Psoriasis

BIRMINGHAM, England - Methotrexate is not disease modifying in patients with psoriatic arthritis, and it has a borderline effect on psoriatic arthritis response criteria.

Placebo-controlled trial findings show that although methotrexate therapy results in some symptomatic improvement after 6 months of therapy, the drug has little effect on measures that suggest disease modification, including joint swelling and the acute phase response.

These findings call into question the use of methotrexate monotherapy in psoriatic arthritis and should herald in a change in U.K. guidelines and National Institute for Health and Clinical Excellence recommendations, said Dr. Gabrielle S. Kingsley at the annual meeting of the British Society for Rheumatology.

In the United Kingdom, the use of biologic agents in psoriatic arthritis was possible only after treatment with two disease-modifying antirheumatic drugs (DMARDs) had failed, said Dr. Kingsley of the division of immunology, infection, and inflammatory diseases at King's College London and consultant rheumatologist at the Lewisham Hospital NHS Trust, London.

"But why should people have to take sulfasalazine and methotrexate, which are primarily symptom-modifying drugs, in order to get access to something which might be better?" Dr. Kinglsey asked.

In the double-blind, multicenter MIPA (Methotrexate in Psoriatic Arthritis) trial, patients with active psoriatic arthritis were randomized to treatment with methotrexate at a dose of 15 mg/week (n = 109) or to placebo (n = 112) for 6 months. The mean age of patients was 49 years, and their median disease duration was 5 years.

Around one-third of patients in each arm withdrew because of adverse events or for other reasons, with the result that 71 methotrexate- and 77 placebo-treated patients completed the trial.

The primary outcome measure was change in psoriatic arthritis response criteria (PsARC). This was improved with methotrexate treatment when compared with placebo. However, because only two out of four outcome criteria need to be improved, "this is a fairly low hurdle to jump over," Dr. Kingsley said. American College of Rheumatology-20 criteria at 6 months were not improved, and neither the PsARC nor the ACR-20 criteria were improved by methotrexate after 3 months' therapy.

Looking at the individual components of PsARC - tender joint count, swollen joint count, patient global assessment and physician global assessment - only the symptomatic parameters were significantly improved by methotrexate when compared with placebo.

"Rheumatologists need to reappraise how they use methotrexate, and indeed sulfasalazine, neither of which are truly disease-modifying drugs, and they should be considering using other options," Dr. Kingsley said. She noted that the NICE treatment pathway for psoriatic arthritis should be reevaluated.

"Methotrexate is widely used in psoriatic arthritis almost entirely based on the fact that it works in rheumatoid arthritis," Dr. Kingsley said. Before the MIPA trial, no randomized, controlled trial had looked at the role of methotrexate in psoriatic arthritis because it was widely believed that the drug was effective. She added that the MIPA trial results had vindicated the use of a placebo-controlled design, and had shown that "if you are going to have treatment pathways, these do need to be based on solid evidence."

Dr. Deborah E. Bax, BSR president and consultant physician in rheumatology at the Royal Hallamshire Hospital in Sheffield, England, commented, "These results are very thought provoking. They question our clinical practice and could have huge implications for us and for our patients."

"I don't think these results are practice changing at the moment," commented Dr. Philip S. Helliwell, senior lecturer in rheumatology at Leeds (England ) University. Dr. Helliwell observed that the distinction between oligo- and polyarticular disease was not made, which could have diluted the findings.

Dr. Helliwell also said that the dose of methotrexate, although standard at the time the MIPA trial began, was possibly too low to have an effect. He noted that very good results were currently being obtained with methotrexate at doses of up to 25 mg/week in an ongoing trial of intensive vs. routine treatment psoriatic arthritis.

Disclosures: Dr. Kingsley, Dr. Bax, and Dr. Helliwell had no relevant financial disclosures. Arthritis Research UK funded the trial.

BIRMINGHAM, England - Methotrexate is not disease modifying in patients with psoriatic arthritis, and it has a borderline effect on psoriatic arthritis response criteria.

Placebo-controlled trial findings show that although methotrexate therapy results in some symptomatic improvement after 6 months of therapy, the drug has little effect on measures that suggest disease modification, including joint swelling and the acute phase response.

These findings call into question the use of methotrexate monotherapy in psoriatic arthritis and should herald in a change in U.K. guidelines and National Institute for Health and Clinical Excellence recommendations, said Dr. Gabrielle S. Kingsley at the annual meeting of the British Society for Rheumatology.

In the United Kingdom, the use of biologic agents in psoriatic arthritis was possible only after treatment with two disease-modifying antirheumatic drugs (DMARDs) had failed, said Dr. Kingsley of the division of immunology, infection, and inflammatory diseases at King's College London and consultant rheumatologist at the Lewisham Hospital NHS Trust, London.

"But why should people have to take sulfasalazine and methotrexate, which are primarily symptom-modifying drugs, in order to get access to something which might be better?" Dr. Kinglsey asked.

In the double-blind, multicenter MIPA (Methotrexate in Psoriatic Arthritis) trial, patients with active psoriatic arthritis were randomized to treatment with methotrexate at a dose of 15 mg/week (n = 109) or to placebo (n = 112) for 6 months. The mean age of patients was 49 years, and their median disease duration was 5 years.

Around one-third of patients in each arm withdrew because of adverse events or for other reasons, with the result that 71 methotrexate- and 77 placebo-treated patients completed the trial.

The primary outcome measure was change in psoriatic arthritis response criteria (PsARC). This was improved with methotrexate treatment when compared with placebo. However, because only two out of four outcome criteria need to be improved, "this is a fairly low hurdle to jump over," Dr. Kingsley said. American College of Rheumatology-20 criteria at 6 months were not improved, and neither the PsARC nor the ACR-20 criteria were improved by methotrexate after 3 months' therapy.

Looking at the individual components of PsARC - tender joint count, swollen joint count, patient global assessment and physician global assessment - only the symptomatic parameters were significantly improved by methotrexate when compared with placebo.

"Rheumatologists need to reappraise how they use methotrexate, and indeed sulfasalazine, neither of which are truly disease-modifying drugs, and they should be considering using other options," Dr. Kingsley said. She noted that the NICE treatment pathway for psoriatic arthritis should be reevaluated.

"Methotrexate is widely used in psoriatic arthritis almost entirely based on the fact that it works in rheumatoid arthritis," Dr. Kingsley said. Before the MIPA trial, no randomized, controlled trial had looked at the role of methotrexate in psoriatic arthritis because it was widely believed that the drug was effective. She added that the MIPA trial results had vindicated the use of a placebo-controlled design, and had shown that "if you are going to have treatment pathways, these do need to be based on solid evidence."

Dr. Deborah E. Bax, BSR president and consultant physician in rheumatology at the Royal Hallamshire Hospital in Sheffield, England, commented, "These results are very thought provoking. They question our clinical practice and could have huge implications for us and for our patients."

"I don't think these results are practice changing at the moment," commented Dr. Philip S. Helliwell, senior lecturer in rheumatology at Leeds (England ) University. Dr. Helliwell observed that the distinction between oligo- and polyarticular disease was not made, which could have diluted the findings.

Dr. Helliwell also said that the dose of methotrexate, although standard at the time the MIPA trial began, was possibly too low to have an effect. He noted that very good results were currently being obtained with methotrexate at doses of up to 25 mg/week in an ongoing trial of intensive vs. routine treatment psoriatic arthritis.

Disclosures: Dr. Kingsley, Dr. Bax, and Dr. Helliwell had no relevant financial disclosures. Arthritis Research UK funded the trial.

BIRMINGHAM, England - Methotrexate is not disease modifying in patients with psoriatic arthritis, and it has a borderline effect on psoriatic arthritis response criteria.

Placebo-controlled trial findings show that although methotrexate therapy results in some symptomatic improvement after 6 months of therapy, the drug has little effect on measures that suggest disease modification, including joint swelling and the acute phase response.

These findings call into question the use of methotrexate monotherapy in psoriatic arthritis and should herald in a change in U.K. guidelines and National Institute for Health and Clinical Excellence recommendations, said Dr. Gabrielle S. Kingsley at the annual meeting of the British Society for Rheumatology.

In the United Kingdom, the use of biologic agents in psoriatic arthritis was possible only after treatment with two disease-modifying antirheumatic drugs (DMARDs) had failed, said Dr. Kingsley of the division of immunology, infection, and inflammatory diseases at King's College London and consultant rheumatologist at the Lewisham Hospital NHS Trust, London.

"But why should people have to take sulfasalazine and methotrexate, which are primarily symptom-modifying drugs, in order to get access to something which might be better?" Dr. Kinglsey asked.

In the double-blind, multicenter MIPA (Methotrexate in Psoriatic Arthritis) trial, patients with active psoriatic arthritis were randomized to treatment with methotrexate at a dose of 15 mg/week (n = 109) or to placebo (n = 112) for 6 months. The mean age of patients was 49 years, and their median disease duration was 5 years.

Around one-third of patients in each arm withdrew because of adverse events or for other reasons, with the result that 71 methotrexate- and 77 placebo-treated patients completed the trial.

The primary outcome measure was change in psoriatic arthritis response criteria (PsARC). This was improved with methotrexate treatment when compared with placebo. However, because only two out of four outcome criteria need to be improved, "this is a fairly low hurdle to jump over," Dr. Kingsley said. American College of Rheumatology-20 criteria at 6 months were not improved, and neither the PsARC nor the ACR-20 criteria were improved by methotrexate after 3 months' therapy.

Looking at the individual components of PsARC - tender joint count, swollen joint count, patient global assessment and physician global assessment - only the symptomatic parameters were significantly improved by methotrexate when compared with placebo.

"Rheumatologists need to reappraise how they use methotrexate, and indeed sulfasalazine, neither of which are truly disease-modifying drugs, and they should be considering using other options," Dr. Kingsley said. She noted that the NICE treatment pathway for psoriatic arthritis should be reevaluated.

"Methotrexate is widely used in psoriatic arthritis almost entirely based on the fact that it works in rheumatoid arthritis," Dr. Kingsley said. Before the MIPA trial, no randomized, controlled trial had looked at the role of methotrexate in psoriatic arthritis because it was widely believed that the drug was effective. She added that the MIPA trial results had vindicated the use of a placebo-controlled design, and had shown that "if you are going to have treatment pathways, these do need to be based on solid evidence."

Dr. Deborah E. Bax, BSR president and consultant physician in rheumatology at the Royal Hallamshire Hospital in Sheffield, England, commented, "These results are very thought provoking. They question our clinical practice and could have huge implications for us and for our patients."

"I don't think these results are practice changing at the moment," commented Dr. Philip S. Helliwell, senior lecturer in rheumatology at Leeds (England ) University. Dr. Helliwell observed that the distinction between oligo- and polyarticular disease was not made, which could have diluted the findings.

Dr. Helliwell also said that the dose of methotrexate, although standard at the time the MIPA trial began, was possibly too low to have an effect. He noted that very good results were currently being obtained with methotrexate at doses of up to 25 mg/week in an ongoing trial of intensive vs. routine treatment psoriatic arthritis.

Disclosures: Dr. Kingsley, Dr. Bax, and Dr. Helliwell had no relevant financial disclosures. Arthritis Research UK funded the trial.

Dr. Stephen E. Wolverton on why short-course use of corticosteroids is not a cause of osteonecrosis. Damian McNamara reports from Miami.

View Video Now.

Dr. Stephen E. Wolverton on why short-course use of corticosteroids is not a cause of osteonecrosis. Damian McNamara reports from Miami.

View Video Now.

Dr. Stephen E. Wolverton on why short-course use of corticosteroids is not a cause of osteonecrosis. Damian McNamara reports from Miami.

View Video Now.

NEW YORK – There is an 18% risk for congenital heart block in the subsequent pregnancy of a woman who has already had one child born with the condition, judging from registry data on outcomes of 136 such subsequent pregnancies, according to Dr. Jill P. Buyon.

