Amy Rothman Schonfeld

Major Finding: Physiologic doses of estrogen significantly increased bone mineral density z scores in the lumbar spine and hip in adolescent girls with anorexia nervosa.

Data Source: A prospective trial of 110 girls with anorexia nervosa randomized to receive estrogen replacement or placebo, and 40 healthy controls who were followed for 18 months.

Disclosures: Dr. Misra received support from Genentech.

BOSTON – Significant increases in bone mineral density at the spine and hip were seen in adolescent girls with anorexia nervosa treated with physiological doses of estrogen, as compared with placebo, according to Dr. Madhusmita Misra, who presented the findings at the meeting.

“We know that low bone mineral density is common in adolescent girls with anorexia nervosa. On dual-energy x-ray absorptiometry (DXA), about 50% have low z scores at one or more sites and they also have low bone accrual rates. This is a special concern during adolescence, when peak bone mass accrual normally occurs,” said Dr. Misra, a pediatrician at Harvard Medical School and Massachusetts General Hospital in Boston.

While previous studies have shown that giving oral estrogen combined with progesterone as birth control pills is not effective at increasing bone density in these girls, the effect of giving estrogen in a more natural or physiologic form to mimic puberty or as a transdermal patch had not been studied before.

In a prospective, randomized study, 110 girls with anorexia nervosa and 40 normal-weight girls of similar pubertal stage and bone age between the ages of 12 and 19 years were enrolled. The girls with anorexia nervosa were randomized to receive either placebo or estrogen, but which type of estrogen they received depended upon their bone maturity based on wrist and hand x-rays.

In order to avoid adversely affecting growth with estrogen, those with immature bone age (n = 14) received low-dose oral ethinyl estradiol in gradually increasing doses (3.75 mcg daily for 0-6 months, 7.5 mcg daily for 6-12 months, and 11.25 mcg daily for 12-18 months) while those with mature bone age (n = 96) received transdermal estradiol at full replacement doses (100 mcg 17-beta estradiol). All received calcium and vitamin D supplementation and were followed for 18 months (J. Bone Miner. Res. 2011 June 22 [doi.10.1002/jbmr.447]).

The results showed that after 18 months, spine and hip bone mineral density z scores increased significantly in girls with anorexia nervosa who received estrogen replacement, compared with those who received placebo, even after controlling for baseline age and weight.

Changes in lumbar bone mineral density were significantly lower at 6, 12, and 18 months in anorexic girls who did not receive estrogen, compared with either anorexic girls who received estrogen or healthy controls.

No significant differences were seen in these measures between anorexic girls who received estrogen and healthy controls. Similar trends were seen for hip bone mineral density, with significant differences at all time points between non–estrogen-treated anorexic girls and healthy controls; differences between treated and untreated anorexic girls were significant only at 18 months.

The two anorexic groups did not differ in body mass index, fat mass, or lean mass after estrogen treatment, indicating that estrogen replacement does not cause weight gain or changes in body composition.

“This is very encouraging and exciting data,” said Dr. Misra.

“I would strongly emphasize that the first step in treating anorexia nervosa has to be to encourage weight gain and menses resumption. As we know, there may be many girls who are recalcitrant about formal treatment, and the adolescent years are a difficult time to accrue bone mass. This is a strategy to optimize bone accrual in girls with anorexia nervosa, even if they are not recovering otherwise.”

She added that it was important to note that although estrogen replacement improves bone density, it often falls short of complete restoration of bone density to normal levels.

'This is a strategy to optimize bone accrual in girls with anorexia nervosa, even if they are not recovering.'

Source DR. MISRA

Major Finding: Physiologic doses of estrogen significantly increased bone mineral density z scores in the lumbar spine and hip in adolescent girls with anorexia nervosa.

Data Source: A prospective trial of 110 girls with anorexia nervosa randomized to receive estrogen replacement or placebo, and 40 healthy controls who were followed for 18 months.

Disclosures: Dr. Misra received support from Genentech.

BOSTON – Significant increases in bone mineral density at the spine and hip were seen in adolescent girls with anorexia nervosa treated with physiological doses of estrogen, as compared with placebo, according to Dr. Madhusmita Misra, who presented the findings at the meeting.

“We know that low bone mineral density is common in adolescent girls with anorexia nervosa. On dual-energy x-ray absorptiometry (DXA), about 50% have low z scores at one or more sites and they also have low bone accrual rates. This is a special concern during adolescence, when peak bone mass accrual normally occurs,” said Dr. Misra, a pediatrician at Harvard Medical School and Massachusetts General Hospital in Boston.

While previous studies have shown that giving oral estrogen combined with progesterone as birth control pills is not effective at increasing bone density in these girls, the effect of giving estrogen in a more natural or physiologic form to mimic puberty or as a transdermal patch had not been studied before.

In a prospective, randomized study, 110 girls with anorexia nervosa and 40 normal-weight girls of similar pubertal stage and bone age between the ages of 12 and 19 years were enrolled. The girls with anorexia nervosa were randomized to receive either placebo or estrogen, but which type of estrogen they received depended upon their bone maturity based on wrist and hand x-rays.

In order to avoid adversely affecting growth with estrogen, those with immature bone age (n = 14) received low-dose oral ethinyl estradiol in gradually increasing doses (3.75 mcg daily for 0-6 months, 7.5 mcg daily for 6-12 months, and 11.25 mcg daily for 12-18 months) while those with mature bone age (n = 96) received transdermal estradiol at full replacement doses (100 mcg 17-beta estradiol). All received calcium and vitamin D supplementation and were followed for 18 months (J. Bone Miner. Res. 2011 June 22 [doi.10.1002/jbmr.447]).

The results showed that after 18 months, spine and hip bone mineral density z scores increased significantly in girls with anorexia nervosa who received estrogen replacement, compared with those who received placebo, even after controlling for baseline age and weight.

Changes in lumbar bone mineral density were significantly lower at 6, 12, and 18 months in anorexic girls who did not receive estrogen, compared with either anorexic girls who received estrogen or healthy controls.

No significant differences were seen in these measures between anorexic girls who received estrogen and healthy controls. Similar trends were seen for hip bone mineral density, with significant differences at all time points between non–estrogen-treated anorexic girls and healthy controls; differences between treated and untreated anorexic girls were significant only at 18 months.

The two anorexic groups did not differ in body mass index, fat mass, or lean mass after estrogen treatment, indicating that estrogen replacement does not cause weight gain or changes in body composition.

“This is very encouraging and exciting data,” said Dr. Misra.

“I would strongly emphasize that the first step in treating anorexia nervosa has to be to encourage weight gain and menses resumption. As we know, there may be many girls who are recalcitrant about formal treatment, and the adolescent years are a difficult time to accrue bone mass. This is a strategy to optimize bone accrual in girls with anorexia nervosa, even if they are not recovering otherwise.”

She added that it was important to note that although estrogen replacement improves bone density, it often falls short of complete restoration of bone density to normal levels.

'This is a strategy to optimize bone accrual in girls with anorexia nervosa, even if they are not recovering.'

Source DR. MISRA

Major Finding: Physiologic doses of estrogen significantly increased bone mineral density z scores in the lumbar spine and hip in adolescent girls with anorexia nervosa.

Data Source: A prospective trial of 110 girls with anorexia nervosa randomized to receive estrogen replacement or placebo, and 40 healthy controls who were followed for 18 months.

Disclosures: Dr. Misra received support from Genentech.

BOSTON – Significant increases in bone mineral density at the spine and hip were seen in adolescent girls with anorexia nervosa treated with physiological doses of estrogen, as compared with placebo, according to Dr. Madhusmita Misra, who presented the findings at the meeting.

“We know that low bone mineral density is common in adolescent girls with anorexia nervosa. On dual-energy x-ray absorptiometry (DXA), about 50% have low z scores at one or more sites and they also have low bone accrual rates. This is a special concern during adolescence, when peak bone mass accrual normally occurs,” said Dr. Misra, a pediatrician at Harvard Medical School and Massachusetts General Hospital in Boston.

While previous studies have shown that giving oral estrogen combined with progesterone as birth control pills is not effective at increasing bone density in these girls, the effect of giving estrogen in a more natural or physiologic form to mimic puberty or as a transdermal patch had not been studied before.

In a prospective, randomized study, 110 girls with anorexia nervosa and 40 normal-weight girls of similar pubertal stage and bone age between the ages of 12 and 19 years were enrolled. The girls with anorexia nervosa were randomized to receive either placebo or estrogen, but which type of estrogen they received depended upon their bone maturity based on wrist and hand x-rays.

In order to avoid adversely affecting growth with estrogen, those with immature bone age (n = 14) received low-dose oral ethinyl estradiol in gradually increasing doses (3.75 mcg daily for 0-6 months, 7.5 mcg daily for 6-12 months, and 11.25 mcg daily for 12-18 months) while those with mature bone age (n = 96) received transdermal estradiol at full replacement doses (100 mcg 17-beta estradiol). All received calcium and vitamin D supplementation and were followed for 18 months (J. Bone Miner. Res. 2011 June 22 [doi.10.1002/jbmr.447]).

The results showed that after 18 months, spine and hip bone mineral density z scores increased significantly in girls with anorexia nervosa who received estrogen replacement, compared with those who received placebo, even after controlling for baseline age and weight.

Changes in lumbar bone mineral density were significantly lower at 6, 12, and 18 months in anorexic girls who did not receive estrogen, compared with either anorexic girls who received estrogen or healthy controls.

No significant differences were seen in these measures between anorexic girls who received estrogen and healthy controls. Similar trends were seen for hip bone mineral density, with significant differences at all time points between non–estrogen-treated anorexic girls and healthy controls; differences between treated and untreated anorexic girls were significant only at 18 months.

The two anorexic groups did not differ in body mass index, fat mass, or lean mass after estrogen treatment, indicating that estrogen replacement does not cause weight gain or changes in body composition.

“This is very encouraging and exciting data,” said Dr. Misra.

“I would strongly emphasize that the first step in treating anorexia nervosa has to be to encourage weight gain and menses resumption. As we know, there may be many girls who are recalcitrant about formal treatment, and the adolescent years are a difficult time to accrue bone mass. This is a strategy to optimize bone accrual in girls with anorexia nervosa, even if they are not recovering otherwise.”

She added that it was important to note that although estrogen replacement improves bone density, it often falls short of complete restoration of bone density to normal levels.

'This is a strategy to optimize bone accrual in girls with anorexia nervosa, even if they are not recovering.'

Source DR. MISRA

Major finding: The relapse rate for patients with antineutrophil cytoplasmic antibody–associated vasculitis was 43% in a pooled analysis of studies in which patients were tapered completely from glucocorticoids, compared with 14% in studies of patients allowed to continue glucocorticoid therapy. Early discontinuation was associated with a higher relapse rate than was later discontinuation.

Data Source: Meta-analysis of 13 studies involving 983 patients investigating the treatment of AAV that included a predefined glucocorticoid dose and protocol for tapering.

Disclosures: Dr. Yazici has served as a consultant or speaker for, or has received research support from, BMS, Celgene, Centocor, Genentech, Merck, Novartis, Roche, and UCB.

NEW YORK – Early discontinuation of glucocorticoid therapy may greatly increase the risk of relapse in antineutrophil cytoplasmic antibody–associated vasculitis, said Dr. Yusuf Yazici.

He discussed a study that addressed the controversial question of whether low-dose glucocorticoids contribute to maintaining remission of the disease.

Patients successfully treated for antineutrophil cytoplasmic antibody–associated vasculitis (AAV) face high rates of relapse, up to 38% at 30 months. Although glucocorticoids are often used to prevent relapse in AAV, high-quality evidence to guide treatment is lacking, Dr. Yazici said.

“Our aim is always to get patients off steroid therapy, but maybe that is a misguided aim,” said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet's Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases.

Dr. Yazici cited findings from a meta-analysis of studies investigating the treatment of AAV that included a predefined glucocorticoid dose and protocol for tapering (Arthritis Care Res. 2010;62:1166-73). Thirteen studies involving 983 patients were identified for inclusion, including five observational and eight randomized controlled trials. None of the studies directly compared glucocorticoid regimens.

To elucidate the role of glucocorticoid therapy in relapse, the authors divided the studies into those that had a zero glucocorticoid target dose (aimed to get patients completely off glucocorticoid therapy, n = 695) and those having a nonzero glucocorticoid target dose (low glucocorticoid maintenance dose allowed, n = 288).

