Amy Rothman Schonfeld

By linking two Norwegian national data registries, investigators confirmed previous findings that the incidence of rheumatoid arthritis is increased in women in the 2 years following delivery, compared with the subsequent 2 years post partum.

The results also showed an elevated incidence of other chronic arthritides in the first 2 postpartum years, said Dr. Marianne Wallenius of the department of rheumatology at St. Olav's Hospital in Trondheim, Norway, and her colleagues.

The impact of studies like that of Dr. Wallenius and her colleagues “goes beyond the field of rheumatologists interested in female health issues, but these studies may contribute to a better understanding of the fundamental question why one person gets RA and another does not,” noted Dr. Radboud J.E.M. Dolhain of Erasmus University Medical Centre, Rotterdam, the Netherlands, in an accompanying editorial (Ann. Rheum. Dis. 2010;69:317-8).

One hypothesis is that pregnancy exerts a protective effect on RA and other arthritides, which then disappears after delivery, allowing disease to flare. But this study did not look at incidence during pregnancy. More epidemiologic data are needed “to determine whether this is a true increased incidence or whether rather the incidence of RA and other forms of arthritis is postponed to after delivery,” Dr. Dolhain said.

The investigators linked data from a registry of people with inflammatory arthropathies who were taking disease-modifying antirheumatic drugs (the NOR-DMARD Registry) with the Medical Birth Registry of Norway that has recorded all births in Norway since 1967. They were able to locate 293 women with arthritis whose disease was first diagnosed after delivery. Of these, 183 were diagnosed with RA and 110 with other chronic arthritides (OCA), including 51 with psoriatic arthritis, 14 with ankylosing spondylitides and 45 with unspecified arthritis.

Of those with RA, 38% (69 women) were diagnosed in the first 2 years post partum, compared with 28% (31 women) who were diagnosed with OCA. The incidence of disease peaked in the first 2 years after pregnancy, compared with the subsequent 2 years for those who were diagnosed solely with RA (incident rate ratio, 1.73) or for the entire RA-plus-OCA group (IRR, 1.44) after all pregnancies were considered, but not for those who were diagnosed only with OCA (IRR, 1.05) (Ann. Rheum. Dis. 2010;69:332-6).

Disclosures: Research was supported by the liaison committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The NOR-DMARD registry is supported by all makers of biologic drugs for RA in Europe.

By linking two Norwegian national data registries, investigators confirmed previous findings that the incidence of rheumatoid arthritis is increased in women in the 2 years following delivery, compared with the subsequent 2 years post partum.

The results also showed an elevated incidence of other chronic arthritides in the first 2 postpartum years, said Dr. Marianne Wallenius of the department of rheumatology at St. Olav's Hospital in Trondheim, Norway, and her colleagues.

The impact of studies like that of Dr. Wallenius and her colleagues “goes beyond the field of rheumatologists interested in female health issues, but these studies may contribute to a better understanding of the fundamental question why one person gets RA and another does not,” noted Dr. Radboud J.E.M. Dolhain of Erasmus University Medical Centre, Rotterdam, the Netherlands, in an accompanying editorial (Ann. Rheum. Dis. 2010;69:317-8).

One hypothesis is that pregnancy exerts a protective effect on RA and other arthritides, which then disappears after delivery, allowing disease to flare. But this study did not look at incidence during pregnancy. More epidemiologic data are needed “to determine whether this is a true increased incidence or whether rather the incidence of RA and other forms of arthritis is postponed to after delivery,” Dr. Dolhain said.

The investigators linked data from a registry of people with inflammatory arthropathies who were taking disease-modifying antirheumatic drugs (the NOR-DMARD Registry) with the Medical Birth Registry of Norway that has recorded all births in Norway since 1967. They were able to locate 293 women with arthritis whose disease was first diagnosed after delivery. Of these, 183 were diagnosed with RA and 110 with other chronic arthritides (OCA), including 51 with psoriatic arthritis, 14 with ankylosing spondylitides and 45 with unspecified arthritis.

Of those with RA, 38% (69 women) were diagnosed in the first 2 years post partum, compared with 28% (31 women) who were diagnosed with OCA. The incidence of disease peaked in the first 2 years after pregnancy, compared with the subsequent 2 years for those who were diagnosed solely with RA (incident rate ratio, 1.73) or for the entire RA-plus-OCA group (IRR, 1.44) after all pregnancies were considered, but not for those who were diagnosed only with OCA (IRR, 1.05) (Ann. Rheum. Dis. 2010;69:332-6).

Disclosures: Research was supported by the liaison committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The NOR-DMARD registry is supported by all makers of biologic drugs for RA in Europe.

By linking two Norwegian national data registries, investigators confirmed previous findings that the incidence of rheumatoid arthritis is increased in women in the 2 years following delivery, compared with the subsequent 2 years post partum.

The results also showed an elevated incidence of other chronic arthritides in the first 2 postpartum years, said Dr. Marianne Wallenius of the department of rheumatology at St. Olav's Hospital in Trondheim, Norway, and her colleagues.

The impact of studies like that of Dr. Wallenius and her colleagues “goes beyond the field of rheumatologists interested in female health issues, but these studies may contribute to a better understanding of the fundamental question why one person gets RA and another does not,” noted Dr. Radboud J.E.M. Dolhain of Erasmus University Medical Centre, Rotterdam, the Netherlands, in an accompanying editorial (Ann. Rheum. Dis. 2010;69:317-8).

One hypothesis is that pregnancy exerts a protective effect on RA and other arthritides, which then disappears after delivery, allowing disease to flare. But this study did not look at incidence during pregnancy. More epidemiologic data are needed “to determine whether this is a true increased incidence or whether rather the incidence of RA and other forms of arthritis is postponed to after delivery,” Dr. Dolhain said.

The investigators linked data from a registry of people with inflammatory arthropathies who were taking disease-modifying antirheumatic drugs (the NOR-DMARD Registry) with the Medical Birth Registry of Norway that has recorded all births in Norway since 1967. They were able to locate 293 women with arthritis whose disease was first diagnosed after delivery. Of these, 183 were diagnosed with RA and 110 with other chronic arthritides (OCA), including 51 with psoriatic arthritis, 14 with ankylosing spondylitides and 45 with unspecified arthritis.

Of those with RA, 38% (69 women) were diagnosed in the first 2 years post partum, compared with 28% (31 women) who were diagnosed with OCA. The incidence of disease peaked in the first 2 years after pregnancy, compared with the subsequent 2 years for those who were diagnosed solely with RA (incident rate ratio, 1.73) or for the entire RA-plus-OCA group (IRR, 1.44) after all pregnancies were considered, but not for those who were diagnosed only with OCA (IRR, 1.05) (Ann. Rheum. Dis. 2010;69:332-6).

Disclosures: Research was supported by the liaison committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The NOR-DMARD registry is supported by all makers of biologic drugs for RA in Europe.

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

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

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

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

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

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

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

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

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

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

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

An urgent response is required if a child says that food is “sticking to his mouth.” This suggests a bulbar muscle weakness of central origin, with impaired swallowing and the potential for aspiration. This may necessitate placing the child on a soft diet or even hospitalization, said Dr. Eberhard.

JDM can produce other serious sequelae, including pulmonary fibrosis and perforation of the esophagus or small bowel.

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

Disclosures: Dr. Eberhard had no relevant financial disclosures.

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

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

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

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

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

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

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

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

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

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

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

An urgent response is required if a child says that food is “sticking to his mouth.” This suggests a bulbar muscle weakness of central origin, with impaired swallowing and the potential for aspiration. This may necessitate placing the child on a soft diet or even hospitalization, said Dr. Eberhard.

JDM can produce other serious sequelae, including pulmonary fibrosis and perforation of the esophagus or small bowel.

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

Disclosures: Dr. Eberhard had no relevant financial disclosures.

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

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

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

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

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

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

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

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

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

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

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

An urgent response is required if a child says that food is “sticking to his mouth.” This suggests a bulbar muscle weakness of central origin, with impaired swallowing and the potential for aspiration. This may necessitate placing the child on a soft diet or even hospitalization, said Dr. Eberhard.

JDM can produce other serious sequelae, including pulmonary fibrosis and perforation of the esophagus or small bowel.

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

Disclosures: Dr. Eberhard had no relevant financial disclosures.

NEW YORK — A combination of rituximab and cyclophosphamide offers significant long-term benefits to children with systemic lupus erythematosus, according to Dr. Thomas J.A. Lehman, who presented the results at a meeting sponsored by New York University.

“This combination is extremely effective, much more than either drug alone,” in the treatment of systemic lupus erythematosus (SLE), said Dr. Lehman, chief of the division of pediatric rheumatology at the Hospital for Special Surgery and professor of clinical pediatrics at Cornell University, both in New York.

SLE Disease Activity Index (SLEDAI) scores dropped from a mean of 9.79 before treatment to 1.43 after 12 months of treatment (P = .0009) for the group of 14 patients. C3 complement levels significantly increased (P = .0023), whereas the sedimentation rate fell (P = .0134). No changes were seen in hemoglobin levels or white blood cell levels.

Another marker of success was that patients were able to reduce their need for daily prednisone therapy. The mean daily dose fell by about two-thirds, from 33.3 mg/day to 11.96 mg/day after 12 months (P = .0004).