In the absence of neonatal cardiac involvement, the risk for congenital heart block in the subsequent pregnancy of a woman who gave birth to a previous child with malar rash (a manifestation of neonatal lupus) is 13% if only data collected prospectively are utilized, or 18% if all data are evaluated. These risks are substantially higher than the 2% risk of congenital heart block for primigravid women with anti-SSA/Ro antibodies. The occurrence of cutaneous disease in a child born subsequent to the birth of a child with cutaneous disease is even higher, approaching 30%, Dr. Buyon said at a rheumatology meeting sponsored by New York University.

Because neonatal lupus is so uncommon, physicians have little information on which to base their advice to these concerned women. The data from the NYU Research Registry for Neonatal Lupus is a starting point for advice. To date, the NYU registry (sponsored by the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases) has collected information on 442 families, with a total of 484 pregnancies involving neonatal lupus. Among the 484 pregnancies recorded in the registry, outcomes included 280 cases of congenital heart block, 150 cases of rash, and 38 cases involving both manifestations of neonatal lupus. The remaining 16 cases comprised 7 newborns with isolated cardiomyopathy, and another 9 with isolated hepatic/hematologic involvement.

The underlying mechanism of neonatal lupus is passively acquired autoimmunity. Although some of the mothers have symptomatic lupus or Sjögren’s syndrome, most have been asymptomatic when their unborn child developed heart block at 18-24 weeks’ gestation, or their neonate developed rash at 6 weeks post partum. Long-term follow up of the registry participants has shown that 50% of the women remain asymptomatic 4 years after the birth of their first child with either congenital heart block or cutaneous neonatal lupus. Some of the women have remained asymptomatic for up to 15-20 years of follow-up, said Dr. Buyon, professor of medicine at New York University.

Specifically, in follow-up of 51 mothers, half remained asymptomatic at a mean of 4 years. Half developed symptoms of a rheumatic disease, including four cases of Sjögren’s syndrome and five of systemic lupus erythematosus, two of which involved lupus nephritis. Mothers with anti-SSA/Ro and anti-SSB/La were twice as likely to develop an autoimmune disease as were mothers with anti-SSA/Ro only (Ann. Rheum. Dis. 2009;68:828-35).

Neonatal lupus is relatively rare and involves the fetus’s passive acquisition of autoantibodies. Affected children come to clinical attention when they either develop congenital heart block at about 20 weeks’ gestation or are born with a cutaneous rash. The mothers often are asymptomatic. The problems in their unborn or newborn child often are the first sign of their own health risks. The mother is likely to hear conflicting and confusing advice from her obstetrician and/or pediatrician.

The fetal heart block can be first, second, or third degree. Mortality in affected pregnancies is about 20%, and more than 65% of the surviving neonates required pacing. There is no equivalent adult-onset counterpart to neonatal lupus that presents as heart block. The cutaneous presentation, which involves annular or elliptical lesions on the face, scalp, trunk, and/or extremities, resembles the presentation of adult-onset systemic cutaneous lupus erythematosus. In infants, the condition is transient.

Despite being exposed to the same circulating antibodies as the fetus, the maternal heart is unaffected.

Dr. Buyon noted that she had no relevant financial relationships to disclose with regard to the study of neonatal lupus except for support from the U.S. National Institute of Arthritis and Musculoskeletal and Skin Disease, the American Heart Association, the Kirkland Center, and the Alliance for Lupus Research.

NEW YORK – There is an 18% risk for congenital heart block in the subsequent pregnancy of a woman who has already had one child born with the condition, judging from registry data on outcomes of 136 such subsequent pregnancies, according to Dr. Jill P. Buyon.

In the absence of neonatal cardiac involvement, the risk for congenital heart block in the subsequent pregnancy of a woman who gave birth to a previous child with malar rash (a manifestation of neonatal lupus) is 13% if only data collected prospectively are utilized, or 18% if all data are evaluated. These risks are substantially higher than the 2% risk of congenital heart block for primigravid women with anti-SSA/Ro antibodies. The occurrence of cutaneous disease in a child born subsequent to the birth of a child with cutaneous disease is even higher, approaching 30%, Dr. Buyon said at a rheumatology meeting sponsored by New York University.

Because neonatal lupus is so uncommon, physicians have little information on which to base their advice to these concerned women. The data from the NYU Research Registry for Neonatal Lupus is a starting point for advice. To date, the NYU registry (sponsored by the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases) has collected information on 442 families, with a total of 484 pregnancies involving neonatal lupus. Among the 484 pregnancies recorded in the registry, outcomes included 280 cases of congenital heart block, 150 cases of rash, and 38 cases involving both manifestations of neonatal lupus. The remaining 16 cases comprised 7 newborns with isolated cardiomyopathy, and another 9 with isolated hepatic/hematologic involvement.

The underlying mechanism of neonatal lupus is passively acquired autoimmunity. Although some of the mothers have symptomatic lupus or Sjögren’s syndrome, most have been asymptomatic when their unborn child developed heart block at 18-24 weeks’ gestation, or their neonate developed rash at 6 weeks post partum. Long-term follow up of the registry participants has shown that 50% of the women remain asymptomatic 4 years after the birth of their first child with either congenital heart block or cutaneous neonatal lupus. Some of the women have remained asymptomatic for up to 15-20 years of follow-up, said Dr. Buyon, professor of medicine at New York University.

Specifically, in follow-up of 51 mothers, half remained asymptomatic at a mean of 4 years. Half developed symptoms of a rheumatic disease, including four cases of Sjögren’s syndrome and five of systemic lupus erythematosus, two of which involved lupus nephritis. Mothers with anti-SSA/Ro and anti-SSB/La were twice as likely to develop an autoimmune disease as were mothers with anti-SSA/Ro only (Ann. Rheum. Dis. 2009;68:828-35).

Neonatal lupus is relatively rare and involves the fetus’s passive acquisition of autoantibodies. Affected children come to clinical attention when they either develop congenital heart block at about 20 weeks’ gestation or are born with a cutaneous rash. The mothers often are asymptomatic. The problems in their unborn or newborn child often are the first sign of their own health risks. The mother is likely to hear conflicting and confusing advice from her obstetrician and/or pediatrician.

The fetal heart block can be first, second, or third degree. Mortality in affected pregnancies is about 20%, and more than 65% of the surviving neonates required pacing. There is no equivalent adult-onset counterpart to neonatal lupus that presents as heart block. The cutaneous presentation, which involves annular or elliptical lesions on the face, scalp, trunk, and/or extremities, resembles the presentation of adult-onset systemic cutaneous lupus erythematosus. In infants, the condition is transient.

Despite being exposed to the same circulating antibodies as the fetus, the maternal heart is unaffected.

Dr. Buyon noted that she had no relevant financial relationships to disclose with regard to the study of neonatal lupus except for support from the U.S. National Institute of Arthritis and Musculoskeletal and Skin Disease, the American Heart Association, the Kirkland Center, and the Alliance for Lupus Research.

NEW YORK – There is an 18% risk for congenital heart block in the subsequent pregnancy of a woman who has already had one child born with the condition, judging from registry data on outcomes of 136 such subsequent pregnancies, according to Dr. Jill P. Buyon.

In the absence of neonatal cardiac involvement, the risk for congenital heart block in the subsequent pregnancy of a woman who gave birth to a previous child with malar rash (a manifestation of neonatal lupus) is 13% if only data collected prospectively are utilized, or 18% if all data are evaluated. These risks are substantially higher than the 2% risk of congenital heart block for primigravid women with anti-SSA/Ro antibodies. The occurrence of cutaneous disease in a child born subsequent to the birth of a child with cutaneous disease is even higher, approaching 30%, Dr. Buyon said at a rheumatology meeting sponsored by New York University.

Because neonatal lupus is so uncommon, physicians have little information on which to base their advice to these concerned women. The data from the NYU Research Registry for Neonatal Lupus is a starting point for advice. To date, the NYU registry (sponsored by the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases) has collected information on 442 families, with a total of 484 pregnancies involving neonatal lupus. Among the 484 pregnancies recorded in the registry, outcomes included 280 cases of congenital heart block, 150 cases of rash, and 38 cases involving both manifestations of neonatal lupus. The remaining 16 cases comprised 7 newborns with isolated cardiomyopathy, and another 9 with isolated hepatic/hematologic involvement.

The underlying mechanism of neonatal lupus is passively acquired autoimmunity. Although some of the mothers have symptomatic lupus or Sjögren’s syndrome, most have been asymptomatic when their unborn child developed heart block at 18-24 weeks’ gestation, or their neonate developed rash at 6 weeks post partum. Long-term follow up of the registry participants has shown that 50% of the women remain asymptomatic 4 years after the birth of their first child with either congenital heart block or cutaneous neonatal lupus. Some of the women have remained asymptomatic for up to 15-20 years of follow-up, said Dr. Buyon, professor of medicine at New York University.

Specifically, in follow-up of 51 mothers, half remained asymptomatic at a mean of 4 years. Half developed symptoms of a rheumatic disease, including four cases of Sjögren’s syndrome and five of systemic lupus erythematosus, two of which involved lupus nephritis. Mothers with anti-SSA/Ro and anti-SSB/La were twice as likely to develop an autoimmune disease as were mothers with anti-SSA/Ro only (Ann. Rheum. Dis. 2009;68:828-35).

Neonatal lupus is relatively rare and involves the fetus’s passive acquisition of autoantibodies. Affected children come to clinical attention when they either develop congenital heart block at about 20 weeks’ gestation or are born with a cutaneous rash. The mothers often are asymptomatic. The problems in their unborn or newborn child often are the first sign of their own health risks. The mother is likely to hear conflicting and confusing advice from her obstetrician and/or pediatrician.

The fetal heart block can be first, second, or third degree. Mortality in affected pregnancies is about 20%, and more than 65% of the surviving neonates required pacing. There is no equivalent adult-onset counterpart to neonatal lupus that presents as heart block. The cutaneous presentation, which involves annular or elliptical lesions on the face, scalp, trunk, and/or extremities, resembles the presentation of adult-onset systemic cutaneous lupus erythematosus. In infants, the condition is transient.

Despite being exposed to the same circulating antibodies as the fetus, the maternal heart is unaffected.

Dr. Buyon noted that she had no relevant financial relationships to disclose with regard to the study of neonatal lupus except for support from the U.S. National Institute of Arthritis and Musculoskeletal and Skin Disease, the American Heart Association, the Kirkland Center, and the Alliance for Lupus Research.

ATLANTA - Patients with psoriasis had a significantly increased risk for developing atrial fibrillation or need for coronary artery revascularization, in a review of the entire Danish population during 1997-2006.

The report is the first to find a link between psoriasis and these two types of cardiovascular disease events, Dr. Ole Ahlehoff reported in two posters at the annual meeting of the American College of Cardiology.

The analysis also showed that patients with psoriasis had a significantly increased risk for ischemic stroke and, in those with severe psoriasis, for all-cause death.
 
The link between psoriasis and these events occurs "presumably because of inflammation" mediated by T helper cells, said Dr. Ahlehoff, a research fellow at Copenhagen University Hospital Gentofte.
 
"Our study of nationwide data from an unselected cohort firmly establishes psoriasis as a clinically relevant risk factor for cardiovascular disease." His report added a new dimension to existing evidence because it "provides data from an independent cohort on a national scale that avoids selection bias," he said.

"We need to consider psoriasis patients as a group at increased risk" for cardiovascular disease events, he said in an interview. "The vast majority of patients with psoriasis probably meet criteria for [needing] weight loss and increased activity. The main point of our study is that physicians caring for patients with psoriasis should be more aware of possible cardiovascular disease risk" and "make sure that lifestyle changes occur, and that they screen for hypertension and lipidemia." At the least, patients with psoriasis should reach blood pressure and lipid levels that meet goals for the general population, he said.

"I personally feel that we're reaching the point where we need to reconsider how to manage patients with psoriasis" by giving greater consideration to "earlier risk factor intervention," such as statin therapy, Dr. Ahlehoff added. He admitted that this type of approach cannot be based on results from a single epidemiologic study, such as his presentation, but he noted that his findings are part of "mounting evidence" from several studies that psoriasis is a disease equivalent for cardiovascular disease, comparable to diabetes or rheumatoid arthritis. He also noted that other study results documented that statin treatment improves patients' psoriatic symptoms, further bolstering a link between the inflammatory processes involved in psoriasis and cardiovascular disease.
 
