Sharon Worcester

CHICAGO (EGMN) – The list of off-label uses for biologic agents is growing, and rheumatologists should stay abreast of even the nonrheumatologic uses, according to Dr. Eric Ruderman, who provided an update on dermatologic, ophthalmologic, and other uses at a symposium sponsored by the American College of Rheumatology.

"My goal is to give you some guidance when somebody asks, because what you’re going to find is that the dermatologists, ophthalmologists, and others are going to ask you as the rheumatologist, who is supposedly the expert in biologic therapy, what is the role for this, that, or the other drug," said Dr. Ruderman, a rheumatologist at Northwestern University, Chicago.

There are scant data to support off-label uses, and these typically come from retrospective reports, small case series, or anecdotal experience, with a few exceptions, he said.

In dermatology, for example, infliximab is increasingly being used to treat hidradenitis suppurativa and neutrophilic dermatoses despite a lack of data from randomized controlled trials to support this practice. Findings from a small double-blind crossover trial involving 38 patients who were treated for 8 weeks, however, did suggest that infliximab improves pain, disease severity, and quality of life.

Some benefit was also shown with adalimumab in this disease in a recent case series, while benefits with etanercept were less clear in two open-label trials. Patients in the etanercept trials also had worsening of their condition after etanercept was discontinued.

As for neutrophilic dermatoses, infliximab appears to be useful for pyoderma gangrenosum and possibly for Sweet’s syndrome. In a double-blind study of 30 patients with pyoderma gangrenosum, a single dose of 5 mg/kg was associated with a 46% improvement, compared with 6% for placebo. Furthermore, nonresponders on placebo at 2 weeks were treated with infliximab with a 60% response rate, and 21% of treated patients achieved remission.

Case reports also show a benefit of infliximab in patients with Sweet’s syndrome, but no controlled data are available for this condition, Dr. Ruderman said.

Biologic therapies being used for ophthalmologic conditions include infliximab, adalimumab, and/or daclizumab for childhood uveitis and other types of uveitis, he noted.

Retrospective case series have shown benefit with infliximab, adalimumab, and daclizumab in childhood uveitis, and an open-label prospective study comparing adalimumab with infliximab demonstrated greater benefit with adalimumab (60% vs. 20% remission at 40 months), he said.

Infliximab also may have some benefit in ocular sarcoidosis, with case reports and small open-label series demonstrating some benefit. Etanercept in this disease, however, appears to be no more effective than placebo, based on findings of a randomized study of 18 patients treated for 6 months.

In Behçet’s uveitis, case reports and findings from two small open trials suggest some benefit with infliximab. In the open trials, 9 of 12 patients responded to a dose of 5 mg/kg, Dr. Ruderman said, adding that treatment helped reduce steroid use, but relapse was frequent after treatment discontinuation, suggesting that ongoing therapy is necessary.

Other conditions in which biologics are currently being used include pulmonary and extrapulmonary sarcoidosis, asthma, and chronic obstructive pulmonary disease (COPD).

In one "nicely done" randomized, controlled, multicenter study of 138 pulmonary sarcoidosis patients, infliximab was superior to placebo for improving the percent predicted forced vital capacity at 24 weeks, and also led to improvement in extrapulmonary disease, Dr. Ruderman said.

Improvements in scores on the extrapulmonary physician organ severity tool (ePOST) were better in the treatment versus placebo group at 24 weeks, even after adjusting for the number of organs involved, he said.

Findings from an open-label study of etanercept in this disease, however, showed that only 5 of 17 patients had "success," which was defined as lack of deterioration on x-rays or pulmonary function tests.

Case reports and retrospective data – but not randomized controlled data – have also shown some benefit of infliximab for cutaneous sarcoidosis. In 54 patients who received 116 courses of therapy, resolution or near resolution of lupus pernio was achieved in 77% of patients versus 11%-29% of those treated with steroids and other therapy. Some case reports show benefit in neurosarcoidosis, as well, but no solid data are available to back those up, Dr. Ruderman said.

For asthma, there may be a role for tumor necrosis factor inhibitors, although one randomized controlled trial showed no benefit with golimumab.

The Brigham RA Sequential Study, for example, demonstrated improvement with TNF inhibitors in nine patients with both rheumatoid arthritis (RA) and asthma, and findings from a small, controlled trial of etanercept showed some benefit on several measures of response. The benefits in that study, however, were not clear-cut, and two other etanercept trials, as well as one infliximab trial, failed to show any benefit in asthma.

Similarly, golimumab showed no benefit in a 52-week randomized, controlled trial of 231 patients with severe uncontrolled asthma. Patients in that trial had no improvements over placebo in forced expiratory volume in 1 second (FEV₁) or exacerbations, and they experienced frequent severe infections, Dr. Ruderman said.

Two studies found that infliximab therapy provided no benefit in the management of COPD. The first was a 24-week study of 3 mg/kg, 5 mg/kg, and placebo in 159 patients. The findings showed no improvement in health status or FEV₁, no lessening of exacerbations with treatment vs. placebo, and an increase in the risk of pneumonia in the treated group. The second study was an observational study involving a cohort of 15,771 patients with both RA and COPD. In this study, however, treatment with etanercept was associated with a 50% reduction in the rate of COPD hospitalization.

"I don’t know entirely what to make of that," Dr. Ruderman said, adding that it might be a result of improvement in the RA and thus overall health.

It’s an interesting observation, but overall the findings don’t say much about the off-label use of TNF inhibitors in COPD, he said.

Dr. Ruderman reported receiving consulting fees and/or research grants from Abbott, Allos, Amgen, Biogenidec, Celgene, Centocor, Crescendo, CVS/Caremark, Pfizer, and UCB.

CHICAGO (EGMN) – The list of off-label uses for biologic agents is growing, and rheumatologists should stay abreast of even the nonrheumatologic uses, according to Dr. Eric Ruderman, who provided an update on dermatologic, ophthalmologic, and other uses at a symposium sponsored by the American College of Rheumatology.

"My goal is to give you some guidance when somebody asks, because what you’re going to find is that the dermatologists, ophthalmologists, and others are going to ask you as the rheumatologist, who is supposedly the expert in biologic therapy, what is the role for this, that, or the other drug," said Dr. Ruderman, a rheumatologist at Northwestern University, Chicago.

There are scant data to support off-label uses, and these typically come from retrospective reports, small case series, or anecdotal experience, with a few exceptions, he said.

In dermatology, for example, infliximab is increasingly being used to treat hidradenitis suppurativa and neutrophilic dermatoses despite a lack of data from randomized controlled trials to support this practice. Findings from a small double-blind crossover trial involving 38 patients who were treated for 8 weeks, however, did suggest that infliximab improves pain, disease severity, and quality of life.

Some benefit was also shown with adalimumab in this disease in a recent case series, while benefits with etanercept were less clear in two open-label trials. Patients in the etanercept trials also had worsening of their condition after etanercept was discontinued.

As for neutrophilic dermatoses, infliximab appears to be useful for pyoderma gangrenosum and possibly for Sweet’s syndrome. In a double-blind study of 30 patients with pyoderma gangrenosum, a single dose of 5 mg/kg was associated with a 46% improvement, compared with 6% for placebo. Furthermore, nonresponders on placebo at 2 weeks were treated with infliximab with a 60% response rate, and 21% of treated patients achieved remission.

Case reports also show a benefit of infliximab in patients with Sweet’s syndrome, but no controlled data are available for this condition, Dr. Ruderman said.

Biologic therapies being used for ophthalmologic conditions include infliximab, adalimumab, and/or daclizumab for childhood uveitis and other types of uveitis, he noted.

Retrospective case series have shown benefit with infliximab, adalimumab, and daclizumab in childhood uveitis, and an open-label prospective study comparing adalimumab with infliximab demonstrated greater benefit with adalimumab (60% vs. 20% remission at 40 months), he said.

Infliximab also may have some benefit in ocular sarcoidosis, with case reports and small open-label series demonstrating some benefit. Etanercept in this disease, however, appears to be no more effective than placebo, based on findings of a randomized study of 18 patients treated for 6 months.

In Behçet’s uveitis, case reports and findings from two small open trials suggest some benefit with infliximab. In the open trials, 9 of 12 patients responded to a dose of 5 mg/kg, Dr. Ruderman said, adding that treatment helped reduce steroid use, but relapse was frequent after treatment discontinuation, suggesting that ongoing therapy is necessary.

Other conditions in which biologics are currently being used include pulmonary and extrapulmonary sarcoidosis, asthma, and chronic obstructive pulmonary disease (COPD).

In one "nicely done" randomized, controlled, multicenter study of 138 pulmonary sarcoidosis patients, infliximab was superior to placebo for improving the percent predicted forced vital capacity at 24 weeks, and also led to improvement in extrapulmonary disease, Dr. Ruderman said.

Improvements in scores on the extrapulmonary physician organ severity tool (ePOST) were better in the treatment versus placebo group at 24 weeks, even after adjusting for the number of organs involved, he said.

Findings from an open-label study of etanercept in this disease, however, showed that only 5 of 17 patients had "success," which was defined as lack of deterioration on x-rays or pulmonary function tests.

Case reports and retrospective data – but not randomized controlled data – have also shown some benefit of infliximab for cutaneous sarcoidosis. In 54 patients who received 116 courses of therapy, resolution or near resolution of lupus pernio was achieved in 77% of patients versus 11%-29% of those treated with steroids and other therapy. Some case reports show benefit in neurosarcoidosis, as well, but no solid data are available to back those up, Dr. Ruderman said.

For asthma, there may be a role for tumor necrosis factor inhibitors, although one randomized controlled trial showed no benefit with golimumab.

The Brigham RA Sequential Study, for example, demonstrated improvement with TNF inhibitors in nine patients with both rheumatoid arthritis (RA) and asthma, and findings from a small, controlled trial of etanercept showed some benefit on several measures of response. The benefits in that study, however, were not clear-cut, and two other etanercept trials, as well as one infliximab trial, failed to show any benefit in asthma.

Similarly, golimumab showed no benefit in a 52-week randomized, controlled trial of 231 patients with severe uncontrolled asthma. Patients in that trial had no improvements over placebo in forced expiratory volume in 1 second (FEV₁) or exacerbations, and they experienced frequent severe infections, Dr. Ruderman said.

Two studies found that infliximab therapy provided no benefit in the management of COPD. The first was a 24-week study of 3 mg/kg, 5 mg/kg, and placebo in 159 patients. The findings showed no improvement in health status or FEV₁, no lessening of exacerbations with treatment vs. placebo, and an increase in the risk of pneumonia in the treated group. The second study was an observational study involving a cohort of 15,771 patients with both RA and COPD. In this study, however, treatment with etanercept was associated with a 50% reduction in the rate of COPD hospitalization.

"I don’t know entirely what to make of that," Dr. Ruderman said, adding that it might be a result of improvement in the RA and thus overall health.

It’s an interesting observation, but overall the findings don’t say much about the off-label use of TNF inhibitors in COPD, he said.

Dr. Ruderman reported receiving consulting fees and/or research grants from Abbott, Allos, Amgen, Biogenidec, Celgene, Centocor, Crescendo, CVS/Caremark, Pfizer, and UCB.

CHICAGO (EGMN) – The list of off-label uses for biologic agents is growing, and rheumatologists should stay abreast of even the nonrheumatologic uses, according to Dr. Eric Ruderman, who provided an update on dermatologic, ophthalmologic, and other uses at a symposium sponsored by the American College of Rheumatology.

"My goal is to give you some guidance when somebody asks, because what you’re going to find is that the dermatologists, ophthalmologists, and others are going to ask you as the rheumatologist, who is supposedly the expert in biologic therapy, what is the role for this, that, or the other drug," said Dr. Ruderman, a rheumatologist at Northwestern University, Chicago.

There are scant data to support off-label uses, and these typically come from retrospective reports, small case series, or anecdotal experience, with a few exceptions, he said.

In dermatology, for example, infliximab is increasingly being used to treat hidradenitis suppurativa and neutrophilic dermatoses despite a lack of data from randomized controlled trials to support this practice. Findings from a small double-blind crossover trial involving 38 patients who were treated for 8 weeks, however, did suggest that infliximab improves pain, disease severity, and quality of life.

Some benefit was also shown with adalimumab in this disease in a recent case series, while benefits with etanercept were less clear in two open-label trials. Patients in the etanercept trials also had worsening of their condition after etanercept was discontinued.

As for neutrophilic dermatoses, infliximab appears to be useful for pyoderma gangrenosum and possibly for Sweet’s syndrome. In a double-blind study of 30 patients with pyoderma gangrenosum, a single dose of 5 mg/kg was associated with a 46% improvement, compared with 6% for placebo. Furthermore, nonresponders on placebo at 2 weeks were treated with infliximab with a 60% response rate, and 21% of treated patients achieved remission.

Case reports also show a benefit of infliximab in patients with Sweet’s syndrome, but no controlled data are available for this condition, Dr. Ruderman said.

Biologic therapies being used for ophthalmologic conditions include infliximab, adalimumab, and/or daclizumab for childhood uveitis and other types of uveitis, he noted.

Retrospective case series have shown benefit with infliximab, adalimumab, and daclizumab in childhood uveitis, and an open-label prospective study comparing adalimumab with infliximab demonstrated greater benefit with adalimumab (60% vs. 20% remission at 40 months), he said.

Infliximab also may have some benefit in ocular sarcoidosis, with case reports and small open-label series demonstrating some benefit. Etanercept in this disease, however, appears to be no more effective than placebo, based on findings of a randomized study of 18 patients treated for 6 months.

In Behçet’s uveitis, case reports and findings from two small open trials suggest some benefit with infliximab. In the open trials, 9 of 12 patients responded to a dose of 5 mg/kg, Dr. Ruderman said, adding that treatment helped reduce steroid use, but relapse was frequent after treatment discontinuation, suggesting that ongoing therapy is necessary.

Other conditions in which biologics are currently being used include pulmonary and extrapulmonary sarcoidosis, asthma, and chronic obstructive pulmonary disease (COPD).

In one "nicely done" randomized, controlled, multicenter study of 138 pulmonary sarcoidosis patients, infliximab was superior to placebo for improving the percent predicted forced vital capacity at 24 weeks, and also led to improvement in extrapulmonary disease, Dr. Ruderman said.

Improvements in scores on the extrapulmonary physician organ severity tool (ePOST) were better in the treatment versus placebo group at 24 weeks, even after adjusting for the number of organs involved, he said.

Findings from an open-label study of etanercept in this disease, however, showed that only 5 of 17 patients had "success," which was defined as lack of deterioration on x-rays or pulmonary function tests.

Case reports and retrospective data – but not randomized controlled data – have also shown some benefit of infliximab for cutaneous sarcoidosis. In 54 patients who received 116 courses of therapy, resolution or near resolution of lupus pernio was achieved in 77% of patients versus 11%-29% of those treated with steroids and other therapy. Some case reports show benefit in neurosarcoidosis, as well, but no solid data are available to back those up, Dr. Ruderman said.

For asthma, there may be a role for tumor necrosis factor inhibitors, although one randomized controlled trial showed no benefit with golimumab.

The Brigham RA Sequential Study, for example, demonstrated improvement with TNF inhibitors in nine patients with both rheumatoid arthritis (RA) and asthma, and findings from a small, controlled trial of etanercept showed some benefit on several measures of response. The benefits in that study, however, were not clear-cut, and two other etanercept trials, as well as one infliximab trial, failed to show any benefit in asthma.

