvenile rheumatoid arthritis and inflammatory bowel disease, so it is not clear whether their low density was due to their treatment with glucocorticoids or to their systemic condition.

The mean height z score of the children in the control group was positive (0.35), whereas the mean height z score of the glucocorticoid treated children was negative (- 0.17), the study found.

At the lumbar spine, the same bone mineral density per unit area was found in both the control and glucocorticoid treated groups, however.

“For what bone [both groups] have, the density is the same, but [the glucocorticoid group doesn't] have as much bone because they don't grow as much,” Dr. Buckley said. The bone density for the treatment group could be due to the glucocorticoid, which causes weight gain, and weight stimulates bone density growth.

The mean body mass index z score for children with nephrotic syndrome was 1.24, while the score for controls was 0.34. There was also a higher percentage of obese children in the nephrotic syndrome group, compared with the control group (38% vs. 16%, respectively), the study found.

A more detailed look at the children's bone density found that those with nephrotic syndrome had slightly lower trabecular bone density (mean z score - 0.27, vs. 0), but much greater cortical bone density (mean z score 0.87, vs. 0). This situation also suggests that while there may be a process interfering with bone accumulation, there is also some compensation due to weight gain, Dr. Buckley said.

Children with nephrotic syndrome go on and off glucocorticoid treatment, which could allow for some periods of recovery, so these findings may not extrapolate to children treated chronically, Dr. Buckley noted.

“What it tells us is that in the short run, these kids are not at risk for fracture—they have pretty good density,” she said. “But what it doesn't tell us is the risk of fracture in the future.”

Adults not taking glucocorticoids whose rate was one standard deviation below the mean as a child have a four times higher risk of fracture, studies show.

The evidence also shows that adult patients who take glucocorticoids lose bone mineral density early and quickly, and their risk of fracture goes up rapidly. However, over time, it has been found that the loss stabilizes, and when glucocorticoids are stopped there is some recovery, though it is not clear how much recovery and whether patients fracture risk returns to the level it was before glucocorticoid use.

In adults, “we think now that there probably is almost no safe dose of glucocorticoids that couldn't possibly lead to some decrease in bone mass,” said Dr. Buckley.

'In the short run, these kids are not at risk of fracture—they have pretty good density.' DR. BUCKLEY

SNOWMASS, COLO. — Extraarticular disease occurs in almost half of all rheumatoid arthritis patients, and greatly increases the risk of premature mortality, Dr. Eric L. Matteson reported at a symposium sponsored by the American College of Rheumatology.

In a review of 609 incident cases of rheumatoid arthritis occurring in Rochester between 1955 and 1995 and followed through 2000, Dr. Matteson of the Mayo Clinic, Rochester, Minn., and his colleagues found that 46% of patients with rheumatoid arthritis developed some extraarticular disease.

The most common extraarticular manifestations in patients included subcutaneous nodules (34%), Sjögren's syndrome (11%), pulmonary fibrosis (7%), pericarditis (5%), and pleuritis (5%). The least common—occurring in 1% or fewer of patients—included neuropathy, xerostomia, and amyloidosis.

Their review also found that the likelihood of premature mortality was greatly increased by extraarticular disease; for example, a female rheumatoid arthritis patient aged 50 years with vasculitis, pericarditis, pleuritis, or pulmonary fibrosis had a life expectancy that was 13–15 years shorter than that of a healthy peer. Male patients with the same manifestations were found to have a life expectancy 15 years shorter than that of healthy peers.

When Dr. Matteson and his colleagues plotted the survival curve of the patients against that of the general Rochester population, there was a significant difference in survival. But when they took out the patients with extraarticular disease and compared only patients with rheumatoid arthritis without extraarticular disease, there was no difference. “The impact is profound,” he said.

Analysis of data showed that the relevant factors most associated with extraarticular disease in patients were antinuclear antibody positivity, male gender, and smoking.

Extraarticular disease was reported by 60% of the rheumatoid arthritis patients who reported having ever smoked. The association has been noted before in other investigations, and some of that evidence suggests that smoking actually drives the disease process, he said.

Rates of extraarticular disease may be different now in the era of biologic treatment, Dr. Matteson allowed. However, during the time of this review, there was no improvement in the incidence rate of extraarticular disease.

SNOWMASS, COLO. — Extraarticular disease occurs in almost half of all rheumatoid arthritis patients, and greatly increases the risk of premature mortality, Dr. Eric L. Matteson reported at a symposium sponsored by the American College of Rheumatology.