His study reviewed national registry records in Denmark during 1997-2006, which included roughly 4.5 million people aged 10 years or older. During the 10-year span, about 40,000 developed new-onset psoriasis, based on their filling at least two prescriptions for vitamin D, an agent used exclusively to treat psoriasis in Denmark. Dr. Ahlehoff estimated that about 80%-90% of the patients in this group had plaque psoriasis, with most of the rest having psoriatic arthritis. Among these 40,000, the researchers identified about 3,000 as having severe psoriasis, defined as patients hospitalized at least three times with a primary diagnosis of psoriasis during the study period.

The analysis examined the incidence rate of all-cause death and several cardiovascular disease events during the study period in both the psoriasis patients and the rest of the Danish population, with an average follow-up of 5 years.

In an analysis that adjusted for a variety of clinical and demographic variable, including age, gender, calendar year, medications, comorbidities, and socioeconomic status, patients with severe psoriasis had a statistically significant 53% increased risk of all-cause death compared with the general population (see chart). Patients with severe psoriasis also had a statistically significant 88% increased risk for needing coronary artery revascularization, a significant 51% increased risk for developing atrial fibrillation, and a significant 58% increased risk for having an ischemic stroke. The increased stroke risk remained at that level when the analysis excluded patients with atrial fibrillation.

Patients with mild psoriasis also had significantly increased rates of coronary revascularization, atrial fibrillation, and ischemic stroke, although the magnitudes of the increased rates were not as high as in the severe patients.

The analysis also showed that the increased risk linked with psoriasis was magnified in patients who were younger than 50 at the time the study began.

Younger adults with severe psoriasis had a twofold greater risk of atrial fibrillation, ischemic stroke, or need for coronary revascularization, compared with the general adult population.

Dr. Ahlehoff said that he and his associates had no disclosures.

ATLANTA - Patients with psoriasis had a significantly increased risk for developing atrial fibrillation or need for coronary artery revascularization, in a review of the entire Danish population during 1997-2006.

The report is the first to find a link between psoriasis and these two types of cardiovascular disease events, Dr. Ole Ahlehoff reported in two posters at the annual meeting of the American College of Cardiology.

The analysis also showed that patients with psoriasis had a significantly increased risk for ischemic stroke and, in those with severe psoriasis, for all-cause death.
 
The link between psoriasis and these events occurs "presumably because of inflammation" mediated by T helper cells, said Dr. Ahlehoff, a research fellow at Copenhagen University Hospital Gentofte.
 
"Our study of nationwide data from an unselected cohort firmly establishes psoriasis as a clinically relevant risk factor for cardiovascular disease." His report added a new dimension to existing evidence because it "provides data from an independent cohort on a national scale that avoids selection bias," he said.

"We need to consider psoriasis patients as a group at increased risk" for cardiovascular disease events, he said in an interview. "The vast majority of patients with psoriasis probably meet criteria for [needing] weight loss and increased activity. The main point of our study is that physicians caring for patients with psoriasis should be more aware of possible cardiovascular disease risk" and "make sure that lifestyle changes occur, and that they screen for hypertension and lipidemia." At the least, patients with psoriasis should reach blood pressure and lipid levels that meet goals for the general population, he said.

"I personally feel that we're reaching the point where we need to reconsider how to manage patients with psoriasis" by giving greater consideration to "earlier risk factor intervention," such as statin therapy, Dr. Ahlehoff added. He admitted that this type of approach cannot be based on results from a single epidemiologic study, such as his presentation, but he noted that his findings are part of "mounting evidence" from several studies that psoriasis is a disease equivalent for cardiovascular disease, comparable to diabetes or rheumatoid arthritis. He also noted that other study results documented that statin treatment improves patients' psoriatic symptoms, further bolstering a link between the inflammatory processes involved in psoriasis and cardiovascular disease.
 
His study reviewed national registry records in Denmark during 1997-2006, which included roughly 4.5 million people aged 10 years or older. During the 10-year span, about 40,000 developed new-onset psoriasis, based on their filling at least two prescriptions for vitamin D, an agent used exclusively to treat psoriasis in Denmark. Dr. Ahlehoff estimated that about 80%-90% of the patients in this group had plaque psoriasis, with most of the rest having psoriatic arthritis. Among these 40,000, the researchers identified about 3,000 as having severe psoriasis, defined as patients hospitalized at least three times with a primary diagnosis of psoriasis during the study period.

The analysis examined the incidence rate of all-cause death and several cardiovascular disease events during the study period in both the psoriasis patients and the rest of the Danish population, with an average follow-up of 5 years.

In an analysis that adjusted for a variety of clinical and demographic variable, including age, gender, calendar year, medications, comorbidities, and socioeconomic status, patients with severe psoriasis had a statistically significant 53% increased risk of all-cause death compared with the general population (see chart). Patients with severe psoriasis also had a statistically significant 88% increased risk for needing coronary artery revascularization, a significant 51% increased risk for developing atrial fibrillation, and a significant 58% increased risk for having an ischemic stroke. The increased stroke risk remained at that level when the analysis excluded patients with atrial fibrillation.

Patients with mild psoriasis also had significantly increased rates of coronary revascularization, atrial fibrillation, and ischemic stroke, although the magnitudes of the increased rates were not as high as in the severe patients.

The analysis also showed that the increased risk linked with psoriasis was magnified in patients who were younger than 50 at the time the study began.

Younger adults with severe psoriasis had a twofold greater risk of atrial fibrillation, ischemic stroke, or need for coronary revascularization, compared with the general adult population.

Dr. Ahlehoff said that he and his associates had no disclosures.

ATLANTA - Patients with psoriasis had a significantly increased risk for developing atrial fibrillation or need for coronary artery revascularization, in a review of the entire Danish population during 1997-2006.

The report is the first to find a link between psoriasis and these two types of cardiovascular disease events, Dr. Ole Ahlehoff reported in two posters at the annual meeting of the American College of Cardiology.

The analysis also showed that patients with psoriasis had a significantly increased risk for ischemic stroke and, in those with severe psoriasis, for all-cause death.
 
The link between psoriasis and these events occurs "presumably because of inflammation" mediated by T helper cells, said Dr. Ahlehoff, a research fellow at Copenhagen University Hospital Gentofte.
 
"Our study of nationwide data from an unselected cohort firmly establishes psoriasis as a clinically relevant risk factor for cardiovascular disease." His report added a new dimension to existing evidence because it "provides data from an independent cohort on a national scale that avoids selection bias," he said.

"We need to consider psoriasis patients as a group at increased risk" for cardiovascular disease events, he said in an interview. "The vast majority of patients with psoriasis probably meet criteria for [needing] weight loss and increased activity. The main point of our study is that physicians caring for patients with psoriasis should be more aware of possible cardiovascular disease risk" and "make sure that lifestyle changes occur, and that they screen for hypertension and lipidemia." At the least, patients with psoriasis should reach blood pressure and lipid levels that meet goals for the general population, he said.

"I personally feel that we're reaching the point where we need to reconsider how to manage patients with psoriasis" by giving greater consideration to "earlier risk factor intervention," such as statin therapy, Dr. Ahlehoff added. He admitted that this type of approach cannot be based on results from a single epidemiologic study, such as his presentation, but he noted that his findings are part of "mounting evidence" from several studies that psoriasis is a disease equivalent for cardiovascular disease, comparable to diabetes or rheumatoid arthritis. He also noted that other study results documented that statin treatment improves patients' psoriatic symptoms, further bolstering a link between the inflammatory processes involved in psoriasis and cardiovascular disease.
 
His study reviewed national registry records in Denmark during 1997-2006, which included roughly 4.5 million people aged 10 years or older. During the 10-year span, about 40,000 developed new-onset psoriasis, based on their filling at least two prescriptions for vitamin D, an agent used exclusively to treat psoriasis in Denmark. Dr. Ahlehoff estimated that about 80%-90% of the patients in this group had plaque psoriasis, with most of the rest having psoriatic arthritis. Among these 40,000, the researchers identified about 3,000 as having severe psoriasis, defined as patients hospitalized at least three times with a primary diagnosis of psoriasis during the study period.

The analysis examined the incidence rate of all-cause death and several cardiovascular disease events during the study period in both the psoriasis patients and the rest of the Danish population, with an average follow-up of 5 years.

In an analysis that adjusted for a variety of clinical and demographic variable, including age, gender, calendar year, medications, comorbidities, and socioeconomic status, patients with severe psoriasis had a statistically significant 53% increased risk of all-cause death compared with the general population (see chart). Patients with severe psoriasis also had a statistically significant 88% increased risk for needing coronary artery revascularization, a significant 51% increased risk for developing atrial fibrillation, and a significant 58% increased risk for having an ischemic stroke. The increased stroke risk remained at that level when the analysis excluded patients with atrial fibrillation.

Patients with mild psoriasis also had significantly increased rates of coronary revascularization, atrial fibrillation, and ischemic stroke, although the magnitudes of the increased rates were not as high as in the severe patients.

The analysis also showed that the increased risk linked with psoriasis was magnified in patients who were younger than 50 at the time the study began.

Younger adults with severe psoriasis had a twofold greater risk of atrial fibrillation, ischemic stroke, or need for coronary revascularization, compared with the general adult population.

Dr. Ahlehoff said that he and his associates had no disclosures.

NEW YORK – Rituximab may offer an alternative treatment for children whose juvenile dermatomyositis does not respond to available therapies, depending on the outcome of an ongoing trial, Dr. B. Anne Eberhard said at a meeting sponsored by New York University.

There are no U.S. Food and Drug Administration–approved medications for juvenile dermatomyositis (JDM).

The RIM (Rituximab in Myositis) trial is a randomized, phase II, placebo-phase controlled, multicenter trial investigating the effect of rituximab on refractory dermatomyositis in children and adults. The study intended to enroll 50 children with JDM, and it will assess efficacy, safety, and determinants of treatment response and disease pathogenesis, including clinical, demographic, and immunopathologic factors.

The RIM trial results will be presented at the annual meeting of the American Academy of Rheumatology in November 2010, Dr. Chester V. Oddis said in an interview.

The study is sponsored by Genentech Inc., Biogen Idec Inc., and the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases, according to Dr. Oddis, who is the principal investigator and a professor of rheumatology at the University of Pittsburgh.

Dr. Eberhard noted that prednisone and methotrexate are the mainstays of treatment, for now. However, outcomes can be unsatisfactory either because symptoms remain poorly controlled or because side effects occur.

JDM is a relatively rare idiopathic inflammatory myopathy that can be physically disabling, disfiguring, and life threatening if left unchecked.

To facilitate diagnosis of JDM, the Childhood Myositis Assessment Scale (CMAS) was recently developed to allow clinicians to assess children for JDM in the office without the need for specialized equipment. The CMAS is a 14-activity, observational, performance-based assessment that measures physical function, strength, and endurance, explained Dr. Eberhard, who is a pediatric rheumatologist at the Albert Einstein College of Medicine in New York. For instance, it can be used to compare, from one visit to another, how well a child can raise his head or leg, go from a supine to sitting position, rise from a chair, or step on a stool. An abbreviated 9-maneuver test is also available.

Dr. Eberhard outlined other relatively simple ways to diagnose JDM in the office or at the bedside. The first is visual examination of the body, with a focus on skin changes, including the characteristic malar or butterfly rash on the bridge of the nose, cheeks and face; the classic reddish/purple heliotrope rash; and Gottron’s papules on the extensor surfaces of the fingers. The rash typically appears on skin areas that are exposed to the sun, including elbows, knees, and ankles, so sunscreens and sun avoidance are advised for JDM patients. About 25% of patients present with subcutaneous calcinosis, which eventually affects 70% of patients.

To look for vasculopathy, examine the nail-bed capillaries with an ophthalmoscope, said Dr. Eberhard. In contrast to their normal, straight, “picket-fence” appearance, the capillaries in children with JDM show dilation and extensive branching; there may even be capillary loss. “You can quantify the disease and monitor improvement with treatment by examining nail-bed capillaries,” she said.

