Nancy Walsh

VIENNA — Patients with psoriasis are at a higher risk for comorbidities including arthritis, heart disease, diabetes, cancer, and hypertension than is the general population, according to new data presented by Dr. Wayne P. Gulliver at the 16th Congress of the European Academy of Dermatology and Venereology.

The Newfoundland and Labra-dor Centre for Health Information database contains health records for more than 3,200 patients with psoriasis from this genetically distinct founder population.

Analysis of data from this cohort is expected to advance understanding of the genetics and pathophysiology of complex diseases such as psoriasis, said Dr. Gulliver, chairman and medical director of a medical research organization in St. John's, Nfld.

Since the 1960s, it's been known that psoriasis patients are at risk for concomitant disease, with the first associations found to be gout and sarcoidosis. Studies in Sweden during the 1980s found associations with excess rates of viral infections, alcoholism, hypertension, pneumonia, cirrhosis, urti- caria, and rheumatoid arthritis in men and women; with iritis and ankylosing spondylitis in men; and with lung cancer, diabetes, obesity, myocardial infarction, and asthma in women (Dermatologica 1986;172:298–304).

German studies showed that diabetes, obesity, hypertension, and heart failure were overrepresented in psoriasis patients (J. Am. Acad. Dermatol. 1995;32:982–6).

More recently, studies have suggested a link between psoriasis and increased rates of metabolic syndrome and hyperlipidemia—as well as a resulting increase in cardiovascular risk, Dr. Gulliver wrote in a poster.

This observation has now been confirmed in the Newfoundland and Labrador psoriasis population, with heart disease being elevated in mild to moderate and severe psoriasis patients, compared with the general population. Of 100 patients aged 50 years and older with mild to moderate psoriasis, 28% had heart disease, whereas 21% of 100 patients with severe psoriasis had heart disease; in the general population aged 30–64 years, heart disease rate was 17%.

Mortality also reflects the increased prevalence of these comorbidities, with 44.4% of the 169 reported deaths in psoriasis patients relating to cardiovascular disease, compared with 36.1% of deaths in the general population of Newfoundland and Labrador, noted Dr. Gulliver, who is also chairman of the dermatology division, Memorial University of Newfoundland, St. John's.

Moreover, psoriasis patients in this cohort died about 10 years earlier than the general population. The mean age at death in men with psoriasis was 68.8 years, whereas the national average was 77.4 years. The mean age at death for women with psoriasis was 72.7 years, compared with 82.5 years in women in the general population.

Pharmacokinetic studies are ongoing, with certain genetic markers for psoriasis having recently been identified. If further analyses can identify genetic linkages between psoriasis and comorbidities, genetic screening could be used for early recognition, Dr. Gulliver noted.

VIENNA — Patients with psoriasis are at a higher risk for comorbidities including arthritis, heart disease, diabetes, cancer, and hypertension than is the general population, according to new data presented by Dr. Wayne P. Gulliver at the 16th Congress of the European Academy of Dermatology and Venereology.

The Newfoundland and Labra-dor Centre for Health Information database contains health records for more than 3,200 patients with psoriasis from this genetically distinct founder population.

Analysis of data from this cohort is expected to advance understanding of the genetics and pathophysiology of complex diseases such as psoriasis, said Dr. Gulliver, chairman and medical director of a medical research organization in St. John's, Nfld.

Since the 1960s, it's been known that psoriasis patients are at risk for concomitant disease, with the first associations found to be gout and sarcoidosis. Studies in Sweden during the 1980s found associations with excess rates of viral infections, alcoholism, hypertension, pneumonia, cirrhosis, urti- caria, and rheumatoid arthritis in men and women; with iritis and ankylosing spondylitis in men; and with lung cancer, diabetes, obesity, myocardial infarction, and asthma in women (Dermatologica 1986;172:298–304).

German studies showed that diabetes, obesity, hypertension, and heart failure were overrepresented in psoriasis patients (J. Am. Acad. Dermatol. 1995;32:982–6).

More recently, studies have suggested a link between psoriasis and increased rates of metabolic syndrome and hyperlipidemia—as well as a resulting increase in cardiovascular risk, Dr. Gulliver wrote in a poster.

This observation has now been confirmed in the Newfoundland and Labrador psoriasis population, with heart disease being elevated in mild to moderate and severe psoriasis patients, compared with the general population. Of 100 patients aged 50 years and older with mild to moderate psoriasis, 28% had heart disease, whereas 21% of 100 patients with severe psoriasis had heart disease; in the general population aged 30–64 years, heart disease rate was 17%.

Mortality also reflects the increased prevalence of these comorbidities, with 44.4% of the 169 reported deaths in psoriasis patients relating to cardiovascular disease, compared with 36.1% of deaths in the general population of Newfoundland and Labrador, noted Dr. Gulliver, who is also chairman of the dermatology division, Memorial University of Newfoundland, St. John's.

Moreover, psoriasis patients in this cohort died about 10 years earlier than the general population. The mean age at death in men with psoriasis was 68.8 years, whereas the national average was 77.4 years. The mean age at death for women with psoriasis was 72.7 years, compared with 82.5 years in women in the general population.

Pharmacokinetic studies are ongoing, with certain genetic markers for psoriasis having recently been identified. If further analyses can identify genetic linkages between psoriasis and comorbidities, genetic screening could be used for early recognition, Dr. Gulliver noted.

VIENNA — Patients with psoriasis are at a higher risk for comorbidities including arthritis, heart disease, diabetes, cancer, and hypertension than is the general population, according to new data presented by Dr. Wayne P. Gulliver at the 16th Congress of the European Academy of Dermatology and Venereology.

The Newfoundland and Labra-dor Centre for Health Information database contains health records for more than 3,200 patients with psoriasis from this genetically distinct founder population.

Analysis of data from this cohort is expected to advance understanding of the genetics and pathophysiology of complex diseases such as psoriasis, said Dr. Gulliver, chairman and medical director of a medical research organization in St. John's, Nfld.

Since the 1960s, it's been known that psoriasis patients are at risk for concomitant disease, with the first associations found to be gout and sarcoidosis. Studies in Sweden during the 1980s found associations with excess rates of viral infections, alcoholism, hypertension, pneumonia, cirrhosis, urti- caria, and rheumatoid arthritis in men and women; with iritis and ankylosing spondylitis in men; and with lung cancer, diabetes, obesity, myocardial infarction, and asthma in women (Dermatologica 1986;172:298–304).

German studies showed that diabetes, obesity, hypertension, and heart failure were overrepresented in psoriasis patients (J. Am. Acad. Dermatol. 1995;32:982–6).

More recently, studies have suggested a link between psoriasis and increased rates of metabolic syndrome and hyperlipidemia—as well as a resulting increase in cardiovascular risk, Dr. Gulliver wrote in a poster.

This observation has now been confirmed in the Newfoundland and Labrador psoriasis population, with heart disease being elevated in mild to moderate and severe psoriasis patients, compared with the general population. Of 100 patients aged 50 years and older with mild to moderate psoriasis, 28% had heart disease, whereas 21% of 100 patients with severe psoriasis had heart disease; in the general population aged 30–64 years, heart disease rate was 17%.

Mortality also reflects the increased prevalence of these comorbidities, with 44.4% of the 169 reported deaths in psoriasis patients relating to cardiovascular disease, compared with 36.1% of deaths in the general population of Newfoundland and Labrador, noted Dr. Gulliver, who is also chairman of the dermatology division, Memorial University of Newfoundland, St. John's.

Moreover, psoriasis patients in this cohort died about 10 years earlier than the general population. The mean age at death in men with psoriasis was 68.8 years, whereas the national average was 77.4 years. The mean age at death for women with psoriasis was 72.7 years, compared with 82.5 years in women in the general population.

Pharmacokinetic studies are ongoing, with certain genetic markers for psoriasis having recently been identified. If further analyses can identify genetic linkages between psoriasis and comorbidities, genetic screening could be used for early recognition, Dr. Gulliver noted.

NEW YORK — True brittle diabetes is a rarity, with characteristic blood glucose lability, frequent hospitalizations, and life disruption often reflecting underlying psychiatric or organic disease, according to Dr. Irl B. Hirsch.

Diagnosis and management of this potentially lethal condition present significant challenges, as was shown in several cases Dr. Hirsch presented at a meeting sponsored by the American Diabetes Association.

One case involved a 23-year-old woman who presented with a 15-year history of type 1 diabetes in 2000. She had been on an insulin pump for 5 years, and her hemoglobin A_1c (HbA_1c) levels ranged from 9% to 12%. As a teenager, she had had an eating disorder and had multiple hospitalizations for diabetic ketoacidosis. In the previous 2 years, she had been hospitalized twice for gastroparesis, and had developed severe peripheral neuropathy and osteoporosis.

By 2002 she developed nonproliferative retinopathy and proteinuria. “All those years of poor control were already catching up with her at age 25,” said Dr. Hirsch, professor of medicine in the division of metabolism, endocrinology, and nutrition at the University of Washington, Seattle.

In 2004 she had an unplanned pregnancy and was hospitalized for 4 months, delivering the child 3 months prematurely. Her glucose was well controlled while she was in the hospital, but subsequently it became elevated once again, reaching 10.4%.

Finally, in the summer of 2006, she had a kidney-pancreas transplant. “So the question is, does she have brittle diabetes?” Dr. Hirsch asked.

A diagnostic work-up determined that she had underlying celiac disease, with an important clue being the osteoporosis. “When you see osteoporosis in a young person, you have to think about calcium absorption,” he said. “Celiac disease often goes hand in hand with type 1 diabetes.” These patients can have extremely irregular blood glucose patterns because their food absorption is so erratic, he added.

A further concern with these patients is that between one-third and one-half of all teenage girls with type 1 diabetes will withhold insulin at some time for weight loss. “Unfortunately, this is a very effective and dangerous way to lose weight.”

A second case involved a 30-year-old man who had nine hospitalizations during the first half of 2006 because of severe gastroparesis. The patient was eventually diagnosed with cannabis hyperemesis syndrome, a condition associated with long-term cannabis use that is characterized by cyclical episodes of vomiting in a susceptible patient.

The likely mechanism for this little-known phenomenon is a slowing of gastric emptying caused by the cannabis. “This patient does not have brittle diabetes when he's not smoking dope,” he said.

A third case involved a single, 29-year-old woman with a 20-year history of type 1 diabetes and an HbA_1c of 12% despite being on an insulin pump. She had frequent hospitalizations for pyelonephritis during the previous 10 years, although none for diabetic ketoacidosis.

“These patients are very good at taking just enough insulin to stay out of really bad ketoacidosis even though they're ketotic most of the time,” Dr. Hirsch said.

In 2001 she switched from the insulin pump to glargine and lispro, with no change in HbA_1c. She denied having depression and refused evaluation by a psychiatrist or psychologist.

In 2002 she developed mucormycosis and was hospitalized for 2 weeks and released on home intravenous antibiotics. “One week after discharge, the mother found the patient dead at home. The home antibiotics had never been opened,” he said.

Like many patients with uncontrolled or brittle diabetes, this patient had severe major depression. With no family support, she was totally incapable of taking care of the diabetes and too depressed and overwhelmed even to take the antibiotics.

It can be quite dramatic how poorly some of these patients do, Dr. Hirsch continued. In one series where 20 patients whose mean age was 19 were followed for 8 years, 2 of the patients died. In another series of 33 patients followed for a decade, 5 were lost, and of the remaining patients, 19% died from diabetic ketoacidosis, hypoglycemia, or end-stage renal disease. “What you want to do when you present cases to a group like this is talk about … how everybody lived happily ever after. That doesn't often happen with brittle diabetes.”

NEW YORK — True brittle diabetes is a rarity, with characteristic blood glucose lability, frequent hospitalizations, and life disruption often reflecting underlying psychiatric or organic disease, according to Dr. Irl B. Hirsch.

Diagnosis and management of this potentially lethal condition present significant challenges, as was shown in several cases Dr. Hirsch presented at a meeting sponsored by the American Diabetes Association.

One case involved a 23-year-old woman who presented with a 15-year history of type 1 diabetes in 2000. She had been on an insulin pump for 5 years, and her hemoglobin A_1c (HbA_1c) levels ranged from 9% to 12%. As a teenager, she had had an eating disorder and had multiple hospitalizations for diabetic ketoacidosis. In the previous 2 years, she had been hospitalized twice for gastroparesis, and had developed severe peripheral neuropathy and osteoporosis.

By 2002 she developed nonproliferative retinopathy and proteinuria. “All those years of poor control were already catching up with her at age 25,” said Dr. Hirsch, professor of medicine in the division of metabolism, endocrinology, and nutrition at the University of Washington, Seattle.

In 2004 she had an unplanned pregnancy and was hospitalized for 4 months, delivering the child 3 months prematurely. Her glucose was well controlled while she was in the hospital, but subsequently it became elevated once again, reaching 10.4%.

Finally, in the summer of 2006, she had a kidney-pancreas transplant. “So the question is, does she have brittle diabetes?” Dr. Hirsch asked.

A diagnostic work-up determined that she had underlying celiac disease, with an important clue being the osteoporosis. “When you see osteoporosis in a young person, you have to think about calcium absorption,” he said. “Celiac disease often goes hand in hand with type 1 diabetes.” These patients can have extremely irregular blood glucose patterns because their food absorption is so erratic, he added.

A further concern with these patients is that between one-third and one-half of all teenage girls with type 1 diabetes will withhold insulin at some time for weight loss. “Unfortunately, this is a very effective and dangerous way to lose weight.”