The investigators found that 36% of the overall group relapsed. Upon further examination, the relapse rate was 43% for those in the zero glucocorticoid target dose group, compared with 14% in those allowed to continue glucocorticoids – approximately a threefold increase.

Even for those who discontinue glucocorticoids, timing is important. When the investigators divided patients in the zero target dose into those who had to reach zero within 12 months (the early zero group) and those who were allowed to reach zero after 12 months (the late zero group), there was a 48% relapse rate for the early zero group, compared with a 29% rate for the late zero group. While the early zero glucocorticoid target dose group had significantly more relapses than the nonzero group (P less than .001), the late zero glucocorticoid target dose group was similar to the nonzero group. By grouping the late zero and nonzero groups, the authors concluded that early discontinuation of glucocorticoid was associated with a 20% increased risk of relapse (28% vs. 48%).

The results suggest that glucocorticoid dose should be monitored, and that patients with AAV should be kept on 5.0–7.5 mg of glucocorticoids for at least a year after reaching remission, said Dr. Yazici.

Major finding: The relapse rate for patients with antineutrophil cytoplasmic antibody–associated vasculitis was 43% in a pooled analysis of studies in which patients were tapered completely from glucocorticoids, compared with 14% in studies of patients allowed to continue glucocorticoid therapy. Early discontinuation was associated with a higher relapse rate than was later discontinuation.

Data Source: Meta-analysis of 13 studies involving 983 patients investigating the treatment of AAV that included a predefined glucocorticoid dose and protocol for tapering.

Disclosures: Dr. Yazici has served as a consultant or speaker for, or has received research support from, BMS, Celgene, Centocor, Genentech, Merck, Novartis, Roche, and UCB.

NEW YORK – Early discontinuation of glucocorticoid therapy may greatly increase the risk of relapse in antineutrophil cytoplasmic antibody–associated vasculitis, said Dr. Yusuf Yazici.

He discussed a study that addressed the controversial question of whether low-dose glucocorticoids contribute to maintaining remission of the disease.

Patients successfully treated for antineutrophil cytoplasmic antibody–associated vasculitis (AAV) face high rates of relapse, up to 38% at 30 months. Although glucocorticoids are often used to prevent relapse in AAV, high-quality evidence to guide treatment is lacking, Dr. Yazici said.

“Our aim is always to get patients off steroid therapy, but maybe that is a misguided aim,” said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet's Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases.

Dr. Yazici cited findings from a meta-analysis of studies investigating the treatment of AAV that included a predefined glucocorticoid dose and protocol for tapering (Arthritis Care Res. 2010;62:1166-73). Thirteen studies involving 983 patients were identified for inclusion, including five observational and eight randomized controlled trials. None of the studies directly compared glucocorticoid regimens.

To elucidate the role of glucocorticoid therapy in relapse, the authors divided the studies into those that had a zero glucocorticoid target dose (aimed to get patients completely off glucocorticoid therapy, n = 695) and those having a nonzero glucocorticoid target dose (low glucocorticoid maintenance dose allowed, n = 288).

The investigators found that 36% of the overall group relapsed. Upon further examination, the relapse rate was 43% for those in the zero glucocorticoid target dose group, compared with 14% in those allowed to continue glucocorticoids – approximately a threefold increase.

Even for those who discontinue glucocorticoids, timing is important. When the investigators divided patients in the zero target dose into those who had to reach zero within 12 months (the early zero group) and those who were allowed to reach zero after 12 months (the late zero group), there was a 48% relapse rate for the early zero group, compared with a 29% rate for the late zero group. While the early zero glucocorticoid target dose group had significantly more relapses than the nonzero group (P less than .001), the late zero glucocorticoid target dose group was similar to the nonzero group. By grouping the late zero and nonzero groups, the authors concluded that early discontinuation of glucocorticoid was associated with a 20% increased risk of relapse (28% vs. 48%).

The results suggest that glucocorticoid dose should be monitored, and that patients with AAV should be kept on 5.0–7.5 mg of glucocorticoids for at least a year after reaching remission, said Dr. Yazici.

Major finding: The relapse rate for patients with antineutrophil cytoplasmic antibody–associated vasculitis was 43% in a pooled analysis of studies in which patients were tapered completely from glucocorticoids, compared with 14% in studies of patients allowed to continue glucocorticoid therapy. Early discontinuation was associated with a higher relapse rate than was later discontinuation.

Data Source: Meta-analysis of 13 studies involving 983 patients investigating the treatment of AAV that included a predefined glucocorticoid dose and protocol for tapering.

Disclosures: Dr. Yazici has served as a consultant or speaker for, or has received research support from, BMS, Celgene, Centocor, Genentech, Merck, Novartis, Roche, and UCB.

NEW YORK – Early discontinuation of glucocorticoid therapy may greatly increase the risk of relapse in antineutrophil cytoplasmic antibody–associated vasculitis, said Dr. Yusuf Yazici.

He discussed a study that addressed the controversial question of whether low-dose glucocorticoids contribute to maintaining remission of the disease.

Patients successfully treated for antineutrophil cytoplasmic antibody–associated vasculitis (AAV) face high rates of relapse, up to 38% at 30 months. Although glucocorticoids are often used to prevent relapse in AAV, high-quality evidence to guide treatment is lacking, Dr. Yazici said.

“Our aim is always to get patients off steroid therapy, but maybe that is a misguided aim,” said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet's Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases.

Dr. Yazici cited findings from a meta-analysis of studies investigating the treatment of AAV that included a predefined glucocorticoid dose and protocol for tapering (Arthritis Care Res. 2010;62:1166-73). Thirteen studies involving 983 patients were identified for inclusion, including five observational and eight randomized controlled trials. None of the studies directly compared glucocorticoid regimens.

To elucidate the role of glucocorticoid therapy in relapse, the authors divided the studies into those that had a zero glucocorticoid target dose (aimed to get patients completely off glucocorticoid therapy, n = 695) and those having a nonzero glucocorticoid target dose (low glucocorticoid maintenance dose allowed, n = 288).

The investigators found that 36% of the overall group relapsed. Upon further examination, the relapse rate was 43% for those in the zero glucocorticoid target dose group, compared with 14% in those allowed to continue glucocorticoids – approximately a threefold increase.

Even for those who discontinue glucocorticoids, timing is important. When the investigators divided patients in the zero target dose into those who had to reach zero within 12 months (the early zero group) and those who were allowed to reach zero after 12 months (the late zero group), there was a 48% relapse rate for the early zero group, compared with a 29% rate for the late zero group. While the early zero glucocorticoid target dose group had significantly more relapses than the nonzero group (P less than .001), the late zero glucocorticoid target dose group was similar to the nonzero group. By grouping the late zero and nonzero groups, the authors concluded that early discontinuation of glucocorticoid was associated with a 20% increased risk of relapse (28% vs. 48%).

The results suggest that glucocorticoid dose should be monitored, and that patients with AAV should be kept on 5.0–7.5 mg of glucocorticoids for at least a year after reaching remission, said Dr. Yazici.

BOSTON – After more than 2 decades of follow-up, mortality rates were significantly higher in patients who had been treated with recombinant growth hormone for short stature as children, especially those who received the highest doses.

Notable increases in mortality were observed related to bone tumors and diseases of the circulatory system such a subarachnoid or intracerebral hemorrhage, according to Dr. Jean-Claude Carel of the Hôpital Robert Debré and Université Denis Diderot in Paris, who presented the results at the annual meeting of the Endocrine Society.

According to Dr. Carel, although there has been a considerable amount of data linking recombinant growth hormone and health, few studies have provided long-term follow-up. The data released were French data from the SAGHE (Safety and Appropriateness of Growth Hormone Treatments in Europe) trial, a large study from eight European countries evaluating the health of individuals treated in childhood for idiopathic growth hormone deficiency (75% of the group), idiopathic short stature, and body length at birth that was short for gestational age. The study was initiated first in France (2 years before the rest of Europe), and thus the longest follow-up is available for this cohort.

The group consisted of 6,928 children who were treated during 1985-1996. Follow-up data on vital status were available in September 2009 for almost 95% of the patients, providing 116,403 person-years of observation. The mean age at the end of treatment was 15 years and the mean duration of treatment was almost 9 years. During the follow-up, 93 deaths were observed, compared with 69.6 expected deaths, yielding a higher standardized mortality ratio (SMR) of 1.33, which Dr. Carel said was significant but moderate.

Although the mean dose was 24.6 mcg/kg per day – lower than doses currently recommended today – there was a significant trend of increasing mortality and growth hormone dose (P = .04). In multivariate analysis adjusted for height at the start of treatment, mortality rates in the 285 who received high doses (greater than 50 mcg/kg per day) was almost three times that of the low-dose group (adjusted SMR, 2.94; 95% confidence interval, 1.22-7.07). No significant effects were seen for treatment duration or overall growth hormone exposure. Mortality was elevated in children with the shortest stature at treatment initiation (SMR, 1.57).

Further analysis about cause of death found that although overall cancer-related mortality was not higher than that of the general population, deaths resulting from bone tumors were five times higher than expected (SMR, 5.00; 95% CI, 1.01-14.63), and deaths resulting from diseases of the circulatory system were threefold higher (SMR, 3.07; 95% CI, 1.40-5.83). Particularly concerning were findings of more than a sixfold increase in deaths resulting from subarachnoid or intracerebral hemorrhage (SMR, 6.66; 95% CI, 1.79-17.05) and a sevenfold increase in other heart diseases (cardiomyopathy and cardiomegaly, SMR, 7.11; 95% CI, 0.80-25.67).

"These preliminary results should be taken with caution due to the low event rate, limited power, and potentially undetected confounders. Causality cannot be determined. Additional data are needed, including additional data from other European countries participating" in SAGHE, said Dr. Carel.

Dr. Carel reported ties to Lilly USA and Pfizer Global Research and Development.

BOSTON – After more than 2 decades of follow-up, mortality rates were significantly higher in patients who had been treated with recombinant growth hormone for short stature as children, especially those who received the highest doses.

Notable increases in mortality were observed related to bone tumors and diseases of the circulatory system such a subarachnoid or intracerebral hemorrhage, according to Dr. Jean-Claude Carel of the Hôpital Robert Debré and Université Denis Diderot in Paris, who presented the results at the annual meeting of the Endocrine Society.

According to Dr. Carel, although there has been a considerable amount of data linking recombinant growth hormone and health, few studies have provided long-term follow-up. The data released were French data from the SAGHE (Safety and Appropriateness of Growth Hormone Treatments in Europe) trial, a large study from eight European countries evaluating the health of individuals treated in childhood for idiopathic growth hormone deficiency (75% of the group), idiopathic short stature, and body length at birth that was short for gestational age. The study was initiated first in France (2 years before the rest of Europe), and thus the longest follow-up is available for this cohort.

The group consisted of 6,928 children who were treated during 1985-1996. Follow-up data on vital status were available in September 2009 for almost 95% of the patients, providing 116,403 person-years of observation. The mean age at the end of treatment was 15 years and the mean duration of treatment was almost 9 years. During the follow-up, 93 deaths were observed, compared with 69.6 expected deaths, yielding a higher standardized mortality ratio (SMR) of 1.33, which Dr. Carel said was significant but moderate.

Although the mean dose was 24.6 mcg/kg per day – lower than doses currently recommended today – there was a significant trend of increasing mortality and growth hormone dose (P = .04). In multivariate analysis adjusted for height at the start of treatment, mortality rates in the 285 who received high doses (greater than 50 mcg/kg per day) was almost three times that of the low-dose group (adjusted SMR, 2.94; 95% confidence interval, 1.22-7.07). No significant effects were seen for treatment duration or overall growth hormone exposure. Mortality was elevated in children with the shortest stature at treatment initiation (SMR, 1.57).

Further analysis about cause of death found that although overall cancer-related mortality was not higher than that of the general population, deaths resulting from bone tumors were five times higher than expected (SMR, 5.00; 95% CI, 1.01-14.63), and deaths resulting from diseases of the circulatory system were threefold higher (SMR, 3.07; 95% CI, 1.40-5.83). Particularly concerning were findings of more than a sixfold increase in deaths resulting from subarachnoid or intracerebral hemorrhage (SMR, 6.66; 95% CI, 1.79-17.05) and a sevenfold increase in other heart diseases (cardiomyopathy and cardiomegaly, SMR, 7.11; 95% CI, 0.80-25.67).

"These preliminary results should be taken with caution due to the low event rate, limited power, and potentially undetected confounders. Causality cannot be determined. Additional data are needed, including additional data from other European countries participating" in SAGHE, said Dr. Carel.

Dr. Carel reported ties to Lilly USA and Pfizer Global Research and Development.