Symmetrical proximal weakness is another hallmark of JDM. Dr. Eberhard said that she immediately thinks of JDM when she hears that a child is having difficulty getting up the school bus stairs.

An urgent response is required if a child says that food is “sticking to his mouth”. This suggests a bulbar muscle weakness of central origin, with impaired swallowing and the potential for aspiration. This may necessitate placing the child on a soft diet or even hospitalization, said Dr. Eberhard.
JDM can produce other serious sequelae, including pulmonary fibrosis and perforation of the esophagus or small bowel.

The original five diagnostic criteria that were first presented in 1975 did not change for the subsequent 35 years (N. Engl. J. Med. 1975:292:344-7). In addition to symmetrical proximal weakness and rash, the diagnostic criteria are raised serum muscle enzymes, electromyogram evidence of myositis, and histologic evidence of myositis. Diagnosis of JDM requires the presence of four of the five criteria, she said.

Dr. Eberhard had no relevant financial disclosures.

^{Image above courtesy: Dermatology Online Journal via Wikipedia Commons.}

NEW YORK – Rituximab may offer an alternative treatment for children whose juvenile dermatomyositis does not respond to available therapies, depending on the outcome of an ongoing trial, Dr. B. Anne Eberhard said at a meeting sponsored by New York University.

There are no U.S. Food and Drug Administration–approved medications for juvenile dermatomyositis (JDM).

The RIM (Rituximab in Myositis) trial is a randomized, phase II, placebo-phase controlled, multicenter trial investigating the effect of rituximab on refractory dermatomyositis in children and adults. The study intended to enroll 50 children with JDM, and it will assess efficacy, safety, and determinants of treatment response and disease pathogenesis, including clinical, demographic, and immunopathologic factors.

The RIM trial results will be presented at the annual meeting of the American Academy of Rheumatology in November 2010, Dr. Chester V. Oddis said in an interview.

The study is sponsored by Genentech Inc., Biogen Idec Inc., and the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases, according to Dr. Oddis, who is the principal investigator and a professor of rheumatology at the University of Pittsburgh.

Dr. Eberhard noted that prednisone and methotrexate are the mainstays of treatment, for now. However, outcomes can be unsatisfactory either because symptoms remain poorly controlled or because side effects occur.

JDM is a relatively rare idiopathic inflammatory myopathy that can be physically disabling, disfiguring, and life threatening if left unchecked.

To facilitate diagnosis of JDM, the Childhood Myositis Assessment Scale (CMAS) was recently developed to allow clinicians to assess children for JDM in the office without the need for specialized equipment. The CMAS is a 14-activity, observational, performance-based assessment that measures physical function, strength, and endurance, explained Dr. Eberhard, who is a pediatric rheumatologist at the Albert Einstein College of Medicine in New York. For instance, it can be used to compare, from one visit to another, how well a child can raise his head or leg, go from a supine to sitting position, rise from a chair, or step on a stool. An abbreviated 9-maneuver test is also available.

Dr. Eberhard outlined other relatively simple ways to diagnose JDM in the office or at the bedside. The first is visual examination of the body, with a focus on skin changes, including the characteristic malar or butterfly rash on the bridge of the nose, cheeks and face; the classic reddish/purple heliotrope rash; and Gottron’s papules on the extensor surfaces of the fingers. The rash typically appears on skin areas that are exposed to the sun, including elbows, knees, and ankles, so sunscreens and sun avoidance are advised for JDM patients. About 25% of patients present with subcutaneous calcinosis, which eventually affects 70% of patients.

To look for vasculopathy, examine the nail-bed capillaries with an ophthalmoscope, said Dr. Eberhard. In contrast to their normal, straight, “picket-fence” appearance, the capillaries in children with JDM show dilation and extensive branching; there may even be capillary loss. “You can quantify the disease and monitor improvement with treatment by examining nail-bed capillaries,” she said.

Symmetrical proximal weakness is another hallmark of JDM. Dr. Eberhard said that she immediately thinks of JDM when she hears that a child is having difficulty getting up the school bus stairs.

An urgent response is required if a child says that food is “sticking to his mouth”. This suggests a bulbar muscle weakness of central origin, with impaired swallowing and the potential for aspiration. This may necessitate placing the child on a soft diet or even hospitalization, said Dr. Eberhard.
JDM can produce other serious sequelae, including pulmonary fibrosis and perforation of the esophagus or small bowel.

The original five diagnostic criteria that were first presented in 1975 did not change for the subsequent 35 years (N. Engl. J. Med. 1975:292:344-7). In addition to symmetrical proximal weakness and rash, the diagnostic criteria are raised serum muscle enzymes, electromyogram evidence of myositis, and histologic evidence of myositis. Diagnosis of JDM requires the presence of four of the five criteria, she said.

Dr. Eberhard had no relevant financial disclosures.

^{Image above courtesy: Dermatology Online Journal via Wikipedia Commons.}

NEW YORK – Rituximab may offer an alternative treatment for children whose juvenile dermatomyositis does not respond to available therapies, depending on the outcome of an ongoing trial, Dr. B. Anne Eberhard said at a meeting sponsored by New York University.

There are no U.S. Food and Drug Administration–approved medications for juvenile dermatomyositis (JDM).

The RIM (Rituximab in Myositis) trial is a randomized, phase II, placebo-phase controlled, multicenter trial investigating the effect of rituximab on refractory dermatomyositis in children and adults. The study intended to enroll 50 children with JDM, and it will assess efficacy, safety, and determinants of treatment response and disease pathogenesis, including clinical, demographic, and immunopathologic factors.

The RIM trial results will be presented at the annual meeting of the American Academy of Rheumatology in November 2010, Dr. Chester V. Oddis said in an interview.

The study is sponsored by Genentech Inc., Biogen Idec Inc., and the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases, according to Dr. Oddis, who is the principal investigator and a professor of rheumatology at the University of Pittsburgh.

Dr. Eberhard noted that prednisone and methotrexate are the mainstays of treatment, for now. However, outcomes can be unsatisfactory either because symptoms remain poorly controlled or because side effects occur.

JDM is a relatively rare idiopathic inflammatory myopathy that can be physically disabling, disfiguring, and life threatening if left unchecked.

To facilitate diagnosis of JDM, the Childhood Myositis Assessment Scale (CMAS) was recently developed to allow clinicians to assess children for JDM in the office without the need for specialized equipment. The CMAS is a 14-activity, observational, performance-based assessment that measures physical function, strength, and endurance, explained Dr. Eberhard, who is a pediatric rheumatologist at the Albert Einstein College of Medicine in New York. For instance, it can be used to compare, from one visit to another, how well a child can raise his head or leg, go from a supine to sitting position, rise from a chair, or step on a stool. An abbreviated 9-maneuver test is also available.

Dr. Eberhard outlined other relatively simple ways to diagnose JDM in the office or at the bedside. The first is visual examination of the body, with a focus on skin changes, including the characteristic malar or butterfly rash on the bridge of the nose, cheeks and face; the classic reddish/purple heliotrope rash; and Gottron’s papules on the extensor surfaces of the fingers. The rash typically appears on skin areas that are exposed to the sun, including elbows, knees, and ankles, so sunscreens and sun avoidance are advised for JDM patients. About 25% of patients present with subcutaneous calcinosis, which eventually affects 70% of patients.

To look for vasculopathy, examine the nail-bed capillaries with an ophthalmoscope, said Dr. Eberhard. In contrast to their normal, straight, “picket-fence” appearance, the capillaries in children with JDM show dilation and extensive branching; there may even be capillary loss. “You can quantify the disease and monitor improvement with treatment by examining nail-bed capillaries,” she said.

Symmetrical proximal weakness is another hallmark of JDM. Dr. Eberhard said that she immediately thinks of JDM when she hears that a child is having difficulty getting up the school bus stairs.

An urgent response is required if a child says that food is “sticking to his mouth”. This suggests a bulbar muscle weakness of central origin, with impaired swallowing and the potential for aspiration. This may necessitate placing the child on a soft diet or even hospitalization, said Dr. Eberhard.
JDM can produce other serious sequelae, including pulmonary fibrosis and perforation of the esophagus or small bowel.

The original five diagnostic criteria that were first presented in 1975 did not change for the subsequent 35 years (N. Engl. J. Med. 1975:292:344-7). In addition to symmetrical proximal weakness and rash, the diagnostic criteria are raised serum muscle enzymes, electromyogram evidence of myositis, and histologic evidence of myositis. Diagnosis of JDM requires the presence of four of the five criteria, she said.

Dr. Eberhard had no relevant financial disclosures.

^{Image above courtesy: Dermatology Online Journal via Wikipedia Commons.}

SNOWMASS, Colo. – An effective vaccine against Epstein-Barr virus infection could conceivably turn systemic lupus erythematosus into a disease of historical interest within a couple of decades – but that’s far easier said than done.

“There have been three trials of capsid-based EBV vaccines. All have failed because the vaccines didn’t protect,” said

at a symposium sponsored by the American College of Rheumatology. Most people may be infected with five to nine substrains of the virus, he added. “We go through life possibly being reinfected by other strains as life progresses. Even the defenses that prevent us from getting mononucleosis over and over again are not sufficient to prevent reinfection. So finding a way to prevent the viral infection is going to be very complicated.”

For decades, Dr. Harley has been developing the hypothesis that EBV (in conjunction with genetic predisposition) is the cause of SLE. It’s a hypothesis that initially went nowhere, but it has gained considerable traction as a result of mounting evidence that has converged from epidemiologic, immunologic, and genetic studies conducted in many different centers.

When he first zeroed in on EBV as likely having a causative role in lupus, Dr. Harley understood that he would face scientific skepticism. For decades, it seemed that whenever researchers couldn’t explain the pathogenesis of various poorly understood diseases, they’d try to pin it on EBV. But not much has stuck to the Teflonlike virus.

“EBV ... has been blamed for everything, and yet very little has been established as being causative,” observed Dr. Harley, chair of the arthritis and immunology research program at the Oklahoma Medical Research Foundation in Oklahoma City.

Back in the 1980s, he laid the groundwork for his future studies of EBV when he recognized the unique research potential of the Department of Defense Serum Repository, which contains frozen serial specimens from more than 5 million armed forces personnel. He and his coworkers identified 130 individuals who developed SLE and for whom they found serum samples dating back to years before disease onset. This enabled the investigators to characterize – for the first time – the cascade of autoantibody production that often begins many years before SLE diagnosis (N. Engl. J. Med. 2003;349:1526-33).

The SLE patients tended to mount their immune response in a characteristic way. The first antibody to appear was directed against the viral protein EBV nuclear antigen–1 (EBNA-1). This antibody cross-reacted with the lupus-associated autoantigens Ro and Sm in lupus patients. Then, through molecular mimicry with self-antigens and the process of B-cell epitope spreading, the cross-reactive antibodies targeted non–cross-reactive autoepitopes and spread to a widening array of autoantigens, with generation of pathogenic autoimmunity. (Healthy individuals mount a far more limited immune response to EBV and EBNA-1 and do not produce cross-reactive antibodies.)

EBNA-1 is both immunogenic and antigenic. The researchers showed that nearly all military personnel who had SLE were seropositive for EBNA-1, whereas 12% of the military controls were not. This is consistent with the notion that, to lay the groundwork for SLE, an individual not only has to be infected with EBV but must also mount an immune response to EBNA-1.

“The host response to EBNA-1 is critical in the pathogenesis of SLE,” stressed Dr. Harley, who is also the George Lynn Cross Research Professor at the University of Oklahoma Health Sciences Center. EBV is a strong candidate for having a pathogenic role in SLE because it is a ubiquitous infection, with 95% or more of adults in the general population being seropositive. The virus persists in the host for life as a latent infection with a viral reservoir in B-lymphocytes. Low levels of lytic virus emerging in latency provoke persistent immune stimulation.

“It’s remarkable that about 7% of our T-cell repertoire is directed against EBV,” the immunologist continued.