A second case involved a 30-year-old man who had nine hospitalizations during the first half of 2006 because of severe gastroparesis. The patient was eventually diagnosed with cannabis hyperemesis syndrome, a condition associated with long-term cannabis use that is characterized by cyclical episodes of vomiting in a susceptible patient.

The likely mechanism for this little-known phenomenon is a slowing of gastric emptying caused by the cannabis. “This patient does not have brittle diabetes when he's not smoking dope,” he said.

A third case involved a single, 29-year-old woman with a 20-year history of type 1 diabetes and an HbA_1c of 12% despite being on an insulin pump. She had frequent hospitalizations for pyelonephritis during the previous 10 years, although none for diabetic ketoacidosis.

“These patients are very good at taking just enough insulin to stay out of really bad ketoacidosis even though they're ketotic most of the time,” Dr. Hirsch said.

In 2001 she switched from the insulin pump to glargine and lispro, with no change in HbA_1c. She denied having depression and refused evaluation by a psychiatrist or psychologist.

In 2002 she developed mucormycosis and was hospitalized for 2 weeks and released on home intravenous antibiotics. “One week after discharge, the mother found the patient dead at home. The home antibiotics had never been opened,” he said.

Like many patients with uncontrolled or brittle diabetes, this patient had severe major depression. With no family support, she was totally incapable of taking care of the diabetes and too depressed and overwhelmed even to take the antibiotics.

It can be quite dramatic how poorly some of these patients do, Dr. Hirsch continued. In one series where 20 patients whose mean age was 19 were followed for 8 years, 2 of the patients died. In another series of 33 patients followed for a decade, 5 were lost, and of the remaining patients, 19% died from diabetic ketoacidosis, hypoglycemia, or end-stage renal disease. “What you want to do when you present cases to a group like this is talk about … how everybody lived happily ever after. That doesn't often happen with brittle diabetes.”

NEW YORK — True brittle diabetes is a rarity, with characteristic blood glucose lability, frequent hospitalizations, and life disruption often reflecting underlying psychiatric or organic disease, according to Dr. Irl B. Hirsch.

Diagnosis and management of this potentially lethal condition present significant challenges, as was shown in several cases Dr. Hirsch presented at a meeting sponsored by the American Diabetes Association.

One case involved a 23-year-old woman who presented with a 15-year history of type 1 diabetes in 2000. She had been on an insulin pump for 5 years, and her hemoglobin A_1c (HbA_1c) levels ranged from 9% to 12%. As a teenager, she had had an eating disorder and had multiple hospitalizations for diabetic ketoacidosis. In the previous 2 years, she had been hospitalized twice for gastroparesis, and had developed severe peripheral neuropathy and osteoporosis.

By 2002 she developed nonproliferative retinopathy and proteinuria. “All those years of poor control were already catching up with her at age 25,” said Dr. Hirsch, professor of medicine in the division of metabolism, endocrinology, and nutrition at the University of Washington, Seattle.

In 2004 she had an unplanned pregnancy and was hospitalized for 4 months, delivering the child 3 months prematurely. Her glucose was well controlled while she was in the hospital, but subsequently it became elevated once again, reaching 10.4%.

Finally, in the summer of 2006, she had a kidney-pancreas transplant. “So the question is, does she have brittle diabetes?” Dr. Hirsch asked.

A diagnostic work-up determined that she had underlying celiac disease, with an important clue being the osteoporosis. “When you see osteoporosis in a young person, you have to think about calcium absorption,” he said. “Celiac disease often goes hand in hand with type 1 diabetes.” These patients can have extremely irregular blood glucose patterns because their food absorption is so erratic, he added.

A further concern with these patients is that between one-third and one-half of all teenage girls with type 1 diabetes will withhold insulin at some time for weight loss. “Unfortunately, this is a very effective and dangerous way to lose weight.”

A second case involved a 30-year-old man who had nine hospitalizations during the first half of 2006 because of severe gastroparesis. The patient was eventually diagnosed with cannabis hyperemesis syndrome, a condition associated with long-term cannabis use that is characterized by cyclical episodes of vomiting in a susceptible patient.

The likely mechanism for this little-known phenomenon is a slowing of gastric emptying caused by the cannabis. “This patient does not have brittle diabetes when he's not smoking dope,” he said.

A third case involved a single, 29-year-old woman with a 20-year history of type 1 diabetes and an HbA_1c of 12% despite being on an insulin pump. She had frequent hospitalizations for pyelonephritis during the previous 10 years, although none for diabetic ketoacidosis.

“These patients are very good at taking just enough insulin to stay out of really bad ketoacidosis even though they're ketotic most of the time,” Dr. Hirsch said.

In 2001 she switched from the insulin pump to glargine and lispro, with no change in HbA_1c. She denied having depression and refused evaluation by a psychiatrist or psychologist.

In 2002 she developed mucormycosis and was hospitalized for 2 weeks and released on home intravenous antibiotics. “One week after discharge, the mother found the patient dead at home. The home antibiotics had never been opened,” he said.

Like many patients with uncontrolled or brittle diabetes, this patient had severe major depression. With no family support, she was totally incapable of taking care of the diabetes and too depressed and overwhelmed even to take the antibiotics.

It can be quite dramatic how poorly some of these patients do, Dr. Hirsch continued. In one series where 20 patients whose mean age was 19 were followed for 8 years, 2 of the patients died. In another series of 33 patients followed for a decade, 5 were lost, and of the remaining patients, 19% died from diabetic ketoacidosis, hypoglycemia, or end-stage renal disease. “What you want to do when you present cases to a group like this is talk about … how everybody lived happily ever after. That doesn't often happen with brittle diabetes.”

CHICAGO — Unilateral thyroidectomy is the procedure of choice for symptomatic benign multinodular goiter, Dr. Sarah Olson said at the annual meeting of the Central Surgical Association.

Multinodular goiter is the most common form of benign thyroid disease in the United States and is characterized by symptoms that include dysphagia and shortness of breath. The extent of surgery required—unilateral lobectomy or bilateral resection—is controversial, however, with many surgeons recommending total thyroidectomy for all patients.

“Bilateral surgery should be associated with a lower recurrence rate, but also may have potentially higher morbidity, so we undertook a retrospective analysis of data from an ongoing prospective endocrine database,” said Dr. Olson of the University of Wisconsin, Madison.

Between May 1994 and November 2004, 883 patients underwent thyroid surgery at the university. Of these, 237 patients underwent thyroidectomy for multinodular goiter, with the decision on unilateral or bilateral surgery being at the discretion of the individual surgeon. A total of 140 patients had unilateral lobectomy, with the remaining 97 undergoing total or subtotal thyroidectomy. The patients' mean age was 51 years, and 196 (83%) were female.

With up to 134 months of follow-up, patients who had unilateral resection had an 11% recurrence rate, whereas those in the bilateral group had a recurrence rate of 3%, a statistically significant difference.

The overall postoperative complication rate in the bilateral resection group was significantly higher, at 9%, compared with the unilateral group, at 2%. This difference in complication rate was in large part because of transient hypocalcemia, which was seen in 6% of the bilateral group but in none of the unilateral group, Dr. Olson said.

Of the 18 patients who subsequently required a second procedure for a recurrence of multinodular goiter, there was only one postoperative complication, for a complication rate of 5.5%. “This compares favorably with patients undergoing initial thyroidectomy,” she said.

An audience member, Dr. Christopher R. McHenry of MetroHealth Medical Center, Cleveland, said that “lobectomy is the procedure of choice for symptomatic unilateral multinodular goiter, but only when significant disease is absent in the contralateral lobe.”

Lobectomy is the procedure of choice, but only when significant disease isabsent in the contralateral lobe. DR. MCHENRY

CHICAGO — Unilateral thyroidectomy is the procedure of choice for symptomatic benign multinodular goiter, Dr. Sarah Olson said at the annual meeting of the Central Surgical Association.

Multinodular goiter is the most common form of benign thyroid disease in the United States and is characterized by symptoms that include dysphagia and shortness of breath. The extent of surgery required—unilateral lobectomy or bilateral resection—is controversial, however, with many surgeons recommending total thyroidectomy for all patients.

“Bilateral surgery should be associated with a lower recurrence rate, but also may have potentially higher morbidity, so we undertook a retrospective analysis of data from an ongoing prospective endocrine database,” said Dr. Olson of the University of Wisconsin, Madison.

Between May 1994 and November 2004, 883 patients underwent thyroid surgery at the university. Of these, 237 patients underwent thyroidectomy for multinodular goiter, with the decision on unilateral or bilateral surgery being at the discretion of the individual surgeon. A total of 140 patients had unilateral lobectomy, with the remaining 97 undergoing total or subtotal thyroidectomy. The patients' mean age was 51 years, and 196 (83%) were female.

With up to 134 months of follow-up, patients who had unilateral resection had an 11% recurrence rate, whereas those in the bilateral group had a recurrence rate of 3%, a statistically significant difference.

The overall postoperative complication rate in the bilateral resection group was significantly higher, at 9%, compared with the unilateral group, at 2%. This difference in complication rate was in large part because of transient hypocalcemia, which was seen in 6% of the bilateral group but in none of the unilateral group, Dr. Olson said.

Of the 18 patients who subsequently required a second procedure for a recurrence of multinodular goiter, there was only one postoperative complication, for a complication rate of 5.5%. “This compares favorably with patients undergoing initial thyroidectomy,” she said.

An audience member, Dr. Christopher R. McHenry of MetroHealth Medical Center, Cleveland, said that “lobectomy is the procedure of choice for symptomatic unilateral multinodular goiter, but only when significant disease is absent in the contralateral lobe.”

Lobectomy is the procedure of choice, but only when significant disease isabsent in the contralateral lobe. DR. MCHENRY

CHICAGO — Unilateral thyroidectomy is the procedure of choice for symptomatic benign multinodular goiter, Dr. Sarah Olson said at the annual meeting of the Central Surgical Association.

Multinodular goiter is the most common form of benign thyroid disease in the United States and is characterized by symptoms that include dysphagia and shortness of breath. The extent of surgery required—unilateral lobectomy or bilateral resection—is controversial, however, with many surgeons recommending total thyroidectomy for all patients.

“Bilateral surgery should be associated with a lower recurrence rate, but also may have potentially higher morbidity, so we undertook a retrospective analysis of data from an ongoing prospective endocrine database,” said Dr. Olson of the University of Wisconsin, Madison.

Between May 1994 and November 2004, 883 patients underwent thyroid surgery at the university. Of these, 237 patients underwent thyroidectomy for multinodular goiter, with the decision on unilateral or bilateral surgery being at the discretion of the individual surgeon. A total of 140 patients had unilateral lobectomy, with the remaining 97 undergoing total or subtotal thyroidectomy. The patients' mean age was 51 years, and 196 (83%) were female.

With up to 134 months of follow-up, patients who had unilateral resection had an 11% recurrence rate, whereas those in the bilateral group had a recurrence rate of 3%, a statistically significant difference.

The overall postoperative complication rate in the bilateral resection group was significantly higher, at 9%, compared with the unilateral group, at 2%. This difference in complication rate was in large part because of transient hypocalcemia, which was seen in 6% of the bilateral group but in none of the unilateral group, Dr. Olson said.

Of the 18 patients who subsequently required a second procedure for a recurrence of multinodular goiter, there was only one postoperative complication, for a complication rate of 5.5%. “This compares favorably with patients undergoing initial thyroidectomy,” she said.

An audience member, Dr. Christopher R. McHenry of MetroHealth Medical Center, Cleveland, said that “lobectomy is the procedure of choice for symptomatic unilateral multinodular goiter, but only when significant disease is absent in the contralateral lobe.”

Lobectomy is the procedure of choice, but only when significant disease isabsent in the contralateral lobe. DR. MCHENRY

NEW YORK — Any pregnant woman who has anti-Ro/La antibodies should have weekly fetal echocardiograms beginning at 16 weeks' gestation to look for possible signs of congenital heart block, Dr. Jill P. Buyon said at a rheumatology meeting sponsored by New York University.

During pregnancy these autoantibodies, typically found in high titers in patients with systemic lupus erythematosus and Sjögren's syndrome but also in some asymptomatic individuals, begin to cross the placenta as early as 11 weeks. The autoantibodies accumulate in the fetal circulation and are associated with the development of various manifestations of neonatal lupus, particularly prolongation of the mechanical PR interval and congenital atrioventricular block.

The importance of early detection of these autoantibodies in the fetus is underscored by the fact that once third-degree, or complete, heart block has developed, it is irreversible with current therapies, according to Dr. Buyon, professor of medicine, department of rheumatology, New York University, New York City.

Moreover, anti-Ro/La congenital heart block carries a 20% mortality, and at present the majority of children who survive need a pacemaker.

Intense research interest therefore is focused on identifying markers of early cardiac injury, at a point before fibrosis and scarring are permanent, and on the potential for therapeutic interventions to reverse early changes.

The use of cardiac monitoring to detect prolongations of the PR interval greater than 150 milliseconds was recently evaluated in the observational PR Interval and Dexamethasone Evaluation (PRIDE) study of pregnant women who were positive for anti-Ro and/or anti-La antibodies. The study also attempted to provide some data on outcomes following the administration of steroids.

Fetal echocardiography was performed weekly between weeks 16 and 26, and then biweekly between weeks 26 and 34, according to Dr. Buyon, one of the study investigators. She and her colleagues were looking for prolongation of the PR interval, evidence of tricuspid regurgitation, and unexplained atrial echodensities.

Among the 88 patients who completed an evaluable course, there were three cases of third-degree heart block.

One of these patients had a normal PR interval, but some tricuspid regurgitation was noted at 17 weeks and atrial echodensity, at 22 weeks. A week later the fetus was in third-degree heart block and, despite treatment with maternal dexamethasone, 4 mg/day, severe hydrops developed and the pregnancy was terminated.