In a review of 609 incident cases of rheumatoid arthritis occurring in Rochester between 1955 and 1995 and followed through 2000, Dr. Matteson of the Mayo Clinic, Rochester, Minn., and his colleagues found that 46% of patients with rheumatoid arthritis developed some extraarticular disease.

The most common extraarticular manifestations in patients included subcutaneous nodules (34%), Sjögren's syndrome (11%), pulmonary fibrosis (7%), pericarditis (5%), and pleuritis (5%). The least common—occurring in 1% or fewer of patients—included neuropathy, xerostomia, and amyloidosis.

Their review also found that the likelihood of premature mortality was greatly increased by extraarticular disease; for example, a female rheumatoid arthritis patient aged 50 years with vasculitis, pericarditis, pleuritis, or pulmonary fibrosis had a life expectancy that was 13–15 years shorter than that of a healthy peer. Male patients with the same manifestations were found to have a life expectancy 15 years shorter than that of healthy peers.

When Dr. Matteson and his colleagues plotted the survival curve of the patients against that of the general Rochester population, there was a significant difference in survival. But when they took out the patients with extraarticular disease and compared only patients with rheumatoid arthritis without extraarticular disease, there was no difference. “The impact is profound,” he said.

Analysis of data showed that the relevant factors most associated with extraarticular disease in patients were antinuclear antibody positivity, male gender, and smoking.

Extraarticular disease was reported by 60% of the rheumatoid arthritis patients who reported having ever smoked. The association has been noted before in other investigations, and some of that evidence suggests that smoking actually drives the disease process, he said.

Rates of extraarticular disease may be different now in the era of biologic treatment, Dr. Matteson allowed. However, during the time of this review, there was no improvement in the incidence rate of extraarticular disease.

SNOWMASS, COLO. — Extraarticular disease occurs in almost half of all rheumatoid arthritis patients, and greatly increases the risk of premature mortality, Dr. Eric L. Matteson reported at a symposium sponsored by the American College of Rheumatology.

In a review of 609 incident cases of rheumatoid arthritis occurring in Rochester between 1955 and 1995 and followed through 2000, Dr. Matteson of the Mayo Clinic, Rochester, Minn., and his colleagues found that 46% of patients with rheumatoid arthritis developed some extraarticular disease.

The most common extraarticular manifestations in patients included subcutaneous nodules (34%), Sjögren's syndrome (11%), pulmonary fibrosis (7%), pericarditis (5%), and pleuritis (5%). The least common—occurring in 1% or fewer of patients—included neuropathy, xerostomia, and amyloidosis.

Their review also found that the likelihood of premature mortality was greatly increased by extraarticular disease; for example, a female rheumatoid arthritis patient aged 50 years with vasculitis, pericarditis, pleuritis, or pulmonary fibrosis had a life expectancy that was 13–15 years shorter than that of a healthy peer. Male patients with the same manifestations were found to have a life expectancy 15 years shorter than that of healthy peers.

When Dr. Matteson and his colleagues plotted the survival curve of the patients against that of the general Rochester population, there was a significant difference in survival. But when they took out the patients with extraarticular disease and compared only patients with rheumatoid arthritis without extraarticular disease, there was no difference. “The impact is profound,” he said.

Analysis of data showed that the relevant factors most associated with extraarticular disease in patients were antinuclear antibody positivity, male gender, and smoking.

Extraarticular disease was reported by 60% of the rheumatoid arthritis patients who reported having ever smoked. The association has been noted before in other investigations, and some of that evidence suggests that smoking actually drives the disease process, he said.

Rates of extraarticular disease may be different now in the era of biologic treatment, Dr. Matteson allowed. However, during the time of this review, there was no improvement in the incidence rate of extraarticular disease.

SNOWMASS, COLO. — Lupus treatment should not be discontinued in anticipation of a pregnancy, Dr. W. Joseph McCune said at a symposium sponsored by the American College of Rheumatology.

Terminating drug treatment results in flares, and it is now clear that “there is really nothing worse for a lupus pregnancy than a flare, either immediately before the pregnancy or during the pregnancy,” said Dr. McCune, director of rheumatology outpatient services at the University of Michigan, Ann Arbor.

Instead of cessation of therapy, many physicians are trying to continue their patients on a corticosteroid (when necessary) and hydroxychloroquine, with informed consent and disclosure that the drug is known to cross the placenta.

Hydroxychloroquine is a drug that is not the most potent agent for resolving manifestations of lupus, but one that is very good at preventing serious disease developments and flares, Dr. McCune said.

Antimalarials have a number of potentially beneficial side effects, such as improving glucose tolerance, noted Dr. McCune, who previously reviewed and reported on evidence suggesting that antimalarials positively affect both cholesterol levels and thrombosis in lupus patients with increased cardiovascular risk.