Because EBV infection is so common in adults, Dr. Harley and coworkers studied seropositivity rates in a series of children and teens. The investigators demonstrated that 116 of 117 individuals with SLE (average age, 15.6 years) were seropositive against EBV, compared with two-thirds of controls. Indeed, EBV seropositivity was associated with a 50-fold increased probability of lupus (J. Clin. Invest. 1997;100:3019-26). Other investigators have independently replicated this work in more than half a dozen other cohorts.

 

There are additional differences between SLE patients and healthy controls in terms of response to EBV infection. Patients with SLE have 15- to 40-fold higher EBV loads, 10-100 times more EBV-infected B cells, and defective CD8 T-cell responses against EBV.

In an interview, Dr. Harley predicted that as EBV’s role in the pathogenesis of SLE becomes more fully understood, “there will be new opportunities for treatment.” For example, once the specific T-cell responses to the virus in SLE are better grasped, clinical studies of anti–T-cell therapies directed at those mechanisms will be appropriate.

“I expect most of the biologics will be evaluated in SLE before too long,” the physician added.

“If you accept the idea that the virus is a necessary condition in order to develop lupus—just hypothetically—then if a way was developed to rid the body of the virus and the virus’ presence was needed to sustain the disease, then that would be a new therapeutic approach. The virus has been adapted to human beings for something like 20 million years. So it has found a wonderful niche in our peculiar environment, and it has many presumably unknown ways of sustaining that infection. Nevertheless, a focused effort on trying to understand how the virus works would be a therapeutic approach that hasn’t been explored yet,” he said.

In terms of genetic predisposition, Dr. Harley and colleagues have identified 13 new genes associated with SLE.

Dr. Harley disclosed that he is on the board of directors of IVAX Diagnostics Inc., and JK Autoimmunity Inc. He is also a consultant to UCB and Bio-Rad Laboratories Inc.

SNOWMASS, Colo. – An effective vaccine against Epstein-Barr virus infection could conceivably turn systemic lupus erythematosus into a disease of historical interest within a couple of decades – but that’s far easier said than done.

“There have been three trials of capsid-based EBV vaccines. All have failed because the vaccines didn’t protect,” said

at a symposium sponsored by the American College of Rheumatology. Most people may be infected with five to nine substrains of the virus, he added. “We go through life possibly being reinfected by other strains as life progresses. Even the defenses that prevent us from getting mononucleosis over and over again are not sufficient to prevent reinfection. So finding a way to prevent the viral infection is going to be very complicated.”

For decades, Dr. Harley has been developing the hypothesis that EBV (in conjunction with genetic predisposition) is the cause of SLE. It’s a hypothesis that initially went nowhere, but it has gained considerable traction as a result of mounting evidence that has converged from epidemiologic, immunologic, and genetic studies conducted in many different centers.

When he first zeroed in on EBV as likely having a causative role in lupus, Dr. Harley understood that he would face scientific skepticism. For decades, it seemed that whenever researchers couldn’t explain the pathogenesis of various poorly understood diseases, they’d try to pin it on EBV. But not much has stuck to the Teflonlike virus.

“EBV ... has been blamed for everything, and yet very little has been established as being causative,” observed Dr. Harley, chair of the arthritis and immunology research program at the Oklahoma Medical Research Foundation in Oklahoma City.

Back in the 1980s, he laid the groundwork for his future studies of EBV when he recognized the unique research potential of the Department of Defense Serum Repository, which contains frozen serial specimens from more than 5 million armed forces personnel. He and his coworkers identified 130 individuals who developed SLE and for whom they found serum samples dating back to years before disease onset. This enabled the investigators to characterize – for the first time – the cascade of autoantibody production that often begins many years before SLE diagnosis (N. Engl. J. Med. 2003;349:1526-33).

The SLE patients tended to mount their immune response in a characteristic way. The first antibody to appear was directed against the viral protein EBV nuclear antigen–1 (EBNA-1). This antibody cross-reacted with the lupus-associated autoantigens Ro and Sm in lupus patients. Then, through molecular mimicry with self-antigens and the process of B-cell epitope spreading, the cross-reactive antibodies targeted non–cross-reactive autoepitopes and spread to a widening array of autoantigens, with generation of pathogenic autoimmunity. (Healthy individuals mount a far more limited immune response to EBV and EBNA-1 and do not produce cross-reactive antibodies.)

EBNA-1 is both immunogenic and antigenic. The researchers showed that nearly all military personnel who had SLE were seropositive for EBNA-1, whereas 12% of the military controls were not. This is consistent with the notion that, to lay the groundwork for SLE, an individual not only has to be infected with EBV but must also mount an immune response to EBNA-1.

“The host response to EBNA-1 is critical in the pathogenesis of SLE,” stressed Dr. Harley, who is also the George Lynn Cross Research Professor at the University of Oklahoma Health Sciences Center. EBV is a strong candidate for having a pathogenic role in SLE because it is a ubiquitous infection, with 95% or more of adults in the general population being seropositive. The virus persists in the host for life as a latent infection with a viral reservoir in B-lymphocytes. Low levels of lytic virus emerging in latency provoke persistent immune stimulation.

“It’s remarkable that about 7% of our T-cell repertoire is directed against EBV,” the immunologist continued.

Because EBV infection is so common in adults, Dr. Harley and coworkers studied seropositivity rates in a series of children and teens. The investigators demonstrated that 116 of 117 individuals with SLE (average age, 15.6 years) were seropositive against EBV, compared with two-thirds of controls. Indeed, EBV seropositivity was associated with a 50-fold increased probability of lupus (J. Clin. Invest. 1997;100:3019-26). Other investigators have independently replicated this work in more than half a dozen other cohorts.

 

There are additional differences between SLE patients and healthy controls in terms of response to EBV infection. Patients with SLE have 15- to 40-fold higher EBV loads, 10-100 times more EBV-infected B cells, and defective CD8 T-cell responses against EBV.

In an interview, Dr. Harley predicted that as EBV’s role in the pathogenesis of SLE becomes more fully understood, “there will be new opportunities for treatment.” For example, once the specific T-cell responses to the virus in SLE are better grasped, clinical studies of anti–T-cell therapies directed at those mechanisms will be appropriate.

“I expect most of the biologics will be evaluated in SLE before too long,” the physician added.

“If you accept the idea that the virus is a necessary condition in order to develop lupus—just hypothetically—then if a way was developed to rid the body of the virus and the virus’ presence was needed to sustain the disease, then that would be a new therapeutic approach. The virus has been adapted to human beings for something like 20 million years. So it has found a wonderful niche in our peculiar environment, and it has many presumably unknown ways of sustaining that infection. Nevertheless, a focused effort on trying to understand how the virus works would be a therapeutic approach that hasn’t been explored yet,” he said.

In terms of genetic predisposition, Dr. Harley and colleagues have identified 13 new genes associated with SLE.

Dr. Harley disclosed that he is on the board of directors of IVAX Diagnostics Inc., and JK Autoimmunity Inc. He is also a consultant to UCB and Bio-Rad Laboratories Inc.

SNOWMASS, Colo. – An effective vaccine against Epstein-Barr virus infection could conceivably turn systemic lupus erythematosus into a disease of historical interest within a couple of decades – but that’s far easier said than done.

“There have been three trials of capsid-based EBV vaccines. All have failed because the vaccines didn’t protect,” said

at a symposium sponsored by the American College of Rheumatology. Most people may be infected with five to nine substrains of the virus, he added. “We go through life possibly being reinfected by other strains as life progresses. Even the defenses that prevent us from getting mononucleosis over and over again are not sufficient to prevent reinfection. So finding a way to prevent the viral infection is going to be very complicated.”

For decades, Dr. Harley has been developing the hypothesis that EBV (in conjunction with genetic predisposition) is the cause of SLE. It’s a hypothesis that initially went nowhere, but it has gained considerable traction as a result of mounting evidence that has converged from epidemiologic, immunologic, and genetic studies conducted in many different centers.

When he first zeroed in on EBV as likely having a causative role in lupus, Dr. Harley understood that he would face scientific skepticism. For decades, it seemed that whenever researchers couldn’t explain the pathogenesis of various poorly understood diseases, they’d try to pin it on EBV. But not much has stuck to the Teflonlike virus.

“EBV ... has been blamed for everything, and yet very little has been established as being causative,” observed Dr. Harley, chair of the arthritis and immunology research program at the Oklahoma Medical Research Foundation in Oklahoma City.

Back in the 1980s, he laid the groundwork for his future studies of EBV when he recognized the unique research potential of the Department of Defense Serum Repository, which contains frozen serial specimens from more than 5 million armed forces personnel. He and his coworkers identified 130 individuals who developed SLE and for whom they found serum samples dating back to years before disease onset. This enabled the investigators to characterize – for the first time – the cascade of autoantibody production that often begins many years before SLE diagnosis (N. Engl. J. Med. 2003;349:1526-33).

The SLE patients tended to mount their immune response in a characteristic way. The first antibody to appear was directed against the viral protein EBV nuclear antigen–1 (EBNA-1). This antibody cross-reacted with the lupus-associated autoantigens Ro and Sm in lupus patients. Then, through molecular mimicry with self-antigens and the process of B-cell epitope spreading, the cross-reactive antibodies targeted non–cross-reactive autoepitopes and spread to a widening array of autoantigens, with generation of pathogenic autoimmunity. (Healthy individuals mount a far more limited immune response to EBV and EBNA-1 and do not produce cross-reactive antibodies.)

EBNA-1 is both immunogenic and antigenic. The researchers showed that nearly all military personnel who had SLE were seropositive for EBNA-1, whereas 12% of the military controls were not. This is consistent with the notion that, to lay the groundwork for SLE, an individual not only has to be infected with EBV but must also mount an immune response to EBNA-1.

“The host response to EBNA-1 is critical in the pathogenesis of SLE,” stressed Dr. Harley, who is also the George Lynn Cross Research Professor at the University of Oklahoma Health Sciences Center. EBV is a strong candidate for having a pathogenic role in SLE because it is a ubiquitous infection, with 95% or more of adults in the general population being seropositive. The virus persists in the host for life as a latent infection with a viral reservoir in B-lymphocytes. Low levels of lytic virus emerging in latency provoke persistent immune stimulation.

“It’s remarkable that about 7% of our T-cell repertoire is directed against EBV,” the immunologist continued.

Because EBV infection is so common in adults, Dr. Harley and coworkers studied seropositivity rates in a series of children and teens. The investigators demonstrated that 116 of 117 individuals with SLE (average age, 15.6 years) were seropositive against EBV, compared with two-thirds of controls. Indeed, EBV seropositivity was associated with a 50-fold increased probability of lupus (J. Clin. Invest. 1997;100:3019-26). Other investigators have independently replicated this work in more than half a dozen other cohorts.

 

There are additional differences between SLE patients and healthy controls in terms of response to EBV infection. Patients with SLE have 15- to 40-fold higher EBV loads, 10-100 times more EBV-infected B cells, and defective CD8 T-cell responses against EBV.

In an interview, Dr. Harley predicted that as EBV’s role in the pathogenesis of SLE becomes more fully understood, “there will be new opportunities for treatment.” For example, once the specific T-cell responses to the virus in SLE are better grasped, clinical studies of anti–T-cell therapies directed at those mechanisms will be appropriate.

“I expect most of the biologics will be evaluated in SLE before too long,” the physician added.

“If you accept the idea that the virus is a necessary condition in order to develop lupus—just hypothetically—then if a way was developed to rid the body of the virus and the virus’ presence was needed to sustain the disease, then that would be a new therapeutic approach. The virus has been adapted to human beings for something like 20 million years. So it has found a wonderful niche in our peculiar environment, and it has many presumably unknown ways of sustaining that infection. Nevertheless, a focused effort on trying to understand how the virus works would be a therapeutic approach that hasn’t been explored yet,” he said.

In terms of genetic predisposition, Dr. Harley and colleagues have identified 13 new genes associated with SLE.

Dr. Harley disclosed that he is on the board of directors of IVAX Diagnostics Inc., and JK Autoimmunity Inc. He is also a consultant to UCB and Bio-Rad Laboratories Inc.

MIAMI – The rate of serious infectious events is significantly higher for rheumatoid arthritis patients who are treated with methotrexate vs. placebo, according to a meta-analysis of 17 randomized controlled trials.