The second fetus had a normal PR interval between weeks 16 and 18 along with mild tricuspid regurgitation at week 17. The mother missed an appointment and, by the next time she was seen, third-degree block had developed in the fetus. This persisted despite administration of dexamethasone, and the child continued to be followed after birth (Arthritis Rheum. 2006;54:S689).

The third fetus also had a normal PR interval at 18 weeks, but 10 days later the fetus was in third-degree block and hydropic. Treatment with dexamethasone was unsuccessful, and the pregnancy was terminated at 20.5 weeks.

First-degree block was detected in an additional three fetuses. In one, the PR was normal at weeks 16–18, was prolonged at week 19, and normalized within 7 days of dexamethasone treatment.

The second had a prolonged PR interval at week 22 that resolved within 3 days of dexamethasone treatment. These two patients both had normal electrocardiograms at birth.

The third fetus had normal PR intervals throughout gestation but an electrocardiogram at birth showed first-degree block that has persisted to age 3 years.

Dexamethasone was also used in nine cases of second-degree block. Of these, four fetuses progressed to third-degree block, four remained in second, and only one was born in normal sinus rhythm. “This was a little disappointing,” Dr. Buyon said.

Of the 79 neonates for whom birth electrocardiograms were available, 78 were normal, and all 46 for whom 1-year follow-up electrocardiograms were available were normal, she said.

In conclusion, the study suggests the following, according to Dr. Buyon:

▸ First-degree block in utero is reversible with dexamethasone, but if present at birth, close observation by a cardiologist is needed because of the possibility of later progression.

▸ There has not been evidence of conduction abnormalities developing later in neonates whose electrocardiogram was normal at birth.

▸ Advanced cardiomyopathy can occur within 7 days of a normal PR interval, so even weekly evaluation may not be sufficient.

▸ Tricuspid regurgitation may be an important early marker of injury.

Dexamethasone treatment poses significant hazards to both mother and fetus, with maternal risks including diabetes and hypertension, and fetal risks including intrauterine growth retardation, adrenal suppression, and decreased brain growth. Moreover, as was seen in PRIDE, efficacy is hardly guaranteed. Accordingly, other therapeutic approaches are being investigated, including inhibition of transforming growth factor-β to limit fibrosis and prophylaxis with intravenous immune globulin (see box).

Next: Will IVIG Prevent Heart Block?

Intravenous immune globulin (IVIG) has a history of safely being used in pregnancy, primarily for autoimmune thrombocytopenia and immune deficiency syndromes. A few cases of successful use in congenital heart block have also been reported.

To determine if this prophylactic approach could reliably decrease the placental transport of anti-SS-A/Ro and anti-SS-B/La antibodies, the Preventive IVIG Therapy for Congenital Heart Block (PITCH) trial is now enrolling patients.

Sponsored by New York University School of Medicine and the Alliance for Lupus Research, the trial aims to enroll 19 women who are antibody positive and have already had a child with congenital heart block or a rash that might have been neonatal lupus. Such mothers are at much higher risk of having another child with congenital heart block than are mothers positive for anti-Ro/La who have not already had an affected child.

Participants will be given 400 mg/kg of IVIG every 3 weeks for a total of five treatments between weeks 12 and 24 of pregnancy.

If fewer than three fetuses develop second- or third-degree heart block, another 35 women will be enrolled in the PITCHtrial.

“Then, if there are fewer than six cases of heart block out of 54, we will be on the way to having a prophylactic therapy,” said Dr. Buyon, who is principal investigator for the trial.

Information about PITCH is available at

http://clinicaltrials.gov/show/NCT00460928

NEW YORK — Any pregnant woman who has anti-Ro/La antibodies should have weekly fetal echocardiograms beginning at 16 weeks' gestation to look for possible signs of congenital heart block, Dr. Jill P. Buyon said at a rheumatology meeting sponsored by New York University.

During pregnancy these autoantibodies, typically found in high titers in patients with systemic lupus erythematosus and Sjögren's syndrome but also in some asymptomatic individuals, begin to cross the placenta as early as 11 weeks. The autoantibodies accumulate in the fetal circulation and are associated with the development of various manifestations of neonatal lupus, particularly prolongation of the mechanical PR interval and congenital atrioventricular block.

The importance of early detection of these autoantibodies in the fetus is underscored by the fact that once third-degree, or complete, heart block has developed, it is irreversible with current therapies, according to Dr. Buyon, professor of medicine, department of rheumatology, New York University, New York City.

Moreover, anti-Ro/La congenital heart block carries a 20% mortality, and at present the majority of children who survive need a pacemaker.

Intense research interest therefore is focused on identifying markers of early cardiac injury, at a point before fibrosis and scarring are permanent, and on the potential for therapeutic interventions to reverse early changes.

The use of cardiac monitoring to detect prolongations of the PR interval greater than 150 milliseconds was recently evaluated in the observational PR Interval and Dexamethasone Evaluation (PRIDE) study of pregnant women who were positive for anti-Ro and/or anti-La antibodies. The study also attempted to provide some data on outcomes following the administration of steroids.

Fetal echocardiography was performed weekly between weeks 16 and 26, and then biweekly between weeks 26 and 34, according to Dr. Buyon, one of the study investigators. She and her colleagues were looking for prolongation of the PR interval, evidence of tricuspid regurgitation, and unexplained atrial echodensities.

Among the 88 patients who completed an evaluable course, there were three cases of third-degree heart block.

One of these patients had a normal PR interval, but some tricuspid regurgitation was noted at 17 weeks and atrial echodensity, at 22 weeks. A week later the fetus was in third-degree heart block and, despite treatment with maternal dexamethasone, 4 mg/day, severe hydrops developed and the pregnancy was terminated.

The second fetus had a normal PR interval between weeks 16 and 18 along with mild tricuspid regurgitation at week 17. The mother missed an appointment and, by the next time she was seen, third-degree block had developed in the fetus. This persisted despite administration of dexamethasone, and the child continued to be followed after birth (Arthritis Rheum. 2006;54:S689).

The third fetus also had a normal PR interval at 18 weeks, but 10 days later the fetus was in third-degree block and hydropic. Treatment with dexamethasone was unsuccessful, and the pregnancy was terminated at 20.5 weeks.

First-degree block was detected in an additional three fetuses. In one, the PR was normal at weeks 16–18, was prolonged at week 19, and normalized within 7 days of dexamethasone treatment.

The second had a prolonged PR interval at week 22 that resolved within 3 days of dexamethasone treatment. These two patients both had normal electrocardiograms at birth.

The third fetus had normal PR intervals throughout gestation but an electrocardiogram at birth showed first-degree block that has persisted to age 3 years.

Dexamethasone was also used in nine cases of second-degree block. Of these, four fetuses progressed to third-degree block, four remained in second, and only one was born in normal sinus rhythm. “This was a little disappointing,” Dr. Buyon said.

Of the 79 neonates for whom birth electrocardiograms were available, 78 were normal, and all 46 for whom 1-year follow-up electrocardiograms were available were normal, she said.

In conclusion, the study suggests the following, according to Dr. Buyon:

▸ First-degree block in utero is reversible with dexamethasone, but if present at birth, close observation by a cardiologist is needed because of the possibility of later progression.

▸ There has not been evidence of conduction abnormalities developing later in neonates whose electrocardiogram was normal at birth.

▸ Advanced cardiomyopathy can occur within 7 days of a normal PR interval, so even weekly evaluation may not be sufficient.

▸ Tricuspid regurgitation may be an important early marker of injury.

Dexamethasone treatment poses significant hazards to both mother and fetus, with maternal risks including diabetes and hypertension, and fetal risks including intrauterine growth retardation, adrenal suppression, and decreased brain growth. Moreover, as was seen in PRIDE, efficacy is hardly guaranteed. Accordingly, other therapeutic approaches are being investigated, including inhibition of transforming growth factor-β to limit fibrosis and prophylaxis with intravenous immune globulin (see box).

Next: Will IVIG Prevent Heart Block?

Intravenous immune globulin (IVIG) has a history of safely being used in pregnancy, primarily for autoimmune thrombocytopenia and immune deficiency syndromes. A few cases of successful use in congenital heart block have also been reported.

To determine if this prophylactic approach could reliably decrease the placental transport of anti-SS-A/Ro and anti-SS-B/La antibodies, the Preventive IVIG Therapy for Congenital Heart Block (PITCH) trial is now enrolling patients.

Sponsored by New York University School of Medicine and the Alliance for Lupus Research, the trial aims to enroll 19 women who are antibody positive and have already had a child with congenital heart block or a rash that might have been neonatal lupus. Such mothers are at much higher risk of having another child with congenital heart block than are mothers positive for anti-Ro/La who have not already had an affected child.

Participants will be given 400 mg/kg of IVIG every 3 weeks for a total of five treatments between weeks 12 and 24 of pregnancy.

If fewer than three fetuses develop second- or third-degree heart block, another 35 women will be enrolled in the PITCHtrial.

“Then, if there are fewer than six cases of heart block out of 54, we will be on the way to having a prophylactic therapy,” said Dr. Buyon, who is principal investigator for the trial.

Information about PITCH is available at

http://clinicaltrials.gov/show/NCT00460928

NEW YORK — Any pregnant woman who has anti-Ro/La antibodies should have weekly fetal echocardiograms beginning at 16 weeks' gestation to look for possible signs of congenital heart block, Dr. Jill P. Buyon said at a rheumatology meeting sponsored by New York University.

During pregnancy these autoantibodies, typically found in high titers in patients with systemic lupus erythematosus and Sjögren's syndrome but also in some asymptomatic individuals, begin to cross the placenta as early as 11 weeks. The autoantibodies accumulate in the fetal circulation and are associated with the development of various manifestations of neonatal lupus, particularly prolongation of the mechanical PR interval and congenital atrioventricular block.

The importance of early detection of these autoantibodies in the fetus is underscored by the fact that once third-degree, or complete, heart block has developed, it is irreversible with current therapies, according to Dr. Buyon, professor of medicine, department of rheumatology, New York University, New York City.

Moreover, anti-Ro/La congenital heart block carries a 20% mortality, and at present the majority of children who survive need a pacemaker.

Intense research interest therefore is focused on identifying markers of early cardiac injury, at a point before fibrosis and scarring are permanent, and on the potential for therapeutic interventions to reverse early changes.

The use of cardiac monitoring to detect prolongations of the PR interval greater than 150 milliseconds was recently evaluated in the observational PR Interval and Dexamethasone Evaluation (PRIDE) study of pregnant women who were positive for anti-Ro and/or anti-La antibodies. The study also attempted to provide some data on outcomes following the administration of steroids.

Fetal echocardiography was performed weekly between weeks 16 and 26, and then biweekly between weeks 26 and 34, according to Dr. Buyon, one of the study investigators. She and her colleagues were looking for prolongation of the PR interval, evidence of tricuspid regurgitation, and unexplained atrial echodensities.

Among the 88 patients who completed an evaluable course, there were three cases of third-degree heart block.

One of these patients had a normal PR interval, but some tricuspid regurgitation was noted at 17 weeks and atrial echodensity, at 22 weeks. A week later the fetus was in third-degree heart block and, despite treatment with maternal dexamethasone, 4 mg/day, severe hydrops developed and the pregnancy was terminated.

The second fetus had a normal PR interval between weeks 16 and 18 along with mild tricuspid regurgitation at week 17. The mother missed an appointment and, by the next time she was seen, third-degree block had developed in the fetus. This persisted despite administration of dexamethasone, and the child continued to be followed after birth (Arthritis Rheum. 2006;54:S689).

The third fetus also had a normal PR interval at 18 weeks, but 10 days later the fetus was in third-degree block and hydropic. Treatment with dexamethasone was unsuccessful, and the pregnancy was terminated at 20.5 weeks.

First-degree block was detected in an additional three fetuses. In one, the PR was normal at weeks 16–18, was prolonged at week 19, and normalized within 7 days of dexamethasone treatment.

The second had a prolonged PR interval at week 22 that resolved within 3 days of dexamethasone treatment. These two patients both had normal electrocardiograms at birth.

The third fetus had normal PR intervals throughout gestation but an electrocardiogram at birth showed first-degree block that has persisted to age 3 years.

Dexamethasone was also used in nine cases of second-degree block. Of these, four fetuses progressed to third-degree block, four remained in second, and only one was born in normal sinus rhythm. “This was a little disappointing,” Dr. Buyon said.

Of the 79 neonates for whom birth electrocardiograms were available, 78 were normal, and all 46 for whom 1-year follow-up electrocardiograms were available were normal, she said.

In conclusion, the study suggests the following, according to Dr. Buyon:

▸ First-degree block in utero is reversible with dexamethasone, but if present at birth, close observation by a cardiologist is needed because of the possibility of later progression.

▸ There has not been evidence of conduction abnormalities developing later in neonates whose electrocardiogram was normal at birth.

▸ Advanced cardiomyopathy can occur within 7 days of a normal PR interval, so even weekly evaluation may not be sufficient.

▸ Tricuspid regurgitation may be an important early marker of injury.

Dexamethasone treatment poses significant hazards to both mother and fetus, with maternal risks including diabetes and hypertension, and fetal risks including intrauterine growth retardation, adrenal suppression, and decreased brain growth. Moreover, as was seen in PRIDE, efficacy is hardly guaranteed. Accordingly, other therapeutic approaches are being investigated, including inhibition of transforming growth factor-β to limit fibrosis and prophylaxis with intravenous immune globulin (see box).

Next: Will IVIG Prevent Heart Block?

