Rheumatoid Arthritis

WASHINGTON — Heterotopic ossification of the elbow usually occurs within 6 weeks of fractures and other injuries, and surgery is best timed at about 6 months after the problem becomes apparent, Thomas Fischer, M.D., said at the annual meeting of the American Academy of Orthopaedic Surgeons.

While most heterotopic ossification forms as a result of trauma, it also can develop in patients who have had repetitive interventions on the elbow or prolonged immobilization, as well as in patients with ankylosing spondylitis or hypertrophic osteoarthritis, noted Dr. Fischer of Indiana University Medical Center and Indiana Hand Center, Indianapolis.

Physicians have routinely delayed surgical resection for years, but now it appears that initiating surgery at 6 months—or possibly even earlier—is ideal, he said.

Muscle atrophy, cartilage degeneration, and capsular and ligamentous contracture tend to be less severe with earlier intervention. Resection is easier, and patients recover faster. Patients must have enough time before surgical resection, however, to recover from the often numerous orthopedic injuries and trauma—either local or systemic—that cause the heterotopic ossification, and the area must be well demarcated, he said.

Six months gives most patients time to resolve many of their injuries, Dr. Fischer explained in a later interview. It gives the extremity time to resolve injury edema, and by 6 months, the heterotopic ossification is not usually going to grow in extent or spread; “the limits of its area are well determined.”

“My partner does [surgery] at 3-4 months,” he said. Dr. Fischer told physicians at the meeting that he prefers to wait 6 months. Patients need to be recovered and cooperative enough to participate in an “immediate and fast-paced postop functional aftercare program,” Dr. Fischer said. It's helpful if therapists get involved preoperatively, he noted, partly to assess patients' ability to persist with exercises after surgery.

The incidence of heterotopic ossification has varied significantly from study to study and by the type of precipitating injury or trauma. The literature indicates that about 3% of those with simple dislocation, 1%-3% of those with burns, 16%-38% of those with fracture and dislocation, and 76%-89% of those with head injury and elbow trauma, for instance, develop it.

“I don't have a good number to quote my patients for what their risk of [heterotopic ossification] is, but whenever I see fractures and injuries around the elbow, I tell them that the 2- to 6-week period after injury is the chief period of incidence,” said Dr. Fischer, adding that most of his patients with heterotopic ossification have been critically injured. “I personally haven't seen the onset of [heterotopic ossification] after 6 weeks.”

The mere presence of heterotopic ossification is “not necessarily an indication for surgery,” he said. “I'm talking about [ossification] that results in a significant loss of motion, and loss of function of the upper extremity.”

A 50% reduction in elbow mobility can reduce upper extremity function by almost 80%, he noted. In addition to local swelling, edema, and warmth, the physical exam reveals a “doorstop effect” with flexion and extension, “where you feel a mechanically rigid end point,” Dr. Fischer said.

With the exception of pediatric patients, who can “sometimes spontaneously resorb heterotopic ossification,” most cases involving the elbow result in progressive loss of motion, he said.

Knowledge of the pathophysiology of heterotopic ossification is improving. Ectopic bone is known to be more metabolically active than native bone and is not covered by periosteum. In some cases, up to two times the normal number of osteoblasts have been found in ectopic bone.

Bone scans used to be routine for the evaluation of possible heterotopic ossification, but “based on the latest literature, I can't see a reason to use [them] anymore,” Dr. Fischer said. “It's not the meter we thought it was.”

MRIs “don't help me a lot either because I can't tell the difference between dark spots from calcium and dark spots from other things,” he said. High-definition CT is more useful. “I can use this as a map in the operating room—the definition of the planes between bone and soft tissue is much better,” Dr. Fischer said.

WASHINGTON — Heterotopic ossification of the elbow usually occurs within 6 weeks of fractures and other injuries, and surgery is best timed at about 6 months after the problem becomes apparent, Thomas Fischer, M.D., said at the annual meeting of the American Academy of Orthopaedic Surgeons.

While most heterotopic ossification forms as a result of trauma, it also can develop in patients who have had repetitive interventions on the elbow or prolonged immobilization, as well as in patients with ankylosing spondylitis or hypertrophic osteoarthritis, noted Dr. Fischer of Indiana University Medical Center and Indiana Hand Center, Indianapolis.

Physicians have routinely delayed surgical resection for years, but now it appears that initiating surgery at 6 months—or possibly even earlier—is ideal, he said.

Muscle atrophy, cartilage degeneration, and capsular and ligamentous contracture tend to be less severe with earlier intervention. Resection is easier, and patients recover faster. Patients must have enough time before surgical resection, however, to recover from the often numerous orthopedic injuries and trauma—either local or systemic—that cause the heterotopic ossification, and the area must be well demarcated, he said.

Six months gives most patients time to resolve many of their injuries, Dr. Fischer explained in a later interview. It gives the extremity time to resolve injury edema, and by 6 months, the heterotopic ossification is not usually going to grow in extent or spread; “the limits of its area are well determined.”

“My partner does [surgery] at 3-4 months,” he said. Dr. Fischer told physicians at the meeting that he prefers to wait 6 months. Patients need to be recovered and cooperative enough to participate in an “immediate and fast-paced postop functional aftercare program,” Dr. Fischer said. It's helpful if therapists get involved preoperatively, he noted, partly to assess patients' ability to persist with exercises after surgery.

The incidence of heterotopic ossification has varied significantly from study to study and by the type of precipitating injury or trauma. The literature indicates that about 3% of those with simple dislocation, 1%-3% of those with burns, 16%-38% of those with fracture and dislocation, and 76%-89% of those with head injury and elbow trauma, for instance, develop it.

“I don't have a good number to quote my patients for what their risk of [heterotopic ossification] is, but whenever I see fractures and injuries around the elbow, I tell them that the 2- to 6-week period after injury is the chief period of incidence,” said Dr. Fischer, adding that most of his patients with heterotopic ossification have been critically injured. “I personally haven't seen the onset of [heterotopic ossification] after 6 weeks.”

The mere presence of heterotopic ossification is “not necessarily an indication for surgery,” he said. “I'm talking about [ossification] that results in a significant loss of motion, and loss of function of the upper extremity.”

A 50% reduction in elbow mobility can reduce upper extremity function by almost 80%, he noted. In addition to local swelling, edema, and warmth, the physical exam reveals a “doorstop effect” with flexion and extension, “where you feel a mechanically rigid end point,” Dr. Fischer said.

With the exception of pediatric patients, who can “sometimes spontaneously resorb heterotopic ossification,” most cases involving the elbow result in progressive loss of motion, he said.

Knowledge of the pathophysiology of heterotopic ossification is improving. Ectopic bone is known to be more metabolically active than native bone and is not covered by periosteum. In some cases, up to two times the normal number of osteoblasts have been found in ectopic bone.

Bone scans used to be routine for the evaluation of possible heterotopic ossification, but “based on the latest literature, I can't see a reason to use [them] anymore,” Dr. Fischer said. “It's not the meter we thought it was.”

MRIs “don't help me a lot either because I can't tell the difference between dark spots from calcium and dark spots from other things,” he said. High-definition CT is more useful. “I can use this as a map in the operating room—the definition of the planes between bone and soft tissue is much better,” Dr. Fischer said.

WASHINGTON — Heterotopic ossification of the elbow usually occurs within 6 weeks of fractures and other injuries, and surgery is best timed at about 6 months after the problem becomes apparent, Thomas Fischer, M.D., said at the annual meeting of the American Academy of Orthopaedic Surgeons.