BOSTON – After more than 2 decades of follow-up, mortality rates were significantly higher in patients who had been treated with recombinant growth hormone for short stature as children, especially those who received the highest doses.

Notable increases in mortality were observed related to bone tumors and diseases of the circulatory system such a subarachnoid or intracerebral hemorrhage, according to Dr. Jean-Claude Carel of the Hôpital Robert Debré and Université Denis Diderot in Paris, who presented the results at the annual meeting of the Endocrine Society.

According to Dr. Carel, although there has been a considerable amount of data linking recombinant growth hormone and health, few studies have provided long-term follow-up. The data released were French data from the SAGHE (Safety and Appropriateness of Growth Hormone Treatments in Europe) trial, a large study from eight European countries evaluating the health of individuals treated in childhood for idiopathic growth hormone deficiency (75% of the group), idiopathic short stature, and body length at birth that was short for gestational age. The study was initiated first in France (2 years before the rest of Europe), and thus the longest follow-up is available for this cohort.

The group consisted of 6,928 children who were treated during 1985-1996. Follow-up data on vital status were available in September 2009 for almost 95% of the patients, providing 116,403 person-years of observation. The mean age at the end of treatment was 15 years and the mean duration of treatment was almost 9 years. During the follow-up, 93 deaths were observed, compared with 69.6 expected deaths, yielding a higher standardized mortality ratio (SMR) of 1.33, which Dr. Carel said was significant but moderate.

Although the mean dose was 24.6 mcg/kg per day – lower than doses currently recommended today – there was a significant trend of increasing mortality and growth hormone dose (P = .04). In multivariate analysis adjusted for height at the start of treatment, mortality rates in the 285 who received high doses (greater than 50 mcg/kg per day) was almost three times that of the low-dose group (adjusted SMR, 2.94; 95% confidence interval, 1.22-7.07). No significant effects were seen for treatment duration or overall growth hormone exposure. Mortality was elevated in children with the shortest stature at treatment initiation (SMR, 1.57).

Further analysis about cause of death found that although overall cancer-related mortality was not higher than that of the general population, deaths resulting from bone tumors were five times higher than expected (SMR, 5.00; 95% CI, 1.01-14.63), and deaths resulting from diseases of the circulatory system were threefold higher (SMR, 3.07; 95% CI, 1.40-5.83). Particularly concerning were findings of more than a sixfold increase in deaths resulting from subarachnoid or intracerebral hemorrhage (SMR, 6.66; 95% CI, 1.79-17.05) and a sevenfold increase in other heart diseases (cardiomyopathy and cardiomegaly, SMR, 7.11; 95% CI, 0.80-25.67).

"These preliminary results should be taken with caution due to the low event rate, limited power, and potentially undetected confounders. Causality cannot be determined. Additional data are needed, including additional data from other European countries participating" in SAGHE, said Dr. Carel.

Dr. Carel reported ties to Lilly USA and Pfizer Global Research and Development.

BOSTON – After more than 2 decades of follow-up, mortality rates were significantly higher in patients who had been treated with recombinant growth hormone for short stature as children, especially those who received the highest doses.

Notable increases in mortality were observed related to bone tumors and diseases of the circulatory system such a subarachnoid or intracerebral hemorrhage, according to Dr. Jean-Claude Carel of the Hôpital Robert Debré and Université Denis Diderot in Paris, who presented the results at the annual meeting of the Endocrine Society.

According to Dr. Carel, although there has been a considerable amount of data linking recombinant growth hormone and health, few studies have provided long-term follow-up. The data released were French data from the SAGHE (Safety and Appropriateness of Growth Hormone Treatments in Europe) trial, a large study from eight European countries evaluating the health of individuals treated in childhood for idiopathic growth hormone deficiency (75% of the group), idiopathic short stature, and body length at birth that was short for gestational age. The study was initiated first in France (2 years before the rest of Europe), and thus the longest follow-up is available for this cohort.

The group consisted of 6,928 children who were treated during 1985-1996. Follow-up data on vital status were available in September 2009 for almost 95% of the patients, providing 116,403 person-years of observation. The mean age at the end of treatment was 15 years and the mean duration of treatment was almost 9 years. During the follow-up, 93 deaths were observed, compared with 69.6 expected deaths, yielding a higher standardized mortality ratio (SMR) of 1.33, which Dr. Carel said was significant but moderate.

Although the mean dose was 24.6 mcg/kg per day – lower than doses currently recommended today – there was a significant trend of increasing mortality and growth hormone dose (P = .04). In multivariate analysis adjusted for height at the start of treatment, mortality rates in the 285 who received high doses (greater than 50 mcg/kg per day) was almost three times that of the low-dose group (adjusted SMR, 2.94; 95% confidence interval, 1.22-7.07). No significant effects were seen for treatment duration or overall growth hormone exposure. Mortality was elevated in children with the shortest stature at treatment initiation (SMR, 1.57).

Further analysis about cause of death found that although overall cancer-related mortality was not higher than that of the general population, deaths resulting from bone tumors were five times higher than expected (SMR, 5.00; 95% CI, 1.01-14.63), and deaths resulting from diseases of the circulatory system were threefold higher (SMR, 3.07; 95% CI, 1.40-5.83). Particularly concerning were findings of more than a sixfold increase in deaths resulting from subarachnoid or intracerebral hemorrhage (SMR, 6.66; 95% CI, 1.79-17.05) and a sevenfold increase in other heart diseases (cardiomyopathy and cardiomegaly, SMR, 7.11; 95% CI, 0.80-25.67).

"These preliminary results should be taken with caution due to the low event rate, limited power, and potentially undetected confounders. Causality cannot be determined. Additional data are needed, including additional data from other European countries participating" in SAGHE, said Dr. Carel.

Dr. Carel reported ties to Lilly USA and Pfizer Global Research and Development.

BOSTON – After more than 2 decades of follow-up, mortality rates were significantly higher in patients who had been treated with recombinant growth hormone for short stature as children, especially those who received the highest doses.

Notable increases in mortality were observed related to bone tumors and diseases of the circulatory system such a subarachnoid or intracerebral hemorrhage, according to Dr. Jean-Claude Carel of the Hôpital Robert Debré and Université Denis Diderot in Paris, who presented the results at the annual meeting of the Endocrine Society.

According to Dr. Carel, although there has been a considerable amount of data linking recombinant growth hormone and health, few studies have provided long-term follow-up. The data released were French data from the SAGHE (Safety and Appropriateness of Growth Hormone Treatments in Europe) trial, a large study from eight European countries evaluating the health of individuals treated in childhood for idiopathic growth hormone deficiency (75% of the group), idiopathic short stature, and body length at birth that was short for gestational age. The study was initiated first in France (2 years before the rest of Europe), and thus the longest follow-up is available for this cohort.

The group consisted of 6,928 children who were treated during 1985-1996. Follow-up data on vital status were available in September 2009 for almost 95% of the patients, providing 116,403 person-years of observation. The mean age at the end of treatment was 15 years and the mean duration of treatment was almost 9 years. During the follow-up, 93 deaths were observed, compared with 69.6 expected deaths, yielding a higher standardized mortality ratio (SMR) of 1.33, which Dr. Carel said was significant but moderate.

Although the mean dose was 24.6 mcg/kg per day – lower than doses currently recommended today – there was a significant trend of increasing mortality and growth hormone dose (P = .04). In multivariate analysis adjusted for height at the start of treatment, mortality rates in the 285 who received high doses (greater than 50 mcg/kg per day) was almost three times that of the low-dose group (adjusted SMR, 2.94; 95% confidence interval, 1.22-7.07). No significant effects were seen for treatment duration or overall growth hormone exposure. Mortality was elevated in children with the shortest stature at treatment initiation (SMR, 1.57).

Further analysis about cause of death found that although overall cancer-related mortality was not higher than that of the general population, deaths resulting from bone tumors were five times higher than expected (SMR, 5.00; 95% CI, 1.01-14.63), and deaths resulting from diseases of the circulatory system were threefold higher (SMR, 3.07; 95% CI, 1.40-5.83). Particularly concerning were findings of more than a sixfold increase in deaths resulting from subarachnoid or intracerebral hemorrhage (SMR, 6.66; 95% CI, 1.79-17.05) and a sevenfold increase in other heart diseases (cardiomyopathy and cardiomegaly, SMR, 7.11; 95% CI, 0.80-25.67).

"These preliminary results should be taken with caution due to the low event rate, limited power, and potentially undetected confounders. Causality cannot be determined. Additional data are needed, including additional data from other European countries participating" in SAGHE, said Dr. Carel.

Dr. Carel reported ties to Lilly USA and Pfizer Global Research and Development.

BOSTON – After more than 2 decades of follow-up, mortality rates were significantly higher in patients who had been treated with recombinant growth hormone for short stature as children, especially those who received the highest doses.

Notable increases in mortality were observed related to bone tumors and diseases of the circulatory system such a subarachnoid or intracerebral hemorrhage, according to Dr. Jean-Claude Carel of the Hôpital Robert Debré and Université Denis Diderot in Paris, who presented the results at the annual meeting of the Endocrine Society.

According to Dr. Carel, although there has been a considerable amount of data linking recombinant growth hormone and health, few studies have provided long-term follow-up. The data released were French data from the SAGHE (Safety and Appropriateness of Growth Hormone Treatments in Europe) trial, a large study from eight European countries evaluating the health of individuals treated in childhood for idiopathic growth hormone deficiency (75% of the group), idiopathic short stature, and body length at birth that was short for gestational age. The study was initiated first in France (2 years before the rest of Europe), and thus the longest follow-up is available for this cohort.

The group consisted of 6,928 children who were treated during 1985-1996. Follow-up data on vital status were available in September 2009 for almost 95% of the patients, providing 116,403 person-years of observation. The mean age at the end of treatment was 15 years and the mean duration of treatment was almost 9 years. During the follow-up, 93 deaths were observed, compared with 69.6 expected deaths, yielding a higher standardized mortality ratio (SMR) of 1.33, which Dr. Carel said was significant but moderate.

Although the mean dose was 24.6 mcg/kg per day – lower than doses currently recommended today – there was a significant trend of increasing mortality and growth hormone dose (P = .04). In multivariate analysis adjusted for height at the start of treatment, mortality rates in the 285 who received high doses (greater than 50 mcg/kg per day) was almost three times that of the low-dose group (adjusted SMR, 2.94; 95% confidence interval, 1.22-7.07). No significant effects were seen for treatment duration or overall growth hormone exposure. Mortality was elevated in children with the shortest stature at treatment initiation (SMR, 1.57).

Further analysis about cause of death found that although overall cancer-related mortality was not higher than that of the general population, deaths resulting from bone tumors were five times higher than expected (SMR, 5.00; 95% CI, 1.01-14.63), and deaths resulting from diseases of the circulatory system were threefold higher (SMR, 3.07; 95% CI, 1.40-5.83). Particularly concerning were findings of more than a sixfold increase in deaths resulting from subarachnoid or intracerebral hemorrhage (SMR, 6.66; 95% CI, 1.79-17.05) and a sevenfold increase in other heart diseases (cardiomyopathy and cardiomegaly, SMR, 7.11; 95% CI, 0.80-25.67).

"These preliminary results should be taken with caution due to the low event rate, limited power, and potentially undetected confounders. Causality cannot be determined. Additional data are needed, including additional data from other European countries participating" in SAGHE, said Dr. Carel.

Dr. Carel reported ties to Lilly USA and Pfizer Global Research and Development.

NEW YORK – Early discontinuation of glucocorticoid therapy may greatly increase the risk of relapse in antineutrophil cytoplasmic antibody–associated vasculitis, Dr. Yusuf Yazici said at a rheumatology meeting sponsored by New York University.

He discussed a study that addressed the controversial question of whether low-dose glucocorticoids contribute to maintaining remission of the disease.

Patients successfully treated for antineutrophil cytoplasmic antibody–associated vasculitis (AAV) face high rates of relapse, up to 38% at 30 months. Although glucocorticoids are often used to prevent relapse in AAV, high-quality evidence to guide treatment is lacking, Dr. Yazici said during an update on the treatment of vasculitis.

"Our aim is always to get patients off steroid therapy, but maybe that is a misguided aim," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases.

Dr. Yazici cited findings from a meta-analysis of studies investigating the treatment of AAV that included a predefined glucocorticoid dose and protocol for tapering (Arthritis Care Res. 2010;62:1166-73). Thirteen studies involving 983 patients were identified for inclusion, including five observational and eight randomized controlled trials. None of the studies directly compared glucocorticoid regimens.