Intravenous immune globulin (IVIG) has a history of safely being used in pregnancy, primarily for autoimmune thrombocytopenia and immune deficiency syndromes. A few cases of successful use in congenital heart block have also been reported.

To determine if this prophylactic approach could reliably decrease the placental transport of anti-SS-A/Ro and anti-SS-B/La antibodies, the Preventive IVIG Therapy for Congenital Heart Block (PITCH) trial is now enrolling patients.

Sponsored by New York University School of Medicine and the Alliance for Lupus Research, the trial aims to enroll 19 women who are antibody positive and have already had a child with congenital heart block or a rash that might have been neonatal lupus. Such mothers are at much higher risk of having another child with congenital heart block than are mothers positive for anti-Ro/La who have not already had an affected child.

Participants will be given 400 mg/kg of IVIG every 3 weeks for a total of five treatments between weeks 12 and 24 of pregnancy.

If fewer than three fetuses develop second- or third-degree heart block, another 35 women will be enrolled in the PITCHtrial.

“Then, if there are fewer than six cases of heart block out of 54, we will be on the way to having a prophylactic therapy,” said Dr. Buyon, who is principal investigator for the trial.

Information about PITCH is available at

http://clinicaltrials.gov/show/NCT00460928

MONTREAL — There is no cure for Peyronie's disease, but management can offer patients stabilization in its early phase, Dr. Laurence A. Levine said at a congress sponsored by the Canadian Society for the Study of the Aging Male.

The condition, first reported by Francois de la Peyronie in 1743, is characterized by the development of a penile plaque in the tunica albuginea of the corpora cavernosa. Deviation, shortening, and an hourglass-like shape can result. During the early inflammatory phase of the disease, patients can experience pain with erection.

Peyronie's disease is a disorder of wound healing that occurs in a genetically susceptible patient, probably in response to minor trauma, Dr. Levine said.

A proliferative fibrotic reaction results in an inelastic scar. Disturbances of collagen and elastin are seen, along with overexpression of cytokines such as transforming growth factor-β and imbalances of nitric oxide and nitric oxide synthase.

The standard treatment is surgery, but that must wait until the disease stabilizes and pain ceases. In the interim, and for patients unwilling to undergo surgery, therapies based on current thinking about pathogenesis can help.

“In a survey we did in Chicago, the most commonly used remedies were vitamin E and Potaba,” said Dr. Levine, of the department of urology at Rush Presbyterian-St. Luke's Medical Center, Chicago. Yet studies have found no benefit for vitamin E and only reduction in plaque size for the antifibrotic Potaba (aminobenzoate potassium). Colchicine, tamoxifen, and carnitine also have been found ineffective.

“The two oral agents I use are pentoxifylline and L-arginine,” he said. Pentoxifylline, given in a dose of 400 mg three times a day, is inexpensive, has low toxicity, and appears to have antifibrotic activity. L-arginine is an over-the-counter amino acid that is a precursor to nitric oxide and has been shown in vitro to have antifibrotic activity. The dosage is 500 mg twice a day.

Another approach is injection therapy. Steroids and superoxide dismutase have been tried and found to be ineffective or toxic. Studies have shown verapamil can reduce fibroblast proliferation, resulting in reduced production of collagen and other extracellular matrix macromolecules, he said at the meeting, which was cosponsored by the International Society for the Study of the Aging Male.

Uncontrolled studies have suggested up to 60% of patients can be helped with verapamil injections. “I use a multiple puncture technique with a short, five-eighths inch, 25-gauge needle.

“You don't want to use a smaller needle for fear of snapping it off in the scar,” he said. Verapamil 10 mg is mixed with 6 cc of saline to give a total volume of 10 cc, and the usual course of treatment is 12 injections at 2-week intervals.

Intralesional interferon has been used with some benefit, but “it does not appear to be as robust as what we see with verapamil,” he said.

Topical verapamil is popular. Manufacturers are making substantial claims about its efficacy, but there is no published evidence of benefit, according to Dr. Levine.

It does not penetrate into the tunica albuginea, he said.

Medical therapies also can be used in conjunction with mechanical stretching. Since studies have shown 50% of patients worsen with no treatment, it's important to treat early, Dr. Levine added.

MONTREAL — There is no cure for Peyronie's disease, but management can offer patients stabilization in its early phase, Dr. Laurence A. Levine said at a congress sponsored by the Canadian Society for the Study of the Aging Male.

The condition, first reported by Francois de la Peyronie in 1743, is characterized by the development of a penile plaque in the tunica albuginea of the corpora cavernosa. Deviation, shortening, and an hourglass-like shape can result. During the early inflammatory phase of the disease, patients can experience pain with erection.

Peyronie's disease is a disorder of wound healing that occurs in a genetically susceptible patient, probably in response to minor trauma, Dr. Levine said.

A proliferative fibrotic reaction results in an inelastic scar. Disturbances of collagen and elastin are seen, along with overexpression of cytokines such as transforming growth factor-β and imbalances of nitric oxide and nitric oxide synthase.

The standard treatment is surgery, but that must wait until the disease stabilizes and pain ceases. In the interim, and for patients unwilling to undergo surgery, therapies based on current thinking about pathogenesis can help.

“In a survey we did in Chicago, the most commonly used remedies were vitamin E and Potaba,” said Dr. Levine, of the department of urology at Rush Presbyterian-St. Luke's Medical Center, Chicago. Yet studies have found no benefit for vitamin E and only reduction in plaque size for the antifibrotic Potaba (aminobenzoate potassium). Colchicine, tamoxifen, and carnitine also have been found ineffective.

“The two oral agents I use are pentoxifylline and L-arginine,” he said. Pentoxifylline, given in a dose of 400 mg three times a day, is inexpensive, has low toxicity, and appears to have antifibrotic activity. L-arginine is an over-the-counter amino acid that is a precursor to nitric oxide and has been shown in vitro to have antifibrotic activity. The dosage is 500 mg twice a day.

Another approach is injection therapy. Steroids and superoxide dismutase have been tried and found to be ineffective or toxic. Studies have shown verapamil can reduce fibroblast proliferation, resulting in reduced production of collagen and other extracellular matrix macromolecules, he said at the meeting, which was cosponsored by the International Society for the Study of the Aging Male.

Uncontrolled studies have suggested up to 60% of patients can be helped with verapamil injections. “I use a multiple puncture technique with a short, five-eighths inch, 25-gauge needle.

“You don't want to use a smaller needle for fear of snapping it off in the scar,” he said. Verapamil 10 mg is mixed with 6 cc of saline to give a total volume of 10 cc, and the usual course of treatment is 12 injections at 2-week intervals.

Intralesional interferon has been used with some benefit, but “it does not appear to be as robust as what we see with verapamil,” he said.

Topical verapamil is popular. Manufacturers are making substantial claims about its efficacy, but there is no published evidence of benefit, according to Dr. Levine.

It does not penetrate into the tunica albuginea, he said.

Medical therapies also can be used in conjunction with mechanical stretching. Since studies have shown 50% of patients worsen with no treatment, it's important to treat early, Dr. Levine added.

MONTREAL — There is no cure for Peyronie's disease, but management can offer patients stabilization in its early phase, Dr. Laurence A. Levine said at a congress sponsored by the Canadian Society for the Study of the Aging Male.

The condition, first reported by Francois de la Peyronie in 1743, is characterized by the development of a penile plaque in the tunica albuginea of the corpora cavernosa. Deviation, shortening, and an hourglass-like shape can result. During the early inflammatory phase of the disease, patients can experience pain with erection.

Peyronie's disease is a disorder of wound healing that occurs in a genetically susceptible patient, probably in response to minor trauma, Dr. Levine said.

A proliferative fibrotic reaction results in an inelastic scar. Disturbances of collagen and elastin are seen, along with overexpression of cytokines such as transforming growth factor-β and imbalances of nitric oxide and nitric oxide synthase.

The standard treatment is surgery, but that must wait until the disease stabilizes and pain ceases. In the interim, and for patients unwilling to undergo surgery, therapies based on current thinking about pathogenesis can help.

“In a survey we did in Chicago, the most commonly used remedies were vitamin E and Potaba,” said Dr. Levine, of the department of urology at Rush Presbyterian-St. Luke's Medical Center, Chicago. Yet studies have found no benefit for vitamin E and only reduction in plaque size for the antifibrotic Potaba (aminobenzoate potassium). Colchicine, tamoxifen, and carnitine also have been found ineffective.

“The two oral agents I use are pentoxifylline and L-arginine,” he said. Pentoxifylline, given in a dose of 400 mg three times a day, is inexpensive, has low toxicity, and appears to have antifibrotic activity. L-arginine is an over-the-counter amino acid that is a precursor to nitric oxide and has been shown in vitro to have antifibrotic activity. The dosage is 500 mg twice a day.

Another approach is injection therapy. Steroids and superoxide dismutase have been tried and found to be ineffective or toxic. Studies have shown verapamil can reduce fibroblast proliferation, resulting in reduced production of collagen and other extracellular matrix macromolecules, he said at the meeting, which was cosponsored by the International Society for the Study of the Aging Male.

Uncontrolled studies have suggested up to 60% of patients can be helped with verapamil injections. “I use a multiple puncture technique with a short, five-eighths inch, 25-gauge needle.

“You don't want to use a smaller needle for fear of snapping it off in the scar,” he said. Verapamil 10 mg is mixed with 6 cc of saline to give a total volume of 10 cc, and the usual course of treatment is 12 injections at 2-week intervals.

Intralesional interferon has been used with some benefit, but “it does not appear to be as robust as what we see with verapamil,” he said.

Topical verapamil is popular. Manufacturers are making substantial claims about its efficacy, but there is no published evidence of benefit, according to Dr. Levine.

It does not penetrate into the tunica albuginea, he said.

Medical therapies also can be used in conjunction with mechanical stretching. Since studies have shown 50% of patients worsen with no treatment, it's important to treat early, Dr. Levine added.

NEW YORK — Any pregnant woman who has anti-Ro/La antibodies should have weekly fetal echocardiograms beginning at 16 weeks' gestation to look for possible signs of congenital heart block, Dr. Jill P. Buyon said at a rheumatology meeting sponsored by New York University.

During pregnancy these autoantibodies, which are typically found in high titers in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome, but also in some asymptomatic individuals, begin to cross the placenta as early as 11 weeks.

The autoantibodies accumulate in the fetal circulation and are associated with the development of various manifestations of neonatal lupus, particularly prolongation of the mechanical PR interval and congenital atrioventricular block.

The importance of early detection of these autoantibodies in the fetus is underscored by the fact that once third-degree, or complete, heart block has developed, it is irreversible with current therapies, according to Dr. Buyon, professor of medicine, department of rheumatology, New York University, New York City.

Moreover, anti-Ro/La congenital heart block carries a 20% mortality, and at present the majority of children who survive need a pacemaker.

Intense research interest therefore is focused on identifying markers of early cardiac injury, at a point before fibrosis and scarring are permanent, and on the potential for therapeutic interventions to reverse early changes.

The use of cardiac monitoring to detect prolongations of the PR interval greater than 150 milliseconds was recently evaluated in the observational PR Interval and Dexamethasone Evaluation (PRIDE) study of pregnant women who were positive for anti-Ro and/or anti-La antibodies. The study also attempted to provide some data on outcomes following the administration of steroids.

Fetal echocardiography was performed weekly between weeks 16 and 26, and then biweekly between weeks 26 and 34, according to Dr. Buyon, one of the study investigators.

She and her colleagues were looking for prolongation of the PR interval, evidence of tricuspid regurgitation, and unexplained atrial echodensities.

Among the 88 patients who completed an evaluable course, there were three cases of third-degree heart block.

One of these patients had a normal PR interval, but some tricuspid regurgitation was noted at 17 weeks and atrial echodensity, at 22 weeks.

A week later the fetus was in third-degree heart block and, despite treatment with maternal dexamethasone, 4 mg/day, severe hydrops developed and the pregnancy was terminated.

The second fetus had a normal PR interval between weeks 16 and 18 along with mild tricuspid regurgitation at week 17. The mother missed an appointment and, by the next time she was seen, third-degree block had developed in the fetus. This persisted despite administration of dexamethasone, and the child continued to be followed after birth (Arthritis Rheum. 2006;54:S689).

The third fetus also had a normal PR interval at 18 weeks, but 10 days later the fetus was in third-degree block and hydropic. Treatment with dexamethasone was unsuccessful, and the pregnancy was terminated at 20.5 weeks.

First-degree block was detected in an additional three fetuses. In one, the PR was normal at weeks 16–18, was prolonged at week 19, and normalized within 7 days of dexamethasone treatment.

The second had a prolonged PR interval at week 22 that resolved within 3 days of dexamethasone treatment. These two patients both had normal electrocardiograms at birth.

The third fetus had normal PR intervals throughout gestation but an electrocardiogram at birth showed first-degree block that has persisted to age 3 years.

Dexamethasone was also used in nine cases of second-degree block. Of these, four fetuses progressed to third-degree block, four remained in second, and one was born in normal sinus rhythm. “This was a little disappointing,” Dr. Buyon said.

Of the 79 neonates for whom birth electrocardiograms were available, 78 were normal, and all 46 for whom 1-year follow-up electrocardiograms were available were normal, she said.

In conclusion, the study suggests the following, according to Dr. Buyon:

▸ First-degree block in utero is reversible with dexamethasone, but if present at birth, close observation by a cardiologist is needed because of the possibility of later progression.

▸ There has not been evidence of conduction abnormalities developing later in neonates whose electrocardiogram was normal at birth.

▸ Advanced cardiomyopathy can occur within 7 days of a normal PR interval, so even a weekly evaluation may not always be sufficient.

▸ Tricuspid regurgitation may be an important early marker of injury.