The protocol consists of a doublet of rituximab (750 mg/m

The doublet is repeated on days 14 and 15, and then the 2-week schedule is repeated at 6 and 18 months. These drugs have not been approved for the treatment of SLE in children.

Patients receive high-dose intravenous corticosteroids and intravenous diphenhydramine prior to rituximab infusion. Over the course of 3 years, most patients received at least three courses of therapy.

The group consisted of 11 females and 3 males who were about 12 years old when they were diagnosed with SLE.

Treatment with this protocol generally began 2 years after diagnosis, when the children were more than 14 years old. Five children were Asian, four children were Hispanic, three were white, and two were black. Six of the children had received prior cyclophosphamide monotherapy.

No serious adverse events were reported. Four patients had adverse events, including one each of urinary tract infection, herpes zoster, cellulitis, and lymphadenitis. All events resolved with treatment.

Four children were followed for at least 18 months after being diagnosed with biopsy-confirmed diffuse proliferative glomerular nephritis.

After undergoing the rituximab/cyclophosphamide treatment, all had normal complement levels and no indication of hematuria, proteinuria, or other urinary abnormalities and two of the four had negative antinuclear antibody (ANA) testing more than 1 year after treatment. “All these patients believe that they are cured,” says Dr. Lehman.

Dr. Lehman said that he is generally reluctant to discontinue prednisone, so all patients continue to receive approximately 10 mg/day of the drug. He reported that none of the children on prednisone showed signs of steroid toxicity such as depression, hirsutism, or Cushing's syndrome.

This protocol may not be appropriate for all children with SLE, according to Dr. Lehman. Not all children with SLE require aggressive therapy.

Data from studies done in the 1970s demonstrate that 30% of children with SLE do well with long-term, low-dose prednisone, whereas 30% develop steroid complications and 40% die or require dialysis, he said.

Aggressive therapy should be considered for children with persistent anemia (hemoglobin less than 10 g), persistent diastolic hypertension, pulmonary hypertension, or persistent hematuria (greater than 20 RBC/high-power field), or who have had recurrent emergency admissions for any reason.

The prevalence of SLE among children is estimated to be between 5 and 10 cases per 100,000 children. An estimated 8% of cases develop before children are 14 years of age, and about 15% develop before age 16.

Disclosures: The study received no commercial funding. Dr. Lehman is on the speakers bureau of Abbott Laboratories, Amgen Inc., and Pfizer Inc.

'This combination is extremely effective, much more than either drug alone' in the treatment of pediatric SLE.

Source DR. LEHMAN

NEW YORK — A combination of rituximab and cyclophosphamide offers significant long-term benefits to children with systemic lupus erythematosus, according to Dr. Thomas J.A. Lehman, who presented the results at a meeting sponsored by New York University.

“This combination is extremely effective, much more than either drug alone,” in the treatment of systemic lupus erythematosus (SLE), said Dr. Lehman, chief of the division of pediatric rheumatology at the Hospital for Special Surgery and professor of clinical pediatrics at Cornell University, both in New York.

SLE Disease Activity Index (SLEDAI) scores dropped from a mean of 9.79 before treatment to 1.43 after 12 months of treatment (P = .0009) for the group of 14 patients. C3 complement levels significantly increased (P = .0023), whereas the sedimentation rate fell (P = .0134). No changes were seen in hemoglobin levels or white blood cell levels.

Another marker of success was that patients were able to reduce their need for daily prednisone therapy. The mean daily dose fell by about two-thirds, from 33.3 mg/day to 11.96 mg/day after 12 months (P = .0004).

The protocol consists of a doublet of rituximab (750 mg/m

The doublet is repeated on days 14 and 15, and then the 2-week schedule is repeated at 6 and 18 months. These drugs have not been approved for the treatment of SLE in children.

Patients receive high-dose intravenous corticosteroids and intravenous diphenhydramine prior to rituximab infusion. Over the course of 3 years, most patients received at least three courses of therapy.

The group consisted of 11 females and 3 males who were about 12 years old when they were diagnosed with SLE.

Treatment with this protocol generally began 2 years after diagnosis, when the children were more than 14 years old. Five children were Asian, four children were Hispanic, three were white, and two were black. Six of the children had received prior cyclophosphamide monotherapy.

No serious adverse events were reported. Four patients had adverse events, including one each of urinary tract infection, herpes zoster, cellulitis, and lymphadenitis. All events resolved with treatment.

Four children were followed for at least 18 months after being diagnosed with biopsy-confirmed diffuse proliferative glomerular nephritis.

After undergoing the rituximab/cyclophosphamide treatment, all had normal complement levels and no indication of hematuria, proteinuria, or other urinary abnormalities and two of the four had negative antinuclear antibody (ANA) testing more than 1 year after treatment. “All these patients believe that they are cured,” says Dr. Lehman.

Dr. Lehman said that he is generally reluctant to discontinue prednisone, so all patients continue to receive approximately 10 mg/day of the drug. He reported that none of the children on prednisone showed signs of steroid toxicity such as depression, hirsutism, or Cushing's syndrome.

This protocol may not be appropriate for all children with SLE, according to Dr. Lehman. Not all children with SLE require aggressive therapy.

Data from studies done in the 1970s demonstrate that 30% of children with SLE do well with long-term, low-dose prednisone, whereas 30% develop steroid complications and 40% die or require dialysis, he said.

Aggressive therapy should be considered for children with persistent anemia (hemoglobin less than 10 g), persistent diastolic hypertension, pulmonary hypertension, or persistent hematuria (greater than 20 RBC/high-power field), or who have had recurrent emergency admissions for any reason.

The prevalence of SLE among children is estimated to be between 5 and 10 cases per 100,000 children. An estimated 8% of cases develop before children are 14 years of age, and about 15% develop before age 16.

Disclosures: The study received no commercial funding. Dr. Lehman is on the speakers bureau of Abbott Laboratories, Amgen Inc., and Pfizer Inc.

'This combination is extremely effective, much more than either drug alone' in the treatment of pediatric SLE.

Source DR. LEHMAN

NEW YORK — A combination of rituximab and cyclophosphamide offers significant long-term benefits to children with systemic lupus erythematosus, according to Dr. Thomas J.A. Lehman, who presented the results at a meeting sponsored by New York University.

“This combination is extremely effective, much more than either drug alone,” in the treatment of systemic lupus erythematosus (SLE), said Dr. Lehman, chief of the division of pediatric rheumatology at the Hospital for Special Surgery and professor of clinical pediatrics at Cornell University, both in New York.

SLE Disease Activity Index (SLEDAI) scores dropped from a mean of 9.79 before treatment to 1.43 after 12 months of treatment (P = .0009) for the group of 14 patients. C3 complement levels significantly increased (P = .0023), whereas the sedimentation rate fell (P = .0134). No changes were seen in hemoglobin levels or white blood cell levels.

Another marker of success was that patients were able to reduce their need for daily prednisone therapy. The mean daily dose fell by about two-thirds, from 33.3 mg/day to 11.96 mg/day after 12 months (P = .0004).

The protocol consists of a doublet of rituximab (750 mg/m

The doublet is repeated on days 14 and 15, and then the 2-week schedule is repeated at 6 and 18 months. These drugs have not been approved for the treatment of SLE in children.

Patients receive high-dose intravenous corticosteroids and intravenous diphenhydramine prior to rituximab infusion. Over the course of 3 years, most patients received at least three courses of therapy.

The group consisted of 11 females and 3 males who were about 12 years old when they were diagnosed with SLE.

Treatment with this protocol generally began 2 years after diagnosis, when the children were more than 14 years old. Five children were Asian, four children were Hispanic, three were white, and two were black. Six of the children had received prior cyclophosphamide monotherapy.

No serious adverse events were reported. Four patients had adverse events, including one each of urinary tract infection, herpes zoster, cellulitis, and lymphadenitis. All events resolved with treatment.

Four children were followed for at least 18 months after being diagnosed with biopsy-confirmed diffuse proliferative glomerular nephritis.

After undergoing the rituximab/cyclophosphamide treatment, all had normal complement levels and no indication of hematuria, proteinuria, or other urinary abnormalities and two of the four had negative antinuclear antibody (ANA) testing more than 1 year after treatment. “All these patients believe that they are cured,” says Dr. Lehman.

Dr. Lehman said that he is generally reluctant to discontinue prednisone, so all patients continue to receive approximately 10 mg/day of the drug. He reported that none of the children on prednisone showed signs of steroid toxicity such as depression, hirsutism, or Cushing's syndrome.

This protocol may not be appropriate for all children with SLE, according to Dr. Lehman. Not all children with SLE require aggressive therapy.

Data from studies done in the 1970s demonstrate that 30% of children with SLE do well with long-term, low-dose prednisone, whereas 30% develop steroid complications and 40% die or require dialysis, he said.

Aggressive therapy should be considered for children with persistent anemia (hemoglobin less than 10 g), persistent diastolic hypertension, pulmonary hypertension, or persistent hematuria (greater than 20 RBC/high-power field), or who have had recurrent emergency admissions for any reason.

The prevalence of SLE among children is estimated to be between 5 and 10 cases per 100,000 children. An estimated 8% of cases develop before children are 14 years of age, and about 15% develop before age 16.