The rate of infectious events that required hospitalization and/or parenteral antibiotic treatment was 2.3 per 100 patient-years of exposure.

This finding offers clinicians a number to consider when they compare serious infectious risks between methotrexate and other treatments, including biologic agents, Dr. Jennifer Powers said during a poster discussion session at the annual meeting of the American Academy of Dermatology.

Dr. Daniel E. Furst noted in an interview that the issue of infection in patients on methotrexate is one physicians often forget about, but it is significant because methotrexate’s infection risk should be a factor when physicians consider whether to initiate biologic therapy.

Unfortunately, the research does not address whether the infection risk is even higher in patients who receive both methotrexate and a biologic agent than in patients on one or the other as monotherapy. But the findings still are of interest, said Dr. Furst, who is the Carl M. Pearson Professor of Rheumatology at the University of California, Los Angeles.

In contrast, there was no statistically significant higher risk for a serious infectious event (SIE) associated with methotrexate in a meta-analysis of five psoriasis trials (2.2 serious infectious events per 100 patient-years) or a meta-analysis of five psoriatic arthritis studies (0.9 events per 100 patient-years).

The small number of eligible studies in psoriasis and psoriatic arthritis might explain the lack of statistical significance, said Dr. Powers, a first-year resident at Grand Rapids (Michigan) Medical Education and Research Center. It could also be that patients with rheumatoid arthritis generally are sicker. The Food and Drug Administration first approved methotrexate in 1953 and granted a new indication to treat rheumatoid arthritis in 1988. These approvals predate the era when the agency required more stringent reporting of infectious adverse events, Dr. Powers said.

She and her colleague, Dr. Richard W. Martin, conducted a literature search for randomized, placebo-controlled studies published from January 2005 through May 2009 in Embase Biomedical Answers, the National Library of Medicine’s Medline database, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the Cochrane Library. Patients in each study received oral methotrexate (7.5-30 mg/wk) for at least 12 weeks.

Previous observational studies reported conflicting results. “It was interesting to me when going over the literature [to find] how controversial infection with methotrexate is and how little consensus there is,” Dr. Powers said. “These are rare cases, but they are out there.”

“There are not great data about [SIEs] in methotrexate,” Dr. Powers said. “So there was a hole in the literature we wanted to fill.”

Randomized, controlled studies were included in the meta-analyses only if they met objective quality criteria. For example, participants had to be adults with clearly defined disease, and they could not be taking more than 10-mg prednisone. Also, studies were excluded if 20% or more of patients were lost to follow-up.

Biologic agents have transformed psoriasis treatment, but they are associated with increased serious infectious events and significant expense, which revives interest in the comparative efficacy of standard vs. new therapies, the authors wrote.

“This is really an important counterpoint when we are discussing SIE risks for methotrexate. ... It is generally accepted that methotrexate has lower risk of SIE than biologics,” Dr. Powers said. For example, the product labeling for ustekinumab (Stelara) notes that serious infections have occurred. In addition, the risk of serious infections that can lead to hospitalization and death are included on black box warnings for etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira).

A meeting attendee said the findings would be more robust if the methotrexate trials in the meta-analyses went beyond 12 weeks. Dr. Powers agreed, adding that these results, “are definitely limited by the fact that there are trials out there that do not follow patients for a longer time.”

None of the investigators had any relevant financial disclosures.

MIAMI – The rate of serious infectious events is significantly higher for rheumatoid arthritis patients who are treated with methotrexate vs. placebo, according to a meta-analysis of 17 randomized controlled trials.

The rate of infectious events that required hospitalization and/or parenteral antibiotic treatment was 2.3 per 100 patient-years of exposure.

This finding offers clinicians a number to consider when they compare serious infectious risks between methotrexate and other treatments, including biologic agents, Dr. Jennifer Powers said during a poster discussion session at the annual meeting of the American Academy of Dermatology.

Dr. Daniel E. Furst noted in an interview that the issue of infection in patients on methotrexate is one physicians often forget about, but it is significant because methotrexate’s infection risk should be a factor when physicians consider whether to initiate biologic therapy.

Unfortunately, the research does not address whether the infection risk is even higher in patients who receive both methotrexate and a biologic agent than in patients on one or the other as monotherapy. But the findings still are of interest, said Dr. Furst, who is the Carl M. Pearson Professor of Rheumatology at the University of California, Los Angeles.

In contrast, there was no statistically significant higher risk for a serious infectious event (SIE) associated with methotrexate in a meta-analysis of five psoriasis trials (2.2 serious infectious events per 100 patient-years) or a meta-analysis of five psoriatic arthritis studies (0.9 events per 100 patient-years).

The small number of eligible studies in psoriasis and psoriatic arthritis might explain the lack of statistical significance, said Dr. Powers, a first-year resident at Grand Rapids (Michigan) Medical Education and Research Center. It could also be that patients with rheumatoid arthritis generally are sicker. The Food and Drug Administration first approved methotrexate in 1953 and granted a new indication to treat rheumatoid arthritis in 1988. These approvals predate the era when the agency required more stringent reporting of infectious adverse events, Dr. Powers said.

She and her colleague, Dr. Richard W. Martin, conducted a literature search for randomized, placebo-controlled studies published from January 2005 through May 2009 in Embase Biomedical Answers, the National Library of Medicine’s Medline database, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the Cochrane Library. Patients in each study received oral methotrexate (7.5-30 mg/wk) for at least 12 weeks.

Previous observational studies reported conflicting results. “It was interesting to me when going over the literature [to find] how controversial infection with methotrexate is and how little consensus there is,” Dr. Powers said. “These are rare cases, but they are out there.”

“There are not great data about [SIEs] in methotrexate,” Dr. Powers said. “So there was a hole in the literature we wanted to fill.”

Randomized, controlled studies were included in the meta-analyses only if they met objective quality criteria. For example, participants had to be adults with clearly defined disease, and they could not be taking more than 10-mg prednisone. Also, studies were excluded if 20% or more of patients were lost to follow-up.

Biologic agents have transformed psoriasis treatment, but they are associated with increased serious infectious events and significant expense, which revives interest in the comparative efficacy of standard vs. new therapies, the authors wrote.

“This is really an important counterpoint when we are discussing SIE risks for methotrexate. ... It is generally accepted that methotrexate has lower risk of SIE than biologics,” Dr. Powers said. For example, the product labeling for ustekinumab (Stelara) notes that serious infections have occurred. In addition, the risk of serious infections that can lead to hospitalization and death are included on black box warnings for etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira).

A meeting attendee said the findings would be more robust if the methotrexate trials in the meta-analyses went beyond 12 weeks. Dr. Powers agreed, adding that these results, “are definitely limited by the fact that there are trials out there that do not follow patients for a longer time.”

None of the investigators had any relevant financial disclosures.

MIAMI – The rate of serious infectious events is significantly higher for rheumatoid arthritis patients who are treated with methotrexate vs. placebo, according to a meta-analysis of 17 randomized controlled trials.

The rate of infectious events that required hospitalization and/or parenteral antibiotic treatment was 2.3 per 100 patient-years of exposure.

This finding offers clinicians a number to consider when they compare serious infectious risks between methotrexate and other treatments, including biologic agents, Dr. Jennifer Powers said during a poster discussion session at the annual meeting of the American Academy of Dermatology.

Dr. Daniel E. Furst noted in an interview that the issue of infection in patients on methotrexate is one physicians often forget about, but it is significant because methotrexate’s infection risk should be a factor when physicians consider whether to initiate biologic therapy.

Unfortunately, the research does not address whether the infection risk is even higher in patients who receive both methotrexate and a biologic agent than in patients on one or the other as monotherapy. But the findings still are of interest, said Dr. Furst, who is the Carl M. Pearson Professor of Rheumatology at the University of California, Los Angeles.

In contrast, there was no statistically significant higher risk for a serious infectious event (SIE) associated with methotrexate in a meta-analysis of five psoriasis trials (2.2 serious infectious events per 100 patient-years) or a meta-analysis of five psoriatic arthritis studies (0.9 events per 100 patient-years).

The small number of eligible studies in psoriasis and psoriatic arthritis might explain the lack of statistical significance, said Dr. Powers, a first-year resident at Grand Rapids (Michigan) Medical Education and Research Center. It could also be that patients with rheumatoid arthritis generally are sicker. The Food and Drug Administration first approved methotrexate in 1953 and granted a new indication to treat rheumatoid arthritis in 1988. These approvals predate the era when the agency required more stringent reporting of infectious adverse events, Dr. Powers said.

She and her colleague, Dr. Richard W. Martin, conducted a literature search for randomized, placebo-controlled studies published from January 2005 through May 2009 in Embase Biomedical Answers, the National Library of Medicine’s Medline database, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the Cochrane Library. Patients in each study received oral methotrexate (7.5-30 mg/wk) for at least 12 weeks.

Previous observational studies reported conflicting results. “It was interesting to me when going over the literature [to find] how controversial infection with methotrexate is and how little consensus there is,” Dr. Powers said. “These are rare cases, but they are out there.”

“There are not great data about [SIEs] in methotrexate,” Dr. Powers said. “So there was a hole in the literature we wanted to fill.”

Randomized, controlled studies were included in the meta-analyses only if they met objective quality criteria. For example, participants had to be adults with clearly defined disease, and they could not be taking more than 10-mg prednisone. Also, studies were excluded if 20% or more of patients were lost to follow-up.

Biologic agents have transformed psoriasis treatment, but they are associated with increased serious infectious events and significant expense, which revives interest in the comparative efficacy of standard vs. new therapies, the authors wrote.

“This is really an important counterpoint when we are discussing SIE risks for methotrexate. ... It is generally accepted that methotrexate has lower risk of SIE than biologics,” Dr. Powers said. For example, the product labeling for ustekinumab (Stelara) notes that serious infections have occurred. In addition, the risk of serious infections that can lead to hospitalization and death are included on black box warnings for etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira).

A meeting attendee said the findings would be more robust if the methotrexate trials in the meta-analyses went beyond 12 weeks. Dr. Powers agreed, adding that these results, “are definitely limited by the fact that there are trials out there that do not follow patients for a longer time.”

None of the investigators had any relevant financial disclosures.

SNOWMASS, Colo. – Optimal treatment of chronic erythematous candidiasis in patients with Sjögren’s syndrome is complicated by the severe burden of dental caries associated with the rheumatic condition.

“The problem with the usual liquid nystatin preparations used for oral thrush is they contain a lot of sugar. They are not good for patients with Sjögren’s syndrome,” Dr. Alan N. Baer said at a symposium sponsored by the American College of Rheumatology.

“We use the nystatin vaginal tablets, which don’t contain the excess sugar. The patient places a nystatin vaginal tablet in the mouth twice a day, allowing it to dissolve slowly. It’s not the greatest taste in the world, but patients get tremendous benefit from clearing this infection,” explained Dr. Baer, director of the multidisciplinary Jerome L. Greene Sjögren’s Syndrome Center at Johns Hopkins University in Baltimore.

Clotrimazole vaginal tablets can be employed as topical therapy in identical fashion,he added.

In patients with Sjögren’s syndrome who have mild salivary hypofunction, oral fluconazole or another systemic antifungal agent is effective therapy. The vaginal tablets are reserved for patients with severe chronic hyposalivation that precludes the achievement of therapeutic levels of the systemic antifungal in the mouth.

Chronic erythematous candidiasis is distinct from pseudomembranous candidiasis, which is by far the most common form of oral candidiasis in settings other than Sjögren’s syndrome. Pseudomembranous candidiasis features distinctive white plaques or specks that can be wiped off. Chronic erythematous candidiasis, in contrast, is marked by flat red patches. It affects one-third of Sjögren’s syndrome patients who have chronic hyposalivation. Symptoms include a mucosal burning sensation, metallic taste, and intolerance to spicy or acidic foods.

Sjögren’s syndrome patients commonly have dry mouth, which also is responsive to conservative measures. Saliva substitutes can bring relief, as can oral pilocarpine or cevimeline, but relatively few patients seem to stick with any of these measures long term. Instead, they often prefer simply to carry a water bottle and drink from it frequently. If they choose this option, it’s important to tell them to take only small sips – just enough to moisten the mouth. Large quantities will dilute the beneficial mucins in the oral cavity, thereby aggravating their condition, according to Dr. Baer.