Dexamethasone treatment poses significant hazards to both mother and fetus, with maternal risks including diabetes and hypertension, and fetal risks including intrauterine growth retardation, adrenal suppression, and decreased brain growth. Moreover, as was seen in PRIDE, efficacy is hardly guaranteed.

Accordingly, other therapeutic approaches are currently being investigated, including inhibition of transforming growth factor-β to limit fibrosis and prophylaxis with intravenous immune globulin (see box).

Next: IVIG for Heart Block Prevention?

Intravenous immune globulin (IVIG) has a history of safely being used in pregnancy, primarily for autoimmune thrombocytopenia and immune deficiency syndromes. A few cases of successful use in congenital heart block have also been reported.

To determine if this prophylactic approach could reliably decrease the placental transport of anti-Ro/SSA and anti-La/SSB antibodies, the Preventive IVIG Therapy for Congenital Heart Block (PITCH) trial is now enrolling patients. Sponsored by New York University School of Medicine and the Alliance for Lupus Research, the trial aims to enroll 19 women who are antibody positive and have already had a child with congenital heart block or a rash that might have been neonatal lupus. Such mothers are at much higher risk of having another child with congenital heart block than are mothers positive for anti-Ro/La who have not already had an affected child.

Participants will be given 400 mg/kg of IVIG every 3 weeks for a total of five treatments between weeks 12 and 24 of pregnancy. If fewer than three fetuses develop second- or third-degree heart block, another 35 women will be enrolled.

“Then, if there are fewer than six cases of heart block out of 54, we will be on the way to having a prophylactic therapy,” said Dr. Buyon, who is principal investigator for the trial.

Additional information about the PITCH trial is available online at

http://clinicaltrials.gov/show/NCT00460928

NEW YORK — Any pregnant woman who has anti-Ro/La antibodies should have weekly fetal echocardiograms beginning at 16 weeks' gestation to look for possible signs of congenital heart block, Dr. Jill P. Buyon said at a rheumatology meeting sponsored by New York University.

During pregnancy these autoantibodies, which are typically found in high titers in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome, but also in some asymptomatic individuals, begin to cross the placenta as early as 11 weeks.

The autoantibodies accumulate in the fetal circulation and are associated with the development of various manifestations of neonatal lupus, particularly prolongation of the mechanical PR interval and congenital atrioventricular block.

The importance of early detection of these autoantibodies in the fetus is underscored by the fact that once third-degree, or complete, heart block has developed, it is irreversible with current therapies, according to Dr. Buyon, professor of medicine, department of rheumatology, New York University, New York City.

Moreover, anti-Ro/La congenital heart block carries a 20% mortality, and at present the majority of children who survive need a pacemaker.

Intense research interest therefore is focused on identifying markers of early cardiac injury, at a point before fibrosis and scarring are permanent, and on the potential for therapeutic interventions to reverse early changes.

The use of cardiac monitoring to detect prolongations of the PR interval greater than 150 milliseconds was recently evaluated in the observational PR Interval and Dexamethasone Evaluation (PRIDE) study of pregnant women who were positive for anti-Ro and/or anti-La antibodies. The study also attempted to provide some data on outcomes following the administration of steroids.

Fetal echocardiography was performed weekly between weeks 16 and 26, and then biweekly between weeks 26 and 34, according to Dr. Buyon, one of the study investigators.

She and her colleagues were looking for prolongation of the PR interval, evidence of tricuspid regurgitation, and unexplained atrial echodensities.

Among the 88 patients who completed an evaluable course, there were three cases of third-degree heart block.

One of these patients had a normal PR interval, but some tricuspid regurgitation was noted at 17 weeks and atrial echodensity, at 22 weeks.

A week later the fetus was in third-degree heart block and, despite treatment with maternal dexamethasone, 4 mg/day, severe hydrops developed and the pregnancy was terminated.

The second fetus had a normal PR interval between weeks 16 and 18 along with mild tricuspid regurgitation at week 17. The mother missed an appointment and, by the next time she was seen, third-degree block had developed in the fetus. This persisted despite administration of dexamethasone, and the child continued to be followed after birth (Arthritis Rheum. 2006;54:S689).

The third fetus also had a normal PR interval at 18 weeks, but 10 days later the fetus was in third-degree block and hydropic. Treatment with dexamethasone was unsuccessful, and the pregnancy was terminated at 20.5 weeks.

First-degree block was detected in an additional three fetuses. In one, the PR was normal at weeks 16–18, was prolonged at week 19, and normalized within 7 days of dexamethasone treatment.

The second had a prolonged PR interval at week 22 that resolved within 3 days of dexamethasone treatment. These two patients both had normal electrocardiograms at birth.

The third fetus had normal PR intervals throughout gestation but an electrocardiogram at birth showed first-degree block that has persisted to age 3 years.

Dexamethasone was also used in nine cases of second-degree block. Of these, four fetuses progressed to third-degree block, four remained in second, and one was born in normal sinus rhythm. “This was a little disappointing,” Dr. Buyon said.

Of the 79 neonates for whom birth electrocardiograms were available, 78 were normal, and all 46 for whom 1-year follow-up electrocardiograms were available were normal, she said.

In conclusion, the study suggests the following, according to Dr. Buyon:

▸ First-degree block in utero is reversible with dexamethasone, but if present at birth, close observation by a cardiologist is needed because of the possibility of later progression.

▸ There has not been evidence of conduction abnormalities developing later in neonates whose electrocardiogram was normal at birth.

▸ Advanced cardiomyopathy can occur within 7 days of a normal PR interval, so even a weekly evaluation may not always be sufficient.

▸ Tricuspid regurgitation may be an important early marker of injury.

Dexamethasone treatment poses significant hazards to both mother and fetus, with maternal risks including diabetes and hypertension, and fetal risks including intrauterine growth retardation, adrenal suppression, and decreased brain growth. Moreover, as was seen in PRIDE, efficacy is hardly guaranteed.

Accordingly, other therapeutic approaches are currently being investigated, including inhibition of transforming growth factor-β to limit fibrosis and prophylaxis with intravenous immune globulin (see box).

Next: IVIG for Heart Block Prevention?

Intravenous immune globulin (IVIG) has a history of safely being used in pregnancy, primarily for autoimmune thrombocytopenia and immune deficiency syndromes. A few cases of successful use in congenital heart block have also been reported.

To determine if this prophylactic approach could reliably decrease the placental transport of anti-Ro/SSA and anti-La/SSB antibodies, the Preventive IVIG Therapy for Congenital Heart Block (PITCH) trial is now enrolling patients. Sponsored by New York University School of Medicine and the Alliance for Lupus Research, the trial aims to enroll 19 women who are antibody positive and have already had a child with congenital heart block or a rash that might have been neonatal lupus. Such mothers are at much higher risk of having another child with congenital heart block than are mothers positive for anti-Ro/La who have not already had an affected child.

Participants will be given 400 mg/kg of IVIG every 3 weeks for a total of five treatments between weeks 12 and 24 of pregnancy. If fewer than three fetuses develop second- or third-degree heart block, another 35 women will be enrolled.

“Then, if there are fewer than six cases of heart block out of 54, we will be on the way to having a prophylactic therapy,” said Dr. Buyon, who is principal investigator for the trial.

Additional information about the PITCH trial is available online at

http://clinicaltrials.gov/show/NCT00460928

NEW YORK — Any pregnant woman who has anti-Ro/La antibodies should have weekly fetal echocardiograms beginning at 16 weeks' gestation to look for possible signs of congenital heart block, Dr. Jill P. Buyon said at a rheumatology meeting sponsored by New York University.

During pregnancy these autoantibodies, which are typically found in high titers in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome, but also in some asymptomatic individuals, begin to cross the placenta as early as 11 weeks.

The autoantibodies accumulate in the fetal circulation and are associated with the development of various manifestations of neonatal lupus, particularly prolongation of the mechanical PR interval and congenital atrioventricular block.

The importance of early detection of these autoantibodies in the fetus is underscored by the fact that once third-degree, or complete, heart block has developed, it is irreversible with current therapies, according to Dr. Buyon, professor of medicine, department of rheumatology, New York University, New York City.

Moreover, anti-Ro/La congenital heart block carries a 20% mortality, and at present the majority of children who survive need a pacemaker.

Intense research interest therefore is focused on identifying markers of early cardiac injury, at a point before fibrosis and scarring are permanent, and on the potential for therapeutic interventions to reverse early changes.

The use of cardiac monitoring to detect prolongations of the PR interval greater than 150 milliseconds was recently evaluated in the observational PR Interval and Dexamethasone Evaluation (PRIDE) study of pregnant women who were positive for anti-Ro and/or anti-La antibodies. The study also attempted to provide some data on outcomes following the administration of steroids.

Fetal echocardiography was performed weekly between weeks 16 and 26, and then biweekly between weeks 26 and 34, according to Dr. Buyon, one of the study investigators.

She and her colleagues were looking for prolongation of the PR interval, evidence of tricuspid regurgitation, and unexplained atrial echodensities.

Among the 88 patients who completed an evaluable course, there were three cases of third-degree heart block.

One of these patients had a normal PR interval, but some tricuspid regurgitation was noted at 17 weeks and atrial echodensity, at 22 weeks.

A week later the fetus was in third-degree heart block and, despite treatment with maternal dexamethasone, 4 mg/day, severe hydrops developed and the pregnancy was terminated.

The second fetus had a normal PR interval between weeks 16 and 18 along with mild tricuspid regurgitation at week 17. The mother missed an appointment and, by the next time she was seen, third-degree block had developed in the fetus. This persisted despite administration of dexamethasone, and the child continued to be followed after birth (Arthritis Rheum. 2006;54:S689).

The third fetus also had a normal PR interval at 18 weeks, but 10 days later the fetus was in third-degree block and hydropic. Treatment with dexamethasone was unsuccessful, and the pregnancy was terminated at 20.5 weeks.

First-degree block was detected in an additional three fetuses. In one, the PR was normal at weeks 16–18, was prolonged at week 19, and normalized within 7 days of dexamethasone treatment.

The second had a prolonged PR interval at week 22 that resolved within 3 days of dexamethasone treatment. These two patients both had normal electrocardiograms at birth.

The third fetus had normal PR intervals throughout gestation but an electrocardiogram at birth showed first-degree block that has persisted to age 3 years.

Dexamethasone was also used in nine cases of second-degree block. Of these, four fetuses progressed to third-degree block, four remained in second, and one was born in normal sinus rhythm. “This was a little disappointing,” Dr. Buyon said.

Of the 79 neonates for whom birth electrocardiograms were available, 78 were normal, and all 46 for whom 1-year follow-up electrocardiograms were available were normal, she said.

In conclusion, the study suggests the following, according to Dr. Buyon:

▸ First-degree block in utero is reversible with dexamethasone, but if present at birth, close observation by a cardiologist is needed because of the possibility of later progression.

▸ There has not been evidence of conduction abnormalities developing later in neonates whose electrocardiogram was normal at birth.

▸ Advanced cardiomyopathy can occur within 7 days of a normal PR interval, so even a weekly evaluation may not always be sufficient.

▸ Tricuspid regurgitation may be an important early marker of injury.

Dexamethasone treatment poses significant hazards to both mother and fetus, with maternal risks including diabetes and hypertension, and fetal risks including intrauterine growth retardation, adrenal suppression, and decreased brain growth. Moreover, as was seen in PRIDE, efficacy is hardly guaranteed.

Accordingly, other therapeutic approaches are currently being investigated, including inhibition of transforming growth factor-β to limit fibrosis and prophylaxis with intravenous immune globulin (see box).

Next: IVIG for Heart Block Prevention?

Intravenous immune globulin (IVIG) has a history of safely being used in pregnancy, primarily for autoimmune thrombocytopenia and immune deficiency syndromes. A few cases of successful use in congenital heart block have also been reported.

To determine if this prophylactic approach could reliably decrease the placental transport of anti-Ro/SSA and anti-La/SSB antibodies, the Preventive IVIG Therapy for Congenital Heart Block (PITCH) trial is now enrolling patients. Sponsored by New York University School of Medicine and the Alliance for Lupus Research, the trial aims to enroll 19 women who are antibody positive and have already had a child with congenital heart block or a rash that might have been neonatal lupus. Such mothers are at much higher risk of having another child with congenital heart block than are mothers positive for anti-Ro/La who have not already had an affected child.

Participants will be given 400 mg/kg of IVIG every 3 weeks for a total of five treatments between weeks 12 and 24 of pregnancy. If fewer than three fetuses develop second- or third-degree heart block, another 35 women will be enrolled.

“Then, if there are fewer than six cases of heart block out of 54, we will be on the way to having a prophylactic therapy,” said Dr. Buyon, who is principal investigator for the trial.

Additional information about the PITCH trial is available online at

http://clinicaltrials.gov/show/NCT00460928

For the first time, systemic arterial stiffening has been linked with left ventricular hypertrophy and dysfunction in patients with pediatric-onset lupus, according to Dr. Pak-Cheong Chow and colleagues from the department of paediatrics and adolescent medicine of the University of Hong Kong.

An increase in carotid arterial stiffness was previously observed among patients with adult-onset systemic lupus erythematosus (SLE), but these older patients typically also have premature atherosclerosis, hypertension, dyslipidemia, and other potentially confounding factors.

Systemic arterial stiffness has been documented in children with other vasculitic diseases, such as polyarteritis nodosa, but arterial function in young SLE patients has not been studied, the investigators said.

In order to investigate this aspect of pediatric-onset lupus, they studied 32 patients and 15 controls, performing pulsed-wave Doppler and standard M-mode echocardiography, tissue Doppler imaging, and imaging of the right and left common carotid arteries.