Disclosures: The study received no commercial funding. Dr. Lehman is on the speakers bureau of Abbott Laboratories, Amgen Inc., and Pfizer Inc.

'This combination is extremely effective, much more than either drug alone' in the treatment of pediatric SLE.

Source DR. LEHMAN

NEW YORK — Although the majority of children with Kawasaki disease responds well to intravenous immunoglobulin therapy, 10%–15% of these patients are refractory to the first course of IVIG, and 50% of those continue to manifest fever after the second IVIG dose.

At a meeting sponsored by New York University, Dr. Philip J. Kahn described current treatment options for the child with refractory Kawasaki disease.

“Kawasaki disease is the No. 1 cause of acquired heart disease in children in developed countries. In 2000, over 4,000 hospitalizations in the United States were attributed to Kawasaki disease,” said Dr. Kahn, a pediatric rheumatologist at the NYU Langone Medical Center. “In the United States, all patients diagnosed with Kawasaki disease are treated, primarily because the children appear very ill, and they face a 20% risk of aneurysm if left untreated.”

Fortunately, IVIG reduces the risk of aneurysm to less than 5%, according to Dr. Kahn.

He recommended 2 g/kg over 8-12 hours, although the dose may be divided over 2 days.

Clinicians may also follow a protocol of 400 mg/kg per day for 4 days, especially when myocarditis is present.

Aspirin does not appear to lower the risk of aneurysm, said Dr. Kahn.

Because of the risk of aneurysm, failure to respond to IVIG is a serious concern. Patients who continue to have recrudescent or persistent fever 48 hours after the first IVIG dose should receive a second IVIG dose, according to Dr. Kahn.

If fever persists after the second dose, rethink your diagnosis, said Dr. Kahn.

Consideration should be given to other possible etiologies, such as infection (for example, streptococcus, staphylococcus, Epstein-Barr virus, adenovirus, measles, Rocky Mountain spotted fever, or leptospirosis), drug reaction (for example, to antibiotics, anticonvulsants, or antifungals), autoimmune disease (such as systemic juvenile idiopathic arthritis or polyarteritis nodosa), or acrodynia (for example, a mercury hypersensitivity reaction).

If the child is still thought to have Kawasaki disease, other treatment options are available. Steroids can shorten the duration of fever and hospital stays. A recent report found fewer coronary lesions in high-risk Kawasaki disease patients who were given pulse methylprednisolone with IVIG than in those given IVIG alone (Eur. J. Pediatr. 2009;168:181–5.)

Because tumor necrosis factor–alpha is elevated during the acute phase of Kawasaki disease and high levels are found in patients who develop aneurysms, studies have investigated the use of infliximab, an anti-TNF-alpha agent.

Indeed, fever ceased within 24 hours in 11 of 12 Kawasaki disease patients who were refractory to IVIG and were treated with infliximab (5 mg/kg), and the treatment was found to be safe and well tolerated (J. Pediatr. 2008;153:833–8.)

Other medications that have been used to treat IVIG-refractory Kawasaki disease include the protease inhibitor ulinastatin (combined with aspirin), the platelet GPIIb/IIIa inhibitor abciximab, and pentoxifylline, which acts by inhibiting the synthesis of TNF.

Immunosuppressants have sometimes been used to treat the vasculitis that is associated with Kawasaki disease, and in Japan some patients have undergone plasmapheresis.

Interestingly, the incidence of Kawasaki disease in children who are aged younger than 5 years is much higher in Japan (112 per 100,000) than in the United States, where it is higher in children of Asian descent (32.5 per 100,000) than in children of non-Asian descent (9.1 per 100,000), according to Dr. Kahn. Unlike the United States, where all children diagnosed with Kawasaki disease receive treatment, in Japan the clinicians utilize scoring systems to identify patients who are at high risk for aneurysm development, and they treat only those selected patients.

Some medications discussed in this review are not approved for use in Kawasaki disease.

Disclosures: Dr. Kahn had no financial disclosures to report.

Giant fusiform aneurysms of the left coronary artery and left anterior descending artery are visible in a child with Kawasaki.

Source © 2008 Elsevier Inc.

NEW YORK — Although the majority of children with Kawasaki disease responds well to intravenous immunoglobulin therapy, 10%–15% of these patients are refractory to the first course of IVIG, and 50% of those continue to manifest fever after the second IVIG dose.

At a meeting sponsored by New York University, Dr. Philip J. Kahn described current treatment options for the child with refractory Kawasaki disease.

“Kawasaki disease is the No. 1 cause of acquired heart disease in children in developed countries. In 2000, over 4,000 hospitalizations in the United States were attributed to Kawasaki disease,” said Dr. Kahn, a pediatric rheumatologist at the NYU Langone Medical Center. “In the United States, all patients diagnosed with Kawasaki disease are treated, primarily because the children appear very ill, and they face a 20% risk of aneurysm if left untreated.”

Fortunately, IVIG reduces the risk of aneurysm to less than 5%, according to Dr. Kahn.

He recommended 2 g/kg over 8-12 hours, although the dose may be divided over 2 days.

Clinicians may also follow a protocol of 400 mg/kg per day for 4 days, especially when myocarditis is present.

Aspirin does not appear to lower the risk of aneurysm, said Dr. Kahn.

Because of the risk of aneurysm, failure to respond to IVIG is a serious concern. Patients who continue to have recrudescent or persistent fever 48 hours after the first IVIG dose should receive a second IVIG dose, according to Dr. Kahn.

If fever persists after the second dose, rethink your diagnosis, said Dr. Kahn.

Consideration should be given to other possible etiologies, such as infection (for example, streptococcus, staphylococcus, Epstein-Barr virus, adenovirus, measles, Rocky Mountain spotted fever, or leptospirosis), drug reaction (for example, to antibiotics, anticonvulsants, or antifungals), autoimmune disease (such as systemic juvenile idiopathic arthritis or polyarteritis nodosa), or acrodynia (for example, a mercury hypersensitivity reaction).

If the child is still thought to have Kawasaki disease, other treatment options are available. Steroids can shorten the duration of fever and hospital stays. A recent report found fewer coronary lesions in high-risk Kawasaki disease patients who were given pulse methylprednisolone with IVIG than in those given IVIG alone (Eur. J. Pediatr. 2009;168:181–5.)

Because tumor necrosis factor–alpha is elevated during the acute phase of Kawasaki disease and high levels are found in patients who develop aneurysms, studies have investigated the use of infliximab, an anti-TNF-alpha agent.

Indeed, fever ceased within 24 hours in 11 of 12 Kawasaki disease patients who were refractory to IVIG and were treated with infliximab (5 mg/kg), and the treatment was found to be safe and well tolerated (J. Pediatr. 2008;153:833–8.)

Other medications that have been used to treat IVIG-refractory Kawasaki disease include the protease inhibitor ulinastatin (combined with aspirin), the platelet GPIIb/IIIa inhibitor abciximab, and pentoxifylline, which acts by inhibiting the synthesis of TNF.

Immunosuppressants have sometimes been used to treat the vasculitis that is associated with Kawasaki disease, and in Japan some patients have undergone plasmapheresis.

Interestingly, the incidence of Kawasaki disease in children who are aged younger than 5 years is much higher in Japan (112 per 100,000) than in the United States, where it is higher in children of Asian descent (32.5 per 100,000) than in children of non-Asian descent (9.1 per 100,000), according to Dr. Kahn. Unlike the United States, where all children diagnosed with Kawasaki disease receive treatment, in Japan the clinicians utilize scoring systems to identify patients who are at high risk for aneurysm development, and they treat only those selected patients.

Some medications discussed in this review are not approved for use in Kawasaki disease.

Disclosures: Dr. Kahn had no financial disclosures to report.

Giant fusiform aneurysms of the left coronary artery and left anterior descending artery are visible in a child with Kawasaki.

Source © 2008 Elsevier Inc.

NEW YORK — Although the majority of children with Kawasaki disease responds well to intravenous immunoglobulin therapy, 10%–15% of these patients are refractory to the first course of IVIG, and 50% of those continue to manifest fever after the second IVIG dose.

At a meeting sponsored by New York University, Dr. Philip J. Kahn described current treatment options for the child with refractory Kawasaki disease.

“Kawasaki disease is the No. 1 cause of acquired heart disease in children in developed countries. In 2000, over 4,000 hospitalizations in the United States were attributed to Kawasaki disease,” said Dr. Kahn, a pediatric rheumatologist at the NYU Langone Medical Center. “In the United States, all patients diagnosed with Kawasaki disease are treated, primarily because the children appear very ill, and they face a 20% risk of aneurysm if left untreated.”

Fortunately, IVIG reduces the risk of aneurysm to less than 5%, according to Dr. Kahn.

He recommended 2 g/kg over 8-12 hours, although the dose may be divided over 2 days.

Clinicians may also follow a protocol of 400 mg/kg per day for 4 days, especially when myocarditis is present.

Aspirin does not appear to lower the risk of aneurysm, said Dr. Kahn.

Because of the risk of aneurysm, failure to respond to IVIG is a serious concern. Patients who continue to have recrudescent or persistent fever 48 hours after the first IVIG dose should receive a second IVIG dose, according to Dr. Kahn.