Similarly, golimumab showed no benefit in a 52-week randomized, controlled trial of 231 patients with severe uncontrolled asthma. Patients in that trial had no improvements over placebo in forced expiratory volume in 1 second (FEV₁) or exacerbations, and they experienced frequent severe infections, Dr. Ruderman said.

Two studies found that infliximab therapy provided no benefit in the management of COPD. The first was a 24-week study of 3 mg/kg, 5 mg/kg, and placebo in 159 patients. The findings showed no improvement in health status or FEV₁, no lessening of exacerbations with treatment vs. placebo, and an increase in the risk of pneumonia in the treated group. The second study was an observational study involving a cohort of 15,771 patients with both RA and COPD. In this study, however, treatment with etanercept was associated with a 50% reduction in the rate of COPD hospitalization.

"I don’t know entirely what to make of that," Dr. Ruderman said, adding that it might be a result of improvement in the RA and thus overall health.

It’s an interesting observation, but overall the findings don’t say much about the off-label use of TNF inhibitors in COPD, he said.

Dr. Ruderman reported receiving consulting fees and/or research grants from Abbott, Allos, Amgen, Biogenidec, Celgene, Centocor, Crescendo, CVS/Caremark, Pfizer, and UCB.

DESTIN, FLA. – Consider screening for celiac disease in children with juvenile idiopathic arthritis, arthromyalgias, and myositis, advised Dr. Alexa B. Adams at the Congress of Clinical Rheumatology.

Celiac disease has a strong association with numerous autoimmune disorders. Untreated celiac disease poses serious health consequences, such as short stature, failure to thrive, osteopenia/osteoporosis, and enteropathy-associated T-cell lymphoma. Early diagnosis and treatment could obviate or reduce the need for the more aggressive treatments that are typically prescribed for these associated autoimmune disorders, said Dr. Adams, a pediatric rheumatologist and pediatrician at Cornell University, New York.

The identification and treatment of celiac disease in the setting of autoimmune disorders also appear to have the potential to alter the course of subsequent autoimmune disease, she said.

A link between celiac disease and juvenile idiopathic arthritis (JIA), for example, is well established. Several studies have demonstrated an increased prevalence of celiac disease among children with JIA, and cases of celiac disease in association with juvenile spondyloarthropathies and with pauciarticular, polyarticular, and psoriatic arthritis also have been reported. Furthermore, data show that a gluten-free diet can improve the musculoskeletal symptoms that are associated with celiac disease.

The mechanisms for the association between JIA and celiac disease are unknown, but may be related to ongoing intestinal permeability in untreated celiac disease, Dr. Adams said, adding that she advocates screening for celiac disease in all JIA patients.

She described a case involving a 6-year-old boy who presented with pain and swelling of the knee as well as morning stiffness. He had previously been treated for Lyme disease, and he had a 2-year history of headaches, behavioral problems, and poor growth, compared with his identical twin.

Based on physical and laboratory examinations (serology was negative for celiac disease) and after the young patient was referred to pediatric infectious disease and neurology specialties where he underwent lumbar puncture and brain MRI, the treatment focused on possible central nervous system Lyme disease. Although his joint complaints were resolved, he had persistent headaches, poor growth, and worsening transaminitis.

The boy tested negative for infectious and autoimmune hepatitis. An abdominal ultrasound showed fatty infiltration of the liver. Ultimately, the child was referred to a pediatric gastroenterologist. Work-up, including duodenal biopsy, showed findings that were consistent with celiac disease, and a gluten-free diet was initiated.

"On a gluten-free diet, the child’s headaches resolved, he had no recurrence of joint pain, he was growing and gaining weight, and he had no further behavioral issues," Dr. Adams said.

An early diagnosis of celiac disease in a JIA patient and early initiation of a gluten-free diet can prevent unnecessary treatment with NSAIDs, disease-modifying antirheumatic drugs, and anti–tumor necrosis factor agents. The patent can also avoid unnecessary imaging and joint injections.

Associations between celiac disease and adult rheumatoid arthritis/seronegative arthritides also exist, but are not as robust as that seen between celiac disease and JIA.

The coexistence of adult RA and positive celiac antibodies – including EmA (endomysial antibodies) and gliadin IgA – has been well described, but an association with biopsy-proven celiac disease has not borne out, Dr. Adams said.

The same is true in adult spondyloarthropathy.

It is possible that there are age-related differences in gluten tolerance or in the pathogenesis of arthritis and/or gut permeability that can explain the age-related differences, but this remains unclear, she noted.

As for celiac disease and myositis, the associations are well documented in both the pediatric rheumatology and pediatric gastroenterology literature, and also (although only more recently) in the adult literature.

Interestingly, a high prevalence of the DQAI*0501 allele is found in both diseases, Dr. Adams noted.

Because treatment of inflammatory myositis often requires significant use of glucocorticoids and sometimes additional immunosuppressive therapy, screening for celiac disease should be considered in myositis patients, she said, describing two cases involving young girls who were diagnosed with myositis and polymyositis, respectively. Both failed to respond adequately to prednisone/methotrexate, and both are doing well now on only a gluten-free diet after being diagnosed with celiac disease on biopsy.

Screen for celiac disease in patients with vague musculoskeletal complaints who don’t respond to treatment, she said. These are the patients with whom "you just don’t know what to do," she said, adding that these are the patients who don’t clearly have arthritis, whose symptoms are out of proportion to findings on examination, whose symptoms impact their participation in sports or other activities, and who fail to respond well to a number of treatments. Often these patients will be diagnosed with fibromyalgia – a diagnosis that is unusual in young patients and should raise concern about possible other causes, she added.

In these cases, maintain a high index of suspicion for celiac disease, she said, describing the case of a 16-year-old girl who had given up sports because of a 2-year history of increasing pain in the calves, forearms, Achilles tendon, heels, and back. The skin on her thighs and calves was sensitive to touch, but she had no GI symptoms and had normal growth.

Massage, chiropractic manipulation, acupuncture, electrical stimulation, and saline injection in her calf all failed to alleviate her symptoms. The child was diagnosed with fibromyalgia and treated with gabapentin, an over-the-counter NSAID, as well as intensive physical therapy.

After a gastroenterology referral, she was diagnosed with celiac disease based on biopsy findings, and was started on a gluten-free diet. At 5 months, she was symptom free and was once again active in sports activities.

Given the consistent findings associating celiac disease with certain autoimmune disorders, and the safety and effectiveness of the gluten-free diet that is used to treat celiac disease, screening deserves consideration in these patients, she concluded.

An association between celiac disease and systemic autoimmune disease has been reported, but is less established than the association between celiac disease and nonsystemic autoimmune disorders, Dr. Adams said.

Reports of a link between celiac disease and systemic lupus erythematosus (SLE), for example, are limited to case reports, and at this point should be "taken with a grain of salt," she said.

However, it does appear that in children the celiac disease diagnosis typically precedes the SLE diagnosis, whereas the converse is true in adults.

Also, reports of SLE following celiac disease despite histologic normalization of the celiac disease on biopsy suggest that the treatment of celiac disease via a gluten-free diet does not modify the disease course in SLE, as it appears to do in cases of arthritis and myositis (J. Clin. Gastroenterol. 2008;42:252-5), Dr. Adams said.

There does, however, appear to be a fairly strong association between celiac disease and Sjögren’s syndrome.

A 2003 report said Sjögren’s syndrome is present in up to 15% of patients with biopsy-proven celiac disease, and demonstrated that anti-tTG (tissue transglutaminase, a marker for celiac disease) is more prevalent in Sjögren’s syndrome than in other systemic rheumatic diseases (J. Rheumatol. 2003;30:2613-9).

Systemic sclerosis and morphia have also been reported in association with celiac disease, Dr. Adams said.

The strongest associations between celiac disease and systemic autoimmune disease are with adult idiopathic diabetes mellitus, autoimmune thyroid disease, Addison’s disease, and polyendocrinopathies, she added.

More data are needed to define the prevalence of celiac disease in various subtypes of systemic autoimmune disease, she concluded.

Dr. Adams serves as a speaker for Abbott Pharmaceuticals. She had no other relevant disclosures.

DESTIN, FLA. – Consider screening for celiac disease in children with juvenile idiopathic arthritis, arthromyalgias, and myositis, advised Dr. Alexa B. Adams at the Congress of Clinical Rheumatology.

Celiac disease has a strong association with numerous autoimmune disorders. Untreated celiac disease poses serious health consequences, such as short stature, failure to thrive, osteopenia/osteoporosis, and enteropathy-associated T-cell lymphoma. Early diagnosis and treatment could obviate or reduce the need for the more aggressive treatments that are typically prescribed for these associated autoimmune disorders, said Dr. Adams, a pediatric rheumatologist and pediatrician at Cornell University, New York.

The identification and treatment of celiac disease in the setting of autoimmune disorders also appear to have the potential to alter the course of subsequent autoimmune disease, she said.

A link between celiac disease and juvenile idiopathic arthritis (JIA), for example, is well established. Several studies have demonstrated an increased prevalence of celiac disease among children with JIA, and cases of celiac disease in association with juvenile spondyloarthropathies and with pauciarticular, polyarticular, and psoriatic arthritis also have been reported. Furthermore, data show that a gluten-free diet can improve the musculoskeletal symptoms that are associated with celiac disease.

The mechanisms for the association between JIA and celiac disease are unknown, but may be related to ongoing intestinal permeability in untreated celiac disease, Dr. Adams said, adding that she advocates screening for celiac disease in all JIA patients.

She described a case involving a 6-year-old boy who presented with pain and swelling of the knee as well as morning stiffness. He had previously been treated for Lyme disease, and he had a 2-year history of headaches, behavioral problems, and poor growth, compared with his identical twin.

Based on physical and laboratory examinations (serology was negative for celiac disease) and after the young patient was referred to pediatric infectious disease and neurology specialties where he underwent lumbar puncture and brain MRI, the treatment focused on possible central nervous system Lyme disease. Although his joint complaints were resolved, he had persistent headaches, poor growth, and worsening transaminitis.

The boy tested negative for infectious and autoimmune hepatitis. An abdominal ultrasound showed fatty infiltration of the liver. Ultimately, the child was referred to a pediatric gastroenterologist. Work-up, including duodenal biopsy, showed findings that were consistent with celiac disease, and a gluten-free diet was initiated.

"On a gluten-free diet, the child’s headaches resolved, he had no recurrence of joint pain, he was growing and gaining weight, and he had no further behavioral issues," Dr. Adams said.

An early diagnosis of celiac disease in a JIA patient and early initiation of a gluten-free diet can prevent unnecessary treatment with NSAIDs, disease-modifying antirheumatic drugs, and anti–tumor necrosis factor agents. The patent can also avoid unnecessary imaging and joint injections.

Associations between celiac disease and adult rheumatoid arthritis/seronegative arthritides also exist, but are not as robust as that seen between celiac disease and JIA.

The coexistence of adult RA and positive celiac antibodies – including EmA (endomysial antibodies) and gliadin IgA – has been well described, but an association with biopsy-proven celiac disease has not borne out, Dr. Adams said.

The same is true in adult spondyloarthropathy.

It is possible that there are age-related differences in gluten tolerance or in the pathogenesis of arthritis and/or gut permeability that can explain the age-related differences, but this remains unclear, she noted.

As for celiac disease and myositis, the associations are well documented in both the pediatric rheumatology and pediatric gastroenterology literature, and also (although only more recently) in the adult literature.

Interestingly, a high prevalence of the DQAI*0501 allele is found in both diseases, Dr. Adams noted.

Because treatment of inflammatory myositis often requires significant use of glucocorticoids and sometimes additional immunosuppressive therapy, screening for celiac disease should be considered in myositis patients, she said, describing two cases involving young girls who were diagnosed with myositis and polymyositis, respectively. Both failed to respond adequately to prednisone/methotrexate, and both are doing well now on only a gluten-free diet after being diagnosed with celiac disease on biopsy.

Screen for celiac disease in patients with vague musculoskeletal complaints who don’t respond to treatment, she said. These are the patients with whom "you just don’t know what to do," she said, adding that these are the patients who don’t clearly have arthritis, whose symptoms are out of proportion to findings on examination, whose symptoms impact their participation in sports or other activities, and who fail to respond well to a number of treatments. Often these patients will be diagnosed with fibromyalgia – a diagnosis that is unusual in young patients and should raise concern about possible other causes, she added.

In these cases, maintain a high index of suspicion for celiac disease, she said, describing the case of a 16-year-old girl who had given up sports because of a 2-year history of increasing pain in the calves, forearms, Achilles tendon, heels, and back. The skin on her thighs and calves was sensitive to touch, but she had no GI symptoms and had normal growth.

Massage, chiropractic manipulation, acupuncture, electrical stimulation, and saline injection in her calf all failed to alleviate her symptoms. The child was diagnosed with fibromyalgia and treated with gabapentin, an over-the-counter NSAID, as well as intensive physical therapy.

After a gastroenterology referral, she was diagnosed with celiac disease based on biopsy findings, and was started on a gluten-free diet. At 5 months, she was symptom free and was once again active in sports activities.

Given the consistent findings associating celiac disease with certain autoimmune disorders, and the safety and effectiveness of the gluten-free diet that is used to treat celiac disease, screening deserves consideration in these patients, she concluded.

An association between celiac disease and systemic autoimmune disease has been reported, but is less established than the association between celiac disease and nonsystemic autoimmune disorders, Dr. Adams said.

Reports of a link between celiac disease and systemic lupus erythematosus (SLE), for example, are limited to case reports, and at this point should be "taken with a grain of salt," she said.

However, it does appear that in children the celiac disease diagnosis typically precedes the SLE diagnosis, whereas the converse is true in adults.

Also, reports of SLE following celiac disease despite histologic normalization of the celiac disease on biopsy suggest that the treatment of celiac disease via a gluten-free diet does not modify the disease course in SLE, as it appears to do in cases of arthritis and myositis (J. Clin. Gastroenterol. 2008;42:252-5), Dr. Adams said.

There does, however, appear to be a fairly strong association between celiac disease and Sjögren’s syndrome.

A 2003 report said Sjögren’s syndrome is present in up to 15% of patients with biopsy-proven celiac disease, and demonstrated that anti-tTG (tissue transglutaminase, a marker for celiac disease) is more prevalent in Sjögren’s syndrome than in other systemic rheumatic diseases (J. Rheumatol. 2003;30:2613-9).

Systemic sclerosis and morphia have also been reported in association with celiac disease, Dr. Adams said.

The strongest associations between celiac disease and systemic autoimmune disease are with adult idiopathic diabetes mellitus, autoimmune thyroid disease, Addison’s disease, and polyendocrinopathies, she added.

More data are needed to define the prevalence of celiac disease in various subtypes of systemic autoimmune disease, she concluded.

Dr. Adams serves as a speaker for Abbott Pharmaceuticals. She had no other relevant disclosures.

DESTIN, FLA. – Consider screening for celiac disease in children with juvenile idiopathic arthritis, arthromyalgias, and myositis, advised Dr. Alexa B. Adams at the Congress of Clinical Rheumatology.

Celiac disease has a strong association with numerous autoimmune disorders. Untreated celiac disease poses serious health consequences, such as short stature, failure to thrive, osteopenia/osteoporosis, and enteropathy-associated T-cell lymphoma. Early diagnosis and treatment could obviate or reduce the need for the more aggressive treatments that are typically prescribed for these associated autoimmune disorders, said Dr. Adams, a pediatric rheumatologist and pediatrician at Cornell University, New York.

The identification and treatment of celiac disease in the setting of autoimmune disorders also appear to have the potential to alter the course of subsequent autoimmune disease, she said.