Mean age at diagnosis was 11.7 years, mean disease duration was 6.3 years, and mean systemic lupus erythematosus disease activity index (SLEDAI) was 4. A total of 21 patients had nephritis, 11 had antiphospholipid antibodies, and two had antiphospholipid syndrome. At the time of the study, 28 patients were receiving prednisone, with a mean daily dose of 5.4 mg.

Echocardiographic findings among the lupus group included thicker interventricular septum, thicker left ventricular (LV) posterior wall, greater indexed LV mass, and lower LV fractional shortening and ejection fraction compared with controls.

They also showed reductions in LV free wall systolic strain and strain rate, as well as a lower mitral annular systolic velocity, findings that are indicative of LV systolic dysfunction. Patients also had significantly lower E wave velocity, E deceleration time, E/A ratio, and diastolic strain rates, suggesting LV diastolic dysfunction relating to impaired relaxation.

In addition, the average carotid arterial stiffness index was significantly greater among the lupus patients, and on univariate analysis, this index correlated significantly with SLEDAI, albeit not with age, body mass, diastolic blood pressure, damage index, daily prednisone dosage, or duration of disease. On multiple linear regression analysis, SLEDAI and systolic blood pressure remained significantly correlated with carotid stiffness index after adjustment for these variables.

With regard to the relation between arterial stiffness and LV structure and function, the average carotid arterial stiffness index correlated positively with LV posterior wall thickness, interventricular septal thickness, indexed LV mass, and myocardial performance index. Negative correlations were seen with E wave velocity, em velocity, or strain rates.

Multiple regression analysis determined carotid arterial stiffness was a significant determinant of indexed LV mass, em velocity, and left ventricular strain rate after adjustment for age, sex, body mass index, and blood pressure.

“Our study provides the first evidence that systemic arterial stiffening is associated with LV hypertrophy and dysfunction in a young cohort of patients with pediatric-onset SLE,” wrote the authors (J. Rheumatol. 2007;34 [Epub ahead of print]).

The study also found that arterial stiffness correlated with the disease activity score and was an independent determinant of LV mass and function.

The authors noted arterial stiffening in SLE likely links to immune complex-induced complement activation and inflammatory cell infiltration in the arterial wall. Longitudinal studies are needed to see if reducing stiffness and improving ventricular function reduce the risk of early cardiovascular disease in these patients.

For the first time, systemic arterial stiffening has been linked with left ventricular hypertrophy and dysfunction in patients with pediatric-onset lupus, according to Dr. Pak-Cheong Chow and colleagues from the department of paediatrics and adolescent medicine of the University of Hong Kong.

An increase in carotid arterial stiffness was previously observed among patients with adult-onset systemic lupus erythematosus (SLE), but these older patients typically also have premature atherosclerosis, hypertension, dyslipidemia, and other potentially confounding factors.

Systemic arterial stiffness has been documented in children with other vasculitic diseases, such as polyarteritis nodosa, but arterial function in young SLE patients has not been studied, the investigators said.

In order to investigate this aspect of pediatric-onset lupus, they studied 32 patients and 15 controls, performing pulsed-wave Doppler and standard M-mode echocardiography, tissue Doppler imaging, and imaging of the right and left common carotid arteries.

Mean age at diagnosis was 11.7 years, mean disease duration was 6.3 years, and mean systemic lupus erythematosus disease activity index (SLEDAI) was 4. A total of 21 patients had nephritis, 11 had antiphospholipid antibodies, and two had antiphospholipid syndrome. At the time of the study, 28 patients were receiving prednisone, with a mean daily dose of 5.4 mg.

Echocardiographic findings among the lupus group included thicker interventricular septum, thicker left ventricular (LV) posterior wall, greater indexed LV mass, and lower LV fractional shortening and ejection fraction compared with controls.

They also showed reductions in LV free wall systolic strain and strain rate, as well as a lower mitral annular systolic velocity, findings that are indicative of LV systolic dysfunction. Patients also had significantly lower E wave velocity, E deceleration time, E/A ratio, and diastolic strain rates, suggesting LV diastolic dysfunction relating to impaired relaxation.

In addition, the average carotid arterial stiffness index was significantly greater among the lupus patients, and on univariate analysis, this index correlated significantly with SLEDAI, albeit not with age, body mass, diastolic blood pressure, damage index, daily prednisone dosage, or duration of disease. On multiple linear regression analysis, SLEDAI and systolic blood pressure remained significantly correlated with carotid stiffness index after adjustment for these variables.

With regard to the relation between arterial stiffness and LV structure and function, the average carotid arterial stiffness index correlated positively with LV posterior wall thickness, interventricular septal thickness, indexed LV mass, and myocardial performance index. Negative correlations were seen with E wave velocity, em velocity, or strain rates.

Multiple regression analysis determined carotid arterial stiffness was a significant determinant of indexed LV mass, em velocity, and left ventricular strain rate after adjustment for age, sex, body mass index, and blood pressure.

“Our study provides the first evidence that systemic arterial stiffening is associated with LV hypertrophy and dysfunction in a young cohort of patients with pediatric-onset SLE,” wrote the authors (J. Rheumatol. 2007;34 [Epub ahead of print]).

The study also found that arterial stiffness correlated with the disease activity score and was an independent determinant of LV mass and function.

The authors noted arterial stiffening in SLE likely links to immune complex-induced complement activation and inflammatory cell infiltration in the arterial wall. Longitudinal studies are needed to see if reducing stiffness and improving ventricular function reduce the risk of early cardiovascular disease in these patients.

For the first time, systemic arterial stiffening has been linked with left ventricular hypertrophy and dysfunction in patients with pediatric-onset lupus, according to Dr. Pak-Cheong Chow and colleagues from the department of paediatrics and adolescent medicine of the University of Hong Kong.

An increase in carotid arterial stiffness was previously observed among patients with adult-onset systemic lupus erythematosus (SLE), but these older patients typically also have premature atherosclerosis, hypertension, dyslipidemia, and other potentially confounding factors.

Systemic arterial stiffness has been documented in children with other vasculitic diseases, such as polyarteritis nodosa, but arterial function in young SLE patients has not been studied, the investigators said.

In order to investigate this aspect of pediatric-onset lupus, they studied 32 patients and 15 controls, performing pulsed-wave Doppler and standard M-mode echocardiography, tissue Doppler imaging, and imaging of the right and left common carotid arteries.

Mean age at diagnosis was 11.7 years, mean disease duration was 6.3 years, and mean systemic lupus erythematosus disease activity index (SLEDAI) was 4. A total of 21 patients had nephritis, 11 had antiphospholipid antibodies, and two had antiphospholipid syndrome. At the time of the study, 28 patients were receiving prednisone, with a mean daily dose of 5.4 mg.

Echocardiographic findings among the lupus group included thicker interventricular septum, thicker left ventricular (LV) posterior wall, greater indexed LV mass, and lower LV fractional shortening and ejection fraction compared with controls.

They also showed reductions in LV free wall systolic strain and strain rate, as well as a lower mitral annular systolic velocity, findings that are indicative of LV systolic dysfunction. Patients also had significantly lower E wave velocity, E deceleration time, E/A ratio, and diastolic strain rates, suggesting LV diastolic dysfunction relating to impaired relaxation.

In addition, the average carotid arterial stiffness index was significantly greater among the lupus patients, and on univariate analysis, this index correlated significantly with SLEDAI, albeit not with age, body mass, diastolic blood pressure, damage index, daily prednisone dosage, or duration of disease. On multiple linear regression analysis, SLEDAI and systolic blood pressure remained significantly correlated with carotid stiffness index after adjustment for these variables.

With regard to the relation between arterial stiffness and LV structure and function, the average carotid arterial stiffness index correlated positively with LV posterior wall thickness, interventricular septal thickness, indexed LV mass, and myocardial performance index. Negative correlations were seen with E wave velocity, em velocity, or strain rates.

Multiple regression analysis determined carotid arterial stiffness was a significant determinant of indexed LV mass, em velocity, and left ventricular strain rate after adjustment for age, sex, body mass index, and blood pressure.

“Our study provides the first evidence that systemic arterial stiffening is associated with LV hypertrophy and dysfunction in a young cohort of patients with pediatric-onset SLE,” wrote the authors (J. Rheumatol. 2007;34 [Epub ahead of print]).

The study also found that arterial stiffness correlated with the disease activity score and was an independent determinant of LV mass and function.

The authors noted arterial stiffening in SLE likely links to immune complex-induced complement activation and inflammatory cell infiltration in the arterial wall. Longitudinal studies are needed to see if reducing stiffness and improving ventricular function reduce the risk of early cardiovascular disease in these patients.

NEW YORK — Don't feel guilty about overdiagnosing and overtreating Kawasaki disease, Dr. Jeffrey R. Starke said at a meeting sponsored by the American College of Emergency Physicians.

“If you look at the risk-benefit ratio of treatment versus the complications if we don't treat, it's clear we should err on the side of overtreatment, especially in children younger than 12 months who are at high risk for developing severe coronary artery abnormalities,” Dr. Starke said.

These youngest patients also are more likely to present with incomplete Kawasaki disease. This diagnosis should be considered in infants under 6 months with fever for longer than 6 days and unexplained systemic inflammation. An incomplete Kawasaki diseasediagnosis also should be considered in children with fever for over 5 days and two or three, rather than four, of the features of Kawasaki disease (see box).

In such a patient, if the C-reactive protein is 3 mg/dL or greater and/or the erythrocyte sedimentation rate is 40 mm/hour or more, supplemental laboratory criteria should be obtained. If three or more are present, the child should have an echocardiogram and treatment should begin.

If there are fewer than three of the laboratory criteria, an echocardiogram is needed. If the echo shows cardiac abnormalities, treat. If it is negative and the fever abates, disease is unlikely. If fever persists, repeat the echo, said Dr. Starke, vice chairman of pediatrics at Baylor College of Medicine, Houston.

Standard treatment with intravenous immunoglobulin (IVIG), 2 g/kg as a single infusion is quite safe, though expensive, which is another reason to err on the side of treatment. On occasion, treatment can begin before an echocardiogram. Aspirin is routinely given, though a recent review found insufficient evidence supporting this practice (Cochrane Database Syst. Rev. 2006;doi:10.1002/14651858.CD004175.pub2). High doses of 80–100 mg/kg per day should be given initially.

Some continue the high dose for 14 days and then reduce the dose to 3–5 mg/kg per day, while others maintain the high dose only until 24–48 hours after the patient defervesces, and then switch to the low dose for 2 months for antiplatelet effects.

“I don't know of a single infectious disease expert or rheumatologist who doesn't still use aspirin in addition to IVIG in the treatment of Kawasaki disease,” Dr. Starke said.

Some data suggest some benefit of adding corticosteroids to treatment. In a recent prospective randomized trial of 178 Kawasaki patients, children on prednisolone with IVIG had a shorter duration of fever and a faster fall in C-reactive protein, but no difference in coronary artery dilation at 1 month (J. Pediatr. 2006;149:336–41).

If the fever persists or returns more than 36 hours after completion of the IVIG infusion, a second dose can be given.

“But be patient. It's very common for kids to continue to run a fever the day after you give the IVIG dose, even as other symptoms are improving,” he said.

Clinical Diagnostic Features of Kawasaki Disease

Diagnostic Criteria

Fever greater than 39 degrees C for 5 days, plus four of the following:

Conjunctivitis, usually bulbar and bilateral

Mucus membrane changes such as redness and cracking

Rash, either generalized or local

Enlarged cervical lymph nodes, usually unilateral and nontender

Peripheral changes such as swelling or peeling

Incomplete Kawasaki Supplemental Laboratory Criteria

Albumin 3 g/dL or less

Anemia for age

Elevation of alanine aminotransferase

Platelets 450,000/mm

While blood cell count 15,000/mm

Urine white blood cell count 10/HPF or more

Sources: Dr. Starke; Circulation 2004;110:2747–71.

NEW YORK — Don't feel guilty about overdiagnosing and overtreating Kawasaki disease, Dr. Jeffrey R. Starke said at a meeting sponsored by the American College of Emergency Physicians.

“If you look at the risk-benefit ratio of treatment versus the complications if we don't treat, it's clear we should err on the side of overtreatment, especially in children younger than 12 months who are at high risk for developing severe coronary artery abnormalities,” Dr. Starke said.

These youngest patients also are more likely to present with incomplete Kawasaki disease. This diagnosis should be considered in infants under 6 months with fever for longer than 6 days and unexplained systemic inflammation. An incomplete Kawasaki diseasediagnosis also should be considered in children with fever for over 5 days and two or three, rather than four, of the features of Kawasaki disease (see box).

In such a patient, if the C-reactive protein is 3 mg/dL or greater and/or the erythrocyte sedimentation rate is 40 mm/hour or more, supplemental laboratory criteria should be obtained. If three or more are present, the child should have an echocardiogram and treatment should begin.

If there are fewer than three of the laboratory criteria, an echocardiogram is needed. If the echo shows cardiac abnormalities, treat. If it is negative and the fever abates, disease is unlikely. If fever persists, repeat the echo, said Dr. Starke, vice chairman of pediatrics at Baylor College of Medicine, Houston.

Standard treatment with intravenous immunoglobulin (IVIG), 2 g/kg as a single infusion is quite safe, though expensive, which is another reason to err on the side of treatment. On occasion, treatment can begin before an echocardiogram. Aspirin is routinely given, though a recent review found insufficient evidence supporting this practice (Cochrane Database Syst. Rev. 2006;doi:10.1002/14651858.CD004175.pub2). High doses of 80–100 mg/kg per day should be given initially.