While most heterotopic ossification forms as a result of trauma, it also can develop in patients who have had repetitive interventions on the elbow or prolonged immobilization, as well as in patients with ankylosing spondylitis or hypertrophic osteoarthritis, noted Dr. Fischer of Indiana University Medical Center and Indiana Hand Center, Indianapolis.

Physicians have routinely delayed surgical resection for years, but now it appears that initiating surgery at 6 months—or possibly even earlier—is ideal, he said.

Muscle atrophy, cartilage degeneration, and capsular and ligamentous contracture tend to be less severe with earlier intervention. Resection is easier, and patients recover faster. Patients must have enough time before surgical resection, however, to recover from the often numerous orthopedic injuries and trauma—either local or systemic—that cause the heterotopic ossification, and the area must be well demarcated, he said.

Six months gives most patients time to resolve many of their injuries, Dr. Fischer explained in a later interview. It gives the extremity time to resolve injury edema, and by 6 months, the heterotopic ossification is not usually going to grow in extent or spread; “the limits of its area are well determined.”

“My partner does [surgery] at 3-4 months,” he said. Dr. Fischer told physicians at the meeting that he prefers to wait 6 months. Patients need to be recovered and cooperative enough to participate in an “immediate and fast-paced postop functional aftercare program,” Dr. Fischer said. It's helpful if therapists get involved preoperatively, he noted, partly to assess patients' ability to persist with exercises after surgery.

The incidence of heterotopic ossification has varied significantly from study to study and by the type of precipitating injury or trauma. The literature indicates that about 3% of those with simple dislocation, 1%-3% of those with burns, 16%-38% of those with fracture and dislocation, and 76%-89% of those with head injury and elbow trauma, for instance, develop it.

“I don't have a good number to quote my patients for what their risk of [heterotopic ossification] is, but whenever I see fractures and injuries around the elbow, I tell them that the 2- to 6-week period after injury is the chief period of incidence,” said Dr. Fischer, adding that most of his patients with heterotopic ossification have been critically injured. “I personally haven't seen the onset of [heterotopic ossification] after 6 weeks.”

The mere presence of heterotopic ossification is “not necessarily an indication for surgery,” he said. “I'm talking about [ossification] that results in a significant loss of motion, and loss of function of the upper extremity.”

A 50% reduction in elbow mobility can reduce upper extremity function by almost 80%, he noted. In addition to local swelling, edema, and warmth, the physical exam reveals a “doorstop effect” with flexion and extension, “where you feel a mechanically rigid end point,” Dr. Fischer said.

With the exception of pediatric patients, who can “sometimes spontaneously resorb heterotopic ossification,” most cases involving the elbow result in progressive loss of motion, he said.

Knowledge of the pathophysiology of heterotopic ossification is improving. Ectopic bone is known to be more metabolically active than native bone and is not covered by periosteum. In some cases, up to two times the normal number of osteoblasts have been found in ectopic bone.

Bone scans used to be routine for the evaluation of possible heterotopic ossification, but “based on the latest literature, I can't see a reason to use [them] anymore,” Dr. Fischer said. “It's not the meter we thought it was.”

MRIs “don't help me a lot either because I can't tell the difference between dark spots from calcium and dark spots from other things,” he said. High-definition CT is more useful. “I can use this as a map in the operating room—the definition of the planes between bone and soft tissue is much better,” Dr. Fischer said.

Short-term use of celecoxib did not affect renal function in patients with decompensated liver cirrhosis and ascites who participated in a small randomized trial.

In the double-blind study of 28 patients conducted by Joan Clària, Ph.D., of the University of Barcelona (Spain) and his colleagues, the glomerular filtration rate, renal plasma flow, and serum creatine levels worsened significantly in patients who received five therapeutic doses of naproxen during a 3-day period, compared with baseline values. None of these changes occurred in patients who received five therapeutic doses of celecoxib (Celebrex) or placebo (Hepatology 2005;41:579-87).

Naproxen significantly inhibited platelet aggregation and ex vivo thromboxane B2 synthesis and decreased urinary excretion of prostaglandin E2. Naproxen patients had significantly reduced diuretic and natriuretic responses to furosemide, which normally increases urine volume and urinary sodium excretion. Short-term celecoxib therapy does not reduce platelet or renal function, or response to diuretic drugs, in patients with decompensated cirrhosis, the authors concluded.

The analysis excluded seven patients who had hepatorenal syndrome at baseline and three patients who did not have measurements available to calculate glomerular filtration rate or renal plasma flow. A total of 20 patients who were initially randomized did not receive a study drug because their plasma renin activity was less than 4 ng/mL/per hour.

Short-term use of celecoxib did not affect renal function in patients with decompensated liver cirrhosis and ascites who participated in a small randomized trial.

In the double-blind study of 28 patients conducted by Joan Clària, Ph.D., of the University of Barcelona (Spain) and his colleagues, the glomerular filtration rate, renal plasma flow, and serum creatine levels worsened significantly in patients who received five therapeutic doses of naproxen during a 3-day period, compared with baseline values. None of these changes occurred in patients who received five therapeutic doses of celecoxib (Celebrex) or placebo (Hepatology 2005;41:579-87).

Naproxen significantly inhibited platelet aggregation and ex vivo thromboxane B2 synthesis and decreased urinary excretion of prostaglandin E2. Naproxen patients had significantly reduced diuretic and natriuretic responses to furosemide, which normally increases urine volume and urinary sodium excretion. Short-term celecoxib therapy does not reduce platelet or renal function, or response to diuretic drugs, in patients with decompensated cirrhosis, the authors concluded.

The analysis excluded seven patients who had hepatorenal syndrome at baseline and three patients who did not have measurements available to calculate glomerular filtration rate or renal plasma flow. A total of 20 patients who were initially randomized did not receive a study drug because their plasma renin activity was less than 4 ng/mL/per hour.

Short-term use of celecoxib did not affect renal function in patients with decompensated liver cirrhosis and ascites who participated in a small randomized trial.

In the double-blind study of 28 patients conducted by Joan Clària, Ph.D., of the University of Barcelona (Spain) and his colleagues, the glomerular filtration rate, renal plasma flow, and serum creatine levels worsened significantly in patients who received five therapeutic doses of naproxen during a 3-day period, compared with baseline values. None of these changes occurred in patients who received five therapeutic doses of celecoxib (Celebrex) or placebo (Hepatology 2005;41:579-87).

Naproxen significantly inhibited platelet aggregation and ex vivo thromboxane B2 synthesis and decreased urinary excretion of prostaglandin E2. Naproxen patients had significantly reduced diuretic and natriuretic responses to furosemide, which normally increases urine volume and urinary sodium excretion. Short-term celecoxib therapy does not reduce platelet or renal function, or response to diuretic drugs, in patients with decompensated cirrhosis, the authors concluded.

The analysis excluded seven patients who had hepatorenal syndrome at baseline and three patients who did not have measurements available to calculate glomerular filtration rate or renal plasma flow. A total of 20 patients who were initially randomized did not receive a study drug because their plasma renin activity was less than 4 ng/mL/per hour.

WASHINGTON — Patients who undergo anterior cruciate ligament reconstruction may be at increased risk of developing clinical osteoarthritis, according to results from a 10-year follow-up study of 90 patients.

Interestingly, many patients reported not being aware of their condition, and nearly half noted that it had not affected their activity level, according to Justin Roe, M.D., who presented the findings at the annual meeting of the American Academy of Orthopaedic Surgeons.