A link between celiac disease and juvenile idiopathic arthritis (JIA), for example, is well established. Several studies have demonstrated an increased prevalence of celiac disease among children with JIA, and cases of celiac disease in association with juvenile spondyloarthropathies and with pauciarticular, polyarticular, and psoriatic arthritis also have been reported. Furthermore, data show that a gluten-free diet can improve the musculoskeletal symptoms that are associated with celiac disease.

The mechanisms for the association between JIA and celiac disease are unknown, but may be related to ongoing intestinal permeability in untreated celiac disease, Dr. Adams said, adding that she advocates screening for celiac disease in all JIA patients.

She described a case involving a 6-year-old boy who presented with pain and swelling of the knee as well as morning stiffness. He had previously been treated for Lyme disease, and he had a 2-year history of headaches, behavioral problems, and poor growth, compared with his identical twin.

Based on physical and laboratory examinations (serology was negative for celiac disease) and after the young patient was referred to pediatric infectious disease and neurology specialties where he underwent lumbar puncture and brain MRI, the treatment focused on possible central nervous system Lyme disease. Although his joint complaints were resolved, he had persistent headaches, poor growth, and worsening transaminitis.

The boy tested negative for infectious and autoimmune hepatitis. An abdominal ultrasound showed fatty infiltration of the liver. Ultimately, the child was referred to a pediatric gastroenterologist. Work-up, including duodenal biopsy, showed findings that were consistent with celiac disease, and a gluten-free diet was initiated.

"On a gluten-free diet, the child’s headaches resolved, he had no recurrence of joint pain, he was growing and gaining weight, and he had no further behavioral issues," Dr. Adams said.

An early diagnosis of celiac disease in a JIA patient and early initiation of a gluten-free diet can prevent unnecessary treatment with NSAIDs, disease-modifying antirheumatic drugs, and anti–tumor necrosis factor agents. The patent can also avoid unnecessary imaging and joint injections.

Associations between celiac disease and adult rheumatoid arthritis/seronegative arthritides also exist, but are not as robust as that seen between celiac disease and JIA.

The coexistence of adult RA and positive celiac antibodies – including EmA (endomysial antibodies) and gliadin IgA – has been well described, but an association with biopsy-proven celiac disease has not borne out, Dr. Adams said.

The same is true in adult spondyloarthropathy.

It is possible that there are age-related differences in gluten tolerance or in the pathogenesis of arthritis and/or gut permeability that can explain the age-related differences, but this remains unclear, she noted.

As for celiac disease and myositis, the associations are well documented in both the pediatric rheumatology and pediatric gastroenterology literature, and also (although only more recently) in the adult literature.

Interestingly, a high prevalence of the DQAI*0501 allele is found in both diseases, Dr. Adams noted.

Because treatment of inflammatory myositis often requires significant use of glucocorticoids and sometimes additional immunosuppressive therapy, screening for celiac disease should be considered in myositis patients, she said, describing two cases involving young girls who were diagnosed with myositis and polymyositis, respectively. Both failed to respond adequately to prednisone/methotrexate, and both are doing well now on only a gluten-free diet after being diagnosed with celiac disease on biopsy.

Screen for celiac disease in patients with vague musculoskeletal complaints who don’t respond to treatment, she said. These are the patients with whom "you just don’t know what to do," she said, adding that these are the patients who don’t clearly have arthritis, whose symptoms are out of proportion to findings on examination, whose symptoms impact their participation in sports or other activities, and who fail to respond well to a number of treatments. Often these patients will be diagnosed with fibromyalgia – a diagnosis that is unusual in young patients and should raise concern about possible other causes, she added.

In these cases, maintain a high index of suspicion for celiac disease, she said, describing the case of a 16-year-old girl who had given up sports because of a 2-year history of increasing pain in the calves, forearms, Achilles tendon, heels, and back. The skin on her thighs and calves was sensitive to touch, but she had no GI symptoms and had normal growth.

Massage, chiropractic manipulation, acupuncture, electrical stimulation, and saline injection in her calf all failed to alleviate her symptoms. The child was diagnosed with fibromyalgia and treated with gabapentin, an over-the-counter NSAID, as well as intensive physical therapy.

After a gastroenterology referral, she was diagnosed with celiac disease based on biopsy findings, and was started on a gluten-free diet. At 5 months, she was symptom free and was once again active in sports activities.

Given the consistent findings associating celiac disease with certain autoimmune disorders, and the safety and effectiveness of the gluten-free diet that is used to treat celiac disease, screening deserves consideration in these patients, she concluded.

An association between celiac disease and systemic autoimmune disease has been reported, but is less established than the association between celiac disease and nonsystemic autoimmune disorders, Dr. Adams said.

Reports of a link between celiac disease and systemic lupus erythematosus (SLE), for example, are limited to case reports, and at this point should be "taken with a grain of salt," she said.

However, it does appear that in children the celiac disease diagnosis typically precedes the SLE diagnosis, whereas the converse is true in adults.

Also, reports of SLE following celiac disease despite histologic normalization of the celiac disease on biopsy suggest that the treatment of celiac disease via a gluten-free diet does not modify the disease course in SLE, as it appears to do in cases of arthritis and myositis (J. Clin. Gastroenterol. 2008;42:252-5), Dr. Adams said.

There does, however, appear to be a fairly strong association between celiac disease and Sjögren’s syndrome.

A 2003 report said Sjögren’s syndrome is present in up to 15% of patients with biopsy-proven celiac disease, and demonstrated that anti-tTG (tissue transglutaminase, a marker for celiac disease) is more prevalent in Sjögren’s syndrome than in other systemic rheumatic diseases (J. Rheumatol. 2003;30:2613-9).

Systemic sclerosis and morphia have also been reported in association with celiac disease, Dr. Adams said.

The strongest associations between celiac disease and systemic autoimmune disease are with adult idiopathic diabetes mellitus, autoimmune thyroid disease, Addison’s disease, and polyendocrinopathies, she added.

More data are needed to define the prevalence of celiac disease in various subtypes of systemic autoimmune disease, she concluded.

Dr. Adams serves as a speaker for Abbott Pharmaceuticals. She had no other relevant disclosures.

DESTIN, FLA. – Consider screening for celiac disease in children with juvenile idiopathic arthritis, arthromyalgias, and myositis, advised Dr. Alexa B. Adams at the Congress of Clinical Rheumatology.

Celiac disease has a strong association with numerous autoimmune disorders. Untreated celiac disease poses serious health consequences, such as short stature, failure to thrive, osteopenia/osteoporosis, and enteropathy-associated T-cell lymphoma. Early diagnosis and treatment could obviate or reduce the need for the more aggressive treatments that are typically prescribed for these associated autoimmune disorders, said Dr. Adams, a pediatric rheumatologist and pediatrician at Cornell University, New York.

The identification and treatment of celiac disease in the setting of autoimmune disorders also appear to have the potential to alter the course of subsequent autoimmune disease, she said.

A link between celiac disease and juvenile idiopathic arthritis (JIA), for example, is well established. Several studies have demonstrated an increased prevalence of celiac disease among children with JIA, and cases of celiac disease in association with juvenile spondyloarthropathies and with pauciarticular, polyarticular, and psoriatic arthritis also have been reported. Furthermore, data show that a gluten-free diet can improve the musculoskeletal symptoms that are associated with celiac disease.

The mechanisms for the association between JIA and celiac disease are unknown, but may be related to ongoing intestinal permeability in untreated celiac disease, Dr. Adams said, adding that she advocates screening for celiac disease in all JIA patients.

She described a case involving a 6-year-old boy who presented with pain and swelling of the knee as well as morning stiffness. He had previously been treated for Lyme disease, and he had a 2-year history of headaches, behavioral problems, and poor growth, compared with his identical twin.

Based on physical and laboratory examinations (serology was negative for celiac disease) and after the young patient was referred to pediatric infectious disease and neurology specialties where he underwent lumbar puncture and brain MRI, the treatment focused on possible central nervous system Lyme disease. Although his joint complaints were resolved, he had persistent headaches, poor growth, and worsening transaminitis.

The boy tested negative for infectious and autoimmune hepatitis. An abdominal ultrasound showed fatty infiltration of the liver. Ultimately, the child was referred to a pediatric gastroenterologist. Work-up, including duodenal biopsy, showed findings that were consistent with celiac disease, and a gluten-free diet was initiated.

"On a gluten-free diet, the child’s headaches resolved, he had no recurrence of joint pain, he was growing and gaining weight, and he had no further behavioral issues," Dr. Adams said.

An early diagnosis of celiac disease in a JIA patient and early initiation of a gluten-free diet can prevent unnecessary treatment with NSAIDs, disease-modifying antirheumatic drugs, and anti–tumor necrosis factor agents. The patent can also avoid unnecessary imaging and joint injections.

Associations between celiac disease and adult rheumatoid arthritis/seronegative arthritides also exist, but are not as robust as that seen between celiac disease and JIA.

The coexistence of adult RA and positive celiac antibodies – including EmA (endomysial antibodies) and gliadin IgA – has been well described, but an association with biopsy-proven celiac disease has not borne out, Dr. Adams said.

The same is true in adult spondyloarthropathy.

It is possible that there are age-related differences in gluten tolerance or in the pathogenesis of arthritis and/or gut permeability that can explain the age-related differences, but this remains unclear, she noted.

As for celiac disease and myositis, the associations are well documented in both the pediatric rheumatology and pediatric gastroenterology literature, and also (although only more recently) in the adult literature.

Interestingly, a high prevalence of the DQAI*0501 allele is found in both diseases, Dr. Adams noted.

Because treatment of inflammatory myositis often requires significant use of glucocorticoids and sometimes additional immunosuppressive therapy, screening for celiac disease should be considered in myositis patients, she said, describing two cases involving young girls who were diagnosed with myositis and polymyositis, respectively. Both failed to respond adequately to prednisone/methotrexate, and both are doing well now on only a gluten-free diet after being diagnosed with celiac disease on biopsy.

Screen for celiac disease in patients with vague musculoskeletal complaints who don’t respond to treatment, she said. These are the patients with whom "you just don’t know what to do," she said, adding that these are the patients who don’t clearly have arthritis, whose symptoms are out of proportion to findings on examination, whose symptoms impact their participation in sports or other activities, and who fail to respond well to a number of treatments. Often these patients will be diagnosed with fibromyalgia – a diagnosis that is unusual in young patients and should raise concern about possible other causes, she added.

In these cases, maintain a high index of suspicion for celiac disease, she said, describing the case of a 16-year-old girl who had given up sports because of a 2-year history of increasing pain in the calves, forearms, Achilles tendon, heels, and back. The skin on her thighs and calves was sensitive to touch, but she had no GI symptoms and had normal growth.

Massage, chiropractic manipulation, acupuncture, electrical stimulation, and saline injection in her calf all failed to alleviate her symptoms. The child was diagnosed with fibromyalgia and treated with gabapentin, an over-the-counter NSAID, as well as intensive physical therapy.

After a gastroenterology referral, she was diagnosed with celiac disease based on biopsy findings, and was started on a gluten-free diet. At 5 months, she was symptom free and was once again active in sports activities.

Given the consistent findings associating celiac disease with certain autoimmune disorders, and the safety and effectiveness of the gluten-free diet that is used to treat celiac disease, screening deserves consideration in these patients, she concluded.

An association between celiac disease and systemic autoimmune disease has been reported, but is less established than the association between celiac disease and nonsystemic autoimmune disorders, Dr. Adams said.

Reports of a link between celiac disease and systemic lupus erythematosus (SLE), for example, are limited to case reports, and at this point should be "taken with a grain of salt," she said.

However, it does appear that in children the celiac disease diagnosis typically precedes the SLE diagnosis, whereas the converse is true in adults.

Also, reports of SLE following celiac disease despite histologic normalization of the celiac disease on biopsy suggest that the treatment of celiac disease via a gluten-free diet does not modify the disease course in SLE, as it appears to do in cases of arthritis and myositis (J. Clin. Gastroenterol. 2008;42:252-5), Dr. Adams said.

There does, however, appear to be a fairly strong association between celiac disease and Sjögren’s syndrome.

A 2003 report said Sjögren’s syndrome is present in up to 15% of patients with biopsy-proven celiac disease, and demonstrated that anti-tTG (tissue transglutaminase, a marker for celiac disease) is more prevalent in Sjögren’s syndrome than in other systemic rheumatic diseases (J. Rheumatol. 2003;30:2613-9).

Systemic sclerosis and morphia have also been reported in association with celiac disease, Dr. Adams said.

The strongest associations between celiac disease and systemic autoimmune disease are with adult idiopathic diabetes mellitus, autoimmune thyroid disease, Addison’s disease, and polyendocrinopathies, she added.

More data are needed to define the prevalence of celiac disease in various subtypes of systemic autoimmune disease, she concluded.

Dr. Adams serves as a speaker for Abbott Pharmaceuticals. She had no other relevant disclosures.

DESTIN, FLA. – Consider screening for celiac disease in children with juvenile idiopathic arthritis, arthromyalgias, and myositis, advised Dr. Alexa B. Adams at the Congress of Clinical Rheumatology.

Celiac disease has a strong association with numerous autoimmune disorders. Untreated celiac disease poses serious health consequences, such as short stature, failure to thrive, osteopenia/osteoporosis, and enteropathy-associated T-cell lymphoma. Early diagnosis and treatment could obviate or reduce the need for the more aggressive treatments that are typically prescribed for these associated autoimmune disorders, said Dr. Adams, a pediatric rheumatologist and pediatrician at Cornell University, New York.

The identification and treatment of celiac disease in the setting of autoimmune disorders also appear to have the potential to alter the course of subsequent autoimmune disease, she said.

A link between celiac disease and juvenile idiopathic arthritis (JIA), for example, is well established. Several studies have demonstrated an increased prevalence of celiac disease among children with JIA, and cases of celiac disease in association with juvenile spondyloarthropathies and with pauciarticular, polyarticular, and psoriatic arthritis also have been reported. Furthermore, data show that a gluten-free diet can improve the musculoskeletal symptoms that are associated with celiac disease.

The mechanisms for the association between JIA and celiac disease are unknown, but may be related to ongoing intestinal permeability in untreated celiac disease, Dr. Adams said, adding that she advocates screening for celiac disease in all JIA patients.

She described a case involving a 6-year-old boy who presented with pain and swelling of the knee as well as morning stiffness. He had previously been treated for Lyme disease, and he had a 2-year history of headaches, behavioral problems, and poor growth, compared with his identical twin.

Based on physical and laboratory examinations (serology was negative for celiac disease) and after the young patient was referred to pediatric infectious disease and neurology specialties where he underwent lumbar puncture and brain MRI, the treatment focused on possible central nervous system Lyme disease. Although his joint complaints were resolved, he had persistent headaches, poor growth, and worsening transaminitis.

The boy tested negative for infectious and autoimmune hepatitis. An abdominal ultrasound showed fatty infiltration of the liver. Ultimately, the child was referred to a pediatric gastroenterologist. Work-up, including duodenal biopsy, showed findings that were consistent with celiac disease, and a gluten-free diet was initiated.

"On a gluten-free diet, the child’s headaches resolved, he had no recurrence of joint pain, he was growing and gaining weight, and he had no further behavioral issues," Dr. Adams said.

An early diagnosis of celiac disease in a JIA patient and early initiation of a gluten-free diet can prevent unnecessary treatment with NSAIDs, disease-modifying antirheumatic drugs, and anti–tumor necrosis factor agents. The patent can also avoid unnecessary imaging and joint injections.

Associations between celiac disease and adult rheumatoid arthritis/seronegative arthritides also exist, but are not as robust as that seen between celiac disease and JIA.