Some continue the high dose for 14 days and then reduce the dose to 3–5 mg/kg per day, while others maintain the high dose only until 24–48 hours after the patient defervesces, and then switch to the low dose for 2 months for antiplatelet effects.

“I don't know of a single infectious disease expert or rheumatologist who doesn't still use aspirin in addition to IVIG in the treatment of Kawasaki disease,” Dr. Starke said.

Some data suggest some benefit of adding corticosteroids to treatment. In a recent prospective randomized trial of 178 Kawasaki patients, children on prednisolone with IVIG had a shorter duration of fever and a faster fall in C-reactive protein, but no difference in coronary artery dilation at 1 month (J. Pediatr. 2006;149:336–41).

If the fever persists or returns more than 36 hours after completion of the IVIG infusion, a second dose can be given.

“But be patient. It's very common for kids to continue to run a fever the day after you give the IVIG dose, even as other symptoms are improving,” he said.

Clinical Diagnostic Features of Kawasaki Disease

Diagnostic Criteria

Fever greater than 39 degrees C for 5 days, plus four of the following:

Conjunctivitis, usually bulbar and bilateral

Mucus membrane changes such as redness and cracking

Rash, either generalized or local

Enlarged cervical lymph nodes, usually unilateral and nontender

Peripheral changes such as swelling or peeling

Incomplete Kawasaki Supplemental Laboratory Criteria

Albumin 3 g/dL or less

Anemia for age

Elevation of alanine aminotransferase

Platelets 450,000/mm

While blood cell count 15,000/mm

Urine white blood cell count 10/HPF or more

Sources: Dr. Starke; Circulation 2004;110:2747–71.

NEW YORK — Don't feel guilty about overdiagnosing and overtreating Kawasaki disease, Dr. Jeffrey R. Starke said at a meeting sponsored by the American College of Emergency Physicians.

“If you look at the risk-benefit ratio of treatment versus the complications if we don't treat, it's clear we should err on the side of overtreatment, especially in children younger than 12 months who are at high risk for developing severe coronary artery abnormalities,” Dr. Starke said.

These youngest patients also are more likely to present with incomplete Kawasaki disease. This diagnosis should be considered in infants under 6 months with fever for longer than 6 days and unexplained systemic inflammation. An incomplete Kawasaki diseasediagnosis also should be considered in children with fever for over 5 days and two or three, rather than four, of the features of Kawasaki disease (see box).

In such a patient, if the C-reactive protein is 3 mg/dL or greater and/or the erythrocyte sedimentation rate is 40 mm/hour or more, supplemental laboratory criteria should be obtained. If three or more are present, the child should have an echocardiogram and treatment should begin.

If there are fewer than three of the laboratory criteria, an echocardiogram is needed. If the echo shows cardiac abnormalities, treat. If it is negative and the fever abates, disease is unlikely. If fever persists, repeat the echo, said Dr. Starke, vice chairman of pediatrics at Baylor College of Medicine, Houston.

Standard treatment with intravenous immunoglobulin (IVIG), 2 g/kg as a single infusion is quite safe, though expensive, which is another reason to err on the side of treatment. On occasion, treatment can begin before an echocardiogram. Aspirin is routinely given, though a recent review found insufficient evidence supporting this practice (Cochrane Database Syst. Rev. 2006;doi:10.1002/14651858.CD004175.pub2). High doses of 80–100 mg/kg per day should be given initially.

Some continue the high dose for 14 days and then reduce the dose to 3–5 mg/kg per day, while others maintain the high dose only until 24–48 hours after the patient defervesces, and then switch to the low dose for 2 months for antiplatelet effects.

“I don't know of a single infectious disease expert or rheumatologist who doesn't still use aspirin in addition to IVIG in the treatment of Kawasaki disease,” Dr. Starke said.

Some data suggest some benefit of adding corticosteroids to treatment. In a recent prospective randomized trial of 178 Kawasaki patients, children on prednisolone with IVIG had a shorter duration of fever and a faster fall in C-reactive protein, but no difference in coronary artery dilation at 1 month (J. Pediatr. 2006;149:336–41).

If the fever persists or returns more than 36 hours after completion of the IVIG infusion, a second dose can be given.

“But be patient. It's very common for kids to continue to run a fever the day after you give the IVIG dose, even as other symptoms are improving,” he said.

Clinical Diagnostic Features of Kawasaki Disease

Diagnostic Criteria

Fever greater than 39 degrees C for 5 days, plus four of the following:

Conjunctivitis, usually bulbar and bilateral

Mucus membrane changes such as redness and cracking

Rash, either generalized or local

Enlarged cervical lymph nodes, usually unilateral and nontender

Peripheral changes such as swelling or peeling

Incomplete Kawasaki Supplemental Laboratory Criteria

Albumin 3 g/dL or less

Anemia for age

Elevation of alanine aminotransferase

Platelets 450,000/mm

While blood cell count 15,000/mm

Urine white blood cell count 10/HPF or more

Sources: Dr. Starke; Circulation 2004;110:2747–71.

NEW YORK — Replacing the enzyme uricase may offer a new means of treating intractable gout.

Uricase—present in most mammals but lacking in certain primates since the Miocene era, when three mutations in the uricase gene rendered it inoperative—is responsible for breaking down uric acid to the soluble and easily excreted compound allantoin as a final step in the catabolism of purines. Without this enzyme hyperuricemia can, and does, develop in humans, chimpanzees, gorillas, orangutans, and gibbons, Dr. Michael Pillinger said at a rheumatology meeting sponsored by New York University.

Studies are evaluating the possibility of giving a pegylated, recombinant form of uricase to patients whose urate levels are not controlled with conventional antigout therapies. In a phase I trial that included 24 patients, the mean plasma urate concentration fell from 11.1 mg/dL to 1 mg/dL within 24–72 hours after intravenous administration of 4–12 mg pegylated uricase (Arthritis Rheum. 2007;56:1021–8).

After a 40-year hiatus during which few advances occurred in treatment or understanding of the disease, novel approaches to the treatment of gout also are being evaluated. In a recent report, the interleukin-1 inhibitor anakinra was administered to 10 patients with gout that was unresponsive to conventional anti-inflammatory drugs. After only three 100-mg doses of the drug, all 10 patients responded rapidly, with a 79% mean reduction in pain (Arthritis Res. Ther. 2007;9:R28 [Epub doi:10.1186/ar2143]).

Teleologic insights into gout's origins also are emerging, with consideration of questions about why uric acid should have been conserved through evolution at all, and why it is present in higher levels in humans and other primates than in other mammals, Dr. Pillinger said.

An explanation for evolutionary conservation of uric acid can be seen in the process of vaccination, where an adjuvant is needed to trigger the innate immune system to respond to the presence of a foreign antigen and overcome tolerance. Freund's adjuvant, for example, contains mycobacterial debris that provides this stimulus. Mammalian cell debris also can be used in an adjuvant capacity.

But there may be another means of providing the adjuvant stimulation, through endogenous “danger” signals from distressed or injured cells, a theory proposed by Dr. Polly Metzinger of the National Institute of Allergy and Infectious Diseases. In this hypothesis, infection or other cellular injury causes the secretion of some cellular danger signal that stimulates maturation of dendritic cells, upregulation of costimulatory molecules such as CD28, and antigen presentation. The result is an immunogenic response to an endogenous signal, said Dr. Pillinger of New York University, New York.

The precise nature of this danger signal remained unclear until a group of researchers from the University of Massachusetts conducted experiments in which they fractionated cytosol from ultraviolet-irradiated mouse fibroblasts. These researchers were able to identify a low-molecular-weight compound secreted in large amounts by dying cells as nucleotides break down—which turned out to be uric acid.

They then confirmed the role of uric acid by administering uricase to mice who had been immunized with uric acid and demonstrating a reduction in adjuvant activity. The authors wrote, “Up until now, [monosodium urate] crystals were viewed solely as pathogenic and the biological response to them as pathological. Our findings suggest that the formation of these crystals and the ensuing host response could have an important role in immune surveillance and the generation of adaptive immunity” (Nature 2003;425:516–21).

It also turned out that there was a threshold level for uric acid to begin upregulating CD28 on dendritic cells, at approximately 7 mg/dL uric acid—the level at which crystals begin to form. “Nature seems to have evolved this system, including a safety threshold, to play an important role in cell damage and the immune response,” said Dr. Pillinger, who is also chief of rheumatology at the Veterans Administration Hospital and director of medical education, Hospital for Special Surgery, New York.

Support for the danger signal hypothesis also has been demonstrated in a mouse model, where uric acid levels were elevated during tumor rejection, and rejection was delayed if uric acid was inhibited by the administration of allopurinol or uricase (Cancer Res. 2004;64:5059–62).

“Another question is why we have so much more uric acid than other mammals,” he said. Dogs and cats, for example, typically have levels of approximately 1 mg/dL, compared with the 5 or 6 mg/dL in normouricemic humans.

An answer to this question, if somewhat speculative, can be found in mutations of the uricase gene that occurred between 10 and 20 million years ago, at a time when many species of primates became extinct. Fossil records suggest that the primate diet at that time, consisting largely of fruit and grasses, was extremely low in salt, at approximately 0.6 g sodium chloride per day. In effect, vegetarian mammals were in a dietary hypotensive crisis that could be most problematic for those who had evolved to stand upright, Dr. Pillinger said.

Texas nephrologist Dr. Richard J. Johnson, who developed this hypothesis, said, “The uricase mutation may have provided an evolutionary advantage to early hominoids by maintaining blood pressure under the low sodium dietary conditions of that period” (Hypertension 2003;41:1183–90).

An association of gout with elevated blood pressure has long been noted, but these new findings suggest a causative role for hyperuricemia in hypertension, Dr. Pillinger said. One study of five adolescents with essential hypertension found that aggressive treatment with allopurinol normalized their blood pressure. Whether a causal link with uric acid can be found in all patients with hypertension remains to be seen but is intriguing, he said. A blinded trial investigating this question is currently underway.

Uric acid crystals in the urine of a patient with gout. After decades of inactivity, treatment advances are on the horizon. ©Bostwick Laboratories

NEW YORK — Replacing the enzyme uricase may offer a new means of treating intractable gout.

Uricase—present in most mammals but lacking in certain primates since the Miocene era, when three mutations in the uricase gene rendered it inoperative—is responsible for breaking down uric acid to the soluble and easily excreted compound allantoin as a final step in the catabolism of purines. Without this enzyme hyperuricemia can, and does, develop in humans, chimpanzees, gorillas, orangutans, and gibbons, Dr. Michael Pillinger said at a rheumatology meeting sponsored by New York University.

Studies are evaluating the possibility of giving a pegylated, recombinant form of uricase to patients whose urate levels are not controlled with conventional antigout therapies. In a phase I trial that included 24 patients, the mean plasma urate concentration fell from 11.1 mg/dL to 1 mg/dL within 24–72 hours after intravenous administration of 4–12 mg pegylated uricase (Arthritis Rheum. 2007;56:1021–8).

After a 40-year hiatus during which few advances occurred in treatment or understanding of the disease, novel approaches to the treatment of gout also are being evaluated. In a recent report, the interleukin-1 inhibitor anakinra was administered to 10 patients with gout that was unresponsive to conventional anti-inflammatory drugs. After only three 100-mg doses of the drug, all 10 patients responded rapidly, with a 79% mean reduction in pain (Arthritis Res. Ther. 2007;9:R28 [Epub doi:10.1186/ar2143]).

Teleologic insights into gout's origins also are emerging, with consideration of questions about why uric acid should have been conserved through evolution at all, and why it is present in higher levels in humans and other primates than in other mammals, Dr. Pillinger said.

An explanation for evolutionary conservation of uric acid can be seen in the process of vaccination, where an adjuvant is needed to trigger the innate immune system to respond to the presence of a foreign antigen and overcome tolerance. Freund's adjuvant, for example, contains mycobacterial debris that provides this stimulus. Mammalian cell debris also can be used in an adjuvant capacity.

But there may be another means of providing the adjuvant stimulation, through endogenous “danger” signals from distressed or injured cells, a theory proposed by Dr. Polly Metzinger of the National Institute of Allergy and Infectious Diseases. In this hypothesis, infection or other cellular injury causes the secretion of some cellular danger signal that stimulates maturation of dendritic cells, upregulation of costimulatory molecules such as CD28, and antigen presentation. The result is an immunogenic response to an endogenous signal, said Dr. Pillinger of New York University, New York.

The precise nature of this danger signal remained unclear until a group of researchers from the University of Massachusetts conducted experiments in which they fractionated cytosol from ultraviolet-irradiated mouse fibroblasts. These researchers were able to identify a low-molecular-weight compound secreted in large amounts by dying cells as nucleotides break down—which turned out to be uric acid.

They then confirmed the role of uric acid by administering uricase to mice who had been immunized with uric acid and demonstrating a reduction in adjuvant activity. The authors wrote, “Up until now, [monosodium urate] crystals were viewed solely as pathogenic and the biological response to them as pathological. Our findings suggest that the formation of these crystals and the ensuing host response could have an important role in immune surveillance and the generation of adaptive immunity” (Nature 2003;425:516–21).

It also turned out that there was a threshold level for uric acid to begin upregulating CD28 on dendritic cells, at approximately 7 mg/dL uric acid—the level at which crystals begin to form. “Nature seems to have evolved this system, including a safety threshold, to play an important role in cell damage and the immune response,” said Dr. Pillinger, who is also chief of rheumatology at the Veterans Administration Hospital and director of medical education, Hospital for Special Surgery, New York.

Support for the danger signal hypothesis also has been demonstrated in a mouse model, where uric acid levels were elevated during tumor rejection, and rejection was delayed if uric acid was inhibited by the administration of allopurinol or uricase (Cancer Res. 2004;64:5059–62).