If fever persists after the second dose, rethink your diagnosis, said Dr. Kahn.

Consideration should be given to other possible etiologies, such as infection (for example, streptococcus, staphylococcus, Epstein-Barr virus, adenovirus, measles, Rocky Mountain spotted fever, or leptospirosis), drug reaction (for example, to antibiotics, anticonvulsants, or antifungals), autoimmune disease (such as systemic juvenile idiopathic arthritis or polyarteritis nodosa), or acrodynia (for example, a mercury hypersensitivity reaction).

If the child is still thought to have Kawasaki disease, other treatment options are available. Steroids can shorten the duration of fever and hospital stays. A recent report found fewer coronary lesions in high-risk Kawasaki disease patients who were given pulse methylprednisolone with IVIG than in those given IVIG alone (Eur. J. Pediatr. 2009;168:181–5.)

Because tumor necrosis factor–alpha is elevated during the acute phase of Kawasaki disease and high levels are found in patients who develop aneurysms, studies have investigated the use of infliximab, an anti-TNF-alpha agent.

Indeed, fever ceased within 24 hours in 11 of 12 Kawasaki disease patients who were refractory to IVIG and were treated with infliximab (5 mg/kg), and the treatment was found to be safe and well tolerated (J. Pediatr. 2008;153:833–8.)

Other medications that have been used to treat IVIG-refractory Kawasaki disease include the protease inhibitor ulinastatin (combined with aspirin), the platelet GPIIb/IIIa inhibitor abciximab, and pentoxifylline, which acts by inhibiting the synthesis of TNF.

Immunosuppressants have sometimes been used to treat the vasculitis that is associated with Kawasaki disease, and in Japan some patients have undergone plasmapheresis.

Interestingly, the incidence of Kawasaki disease in children who are aged younger than 5 years is much higher in Japan (112 per 100,000) than in the United States, where it is higher in children of Asian descent (32.5 per 100,000) than in children of non-Asian descent (9.1 per 100,000), according to Dr. Kahn. Unlike the United States, where all children diagnosed with Kawasaki disease receive treatment, in Japan the clinicians utilize scoring systems to identify patients who are at high risk for aneurysm development, and they treat only those selected patients.

Some medications discussed in this review are not approved for use in Kawasaki disease.

Disclosures: Dr. Kahn had no financial disclosures to report.

Giant fusiform aneurysms of the left coronary artery and left anterior descending artery are visible in a child with Kawasaki.

Source © 2008 Elsevier Inc.

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Eberhard had no relevant financial disclosures.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Eberhard had no relevant financial disclosures.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Eberhard had no relevant financial disclosures.

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

PHILADELPHIA — Women with rheumatic disease who took etanercept during pregnancy were three times more likely to have a child with a major malformation than a disease-matched comparison group, judging from interim results from a small sample.

Most of the malformations were isolated, and no patterns of birth defect were apparent, according to Christina Chambers, Ph.D., who presented the findings from the Autoimmune Diseases in Pregnancy Project being conducted by the Organization of Teratology Information Specialists (OTIS) at the annual meeting of the American College of Rheumatology.

“These are ongoing studies with a target sample size that is intended to have sufficient power to answer our research questions,” said Dr. Chambers, an associate professor of pediatrics and family and preventive medicine at the University of California in San Diego.

The OTIS study is a prospective observational cohort study with the purpose of evaluating effects of autoimmune diseases and their treatment on pregnancy outcomes and fetal development. Recruitment began in 2000, and is projected to continue through 2015. Current recruitment stands at 944, with a goal of 1,500.

Pregnant women are typically enrolled in the study before they reach 20 weeks of gestation. To be enrolled, the women must have current diagnoses of rheumatoid arthritis (RA), juvenile RA, ankylosing spondylitis, psoriasis and psoriatic arthritis, or Crohn's disease. After birth, the infants are followed for up to a year, during which time they are assessed by their pediatricians and undergo blinded dysmorphological examination by OTIS physicians.

“Evaluating pregnancy outcomes following medication exposure is a not a situation that lends itself to conducting a randomized, controlled trial for obvious ethical reasons,” Dr. Chambers said. While the literature contains case reports, the OTIS study is designed to give clinicians the evidence-based information they need to counsel patients who are pregnant or considering becoming pregnant.

At the time of this progress report, outcome was available for 115 women with RA who had been exposed to etanercept, compared to 55 disease-comparison controls. Outcome was available for 42 women with RA who were exposed to adalimumab, compared with 58 disease-matched women and 84 healthy controls.

The percentage of live births was higher in those treated with etanercept, compared with those with similar rheumatic diseases (92% vs. 85%), and fewer spontaneous abortions occurred in the etanercept-treated group (4% vs. 11%). There were no ectopic pregnancies in either group. One stillbirth was reported in the etanercept cohort and none in the controls. Preterm deliveries were more common in women who were taking etanercept (23% vs. 13%). Taking the drug did not seem to be related to the average birth weight in full term infants.

Of the major malformations among all pregnancies enrolled in OTIS, 12% (14 of 114) were reported in the etanercept group, compared with 3.8% (2 of 53) in the disease-matched controls. “Typically we would see a specific pattern of malformation with a medication that truly causes defects, but our results indicate that most of the defects were isolated with no apparent patterns,” Dr. Chambers said.

For those exposed to adalimumab, the percentage of live births was lower in those receiving the drug (88%), compared with those with similar autoimmune illnesses (93%) and healthy controls (92%). The rate of spontaneous abortions also was higher in the adalimumab-treated cohort (12%) compared with the disease-matched (5%) and healthy cohorts (1%). There were no ectopic pregnancies or stillbirths in the drug-treated group.

Preterm delivery was higher in both the adalimumab-treated (14%) and disease-matched comparison (17%) groups, compared with healthy controls (4%). Mean birth weight was approximately 300 g less in full-term infants whose mothers had received adalimumab, compared with healthy controls, but similar to full-term infants in the disease-matched comparison group. Rates of major malformations were similar (4%–5%) in all groups and within the range of expected numbers in the general population, Dr. Chambers said. “Firm conclusions await the accumulation of target sample size for adalimumab and etanercept and multivariate analysis.”

'Our results indicate that most of the defects were isolated with no apparent patterns.'

Source DR. CHAMBERS

PHILADELPHIA — Women with rheumatic disease who took etanercept during pregnancy were three times more likely to have a child with a major malformation than a disease-matched comparison group, judging from interim results from a small sample.

Most of the malformations were isolated, and no patterns of birth defect were apparent, according to Christina Chambers, Ph.D., who presented the findings from the Autoimmune Diseases in Pregnancy Project being conducted by the Organization of Teratology Information Specialists (OTIS) at the annual meeting of the American College of Rheumatology.

“These are ongoing studies with a target sample size that is intended to have sufficient power to answer our research questions,” said Dr. Chambers, an associate professor of pediatrics and family and preventive medicine at the University of California in San Diego.

The OTIS study is a prospective observational cohort study with the purpose of evaluating effects of autoimmune diseases and their treatment on pregnancy outcomes and fetal development. Recruitment began in 2000, and is projected to continue through 2015. Current recruitment stands at 944, with a goal of 1,500.

Pregnant women are typically enrolled in the study before they reach 20 weeks of gestation. To be enrolled, the women must have current diagnoses of rheumatoid arthritis (RA), juvenile RA, ankylosing spondylitis, psoriasis and psoriatic arthritis, or Crohn's disease. After birth, the infants are followed for up to a year, during which time they are assessed by their pediatricians and undergo blinded dysmorphological examination by OTIS physicians.

“Evaluating pregnancy outcomes following medication exposure is a not a situation that lends itself to conducting a randomized, controlled trial for obvious ethical reasons,” Dr. Chambers said. While the literature contains case reports, the OTIS study is designed to give clinicians the evidence-based information they need to counsel patients who are pregnant or considering becoming pregnant.

At the time of this progress report, outcome was available for 115 women with RA who had been exposed to etanercept, compared to 55 disease-comparison controls. Outcome was available for 42 women with RA who were exposed to adalimumab, compared with 58 disease-matched women and 84 healthy controls.

The percentage of live births was higher in those treated with etanercept, compared with those with similar rheumatic diseases (92% vs. 85%), and fewer spontaneous abortions occurred in the etanercept-treated group (4% vs. 11%). There were no ectopic pregnancies in either group. One stillbirth was reported in the etanercept cohort and none in the controls. Preterm deliveries were more common in women who were taking etanercept (23% vs. 13%). Taking the drug did not seem to be related to the average birth weight in full term infants.

Of the major malformations among all pregnancies enrolled in OTIS, 12% (14 of 114) were reported in the etanercept group, compared with 3.8% (2 of 53) in the disease-matched controls. “Typically we would see a specific pattern of malformation with a medication that truly causes defects, but our results indicate that most of the defects were isolated with no apparent patterns,” Dr. Chambers said.

For those exposed to adalimumab, the percentage of live births was lower in those receiving the drug (88%), compared with those with similar autoimmune illnesses (93%) and healthy controls (92%). The rate of spontaneous abortions also was higher in the adalimumab-treated cohort (12%) compared with the disease-matched (5%) and healthy cohorts (1%). There were no ectopic pregnancies or stillbirths in the drug-treated group.