The coexistence of adult RA and positive celiac antibodies – including EmA (endomysial antibodies) and gliadin IgA – has been well described, but an association with biopsy-proven celiac disease has not borne out, Dr. Adams said.

The same is true in adult spondyloarthropathy.

It is possible that there are age-related differences in gluten tolerance or in the pathogenesis of arthritis and/or gut permeability that can explain the age-related differences, but this remains unclear, she noted.

As for celiac disease and myositis, the associations are well documented in both the pediatric rheumatology and pediatric gastroenterology literature, and also (although only more recently) in the adult literature.

Interestingly, a high prevalence of the DQAI*0501 allele is found in both diseases, Dr. Adams noted.

Because treatment of inflammatory myositis often requires significant use of glucocorticoids and sometimes additional immunosuppressive therapy, screening for celiac disease should be considered in myositis patients, she said, describing two cases involving young girls who were diagnosed with myositis and polymyositis, respectively. Both failed to respond adequately to prednisone/methotrexate, and both are doing well now on only a gluten-free diet after being diagnosed with celiac disease on biopsy.

Screen for celiac disease in patients with vague musculoskeletal complaints who don’t respond to treatment, she said. These are the patients with whom "you just don’t know what to do," she said, adding that these are the patients who don’t clearly have arthritis, whose symptoms are out of proportion to findings on examination, whose symptoms impact their participation in sports or other activities, and who fail to respond well to a number of treatments. Often these patients will be diagnosed with fibromyalgia – a diagnosis that is unusual in young patients and should raise concern about possible other causes, she added.

In these cases, maintain a high index of suspicion for celiac disease, she said, describing the case of a 16-year-old girl who had given up sports because of a 2-year history of increasing pain in the calves, forearms, Achilles tendon, heels, and back. The skin on her thighs and calves was sensitive to touch, but she had no GI symptoms and had normal growth.

Massage, chiropractic manipulation, acupuncture, electrical stimulation, and saline injection in her calf all failed to alleviate her symptoms. The child was diagnosed with fibromyalgia and treated with gabapentin, an over-the-counter NSAID, as well as intensive physical therapy.

After a gastroenterology referral, she was diagnosed with celiac disease based on biopsy findings, and was started on a gluten-free diet. At 5 months, she was symptom free and was once again active in sports activities.

Given the consistent findings associating celiac disease with certain autoimmune disorders, and the safety and effectiveness of the gluten-free diet that is used to treat celiac disease, screening deserves consideration in these patients, she concluded.

An association between celiac disease and systemic autoimmune disease has been reported, but is less established than the association between celiac disease and nonsystemic autoimmune disorders, Dr. Adams said.

Reports of a link between celiac disease and systemic lupus erythematosus (SLE), for example, are limited to case reports, and at this point should be "taken with a grain of salt," she said.

However, it does appear that in children the celiac disease diagnosis typically precedes the SLE diagnosis, whereas the converse is true in adults.

Also, reports of SLE following celiac disease despite histologic normalization of the celiac disease on biopsy suggest that the treatment of celiac disease via a gluten-free diet does not modify the disease course in SLE, as it appears to do in cases of arthritis and myositis (J. Clin. Gastroenterol. 2008;42:252-5), Dr. Adams said.

There does, however, appear to be a fairly strong association between celiac disease and Sjögren’s syndrome.

A 2003 report said Sjögren’s syndrome is present in up to 15% of patients with biopsy-proven celiac disease, and demonstrated that anti-tTG (tissue transglutaminase, a marker for celiac disease) is more prevalent in Sjögren’s syndrome than in other systemic rheumatic diseases (J. Rheumatol. 2003;30:2613-9).

Systemic sclerosis and morphia have also been reported in association with celiac disease, Dr. Adams said.

The strongest associations between celiac disease and systemic autoimmune disease are with adult idiopathic diabetes mellitus, autoimmune thyroid disease, Addison’s disease, and polyendocrinopathies, she added.

More data are needed to define the prevalence of celiac disease in various subtypes of systemic autoimmune disease, she concluded.

Dr. Adams serves as a speaker for Abbott Pharmaceuticals. She had no other relevant disclosures.

DESTIN, FLA. – Consider screening for celiac disease in children with juvenile idiopathic arthritis, arthromyalgias, and myositis, advised Dr. Alexa B. Adams at the Congress of Clinical Rheumatology.

Celiac disease has a strong association with numerous autoimmune disorders. Untreated celiac disease poses serious health consequences, such as short stature, failure to thrive, osteopenia/osteoporosis, and enteropathy-associated T-cell lymphoma. Early diagnosis and treatment could obviate or reduce the need for the more aggressive treatments that are typically prescribed for these associated autoimmune disorders, said Dr. Adams, a pediatric rheumatologist and pediatrician at Cornell University, New York.

The identification and treatment of celiac disease in the setting of autoimmune disorders also appear to have the potential to alter the course of subsequent autoimmune disease, she said.

A link between celiac disease and juvenile idiopathic arthritis (JIA), for example, is well established. Several studies have demonstrated an increased prevalence of celiac disease among children with JIA, and cases of celiac disease in association with juvenile spondyloarthropathies and with pauciarticular, polyarticular, and psoriatic arthritis also have been reported. Furthermore, data show that a gluten-free diet can improve the musculoskeletal symptoms that are associated with celiac disease.

The mechanisms for the association between JIA and celiac disease are unknown, but may be related to ongoing intestinal permeability in untreated celiac disease, Dr. Adams said, adding that she advocates screening for celiac disease in all JIA patients.

She described a case involving a 6-year-old boy who presented with pain and swelling of the knee as well as morning stiffness. He had previously been treated for Lyme disease, and he had a 2-year history of headaches, behavioral problems, and poor growth, compared with his identical twin.

Based on physical and laboratory examinations (serology was negative for celiac disease) and after the young patient was referred to pediatric infectious disease and neurology specialties where he underwent lumbar puncture and brain MRI, the treatment focused on possible central nervous system Lyme disease. Although his joint complaints were resolved, he had persistent headaches, poor growth, and worsening transaminitis.

The boy tested negative for infectious and autoimmune hepatitis. An abdominal ultrasound showed fatty infiltration of the liver. Ultimately, the child was referred to a pediatric gastroenterologist. Work-up, including duodenal biopsy, showed findings that were consistent with celiac disease, and a gluten-free diet was initiated.

"On a gluten-free diet, the child’s headaches resolved, he had no recurrence of joint pain, he was growing and gaining weight, and he had no further behavioral issues," Dr. Adams said.

An early diagnosis of celiac disease in a JIA patient and early initiation of a gluten-free diet can prevent unnecessary treatment with NSAIDs, disease-modifying antirheumatic drugs, and anti–tumor necrosis factor agents. The patent can also avoid unnecessary imaging and joint injections.

Associations between celiac disease and adult rheumatoid arthritis/seronegative arthritides also exist, but are not as robust as that seen between celiac disease and JIA.

The coexistence of adult RA and positive celiac antibodies – including EmA (endomysial antibodies) and gliadin IgA – has been well described, but an association with biopsy-proven celiac disease has not borne out, Dr. Adams said.

The same is true in adult spondyloarthropathy.

It is possible that there are age-related differences in gluten tolerance or in the pathogenesis of arthritis and/or gut permeability that can explain the age-related differences, but this remains unclear, she noted.

As for celiac disease and myositis, the associations are well documented in both the pediatric rheumatology and pediatric gastroenterology literature, and also (although only more recently) in the adult literature.

Interestingly, a high prevalence of the DQAI*0501 allele is found in both diseases, Dr. Adams noted.

Because treatment of inflammatory myositis often requires significant use of glucocorticoids and sometimes additional immunosuppressive therapy, screening for celiac disease should be considered in myositis patients, she said, describing two cases involving young girls who were diagnosed with myositis and polymyositis, respectively. Both failed to respond adequately to prednisone/methotrexate, and both are doing well now on only a gluten-free diet after being diagnosed with celiac disease on biopsy.

Screen for celiac disease in patients with vague musculoskeletal complaints who don’t respond to treatment, she said. These are the patients with whom "you just don’t know what to do," she said, adding that these are the patients who don’t clearly have arthritis, whose symptoms are out of proportion to findings on examination, whose symptoms impact their participation in sports or other activities, and who fail to respond well to a number of treatments. Often these patients will be diagnosed with fibromyalgia – a diagnosis that is unusual in young patients and should raise concern about possible other causes, she added.

In these cases, maintain a high index of suspicion for celiac disease, she said, describing the case of a 16-year-old girl who had given up sports because of a 2-year history of increasing pain in the calves, forearms, Achilles tendon, heels, and back. The skin on her thighs and calves was sensitive to touch, but she had no GI symptoms and had normal growth.

Massage, chiropractic manipulation, acupuncture, electrical stimulation, and saline injection in her calf all failed to alleviate her symptoms. The child was diagnosed with fibromyalgia and treated with gabapentin, an over-the-counter NSAID, as well as intensive physical therapy.

After a gastroenterology referral, she was diagnosed with celiac disease based on biopsy findings, and was started on a gluten-free diet. At 5 months, she was symptom free and was once again active in sports activities.

Given the consistent findings associating celiac disease with certain autoimmune disorders, and the safety and effectiveness of the gluten-free diet that is used to treat celiac disease, screening deserves consideration in these patients, she concluded.

An association between celiac disease and systemic autoimmune disease has been reported, but is less established than the association between celiac disease and nonsystemic autoimmune disorders, Dr. Adams said.

Reports of a link between celiac disease and systemic lupus erythematosus (SLE), for example, are limited to case reports, and at this point should be "taken with a grain of salt," she said.

However, it does appear that in children the celiac disease diagnosis typically precedes the SLE diagnosis, whereas the converse is true in adults.

Also, reports of SLE following celiac disease despite histologic normalization of the celiac disease on biopsy suggest that the treatment of celiac disease via a gluten-free diet does not modify the disease course in SLE, as it appears to do in cases of arthritis and myositis (J. Clin. Gastroenterol. 2008;42:252-5), Dr. Adams said.

There does, however, appear to be a fairly strong association between celiac disease and Sjögren’s syndrome.

A 2003 report said Sjögren’s syndrome is present in up to 15% of patients with biopsy-proven celiac disease, and demonstrated that anti-tTG (tissue transglutaminase, a marker for celiac disease) is more prevalent in Sjögren’s syndrome than in other systemic rheumatic diseases (J. Rheumatol. 2003;30:2613-9).

Systemic sclerosis and morphia have also been reported in association with celiac disease, Dr. Adams said.

The strongest associations between celiac disease and systemic autoimmune disease are with adult idiopathic diabetes mellitus, autoimmune thyroid disease, Addison’s disease, and polyendocrinopathies, she added.

More data are needed to define the prevalence of celiac disease in various subtypes of systemic autoimmune disease, she concluded.

Dr. Adams serves as a speaker for Abbott Pharmaceuticals. She had no other relevant disclosures.

DESTIN, FLA. – Consider screening for celiac disease in children with juvenile idiopathic arthritis, arthromyalgias, and myositis, advised Dr. Alexa B. Adams at the Congress of Clinical Rheumatology.

Celiac disease has a strong association with numerous autoimmune disorders. Untreated celiac disease poses serious health consequences, such as short stature, failure to thrive, osteopenia/osteoporosis, and enteropathy-associated T-cell lymphoma. Early diagnosis and treatment could obviate or reduce the need for the more aggressive treatments that are typically prescribed for these associated autoimmune disorders, said Dr. Adams, a pediatric rheumatologist and pediatrician at Cornell University, New York.

The identification and treatment of celiac disease in the setting of autoimmune disorders also appear to have the potential to alter the course of subsequent autoimmune disease, she said.

A link between celiac disease and juvenile idiopathic arthritis (JIA), for example, is well established. Several studies have demonstrated an increased prevalence of celiac disease among children with JIA, and cases of celiac disease in association with juvenile spondyloarthropathies and with pauciarticular, polyarticular, and psoriatic arthritis also have been reported. Furthermore, data show that a gluten-free diet can improve the musculoskeletal symptoms that are associated with celiac disease.

The mechanisms for the association between JIA and celiac disease are unknown, but may be related to ongoing intestinal permeability in untreated celiac disease, Dr. Adams said, adding that she advocates screening for celiac disease in all JIA patients.

She described a case involving a 6-year-old boy who presented with pain and swelling of the knee as well as morning stiffness. He had previously been treated for Lyme disease, and he had a 2-year history of headaches, behavioral problems, and poor growth, compared with his identical twin.

Based on physical and laboratory examinations (serology was negative for celiac disease) and after the young patient was referred to pediatric infectious disease and neurology specialties where he underwent lumbar puncture and brain MRI, the treatment focused on possible central nervous system Lyme disease. Although his joint complaints were resolved, he had persistent headaches, poor growth, and worsening transaminitis.

The boy tested negative for infectious and autoimmune hepatitis. An abdominal ultrasound showed fatty infiltration of the liver. Ultimately, the child was referred to a pediatric gastroenterologist. Work-up, including duodenal biopsy, showed findings that were consistent with celiac disease, and a gluten-free diet was initiated.

"On a gluten-free diet, the child’s headaches resolved, he had no recurrence of joint pain, he was growing and gaining weight, and he had no further behavioral issues," Dr. Adams said.

An early diagnosis of celiac disease in a JIA patient and early initiation of a gluten-free diet can prevent unnecessary treatment with NSAIDs, disease-modifying antirheumatic drugs, and anti–tumor necrosis factor agents. The patent can also avoid unnecessary imaging and joint injections.

Associations between celiac disease and adult rheumatoid arthritis/seronegative arthritides also exist, but are not as robust as that seen between celiac disease and JIA.

The coexistence of adult RA and positive celiac antibodies – including EmA (endomysial antibodies) and gliadin IgA – has been well described, but an association with biopsy-proven celiac disease has not borne out, Dr. Adams said.

The same is true in adult spondyloarthropathy.

It is possible that there are age-related differences in gluten tolerance or in the pathogenesis of arthritis and/or gut permeability that can explain the age-related differences, but this remains unclear, she noted.

As for celiac disease and myositis, the associations are well documented in both the pediatric rheumatology and pediatric gastroenterology literature, and also (although only more recently) in the adult literature.

Interestingly, a high prevalence of the DQAI*0501 allele is found in both diseases, Dr. Adams noted.

Because treatment of inflammatory myositis often requires significant use of glucocorticoids and sometimes additional immunosuppressive therapy, screening for celiac disease should be considered in myositis patients, she said, describing two cases involving young girls who were diagnosed with myositis and polymyositis, respectively. Both failed to respond adequately to prednisone/methotrexate, and both are doing well now on only a gluten-free diet after being diagnosed with celiac disease on biopsy.

Screen for celiac disease in patients with vague musculoskeletal complaints who don’t respond to treatment, she said. These are the patients with whom "you just don’t know what to do," she said, adding that these are the patients who don’t clearly have arthritis, whose symptoms are out of proportion to findings on examination, whose symptoms impact their participation in sports or other activities, and who fail to respond well to a number of treatments. Often these patients will be diagnosed with fibromyalgia – a diagnosis that is unusual in young patients and should raise concern about possible other causes, she added.

In these cases, maintain a high index of suspicion for celiac disease, she said, describing the case of a 16-year-old girl who had given up sports because of a 2-year history of increasing pain in the calves, forearms, Achilles tendon, heels, and back. The skin on her thighs and calves was sensitive to touch, but she had no GI symptoms and had normal growth.