To elucidate the role of glucocorticoid therapy in relapse, the authors divided the studies into those that had a zero glucocorticoid target dose (i.e., aimed to get patients completely off glucocorticoid therapy, n = 695) and those having a nonzero glucocorticoid target dose (i.e., low glucocorticoid maintenance dose allowed, n = 288).

The investigators found that 36% of the overall group relapsed. Upon further examination, the relapse rate was 43% for those in the zero glucocorticoid target dose group, compared with 14% in those allowed to continue glucocorticoids – approximately a threefold increase.

Even for those who discontinue glucocorticoids, timing is important. When the investigators divided patients in the zero target dose into those who had to reach zero within 12 months (the early zero group) and those who were allowed to reach zero after 12 months (the late zero group), there was a 48% relapse rate for the early zero group, compared with a 29% rate for the late zero group. While the early zero glucocorticoid target dose group had significantly more relapses than the nonzero group (P less than .001), the late zero glucocorticoid target dose group was similar to the nonzero group. By grouping the late zero and nonzero groups, the authors concluded that early discontinuation of glucocorticoid was associated with a 20% increased risk of relapse (28% vs. 48%).

This study has several significant messages, said Dr. Yazici. "Small differences in [glucocorticoid] management may have a major impact on relapse rates. It may not be a bad thing to keep AAV patients on steroids a little longer. This is the first study that has looked into this," he noted.

The results suggest that glucocorticoid dose should be monitored, and that patients with AAV should be kept on 5.0-7.5 mg of glucocorticoids for at least a year after reaching disease remission. For clinical trials, failure to consider concomitant glucocorticoid dosing can affect outcomes, especially remission and relapse, as well as sample size determination, said Dr. Yazici.

Dr. Yazici has served as a consultant or speaker for, or has received research support from, BMS, Celgene, Centocor, Genentech, Merck, Novartis, Roche, and UCB.

NEW YORK – Early discontinuation of glucocorticoid therapy may greatly increase the risk of relapse in antineutrophil cytoplasmic antibody–associated vasculitis, Dr. Yusuf Yazici said at a rheumatology meeting sponsored by New York University.

He discussed a study that addressed the controversial question of whether low-dose glucocorticoids contribute to maintaining remission of the disease.

Patients successfully treated for antineutrophil cytoplasmic antibody–associated vasculitis (AAV) face high rates of relapse, up to 38% at 30 months. Although glucocorticoids are often used to prevent relapse in AAV, high-quality evidence to guide treatment is lacking, Dr. Yazici said during an update on the treatment of vasculitis.

"Our aim is always to get patients off steroid therapy, but maybe that is a misguided aim," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases.

Dr. Yazici cited findings from a meta-analysis of studies investigating the treatment of AAV that included a predefined glucocorticoid dose and protocol for tapering (Arthritis Care Res. 2010;62:1166-73). Thirteen studies involving 983 patients were identified for inclusion, including five observational and eight randomized controlled trials. None of the studies directly compared glucocorticoid regimens.

To elucidate the role of glucocorticoid therapy in relapse, the authors divided the studies into those that had a zero glucocorticoid target dose (i.e., aimed to get patients completely off glucocorticoid therapy, n = 695) and those having a nonzero glucocorticoid target dose (i.e., low glucocorticoid maintenance dose allowed, n = 288).

The investigators found that 36% of the overall group relapsed. Upon further examination, the relapse rate was 43% for those in the zero glucocorticoid target dose group, compared with 14% in those allowed to continue glucocorticoids – approximately a threefold increase.

Even for those who discontinue glucocorticoids, timing is important. When the investigators divided patients in the zero target dose into those who had to reach zero within 12 months (the early zero group) and those who were allowed to reach zero after 12 months (the late zero group), there was a 48% relapse rate for the early zero group, compared with a 29% rate for the late zero group. While the early zero glucocorticoid target dose group had significantly more relapses than the nonzero group (P less than .001), the late zero glucocorticoid target dose group was similar to the nonzero group. By grouping the late zero and nonzero groups, the authors concluded that early discontinuation of glucocorticoid was associated with a 20% increased risk of relapse (28% vs. 48%).

This study has several significant messages, said Dr. Yazici. "Small differences in [glucocorticoid] management may have a major impact on relapse rates. It may not be a bad thing to keep AAV patients on steroids a little longer. This is the first study that has looked into this," he noted.

The results suggest that glucocorticoid dose should be monitored, and that patients with AAV should be kept on 5.0-7.5 mg of glucocorticoids for at least a year after reaching disease remission. For clinical trials, failure to consider concomitant glucocorticoid dosing can affect outcomes, especially remission and relapse, as well as sample size determination, said Dr. Yazici.

Dr. Yazici has served as a consultant or speaker for, or has received research support from, BMS, Celgene, Centocor, Genentech, Merck, Novartis, Roche, and UCB.

NEW YORK – Early discontinuation of glucocorticoid therapy may greatly increase the risk of relapse in antineutrophil cytoplasmic antibody–associated vasculitis, Dr. Yusuf Yazici said at a rheumatology meeting sponsored by New York University.

He discussed a study that addressed the controversial question of whether low-dose glucocorticoids contribute to maintaining remission of the disease.

Patients successfully treated for antineutrophil cytoplasmic antibody–associated vasculitis (AAV) face high rates of relapse, up to 38% at 30 months. Although glucocorticoids are often used to prevent relapse in AAV, high-quality evidence to guide treatment is lacking, Dr. Yazici said during an update on the treatment of vasculitis.

"Our aim is always to get patients off steroid therapy, but maybe that is a misguided aim," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases.

Dr. Yazici cited findings from a meta-analysis of studies investigating the treatment of AAV that included a predefined glucocorticoid dose and protocol for tapering (Arthritis Care Res. 2010;62:1166-73). Thirteen studies involving 983 patients were identified for inclusion, including five observational and eight randomized controlled trials. None of the studies directly compared glucocorticoid regimens.

To elucidate the role of glucocorticoid therapy in relapse, the authors divided the studies into those that had a zero glucocorticoid target dose (i.e., aimed to get patients completely off glucocorticoid therapy, n = 695) and those having a nonzero glucocorticoid target dose (i.e., low glucocorticoid maintenance dose allowed, n = 288).

The investigators found that 36% of the overall group relapsed. Upon further examination, the relapse rate was 43% for those in the zero glucocorticoid target dose group, compared with 14% in those allowed to continue glucocorticoids – approximately a threefold increase.

Even for those who discontinue glucocorticoids, timing is important. When the investigators divided patients in the zero target dose into those who had to reach zero within 12 months (the early zero group) and those who were allowed to reach zero after 12 months (the late zero group), there was a 48% relapse rate for the early zero group, compared with a 29% rate for the late zero group. While the early zero glucocorticoid target dose group had significantly more relapses than the nonzero group (P less than .001), the late zero glucocorticoid target dose group was similar to the nonzero group. By grouping the late zero and nonzero groups, the authors concluded that early discontinuation of glucocorticoid was associated with a 20% increased risk of relapse (28% vs. 48%).

This study has several significant messages, said Dr. Yazici. "Small differences in [glucocorticoid] management may have a major impact on relapse rates. It may not be a bad thing to keep AAV patients on steroids a little longer. This is the first study that has looked into this," he noted.

The results suggest that glucocorticoid dose should be monitored, and that patients with AAV should be kept on 5.0-7.5 mg of glucocorticoids for at least a year after reaching disease remission. For clinical trials, failure to consider concomitant glucocorticoid dosing can affect outcomes, especially remission and relapse, as well as sample size determination, said Dr. Yazici.

Dr. Yazici has served as a consultant or speaker for, or has received research support from, BMS, Celgene, Centocor, Genentech, Merck, Novartis, Roche, and UCB.

NEW YORK – The 18%-20% of systemic lupus erythematosus patients who test positive for platelet C4d face a much greater likelihood of having a future cardiovascular event, stroke, or death than those who are not platelet C4d positive, according to Dr. Susan M. Manzi, who presented the results at a rheumatology meeting sponsored by New York University.

"The only factor that predicted mortality greater than being positive for P-C4d [platelet C4d] was having cancer," said Dr. Manzi, chair of the department of medicine and codirector of the Lupus Center of Excellence at West Penn Allegheny Health System, Pittsburgh.

In the study of 356 patients with systemic lupus erythematosus (SLE), which was carried out between July 2001 and August 2009, 70 tested positive for P-C4d (20%) and 286 tested negative. This confirms a previous study that found that P-C4d was present in 18% of SLE patients and that P-C4d was highly specific for SLE (Arthritis Rheum. 2006;54:670-4). "P-C4d carries a 95% specificity for SLE," said Dr. Manzi, who is also vice chair and professor of medicine at Temple University, Philadelphia.

Patients who were P-C4d positive had twice as many cardiovascular events (36 vs. 18, P = .001). The odds ratio of having a cardiovascular event was 2.09 for positive P-C4d (P = .02), which was much higher than for smoking (OR 1.36), SLE disease duration (0.99), or the presence of renal disease (1.42). The odds ratio for aPL antibodies was 2.30 (P = 0.004).

The results for stroke were even more striking. Thirteen patients with P-C4d had stroke, compared with three in those who tested negative for P-C4d (P = .002). There was nearly a fivefold increased risk of stroke in this group (OR 4.96, CI 1.75-14.06, P = .003). Almost three times as many patients had a pulmonary embolism in the P-C4d group, compared with controls (11 vs. 4, P = .007).

Fourteen SLE patients (4%) died during the follow-up. Of those, more P-C4d-positive patients died compared with those who tested negative for P-C4d (11% vs. 2%, P = .002). Causes of death included infection (4), cardiac arrest (2), congestive heart failure (1), cancer (2), hemorrhage (1), and unspecified (4). The risk of all-cause mortality was increased almost eightfold in those who were P-C4d positive (OR 7.92, CI 2.13-29.48, P = .002). Only cancer (OR 19.74) surpassed being P-C4d as a risk for all-cause mortality in multivariate regression analysis.

"Usually when we measure complement in the circulation, we measure the parent protein C4 in the plasma. When complement is activated, it breaks down into fragments and we see that one fragment, C4d, can covalently bind to cell surfaces. So, as we study how these fragments of complement activation bind to cells, we are exploring their potential use as disease biomarkers and prognostic indicators," Dr. Manzi said.

Dr. Manzi serves on the advisory boards of Bristol-Myers Squibb, Human Genome Sciences, and Cephalon. She receives funding for research from Amgen USA, Aspreva Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Genentech, Human Genome Sciences, and Immunomedics.

NEW YORK – The 18%-20% of systemic lupus erythematosus patients who test positive for platelet C4d face a much greater likelihood of having a future cardiovascular event, stroke, or death than those who are not platelet C4d positive, according to Dr. Susan M. Manzi, who presented the results at a rheumatology meeting sponsored by New York University.

"The only factor that predicted mortality greater than being positive for P-C4d [platelet C4d] was having cancer," said Dr. Manzi, chair of the department of medicine and codirector of the Lupus Center of Excellence at West Penn Allegheny Health System, Pittsburgh.

In the study of 356 patients with systemic lupus erythematosus (SLE), which was carried out between July 2001 and August 2009, 70 tested positive for P-C4d (20%) and 286 tested negative. This confirms a previous study that found that P-C4d was present in 18% of SLE patients and that P-C4d was highly specific for SLE (Arthritis Rheum. 2006;54:670-4). "P-C4d carries a 95% specificity for SLE," said Dr. Manzi, who is also vice chair and professor of medicine at Temple University, Philadelphia.

Patients who were P-C4d positive had twice as many cardiovascular events (36 vs. 18, P = .001). The odds ratio of having a cardiovascular event was 2.09 for positive P-C4d (P = .02), which was much higher than for smoking (OR 1.36), SLE disease duration (0.99), or the presence of renal disease (1.42). The odds ratio for aPL antibodies was 2.30 (P = 0.004).

The results for stroke were even more striking. Thirteen patients with P-C4d had stroke, compared with three in those who tested negative for P-C4d (P = .002). There was nearly a fivefold increased risk of stroke in this group (OR 4.96, CI 1.75-14.06, P = .003). Almost three times as many patients had a pulmonary embolism in the P-C4d group, compared with controls (11 vs. 4, P = .007).