Preterm delivery was higher in both the adalimumab-treated (14%) and disease-matched comparison (17%) groups, compared with healthy controls (4%). Mean birth weight was approximately 300 g less in full-term infants whose mothers had received adalimumab, compared with healthy controls, but similar to full-term infants in the disease-matched comparison group. Rates of major malformations were similar (4%–5%) in all groups and within the range of expected numbers in the general population, Dr. Chambers said. “Firm conclusions await the accumulation of target sample size for adalimumab and etanercept and multivariate analysis.”

'Our results indicate that most of the defects were isolated with no apparent patterns.'

Source DR. CHAMBERS

PHILADELPHIA — Women with rheumatic disease who took etanercept during pregnancy were three times more likely to have a child with a major malformation than a disease-matched comparison group, judging from interim results from a small sample.

Most of the malformations were isolated, and no patterns of birth defect were apparent, according to Christina Chambers, Ph.D., who presented the findings from the Autoimmune Diseases in Pregnancy Project being conducted by the Organization of Teratology Information Specialists (OTIS) at the annual meeting of the American College of Rheumatology.

“These are ongoing studies with a target sample size that is intended to have sufficient power to answer our research questions,” said Dr. Chambers, an associate professor of pediatrics and family and preventive medicine at the University of California in San Diego.

The OTIS study is a prospective observational cohort study with the purpose of evaluating effects of autoimmune diseases and their treatment on pregnancy outcomes and fetal development. Recruitment began in 2000, and is projected to continue through 2015. Current recruitment stands at 944, with a goal of 1,500.

Pregnant women are typically enrolled in the study before they reach 20 weeks of gestation. To be enrolled, the women must have current diagnoses of rheumatoid arthritis (RA), juvenile RA, ankylosing spondylitis, psoriasis and psoriatic arthritis, or Crohn's disease. After birth, the infants are followed for up to a year, during which time they are assessed by their pediatricians and undergo blinded dysmorphological examination by OTIS physicians.

“Evaluating pregnancy outcomes following medication exposure is a not a situation that lends itself to conducting a randomized, controlled trial for obvious ethical reasons,” Dr. Chambers said. While the literature contains case reports, the OTIS study is designed to give clinicians the evidence-based information they need to counsel patients who are pregnant or considering becoming pregnant.

At the time of this progress report, outcome was available for 115 women with RA who had been exposed to etanercept, compared to 55 disease-comparison controls. Outcome was available for 42 women with RA who were exposed to adalimumab, compared with 58 disease-matched women and 84 healthy controls.

The percentage of live births was higher in those treated with etanercept, compared with those with similar rheumatic diseases (92% vs. 85%), and fewer spontaneous abortions occurred in the etanercept-treated group (4% vs. 11%). There were no ectopic pregnancies in either group. One stillbirth was reported in the etanercept cohort and none in the controls. Preterm deliveries were more common in women who were taking etanercept (23% vs. 13%). Taking the drug did not seem to be related to the average birth weight in full term infants.

Of the major malformations among all pregnancies enrolled in OTIS, 12% (14 of 114) were reported in the etanercept group, compared with 3.8% (2 of 53) in the disease-matched controls. “Typically we would see a specific pattern of malformation with a medication that truly causes defects, but our results indicate that most of the defects were isolated with no apparent patterns,” Dr. Chambers said.

For those exposed to adalimumab, the percentage of live births was lower in those receiving the drug (88%), compared with those with similar autoimmune illnesses (93%) and healthy controls (92%). The rate of spontaneous abortions also was higher in the adalimumab-treated cohort (12%) compared with the disease-matched (5%) and healthy cohorts (1%). There were no ectopic pregnancies or stillbirths in the drug-treated group.

Preterm delivery was higher in both the adalimumab-treated (14%) and disease-matched comparison (17%) groups, compared with healthy controls (4%). Mean birth weight was approximately 300 g less in full-term infants whose mothers had received adalimumab, compared with healthy controls, but similar to full-term infants in the disease-matched comparison group. Rates of major malformations were similar (4%–5%) in all groups and within the range of expected numbers in the general population, Dr. Chambers said. “Firm conclusions await the accumulation of target sample size for adalimumab and etanercept and multivariate analysis.”

'Our results indicate that most of the defects were isolated with no apparent patterns.'

Source DR. CHAMBERS

Major Finding: Mothers with rheumatoid arthritis were 1.47 times more likely than unaffected mothers to have a low-birth-weight baby, and 1.20 times more likely to have a baby deemed small for gestational age.

Data Source: From two large databases, researchers selected a sample of women who gave birth (1,912 with RA and 9560 controls).

Disclosures: The researchers made no disclosures.

Pregnant women with rheumatoid arthritis face an increased risk of adverse obstetric outcomes, and they deserve heightened prenatal attention, according to a recent report in the February issue of the Annals of Rheumatic Diseases.

Specifically, mothers with rheumatoid arthritis (RA) were 1.47 times more likely than unaffected mothers to have a low-birth-weight baby and 1.20 times more likely to have a baby deemed small for gestational age.

Women with RA also had a higher risk for developing preeclampsia (adjusted odds ratio, 2.22) or having to undergo a cesarian section (adjusted OR, 1.19), according to investigators from Taipei (Taiwan) Medical University (Ann. Rheum. Dis. 2010 Feb. [doi:10.1136/ard.2008.105262]).

“Our findings suggest a need for more intensive prenatal care among pregnant women with RA. In addition, early intervention should be considered to counter potential adverse obstetric outcomes for pregnant women with RA,” according to Herng Ching Lin, Ph.D., and associates, all of whom are with the university's school of health care administration.

Investigators used two databases in their analysis. The first was the Taiwan National Health Insurance Research Dataset (NHIRD), which included inpatient and ambulatory care claims from 1996 to 2003, and the second was the 2001-2003 National Birth Certificate Registry (NBCR), which is maintained by the government of Taiwan.

From the nearly 500,000 women who had live singleton births in Taiwan between 2001 and 2003, the investigators identified 1,912 mothers with RA (ICD-9-CM, code 714.0) and compared their pregnancy outcomes with those of 9,560 controls who were matched to the cases by age, parity, and year of delivery. The diagnosis of RA in the cases was usually made by a rheumatologist and based on clinical symptoms, radiographic changes, and the presence of rheumatoid factor.

Women with chronic diseases such as hypertension or diabetes that could increase the risk of adverse pregnancy outcomes were excluded.

The two groups of women did not differ significantly in their sociodemographic variables such as marital status, level of education, and household income.

The women with RA were no more likely than their unaffected peers to have preterm births. For women with RA, the mean gestational age was 38.4 weeks (range, 27-43); the mean gestational ages for mothers with and without RA were 38.3 weeks (range, 27-43) and 38.5 weeks (range, 29-41), respectively.

According to the authors, one strength of the study was its homogenous population: More than 98% of Taiwan's residents are of Chinese Han ethnicity.

Although this may have minimized the possibility that race affected the results, it may have also limited whether the results can be generalized to other ethnic groups.

Another strength is its large sample size.

One important limitation of the study was that the NHIRD did not include complete information about RA medications that were taken during pregnancy, a potentially important confounding factor.

A second limitation was that study participants were not differentiated according to RA severity.

Major Finding: Mothers with rheumatoid arthritis were 1.47 times more likely than unaffected mothers to have a low-birth-weight baby, and 1.20 times more likely to have a baby deemed small for gestational age.

Data Source: From two large databases, researchers selected a sample of women who gave birth (1,912 with RA and 9560 controls).

Disclosures: The researchers made no disclosures.

Pregnant women with rheumatoid arthritis face an increased risk of adverse obstetric outcomes, and they deserve heightened prenatal attention, according to a recent report in the February issue of the Annals of Rheumatic Diseases.

Specifically, mothers with rheumatoid arthritis (RA) were 1.47 times more likely than unaffected mothers to have a low-birth-weight baby and 1.20 times more likely to have a baby deemed small for gestational age.

Women with RA also had a higher risk for developing preeclampsia (adjusted odds ratio, 2.22) or having to undergo a cesarian section (adjusted OR, 1.19), according to investigators from Taipei (Taiwan) Medical University (Ann. Rheum. Dis. 2010 Feb. [doi:10.1136/ard.2008.105262]).

“Our findings suggest a need for more intensive prenatal care among pregnant women with RA. In addition, early intervention should be considered to counter potential adverse obstetric outcomes for pregnant women with RA,” according to Herng Ching Lin, Ph.D., and associates, all of whom are with the university's school of health care administration.

Investigators used two databases in their analysis. The first was the Taiwan National Health Insurance Research Dataset (NHIRD), which included inpatient and ambulatory care claims from 1996 to 2003, and the second was the 2001-2003 National Birth Certificate Registry (NBCR), which is maintained by the government of Taiwan.

From the nearly 500,000 women who had live singleton births in Taiwan between 2001 and 2003, the investigators identified 1,912 mothers with RA (ICD-9-CM, code 714.0) and compared their pregnancy outcomes with those of 9,560 controls who were matched to the cases by age, parity, and year of delivery. The diagnosis of RA in the cases was usually made by a rheumatologist and based on clinical symptoms, radiographic changes, and the presence of rheumatoid factor.