Patients initially underwent endoscopic anterior cruciate ligament (ACL) reconstruction with patellar tendon autograft and interference screw fixation. The mean age was 25 years, and the patients were evaluated annually for 5 years, and again at 7 and 10 years after surgery, said Dr. Roe of the North Sydney Orthopaedic Sports Medicine Centre, Australia.

Outcomes were measured using the International Knee Documentation Committee (IKDC) Standard Evaluation and Lysholm knee scoring. Radiographs were taken at 2, 5, 7, and 10 years after surgery.

Five-year data were previously published. At 10 years, 84 patients still had intact grafts (six had ruptures); of these, 75 were evaluated. In that group, 18 patients had a contralateral rupture and 8 had surgery for meniscal or chondral symptoms.

Based on scores and radiographs, 48% had mild to moderate evidence of osteoarthritis, said Dr. Roe. At 2 years, 33% had an increase in pain when kneeling; by 10 years, 58% said they felt increased pain. A quarter of the patients had a loss of range of extension, compared with the contralateral knee, but it was less than five degrees in 20% of that group.

On laxity testing, 97% had a grade of 0-1 on Lachman and pivot shift testing, and 81% had less than 3 mm of tibial displacement.

Despite the clinical findings, 96% of patients said they felt their knee function was normal, and about half were still taking part in moderate to strenuous activity. The patients who were not as active said it was because of other lifestyle issues, Dr. Roe said.

Predictors of abnormal knee radiographs included increased age at surgery, increased laxity at 2 years and swelling with activity at 10 years, he said.

It is not clear why osteoarthritis is appearing in these knees. There is an injury to the entire knee with an ACL rupture. It's probable that the injury—and not the subsequent surgery—contributed most to the development of arthritis, he surmised.

WASHINGTON — Patients who undergo anterior cruciate ligament reconstruction may be at increased risk of developing clinical osteoarthritis, according to results from a 10-year follow-up study of 90 patients.

Interestingly, many patients reported not being aware of their condition, and nearly half noted that it had not affected their activity level, according to Justin Roe, M.D., who presented the findings at the annual meeting of the American Academy of Orthopaedic Surgeons.

Patients initially underwent endoscopic anterior cruciate ligament (ACL) reconstruction with patellar tendon autograft and interference screw fixation. The mean age was 25 years, and the patients were evaluated annually for 5 years, and again at 7 and 10 years after surgery, said Dr. Roe of the North Sydney Orthopaedic Sports Medicine Centre, Australia.

Outcomes were measured using the International Knee Documentation Committee (IKDC) Standard Evaluation and Lysholm knee scoring. Radiographs were taken at 2, 5, 7, and 10 years after surgery.

Five-year data were previously published. At 10 years, 84 patients still had intact grafts (six had ruptures); of these, 75 were evaluated. In that group, 18 patients had a contralateral rupture and 8 had surgery for meniscal or chondral symptoms.

Based on scores and radiographs, 48% had mild to moderate evidence of osteoarthritis, said Dr. Roe. At 2 years, 33% had an increase in pain when kneeling; by 10 years, 58% said they felt increased pain. A quarter of the patients had a loss of range of extension, compared with the contralateral knee, but it was less than five degrees in 20% of that group.

On laxity testing, 97% had a grade of 0-1 on Lachman and pivot shift testing, and 81% had less than 3 mm of tibial displacement.

Despite the clinical findings, 96% of patients said they felt their knee function was normal, and about half were still taking part in moderate to strenuous activity. The patients who were not as active said it was because of other lifestyle issues, Dr. Roe said.

Predictors of abnormal knee radiographs included increased age at surgery, increased laxity at 2 years and swelling with activity at 10 years, he said.

It is not clear why osteoarthritis is appearing in these knees. There is an injury to the entire knee with an ACL rupture. It's probable that the injury—and not the subsequent surgery—contributed most to the development of arthritis, he surmised.

WASHINGTON — Patients who undergo anterior cruciate ligament reconstruction may be at increased risk of developing clinical osteoarthritis, according to results from a 10-year follow-up study of 90 patients.

Interestingly, many patients reported not being aware of their condition, and nearly half noted that it had not affected their activity level, according to Justin Roe, M.D., who presented the findings at the annual meeting of the American Academy of Orthopaedic Surgeons.

Patients initially underwent endoscopic anterior cruciate ligament (ACL) reconstruction with patellar tendon autograft and interference screw fixation. The mean age was 25 years, and the patients were evaluated annually for 5 years, and again at 7 and 10 years after surgery, said Dr. Roe of the North Sydney Orthopaedic Sports Medicine Centre, Australia.

Outcomes were measured using the International Knee Documentation Committee (IKDC) Standard Evaluation and Lysholm knee scoring. Radiographs were taken at 2, 5, 7, and 10 years after surgery.

Five-year data were previously published. At 10 years, 84 patients still had intact grafts (six had ruptures); of these, 75 were evaluated. In that group, 18 patients had a contralateral rupture and 8 had surgery for meniscal or chondral symptoms.

Based on scores and radiographs, 48% had mild to moderate evidence of osteoarthritis, said Dr. Roe. At 2 years, 33% had an increase in pain when kneeling; by 10 years, 58% said they felt increased pain. A quarter of the patients had a loss of range of extension, compared with the contralateral knee, but it was less than five degrees in 20% of that group.

On laxity testing, 97% had a grade of 0-1 on Lachman and pivot shift testing, and 81% had less than 3 mm of tibial displacement.

Despite the clinical findings, 96% of patients said they felt their knee function was normal, and about half were still taking part in moderate to strenuous activity. The patients who were not as active said it was because of other lifestyle issues, Dr. Roe said.

Predictors of abnormal knee radiographs included increased age at surgery, increased laxity at 2 years and swelling with activity at 10 years, he said.

It is not clear why osteoarthritis is appearing in these knees. There is an injury to the entire knee with an ACL rupture. It's probable that the injury—and not the subsequent surgery—contributed most to the development of arthritis, he surmised.

WASHINGTON — Elbow contractures can be treated arthroscopically with better efficacy and faster patient recovery than traditional open surgical techniques, Shawn W. O'Driscoll, M.D., said at the annual meeting of the American Academy of Orthopedic Surgeons.

It's no longer a given that complicated procedures must be converted to open surgery, said Dr. O'Driscoll, professor of orthopedics at the Mayo Clinic in Rochester, Minn. Instead, the deciding factor should be the surgeon's level of experience.

Published data on efficacy are limited, and indications for the arthroscopic approach “are still evolving,” he said during a session on elbow stiffness and arthritis. But “it's pretty clear that [arthroscopic contracture release] is effective.”

An analysis of results from 10 reports of open procedures and 6 small reports of arthroscopic procedures shows that more significant improvements are gained in extension, flexion, and total arc of elbow motion with the arthroscopic approach, compared with the open surgical approach.

Average flexion, for instance, increased from 107 degrees preoperatively to 123 degrees postoperatively when contractures were treated with open surgery.

In comparison, with the arthroscopic approach, flexion increased from 114 degrees before the operation to 133 degrees after the operation, Dr. O'Driscoll said.

The main consideration—and the “one factor that creates anxiety and limits the indications for this operation”—is the risk of ulnar nerve injury, he said.

The arthroscopy procedure involves a straightforward, predictable sequence of steps, but it is “more complex … the difficulty in learning it is higher [than with open surgery], and the risk is higher when you're learning it,” Dr. O'Driscoll noted.