Massage, chiropractic manipulation, acupuncture, electrical stimulation, and saline injection in her calf all failed to alleviate her symptoms. The child was diagnosed with fibromyalgia and treated with gabapentin, an over-the-counter NSAID, as well as intensive physical therapy.

After a gastroenterology referral, she was diagnosed with celiac disease based on biopsy findings, and was started on a gluten-free diet. At 5 months, she was symptom free and was once again active in sports activities.

Given the consistent findings associating celiac disease with certain autoimmune disorders, and the safety and effectiveness of the gluten-free diet that is used to treat celiac disease, screening deserves consideration in these patients, she concluded.

An association between celiac disease and systemic autoimmune disease has been reported, but is less established than the association between celiac disease and nonsystemic autoimmune disorders, Dr. Adams said.

Reports of a link between celiac disease and systemic lupus erythematosus (SLE), for example, are limited to case reports, and at this point should be "taken with a grain of salt," she said.

However, it does appear that in children the celiac disease diagnosis typically precedes the SLE diagnosis, whereas the converse is true in adults.

Also, reports of SLE following celiac disease despite histologic normalization of the celiac disease on biopsy suggest that the treatment of celiac disease via a gluten-free diet does not modify the disease course in SLE, as it appears to do in cases of arthritis and myositis (J. Clin. Gastroenterol. 2008;42:252-5), Dr. Adams said.

There does, however, appear to be a fairly strong association between celiac disease and Sjögren’s syndrome.

A 2003 report said Sjögren’s syndrome is present in up to 15% of patients with biopsy-proven celiac disease, and demonstrated that anti-tTG (tissue transglutaminase, a marker for celiac disease) is more prevalent in Sjögren’s syndrome than in other systemic rheumatic diseases (J. Rheumatol. 2003;30:2613-9).

Systemic sclerosis and morphia have also been reported in association with celiac disease, Dr. Adams said.

The strongest associations between celiac disease and systemic autoimmune disease are with adult idiopathic diabetes mellitus, autoimmune thyroid disease, Addison’s disease, and polyendocrinopathies, she added.

More data are needed to define the prevalence of celiac disease in various subtypes of systemic autoimmune disease, she concluded.

Dr. Adams serves as a speaker for Abbott Pharmaceuticals. She had no other relevant disclosures.

DESTIN, FLA. – Consider screening for celiac disease in children with juvenile idiopathic arthritis, arthromyalgias, and myositis, advised Dr. Alexa B. Adams at the Congress of Clinical Rheumatology.

Celiac disease has a strong association with numerous autoimmune disorders. Untreated celiac disease poses serious health consequences, such as short stature, failure to thrive, osteopenia/osteoporosis, and enteropathy-associated T-cell lymphoma. Early diagnosis and treatment could obviate or reduce the need for the more aggressive treatments that are typically prescribed for these associated autoimmune disorders, said Dr. Adams, a pediatric rheumatologist and pediatrician at Cornell University, New York.

The identification and treatment of celiac disease in the setting of autoimmune disorders also appear to have the potential to alter the course of subsequent autoimmune disease, she said.

A link between celiac disease and juvenile idiopathic arthritis (JIA), for example, is well established. Several studies have demonstrated an increased prevalence of celiac disease among children with JIA, and cases of celiac disease in association with juvenile spondyloarthropathies and with pauciarticular, polyarticular, and psoriatic arthritis also have been reported. Furthermore, data show that a gluten-free diet can improve the musculoskeletal symptoms that are associated with celiac disease.

The mechanisms for the association between JIA and celiac disease are unknown, but may be related to ongoing intestinal permeability in untreated celiac disease, Dr. Adams said, adding that she advocates screening for celiac disease in all JIA patients.

She described a case involving a 6-year-old boy who presented with pain and swelling of the knee as well as morning stiffness. He had previously been treated for Lyme disease, and he had a 2-year history of headaches, behavioral problems, and poor growth, compared with his identical twin.

Based on physical and laboratory examinations (serology was negative for celiac disease) and after the young patient was referred to pediatric infectious disease and neurology specialties where he underwent lumbar puncture and brain MRI, the treatment focused on possible central nervous system Lyme disease. Although his joint complaints were resolved, he had persistent headaches, poor growth, and worsening transaminitis.

The boy tested negative for infectious and autoimmune hepatitis. An abdominal ultrasound showed fatty infiltration of the liver. Ultimately, the child was referred to a pediatric gastroenterologist. Work-up, including duodenal biopsy, showed findings that were consistent with celiac disease, and a gluten-free diet was initiated.

"On a gluten-free diet, the child’s headaches resolved, he had no recurrence of joint pain, he was growing and gaining weight, and he had no further behavioral issues," Dr. Adams said.

An early diagnosis of celiac disease in a JIA patient and early initiation of a gluten-free diet can prevent unnecessary treatment with NSAIDs, disease-modifying antirheumatic drugs, and anti–tumor necrosis factor agents. The patent can also avoid unnecessary imaging and joint injections.

Associations between celiac disease and adult rheumatoid arthritis/seronegative arthritides also exist, but are not as robust as that seen between celiac disease and JIA.

The coexistence of adult RA and positive celiac antibodies – including EmA (endomysial antibodies) and gliadin IgA – has been well described, but an association with biopsy-proven celiac disease has not borne out, Dr. Adams said.

The same is true in adult spondyloarthropathy.

It is possible that there are age-related differences in gluten tolerance or in the pathogenesis of arthritis and/or gut permeability that can explain the age-related differences, but this remains unclear, she noted.

As for celiac disease and myositis, the associations are well documented in both the pediatric rheumatology and pediatric gastroenterology literature, and also (although only more recently) in the adult literature.

Interestingly, a high prevalence of the DQAI*0501 allele is found in both diseases, Dr. Adams noted.

Because treatment of inflammatory myositis often requires significant use of glucocorticoids and sometimes additional immunosuppressive therapy, screening for celiac disease should be considered in myositis patients, she said, describing two cases involving young girls who were diagnosed with myositis and polymyositis, respectively. Both failed to respond adequately to prednisone/methotrexate, and both are doing well now on only a gluten-free diet after being diagnosed with celiac disease on biopsy.

Screen for celiac disease in patients with vague musculoskeletal complaints who don’t respond to treatment, she said. These are the patients with whom "you just don’t know what to do," she said, adding that these are the patients who don’t clearly have arthritis, whose symptoms are out of proportion to findings on examination, whose symptoms impact their participation in sports or other activities, and who fail to respond well to a number of treatments. Often these patients will be diagnosed with fibromyalgia – a diagnosis that is unusual in young patients and should raise concern about possible other causes, she added.

In these cases, maintain a high index of suspicion for celiac disease, she said, describing the case of a 16-year-old girl who had given up sports because of a 2-year history of increasing pain in the calves, forearms, Achilles tendon, heels, and back. The skin on her thighs and calves was sensitive to touch, but she had no GI symptoms and had normal growth.

Massage, chiropractic manipulation, acupuncture, electrical stimulation, and saline injection in her calf all failed to alleviate her symptoms. The child was diagnosed with fibromyalgia and treated with gabapentin, an over-the-counter NSAID, as well as intensive physical therapy.

After a gastroenterology referral, she was diagnosed with celiac disease based on biopsy findings, and was started on a gluten-free diet. At 5 months, she was symptom free and was once again active in sports activities.

Given the consistent findings associating celiac disease with certain autoimmune disorders, and the safety and effectiveness of the gluten-free diet that is used to treat celiac disease, screening deserves consideration in these patients, she concluded.

An association between celiac disease and systemic autoimmune disease has been reported, but is less established than the association between celiac disease and nonsystemic autoimmune disorders, Dr. Adams said.

Reports of a link between celiac disease and systemic lupus erythematosus (SLE), for example, are limited to case reports, and at this point should be "taken with a grain of salt," she said.

However, it does appear that in children the celiac disease diagnosis typically precedes the SLE diagnosis, whereas the converse is true in adults.

Also, reports of SLE following celiac disease despite histologic normalization of the celiac disease on biopsy suggest that the treatment of celiac disease via a gluten-free diet does not modify the disease course in SLE, as it appears to do in cases of arthritis and myositis (J. Clin. Gastroenterol. 2008;42:252-5), Dr. Adams said.

There does, however, appear to be a fairly strong association between celiac disease and Sjögren’s syndrome.

A 2003 report said Sjögren’s syndrome is present in up to 15% of patients with biopsy-proven celiac disease, and demonstrated that anti-tTG (tissue transglutaminase, a marker for celiac disease) is more prevalent in Sjögren’s syndrome than in other systemic rheumatic diseases (J. Rheumatol. 2003;30:2613-9).

Systemic sclerosis and morphia have also been reported in association with celiac disease, Dr. Adams said.

The strongest associations between celiac disease and systemic autoimmune disease are with adult idiopathic diabetes mellitus, autoimmune thyroid disease, Addison’s disease, and polyendocrinopathies, she added.

More data are needed to define the prevalence of celiac disease in various subtypes of systemic autoimmune disease, she concluded.

Dr. Adams serves as a speaker for Abbott Pharmaceuticals. She had no other relevant disclosures.

DESTIN, FLA. – Consider screening for celiac disease in children with juvenile idiopathic arthritis, arthromyalgias, and myositis, advised Dr. Alexa B. Adams at the Congress of Clinical Rheumatology.

Celiac disease has a strong association with numerous autoimmune disorders. Untreated celiac disease poses serious health consequences, such as short stature, failure to thrive, osteopenia/osteoporosis, and enteropathy-associated T-cell lymphoma. Early diagnosis and treatment could obviate or reduce the need for the more aggressive treatments that are typically prescribed for these associated autoimmune disorders, said Dr. Adams, a pediatric rheumatologist and pediatrician at Cornell University, New York.

The identification and treatment of celiac disease in the setting of autoimmune disorders also appear to have the potential to alter the course of subsequent autoimmune disease, she said.

A link between celiac disease and juvenile idiopathic arthritis (JIA), for example, is well established. Several studies have demonstrated an increased prevalence of celiac disease among children with JIA, and cases of celiac disease in association with juvenile spondyloarthropathies and with pauciarticular, polyarticular, and psoriatic arthritis also have been reported. Furthermore, data show that a gluten-free diet can improve the musculoskeletal symptoms that are associated with celiac disease.

The mechanisms for the association between JIA and celiac disease are unknown, but may be related to ongoing intestinal permeability in untreated celiac disease, Dr. Adams said, adding that she advocates screening for celiac disease in all JIA patients.

She described a case involving a 6-year-old boy who presented with pain and swelling of the knee as well as morning stiffness. He had previously been treated for Lyme disease, and he had a 2-year history of headaches, behavioral problems, and poor growth, compared with his identical twin.

Based on physical and laboratory examinations (serology was negative for celiac disease) and after the young patient was referred to pediatric infectious disease and neurology specialties where he underwent lumbar puncture and brain MRI, the treatment focused on possible central nervous system Lyme disease. Although his joint complaints were resolved, he had persistent headaches, poor growth, and worsening transaminitis.

The boy tested negative for infectious and autoimmune hepatitis. An abdominal ultrasound showed fatty infiltration of the liver. Ultimately, the child was referred to a pediatric gastroenterologist. Work-up, including duodenal biopsy, showed findings that were consistent with celiac disease, and a gluten-free diet was initiated.

"On a gluten-free diet, the child’s headaches resolved, he had no recurrence of joint pain, he was growing and gaining weight, and he had no further behavioral issues," Dr. Adams said.

An early diagnosis of celiac disease in a JIA patient and early initiation of a gluten-free diet can prevent unnecessary treatment with NSAIDs, disease-modifying antirheumatic drugs, and anti–tumor necrosis factor agents. The patent can also avoid unnecessary imaging and joint injections.

Associations between celiac disease and adult rheumatoid arthritis/seronegative arthritides also exist, but are not as robust as that seen between celiac disease and JIA.

The coexistence of adult RA and positive celiac antibodies – including EmA (endomysial antibodies) and gliadin IgA – has been well described, but an association with biopsy-proven celiac disease has not borne out, Dr. Adams said.

The same is true in adult spondyloarthropathy.

It is possible that there are age-related differences in gluten tolerance or in the pathogenesis of arthritis and/or gut permeability that can explain the age-related differences, but this remains unclear, she noted.

As for celiac disease and myositis, the associations are well documented in both the pediatric rheumatology and pediatric gastroenterology literature, and also (although only more recently) in the adult literature.

Interestingly, a high prevalence of the DQAI*0501 allele is found in both diseases, Dr. Adams noted.

Because treatment of inflammatory myositis often requires significant use of glucocorticoids and sometimes additional immunosuppressive therapy, screening for celiac disease should be considered in myositis patients, she said, describing two cases involving young girls who were diagnosed with myositis and polymyositis, respectively. Both failed to respond adequately to prednisone/methotrexate, and both are doing well now on only a gluten-free diet after being diagnosed with celiac disease on biopsy.

Screen for celiac disease in patients with vague musculoskeletal complaints who don’t respond to treatment, she said. These are the patients with whom "you just don’t know what to do," she said, adding that these are the patients who don’t clearly have arthritis, whose symptoms are out of proportion to findings on examination, whose symptoms impact their participation in sports or other activities, and who fail to respond well to a number of treatments. Often these patients will be diagnosed with fibromyalgia – a diagnosis that is unusual in young patients and should raise concern about possible other causes, she added.

In these cases, maintain a high index of suspicion for celiac disease, she said, describing the case of a 16-year-old girl who had given up sports because of a 2-year history of increasing pain in the calves, forearms, Achilles tendon, heels, and back. The skin on her thighs and calves was sensitive to touch, but she had no GI symptoms and had normal growth.

Massage, chiropractic manipulation, acupuncture, electrical stimulation, and saline injection in her calf all failed to alleviate her symptoms. The child was diagnosed with fibromyalgia and treated with gabapentin, an over-the-counter NSAID, as well as intensive physical therapy.

After a gastroenterology referral, she was diagnosed with celiac disease based on biopsy findings, and was started on a gluten-free diet. At 5 months, she was symptom free and was once again active in sports activities.

Given the consistent findings associating celiac disease with certain autoimmune disorders, and the safety and effectiveness of the gluten-free diet that is used to treat celiac disease, screening deserves consideration in these patients, she concluded.

An association between celiac disease and systemic autoimmune disease has been reported, but is less established than the association between celiac disease and nonsystemic autoimmune disorders, Dr. Adams said.

Reports of a link between celiac disease and systemic lupus erythematosus (SLE), for example, are limited to case reports, and at this point should be "taken with a grain of salt," she said.

However, it does appear that in children the celiac disease diagnosis typically precedes the SLE diagnosis, whereas the converse is true in adults.

Also, reports of SLE following celiac disease despite histologic normalization of the celiac disease on biopsy suggest that the treatment of celiac disease via a gluten-free diet does not modify the disease course in SLE, as it appears to do in cases of arthritis and myositis (J. Clin. Gastroenterol. 2008;42:252-5), Dr. Adams said.

There does, however, appear to be a fairly strong association between celiac disease and Sjögren’s syndrome.

A 2003 report said Sjögren’s syndrome is present in up to 15% of patients with biopsy-proven celiac disease, and demonstrated that anti-tTG (tissue transglutaminase, a marker for celiac disease) is more prevalent in Sjögren’s syndrome than in other systemic rheumatic diseases (J. Rheumatol. 2003;30:2613-9).

Systemic sclerosis and morphia have also been reported in association with celiac disease, Dr. Adams said.

The strongest associations between celiac disease and systemic autoimmune disease are with adult idiopathic diabetes mellitus, autoimmune thyroid disease, Addison’s disease, and polyendocrinopathies, she added.