Women with chronic diseases such as hypertension or diabetes that could increase the risk of adverse pregnancy outcomes were excluded.

The two groups of women did not differ significantly in their sociodemographic variables such as marital status, level of education, and household income.

The women with RA were no more likely than their unaffected peers to have preterm births. For women with RA, the mean gestational age was 38.4 weeks (range, 27-43); the mean gestational ages for mothers with and without RA were 38.3 weeks (range, 27-43) and 38.5 weeks (range, 29-41), respectively.

According to the authors, one strength of the study was its homogenous population: More than 98% of Taiwan's residents are of Chinese Han ethnicity.

Although this may have minimized the possibility that race affected the results, it may have also limited whether the results can be generalized to other ethnic groups.

Another strength is its large sample size.

One important limitation of the study was that the NHIRD did not include complete information about RA medications that were taken during pregnancy, a potentially important confounding factor.

A second limitation was that study participants were not differentiated according to RA severity.

Major Finding: Mothers with rheumatoid arthritis were 1.47 times more likely than unaffected mothers to have a low-birth-weight baby, and 1.20 times more likely to have a baby deemed small for gestational age.

Data Source: From two large databases, researchers selected a sample of women who gave birth (1,912 with RA and 9560 controls).

Disclosures: The researchers made no disclosures.

Pregnant women with rheumatoid arthritis face an increased risk of adverse obstetric outcomes, and they deserve heightened prenatal attention, according to a recent report in the February issue of the Annals of Rheumatic Diseases.

Specifically, mothers with rheumatoid arthritis (RA) were 1.47 times more likely than unaffected mothers to have a low-birth-weight baby and 1.20 times more likely to have a baby deemed small for gestational age.

Women with RA also had a higher risk for developing preeclampsia (adjusted odds ratio, 2.22) or having to undergo a cesarian section (adjusted OR, 1.19), according to investigators from Taipei (Taiwan) Medical University (Ann. Rheum. Dis. 2010 Feb. [doi:10.1136/ard.2008.105262]).

“Our findings suggest a need for more intensive prenatal care among pregnant women with RA. In addition, early intervention should be considered to counter potential adverse obstetric outcomes for pregnant women with RA,” according to Herng Ching Lin, Ph.D., and associates, all of whom are with the university's school of health care administration.

Investigators used two databases in their analysis. The first was the Taiwan National Health Insurance Research Dataset (NHIRD), which included inpatient and ambulatory care claims from 1996 to 2003, and the second was the 2001-2003 National Birth Certificate Registry (NBCR), which is maintained by the government of Taiwan.

From the nearly 500,000 women who had live singleton births in Taiwan between 2001 and 2003, the investigators identified 1,912 mothers with RA (ICD-9-CM, code 714.0) and compared their pregnancy outcomes with those of 9,560 controls who were matched to the cases by age, parity, and year of delivery. The diagnosis of RA in the cases was usually made by a rheumatologist and based on clinical symptoms, radiographic changes, and the presence of rheumatoid factor.

Women with chronic diseases such as hypertension or diabetes that could increase the risk of adverse pregnancy outcomes were excluded.

The two groups of women did not differ significantly in their sociodemographic variables such as marital status, level of education, and household income.

The women with RA were no more likely than their unaffected peers to have preterm births. For women with RA, the mean gestational age was 38.4 weeks (range, 27-43); the mean gestational ages for mothers with and without RA were 38.3 weeks (range, 27-43) and 38.5 weeks (range, 29-41), respectively.

According to the authors, one strength of the study was its homogenous population: More than 98% of Taiwan's residents are of Chinese Han ethnicity.

Although this may have minimized the possibility that race affected the results, it may have also limited whether the results can be generalized to other ethnic groups.

Another strength is its large sample size.

One important limitation of the study was that the NHIRD did not include complete information about RA medications that were taken during pregnancy, a potentially important confounding factor.

A second limitation was that study participants were not differentiated according to RA severity.

Comorbidities, rather than the effects of inflammatory joint disease, may be why some patients with rheumatoid arthritis remain functionally disabled despite effective treatment for their arthritis.

This study included 380 RA patients from an outpatient clinic with a wide range of disease activity, disease duration, and comorbid conditions, according to Dr. Helga Radner and her associates from the Medical University of Vienna.

The study was based on serial measurements taken from more than 1,600 patient visits between June 2007 and July 2008. Physical disability was measured using the HAQ (Health Assessment Questionnaire) disability index. The Charlson Comorbidity Index (CCI), adjusted for age, was used to assess comorbidity burden, with differing weights given to comorbid conditions such as myocardial infarction (weight = 1), diabetes mellitus with complications (weight = 2), or AIDS (weight = 6).

Analysis of variance indicated a consistent increase in physical disability with increasing comorbidity burden (P less than .01), even after adjustment for disease activity, sex, or disease duration (Ann. Rheum. Dis. 2010 [doi:10.1136/ard.2009. 118430]).

The influential effect of comorbidities on functional disability in patients with RA was seen across all levels of RA disease activity, as measured by the CDAI (Clinical Disease Activity Index). For RA patients with low or moderate/high disease severity, having one or more comorbidities added to the levels of functional disability, “reflecting the well-known contribution of [RA] disease activity to impairment of physical function,” Dr. Radner and her associates said. However, even patients who were thought to be in remission for RA showed significant increases in functional disability when comorbidities were present (P less than .01).

“Based on our analyses, the average HAQ in a group of patients with several comorbid conditions would be somewhere around 0.6, even if the best possible treatment was used. This floor effect of functional improvement is an important aspect when evidence of therapeutic efficacy needs to be provided, such as for reimbursement of interventions,” the authors wrote.

Disclosures: Dr. Radner and her associates report having no conflicts of interest.

Comorbidities, rather than the effects of inflammatory joint disease, may be why some patients with rheumatoid arthritis remain functionally disabled despite effective treatment for their arthritis.

This study included 380 RA patients from an outpatient clinic with a wide range of disease activity, disease duration, and comorbid conditions, according to Dr. Helga Radner and her associates from the Medical University of Vienna.

The study was based on serial measurements taken from more than 1,600 patient visits between June 2007 and July 2008. Physical disability was measured using the HAQ (Health Assessment Questionnaire) disability index. The Charlson Comorbidity Index (CCI), adjusted for age, was used to assess comorbidity burden, with differing weights given to comorbid conditions such as myocardial infarction (weight = 1), diabetes mellitus with complications (weight = 2), or AIDS (weight = 6).

Analysis of variance indicated a consistent increase in physical disability with increasing comorbidity burden (P less than .01), even after adjustment for disease activity, sex, or disease duration (Ann. Rheum. Dis. 2010 [doi:10.1136/ard.2009. 118430]).

The influential effect of comorbidities on functional disability in patients with RA was seen across all levels of RA disease activity, as measured by the CDAI (Clinical Disease Activity Index). For RA patients with low or moderate/high disease severity, having one or more comorbidities added to the levels of functional disability, “reflecting the well-known contribution of [RA] disease activity to impairment of physical function,” Dr. Radner and her associates said. However, even patients who were thought to be in remission for RA showed significant increases in functional disability when comorbidities were present (P less than .01).

“Based on our analyses, the average HAQ in a group of patients with several comorbid conditions would be somewhere around 0.6, even if the best possible treatment was used. This floor effect of functional improvement is an important aspect when evidence of therapeutic efficacy needs to be provided, such as for reimbursement of interventions,” the authors wrote.

Disclosures: Dr. Radner and her associates report having no conflicts of interest.

Comorbidities, rather than the effects of inflammatory joint disease, may be why some patients with rheumatoid arthritis remain functionally disabled despite effective treatment for their arthritis.

This study included 380 RA patients from an outpatient clinic with a wide range of disease activity, disease duration, and comorbid conditions, according to Dr. Helga Radner and her associates from the Medical University of Vienna.

The study was based on serial measurements taken from more than 1,600 patient visits between June 2007 and July 2008. Physical disability was measured using the HAQ (Health Assessment Questionnaire) disability index. The Charlson Comorbidity Index (CCI), adjusted for age, was used to assess comorbidity burden, with differing weights given to comorbid conditions such as myocardial infarction (weight = 1), diabetes mellitus with complications (weight = 2), or AIDS (weight = 6).

Analysis of variance indicated a consistent increase in physical disability with increasing comorbidity burden (P less than .01), even after adjustment for disease activity, sex, or disease duration (Ann. Rheum. Dis. 2010 [doi:10.1136/ard.2009. 118430]).

The influential effect of comorbidities on functional disability in patients with RA was seen across all levels of RA disease activity, as measured by the CDAI (Clinical Disease Activity Index). For RA patients with low or moderate/high disease severity, having one or more comorbidities added to the levels of functional disability, “reflecting the well-known contribution of [RA] disease activity to impairment of physical function,” Dr. Radner and her associates said. However, even patients who were thought to be in remission for RA showed significant increases in functional disability when comorbidities were present (P less than .01).

“Based on our analyses, the average HAQ in a group of patients with several comorbid conditions would be somewhere around 0.6, even if the best possible treatment was used. This floor effect of functional improvement is an important aspect when evidence of therapeutic efficacy needs to be provided, such as for reimbursement of interventions,” the authors wrote.

Disclosures: Dr. Radner and her associates report having no conflicts of interest.