“There was a time when I thought this would never be a safe operation in anyone's hands,” he said. “Now, I think it's an unsafe operation” in the hands of surgeons who do not have the necessary skills and experience.

“I've done over 300 cases now, and my complication rate is lower than it is with open surgery. Patient recovery is faster, and efficacy is better, from my experience,” he said.

Dr. O'Driscoll uses an anterior approach to arthroscopic release that involves synovectomy before osteectomy, and then capsulectomy. He recommended using a scope in the anterolateral or proximal anteromedial portal and a retractor in the proximal anterolateral portal. A second retractor can be used in the anteromedial portal if necessary.

“It's necessary for safety and predictability reasons to use a retractor,” he said. Although some say otherwise, “you need to retract the tissues and create a space within which to work.

“And we don't rely on capsular distension, because in the stiff elbow, it's not possible to distend the capsule by very much,” he noted. “If you try to do it, you get a big fat swollen elbow. You want to avoid that; the elbow should be soft until near the end of the operation.”

A study reported more than 10 years ago showed that the capsular volume capacity is about 25 mL in the normal elbow but only about 6 mL in the contracted elbow, he said.

Dr. O'Driscoll strips the capsule off the proximal humerus and immediately releases tissue along the lateral supracondylar ridge, which “gives you some space to work, to move the scope back farther and get a bigger, better perspective.”

He removes loose bodies as they are encountered and debrides the capsule, defining it as a structure, before cutting it. He incises the capsule starting medially and progresses across laterally.

A distal lateral capsulectomy is the final and most risky step. “You need to be able to see the nerve … or know with absolute certainty where the nerve is and isn't,” Dr. O'Driscoll said. “If you have that degree of confidence, then you're safe to do it.”

A capsulotomy is performed from medial to lateral. The final strip of capsule over the radial nerve is released with a reverse cutting punch biopsy, as shown above. Courtesy Dr. Shawn W. O'Driscoll

WASHINGTON — Elbow contractures can be treated arthroscopically with better efficacy and faster patient recovery than traditional open surgical techniques, Shawn W. O'Driscoll, M.D., said at the annual meeting of the American Academy of Orthopedic Surgeons.

It's no longer a given that complicated procedures must be converted to open surgery, said Dr. O'Driscoll, professor of orthopedics at the Mayo Clinic in Rochester, Minn. Instead, the deciding factor should be the surgeon's level of experience.

Published data on efficacy are limited, and indications for the arthroscopic approach “are still evolving,” he said during a session on elbow stiffness and arthritis. But “it's pretty clear that [arthroscopic contracture release] is effective.”

An analysis of results from 10 reports of open procedures and 6 small reports of arthroscopic procedures shows that more significant improvements are gained in extension, flexion, and total arc of elbow motion with the arthroscopic approach, compared with the open surgical approach.

Average flexion, for instance, increased from 107 degrees preoperatively to 123 degrees postoperatively when contractures were treated with open surgery.

In comparison, with the arthroscopic approach, flexion increased from 114 degrees before the operation to 133 degrees after the operation, Dr. O'Driscoll said.

The main consideration—and the “one factor that creates anxiety and limits the indications for this operation”—is the risk of ulnar nerve injury, he said.

The arthroscopy procedure involves a straightforward, predictable sequence of steps, but it is “more complex … the difficulty in learning it is higher [than with open surgery], and the risk is higher when you're learning it,” Dr. O'Driscoll noted.

“There was a time when I thought this would never be a safe operation in anyone's hands,” he said. “Now, I think it's an unsafe operation” in the hands of surgeons who do not have the necessary skills and experience.

“I've done over 300 cases now, and my complication rate is lower than it is with open surgery. Patient recovery is faster, and efficacy is better, from my experience,” he said.

Dr. O'Driscoll uses an anterior approach to arthroscopic release that involves synovectomy before osteectomy, and then capsulectomy. He recommended using a scope in the anterolateral or proximal anteromedial portal and a retractor in the proximal anterolateral portal. A second retractor can be used in the anteromedial portal if necessary.

“It's necessary for safety and predictability reasons to use a retractor,” he said. Although some say otherwise, “you need to retract the tissues and create a space within which to work.

“And we don't rely on capsular distension, because in the stiff elbow, it's not possible to distend the capsule by very much,” he noted. “If you try to do it, you get a big fat swollen elbow. You want to avoid that; the elbow should be soft until near the end of the operation.”

A study reported more than 10 years ago showed that the capsular volume capacity is about 25 mL in the normal elbow but only about 6 mL in the contracted elbow, he said.

Dr. O'Driscoll strips the capsule off the proximal humerus and immediately releases tissue along the lateral supracondylar ridge, which “gives you some space to work, to move the scope back farther and get a bigger, better perspective.”

He removes loose bodies as they are encountered and debrides the capsule, defining it as a structure, before cutting it. He incises the capsule starting medially and progresses across laterally.

A distal lateral capsulectomy is the final and most risky step. “You need to be able to see the nerve … or know with absolute certainty where the nerve is and isn't,” Dr. O'Driscoll said. “If you have that degree of confidence, then you're safe to do it.”

A capsulotomy is performed from medial to lateral. The final strip of capsule over the radial nerve is released with a reverse cutting punch biopsy, as shown above. Courtesy Dr. Shawn W. O'Driscoll

WASHINGTON — Elbow contractures can be treated arthroscopically with better efficacy and faster patient recovery than traditional open surgical techniques, Shawn W. O'Driscoll, M.D., said at the annual meeting of the American Academy of Orthopedic Surgeons.

It's no longer a given that complicated procedures must be converted to open surgery, said Dr. O'Driscoll, professor of orthopedics at the Mayo Clinic in Rochester, Minn. Instead, the deciding factor should be the surgeon's level of experience.

Published data on efficacy are limited, and indications for the arthroscopic approach “are still evolving,” he said during a session on elbow stiffness and arthritis. But “it's pretty clear that [arthroscopic contracture release] is effective.”

An analysis of results from 10 reports of open procedures and 6 small reports of arthroscopic procedures shows that more significant improvements are gained in extension, flexion, and total arc of elbow motion with the arthroscopic approach, compared with the open surgical approach.

Average flexion, for instance, increased from 107 degrees preoperatively to 123 degrees postoperatively when contractures were treated with open surgery.

In comparison, with the arthroscopic approach, flexion increased from 114 degrees before the operation to 133 degrees after the operation, Dr. O'Driscoll said.

The main consideration—and the “one factor that creates anxiety and limits the indications for this operation”—is the risk of ulnar nerve injury, he said.

The arthroscopy procedure involves a straightforward, predictable sequence of steps, but it is “more complex … the difficulty in learning it is higher [than with open surgery], and the risk is higher when you're learning it,” Dr. O'Driscoll noted.

“There was a time when I thought this would never be a safe operation in anyone's hands,” he said. “Now, I think it's an unsafe operation” in the hands of surgeons who do not have the necessary skills and experience.

“I've done over 300 cases now, and my complication rate is lower than it is with open surgery. Patient recovery is faster, and efficacy is better, from my experience,” he said.

Dr. O'Driscoll uses an anterior approach to arthroscopic release that involves synovectomy before osteectomy, and then capsulectomy. He recommended using a scope in the anterolateral or proximal anteromedial portal and a retractor in the proximal anterolateral portal. A second retractor can be used in the anteromedial portal if necessary.

“It's necessary for safety and predictability reasons to use a retractor,” he said. Although some say otherwise, “you need to retract the tissues and create a space within which to work.