Fourteen SLE patients (4%) died during the follow-up. Of those, more P-C4d-positive patients died compared with those who tested negative for P-C4d (11% vs. 2%, P = .002). Causes of death included infection (4), cardiac arrest (2), congestive heart failure (1), cancer (2), hemorrhage (1), and unspecified (4). The risk of all-cause mortality was increased almost eightfold in those who were P-C4d positive (OR 7.92, CI 2.13-29.48, P = .002). Only cancer (OR 19.74) surpassed being P-C4d as a risk for all-cause mortality in multivariate regression analysis.

"Usually when we measure complement in the circulation, we measure the parent protein C4 in the plasma. When complement is activated, it breaks down into fragments and we see that one fragment, C4d, can covalently bind to cell surfaces. So, as we study how these fragments of complement activation bind to cells, we are exploring their potential use as disease biomarkers and prognostic indicators," Dr. Manzi said.

Dr. Manzi serves on the advisory boards of Bristol-Myers Squibb, Human Genome Sciences, and Cephalon. She receives funding for research from Amgen USA, Aspreva Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Genentech, Human Genome Sciences, and Immunomedics.

NEW YORK – The 18%-20% of systemic lupus erythematosus patients who test positive for platelet C4d face a much greater likelihood of having a future cardiovascular event, stroke, or death than those who are not platelet C4d positive, according to Dr. Susan M. Manzi, who presented the results at a rheumatology meeting sponsored by New York University.

"The only factor that predicted mortality greater than being positive for P-C4d [platelet C4d] was having cancer," said Dr. Manzi, chair of the department of medicine and codirector of the Lupus Center of Excellence at West Penn Allegheny Health System, Pittsburgh.

In the study of 356 patients with systemic lupus erythematosus (SLE), which was carried out between July 2001 and August 2009, 70 tested positive for P-C4d (20%) and 286 tested negative. This confirms a previous study that found that P-C4d was present in 18% of SLE patients and that P-C4d was highly specific for SLE (Arthritis Rheum. 2006;54:670-4). "P-C4d carries a 95% specificity for SLE," said Dr. Manzi, who is also vice chair and professor of medicine at Temple University, Philadelphia.

Patients who were P-C4d positive had twice as many cardiovascular events (36 vs. 18, P = .001). The odds ratio of having a cardiovascular event was 2.09 for positive P-C4d (P = .02), which was much higher than for smoking (OR 1.36), SLE disease duration (0.99), or the presence of renal disease (1.42). The odds ratio for aPL antibodies was 2.30 (P = 0.004).

The results for stroke were even more striking. Thirteen patients with P-C4d had stroke, compared with three in those who tested negative for P-C4d (P = .002). There was nearly a fivefold increased risk of stroke in this group (OR 4.96, CI 1.75-14.06, P = .003). Almost three times as many patients had a pulmonary embolism in the P-C4d group, compared with controls (11 vs. 4, P = .007).

Fourteen SLE patients (4%) died during the follow-up. Of those, more P-C4d-positive patients died compared with those who tested negative for P-C4d (11% vs. 2%, P = .002). Causes of death included infection (4), cardiac arrest (2), congestive heart failure (1), cancer (2), hemorrhage (1), and unspecified (4). The risk of all-cause mortality was increased almost eightfold in those who were P-C4d positive (OR 7.92, CI 2.13-29.48, P = .002). Only cancer (OR 19.74) surpassed being P-C4d as a risk for all-cause mortality in multivariate regression analysis.

"Usually when we measure complement in the circulation, we measure the parent protein C4 in the plasma. When complement is activated, it breaks down into fragments and we see that one fragment, C4d, can covalently bind to cell surfaces. So, as we study how these fragments of complement activation bind to cells, we are exploring their potential use as disease biomarkers and prognostic indicators," Dr. Manzi said.

Dr. Manzi serves on the advisory boards of Bristol-Myers Squibb, Human Genome Sciences, and Cephalon. She receives funding for research from Amgen USA, Aspreva Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Genentech, Human Genome Sciences, and Immunomedics.

NEW YORK – The 18%-20% of systemic lupus erythematosus patients who test positive for platelet C4d face a much greater likelihood of having a future cardiovascular event, stroke, or death than those who are not platelet C4d positive, according to Dr. Susan M. Manzi, who presented the results at a rheumatology meeting sponsored by New York University.

"The only factor that predicted mortality greater than being positive for P-C4d [platelet C4d] was having cancer," said Dr. Manzi, chair of the department of medicine and codirector of the Lupus Center of Excellence at West Penn Allegheny Health System, Pittsburgh.

In the study of 356 patients with systemic lupus erythematosus (SLE), which was carried out between July 2001 and August 2009, 70 tested positive for P-C4d (20%) and 286 tested negative. This confirms a previous study that found that P-C4d was present in 18% of SLE patients and that P-C4d was highly specific for SLE (Arthritis Rheum. 2006;54:670-4). "P-C4d carries a 95% specificity for SLE," said Dr. Manzi, who is also vice chair and professor of medicine at Temple University, Philadelphia.

Patients who were P-C4d positive had twice as many cardiovascular events (36 vs. 18, P = .001). The odds ratio of having a cardiovascular event was 2.09 for positive P-C4d (P = .02), which was much higher than for smoking (OR 1.36), SLE disease duration (0.99), or the presence of renal disease (1.42). The odds ratio for aPL antibodies was 2.30 (P = 0.004).

The results for stroke were even more striking. Thirteen patients with P-C4d had stroke, compared with three in those who tested negative for P-C4d (P = .002). There was nearly a fivefold increased risk of stroke in this group (OR 4.96, CI 1.75-14.06, P = .003). Almost three times as many patients had a pulmonary embolism in the P-C4d group, compared with controls (11 vs. 4, P = .007).

Fourteen SLE patients (4%) died during the follow-up. Of those, more P-C4d-positive patients died compared with those who tested negative for P-C4d (11% vs. 2%, P = .002). Causes of death included infection (4), cardiac arrest (2), congestive heart failure (1), cancer (2), hemorrhage (1), and unspecified (4). The risk of all-cause mortality was increased almost eightfold in those who were P-C4d positive (OR 7.92, CI 2.13-29.48, P = .002). Only cancer (OR 19.74) surpassed being P-C4d as a risk for all-cause mortality in multivariate regression analysis.

"Usually when we measure complement in the circulation, we measure the parent protein C4 in the plasma. When complement is activated, it breaks down into fragments and we see that one fragment, C4d, can covalently bind to cell surfaces. So, as we study how these fragments of complement activation bind to cells, we are exploring their potential use as disease biomarkers and prognostic indicators," Dr. Manzi said.

Dr. Manzi serves on the advisory boards of Bristol-Myers Squibb, Human Genome Sciences, and Cephalon. She receives funding for research from Amgen USA, Aspreva Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Genentech, Human Genome Sciences, and Immunomedics.

NEW YORK – The 18%-20% of systemic lupus erythematosus patients who test positive for platelet C4d face a much greater likelihood of having a future cardiovascular event, stroke, or death than those who are not platelet C4d positive, according to Dr. Susan M. Manzi, who presented the results at a rheumatology meeting sponsored by New York University.

"The only factor that predicted mortality greater than being positive for P-C4d [platelet C4d] was having cancer," said Dr. Manzi, chair of the department of medicine and codirector of the Lupus Center of Excellence at West Penn Allegheny Health System, Pittsburgh.

In the study of 356 patients with systemic lupus erythematosus (SLE), which was carried out between July 2001 and August 2009, 70 tested positive for P-C4d (20%) and 286 tested negative. This confirms a previous study that found that P-C4d was present in 18% of SLE patients and that P-C4d was highly specific for SLE (Arthritis Rheum. 2006;54:670-4). "P-C4d carries a 95% specificity for SLE," said Dr. Manzi, who is also vice chair and professor of medicine at Temple University, Philadelphia.

Patients who were P-C4d positive had twice as many cardiovascular events (36 vs. 18, P = .001). The odds ratio of having a cardiovascular event was 2.09 for positive P-C4d (P = .02), which was much higher than for smoking (OR 1.36), SLE disease duration (0.99), or the presence of renal disease (1.42). The odds ratio for aPL antibodies was 2.30 (P = 0.004).

The results for stroke were even more striking. Thirteen patients with P-C4d had stroke, compared with three in those who tested negative for P-C4d (P = .002). There was nearly a fivefold increased risk of stroke in this group (OR 4.96, CI 1.75-14.06, P = .003). Almost three times as many patients had a pulmonary embolism in the P-C4d group, compared with controls (11 vs. 4, P = .007).

Fourteen SLE patients (4%) died during the follow-up. Of those, more P-C4d-positive patients died compared with those who tested negative for P-C4d (11% vs. 2%, P = .002). Causes of death included infection (4), cardiac arrest (2), congestive heart failure (1), cancer (2), hemorrhage (1), and unspecified (4). The risk of all-cause mortality was increased almost eightfold in those who were P-C4d positive (OR 7.92, CI 2.13-29.48, P = .002). Only cancer (OR 19.74) surpassed being P-C4d as a risk for all-cause mortality in multivariate regression analysis.

"Usually when we measure complement in the circulation, we measure the parent protein C4 in the plasma. When complement is activated, it breaks down into fragments and we see that one fragment, C4d, can covalently bind to cell surfaces. So, as we study how these fragments of complement activation bind to cells, we are exploring their potential use as disease biomarkers and prognostic indicators," Dr. Manzi said.

Dr. Manzi serves on the advisory boards of Bristol-Myers Squibb, Human Genome Sciences, and Cephalon. She receives funding for research from Amgen USA, Aspreva Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Genentech, Human Genome Sciences, and Immunomedics.

NEW YORK – The 18%-20% of systemic lupus erythematosus patients who test positive for platelet C4d face a much greater likelihood of having a future cardiovascular event, stroke, or death than those who are not platelet C4d positive, according to Dr. Susan M. Manzi, who presented the results at a rheumatology meeting sponsored by New York University.

"The only factor that predicted mortality greater than being positive for P-C4d [platelet C4d] was having cancer," said Dr. Manzi, chair of the department of medicine and codirector of the Lupus Center of Excellence at West Penn Allegheny Health System, Pittsburgh.

In the study of 356 patients with systemic lupus erythematosus (SLE), which was carried out between July 2001 and August 2009, 70 tested positive for P-C4d (20%) and 286 tested negative. This confirms a previous study that found that P-C4d was present in 18% of SLE patients and that P-C4d was highly specific for SLE (Arthritis Rheum. 2006;54:670-4). "P-C4d carries a 95% specificity for SLE," said Dr. Manzi, who is also vice chair and professor of medicine at Temple University, Philadelphia.

Patients who were P-C4d positive had twice as many cardiovascular events (36 vs. 18, P = .001). The odds ratio of having a cardiovascular event was 2.09 for positive P-C4d (P = .02), which was much higher than for smoking (OR 1.36), SLE disease duration (0.99), or the presence of renal disease (1.42). The odds ratio for aPL antibodies was 2.30 (P = 0.004).

The results for stroke were even more striking. Thirteen patients with P-C4d had stroke, compared with three in those who tested negative for P-C4d (P = .002). There was nearly a fivefold increased risk of stroke in this group (OR 4.96, CI 1.75-14.06, P = .003). Almost three times as many patients had a pulmonary embolism in the P-C4d group, compared with controls (11 vs. 4, P = .007).

Fourteen SLE patients (4%) died during the follow-up. Of those, more P-C4d-positive patients died compared with those who tested negative for P-C4d (11% vs. 2%, P = .002). Causes of death included infection (4), cardiac arrest (2), congestive heart failure (1), cancer (2), hemorrhage (1), and unspecified (4). The risk of all-cause mortality was increased almost eightfold in those who were P-C4d positive (OR 7.92, CI 2.13-29.48, P = .002). Only cancer (OR 19.74) surpassed being P-C4d as a risk for all-cause mortality in multivariate regression analysis.

"Usually when we measure complement in the circulation, we measure the parent protein C4 in the plasma. When complement is activated, it breaks down into fragments and we see that one fragment, C4d, can covalently bind to cell surfaces. So, as we study how these fragments of complement activation bind to cells, we are exploring their potential use as disease biomarkers and prognostic indicators," Dr. Manzi said.

Dr. Manzi serves on the advisory boards of Bristol-Myers Squibb, Human Genome Sciences, and Cephalon. She receives funding for research from Amgen USA, Aspreva Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Genentech, Human Genome Sciences, and Immunomedics.

NEW YORK – The 18%-20% of systemic lupus erythematosus patients who test positive for platelet C4d face a much greater likelihood of having a future cardiovascular event, stroke, or death than those who are not platelet C4d positive, according to Dr. Susan M. Manzi, who presented the results at a rheumatology meeting sponsored by New York University.