Major Finding: The study confirmed that the incidence of RA increases during the first 2 years post partum.

Data Source: NOR-DMARD Registry and the Medical Birth Registry of Norway.

Disclosures: Research was supported by the liaison committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The NOR-DMARD registry is supported by all makers of biologic drugs for RA in Europe.

By linking two Norwegian national data registries, investigators confirmed previous findings that the incidence of rheumatoid arthritis is increased in women in the 2 years following delivery, compared with the subsequent 2 years post partum. The results also showed an elevated incidence of other chronic arthritides in the first 2 postpartum years, according to a report by Dr. Marianne Wallenius from the department of rheumatology of St. Olav's Hospital in Trondheim, Norway.

These studies may contribute to a better understanding of the fundamental question of why one person gets RA and another does not,” noted Dr. Radboud J.E.M. Dolhain of Erasmus University Medical Centre, Rotterdam, the Netherlands, in an accompanying editorial (Ann. Rheum. Dis. 2010;69:317-8).

One hypothesis is that pregnancy exerts a protective effect on RA and other arthritides, which then disappears after delivery, allowing disease to flare. However, this study did not look at incidence during pregnancy. More epidemiologic data are needed “to determine whether this is a true increased incidence or whether rather the incidence of RA and other forms of arthritis is postponed to after delivery,” according to Dr. Dolhain.

The investigators took a unique approach to studying the incidence of RA and other chronic arthritides following pregnancy. They linked data from a registry of people with inflammatory arthropathies who were taking disease-modifying antirheumatic drugs (the NOR-DMARD Registry) with the Medical Birth Registry of Norway that has recorded all births in Norway since 1967. The investigators were able to locate 293 women with arthritis whose disease was first diagnosed after delivery. Of these, 183 were diagnosed with RA and 110 with other chronic arthritides (OCA), including 51 with psoriatic arthritis, 14 with ankylosing spondylitides, and 45 with unspecified arthritis.

Of those with RA, 38% (69 women) were diagnosed in the first 2 years post partum, compared with 28% (31 women) who were diagnosed with OCA. The results were not significantly different (P = .09).

RA incidence peaked in the first 2 years after pregnancy, compared with the subsequent 2 years for those who were diagnosed solely with RA (incident rate ratio, 1.73; P = .01) or for the entire RA-plus-OCA group (IRR, 1.44; P = .04) after all pregnancies were considered, but not for those who were diagnosed only with OCA (IRR, 1.05; P = .86). Investigators made similar findings when they limited the group to those who were diagnosed only after the first pregnancy (Ann. Rheum. Dis. 2010;69:332-6).

The investigators suggested that the lack of statistical significance for the OCA group may be attributed to the group's being too small, with rather wide confidence intervals around the IRR estimate. One reason the OCA group may have been small was that the NOR-DMARD Registry included patients who had developed a level of disease that required treatment with DMARDs and/or biologic agents, thereby excluding patients with milder disease who did not require such medication.

Major Finding: The study confirmed that the incidence of RA increases during the first 2 years post partum.

Data Source: NOR-DMARD Registry and the Medical Birth Registry of Norway.

Disclosures: Research was supported by the liaison committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The NOR-DMARD registry is supported by all makers of biologic drugs for RA in Europe.

By linking two Norwegian national data registries, investigators confirmed previous findings that the incidence of rheumatoid arthritis is increased in women in the 2 years following delivery, compared with the subsequent 2 years post partum. The results also showed an elevated incidence of other chronic arthritides in the first 2 postpartum years, according to a report by Dr. Marianne Wallenius from the department of rheumatology of St. Olav's Hospital in Trondheim, Norway.

These studies may contribute to a better understanding of the fundamental question of why one person gets RA and another does not,” noted Dr. Radboud J.E.M. Dolhain of Erasmus University Medical Centre, Rotterdam, the Netherlands, in an accompanying editorial (Ann. Rheum. Dis. 2010;69:317-8).

One hypothesis is that pregnancy exerts a protective effect on RA and other arthritides, which then disappears after delivery, allowing disease to flare. However, this study did not look at incidence during pregnancy. More epidemiologic data are needed “to determine whether this is a true increased incidence or whether rather the incidence of RA and other forms of arthritis is postponed to after delivery,” according to Dr. Dolhain.

The investigators took a unique approach to studying the incidence of RA and other chronic arthritides following pregnancy. They linked data from a registry of people with inflammatory arthropathies who were taking disease-modifying antirheumatic drugs (the NOR-DMARD Registry) with the Medical Birth Registry of Norway that has recorded all births in Norway since 1967. The investigators were able to locate 293 women with arthritis whose disease was first diagnosed after delivery. Of these, 183 were diagnosed with RA and 110 with other chronic arthritides (OCA), including 51 with psoriatic arthritis, 14 with ankylosing spondylitides, and 45 with unspecified arthritis.

Of those with RA, 38% (69 women) were diagnosed in the first 2 years post partum, compared with 28% (31 women) who were diagnosed with OCA. The results were not significantly different (P = .09).

RA incidence peaked in the first 2 years after pregnancy, compared with the subsequent 2 years for those who were diagnosed solely with RA (incident rate ratio, 1.73; P = .01) or for the entire RA-plus-OCA group (IRR, 1.44; P = .04) after all pregnancies were considered, but not for those who were diagnosed only with OCA (IRR, 1.05; P = .86). Investigators made similar findings when they limited the group to those who were diagnosed only after the first pregnancy (Ann. Rheum. Dis. 2010;69:332-6).

The investigators suggested that the lack of statistical significance for the OCA group may be attributed to the group's being too small, with rather wide confidence intervals around the IRR estimate. One reason the OCA group may have been small was that the NOR-DMARD Registry included patients who had developed a level of disease that required treatment with DMARDs and/or biologic agents, thereby excluding patients with milder disease who did not require such medication.

Major Finding: The study confirmed that the incidence of RA increases during the first 2 years post partum.

Data Source: NOR-DMARD Registry and the Medical Birth Registry of Norway.

Disclosures: Research was supported by the liaison committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The NOR-DMARD registry is supported by all makers of biologic drugs for RA in Europe.

By linking two Norwegian national data registries, investigators confirmed previous findings that the incidence of rheumatoid arthritis is increased in women in the 2 years following delivery, compared with the subsequent 2 years post partum. The results also showed an elevated incidence of other chronic arthritides in the first 2 postpartum years, according to a report by Dr. Marianne Wallenius from the department of rheumatology of St. Olav's Hospital in Trondheim, Norway.

These studies may contribute to a better understanding of the fundamental question of why one person gets RA and another does not,” noted Dr. Radboud J.E.M. Dolhain of Erasmus University Medical Centre, Rotterdam, the Netherlands, in an accompanying editorial (Ann. Rheum. Dis. 2010;69:317-8).

One hypothesis is that pregnancy exerts a protective effect on RA and other arthritides, which then disappears after delivery, allowing disease to flare. However, this study did not look at incidence during pregnancy. More epidemiologic data are needed “to determine whether this is a true increased incidence or whether rather the incidence of RA and other forms of arthritis is postponed to after delivery,” according to Dr. Dolhain.

The investigators took a unique approach to studying the incidence of RA and other chronic arthritides following pregnancy. They linked data from a registry of people with inflammatory arthropathies who were taking disease-modifying antirheumatic drugs (the NOR-DMARD Registry) with the Medical Birth Registry of Norway that has recorded all births in Norway since 1967. The investigators were able to locate 293 women with arthritis whose disease was first diagnosed after delivery. Of these, 183 were diagnosed with RA and 110 with other chronic arthritides (OCA), including 51 with psoriatic arthritis, 14 with ankylosing spondylitides, and 45 with unspecified arthritis.

Of those with RA, 38% (69 women) were diagnosed in the first 2 years post partum, compared with 28% (31 women) who were diagnosed with OCA. The results were not significantly different (P = .09).

RA incidence peaked in the first 2 years after pregnancy, compared with the subsequent 2 years for those who were diagnosed solely with RA (incident rate ratio, 1.73; P = .01) or for the entire RA-plus-OCA group (IRR, 1.44; P = .04) after all pregnancies were considered, but not for those who were diagnosed only with OCA (IRR, 1.05; P = .86). Investigators made similar findings when they limited the group to those who were diagnosed only after the first pregnancy (Ann. Rheum. Dis. 2010;69:332-6).

The investigators suggested that the lack of statistical significance for the OCA group may be attributed to the group's being too small, with rather wide confidence intervals around the IRR estimate. One reason the OCA group may have been small was that the NOR-DMARD Registry included patients who had developed a level of disease that required treatment with DMARDs and/or biologic agents, thereby excluding patients with milder disease who did not require such medication.

Elevated concentrations of proinflammatory cytokines, cytokine-related factors, and chemokines, indicating activation of the immune system, have been found in the blood of people years before they developed symptoms of rheumatoid arthritis that involved the joints, according to a report by Heidi Kokkonen and coinvestigators at Umeå (Sweden) University. The study was published in the February 2010 issue of Arthritis and Rheumatism.

By comparing blood samples of people diagnosed with RA to normal controls and “prepatients” (those who go on to develop RA), investigators said that they hope the results will help predict an individual's risk of developing RA.