“And we don't rely on capsular distension, because in the stiff elbow, it's not possible to distend the capsule by very much,” he noted. “If you try to do it, you get a big fat swollen elbow. You want to avoid that; the elbow should be soft until near the end of the operation.”

A study reported more than 10 years ago showed that the capsular volume capacity is about 25 mL in the normal elbow but only about 6 mL in the contracted elbow, he said.

Dr. O'Driscoll strips the capsule off the proximal humerus and immediately releases tissue along the lateral supracondylar ridge, which “gives you some space to work, to move the scope back farther and get a bigger, better perspective.”

He removes loose bodies as they are encountered and debrides the capsule, defining it as a structure, before cutting it. He incises the capsule starting medially and progresses across laterally.

A distal lateral capsulectomy is the final and most risky step. “You need to be able to see the nerve … or know with absolute certainty where the nerve is and isn't,” Dr. O'Driscoll said. “If you have that degree of confidence, then you're safe to do it.”

A capsulotomy is performed from medial to lateral. The final strip of capsule over the radial nerve is released with a reverse cutting punch biopsy, as shown above. Courtesy Dr. Shawn W. O'Driscoll

CHICAGO — Waist circumference appears to be an important and previously unrecognized indicator of knee osteoarthritis risk in men, Lauren M. Abbate reported at the 2004 World Congress on Osteoarthritis.

Men with a waist circumference greater than 108 cm were twice as likely to have osteoarthritis of the knee than were men with a waist circumference less than 95 cm, according to findings from the Johnston County Osteoarthritis Project, which involved a randomly selected group of 849 women and 458 men from Johnston County in North Carolina.

Among women there was a stronger association between body mass index (BMI) or weight and knee compared with men, added Ms. Abbate, an epidemiology doctoral student at the University of North Carolina at Chapel Hill.

Large waist circumference among women was associated with an increased risk of knee osteoarthritis in the study, but not independently of BMI.

This finding is similar to data reported from the population-based Chingford Study, she said.

Previous osteoarthritis studies have shown that the effect of BMI differs by gender, but have not evaluated the effect using measures of body fat distribution or composition.

Investigators at the University of North Carolina's Thurston Arthritis Research Center assessed body composition using dual-energy x-ray absorptiometry (DXA), and assessed body fat distribution using waist and hip circumferences.

Radiographic knee osteoarthritis was defined as a Kellgren-Lawrence grade of 2 or more, Ms. Abbate said.

The mean age of the participants was 65 years for both men and women, 27% of the women and 16% of the men were African American.

In women, the mean BMI was 30 kg/m2 and mean weight was 77 kg, and in men, mean BMI was 29 kg/m2 and mean weight 89 kg.

Body composition variables associated with higher odds of knee osteoarthritis in women included fat mass (OR 4.47), percent fat mass (OR 3.25), and lean mass (OR 3.18).

By contrast, in men, waist circumference was the only variable significantly associated with the knee osteoarthritis (2.47). Waist size was also significantly associated with the disease in women (OR 4.33).

Waist-to-hip ratio was not significantly associated with knee osteoarthritis in women (OR 1.56) or men (OR 1.21).

After adjustment for BMI, none of the associations with body composition or body fat distribution variables and knee osteoarthritis in women remained significant.

Waist circumference in men, however, remained a statistically significant predictor of knee osteoarthritis (OR 3.46), Ms. Abbate said.

The findings underscore the importance of weight management for osteoarthritis, particularly, Ms. Abbate said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Waist circumference in men is a previously overlooked risk factor for knee osteoarthritis, above and beyond BMI, said senior author and UNC associate professor of medicine Joanne M. Jordan, M.D.

“This study suggests that in women, BMI is highly associated with radiographic knee osteoarthritis, and that other measures of obesity such as body composition may not be necessary beyond BMI,” Dr. Jordan said. “It also suggests that BMI may not be the best measurement of obesity when assessing risk among men, and that we should investigate the waist circumference measurements in more detail,” she said.

Waist circumference is garnering attention in the cardiovascular literature, where studies suggest that it is increasingly replacing BMI as the preferred indicator of obesity-related cardiovascular risk.

CHICAGO — Waist circumference appears to be an important and previously unrecognized indicator of knee osteoarthritis risk in men, Lauren M. Abbate reported at the 2004 World Congress on Osteoarthritis.

Men with a waist circumference greater than 108 cm were twice as likely to have osteoarthritis of the knee than were men with a waist circumference less than 95 cm, according to findings from the Johnston County Osteoarthritis Project, which involved a randomly selected group of 849 women and 458 men from Johnston County in North Carolina.

Among women there was a stronger association between body mass index (BMI) or weight and knee compared with men, added Ms. Abbate, an epidemiology doctoral student at the University of North Carolina at Chapel Hill.

Large waist circumference among women was associated with an increased risk of knee osteoarthritis in the study, but not independently of BMI.

This finding is similar to data reported from the population-based Chingford Study, she said.

Previous osteoarthritis studies have shown that the effect of BMI differs by gender, but have not evaluated the effect using measures of body fat distribution or composition.

Investigators at the University of North Carolina's Thurston Arthritis Research Center assessed body composition using dual-energy x-ray absorptiometry (DXA), and assessed body fat distribution using waist and hip circumferences.

Radiographic knee osteoarthritis was defined as a Kellgren-Lawrence grade of 2 or more, Ms. Abbate said.

The mean age of the participants was 65 years for both men and women, 27% of the women and 16% of the men were African American.

In women, the mean BMI was 30 kg/m2 and mean weight was 77 kg, and in men, mean BMI was 29 kg/m2 and mean weight 89 kg.

Body composition variables associated with higher odds of knee osteoarthritis in women included fat mass (OR 4.47), percent fat mass (OR 3.25), and lean mass (OR 3.18).

By contrast, in men, waist circumference was the only variable significantly associated with the knee osteoarthritis (2.47). Waist size was also significantly associated with the disease in women (OR 4.33).

Waist-to-hip ratio was not significantly associated with knee osteoarthritis in women (OR 1.56) or men (OR 1.21).

After adjustment for BMI, none of the associations with body composition or body fat distribution variables and knee osteoarthritis in women remained significant.

Waist circumference in men, however, remained a statistically significant predictor of knee osteoarthritis (OR 3.46), Ms. Abbate said.

The findings underscore the importance of weight management for osteoarthritis, particularly, Ms. Abbate said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Waist circumference in men is a previously overlooked risk factor for knee osteoarthritis, above and beyond BMI, said senior author and UNC associate professor of medicine Joanne M. Jordan, M.D.

“This study suggests that in women, BMI is highly associated with radiographic knee osteoarthritis, and that other measures of obesity such as body composition may not be necessary beyond BMI,” Dr. Jordan said. “It also suggests that BMI may not be the best measurement of obesity when assessing risk among men, and that we should investigate the waist circumference measurements in more detail,” she said.

Waist circumference is garnering attention in the cardiovascular literature, where studies suggest that it is increasingly replacing BMI as the preferred indicator of obesity-related cardiovascular risk.

CHICAGO — Waist circumference appears to be an important and previously unrecognized indicator of knee osteoarthritis risk in men, Lauren M. Abbate reported at the 2004 World Congress on Osteoarthritis.

Men with a waist circumference greater than 108 cm were twice as likely to have osteoarthritis of the knee than were men with a waist circumference less than 95 cm, according to findings from the Johnston County Osteoarthritis Project, which involved a randomly selected group of 849 women and 458 men from Johnston County in North Carolina.