More data are needed to define the prevalence of celiac disease in various subtypes of systemic autoimmune disease, she concluded.

Dr. Adams serves as a speaker for Abbott Pharmaceuticals. She had no other relevant disclosures.

DESTIN, FLA. – More is not necessarily better when it comes to vitamin D.

“The optimal intake and blood levels are probably much more moderate than many have led us to believe,” Dr. JoAnn E. Manson said at the meeting.

As a member of the 14-person Institute of Medicine Committee charged with developing a recently published report on dietary reference intakes of vitamin D and calcium, Dr. Manson assisted in a “rigorous comprehensive review” of more than 1,000 studies, and while many researchers and clinicians have argued that people need much higher levels than the 400-800 IU/day intake (depending on age) recommended by the IOM to promote optimal health, the available evidence simply has not borne that out, said Dr. Manson, professor of epidemiology at Harvard University and chief of the division of preventive medicine at Brigham and Women's Hospital, Boston.

Although some IOM report naysayers advocate for levels up to 6,000 IU/day – and the lay press is replete with stories touting vitamin D as a panacea, it is actually very difficult to find any solid data showing increased benefit with higher doses, she said.

In fact, the committee's findings indicate that adequate intake for infants through age 12 months is 400 IU/day, and that the Recommended Dietary Allowance for individuals aged 1-70 years should be at least 600 IU/day, and those over age 70 years it should be 800 IU/day. The upper intake levels are 1,000 and 1,500 IU/day for those ages 0-6 months and 6-12 months, respectively, 2,500 IU/day for those ages 1-3 years, 3,000 IU/day for those ages 4-8 years, and 4,000 IU/day for those over age 8 years, according to the IOM report (J. Clin. Endocrinol. Metab. 2011;96:53-8).

These minimum levels represent the intake needed to meet the vitamin D requirements of 97.5% of the population, and correspond to a serum 25-hydroxyvitamin D (25-OHD) level of 20 ng/mL, which the data indicate is the optimal level. At levels above the upper intake level, which correspond to a serum 25-OHD level of about 50 ng/mL, adverse effects have been reported, Dr. Manson said.

Emerging evidence suggests excess intake may be associated with increased all-cause mortality, cancer, cardiovascular disease, falls, and fractures, she noted.

National Health and Nutrition Examination Survey (NHANES) data from 2008, for example, showed that age-adjusted mortality was highest among those with serum 25-OHD levels below 19 ng/mL in African Americans and below 27.5 ng/mL in the entire cohort, and that mortality decreased with increasing levels – but only to a certain point. At levels in the 50 ng/mL range for African Americans, and above 85 ng/mL in the entire cohort, mortality increased steadily.

Data on the effects of vitamin D on skeletal health, which provided the strongest basis for the IOM committee's report as they were most plentiful and convincing in terms of showing cause and effect (although evidence regarding numerous other diseases such as cancer, diabetes, and more were also considered), also suggest that too much vitamin D can lead to adverse effects. Women's Health Initiative findings, for example, show that adjusted hip fracture rates are highest among those with serum 25-OHD levels of 19.04 ng/mL and those greater than 28.3 ng/mL, and lowest among those between these levels (Ann. Intern. Med. 2008;149:242-50), Dr. Manson said.

In older men in the Osteoporotic Fractures in Men (MrOS) study, the adjusted risk of hip fractures was shown to be highest in those with serum 25-OHD levels less than 19 ng/mL (odds ratio 2.36, compared with those with levels greater than 28 ng/mL), with risk declining steadily in those with levels up to 28 ng/mL (J. Bone Miner. Res. 2010;25:545-53).

Other findings indicate the skeletal benefits of vitamin D are dependent on adequate calcium intake, which the committee determined is 200 and 260 mg/day for those aged 0-6 and 6-12 months, respectively; 700 mg/day for those aged 1-3 years; 1,000 mg/day for those aged 4-8 years, 19-70 years, and for women aged 19-50 years who are pregnant or lactating; 1,200 mg/day for those aged 51 years and older; and 1,300 mg/day for those aged 9-18 years, and for women aged 14-18 years who are pregnant or lactating.

An Agency for Healthcare Research and Quality report in 2009, for example, showed that three randomized controlled trials indicated no significant effect of vitamin D alone on fracture risk, but that one randomized controlled trial showed a benefit in those who received 800 IU of vitamin D₃ plus 1,200 mg/day of calcium for 2 years (odds ratio of fractures 0.80), Dr. Manson said.

Dr. Manson has received funding from the National Institutes of Health to conduct a large-scale randomized trial of vitamin D and omega-3 fatty acids.

DESTIN, FLA. – More is not necessarily better when it comes to vitamin D.

“The optimal intake and blood levels are probably much more moderate than many have led us to believe,” Dr. JoAnn E. Manson said at the meeting.

As a member of the 14-person Institute of Medicine Committee charged with developing a recently published report on dietary reference intakes of vitamin D and calcium, Dr. Manson assisted in a “rigorous comprehensive review” of more than 1,000 studies, and while many researchers and clinicians have argued that people need much higher levels than the 400-800 IU/day intake (depending on age) recommended by the IOM to promote optimal health, the available evidence simply has not borne that out, said Dr. Manson, professor of epidemiology at Harvard University and chief of the division of preventive medicine at Brigham and Women's Hospital, Boston.

Although some IOM report naysayers advocate for levels up to 6,000 IU/day – and the lay press is replete with stories touting vitamin D as a panacea, it is actually very difficult to find any solid data showing increased benefit with higher doses, she said.

In fact, the committee's findings indicate that adequate intake for infants through age 12 months is 400 IU/day, and that the Recommended Dietary Allowance for individuals aged 1-70 years should be at least 600 IU/day, and those over age 70 years it should be 800 IU/day. The upper intake levels are 1,000 and 1,500 IU/day for those ages 0-6 months and 6-12 months, respectively, 2,500 IU/day for those ages 1-3 years, 3,000 IU/day for those ages 4-8 years, and 4,000 IU/day for those over age 8 years, according to the IOM report (J. Clin. Endocrinol. Metab. 2011;96:53-8).

These minimum levels represent the intake needed to meet the vitamin D requirements of 97.5% of the population, and correspond to a serum 25-hydroxyvitamin D (25-OHD) level of 20 ng/mL, which the data indicate is the optimal level. At levels above the upper intake level, which correspond to a serum 25-OHD level of about 50 ng/mL, adverse effects have been reported, Dr. Manson said.

Emerging evidence suggests excess intake may be associated with increased all-cause mortality, cancer, cardiovascular disease, falls, and fractures, she noted.

National Health and Nutrition Examination Survey (NHANES) data from 2008, for example, showed that age-adjusted mortality was highest among those with serum 25-OHD levels below 19 ng/mL in African Americans and below 27.5 ng/mL in the entire cohort, and that mortality decreased with increasing levels – but only to a certain point. At levels in the 50 ng/mL range for African Americans, and above 85 ng/mL in the entire cohort, mortality increased steadily.

Data on the effects of vitamin D on skeletal health, which provided the strongest basis for the IOM committee's report as they were most plentiful and convincing in terms of showing cause and effect (although evidence regarding numerous other diseases such as cancer, diabetes, and more were also considered), also suggest that too much vitamin D can lead to adverse effects. Women's Health Initiative findings, for example, show that adjusted hip fracture rates are highest among those with serum 25-OHD levels of 19.04 ng/mL and those greater than 28.3 ng/mL, and lowest among those between these levels (Ann. Intern. Med. 2008;149:242-50), Dr. Manson said.

In older men in the Osteoporotic Fractures in Men (MrOS) study, the adjusted risk of hip fractures was shown to be highest in those with serum 25-OHD levels less than 19 ng/mL (odds ratio 2.36, compared with those with levels greater than 28 ng/mL), with risk declining steadily in those with levels up to 28 ng/mL (J. Bone Miner. Res. 2010;25:545-53).

Other findings indicate the skeletal benefits of vitamin D are dependent on adequate calcium intake, which the committee determined is 200 and 260 mg/day for those aged 0-6 and 6-12 months, respectively; 700 mg/day for those aged 1-3 years; 1,000 mg/day for those aged 4-8 years, 19-70 years, and for women aged 19-50 years who are pregnant or lactating; 1,200 mg/day for those aged 51 years and older; and 1,300 mg/day for those aged 9-18 years, and for women aged 14-18 years who are pregnant or lactating.

An Agency for Healthcare Research and Quality report in 2009, for example, showed that three randomized controlled trials indicated no significant effect of vitamin D alone on fracture risk, but that one randomized controlled trial showed a benefit in those who received 800 IU of vitamin D₃ plus 1,200 mg/day of calcium for 2 years (odds ratio of fractures 0.80), Dr. Manson said.

Dr. Manson has received funding from the National Institutes of Health to conduct a large-scale randomized trial of vitamin D and omega-3 fatty acids.

DESTIN, FLA. – More is not necessarily better when it comes to vitamin D.

“The optimal intake and blood levels are probably much more moderate than many have led us to believe,” Dr. JoAnn E. Manson said at the meeting.

As a member of the 14-person Institute of Medicine Committee charged with developing a recently published report on dietary reference intakes of vitamin D and calcium, Dr. Manson assisted in a “rigorous comprehensive review” of more than 1,000 studies, and while many researchers and clinicians have argued that people need much higher levels than the 400-800 IU/day intake (depending on age) recommended by the IOM to promote optimal health, the available evidence simply has not borne that out, said Dr. Manson, professor of epidemiology at Harvard University and chief of the division of preventive medicine at Brigham and Women's Hospital, Boston.

Although some IOM report naysayers advocate for levels up to 6,000 IU/day – and the lay press is replete with stories touting vitamin D as a panacea, it is actually very difficult to find any solid data showing increased benefit with higher doses, she said.

In fact, the committee's findings indicate that adequate intake for infants through age 12 months is 400 IU/day, and that the Recommended Dietary Allowance for individuals aged 1-70 years should be at least 600 IU/day, and those over age 70 years it should be 800 IU/day. The upper intake levels are 1,000 and 1,500 IU/day for those ages 0-6 months and 6-12 months, respectively, 2,500 IU/day for those ages 1-3 years, 3,000 IU/day for those ages 4-8 years, and 4,000 IU/day for those over age 8 years, according to the IOM report (J. Clin. Endocrinol. Metab. 2011;96:53-8).

These minimum levels represent the intake needed to meet the vitamin D requirements of 97.5% of the population, and correspond to a serum 25-hydroxyvitamin D (25-OHD) level of 20 ng/mL, which the data indicate is the optimal level. At levels above the upper intake level, which correspond to a serum 25-OHD level of about 50 ng/mL, adverse effects have been reported, Dr. Manson said.

Emerging evidence suggests excess intake may be associated with increased all-cause mortality, cancer, cardiovascular disease, falls, and fractures, she noted.

National Health and Nutrition Examination Survey (NHANES) data from 2008, for example, showed that age-adjusted mortality was highest among those with serum 25-OHD levels below 19 ng/mL in African Americans and below 27.5 ng/mL in the entire cohort, and that mortality decreased with increasing levels – but only to a certain point. At levels in the 50 ng/mL range for African Americans, and above 85 ng/mL in the entire cohort, mortality increased steadily.

Data on the effects of vitamin D on skeletal health, which provided the strongest basis for the IOM committee's report as they were most plentiful and convincing in terms of showing cause and effect (although evidence regarding numerous other diseases such as cancer, diabetes, and more were also considered), also suggest that too much vitamin D can lead to adverse effects. Women's Health Initiative findings, for example, show that adjusted hip fracture rates are highest among those with serum 25-OHD levels of 19.04 ng/mL and those greater than 28.3 ng/mL, and lowest among those between these levels (Ann. Intern. Med. 2008;149:242-50), Dr. Manson said.

In older men in the Osteoporotic Fractures in Men (MrOS) study, the adjusted risk of hip fractures was shown to be highest in those with serum 25-OHD levels less than 19 ng/mL (odds ratio 2.36, compared with those with levels greater than 28 ng/mL), with risk declining steadily in those with levels up to 28 ng/mL (J. Bone Miner. Res. 2010;25:545-53).

Other findings indicate the skeletal benefits of vitamin D are dependent on adequate calcium intake, which the committee determined is 200 and 260 mg/day for those aged 0-6 and 6-12 months, respectively; 700 mg/day for those aged 1-3 years; 1,000 mg/day for those aged 4-8 years, 19-70 years, and for women aged 19-50 years who are pregnant or lactating; 1,200 mg/day for those aged 51 years and older; and 1,300 mg/day for those aged 9-18 years, and for women aged 14-18 years who are pregnant or lactating.

An Agency for Healthcare Research and Quality report in 2009, for example, showed that three randomized controlled trials indicated no significant effect of vitamin D alone on fracture risk, but that one randomized controlled trial showed a benefit in those who received 800 IU of vitamin D₃ plus 1,200 mg/day of calcium for 2 years (odds ratio of fractures 0.80), Dr. Manson said.

Dr. Manson has received funding from the National Institutes of Health to conduct a large-scale randomized trial of vitamin D and omega-3 fatty acids.

DESTIN, FLA. – More is not necessarily better when it comes to vitamin D.

“The optimal intake and blood levels are probably much more moderate than many have led us to believe,” Dr. JoAnn E. Manson said.

As a member of the 14-person Institute of Medicine Committee charged with developing a recently published report on dietary reference intakes of vitamin D and calcium, Dr. Manson assisted in a “rigorous comprehensive review” of more than 1,000 studies, and while many researchers and clinicians have argued that people need much higher levels than the 400-800 IU/day intake (depending on age) recommended by the IOM to promote optimal health, the available evidence simply has not borne that out, said Dr. Manson, professor of epidemiology at Harvard University and chief of the division of preventive medicine at Brigham and Women's Hospital, Boston.

Although some IOM report naysayers advocate for levels up to 6,000 IU/day – and the lay press is replete with stories touting vitamin D as a panacea, it is actually very difficult to find any solid data showing increased benefit with higher doses, she said.

In fact, the committee's findings indicate that adequate intake for infants through age 12 months is 400 IU/day, and that the Recommended Dietary Allowance for individuals aged 1-70 years should be at least 600 IU/day, and in those over age 70 years it should be 800 IU/day. The upper intake levels are 1,000 and 1,500 IU/day for those ages 0-6 months and 6-12 months, respectively, 2,500 IU/day for those ages 1–3 years, 3,000 IU/day for those ages 4–8 years, and 4,000 IU/day for those over age 8 years, according to the IOM report (J. Clin. Endocrinol. Metab. 2011;96:53–8).

These minimum levels represent the intake needed to meet the vitamin D requirements of 97.5% of the population, and correspond to a serum 25-hydroxyvitamin D [25(OH)D] level of 20 ng/mL, which the data indicate is the optimal level. At levels above the upper intake level, which correspond to a serum 25-OHD level of about 50 ng/mL, adverse effects have been reported, Dr. Manson said.

Emerging evidence suggests excess intake may be associated with increased all-cause mortality, cancer, cardiovascular disease, falls, and fractures, she noted.

National Health and Nutrition Examination Survey (NHANES) data from 2008 showed that age-adjusted mortality was highest among those with serum 25(OH)D levels below 19 ng/mL in African Americans and below 27.5 ng/mL in the entire cohort, and that mortality decreased with increasing levels – but only to a certain point. At levels in the 50 ng/mL range for African Americans, and above 85 ng/mL in the entire cohort, mortality increased steadily.