The investigators analyzed samples from the Medical Biobank of Northern Sweden, which invites all adult individuals from the county of Västerbotten to contribute blood samples. Within this population-based cohort, there were 86 individuals who went on develop inflammatory joint disease that fulfilled American College of Rheumatology classification criteria for RA after their donation of blood. For these prepatients, the median time predating the onset of symptoms was 3.3 years (range, 1.1-5 years). Of the 86 prepatients, 69 also provided blood samples at the time of RA diagnosis. For every prepatient, three control subjects were randomly selected from the Biobank register and matched for sex, age, and area of residence.

Several cytokines, cytokine-related factors, and chemokines were upregulated in prepatients, compared with controls. The greatest increases were noted for the Th2-related cytokines, eotaxin, and interleukin-4, with elevated levels also observed for Th1 cytokines, IL-12, interferon-gamma, and IL-10.

A multivariate classification algorithm known as the random forest method, similar to decision trees, was used to estimate which groups of cytokines, cytokine-related factors, or chemokines could best distinguish a particular group of patients. For prepatients, characteristic changes were related to both the Th1 and Th2 lineage, and to Treg cells, representing the adaptive immune system, the authors wrote. Elevation of IL-17 levels did not reach statistical significance.

Levels of at least two-thirds of the cytokines or cytokine-related factors were above the median values for control subjects in 50 of 85 prepatients.

Of the chemokines, MCP-1 and MIP-1 alpha levels were significantly increased in prepatients, compared with controls, as were the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte–colony stimulating factor (G-CSF).

When the authors calculated the sensitivity and specificity of different factors for the development of RA in prepatients, they found that after anti-CCP antibodies and IgM rheumatoid factor (IgM-RF), eotaxin had the highest sensitivity (22.4%) and specificity (95.3%), with an odds ratio of 5.8. About one-half of the cytokines and cytokine-related factors that had significant predicative value for the development of RA in prepatients were related to Th1, Th2, and Treg cells. When all analyzed factors and anti-CCP antibodies were included, the sensitivity level rose to 51.2%, with a specificity of 91.9% for predicting the development of RA among prepatients and control subjects.

The factors distinguishing individuals before and after the onset of RA represented a more general immunologic response, as well as stromal cells and angiogenic factors. After RA diagnosis, significant increases were seen for most of the factors that were measured. IL-17 concentrations actually decreased after RA diagnosis. “This observation endorses the role of IL-17 in the initiating phase [of RA], and, as the pathogenesis progresses, other factors are subsequently brought into action,” wrote the authors (Arthritis Rheum. 2010;62:383-91).

Although the authors were unable to conclude which agent initiates RA pathogenesis, they suggested that their findings present an opportunity for better predicting the risk of developing RA and intervening at an early stage to possibly prevent disease progression.

Elevated concentrations of proinflammatory cytokines, cytokine-related factors, and chemokines, indicating activation of the immune system, have been found in the blood of people years before they developed symptoms of rheumatoid arthritis that involved the joints, according to a report by Heidi Kokkonen and coinvestigators at Umeå (Sweden) University. The study was published in the February 2010 issue of Arthritis and Rheumatism.

By comparing blood samples of people diagnosed with RA to normal controls and “prepatients” (those who go on to develop RA), investigators said that they hope the results will help predict an individual's risk of developing RA.

The investigators analyzed samples from the Medical Biobank of Northern Sweden, which invites all adult individuals from the county of Västerbotten to contribute blood samples. Within this population-based cohort, there were 86 individuals who went on develop inflammatory joint disease that fulfilled American College of Rheumatology classification criteria for RA after their donation of blood. For these prepatients, the median time predating the onset of symptoms was 3.3 years (range, 1.1-5 years). Of the 86 prepatients, 69 also provided blood samples at the time of RA diagnosis. For every prepatient, three control subjects were randomly selected from the Biobank register and matched for sex, age, and area of residence.

Several cytokines, cytokine-related factors, and chemokines were upregulated in prepatients, compared with controls. The greatest increases were noted for the Th2-related cytokines, eotaxin, and interleukin-4, with elevated levels also observed for Th1 cytokines, IL-12, interferon-gamma, and IL-10.

A multivariate classification algorithm known as the random forest method, similar to decision trees, was used to estimate which groups of cytokines, cytokine-related factors, or chemokines could best distinguish a particular group of patients. For prepatients, characteristic changes were related to both the Th1 and Th2 lineage, and to Treg cells, representing the adaptive immune system, the authors wrote. Elevation of IL-17 levels did not reach statistical significance.

Levels of at least two-thirds of the cytokines or cytokine-related factors were above the median values for control subjects in 50 of 85 prepatients.

Of the chemokines, MCP-1 and MIP-1 alpha levels were significantly increased in prepatients, compared with controls, as were the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte–colony stimulating factor (G-CSF).

When the authors calculated the sensitivity and specificity of different factors for the development of RA in prepatients, they found that after anti-CCP antibodies and IgM rheumatoid factor (IgM-RF), eotaxin had the highest sensitivity (22.4%) and specificity (95.3%), with an odds ratio of 5.8. About one-half of the cytokines and cytokine-related factors that had significant predicative value for the development of RA in prepatients were related to Th1, Th2, and Treg cells. When all analyzed factors and anti-CCP antibodies were included, the sensitivity level rose to 51.2%, with a specificity of 91.9% for predicting the development of RA among prepatients and control subjects.

The factors distinguishing individuals before and after the onset of RA represented a more general immunologic response, as well as stromal cells and angiogenic factors. After RA diagnosis, significant increases were seen for most of the factors that were measured. IL-17 concentrations actually decreased after RA diagnosis. “This observation endorses the role of IL-17 in the initiating phase [of RA], and, as the pathogenesis progresses, other factors are subsequently brought into action,” wrote the authors (Arthritis Rheum. 2010;62:383-91).

Although the authors were unable to conclude which agent initiates RA pathogenesis, they suggested that their findings present an opportunity for better predicting the risk of developing RA and intervening at an early stage to possibly prevent disease progression.

Elevated concentrations of proinflammatory cytokines, cytokine-related factors, and chemokines, indicating activation of the immune system, have been found in the blood of people years before they developed symptoms of rheumatoid arthritis that involved the joints, according to a report by Heidi Kokkonen and coinvestigators at Umeå (Sweden) University. The study was published in the February 2010 issue of Arthritis and Rheumatism.

By comparing blood samples of people diagnosed with RA to normal controls and “prepatients” (those who go on to develop RA), investigators said that they hope the results will help predict an individual's risk of developing RA.

The investigators analyzed samples from the Medical Biobank of Northern Sweden, which invites all adult individuals from the county of Västerbotten to contribute blood samples. Within this population-based cohort, there were 86 individuals who went on develop inflammatory joint disease that fulfilled American College of Rheumatology classification criteria for RA after their donation of blood. For these prepatients, the median time predating the onset of symptoms was 3.3 years (range, 1.1-5 years). Of the 86 prepatients, 69 also provided blood samples at the time of RA diagnosis. For every prepatient, three control subjects were randomly selected from the Biobank register and matched for sex, age, and area of residence.

Several cytokines, cytokine-related factors, and chemokines were upregulated in prepatients, compared with controls. The greatest increases were noted for the Th2-related cytokines, eotaxin, and interleukin-4, with elevated levels also observed for Th1 cytokines, IL-12, interferon-gamma, and IL-10.

A multivariate classification algorithm known as the random forest method, similar to decision trees, was used to estimate which groups of cytokines, cytokine-related factors, or chemokines could best distinguish a particular group of patients. For prepatients, characteristic changes were related to both the Th1 and Th2 lineage, and to Treg cells, representing the adaptive immune system, the authors wrote. Elevation of IL-17 levels did not reach statistical significance.

Levels of at least two-thirds of the cytokines or cytokine-related factors were above the median values for control subjects in 50 of 85 prepatients.

Of the chemokines, MCP-1 and MIP-1 alpha levels were significantly increased in prepatients, compared with controls, as were the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte–colony stimulating factor (G-CSF).

When the authors calculated the sensitivity and specificity of different factors for the development of RA in prepatients, they found that after anti-CCP antibodies and IgM rheumatoid factor (IgM-RF), eotaxin had the highest sensitivity (22.4%) and specificity (95.3%), with an odds ratio of 5.8. About one-half of the cytokines and cytokine-related factors that had significant predicative value for the development of RA in prepatients were related to Th1, Th2, and Treg cells. When all analyzed factors and anti-CCP antibodies were included, the sensitivity level rose to 51.2%, with a specificity of 91.9% for predicting the development of RA among prepatients and control subjects.

The factors distinguishing individuals before and after the onset of RA represented a more general immunologic response, as well as stromal cells and angiogenic factors. After RA diagnosis, significant increases were seen for most of the factors that were measured. IL-17 concentrations actually decreased after RA diagnosis. “This observation endorses the role of IL-17 in the initiating phase [of RA], and, as the pathogenesis progresses, other factors are subsequently brought into action,” wrote the authors (Arthritis Rheum. 2010;62:383-91).

Although the authors were unable to conclude which agent initiates RA pathogenesis, they suggested that their findings present an opportunity for better predicting the risk of developing RA and intervening at an early stage to possibly prevent disease progression.