Among women there was a stronger association between body mass index (BMI) or weight and knee compared with men, added Ms. Abbate, an epidemiology doctoral student at the University of North Carolina at Chapel Hill.

Large waist circumference among women was associated with an increased risk of knee osteoarthritis in the study, but not independently of BMI.

This finding is similar to data reported from the population-based Chingford Study, she said.

Previous osteoarthritis studies have shown that the effect of BMI differs by gender, but have not evaluated the effect using measures of body fat distribution or composition.

Investigators at the University of North Carolina's Thurston Arthritis Research Center assessed body composition using dual-energy x-ray absorptiometry (DXA), and assessed body fat distribution using waist and hip circumferences.

Radiographic knee osteoarthritis was defined as a Kellgren-Lawrence grade of 2 or more, Ms. Abbate said.

The mean age of the participants was 65 years for both men and women, 27% of the women and 16% of the men were African American.

In women, the mean BMI was 30 kg/m2 and mean weight was 77 kg, and in men, mean BMI was 29 kg/m2 and mean weight 89 kg.

Body composition variables associated with higher odds of knee osteoarthritis in women included fat mass (OR 4.47), percent fat mass (OR 3.25), and lean mass (OR 3.18).

By contrast, in men, waist circumference was the only variable significantly associated with the knee osteoarthritis (2.47). Waist size was also significantly associated with the disease in women (OR 4.33).

Waist-to-hip ratio was not significantly associated with knee osteoarthritis in women (OR 1.56) or men (OR 1.21).

After adjustment for BMI, none of the associations with body composition or body fat distribution variables and knee osteoarthritis in women remained significant.

Waist circumference in men, however, remained a statistically significant predictor of knee osteoarthritis (OR 3.46), Ms. Abbate said.

The findings underscore the importance of weight management for osteoarthritis, particularly, Ms. Abbate said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Waist circumference in men is a previously overlooked risk factor for knee osteoarthritis, above and beyond BMI, said senior author and UNC associate professor of medicine Joanne M. Jordan, M.D.

“This study suggests that in women, BMI is highly associated with radiographic knee osteoarthritis, and that other measures of obesity such as body composition may not be necessary beyond BMI,” Dr. Jordan said. “It also suggests that BMI may not be the best measurement of obesity when assessing risk among men, and that we should investigate the waist circumference measurements in more detail,” she said.

Waist circumference is garnering attention in the cardiovascular literature, where studies suggest that it is increasingly replacing BMI as the preferred indicator of obesity-related cardiovascular risk.

SNOWMASS, COLO. — Lyme disease patients without erythema migrans were thought to be rare—until they showed up more frequently than expected in a large trial of the Lyme disease vaccine, Linda K. Bockenstedt, M.D., said at a symposium sponsored by the American College of Rheumatology.

In that trial, 269 cases of Lyme disease were detected by serum assay, of which 42, or about 16%, involved patients without erythema migrans. However, those patients did have flulike symptoms, such as malaise, fever, myalgia, migratory arthralgias, occipital headache, and neck stiffness. They did not have any upper respiratory symptoms, such as cough.

Additionally, Dr. Bockenstedt of the rheumatology section at Yale University (New Haven) noted that there may soon be a way to monitor Lyme disease treatment.

A new enzyme-linked immunoabsorbent assay for Lyme disease, the C6 ELISA (Immunetics Inc.), tests for a single small peptide expressed by the Borrelia burgdorferi spirochete during active infection, instead of the whole organism.

Research has shown that antibody titers to this antigen drop fourfold when an infected individual has been successfully treated. Dr. Bockenstedt added that forthcoming study results will confirm the ability of the assay to adequately detect a drop in the antigen level.

SNOWMASS, COLO. — Lyme disease patients without erythema migrans were thought to be rare—until they showed up more frequently than expected in a large trial of the Lyme disease vaccine, Linda K. Bockenstedt, M.D., said at a symposium sponsored by the American College of Rheumatology.

In that trial, 269 cases of Lyme disease were detected by serum assay, of which 42, or about 16%, involved patients without erythema migrans. However, those patients did have flulike symptoms, such as malaise, fever, myalgia, migratory arthralgias, occipital headache, and neck stiffness. They did not have any upper respiratory symptoms, such as cough.

Additionally, Dr. Bockenstedt of the rheumatology section at Yale University (New Haven) noted that there may soon be a way to monitor Lyme disease treatment.

A new enzyme-linked immunoabsorbent assay for Lyme disease, the C6 ELISA (Immunetics Inc.), tests for a single small peptide expressed by the Borrelia burgdorferi spirochete during active infection, instead of the whole organism.

Research has shown that antibody titers to this antigen drop fourfold when an infected individual has been successfully treated. Dr. Bockenstedt added that forthcoming study results will confirm the ability of the assay to adequately detect a drop in the antigen level.

SNOWMASS, COLO. — Lyme disease patients without erythema migrans were thought to be rare—until they showed up more frequently than expected in a large trial of the Lyme disease vaccine, Linda K. Bockenstedt, M.D., said at a symposium sponsored by the American College of Rheumatology.

In that trial, 269 cases of Lyme disease were detected by serum assay, of which 42, or about 16%, involved patients without erythema migrans. However, those patients did have flulike symptoms, such as malaise, fever, myalgia, migratory arthralgias, occipital headache, and neck stiffness. They did not have any upper respiratory symptoms, such as cough.

Additionally, Dr. Bockenstedt of the rheumatology section at Yale University (New Haven) noted that there may soon be a way to monitor Lyme disease treatment.

A new enzyme-linked immunoabsorbent assay for Lyme disease, the C6 ELISA (Immunetics Inc.), tests for a single small peptide expressed by the Borrelia burgdorferi spirochete during active infection, instead of the whole organism.

Research has shown that antibody titers to this antigen drop fourfold when an infected individual has been successfully treated. Dr. Bockenstedt added that forthcoming study results will confirm the ability of the assay to adequately detect a drop in the antigen level.

SNOWMASS, COLO. — The next generation of biological agents will be therapies that capitalize on the ability of regulatory T cells to keep the immune system in check, Randy Noelle, Ph.D., predicted at a symposium sponsored by the American College of Rheumatology.

First discovered 30 years ago, regulatory T-cell research was largely sidelined until interest in the field was renewed about 5 years ago, said Dr. Noelle, a professor of immunology at the Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

“Over the past year, effective strategies have been developed to grow human regulatory T cells in vitro, and I would imagine that within a year you will see groups growing human regulatory T cells for reinfusion into patients for indications such as graft-versus-host disease,” he said.

“They will be the next wave of cell-based therapy that you will use to manage autoimmune disease,” Dr. Noelle told the audience of rheumatologists.

Regulatory T cells are the mechanism by which the body puts the brakes on the immune system functions of attack cells, or executor T cells, Dr. Noelle explained. Both regulatory T cells and executor T cells arise from CD4-positive cells. Research published last fall suggests that expression of the Lag-3 gene in CD4 cells differentiates them into regulatory T cells, which then limit the intensity of the autoimmune response (Immunity 2004;21:503-13).

Regulatory T cells represent about 5%-12% of an individual's CD4-positive T-cell population,

Although it is not known whether regulatory T cells suppress autoimmune activity directly or through cytokine expression, they have been shown to infiltrate tumors and attenuate the immune system response to them.