Dry eyes are the other troublesome sicca symptom that’s extremely common in Sjögren’s syndrome. A humidifier in the bedroom is beneficial. Artificial tears are important. Topical therapy with corticosteroid or cyclosporine eye drops is very helpful. Oral fish oil and flaxseed oil have also been shown to be beneficial, and patients should be encouraged to take one or the other, he continued.

One of the enduring mysteries of Sjögren’s syndrome has been the cause of the sicca symptoms that are disease hallmarks. The explanation can’t lie in straightforward autoimmune destruction of the salivary and lacrimal glands, because the severity of sicca symptoms correlates poorly with histopathologic findings. Investigators at the National Institutes of Health have recently provided evidence to suggest that salivary gland inflammation and dysfunction may be two distinctly different pathophysiologic processes.

“It’s quite likely that inflammation occurring around the salivary gland ducts can impair transmission of impulses down the nerve fibers, leading to the exaggerated glandular dysfunction, as opposed to simply glandular destruction,” he said.

Dr. Baer reported having no relevant financial involvements.

SNOWMASS, Colo. – Optimal treatment of chronic erythematous candidiasis in patients with Sjögren’s syndrome is complicated by the severe burden of dental caries associated with the rheumatic condition.

“The problem with the usual liquid nystatin preparations used for oral thrush is they contain a lot of sugar. They are not good for patients with Sjögren’s syndrome,” Dr. Alan N. Baer said at a symposium sponsored by the American College of Rheumatology.

“We use the nystatin vaginal tablets, which don’t contain the excess sugar. The patient places a nystatin vaginal tablet in the mouth twice a day, allowing it to dissolve slowly. It’s not the greatest taste in the world, but patients get tremendous benefit from clearing this infection,” explained Dr. Baer, director of the multidisciplinary Jerome L. Greene Sjögren’s Syndrome Center at Johns Hopkins University in Baltimore.

Clotrimazole vaginal tablets can be employed as topical therapy in identical fashion,he added.

In patients with Sjögren’s syndrome who have mild salivary hypofunction, oral fluconazole or another systemic antifungal agent is effective therapy. The vaginal tablets are reserved for patients with severe chronic hyposalivation that precludes the achievement of therapeutic levels of the systemic antifungal in the mouth.

Chronic erythematous candidiasis is distinct from pseudomembranous candidiasis, which is by far the most common form of oral candidiasis in settings other than Sjögren’s syndrome. Pseudomembranous candidiasis features distinctive white plaques or specks that can be wiped off. Chronic erythematous candidiasis, in contrast, is marked by flat red patches. It affects one-third of Sjögren’s syndrome patients who have chronic hyposalivation. Symptoms include a mucosal burning sensation, metallic taste, and intolerance to spicy or acidic foods.

Sjögren’s syndrome patients commonly have dry mouth, which also is responsive to conservative measures. Saliva substitutes can bring relief, as can oral pilocarpine or cevimeline, but relatively few patients seem to stick with any of these measures long term. Instead, they often prefer simply to carry a water bottle and drink from it frequently. If they choose this option, it’s important to tell them to take only small sips – just enough to moisten the mouth. Large quantities will dilute the beneficial mucins in the oral cavity, thereby aggravating their condition, according to Dr. Baer.

Dry eyes are the other troublesome sicca symptom that’s extremely common in Sjögren’s syndrome. A humidifier in the bedroom is beneficial. Artificial tears are important. Topical therapy with corticosteroid or cyclosporine eye drops is very helpful. Oral fish oil and flaxseed oil have also been shown to be beneficial, and patients should be encouraged to take one or the other, he continued.

One of the enduring mysteries of Sjögren’s syndrome has been the cause of the sicca symptoms that are disease hallmarks. The explanation can’t lie in straightforward autoimmune destruction of the salivary and lacrimal glands, because the severity of sicca symptoms correlates poorly with histopathologic findings. Investigators at the National Institutes of Health have recently provided evidence to suggest that salivary gland inflammation and dysfunction may be two distinctly different pathophysiologic processes.

“It’s quite likely that inflammation occurring around the salivary gland ducts can impair transmission of impulses down the nerve fibers, leading to the exaggerated glandular dysfunction, as opposed to simply glandular destruction,” he said.

Dr. Baer reported having no relevant financial involvements.

SNOWMASS, Colo. – Optimal treatment of chronic erythematous candidiasis in patients with Sjögren’s syndrome is complicated by the severe burden of dental caries associated with the rheumatic condition.

“The problem with the usual liquid nystatin preparations used for oral thrush is they contain a lot of sugar. They are not good for patients with Sjögren’s syndrome,” Dr. Alan N. Baer said at a symposium sponsored by the American College of Rheumatology.

“We use the nystatin vaginal tablets, which don’t contain the excess sugar. The patient places a nystatin vaginal tablet in the mouth twice a day, allowing it to dissolve slowly. It’s not the greatest taste in the world, but patients get tremendous benefit from clearing this infection,” explained Dr. Baer, director of the multidisciplinary Jerome L. Greene Sjögren’s Syndrome Center at Johns Hopkins University in Baltimore.

Clotrimazole vaginal tablets can be employed as topical therapy in identical fashion,he added.

In patients with Sjögren’s syndrome who have mild salivary hypofunction, oral fluconazole or another systemic antifungal agent is effective therapy. The vaginal tablets are reserved for patients with severe chronic hyposalivation that precludes the achievement of therapeutic levels of the systemic antifungal in the mouth.

Chronic erythematous candidiasis is distinct from pseudomembranous candidiasis, which is by far the most common form of oral candidiasis in settings other than Sjögren’s syndrome. Pseudomembranous candidiasis features distinctive white plaques or specks that can be wiped off. Chronic erythematous candidiasis, in contrast, is marked by flat red patches. It affects one-third of Sjögren’s syndrome patients who have chronic hyposalivation. Symptoms include a mucosal burning sensation, metallic taste, and intolerance to spicy or acidic foods.

Sjögren’s syndrome patients commonly have dry mouth, which also is responsive to conservative measures. Saliva substitutes can bring relief, as can oral pilocarpine or cevimeline, but relatively few patients seem to stick with any of these measures long term. Instead, they often prefer simply to carry a water bottle and drink from it frequently. If they choose this option, it’s important to tell them to take only small sips – just enough to moisten the mouth. Large quantities will dilute the beneficial mucins in the oral cavity, thereby aggravating their condition, according to Dr. Baer.

Dry eyes are the other troublesome sicca symptom that’s extremely common in Sjögren’s syndrome. A humidifier in the bedroom is beneficial. Artificial tears are important. Topical therapy with corticosteroid or cyclosporine eye drops is very helpful. Oral fish oil and flaxseed oil have also been shown to be beneficial, and patients should be encouraged to take one or the other, he continued.

One of the enduring mysteries of Sjögren’s syndrome has been the cause of the sicca symptoms that are disease hallmarks. The explanation can’t lie in straightforward autoimmune destruction of the salivary and lacrimal glands, because the severity of sicca symptoms correlates poorly with histopathologic findings. Investigators at the National Institutes of Health have recently provided evidence to suggest that salivary gland inflammation and dysfunction may be two distinctly different pathophysiologic processes.

“It’s quite likely that inflammation occurring around the salivary gland ducts can impair transmission of impulses down the nerve fibers, leading to the exaggerated glandular dysfunction, as opposed to simply glandular destruction,” he said.

Dr. Baer reported having no relevant financial involvements.

SNOWMASS, Colo. – Treatment of cutaneous lupus erythematosus with hydroxychloroquine appears to delay onset of systemic lupus erythematosus, judging from findings of a retrospective study.

Given the growing body of evidence that cutaneous lupus erythematosus (LE) has systemic implications, “I’m beginning more and more patients earlier on antimalarials,” Dr. Jeffrey P. Callen said at a symposium sponsored by the American College of Rheumatology.

He cited findings from an Oklahoma Medical Research Foundation study in which investigators identified 130 U.S. military personnel who met ACR criteria for systemic LE (SLE). Twenty-six of them were previously treated with hydroxychloroquine (Plaquenil) when their disease was limited to the skin. The median time from their first skin lesions to diagnosis of SLE was 1.08 years, compared with 0.29 years in patients who did not receive hydroxychloroquine for their limited skin involvement.

The hydroxychloroquine-treated cohort also had a lower rate of autoantibody accumulation and fewer autoantibody specificities at the time they were diagnosed with SLE and thereafter. All of this is consistent with the notion that hydroxychloroquine therapy delays SLE onset, according to Dr. Callen, professor of medicine and chief of the division of dermatology at the University of Louisville (Ky).

In contrast, treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) had no impact on the length of time between onset of cutaneous LE and development of SLE (Lupus 2007;16:401-9).

Independent evidence that cutaneous LE not uncommonly progresses to SLE comes from a recent retrospective population-based Mayo Clinic study involving the entire population of Olmsted County, Minn. The investigators found that the collective incidence of all subtypes of cutaneous LE, exclusive of drug-induced LE, was 4.3 cases per 100,000 population during 1965-2005. That’s comparable with published figures for the incidence of SLE. The age- and gender-adjusted prevalence of cutaneous LE in early 2006 was 73.2 cases per 100,000 in this predominantly white population.

Cutaneous LE progressed to SLE in 12% of individuals, with a mean 8.2 years between the two diagnoses (Arch. Dermatol. 2009;145:249-53).

Dr. Callen noted that a prospective, blinded clinical trial would be needed to establish definitively that antimalarial therapy delays or prevents SLE. Even in the absence of such compelling evidence, he said he is a big believer in the early use of antimalarial agents in cutaneous LE for another reason: topical corticosteroids, widely advocated as first-line therapy, are not all that effective.

“They work well in clinical trials. They don’t work in clinical practice,” the dermatologist said.

The reason? They’re so messy and inconvenient that many patients simply do not use them as directed.

Intralesional corticosteroid injections are effective, but the benefits are temporary and many patients would rather take an oral medication than come in to the office for repeated injections, he continued.

His first-line systemic therapy is oral hydroxychloroquine at a maximum dose of 6.5 mg/kg of ideal body weight. At that dose, he has not encountered problems with ocular toxicity. Nonetheless, he tries to lower the dose once a patient’s disease is well controlled. Chloroquine seems to be slightly more effective than hydroxychloroquine but also more oculotoxic, according to Dr. Callen.

Smokers with cutaneous LE respond less robustly to antimalarials. If they can be persuaded to quit they will see further clinical improvement, although it often takes close to a year to become evident.

Sun-protective clothing and a broad-spectrum sunscreen are essential parts of the treatment of cutaneous LE. Dr. Callen recommends Neutrogena UltraSheer, which has desirable characteristics and is easy to find, to his patients with lupus or dermatomyositis.

A careful drug history is a must in patients with subacute cutaneous LE because the skin disease may be drug induced in upwards of one-fifth of cases. The most common offenders are hydrochlorothiazide and terbinafine. Others include ACE inhibitors, calcium channel blockers, bupropion, phenothiazines, anti–tumor necrosis factor agents, and statins. If a patient has been on a drug for more than 6 months prior to onset of cutaneous LE, the lesions are probably not drug induced. Clinical improvement or resolution of drug-induced subacute cutaneous LE typically occurs within a few weeks to 6 months after stopping the offending drug.

“If we in dermatology and you in rheumatology don’t get a careful drug history from the patients and alter the drugs they’re on, we’ll miss the opportunity to cure this disease,” he stressed.

In cutaneous LE patients who do not respond to or cannot tolerate antimalarials, there are good alternative systemic options.

“Thalidomide is a teratogen, but if you pick the right patients it works really well. Almost all patients with cutaneous lupus will respond to thalidomide, more than half with a complete response and the rest partially,” Dr. Callen said.