Data on the effects of vitamin D on skeletal health, which provided the strongest basis for the IOM committee's report as they were most plentiful and convincing in terms of showing cause and effect (although evidence regarding numerous other diseases such as cancer, diabetes, and more were also considered), also suggest that too much vitamin D can lead to adverse effects. Women's Health Initiative findings, for example, show that adjusted hip fracture rates are highest among those with serum 25(OH)D levels of 19.04 ng/mL and those greater than 28.3 ng/mL, and lowest among those between these levels (Ann. Intern. Med. 2008;149:242–50), she said.

In older men in the Osteoporotic Fractures in Men (MrOS) study, the adjusted risk of hip fractures was shown to be highest in those with serum 25(OH)D levels less than 19 ng/mL (odds ratio 2.36, compared with those with levels greater than 28 ng/mL), with risk declining steadily in those with levels up to 28 ng/mL (J. Bone Miner. Res. 2010;25:545–53).

The skeletal benefits of vitamin D are dependent on adequate calcium intake, which the committee determined is 200 and 260 mg/day for those aged 0–6 and 6–12 months, respectively; 700 mg/day for those aged 1–3 years; 1,000 mg/day for those aged 4–8 years, 19–70 years, and for women aged 19–50 years who are pregnant or lactating; 1,200 mg/day for those aged 51 years and older; and 1,300 mg/day for those aged 9–18 years, and for women aged 14-18 years who are pregnant or lactating.

An Agency for Healthcare Research and Quality report in 2009 showed that three randomized controlled trials indicated no significant effect of vitamin D alone on fracture risk, but that one randomized controlled trial showed a benefit in those who received 800 IU of vitamin D₃ plus 1,200 mg/day of calcium for 2 years (OR of fractures 0.80), she said.

Dr. Manson has funding from the National Institutes of Health to conduct a large-scale randomized trial of vitamin D and omega-3 fatty acids.

DESTIN, FLA. – More is not necessarily better when it comes to vitamin D.

“The optimal intake and blood levels are probably much more moderate than many have led us to believe,” Dr. JoAnn E. Manson said.

As a member of the 14-person Institute of Medicine Committee charged with developing a recently published report on dietary reference intakes of vitamin D and calcium, Dr. Manson assisted in a “rigorous comprehensive review” of more than 1,000 studies, and while many researchers and clinicians have argued that people need much higher levels than the 400-800 IU/day intake (depending on age) recommended by the IOM to promote optimal health, the available evidence simply has not borne that out, said Dr. Manson, professor of epidemiology at Harvard University and chief of the division of preventive medicine at Brigham and Women's Hospital, Boston.

Although some IOM report naysayers advocate for levels up to 6,000 IU/day – and the lay press is replete with stories touting vitamin D as a panacea, it is actually very difficult to find any solid data showing increased benefit with higher doses, she said.

In fact, the committee's findings indicate that adequate intake for infants through age 12 months is 400 IU/day, and that the Recommended Dietary Allowance for individuals aged 1-70 years should be at least 600 IU/day, and in those over age 70 years it should be 800 IU/day. The upper intake levels are 1,000 and 1,500 IU/day for those ages 0-6 months and 6-12 months, respectively, 2,500 IU/day for those ages 1–3 years, 3,000 IU/day for those ages 4–8 years, and 4,000 IU/day for those over age 8 years, according to the IOM report (J. Clin. Endocrinol. Metab. 2011;96:53–8).

These minimum levels represent the intake needed to meet the vitamin D requirements of 97.5% of the population, and correspond to a serum 25-hydroxyvitamin D [25(OH)D] level of 20 ng/mL, which the data indicate is the optimal level. At levels above the upper intake level, which correspond to a serum 25-OHD level of about 50 ng/mL, adverse effects have been reported, Dr. Manson said.

Emerging evidence suggests excess intake may be associated with increased all-cause mortality, cancer, cardiovascular disease, falls, and fractures, she noted.

National Health and Nutrition Examination Survey (NHANES) data from 2008 showed that age-adjusted mortality was highest among those with serum 25(OH)D levels below 19 ng/mL in African Americans and below 27.5 ng/mL in the entire cohort, and that mortality decreased with increasing levels – but only to a certain point. At levels in the 50 ng/mL range for African Americans, and above 85 ng/mL in the entire cohort, mortality increased steadily.

Data on the effects of vitamin D on skeletal health, which provided the strongest basis for the IOM committee's report as they were most plentiful and convincing in terms of showing cause and effect (although evidence regarding numerous other diseases such as cancer, diabetes, and more were also considered), also suggest that too much vitamin D can lead to adverse effects. Women's Health Initiative findings, for example, show that adjusted hip fracture rates are highest among those with serum 25(OH)D levels of 19.04 ng/mL and those greater than 28.3 ng/mL, and lowest among those between these levels (Ann. Intern. Med. 2008;149:242–50), she said.

In older men in the Osteoporotic Fractures in Men (MrOS) study, the adjusted risk of hip fractures was shown to be highest in those with serum 25(OH)D levels less than 19 ng/mL (odds ratio 2.36, compared with those with levels greater than 28 ng/mL), with risk declining steadily in those with levels up to 28 ng/mL (J. Bone Miner. Res. 2010;25:545–53).

The skeletal benefits of vitamin D are dependent on adequate calcium intake, which the committee determined is 200 and 260 mg/day for those aged 0–6 and 6–12 months, respectively; 700 mg/day for those aged 1–3 years; 1,000 mg/day for those aged 4–8 years, 19–70 years, and for women aged 19–50 years who are pregnant or lactating; 1,200 mg/day for those aged 51 years and older; and 1,300 mg/day for those aged 9–18 years, and for women aged 14-18 years who are pregnant or lactating.

An Agency for Healthcare Research and Quality report in 2009 showed that three randomized controlled trials indicated no significant effect of vitamin D alone on fracture risk, but that one randomized controlled trial showed a benefit in those who received 800 IU of vitamin D₃ plus 1,200 mg/day of calcium for 2 years (OR of fractures 0.80), she said.

Dr. Manson has funding from the National Institutes of Health to conduct a large-scale randomized trial of vitamin D and omega-3 fatty acids.

DESTIN, FLA. – More is not necessarily better when it comes to vitamin D.

“The optimal intake and blood levels are probably much more moderate than many have led us to believe,” Dr. JoAnn E. Manson said.

As a member of the 14-person Institute of Medicine Committee charged with developing a recently published report on dietary reference intakes of vitamin D and calcium, Dr. Manson assisted in a “rigorous comprehensive review” of more than 1,000 studies, and while many researchers and clinicians have argued that people need much higher levels than the 400-800 IU/day intake (depending on age) recommended by the IOM to promote optimal health, the available evidence simply has not borne that out, said Dr. Manson, professor of epidemiology at Harvard University and chief of the division of preventive medicine at Brigham and Women's Hospital, Boston.

Although some IOM report naysayers advocate for levels up to 6,000 IU/day – and the lay press is replete with stories touting vitamin D as a panacea, it is actually very difficult to find any solid data showing increased benefit with higher doses, she said.

In fact, the committee's findings indicate that adequate intake for infants through age 12 months is 400 IU/day, and that the Recommended Dietary Allowance for individuals aged 1-70 years should be at least 600 IU/day, and in those over age 70 years it should be 800 IU/day. The upper intake levels are 1,000 and 1,500 IU/day for those ages 0-6 months and 6-12 months, respectively, 2,500 IU/day for those ages 1–3 years, 3,000 IU/day for those ages 4–8 years, and 4,000 IU/day for those over age 8 years, according to the IOM report (J. Clin. Endocrinol. Metab. 2011;96:53–8).

These minimum levels represent the intake needed to meet the vitamin D requirements of 97.5% of the population, and correspond to a serum 25-hydroxyvitamin D [25(OH)D] level of 20 ng/mL, which the data indicate is the optimal level. At levels above the upper intake level, which correspond to a serum 25-OHD level of about 50 ng/mL, adverse effects have been reported, Dr. Manson said.

Emerging evidence suggests excess intake may be associated with increased all-cause mortality, cancer, cardiovascular disease, falls, and fractures, she noted.

National Health and Nutrition Examination Survey (NHANES) data from 2008 showed that age-adjusted mortality was highest among those with serum 25(OH)D levels below 19 ng/mL in African Americans and below 27.5 ng/mL in the entire cohort, and that mortality decreased with increasing levels – but only to a certain point. At levels in the 50 ng/mL range for African Americans, and above 85 ng/mL in the entire cohort, mortality increased steadily.

Data on the effects of vitamin D on skeletal health, which provided the strongest basis for the IOM committee's report as they were most plentiful and convincing in terms of showing cause and effect (although evidence regarding numerous other diseases such as cancer, diabetes, and more were also considered), also suggest that too much vitamin D can lead to adverse effects. Women's Health Initiative findings, for example, show that adjusted hip fracture rates are highest among those with serum 25(OH)D levels of 19.04 ng/mL and those greater than 28.3 ng/mL, and lowest among those between these levels (Ann. Intern. Med. 2008;149:242–50), she said.

In older men in the Osteoporotic Fractures in Men (MrOS) study, the adjusted risk of hip fractures was shown to be highest in those with serum 25(OH)D levels less than 19 ng/mL (odds ratio 2.36, compared with those with levels greater than 28 ng/mL), with risk declining steadily in those with levels up to 28 ng/mL (J. Bone Miner. Res. 2010;25:545–53).

The skeletal benefits of vitamin D are dependent on adequate calcium intake, which the committee determined is 200 and 260 mg/day for those aged 0–6 and 6–12 months, respectively; 700 mg/day for those aged 1–3 years; 1,000 mg/day for those aged 4–8 years, 19–70 years, and for women aged 19–50 years who are pregnant or lactating; 1,200 mg/day for those aged 51 years and older; and 1,300 mg/day for those aged 9–18 years, and for women aged 14-18 years who are pregnant or lactating.

An Agency for Healthcare Research and Quality report in 2009 showed that three randomized controlled trials indicated no significant effect of vitamin D alone on fracture risk, but that one randomized controlled trial showed a benefit in those who received 800 IU of vitamin D₃ plus 1,200 mg/day of calcium for 2 years (OR of fractures 0.80), she said.

Dr. Manson has funding from the National Institutes of Health to conduct a large-scale randomized trial of vitamin D and omega-3 fatty acids.

DESTIN, FLA. – Bosentan, which has been shown to prevent digital ulcers in systemic sclerosis, also may have beneficial effects on skin fibrosis.

In a small, prospective, open-label study, treatment with the dual endothelin receptor antagonist was associated with a significant reduction in skin thickening as measured by the modified Rodnan skin score (mRSS), according to Dr. Annegret Kuhn.

The mean change from baseline in the mRSS in the 10 systemic sclerosis patients in the study was 6.4 points on the 0–51 point scale, said Dr. Kuhn of Westfälische Wilhelms-Universität Münster (Germany).

Significant responses were seen in patients with both diffuse and limited disease, and there also was significant healing of digital ulcers. No differences were seen from baseline and week 24, however, on 20-MHz ultrasound, fist-closure evaluation, U.K. systemic sclerosis functional score, or the modified sclerosis health assessment questionnaire (SHAQ) and its visual analogue scale (Rheumatology [Oxford] 2010;49:1336–45).

Patients were treated with 62.5 mg of bosentan twice daily for 4 weeks, then with 125 mg twice daily for 20 weeks. This regimen is similar to the dosing used in the RAPIDS-1 and −2 (Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Systemic Scleroderma–1 and –2) trials, which demonstrated the drug's efficacy for the prevention of digital ulcers. Bosentan is currently approved for use in the United States for pulmonary artery hypertension, and – based on the RAPIDS-1 trial (Arthritis Rheum. 2004;50:3985–93) – it was also approved in Europe in 2007 for prevention of digital ulcers.

The RAPIDS-2 trial that was published this year (Ann. Rheum. Dis. 2011;70:32–8), included treatment for at least 24 weeks, and confirmed the preventive effects seen in RAPIDS-1. Bosentan was not found in either trial to be associated with improved healing in existing ulcers, however.

“Iloprost remains the best treatment for digital ulcers in systemic scleroderma,” Dr. Kuhn said,

But bosentan is recommended for prevention, and it may also improve fibrosis, she noted.

Guidelines that were developed this year by a group of German experts on scleroderma call for first-line treatment with iloprost for the healing of existing ulcers, with repeated infusions for long-term care. They also call for the use of bosentan for prevention, and note that current experimental treatments include sildenafil and atorvastatin, she said.

Treatment of underlying disease (such as Raynaud's phenomenon, vasculopathy, and the like) is also important, as are general preventive measures including nicotine abstinence, cold protection, physical treatments, lymphatic draining, elimination of sympathomimetics, and vasoconstrictors.

Dr. Kuhn had no financial disclosures to report.

DESTIN, FLA. – Bosentan, which has been shown to prevent digital ulcers in systemic sclerosis, also may have beneficial effects on skin fibrosis.

In a small, prospective, open-label study, treatment with the dual endothelin receptor antagonist was associated with a significant reduction in skin thickening as measured by the modified Rodnan skin score (mRSS), according to Dr. Annegret Kuhn.

The mean change from baseline in the mRSS in the 10 systemic sclerosis patients in the study was 6.4 points on the 0–51 point scale, said Dr. Kuhn of Westfälische Wilhelms-Universität Münster (Germany).

Significant responses were seen in patients with both diffuse and limited disease, and there also was significant healing of digital ulcers. No differences were seen from baseline and week 24, however, on 20-MHz ultrasound, fist-closure evaluation, U.K. systemic sclerosis functional score, or the modified sclerosis health assessment questionnaire (SHAQ) and its visual analogue scale (Rheumatology [Oxford] 2010;49:1336–45).

Patients were treated with 62.5 mg of bosentan twice daily for 4 weeks, then with 125 mg twice daily for 20 weeks. This regimen is similar to the dosing used in the RAPIDS-1 and −2 (Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Systemic Scleroderma–1 and –2) trials, which demonstrated the drug's efficacy for the prevention of digital ulcers. Bosentan is currently approved for use in the United States for pulmonary artery hypertension, and – based on the RAPIDS-1 trial (Arthritis Rheum. 2004;50:3985–93) – it was also approved in Europe in 2007 for prevention of digital ulcers.

The RAPIDS-2 trial that was published this year (Ann. Rheum. Dis. 2011;70:32–8), included treatment for at least 24 weeks, and confirmed the preventive effects seen in RAPIDS-1. Bosentan was not found in either trial to be associated with improved healing in existing ulcers, however.

“Iloprost remains the best treatment for digital ulcers in systemic scleroderma,” Dr. Kuhn said,

But bosentan is recommended for prevention, and it may also improve fibrosis, she noted.

Guidelines that were developed this year by a group of German experts on scleroderma call for first-line treatment with iloprost for the healing of existing ulcers, with repeated infusions for long-term care. They also call for the use of bosentan for prevention, and note that current experimental treatments include sildenafil and atorvastatin, she said.

Treatment of underlying disease (such as Raynaud's phenomenon, vasculopathy, and the like) is also important, as are general preventive measures including nicotine abstinence, cold protection, physical treatments, lymphatic draining, elimination of sympathomimetics, and vasoconstrictors.

Dr. Kuhn had no financial disclosures to report.

DESTIN, FLA. – Bosentan, which has been shown to prevent digital ulcers in systemic sclerosis, also may have beneficial effects on skin fibrosis.

In a small, prospective, open-label study, treatment with the dual endothelin receptor antagonist was associated with a significant reduction in skin thickening as measured by the modified Rodnan skin score (mRSS), according to Dr. Annegret Kuhn.

The mean change from baseline in the mRSS in the 10 systemic sclerosis patients in the study was 6.4 points on the 0–51 point scale, said Dr. Kuhn of Westfälische Wilhelms-Universität Münster (Germany).