“Another question is why we have so much more uric acid than other mammals,” he said. Dogs and cats, for example, typically have levels of approximately 1 mg/dL, compared with the 5 or 6 mg/dL in normouricemic humans.

An answer to this question, if somewhat speculative, can be found in mutations of the uricase gene that occurred between 10 and 20 million years ago, at a time when many species of primates became extinct. Fossil records suggest that the primate diet at that time, consisting largely of fruit and grasses, was extremely low in salt, at approximately 0.6 g sodium chloride per day. In effect, vegetarian mammals were in a dietary hypotensive crisis that could be most problematic for those who had evolved to stand upright, Dr. Pillinger said.

Texas nephrologist Dr. Richard J. Johnson, who developed this hypothesis, said, “The uricase mutation may have provided an evolutionary advantage to early hominoids by maintaining blood pressure under the low sodium dietary conditions of that period” (Hypertension 2003;41:1183–90).

An association of gout with elevated blood pressure has long been noted, but these new findings suggest a causative role for hyperuricemia in hypertension, Dr. Pillinger said. One study of five adolescents with essential hypertension found that aggressive treatment with allopurinol normalized their blood pressure. Whether a causal link with uric acid can be found in all patients with hypertension remains to be seen but is intriguing, he said. A blinded trial investigating this question is currently underway.

Uric acid crystals in the urine of a patient with gout. After decades of inactivity, treatment advances are on the horizon. ©Bostwick Laboratories

NEW YORK — Replacing the enzyme uricase may offer a new means of treating intractable gout.

Uricase—present in most mammals but lacking in certain primates since the Miocene era, when three mutations in the uricase gene rendered it inoperative—is responsible for breaking down uric acid to the soluble and easily excreted compound allantoin as a final step in the catabolism of purines. Without this enzyme hyperuricemia can, and does, develop in humans, chimpanzees, gorillas, orangutans, and gibbons, Dr. Michael Pillinger said at a rheumatology meeting sponsored by New York University.

Studies are evaluating the possibility of giving a pegylated, recombinant form of uricase to patients whose urate levels are not controlled with conventional antigout therapies. In a phase I trial that included 24 patients, the mean plasma urate concentration fell from 11.1 mg/dL to 1 mg/dL within 24–72 hours after intravenous administration of 4–12 mg pegylated uricase (Arthritis Rheum. 2007;56:1021–8).

After a 40-year hiatus during which few advances occurred in treatment or understanding of the disease, novel approaches to the treatment of gout also are being evaluated. In a recent report, the interleukin-1 inhibitor anakinra was administered to 10 patients with gout that was unresponsive to conventional anti-inflammatory drugs. After only three 100-mg doses of the drug, all 10 patients responded rapidly, with a 79% mean reduction in pain (Arthritis Res. Ther. 2007;9:R28 [Epub doi:10.1186/ar2143]).

Teleologic insights into gout's origins also are emerging, with consideration of questions about why uric acid should have been conserved through evolution at all, and why it is present in higher levels in humans and other primates than in other mammals, Dr. Pillinger said.

An explanation for evolutionary conservation of uric acid can be seen in the process of vaccination, where an adjuvant is needed to trigger the innate immune system to respond to the presence of a foreign antigen and overcome tolerance. Freund's adjuvant, for example, contains mycobacterial debris that provides this stimulus. Mammalian cell debris also can be used in an adjuvant capacity.

But there may be another means of providing the adjuvant stimulation, through endogenous “danger” signals from distressed or injured cells, a theory proposed by Dr. Polly Metzinger of the National Institute of Allergy and Infectious Diseases. In this hypothesis, infection or other cellular injury causes the secretion of some cellular danger signal that stimulates maturation of dendritic cells, upregulation of costimulatory molecules such as CD28, and antigen presentation. The result is an immunogenic response to an endogenous signal, said Dr. Pillinger of New York University, New York.

The precise nature of this danger signal remained unclear until a group of researchers from the University of Massachusetts conducted experiments in which they fractionated cytosol from ultraviolet-irradiated mouse fibroblasts. These researchers were able to identify a low-molecular-weight compound secreted in large amounts by dying cells as nucleotides break down—which turned out to be uric acid.

They then confirmed the role of uric acid by administering uricase to mice who had been immunized with uric acid and demonstrating a reduction in adjuvant activity. The authors wrote, “Up until now, [monosodium urate] crystals were viewed solely as pathogenic and the biological response to them as pathological. Our findings suggest that the formation of these crystals and the ensuing host response could have an important role in immune surveillance and the generation of adaptive immunity” (Nature 2003;425:516–21).

It also turned out that there was a threshold level for uric acid to begin upregulating CD28 on dendritic cells, at approximately 7 mg/dL uric acid—the level at which crystals begin to form. “Nature seems to have evolved this system, including a safety threshold, to play an important role in cell damage and the immune response,” said Dr. Pillinger, who is also chief of rheumatology at the Veterans Administration Hospital and director of medical education, Hospital for Special Surgery, New York.

Support for the danger signal hypothesis also has been demonstrated in a mouse model, where uric acid levels were elevated during tumor rejection, and rejection was delayed if uric acid was inhibited by the administration of allopurinol or uricase (Cancer Res. 2004;64:5059–62).

“Another question is why we have so much more uric acid than other mammals,” he said. Dogs and cats, for example, typically have levels of approximately 1 mg/dL, compared with the 5 or 6 mg/dL in normouricemic humans.

An answer to this question, if somewhat speculative, can be found in mutations of the uricase gene that occurred between 10 and 20 million years ago, at a time when many species of primates became extinct. Fossil records suggest that the primate diet at that time, consisting largely of fruit and grasses, was extremely low in salt, at approximately 0.6 g sodium chloride per day. In effect, vegetarian mammals were in a dietary hypotensive crisis that could be most problematic for those who had evolved to stand upright, Dr. Pillinger said.

Texas nephrologist Dr. Richard J. Johnson, who developed this hypothesis, said, “The uricase mutation may have provided an evolutionary advantage to early hominoids by maintaining blood pressure under the low sodium dietary conditions of that period” (Hypertension 2003;41:1183–90).

An association of gout with elevated blood pressure has long been noted, but these new findings suggest a causative role for hyperuricemia in hypertension, Dr. Pillinger said. One study of five adolescents with essential hypertension found that aggressive treatment with allopurinol normalized their blood pressure. Whether a causal link with uric acid can be found in all patients with hypertension remains to be seen but is intriguing, he said. A blinded trial investigating this question is currently underway.

Uric acid crystals in the urine of a patient with gout. After decades of inactivity, treatment advances are on the horizon. ©Bostwick Laboratories

NEW YORK — If a child presents in the emergency department with near-miss sudden infant death syndrome or with a Reye's syndrome-like illness, one should consider the possibility of an inborn error of metabolism, Dr. Joan Shook said at a meeting sponsored by the American College of Emergency Physicians.

In particular, think of medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency, which is the most common of the inherited errors of fatty acid metabolism. If the condition goes undiagnosed, it carries a mortality of 25%, she said. MCAD is a mitochondrial enzyme essential for the β-oxidation of medium-chain fatty acids, a process that is required for energy production during fasting.

The pattern of inheritance seen with MCAD deficiency is autosomal recessive, so it's even worth thinking about in cases of full SIDS, because of the clear implications for future children in that family, she said.

The acute illness typically is characterized by vomiting and lethargy in a child 3–15 months of age, said Dr. Shook, professor of pediatrics and head of the section of emergency medicine, Baylor College of Medicine, Houston.

Laboratory tests, including a metabolic work-up, should be ordered promptly. Findings may include hypoketotic hypoglycemia, hyperammonemia, and an increased anion gap. Liver function tests are likely to be elevated.

Triggers for the acute Reye's-like crisis can include a febrile illness or a metabolic stressor such as fasting, surgery, and alcohol consumption. The acute illness can evolve into seizures, coma, cardiac arrest, and death.

Therapeutic measures during the acute episode include prompt rehydration and correction of hypoglycemia, and should address any identifiable stressors. During the acute episode, it's important to obtain urine and plasma, which can be frozen for further investigation, Dr. Shook said.

If the patient's clinical condition deteriorates and death appears imminent, then one should also consider obtaining skin specimens from the undersurface of the arm and the anterior surface of the thigh for later fibroblast culturing and genetic analysis, she said, noting that consent from the family is needed for this.

It is now recognized that many inborn errors of metabolism were likely misdiagnosed as Reye's syndrome before they were identified during the 1980s, and the incidence of Reye's syndrome has markedly diminished since their recognition. “A review of charts in children with Reye's would likely show that 10%–13% were, in fact, MCAD deficiency.”

Neonatal screening for MCAD deficiency is not mandatory in all states, but this may change with further recognition that the disease's morbidity and mortality can be lowered by long-term measures, such as avoidance of catabolism and aggressive resuscitation during acute crises.

Information about screening for MCAD and other inborn metabolic errors can be found at http://genes-r-us.uthscsa.edu

NEW YORK — If a child presents in the emergency department with near-miss sudden infant death syndrome or with a Reye's syndrome-like illness, one should consider the possibility of an inborn error of metabolism, Dr. Joan Shook said at a meeting sponsored by the American College of Emergency Physicians.

In particular, think of medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency, which is the most common of the inherited errors of fatty acid metabolism. If the condition goes undiagnosed, it carries a mortality of 25%, she said. MCAD is a mitochondrial enzyme essential for the β-oxidation of medium-chain fatty acids, a process that is required for energy production during fasting.

The pattern of inheritance seen with MCAD deficiency is autosomal recessive, so it's even worth thinking about in cases of full SIDS, because of the clear implications for future children in that family, she said.

The acute illness typically is characterized by vomiting and lethargy in a child 3–15 months of age, said Dr. Shook, professor of pediatrics and head of the section of emergency medicine, Baylor College of Medicine, Houston.

Laboratory tests, including a metabolic work-up, should be ordered promptly. Findings may include hypoketotic hypoglycemia, hyperammonemia, and an increased anion gap. Liver function tests are likely to be elevated.

Triggers for the acute Reye's-like crisis can include a febrile illness or a metabolic stressor such as fasting, surgery, and alcohol consumption. The acute illness can evolve into seizures, coma, cardiac arrest, and death.

Therapeutic measures during the acute episode include prompt rehydration and correction of hypoglycemia, and should address any identifiable stressors. During the acute episode, it's important to obtain urine and plasma, which can be frozen for further investigation, Dr. Shook said.

If the patient's clinical condition deteriorates and death appears imminent, then one should also consider obtaining skin specimens from the undersurface of the arm and the anterior surface of the thigh for later fibroblast culturing and genetic analysis, she said, noting that consent from the family is needed for this.

It is now recognized that many inborn errors of metabolism were likely misdiagnosed as Reye's syndrome before they were identified during the 1980s, and the incidence of Reye's syndrome has markedly diminished since their recognition. “A review of charts in children with Reye's would likely show that 10%–13% were, in fact, MCAD deficiency.”

Neonatal screening for MCAD deficiency is not mandatory in all states, but this may change with further recognition that the disease's morbidity and mortality can be lowered by long-term measures, such as avoidance of catabolism and aggressive resuscitation during acute crises.

Information about screening for MCAD and other inborn metabolic errors can be found at http://genes-r-us.uthscsa.edu

NEW YORK — If a child presents in the emergency department with near-miss sudden infant death syndrome or with a Reye's syndrome-like illness, one should consider the possibility of an inborn error of metabolism, Dr. Joan Shook said at a meeting sponsored by the American College of Emergency Physicians.

In particular, think of medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency, which is the most common of the inherited errors of fatty acid metabolism. If the condition goes undiagnosed, it carries a mortality of 25%, she said. MCAD is a mitochondrial enzyme essential for the β-oxidation of medium-chain fatty acids, a process that is required for energy production during fasting.

The pattern of inheritance seen with MCAD deficiency is autosomal recessive, so it's even worth thinking about in cases of full SIDS, because of the clear implications for future children in that family, she said.

The acute illness typically is characterized by vomiting and lethargy in a child 3–15 months of age, said Dr. Shook, professor of pediatrics and head of the section of emergency medicine, Baylor College of Medicine, Houston.

Laboratory tests, including a metabolic work-up, should be ordered promptly. Findings may include hypoketotic hypoglycemia, hyperammonemia, and an increased anion gap. Liver function tests are likely to be elevated.

Triggers for the acute Reye's-like crisis can include a febrile illness or a metabolic stressor such as fasting, surgery, and alcohol consumption. The acute illness can evolve into seizures, coma, cardiac arrest, and death.

Therapeutic measures during the acute episode include prompt rehydration and correction of hypoglycemia, and should address any identifiable stressors. During the acute episode, it's important to obtain urine and plasma, which can be frozen for further investigation, Dr. Shook said.

If the patient's clinical condition deteriorates and death appears imminent, then one should also consider obtaining skin specimens from the undersurface of the arm and the anterior surface of the thigh for later fibroblast culturing and genetic analysis, she said, noting that consent from the family is needed for this.

It is now recognized that many inborn errors of metabolism were likely misdiagnosed as Reye's syndrome before they were identified during the 1980s, and the incidence of Reye's syndrome has markedly diminished since their recognition. “A review of charts in children with Reye's would likely show that 10%–13% were, in fact, MCAD deficiency.”

Neonatal screening for MCAD deficiency is not mandatory in all states, but this may change with further recognition that the disease's morbidity and mortality can be lowered by long-term measures, such as avoidance of catabolism and aggressive resuscitation during acute crises.

Information about screening for MCAD and other inborn metabolic errors can be found at http://genes-r-us.uthscsa.edu