"The only factor that predicted mortality greater than being positive for P-C4d [platelet C4d] was having cancer," said Dr. Manzi, chair of the department of medicine and codirector of the Lupus Center of Excellence at West Penn Allegheny Health System, Pittsburgh.

In the study of 356 patients with systemic lupus erythematosus (SLE), which was carried out between July 2001 and August 2009, 70 tested positive for P-C4d (20%) and 286 tested negative. This confirms a previous study that found that P-C4d was present in 18% of SLE patients and that P-C4d was highly specific for SLE (Arthritis Rheum. 2006;54:670-4). "P-C4d carries a 95% specificity for SLE," said Dr. Manzi, who is also vice chair and professor of medicine at Temple University, Philadelphia.

Patients who were P-C4d positive had twice as many cardiovascular events (36 vs. 18, P = .001). The odds ratio of having a cardiovascular event was 2.09 for positive P-C4d (P = .02), which was much higher than for smoking (OR 1.36), SLE disease duration (0.99), or the presence of renal disease (1.42). The odds ratio for aPL antibodies was 2.30 (P = 0.004).

The results for stroke were even more striking. Thirteen patients with P-C4d had stroke, compared with three in those who tested negative for P-C4d (P = .002). There was nearly a fivefold increased risk of stroke in this group (OR 4.96, CI 1.75-14.06, P = .003). Almost three times as many patients had a pulmonary embolism in the P-C4d group, compared with controls (11 vs. 4, P = .007).

Fourteen SLE patients (4%) died during the follow-up. Of those, more P-C4d-positive patients died compared with those who tested negative for P-C4d (11% vs. 2%, P = .002). Causes of death included infection (4), cardiac arrest (2), congestive heart failure (1), cancer (2), hemorrhage (1), and unspecified (4). The risk of all-cause mortality was increased almost eightfold in those who were P-C4d positive (OR 7.92, CI 2.13-29.48, P = .002). Only cancer (OR 19.74) surpassed being P-C4d as a risk for all-cause mortality in multivariate regression analysis.

"Usually when we measure complement in the circulation, we measure the parent protein C4 in the plasma. When complement is activated, it breaks down into fragments and we see that one fragment, C4d, can covalently bind to cell surfaces. So, as we study how these fragments of complement activation bind to cells, we are exploring their potential use as disease biomarkers and prognostic indicators," Dr. Manzi said.

Dr. Manzi serves on the advisory boards of Bristol-Myers Squibb, Human Genome Sciences, and Cephalon. She receives funding for research from Amgen USA, Aspreva Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Genentech, Human Genome Sciences, and Immunomedics.

NEW YORK – The 18%-20% of systemic lupus erythematosus patients who test positive for platelet C4d face a much greater likelihood of having a future cardiovascular event, stroke, or death than those who are not platelet C4d positive, according to Dr. Susan M. Manzi, who presented the results at a rheumatology meeting sponsored by New York University.

"The only factor that predicted mortality greater than being positive for P-C4d [platelet C4d] was having cancer," said Dr. Manzi, chair of the department of medicine and codirector of the Lupus Center of Excellence at West Penn Allegheny Health System, Pittsburgh.

In the study of 356 patients with systemic lupus erythematosus (SLE), which was carried out between July 2001 and August 2009, 70 tested positive for P-C4d (20%) and 286 tested negative. This confirms a previous study that found that P-C4d was present in 18% of SLE patients and that P-C4d was highly specific for SLE (Arthritis Rheum. 2006;54:670-4). "P-C4d carries a 95% specificity for SLE," said Dr. Manzi, who is also vice chair and professor of medicine at Temple University, Philadelphia.

Patients who were P-C4d positive had twice as many cardiovascular events (36 vs. 18, P = .001). The odds ratio of having a cardiovascular event was 2.09 for positive P-C4d (P = .02), which was much higher than for smoking (OR 1.36), SLE disease duration (0.99), or the presence of renal disease (1.42). The odds ratio for aPL antibodies was 2.30 (P = 0.004).

The results for stroke were even more striking. Thirteen patients with P-C4d had stroke, compared with three in those who tested negative for P-C4d (P = .002). There was nearly a fivefold increased risk of stroke in this group (OR 4.96, CI 1.75-14.06, P = .003). Almost three times as many patients had a pulmonary embolism in the P-C4d group, compared with controls (11 vs. 4, P = .007).

Fourteen SLE patients (4%) died during the follow-up. Of those, more P-C4d-positive patients died compared with those who tested negative for P-C4d (11% vs. 2%, P = .002). Causes of death included infection (4), cardiac arrest (2), congestive heart failure (1), cancer (2), hemorrhage (1), and unspecified (4). The risk of all-cause mortality was increased almost eightfold in those who were P-C4d positive (OR 7.92, CI 2.13-29.48, P = .002). Only cancer (OR 19.74) surpassed being P-C4d as a risk for all-cause mortality in multivariate regression analysis.

"Usually when we measure complement in the circulation, we measure the parent protein C4 in the plasma. When complement is activated, it breaks down into fragments and we see that one fragment, C4d, can covalently bind to cell surfaces. So, as we study how these fragments of complement activation bind to cells, we are exploring their potential use as disease biomarkers and prognostic indicators," Dr. Manzi said.

Dr. Manzi serves on the advisory boards of Bristol-Myers Squibb, Human Genome Sciences, and Cephalon. She receives funding for research from Amgen USA, Aspreva Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Genentech, Human Genome Sciences, and Immunomedics.

NEW YORK – The 18%-20% of systemic lupus erythematosus patients who test positive for platelet C4d face a much greater likelihood of having a future cardiovascular event, stroke, or death than those who are not platelet C4d positive, according to Dr. Susan M. Manzi, who presented the results at a rheumatology meeting sponsored by New York University.

"The only factor that predicted mortality greater than being positive for P-C4d [platelet C4d] was having cancer," said Dr. Manzi, chair of the department of medicine and codirector of the Lupus Center of Excellence at West Penn Allegheny Health System, Pittsburgh.

In the study of 356 patients with systemic lupus erythematosus (SLE), which was carried out between July 2001 and August 2009, 70 tested positive for P-C4d (20%) and 286 tested negative. This confirms a previous study that found that P-C4d was present in 18% of SLE patients and that P-C4d was highly specific for SLE (Arthritis Rheum. 2006;54:670-4). "P-C4d carries a 95% specificity for SLE," said Dr. Manzi, who is also vice chair and professor of medicine at Temple University, Philadelphia.

Patients who were P-C4d positive had twice as many cardiovascular events (36 vs. 18, P = .001). The odds ratio of having a cardiovascular event was 2.09 for positive P-C4d (P = .02), which was much higher than for smoking (OR 1.36), SLE disease duration (0.99), or the presence of renal disease (1.42). The odds ratio for aPL antibodies was 2.30 (P = 0.004).

The results for stroke were even more striking. Thirteen patients with P-C4d had stroke, compared with three in those who tested negative for P-C4d (P = .002). There was nearly a fivefold increased risk of stroke in this group (OR 4.96, CI 1.75-14.06, P = .003). Almost three times as many patients had a pulmonary embolism in the P-C4d group, compared with controls (11 vs. 4, P = .007).

Fourteen SLE patients (4%) died during the follow-up. Of those, more P-C4d-positive patients died compared with those who tested negative for P-C4d (11% vs. 2%, P = .002). Causes of death included infection (4), cardiac arrest (2), congestive heart failure (1), cancer (2), hemorrhage (1), and unspecified (4). The risk of all-cause mortality was increased almost eightfold in those who were P-C4d positive (OR 7.92, CI 2.13-29.48, P = .002). Only cancer (OR 19.74) surpassed being P-C4d as a risk for all-cause mortality in multivariate regression analysis.

"Usually when we measure complement in the circulation, we measure the parent protein C4 in the plasma. When complement is activated, it breaks down into fragments and we see that one fragment, C4d, can covalently bind to cell surfaces. So, as we study how these fragments of complement activation bind to cells, we are exploring their potential use as disease biomarkers and prognostic indicators," Dr. Manzi said.

Dr. Manzi serves on the advisory boards of Bristol-Myers Squibb, Human Genome Sciences, and Cephalon. She receives funding for research from Amgen USA, Aspreva Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Genentech, Human Genome Sciences, and Immunomedics.

NEW YORK – Because juvenile dermatomyositis is a rare disease and its symptoms often differ from those seen in adult dermatomyositis, physicians may not recognize it and diagnosis can be delayed, Dr. Brian Feldman said.

He described a recent practice survey that found variability in juvenile dermatomyositis (JDM) treatment and, in the absence of randomized controlled trials, urged clinicians to consult newly created consensus protocols developed by rheumatologists and to gather data that may help to optimize treatment and minimize side effects in the future for those with JDM.

Photo courtesy http://en.wikipedia.org/wiki/File:Dermatomyositis4.jpg

Dr. Feldman described a 15-year-old patient who had progressively deteriorated over a 3-year period despite being seen by pediatricians and dermatologists. His initial symptoms included fatigue and elevated muscle enzymes, including aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK).

Within a year, the patient developed a purple skin rash on his hands, elbows, and knees. He later developed Raynaud's syndrome and muscle weakness with decreased range of motion that interfered with participation in sports and other activities of daily living.

Upon examination, he was quite thin with a scaly rash over his knuckles (Gottron's papules), healing skin ulcerations on his hands (from severe Raynaud's), periungual erythema, and lipodystrophy and erythema of his forearms. Magnetic resonance imaging showed acute inflammation of his shoulder girdle, said Dr. Feldman, chief of pediatric rheumatology at the Hospital for Sick Children in Toronto.

Dr. Feldman said that one of the best diagnostic clues for JDM comes from microscopic examination of nail folds. In this case, the patient had tortuous, bushy nail folds, dilated or missing capillaries (capillary density of 3 per mm of nailfold length while normal ranges from 7-11 per mm), and cuticular overgrowth indicative of JDM.

The different presentation seen with children compared with adults may hinder a correct diagnosis. For instance, calcinosis is seen much more frequently in children than adults. Children are less likely to have some of the systemic symptoms, such as fever, poor weight gain, and pulmonary effects, and they almost never have cardiac problems. Unlike adults with dermatomyositis or polymyositis who appear to have a fourfold increased risk of malignancy, very few cases of malignancy have been associated with JDM. Children are more likely to experience dysphonia/dysphagia but are as likely to have arthritic symptoms (around 58% of each group). Myositis specific antibodies do not seem to play as important a diagnostic role for children as adults.

Children who develop JDM appear to have a better prognosis than adults. Although adults with myositis have appreciable mortality (about 10%) and progressive disability, which may be related to treatment of a long-term condition such as avascular necrosis or osteoporosis with compression fracture, findings from Dr. Feldman's group show that outcomes were often excellent in children. "We have not had a single death from JDM in 30 years," he said.

About two-thirds of children with JDM have a polycyclic, chronic, unremitting disease course, but about one-third follow a monocyclic course and have disease symptoms that last for 2-3 years and then go away, with, or potentially even without, treatment.

In a very small proportion of these patients, symptoms may return many years later. "The message here is that when the disease goes away, it almost certainly is gone forever," Dr. Feldman noted.

It is possible to predict which patients will follow a chronic course and which patients will have early remission. In his experience, the risk of persistent disease falls by half if Gottron's rash disappears within 3 months of diagnosis (Arthritis Rheum. 2008;58:3585-92).

The results of a recent practice survey by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) of almost 200 pediatric rheumatologists in North America found both similarities and differences in treatment approaches to JDM (J. Rheumatol. 2010;37:1953-61).

Corticosteroids and methotrexate (MTX) are mainstays of care, but the route and pattern of corticosteroid administration varied: 82% of respondents initially pulsed with high-dose intravenous methylprednisolone (IVMP) while 18% prescribed oral prednisone. MTX was used concurrently with steroids 84% of the time. Sixteen percent reported also using IV immunoglobulin, with or without MTX, for more severe disease, refractory disease, and prominent cutaneous disease. Hydroxychloroquine was given for milder cases, especially for rash, while cyclophosphamide was prescribed for ulcerative disease or for patients with pulmonary symptoms.

While these findings reflect the current prescribing practices, there are almost no randomized controlled trials of medications for JDM, Dr. Feldman pointed out.

This reflects in part the rare nature of the disease, its complexity, the difficulty of conducting studies in children, and the high cost of randomized controlled trials. There have been studies using advanced analytic techniques to provide strong comparative data in lieu of an randomized controlled trial. One such study by Dr. Feldman and associates (Arthritis Rheum. 2008;59:989-95) showed that more aggressive corticosteroid therapy does not give better 3-year outcomes.