Significant responses were seen in patients with both diffuse and limited disease, and there also was significant healing of digital ulcers. No differences were seen from baseline and week 24, however, on 20-MHz ultrasound, fist-closure evaluation, U.K. systemic sclerosis functional score, or the modified sclerosis health assessment questionnaire (SHAQ) and its visual analogue scale (Rheumatology [Oxford] 2010;49:1336–45).

Patients were treated with 62.5 mg of bosentan twice daily for 4 weeks, then with 125 mg twice daily for 20 weeks. This regimen is similar to the dosing used in the RAPIDS-1 and −2 (Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Systemic Scleroderma–1 and –2) trials, which demonstrated the drug's efficacy for the prevention of digital ulcers. Bosentan is currently approved for use in the United States for pulmonary artery hypertension, and – based on the RAPIDS-1 trial (Arthritis Rheum. 2004;50:3985–93) – it was also approved in Europe in 2007 for prevention of digital ulcers.

The RAPIDS-2 trial that was published this year (Ann. Rheum. Dis. 2011;70:32–8), included treatment for at least 24 weeks, and confirmed the preventive effects seen in RAPIDS-1. Bosentan was not found in either trial to be associated with improved healing in existing ulcers, however.

“Iloprost remains the best treatment for digital ulcers in systemic scleroderma,” Dr. Kuhn said,

But bosentan is recommended for prevention, and it may also improve fibrosis, she noted.

Guidelines that were developed this year by a group of German experts on scleroderma call for first-line treatment with iloprost for the healing of existing ulcers, with repeated infusions for long-term care. They also call for the use of bosentan for prevention, and note that current experimental treatments include sildenafil and atorvastatin, she said.

Treatment of underlying disease (such as Raynaud's phenomenon, vasculopathy, and the like) is also important, as are general preventive measures including nicotine abstinence, cold protection, physical treatments, lymphatic draining, elimination of sympathomimetics, and vasoconstrictors.

Dr. Kuhn had no financial disclosures to report.

DESTIN, FLA. – For now, the lupus patients most likely to respond to recently approved belimumab may be those with moderate to severe disease without renal or central nervous system involvement who have failed to respond to standard therapy, according to Dr. R. John Looney.

More specific details on which patients are most likely to benefit will require further experience with the drug, he said at the meeting.

Belimumab (Benlysta), which was approved in March, is the first new drug for systemic lupus erythematosus (SLE) in 50 years. It has a very good safety profile, although the effect size, while statistically significant, is relatively small, with an average difference in response rate of only about 12 percentage points between treatment and placebo groups in trials. Belimumab is a fully human monoclonal antibody that inhibits B-lymphocyte stimulator, said Dr. Looney, professor of medicine at the University of Rochester (N.Y.).

Still, that reflects improvement of about 25%-30%, he noted.

The standard dosage is 10 mg/kg, given intravenously every 2 weeks for three times, then every 4 weeks, in addition to standard care.

Keep in mind that the onset is somewhat slow, so this “may not be a drug you would use in a flaring patient,” Dr. Looney said. In addition, it has not been studied in severe renal or central nervous system disease, or in combination with cyclophosphamide, he noted.

Furthermore, no particular subgroup has yet been identified in whom the drug has particular benefits, so it is a bit of a challenge to determine which patients should be put on this drug.

“I would consider it in patients with moderate to severe, nonrenal, nonneurologic disease who have failed standard therapy,” Dr. Looney said, explaining that he would consider those to be patients with continued disease activity or patients in whom steroids can't be tapered or stopped despite treatment.

“So I look at this as a drug that might help me get my patients who are on hydroxychloroquine and let's say CellCept [mycophenolate] or Imuran [azathioprine], down to a manageable dose of steroids,” he added.

Determining how long to treat, however, is a challenge.

“We have no good way to look at an individual patient and say they are better and they are better because they are on belimumab,” Dr. Looney said, noting that based on belimumab trial data, three out of four patients who were responders at 1 year would have been responders on placebo, so further study is needed to help guide treatment duration.

“I would also really like to see predictors of response,” he said, noting that such predictors have thus far not been reported.

Further analysis of existing data may be useful for identifying subgroups who will respond best to belimumab. Additional studies in renal and CNS disease would also be useful.

“It may be that you add this drug to current therapies [in renal and CNS patients] and they do that much better,” Dr. Looney said, noting that it would also be useful to look at belimumab treatment in conjunction with cyclophosphamide and rituximab as well “to see what happens when B cells are targeted in two different ways.”

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – For now, the lupus patients most likely to respond to recently approved belimumab may be those with moderate to severe disease without renal or central nervous system involvement who have failed to respond to standard therapy, according to Dr. R. John Looney.

More specific details on which patients are most likely to benefit will require further experience with the drug, he said at the meeting.

Belimumab (Benlysta), which was approved in March, is the first new drug for systemic lupus erythematosus (SLE) in 50 years. It has a very good safety profile, although the effect size, while statistically significant, is relatively small, with an average difference in response rate of only about 12 percentage points between treatment and placebo groups in trials. Belimumab is a fully human monoclonal antibody that inhibits B-lymphocyte stimulator, said Dr. Looney, professor of medicine at the University of Rochester (N.Y.).

Still, that reflects improvement of about 25%-30%, he noted.

The standard dosage is 10 mg/kg, given intravenously every 2 weeks for three times, then every 4 weeks, in addition to standard care.

Keep in mind that the onset is somewhat slow, so this “may not be a drug you would use in a flaring patient,” Dr. Looney said. In addition, it has not been studied in severe renal or central nervous system disease, or in combination with cyclophosphamide, he noted.

Furthermore, no particular subgroup has yet been identified in whom the drug has particular benefits, so it is a bit of a challenge to determine which patients should be put on this drug.

“I would consider it in patients with moderate to severe, nonrenal, nonneurologic disease who have failed standard therapy,” Dr. Looney said, explaining that he would consider those to be patients with continued disease activity or patients in whom steroids can't be tapered or stopped despite treatment.

“So I look at this as a drug that might help me get my patients who are on hydroxychloroquine and let's say CellCept [mycophenolate] or Imuran [azathioprine], down to a manageable dose of steroids,” he added.

Determining how long to treat, however, is a challenge.

“We have no good way to look at an individual patient and say they are better and they are better because they are on belimumab,” Dr. Looney said, noting that based on belimumab trial data, three out of four patients who were responders at 1 year would have been responders on placebo, so further study is needed to help guide treatment duration.

“I would also really like to see predictors of response,” he said, noting that such predictors have thus far not been reported.

Further analysis of existing data may be useful for identifying subgroups who will respond best to belimumab. Additional studies in renal and CNS disease would also be useful.

“It may be that you add this drug to current therapies [in renal and CNS patients] and they do that much better,” Dr. Looney said, noting that it would also be useful to look at belimumab treatment in conjunction with cyclophosphamide and rituximab as well “to see what happens when B cells are targeted in two different ways.”

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – For now, the lupus patients most likely to respond to recently approved belimumab may be those with moderate to severe disease without renal or central nervous system involvement who have failed to respond to standard therapy, according to Dr. R. John Looney.

More specific details on which patients are most likely to benefit will require further experience with the drug, he said at the meeting.

Belimumab (Benlysta), which was approved in March, is the first new drug for systemic lupus erythematosus (SLE) in 50 years. It has a very good safety profile, although the effect size, while statistically significant, is relatively small, with an average difference in response rate of only about 12 percentage points between treatment and placebo groups in trials. Belimumab is a fully human monoclonal antibody that inhibits B-lymphocyte stimulator, said Dr. Looney, professor of medicine at the University of Rochester (N.Y.).

Still, that reflects improvement of about 25%-30%, he noted.

The standard dosage is 10 mg/kg, given intravenously every 2 weeks for three times, then every 4 weeks, in addition to standard care.

Keep in mind that the onset is somewhat slow, so this “may not be a drug you would use in a flaring patient,” Dr. Looney said. In addition, it has not been studied in severe renal or central nervous system disease, or in combination with cyclophosphamide, he noted.

Furthermore, no particular subgroup has yet been identified in whom the drug has particular benefits, so it is a bit of a challenge to determine which patients should be put on this drug.

“I would consider it in patients with moderate to severe, nonrenal, nonneurologic disease who have failed standard therapy,” Dr. Looney said, explaining that he would consider those to be patients with continued disease activity or patients in whom steroids can't be tapered or stopped despite treatment.

“So I look at this as a drug that might help me get my patients who are on hydroxychloroquine and let's say CellCept [mycophenolate] or Imuran [azathioprine], down to a manageable dose of steroids,” he added.

Determining how long to treat, however, is a challenge.

“We have no good way to look at an individual patient and say they are better and they are better because they are on belimumab,” Dr. Looney said, noting that based on belimumab trial data, three out of four patients who were responders at 1 year would have been responders on placebo, so further study is needed to help guide treatment duration.

“I would also really like to see predictors of response,” he said, noting that such predictors have thus far not been reported.

Further analysis of existing data may be useful for identifying subgroups who will respond best to belimumab. Additional studies in renal and CNS disease would also be useful.

“It may be that you add this drug to current therapies [in renal and CNS patients] and they do that much better,” Dr. Looney said, noting that it would also be useful to look at belimumab treatment in conjunction with cyclophosphamide and rituximab as well “to see what happens when B cells are targeted in two different ways.”

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the “amazingly negative” EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222–33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

“So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus,” he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

“If you're looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies,” he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

“In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments,” he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

Dr. Looney disclosed that he has been an advisor for Genentech.

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the “amazingly negative” EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222–33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

“So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus,” he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

“If you're looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies,” he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

“In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments,” he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

Dr. Looney disclosed that he has been an advisor for Genentech.

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the “amazingly negative” EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222–33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

“So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus,” he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

“If you're looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies,” he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

“In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments,” he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

Dr. Looney disclosed that he has been an advisor for Genentech.

CHICAGO – Hydroxychloroquine-related ocular toxicity is rare, but does occur and should be considered in any treated patient complaining of blurred vision, Dr. Alvin Wells said at the symposium.

He described a case involving a 21-year-old woman who was referred for rash and color changes of her hands and feet. She had a weakly positive antinuclear antibody (ANA) titer, and there was concern about possible lupus.

The patient's chief complaint was redness of the face in the presence of cold fingers and toes.

On physical examination she was found to have significant mild erythematous rash on the face and chest, and mild Raynaud's changes of the digits without ulceration or loss of digital pulp. Her laboratory study findings were completely normal except for an ANA titer of 1:640.

The patient was started on hydroxychloroquine at a standard dose of 200 mg twice daily along with 10 mg nifedipine every Monday, Wednesday, and Friday nights. A follow-up visit was scheduled for 8 weeks, but within 10 days she called in complaining of headaches and blurred vision.

Although ocular toxicity is more common with chloroquine, it does occur with hydroxychloroquine as well, and the effect is dose dependent, said Dr. Wells, who is director of the rheumatology and immunotherapy center at Duke University Medical Center in Durham, N.C.

Risk increases with doses greater than 6.5 mg/kg. This patient, who weighed only 110 lbs, was receiving a dose of about 8 mg/kg, he said.

The risk is also increased in those with higher body mass index and those with diabetes.

Affected patients may present with corneal deposits, and retinopathy may also occur. Blurred vision is the most common complaint, and examination of the macula will reveal a “bull's eye maculopathy,” Dr. Wells said.

The effects are reversible upon discontinuation of the drug in 95% of cases, he noted.

Affected patients should have a baseline evaluation within 1 year (and preferably within 6 months), and if it is normal, they should be evaluated yearly thereafter, he recommended.

Dr. Wells reported that he has received consulting fees or other remuneration from Abbott, Amgen, Bristol-Myers Squibb, Genentech, Pfizer, and UCB.

CHICAGO – Hydroxychloroquine-related ocular toxicity is rare, but does occur and should be considered in any treated patient complaining of blurred vision, Dr. Alvin Wells said at the symposium.

He described a case involving a 21-year-old woman who was referred for rash and color changes of her hands and feet. She had a weakly positive antinuclear antibody (ANA) titer, and there was concern about possible lupus.

The patient's chief complaint was redness of the face in the presence of cold fingers and toes.

On physical examination she was found to have significant mild erythematous rash on the face and chest, and mild Raynaud's changes of the digits without ulceration or loss of digital pulp. Her laboratory study findings were completely normal except for an ANA titer of 1:640.

The patient was started on hydroxychloroquine at a standard dose of 200 mg twice daily along with 10 mg nifedipine every Monday, Wednesday, and Friday nights. A follow-up visit was scheduled for 8 weeks, but within 10 days she called in complaining of headaches and blurred vision.

Although ocular toxicity is more common with chloroquine, it does occur with hydroxychloroquine as well, and the effect is dose dependent, said Dr. Wells, who is director of the rheumatology and immunotherapy center at Duke University Medical Center in Durham, N.C.

Risk increases with doses greater than 6.5 mg/kg. This patient, who weighed only 110 lbs, was receiving a dose of about 8 mg/kg, he said.

The risk is also increased in those with higher body mass index and those with diabetes.

Affected patients may present with corneal deposits, and retinopathy may also occur. Blurred vision is the most common complaint, and examination of the macula will reveal a “bull's eye maculopathy,” Dr. Wells said.

The effects are reversible upon discontinuation of the drug in 95% of cases, he noted.

Affected patients should have a baseline evaluation within 1 year (and preferably within 6 months), and if it is normal, they should be evaluated yearly thereafter, he recommended.

Dr. Wells reported that he has received consulting fees or other remuneration from Abbott, Amgen, Bristol-Myers Squibb, Genentech, Pfizer, and UCB.

CHICAGO – Hydroxychloroquine-related ocular toxicity is rare, but does occur and should be considered in any treated patient complaining of blurred vision, Dr. Alvin Wells said at the symposium.

He described a case involving a 21-year-old woman who was referred for rash and color changes of her hands and feet. She had a weakly positive antinuclear antibody (ANA) titer, and there was concern about possible lupus.

The patient's chief complaint was redness of the face in the presence of cold fingers and toes.

On physical examination she was found to have significant mild erythematous rash on the face and chest, and mild Raynaud's changes of the digits without ulceration or loss of digital pulp. Her laboratory study findings were completely normal except for an ANA titer of 1:640.

The patient was started on hydroxychloroquine at a standard dose of 200 mg twice daily along with 10 mg nifedipine every Monday, Wednesday, and Friday nights. A follow-up visit was scheduled for 8 weeks, but within 10 days she called in complaining of headaches and blurred vision.

Although ocular toxicity is more common with chloroquine, it does occur with hydroxychloroquine as well, and the effect is dose dependent, said Dr. Wells, who is director of the rheumatology and immunotherapy center at Duke University Medical Center in Durham, N.C.

Risk increases with doses greater than 6.5 mg/kg. This patient, who weighed only 110 lbs, was receiving a dose of about 8 mg/kg, he said.

The risk is also increased in those with higher body mass index and those with diabetes.

Affected patients may present with corneal deposits, and retinopathy may also occur. Blurred vision is the most common complaint, and examination of the macula will reveal a “bull's eye maculopathy,” Dr. Wells said.

The effects are reversible upon discontinuation of the drug in 95% of cases, he noted.

Affected patients should have a baseline evaluation within 1 year (and preferably within 6 months), and if it is normal, they should be evaluated yearly thereafter, he recommended.

Dr. Wells reported that he has received consulting fees or other remuneration from Abbott, Amgen, Bristol-Myers Squibb, Genentech, Pfizer, and UCB.