It has also been shown in mice that if mature, naive effector T cells are infused into immune-deficient mice, they develop inflammatory bowel disease. However, if regulatory T cells are infused at the same time, the mice remain healthy, Dr. Noelle said.

In addition, studies have demonstrated that T cells can prevent allergy and affect graft acceptance.

“I think they will have a resounding impact on our understanding of the development and pathogenesis of autoimmune diseases,” Dr. Noelle said.

Regulatory T cells suppress the functions of both CD4+ and CD8+ T cells. Dr. Randy Noelle

SNOWMASS, COLO. — The next generation of biological agents will be therapies that capitalize on the ability of regulatory T cells to keep the immune system in check, Randy Noelle, Ph.D., predicted at a symposium sponsored by the American College of Rheumatology.

First discovered 30 years ago, regulatory T-cell research was largely sidelined until interest in the field was renewed about 5 years ago, said Dr. Noelle, a professor of immunology at the Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

“Over the past year, effective strategies have been developed to grow human regulatory T cells in vitro, and I would imagine that within a year you will see groups growing human regulatory T cells for reinfusion into patients for indications such as graft-versus-host disease,” he said.

“They will be the next wave of cell-based therapy that you will use to manage autoimmune disease,” Dr. Noelle told the audience of rheumatologists.

Regulatory T cells are the mechanism by which the body puts the brakes on the immune system functions of attack cells, or executor T cells, Dr. Noelle explained. Both regulatory T cells and executor T cells arise from CD4-positive cells. Research published last fall suggests that expression of the Lag-3 gene in CD4 cells differentiates them into regulatory T cells, which then limit the intensity of the autoimmune response (Immunity 2004;21:503-13).

Regulatory T cells represent about 5%-12% of an individual's CD4-positive T-cell population,

Although it is not known whether regulatory T cells suppress autoimmune activity directly or through cytokine expression, they have been shown to infiltrate tumors and attenuate the immune system response to them.

It has also been shown in mice that if mature, naive effector T cells are infused into immune-deficient mice, they develop inflammatory bowel disease. However, if regulatory T cells are infused at the same time, the mice remain healthy, Dr. Noelle said.

In addition, studies have demonstrated that T cells can prevent allergy and affect graft acceptance.

“I think they will have a resounding impact on our understanding of the development and pathogenesis of autoimmune diseases,” Dr. Noelle said.

Regulatory T cells suppress the functions of both CD4+ and CD8+ T cells. Dr. Randy Noelle

SNOWMASS, COLO. — The next generation of biological agents will be therapies that capitalize on the ability of regulatory T cells to keep the immune system in check, Randy Noelle, Ph.D., predicted at a symposium sponsored by the American College of Rheumatology.

First discovered 30 years ago, regulatory T-cell research was largely sidelined until interest in the field was renewed about 5 years ago, said Dr. Noelle, a professor of immunology at the Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

“Over the past year, effective strategies have been developed to grow human regulatory T cells in vitro, and I would imagine that within a year you will see groups growing human regulatory T cells for reinfusion into patients for indications such as graft-versus-host disease,” he said.

“They will be the next wave of cell-based therapy that you will use to manage autoimmune disease,” Dr. Noelle told the audience of rheumatologists.

Regulatory T cells are the mechanism by which the body puts the brakes on the immune system functions of attack cells, or executor T cells, Dr. Noelle explained. Both regulatory T cells and executor T cells arise from CD4-positive cells. Research published last fall suggests that expression of the Lag-3 gene in CD4 cells differentiates them into regulatory T cells, which then limit the intensity of the autoimmune response (Immunity 2004;21:503-13).

Regulatory T cells represent about 5%-12% of an individual's CD4-positive T-cell population,

Although it is not known whether regulatory T cells suppress autoimmune activity directly or through cytokine expression, they have been shown to infiltrate tumors and attenuate the immune system response to them.

It has also been shown in mice that if mature, naive effector T cells are infused into immune-deficient mice, they develop inflammatory bowel disease. However, if regulatory T cells are infused at the same time, the mice remain healthy, Dr. Noelle said.

In addition, studies have demonstrated that T cells can prevent allergy and affect graft acceptance.

“I think they will have a resounding impact on our understanding of the development and pathogenesis of autoimmune diseases,” Dr. Noelle said.

Regulatory T cells suppress the functions of both CD4+ and CD8+ T cells. Dr. Randy Noelle

The availability of a newly released set of standard magnetic resonance reference images may usher in even greater use of the technology in the evaluation of patients with rheumatoid arthritis.

The European League Against Rheumatism-Outcome Measures in Rheumatoid Arthritis Clinical Trials (EULAR-OMERACT) MRI reference image atlas published last month is intended to improve the performance and generalizability of the MRI scoring system previously developed by the group (Ann. Rheum. Dis. 2005;64 [suppl. 1]:i1-155). In 2002, OMERACT released the Rheumatoid Arthritis MRI Score (RAMRIS) for the evaluation of inflammatory and destructive changes in RA hands and wrists.

Intended for clinical researchers, but also translatable as an educational tool for practicing physicians, the atlas is composed of 1,002 representative images of synovitis, bone erosion, and edema in the metacarpophalangeal and wrist joints.

Selection of the images was decided by consensus among six readers from MRI centers in Auckland, New Zealand; Copenhagen; Leeds, England; and Sydney, Australia. After the initial selection phase, all images were then reviewed to confirm the feature and grade allocated on scoring.

The document displays all severity grades of synovitis in the metacarpophalangeal joints and in each of the wrist joint areas. In addition, it maps out various severity grades of bone erosion and edema in the metacarpal head and phalangeal base and in five selected wrist joint bones (distal radius, scaphoid, lunate, capitate, and metacarpal base). For each individual grade, the atlas includes examples of both the “low” and “high” ends of the spectrum.

The collection of reference images provides a much-needed visual touchstone for MR assessment of RA, said Orrin M. Troum, M.D., of the University of Southern California, Los Angeles. “This is a positive step forward for rheumatologists. … I think ultimately we may be able to do away with x-ray.”

A number of studies have demonstrated the superior sensitivity of MRI compared with conventional radiography, particularly in identifying early disease, which is crucial to improving outcomes for patients with aggressive disease. MRI has been shown to be two to nine times more sensitive than x-rays for the detection of bone erosion.

“It's been well documented that people with RA, if identified and treated earlier, do better,” said Dr. Troum. MRI can make all the difference in the patient with aggressive RA because erosions can be visualized earlier, allowing treatment to be initiated and disease progression to be halted, which all leads to less disability later.

The advent of structure-modifying therapies gave rise to the necessity of MRI assessment in RA patients, said Charles Peterfy, M.D., a musculoskeletal radiologist and a coauthor of the atlas.

Before biologics, there was no real need to have such detailed information about joint structure because having it didn't alter the course of clinical management. The availability of agents that halt disease progression changed everything, he said.

The challenge now is to identify those patients who will go on to develop aggressive disease before severe impairment sets in.

It's estimated that “20%-40% of patients with early disease aren't going to progress,” said Dr. Peterfy, who also is chief medical officer of Synarc, a San Francisco-based company that does MR imaging for clinical trials. Treating these patients empirically with biologics would be much too expensive and would entail an unacceptable level of unnecessary toxicity.

MRI can help identify those with aggressive disease because the technique allows direct visualization and assessment of synovitis and bone edema, which is a probable precursor of bone erosion.

“In early disease, MR identifies the aggressive phenotype much more sensitively than x-ray or any other test does so far,” Dr. Peterfy said.