There have been no apparent, adverse, fetal effects, and “in general, the experience has been that there have been no difficulties using this drug,” in recent reports of approximately 300 lupus patients treated with hydroxychloroquine during pregnancy, Dr. McCune said.

The reports are from various series and a blinded, placebo-controlled clinical trial.

In the 20 patient clinical trial, none of the 10 treated patients developed toxemia of pregnancy, while 3 of the 10 patients in the placebo group did. The infants of the treated mothers had a greater average delivery age and had a better average Apgar score. The hydroxychloroquine treated mothers used less prednisone (Lupus 2001;10:401–4).

There is also evidence from nonpregnant patients that hydroxychloroquine may positively impact antiphospholipid syndrome, which about 30% of lupus patients have, and which is associated with adverse pregnancy outcomes, Dr. McCune said.

SNOWMASS, COLO. — Lupus treatment should not be discontinued in anticipation of a pregnancy, Dr. W. Joseph McCune said at a symposium sponsored by the American College of Rheumatology.

Terminating drug treatment results in flares, and it is now clear that “there is really nothing worse for a lupus pregnancy than a flare, either immediately before the pregnancy or during the pregnancy,” said Dr. McCune, director of rheumatology outpatient services at the University of Michigan, Ann Arbor.

Instead of cessation of therapy, many physicians are trying to continue their patients on a corticosteroid (when necessary) and hydroxychloroquine, with informed consent and disclosure that the drug is known to cross the placenta.

Hydroxychloroquine is a drug that is not the most potent agent for resolving manifestations of lupus, but one that is very good at preventing serious disease developments and flares, Dr. McCune said.

Antimalarials have a number of potentially beneficial side effects, such as improving glucose tolerance, noted Dr. McCune, who previously reviewed and reported on evidence suggesting that antimalarials positively affect both cholesterol levels and thrombosis in lupus patients with increased cardiovascular risk.

There have been no apparent, adverse, fetal effects, and “in general, the experience has been that there have been no difficulties using this drug,” in recent reports of approximately 300 lupus patients treated with hydroxychloroquine during pregnancy, Dr. McCune said.

The reports are from various series and a blinded, placebo-controlled clinical trial.

In the 20 patient clinical trial, none of the 10 treated patients developed toxemia of pregnancy, while 3 of the 10 patients in the placebo group did. The infants of the treated mothers had a greater average delivery age and had a better average Apgar score. The hydroxychloroquine treated mothers used less prednisone (Lupus 2001;10:401–4).

There is also evidence from nonpregnant patients that hydroxychloroquine may positively impact antiphospholipid syndrome, which about 30% of lupus patients have, and which is associated with adverse pregnancy outcomes, Dr. McCune said.

SNOWMASS, COLO. — Lupus treatment should not be discontinued in anticipation of a pregnancy, Dr. W. Joseph McCune said at a symposium sponsored by the American College of Rheumatology.

Terminating drug treatment results in flares, and it is now clear that “there is really nothing worse for a lupus pregnancy than a flare, either immediately before the pregnancy or during the pregnancy,” said Dr. McCune, director of rheumatology outpatient services at the University of Michigan, Ann Arbor.

Instead of cessation of therapy, many physicians are trying to continue their patients on a corticosteroid (when necessary) and hydroxychloroquine, with informed consent and disclosure that the drug is known to cross the placenta.

Hydroxychloroquine is a drug that is not the most potent agent for resolving manifestations of lupus, but one that is very good at preventing serious disease developments and flares, Dr. McCune said.

Antimalarials have a number of potentially beneficial side effects, such as improving glucose tolerance, noted Dr. McCune, who previously reviewed and reported on evidence suggesting that antimalarials positively affect both cholesterol levels and thrombosis in lupus patients with increased cardiovascular risk.

There have been no apparent, adverse, fetal effects, and “in general, the experience has been that there have been no difficulties using this drug,” in recent reports of approximately 300 lupus patients treated with hydroxychloroquine during pregnancy, Dr. McCune said.

The reports are from various series and a blinded, placebo-controlled clinical trial.

In the 20 patient clinical trial, none of the 10 treated patients developed toxemia of pregnancy, while 3 of the 10 patients in the placebo group did. The infants of the treated mothers had a greater average delivery age and had a better average Apgar score. The hydroxychloroquine treated mothers used less prednisone (Lupus 2001;10:401–4).

There is also evidence from nonpregnant patients that hydroxychloroquine may positively impact antiphospholipid syndrome, which about 30% of lupus patients have, and which is associated with adverse pregnancy outcomes, Dr. McCune said.