A recent randomized controlled trial presented at the annual meeting of the American College of Rheumatology looked at dermatomyositis in 76 adults and 48 children and found that 80% had a response to rituximab within a year of treatment. Interpretation of the study may have been limited by the design, which allowed patients to receive add-on medications during the trial.

In light of the CARRA study's findings of heterogeneity in the treatment of JDM and the absence of randomized controlled trials, a group of 12 pediatric rheumatologists met to study treatments in JDM using a new approach: by developing consensus treatment protocols (Arthritis Care Res. 2010;62:219-25).

"This is similar to what has been done in pediatric oncology," said Dr. Feldman, who was one of the participants. "We are hoping physicians throughout the world will take these protocols off the shelf, and by using standardized doses, follow-up, and measurements, we will be able to accumulate enough evidence over time to know which is the best therapy."

In brief, the group recommended three protocols for the treatment of patients with moderately severe JDM: pulse IVMP plus MTX; IVMP, MTX, plus IVIG; or oral prednisone plus MTX. The third protocol is the one followed most often at the Hospital for Sick Children. The treatment protocols are not intended as treatment recommendations, although it is hoped that a physician will choose to follow the standardized protocol that most closely reflects his or her preferred practice. It is presented as a "first step to allow comparison of different approaches to the treatment of JDM," he said.

Dr. Feldman has done contracted research with Bayer Healthcare Pharmaceuticals. He referenced unlabeled/unapproved uses of drugs or products in his presentation.

NEW YORK – Because juvenile dermatomyositis is a rare disease and its symptoms often differ from those seen in adult dermatomyositis, physicians may not recognize it and diagnosis can be delayed, Dr. Brian Feldman said.

He described a recent practice survey that found variability in juvenile dermatomyositis (JDM) treatment and, in the absence of randomized controlled trials, urged clinicians to consult newly created consensus protocols developed by rheumatologists and to gather data that may help to optimize treatment and minimize side effects in the future for those with JDM.

Photo courtesy http://en.wikipedia.org/wiki/File:Dermatomyositis4.jpg

Dr. Feldman described a 15-year-old patient who had progressively deteriorated over a 3-year period despite being seen by pediatricians and dermatologists. His initial symptoms included fatigue and elevated muscle enzymes, including aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK).

Within a year, the patient developed a purple skin rash on his hands, elbows, and knees. He later developed Raynaud's syndrome and muscle weakness with decreased range of motion that interfered with participation in sports and other activities of daily living.

Upon examination, he was quite thin with a scaly rash over his knuckles (Gottron's papules), healing skin ulcerations on his hands (from severe Raynaud's), periungual erythema, and lipodystrophy and erythema of his forearms. Magnetic resonance imaging showed acute inflammation of his shoulder girdle, said Dr. Feldman, chief of pediatric rheumatology at the Hospital for Sick Children in Toronto.

Dr. Feldman said that one of the best diagnostic clues for JDM comes from microscopic examination of nail folds. In this case, the patient had tortuous, bushy nail folds, dilated or missing capillaries (capillary density of 3 per mm of nailfold length while normal ranges from 7-11 per mm), and cuticular overgrowth indicative of JDM.

The different presentation seen with children compared with adults may hinder a correct diagnosis. For instance, calcinosis is seen much more frequently in children than adults. Children are less likely to have some of the systemic symptoms, such as fever, poor weight gain, and pulmonary effects, and they almost never have cardiac problems. Unlike adults with dermatomyositis or polymyositis who appear to have a fourfold increased risk of malignancy, very few cases of malignancy have been associated with JDM. Children are more likely to experience dysphonia/dysphagia but are as likely to have arthritic symptoms (around 58% of each group). Myositis specific antibodies do not seem to play as important a diagnostic role for children as adults.

Children who develop JDM appear to have a better prognosis than adults. Although adults with myositis have appreciable mortality (about 10%) and progressive disability, which may be related to treatment of a long-term condition such as avascular necrosis or osteoporosis with compression fracture, findings from Dr. Feldman's group show that outcomes were often excellent in children. "We have not had a single death from JDM in 30 years," he said.

About two-thirds of children with JDM have a polycyclic, chronic, unremitting disease course, but about one-third follow a monocyclic course and have disease symptoms that last for 2-3 years and then go away, with, or potentially even without, treatment.

In a very small proportion of these patients, symptoms may return many years later. "The message here is that when the disease goes away, it almost certainly is gone forever," Dr. Feldman noted.

It is possible to predict which patients will follow a chronic course and which patients will have early remission. In his experience, the risk of persistent disease falls by half if Gottron's rash disappears within 3 months of diagnosis (Arthritis Rheum. 2008;58:3585-92).

The results of a recent practice survey by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) of almost 200 pediatric rheumatologists in North America found both similarities and differences in treatment approaches to JDM (J. Rheumatol. 2010;37:1953-61).

Corticosteroids and methotrexate (MTX) are mainstays of care, but the route and pattern of corticosteroid administration varied: 82% of respondents initially pulsed with high-dose intravenous methylprednisolone (IVMP) while 18% prescribed oral prednisone. MTX was used concurrently with steroids 84% of the time. Sixteen percent reported also using IV immunoglobulin, with or without MTX, for more severe disease, refractory disease, and prominent cutaneous disease. Hydroxychloroquine was given for milder cases, especially for rash, while cyclophosphamide was prescribed for ulcerative disease or for patients with pulmonary symptoms.

While these findings reflect the current prescribing practices, there are almost no randomized controlled trials of medications for JDM, Dr. Feldman pointed out.

This reflects in part the rare nature of the disease, its complexity, the difficulty of conducting studies in children, and the high cost of randomized controlled trials. There have been studies using advanced analytic techniques to provide strong comparative data in lieu of an randomized controlled trial. One such study by Dr. Feldman and associates (Arthritis Rheum. 2008;59:989-95) showed that more aggressive corticosteroid therapy does not give better 3-year outcomes.

A recent randomized controlled trial presented at the annual meeting of the American College of Rheumatology looked at dermatomyositis in 76 adults and 48 children and found that 80% had a response to rituximab within a year of treatment. Interpretation of the study may have been limited by the design, which allowed patients to receive add-on medications during the trial.

In light of the CARRA study's findings of heterogeneity in the treatment of JDM and the absence of randomized controlled trials, a group of 12 pediatric rheumatologists met to study treatments in JDM using a new approach: by developing consensus treatment protocols (Arthritis Care Res. 2010;62:219-25).

"This is similar to what has been done in pediatric oncology," said Dr. Feldman, who was one of the participants. "We are hoping physicians throughout the world will take these protocols off the shelf, and by using standardized doses, follow-up, and measurements, we will be able to accumulate enough evidence over time to know which is the best therapy."

In brief, the group recommended three protocols for the treatment of patients with moderately severe JDM: pulse IVMP plus MTX; IVMP, MTX, plus IVIG; or oral prednisone plus MTX. The third protocol is the one followed most often at the Hospital for Sick Children. The treatment protocols are not intended as treatment recommendations, although it is hoped that a physician will choose to follow the standardized protocol that most closely reflects his or her preferred practice. It is presented as a "first step to allow comparison of different approaches to the treatment of JDM," he said.

Dr. Feldman has done contracted research with Bayer Healthcare Pharmaceuticals. He referenced unlabeled/unapproved uses of drugs or products in his presentation.

NEW YORK – Because juvenile dermatomyositis is a rare disease and its symptoms often differ from those seen in adult dermatomyositis, physicians may not recognize it and diagnosis can be delayed, Dr. Brian Feldman said.

He described a recent practice survey that found variability in juvenile dermatomyositis (JDM) treatment and, in the absence of randomized controlled trials, urged clinicians to consult newly created consensus protocols developed by rheumatologists and to gather data that may help to optimize treatment and minimize side effects in the future for those with JDM.

Photo courtesy http://en.wikipedia.org/wiki/File:Dermatomyositis4.jpg

Dr. Feldman described a 15-year-old patient who had progressively deteriorated over a 3-year period despite being seen by pediatricians and dermatologists. His initial symptoms included fatigue and elevated muscle enzymes, including aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK).

Within a year, the patient developed a purple skin rash on his hands, elbows, and knees. He later developed Raynaud's syndrome and muscle weakness with decreased range of motion that interfered with participation in sports and other activities of daily living.

Upon examination, he was quite thin with a scaly rash over his knuckles (Gottron's papules), healing skin ulcerations on his hands (from severe Raynaud's), periungual erythema, and lipodystrophy and erythema of his forearms. Magnetic resonance imaging showed acute inflammation of his shoulder girdle, said Dr. Feldman, chief of pediatric rheumatology at the Hospital for Sick Children in Toronto.

Dr. Feldman said that one of the best diagnostic clues for JDM comes from microscopic examination of nail folds. In this case, the patient had tortuous, bushy nail folds, dilated or missing capillaries (capillary density of 3 per mm of nailfold length while normal ranges from 7-11 per mm), and cuticular overgrowth indicative of JDM.

The different presentation seen with children compared with adults may hinder a correct diagnosis. For instance, calcinosis is seen much more frequently in children than adults. Children are less likely to have some of the systemic symptoms, such as fever, poor weight gain, and pulmonary effects, and they almost never have cardiac problems. Unlike adults with dermatomyositis or polymyositis who appear to have a fourfold increased risk of malignancy, very few cases of malignancy have been associated with JDM. Children are more likely to experience dysphonia/dysphagia but are as likely to have arthritic symptoms (around 58% of each group). Myositis specific antibodies do not seem to play as important a diagnostic role for children as adults.

Children who develop JDM appear to have a better prognosis than adults. Although adults with myositis have appreciable mortality (about 10%) and progressive disability, which may be related to treatment of a long-term condition such as avascular necrosis or osteoporosis with compression fracture, findings from Dr. Feldman's group show that outcomes were often excellent in children. "We have not had a single death from JDM in 30 years," he said.

About two-thirds of children with JDM have a polycyclic, chronic, unremitting disease course, but about one-third follow a monocyclic course and have disease symptoms that last for 2-3 years and then go away, with, or potentially even without, treatment.

In a very small proportion of these patients, symptoms may return many years later. "The message here is that when the disease goes away, it almost certainly is gone forever," Dr. Feldman noted.

It is possible to predict which patients will follow a chronic course and which patients will have early remission. In his experience, the risk of persistent disease falls by half if Gottron's rash disappears within 3 months of diagnosis (Arthritis Rheum. 2008;58:3585-92).

The results of a recent practice survey by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) of almost 200 pediatric rheumatologists in North America found both similarities and differences in treatment approaches to JDM (J. Rheumatol. 2010;37:1953-61).

Corticosteroids and methotrexate (MTX) are mainstays of care, but the route and pattern of corticosteroid administration varied: 82% of respondents initially pulsed with high-dose intravenous methylprednisolone (IVMP) while 18% prescribed oral prednisone. MTX was used concurrently with steroids 84% of the time. Sixteen percent reported also using IV immunoglobulin, with or without MTX, for more severe disease, refractory disease, and prominent cutaneous disease. Hydroxychloroquine was given for milder cases, especially for rash, while cyclophosphamide was prescribed for ulcerative disease or for patients with pulmonary symptoms.

While these findings reflect the current prescribing practices, there are almost no randomized controlled trials of medications for JDM, Dr. Feldman pointed out.

This reflects in part the rare nature of the disease, its complexity, the difficulty of conducting studies in children, and the high cost of randomized controlled trials. There have been studies using advanced analytic techniques to provide strong comparative data in lieu of an randomized controlled trial. One such study by Dr. Feldman and associates (Arthritis Rheum. 2008;59:989-95) showed that more aggressive corticosteroid therapy does not give better 3-year outcomes.

A recent randomized controlled trial presented at the annual meeting of the American College of Rheumatology looked at dermatomyositis in 76 adults and 48 children and found that 80% had a response to rituximab within a year of treatment. Interpretation of the study may have been limited by the design, which allowed patients to receive add-on medications during the trial.

In light of the CARRA study's findings of heterogeneity in the treatment of JDM and the absence of randomized controlled trials, a group of 12 pediatric rheumatologists met to study treatments in JDM using a new approach: by developing consensus treatment protocols (Arthritis Care Res. 2010;62:219-25).

"This is similar to what has been done in pediatric oncology," said Dr. Feldman, who was one of the participants. "We are hoping physicians throughout the world will take these protocols off the shelf, and by using standardized doses, follow-up, and measurements, we will be able to accumulate enough evidence over time to know which is the best therapy."