 

The major toxicity with thalidomide is a cumulative dose-dependent sensory neuropathy that is not always reversible upon drug discontinuation. Dr. Callen therefore keeps the dose as low as possible: Maintenance therapy might range from 50 mg/day to 25 mg every second or third day. He said he usually employs thalidomide in conjunction with an antimalarial agent unless the patient has antimalarial toxicity. A response to thalidomide becomes evident within a few weeks, although the full response takes about 3 months. Relapse is common with discontinuation of thalidomide; restarting the drug usually restores the clinical response, he said.

Other systemic options include dapsone (which in a controlled trial proved slightly less effective than chloroquine), methotrexate, azathioprine, and mycophenolate mofetil (CellCept).

The two major subtypes of cutaneous LE are discoid and subacute. Discoid lesions leave scarring and atrophy. Subacute cutaneous LE lesions do not, although there may be residual hypopigmentation. Discoid LE is subcategorized into localized to the head and neck or widespread. The distinction is clinically relevant because widespread discoid LE is more difficult to control, has a higher rate of associated serologic abnormalities, and probably is more likely to progress to SLE.

Dr. Callen disclosed serving as a consultant to Abbott, Amgen, Centocor, Electro-Optical Sciences, and Medicis.

SNOWMASS, Colo. – Treatment of cutaneous lupus erythematosus with hydroxychloroquine appears to delay onset of systemic lupus erythematosus, judging from findings of a retrospective study.

Given the growing body of evidence that cutaneous lupus erythematosus (LE) has systemic implications, “I’m beginning more and more patients earlier on antimalarials,” Dr. Jeffrey P. Callen said at a symposium sponsored by the American College of Rheumatology.

He cited findings from an Oklahoma Medical Research Foundation study in which investigators identified 130 U.S. military personnel who met ACR criteria for systemic LE (SLE). Twenty-six of them were previously treated with hydroxychloroquine (Plaquenil) when their disease was limited to the skin. The median time from their first skin lesions to diagnosis of SLE was 1.08 years, compared with 0.29 years in patients who did not receive hydroxychloroquine for their limited skin involvement.

The hydroxychloroquine-treated cohort also had a lower rate of autoantibody accumulation and fewer autoantibody specificities at the time they were diagnosed with SLE and thereafter. All of this is consistent with the notion that hydroxychloroquine therapy delays SLE onset, according to Dr. Callen, professor of medicine and chief of the division of dermatology at the University of Louisville (Ky).

In contrast, treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) had no impact on the length of time between onset of cutaneous LE and development of SLE (Lupus 2007;16:401-9).

Independent evidence that cutaneous LE not uncommonly progresses to SLE comes from a recent retrospective population-based Mayo Clinic study involving the entire population of Olmsted County, Minn. The investigators found that the collective incidence of all subtypes of cutaneous LE, exclusive of drug-induced LE, was 4.3 cases per 100,000 population during 1965-2005. That’s comparable with published figures for the incidence of SLE. The age- and gender-adjusted prevalence of cutaneous LE in early 2006 was 73.2 cases per 100,000 in this predominantly white population.

Cutaneous LE progressed to SLE in 12% of individuals, with a mean 8.2 years between the two diagnoses (Arch. Dermatol. 2009;145:249-53).

Dr. Callen noted that a prospective, blinded clinical trial would be needed to establish definitively that antimalarial therapy delays or prevents SLE. Even in the absence of such compelling evidence, he said he is a big believer in the early use of antimalarial agents in cutaneous LE for another reason: topical corticosteroids, widely advocated as first-line therapy, are not all that effective.

“They work well in clinical trials. They don’t work in clinical practice,” the dermatologist said.

The reason? They’re so messy and inconvenient that many patients simply do not use them as directed.

Intralesional corticosteroid injections are effective, but the benefits are temporary and many patients would rather take an oral medication than come in to the office for repeated injections, he continued.

His first-line systemic therapy is oral hydroxychloroquine at a maximum dose of 6.5 mg/kg of ideal body weight. At that dose, he has not encountered problems with ocular toxicity. Nonetheless, he tries to lower the dose once a patient’s disease is well controlled. Chloroquine seems to be slightly more effective than hydroxychloroquine but also more oculotoxic, according to Dr. Callen.

Smokers with cutaneous LE respond less robustly to antimalarials. If they can be persuaded to quit they will see further clinical improvement, although it often takes close to a year to become evident.

Sun-protective clothing and a broad-spectrum sunscreen are essential parts of the treatment of cutaneous LE. Dr. Callen recommends Neutrogena UltraSheer, which has desirable characteristics and is easy to find, to his patients with lupus or dermatomyositis.

A careful drug history is a must in patients with subacute cutaneous LE because the skin disease may be drug induced in upwards of one-fifth of cases. The most common offenders are hydrochlorothiazide and terbinafine. Others include ACE inhibitors, calcium channel blockers, bupropion, phenothiazines, anti–tumor necrosis factor agents, and statins. If a patient has been on a drug for more than 6 months prior to onset of cutaneous LE, the lesions are probably not drug induced. Clinical improvement or resolution of drug-induced subacute cutaneous LE typically occurs within a few weeks to 6 months after stopping the offending drug.

“If we in dermatology and you in rheumatology don’t get a careful drug history from the patients and alter the drugs they’re on, we’ll miss the opportunity to cure this disease,” he stressed.

In cutaneous LE patients who do not respond to or cannot tolerate antimalarials, there are good alternative systemic options.

“Thalidomide is a teratogen, but if you pick the right patients it works really well. Almost all patients with cutaneous lupus will respond to thalidomide, more than half with a complete response and the rest partially,” Dr. Callen said.

 

The major toxicity with thalidomide is a cumulative dose-dependent sensory neuropathy that is not always reversible upon drug discontinuation. Dr. Callen therefore keeps the dose as low as possible: Maintenance therapy might range from 50 mg/day to 25 mg every second or third day. He said he usually employs thalidomide in conjunction with an antimalarial agent unless the patient has antimalarial toxicity. A response to thalidomide becomes evident within a few weeks, although the full response takes about 3 months. Relapse is common with discontinuation of thalidomide; restarting the drug usually restores the clinical response, he said.

Other systemic options include dapsone (which in a controlled trial proved slightly less effective than chloroquine), methotrexate, azathioprine, and mycophenolate mofetil (CellCept).

The two major subtypes of cutaneous LE are discoid and subacute. Discoid lesions leave scarring and atrophy. Subacute cutaneous LE lesions do not, although there may be residual hypopigmentation. Discoid LE is subcategorized into localized to the head and neck or widespread. The distinction is clinically relevant because widespread discoid LE is more difficult to control, has a higher rate of associated serologic abnormalities, and probably is more likely to progress to SLE.

Dr. Callen disclosed serving as a consultant to Abbott, Amgen, Centocor, Electro-Optical Sciences, and Medicis.

SNOWMASS, Colo. – Treatment of cutaneous lupus erythematosus with hydroxychloroquine appears to delay onset of systemic lupus erythematosus, judging from findings of a retrospective study.

Given the growing body of evidence that cutaneous lupus erythematosus (LE) has systemic implications, “I’m beginning more and more patients earlier on antimalarials,” Dr. Jeffrey P. Callen said at a symposium sponsored by the American College of Rheumatology.

He cited findings from an Oklahoma Medical Research Foundation study in which investigators identified 130 U.S. military personnel who met ACR criteria for systemic LE (SLE). Twenty-six of them were previously treated with hydroxychloroquine (Plaquenil) when their disease was limited to the skin. The median time from their first skin lesions to diagnosis of SLE was 1.08 years, compared with 0.29 years in patients who did not receive hydroxychloroquine for their limited skin involvement.

The hydroxychloroquine-treated cohort also had a lower rate of autoantibody accumulation and fewer autoantibody specificities at the time they were diagnosed with SLE and thereafter. All of this is consistent with the notion that hydroxychloroquine therapy delays SLE onset, according to Dr. Callen, professor of medicine and chief of the division of dermatology at the University of Louisville (Ky).

In contrast, treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) had no impact on the length of time between onset of cutaneous LE and development of SLE (Lupus 2007;16:401-9).

Independent evidence that cutaneous LE not uncommonly progresses to SLE comes from a recent retrospective population-based Mayo Clinic study involving the entire population of Olmsted County, Minn. The investigators found that the collective incidence of all subtypes of cutaneous LE, exclusive of drug-induced LE, was 4.3 cases per 100,000 population during 1965-2005. That’s comparable with published figures for the incidence of SLE. The age- and gender-adjusted prevalence of cutaneous LE in early 2006 was 73.2 cases per 100,000 in this predominantly white population.

Cutaneous LE progressed to SLE in 12% of individuals, with a mean 8.2 years between the two diagnoses (Arch. Dermatol. 2009;145:249-53).

Dr. Callen noted that a prospective, blinded clinical trial would be needed to establish definitively that antimalarial therapy delays or prevents SLE. Even in the absence of such compelling evidence, he said he is a big believer in the early use of antimalarial agents in cutaneous LE for another reason: topical corticosteroids, widely advocated as first-line therapy, are not all that effective.

“They work well in clinical trials. They don’t work in clinical practice,” the dermatologist said.

The reason? They’re so messy and inconvenient that many patients simply do not use them as directed.

Intralesional corticosteroid injections are effective, but the benefits are temporary and many patients would rather take an oral medication than come in to the office for repeated injections, he continued.

His first-line systemic therapy is oral hydroxychloroquine at a maximum dose of 6.5 mg/kg of ideal body weight. At that dose, he has not encountered problems with ocular toxicity. Nonetheless, he tries to lower the dose once a patient’s disease is well controlled. Chloroquine seems to be slightly more effective than hydroxychloroquine but also more oculotoxic, according to Dr. Callen.

Smokers with cutaneous LE respond less robustly to antimalarials. If they can be persuaded to quit they will see further clinical improvement, although it often takes close to a year to become evident.

Sun-protective clothing and a broad-spectrum sunscreen are essential parts of the treatment of cutaneous LE. Dr. Callen recommends Neutrogena UltraSheer, which has desirable characteristics and is easy to find, to his patients with lupus or dermatomyositis.

A careful drug history is a must in patients with subacute cutaneous LE because the skin disease may be drug induced in upwards of one-fifth of cases. The most common offenders are hydrochlorothiazide and terbinafine. Others include ACE inhibitors, calcium channel blockers, bupropion, phenothiazines, anti–tumor necrosis factor agents, and statins. If a patient has been on a drug for more than 6 months prior to onset of cutaneous LE, the lesions are probably not drug induced. Clinical improvement or resolution of drug-induced subacute cutaneous LE typically occurs within a few weeks to 6 months after stopping the offending drug.

“If we in dermatology and you in rheumatology don’t get a careful drug history from the patients and alter the drugs they’re on, we’ll miss the opportunity to cure this disease,” he stressed.

In cutaneous LE patients who do not respond to or cannot tolerate antimalarials, there are good alternative systemic options.

“Thalidomide is a teratogen, but if you pick the right patients it works really well. Almost all patients with cutaneous lupus will respond to thalidomide, more than half with a complete response and the rest partially,” Dr. Callen said.

 

The major toxicity with thalidomide is a cumulative dose-dependent sensory neuropathy that is not always reversible upon drug discontinuation. Dr. Callen therefore keeps the dose as low as possible: Maintenance therapy might range from 50 mg/day to 25 mg every second or third day. He said he usually employs thalidomide in conjunction with an antimalarial agent unless the patient has antimalarial toxicity. A response to thalidomide becomes evident within a few weeks, although the full response takes about 3 months. Relapse is common with discontinuation of thalidomide; restarting the drug usually restores the clinical response, he said.

Other systemic options include dapsone (which in a controlled trial proved slightly less effective than chloroquine), methotrexate, azathioprine, and mycophenolate mofetil (CellCept).

The two major subtypes of cutaneous LE are discoid and subacute. Discoid lesions leave scarring and atrophy. Subacute cutaneous LE lesions do not, although there may be residual hypopigmentation. Discoid LE is subcategorized into localized to the head and neck or widespread. The distinction is clinically relevant because widespread discoid LE is more difficult to control, has a higher rate of associated serologic abnormalities, and probably is more likely to progress to SLE.

Dr. Callen disclosed serving as a consultant to Abbott, Amgen, Centocor, Electro-Optical Sciences, and Medicis.