In brief, the group recommended three protocols for the treatment of patients with moderately severe JDM: pulse IVMP plus MTX; IVMP, MTX, plus IVIG; or oral prednisone plus MTX. The third protocol is the one followed most often at the Hospital for Sick Children. The treatment protocols are not intended as treatment recommendations, although it is hoped that a physician will choose to follow the standardized protocol that most closely reflects his or her preferred practice. It is presented as a "first step to allow comparison of different approaches to the treatment of JDM," he said.

Dr. Feldman has done contracted research with Bayer Healthcare Pharmaceuticals. He referenced unlabeled/unapproved uses of drugs or products in his presentation.

Vitals: The diagnostic accuracy for spondyloarthritis was 70% when MRI is used.

Data Source: A long-term prospective follow-up of 708 patients with early, inflammatory back pain who were part of the French DESIR cohort.

Disclosures: Dr. Dougados has received grants for research projects and/or honorarium fees for participation at advisory boards/symposiums from Abbott, Bristol-Myers Squibb, Merck, Pfizer, Sanofi, and UCB.

NEW YORK – When magnetic resonance imaging is used instead of plain x-rays in patients with early inflammatory back pain, the diagnostic accuracy for spondyloarthritis jumps from 25% to 70%, according to Dr. Maxime Dougados.

“Seventy-five percent of the time, you cannot make the diagnosis with plain x-rays,” said Dr. Dougados, who is professor of rheumatology at the Paris-Descartes University/Cochin Hospital in Paris and the president-elect of EULAR. He presented the Ira Goldstein Memorial Lecture at the meeting, focusing on spondyloarthritis (SpA).

Dr. Dougados presented the as yet unpublished results from the DESIR cohort, a large French national multicenter database of long-term follow-up of 708 patients presenting with early inflammatory back pain that was initiated by the French Society of Rheumatology.

Patients were recruited between December 2007 and April 2010 if they had inflammatory back pain lasting more than 3 months and less than 3 years. The group will be followed for 10 years in the ongoing study.

At baseline, the mean age of the study population was 35 years, 54% were female and 57% were HLA-B27 positive (Joint Bone Spine 2011 March 30 [doi: 10.1016/j.jbspin.2011.01.013]).

With use of radiological sacroiliac changes, the diagnosis was “obvious” for 26% of the cohort, “doubtful” for 21%, and “normal” for 53%.

“These results indicate that at the first clinical visit, the interview is very important to pick up other clinical symptoms,” said Dr. Dougados. In fact, about 80% were found to have nonaxial clinical manifestations, including articular peripheral involvement, enthesopathy, dactylitis, anterior chest wall pain, uveitis, or psoriasis.

With MRI, 70% of the cohort were determined to have “obvious” sacroiliitis, about 20% had a “doubtful” diagnosis and about 10% were thought to be “normal.”

“These results indicate that you can detect early abnormalities of the sacroiliac joint on MRI even if x-rays are normal,” he said.

According to Dr. Dougados, these imaging findings fit well with recent results from the DECLIC study, in which 163 rheumatologists were asked to diagnose 472 patients with early inflammatory back pain, including 161 patients with spondyloarthritis, according to four different sets of criteria.

The specificity of the modified New York criteria, which relies on radiographic signs of sacroiliitis (unilateral grade III or bilateral grade II), fell well below that of the modified Amor criteria, the modified ESSG (European Spondyloarthropathy Study Group) criteria, and the ASAS (Assessment of Spondyloarthritis International Society) criteria.

The latter three criteria include the option of diagnosing sacroiliitis with MRI.

In the new classification criteria from the ASAS, separate criteria are listed for patients with axial SpA with and without peripheral manifestations and patients with peripheral manifestations only.

For axial SpA, one diagnostic pathway requires sacroiliitis on imaging plus one or more SpA feature. Sacroiliitis on MRI is given as much weight as is sacroiliitis on radiographs (Best Pract. Res. Clin. Rheumatol. 2010;24:589–604).

The other pathway requires HLA-B27 positivity plus two or more SpA features.

In patients who have peripheral manifestations only, the requirements include peripheral arthritis, enthesitis or dactylitis plus one or more spondyloarthritis features, including sacroiliitis on imaging.

Dr. Dougados also spoke about recent findings showing that patients with SpA were more likely to have distinct noninflammatory spinal MRI lesions (known as Fatty Romanus lesions) than were patients with degenerative arthritis or spinal malignancy (Ann. Rheum. Dis. 2010;69:891–94).

“As MRI is becoming more important, rheumatologists should be trained to interpret MRIs,” he said. “You don't need to be a specialist in radiology.”

Vitals

Source Elsevier Global Medical News

Vitals: The diagnostic accuracy for spondyloarthritis was 70% when MRI is used.

Data Source: A long-term prospective follow-up of 708 patients with early, inflammatory back pain who were part of the French DESIR cohort.

Disclosures: Dr. Dougados has received grants for research projects and/or honorarium fees for participation at advisory boards/symposiums from Abbott, Bristol-Myers Squibb, Merck, Pfizer, Sanofi, and UCB.

NEW YORK – When magnetic resonance imaging is used instead of plain x-rays in patients with early inflammatory back pain, the diagnostic accuracy for spondyloarthritis jumps from 25% to 70%, according to Dr. Maxime Dougados.

“Seventy-five percent of the time, you cannot make the diagnosis with plain x-rays,” said Dr. Dougados, who is professor of rheumatology at the Paris-Descartes University/Cochin Hospital in Paris and the president-elect of EULAR. He presented the Ira Goldstein Memorial Lecture at the meeting, focusing on spondyloarthritis (SpA).

Dr. Dougados presented the as yet unpublished results from the DESIR cohort, a large French national multicenter database of long-term follow-up of 708 patients presenting with early inflammatory back pain that was initiated by the French Society of Rheumatology.

Patients were recruited between December 2007 and April 2010 if they had inflammatory back pain lasting more than 3 months and less than 3 years. The group will be followed for 10 years in the ongoing study.

At baseline, the mean age of the study population was 35 years, 54% were female and 57% were HLA-B27 positive (Joint Bone Spine 2011 March 30 [doi: 10.1016/j.jbspin.2011.01.013]).

With use of radiological sacroiliac changes, the diagnosis was “obvious” for 26% of the cohort, “doubtful” for 21%, and “normal” for 53%.

“These results indicate that at the first clinical visit, the interview is very important to pick up other clinical symptoms,” said Dr. Dougados. In fact, about 80% were found to have nonaxial clinical manifestations, including articular peripheral involvement, enthesopathy, dactylitis, anterior chest wall pain, uveitis, or psoriasis.

With MRI, 70% of the cohort were determined to have “obvious” sacroiliitis, about 20% had a “doubtful” diagnosis and about 10% were thought to be “normal.”

“These results indicate that you can detect early abnormalities of the sacroiliac joint on MRI even if x-rays are normal,” he said.

According to Dr. Dougados, these imaging findings fit well with recent results from the DECLIC study, in which 163 rheumatologists were asked to diagnose 472 patients with early inflammatory back pain, including 161 patients with spondyloarthritis, according to four different sets of criteria.

The specificity of the modified New York criteria, which relies on radiographic signs of sacroiliitis (unilateral grade III or bilateral grade II), fell well below that of the modified Amor criteria, the modified ESSG (European Spondyloarthropathy Study Group) criteria, and the ASAS (Assessment of Spondyloarthritis International Society) criteria.

The latter three criteria include the option of diagnosing sacroiliitis with MRI.

In the new classification criteria from the ASAS, separate criteria are listed for patients with axial SpA with and without peripheral manifestations and patients with peripheral manifestations only.

For axial SpA, one diagnostic pathway requires sacroiliitis on imaging plus one or more SpA feature. Sacroiliitis on MRI is given as much weight as is sacroiliitis on radiographs (Best Pract. Res. Clin. Rheumatol. 2010;24:589–604).

The other pathway requires HLA-B27 positivity plus two or more SpA features.

In patients who have peripheral manifestations only, the requirements include peripheral arthritis, enthesitis or dactylitis plus one or more spondyloarthritis features, including sacroiliitis on imaging.

Dr. Dougados also spoke about recent findings showing that patients with SpA were more likely to have distinct noninflammatory spinal MRI lesions (known as Fatty Romanus lesions) than were patients with degenerative arthritis or spinal malignancy (Ann. Rheum. Dis. 2010;69:891–94).

“As MRI is becoming more important, rheumatologists should be trained to interpret MRIs,” he said. “You don't need to be a specialist in radiology.”

Vitals

Source Elsevier Global Medical News

Vitals: The diagnostic accuracy for spondyloarthritis was 70% when MRI is used.

Data Source: A long-term prospective follow-up of 708 patients with early, inflammatory back pain who were part of the French DESIR cohort.

Disclosures: Dr. Dougados has received grants for research projects and/or honorarium fees for participation at advisory boards/symposiums from Abbott, Bristol-Myers Squibb, Merck, Pfizer, Sanofi, and UCB.

NEW YORK – When magnetic resonance imaging is used instead of plain x-rays in patients with early inflammatory back pain, the diagnostic accuracy for spondyloarthritis jumps from 25% to 70%, according to Dr. Maxime Dougados.

“Seventy-five percent of the time, you cannot make the diagnosis with plain x-rays,” said Dr. Dougados, who is professor of rheumatology at the Paris-Descartes University/Cochin Hospital in Paris and the president-elect of EULAR. He presented the Ira Goldstein Memorial Lecture at the meeting, focusing on spondyloarthritis (SpA).

Dr. Dougados presented the as yet unpublished results from the DESIR cohort, a large French national multicenter database of long-term follow-up of 708 patients presenting with early inflammatory back pain that was initiated by the French Society of Rheumatology.

Patients were recruited between December 2007 and April 2010 if they had inflammatory back pain lasting more than 3 months and less than 3 years. The group will be followed for 10 years in the ongoing study.

At baseline, the mean age of the study population was 35 years, 54% were female and 57% were HLA-B27 positive (Joint Bone Spine 2011 March 30 [doi: 10.1016/j.jbspin.2011.01.013]).

With use of radiological sacroiliac changes, the diagnosis was “obvious” for 26% of the cohort, “doubtful” for 21%, and “normal” for 53%.

“These results indicate that at the first clinical visit, the interview is very important to pick up other clinical symptoms,” said Dr. Dougados. In fact, about 80% were found to have nonaxial clinical manifestations, including articular peripheral involvement, enthesopathy, dactylitis, anterior chest wall pain, uveitis, or psoriasis.

With MRI, 70% of the cohort were determined to have “obvious” sacroiliitis, about 20% had a “doubtful” diagnosis and about 10% were thought to be “normal.”

“These results indicate that you can detect early abnormalities of the sacroiliac joint on MRI even if x-rays are normal,” he said.

According to Dr. Dougados, these imaging findings fit well with recent results from the DECLIC study, in which 163 rheumatologists were asked to diagnose 472 patients with early inflammatory back pain, including 161 patients with spondyloarthritis, according to four different sets of criteria.

The specificity of the modified New York criteria, which relies on radiographic signs of sacroiliitis (unilateral grade III or bilateral grade II), fell well below that of the modified Amor criteria, the modified ESSG (European Spondyloarthropathy Study Group) criteria, and the ASAS (Assessment of Spondyloarthritis International Society) criteria.

The latter three criteria include the option of diagnosing sacroiliitis with MRI.

In the new classification criteria from the ASAS, separate criteria are listed for patients with axial SpA with and without peripheral manifestations and patients with peripheral manifestations only.

For axial SpA, one diagnostic pathway requires sacroiliitis on imaging plus one or more SpA feature. Sacroiliitis on MRI is given as much weight as is sacroiliitis on radiographs (Best Pract. Res. Clin. Rheumatol. 2010;24:589–604).

The other pathway requires HLA-B27 positivity plus two or more SpA features.

In patients who have peripheral manifestations only, the requirements include peripheral arthritis, enthesitis or dactylitis plus one or more spondyloarthritis features, including sacroiliitis on imaging.

Dr. Dougados also spoke about recent findings showing that patients with SpA were more likely to have distinct noninflammatory spinal MRI lesions (known as Fatty Romanus lesions) than were patients with degenerative arthritis or spinal malignancy (Ann. Rheum. Dis. 2010;69:891–94).

“As MRI is becoming more important, rheumatologists should be trained to interpret MRIs,” he said. “You don't need to be a specialist in radiology.”

Vitals

Source Elsevier Global Medical News