The MRI atlas may help rheumatologists monitor treatment, adjust dosages, or change treatment regimens altogether. “That's the way I could see MR being used in the clinic,” Dr. Peterfy said.

Core Set of Basic MRI Sequences

It is suggested that future MRI studies that intend to assess inflammatory as well as destructive changes in rheumatoid arthritis joints should include the following:

▸ Imaging in two planes* with T1 weighted images before and after intravenous gadolinium contrast.**

▸ A T2 weighted fat saturated sequence or, if the latter is not available, a STIR (short tau inversion recovery) sequence.

*Can be acquired by obtaining a two-dimensional sequence in two planes, or a three-dimensional sequence with isometric voxels in one plane allowing reconstruction in other planes.

**Intravenous gadolinium injection is probably not essential if only destructive changes (bone erosions) are considered important.

Source: Ann. Rheum. Dis. 2005;64 (suppl. 1):i8-10

The availability of a newly released set of standard magnetic resonance reference images may usher in even greater use of the technology in the evaluation of patients with rheumatoid arthritis.

The European League Against Rheumatism-Outcome Measures in Rheumatoid Arthritis Clinical Trials (EULAR-OMERACT) MRI reference image atlas published last month is intended to improve the performance and generalizability of the MRI scoring system previously developed by the group (Ann. Rheum. Dis. 2005;64 [suppl. 1]:i1-155). In 2002, OMERACT released the Rheumatoid Arthritis MRI Score (RAMRIS) for the evaluation of inflammatory and destructive changes in RA hands and wrists.

Intended for clinical researchers, but also translatable as an educational tool for practicing physicians, the atlas is composed of 1,002 representative images of synovitis, bone erosion, and edema in the metacarpophalangeal and wrist joints.

Selection of the images was decided by consensus among six readers from MRI centers in Auckland, New Zealand; Copenhagen; Leeds, England; and Sydney, Australia. After the initial selection phase, all images were then reviewed to confirm the feature and grade allocated on scoring.

The document displays all severity grades of synovitis in the metacarpophalangeal joints and in each of the wrist joint areas. In addition, it maps out various severity grades of bone erosion and edema in the metacarpal head and phalangeal base and in five selected wrist joint bones (distal radius, scaphoid, lunate, capitate, and metacarpal base). For each individual grade, the atlas includes examples of both the “low” and “high” ends of the spectrum.

The collection of reference images provides a much-needed visual touchstone for MR assessment of RA, said Orrin M. Troum, M.D., of the University of Southern California, Los Angeles. “This is a positive step forward for rheumatologists. … I think ultimately we may be able to do away with x-ray.”

A number of studies have demonstrated the superior sensitivity of MRI compared with conventional radiography, particularly in identifying early disease, which is crucial to improving outcomes for patients with aggressive disease. MRI has been shown to be two to nine times more sensitive than x-rays for the detection of bone erosion.

“It's been well documented that people with RA, if identified and treated earlier, do better,” said Dr. Troum. MRI can make all the difference in the patient with aggressive RA because erosions can be visualized earlier, allowing treatment to be initiated and disease progression to be halted, which all leads to less disability later.

The advent of structure-modifying therapies gave rise to the necessity of MRI assessment in RA patients, said Charles Peterfy, M.D., a musculoskeletal radiologist and a coauthor of the atlas.

Before biologics, there was no real need to have such detailed information about joint structure because having it didn't alter the course of clinical management. The availability of agents that halt disease progression changed everything, he said.

The challenge now is to identify those patients who will go on to develop aggressive disease before severe impairment sets in.

It's estimated that “20%-40% of patients with early disease aren't going to progress,” said Dr. Peterfy, who also is chief medical officer of Synarc, a San Francisco-based company that does MR imaging for clinical trials. Treating these patients empirically with biologics would be much too expensive and would entail an unacceptable level of unnecessary toxicity.

MRI can help identify those with aggressive disease because the technique allows direct visualization and assessment of synovitis and bone edema, which is a probable precursor of bone erosion.

“In early disease, MR identifies the aggressive phenotype much more sensitively than x-ray or any other test does so far,” Dr. Peterfy said.

The MRI atlas may help rheumatologists monitor treatment, adjust dosages, or change treatment regimens altogether. “That's the way I could see MR being used in the clinic,” Dr. Peterfy said.

Core Set of Basic MRI Sequences

It is suggested that future MRI studies that intend to assess inflammatory as well as destructive changes in rheumatoid arthritis joints should include the following:

▸ Imaging in two planes* with T1 weighted images before and after intravenous gadolinium contrast.**

▸ A T2 weighted fat saturated sequence or, if the latter is not available, a STIR (short tau inversion recovery) sequence.

*Can be acquired by obtaining a two-dimensional sequence in two planes, or a three-dimensional sequence with isometric voxels in one plane allowing reconstruction in other planes.

**Intravenous gadolinium injection is probably not essential if only destructive changes (bone erosions) are considered important.

Source: Ann. Rheum. Dis. 2005;64 (suppl. 1):i8-10

The availability of a newly released set of standard magnetic resonance reference images may usher in even greater use of the technology in the evaluation of patients with rheumatoid arthritis.

The European League Against Rheumatism-Outcome Measures in Rheumatoid Arthritis Clinical Trials (EULAR-OMERACT) MRI reference image atlas published last month is intended to improve the performance and generalizability of the MRI scoring system previously developed by the group (Ann. Rheum. Dis. 2005;64 [suppl. 1]:i1-155). In 2002, OMERACT released the Rheumatoid Arthritis MRI Score (RAMRIS) for the evaluation of inflammatory and destructive changes in RA hands and wrists.

Intended for clinical researchers, but also translatable as an educational tool for practicing physicians, the atlas is composed of 1,002 representative images of synovitis, bone erosion, and edema in the metacarpophalangeal and wrist joints.

Selection of the images was decided by consensus among six readers from MRI centers in Auckland, New Zealand; Copenhagen; Leeds, England; and Sydney, Australia. After the initial selection phase, all images were then reviewed to confirm the feature and grade allocated on scoring.

The document displays all severity grades of synovitis in the metacarpophalangeal joints and in each of the wrist joint areas. In addition, it maps out various severity grades of bone erosion and edema in the metacarpal head and phalangeal base and in five selected wrist joint bones (distal radius, scaphoid, lunate, capitate, and metacarpal base). For each individual grade, the atlas includes examples of both the “low” and “high” ends of the spectrum.

The collection of reference images provides a much-needed visual touchstone for MR assessment of RA, said Orrin M. Troum, M.D., of the University of Southern California, Los Angeles. “This is a positive step forward for rheumatologists. … I think ultimately we may be able to do away with x-ray.”

A number of studies have demonstrated the superior sensitivity of MRI compared with conventional radiography, particularly in identifying early disease, which is crucial to improving outcomes for patients with aggressive disease. MRI has been shown to be two to nine times more sensitive than x-rays for the detection of bone erosion.

“It's been well documented that people with RA, if identified and treated earlier, do better,” said Dr. Troum. MRI can make all the difference in the patient with aggressive RA because erosions can be visualized earlier, allowing treatment to be initiated and disease progression to be halted, which all leads to less disability later.

The advent of structure-modifying therapies gave rise to the necessity of MRI assessment in RA patients, said Charles Peterfy, M.D., a musculoskeletal radiologist and a coauthor of the atlas.

Before biologics, there was no real need to have such detailed information about joint structure because having it didn't alter the course of clinical management. The availability of agents that halt disease progression changed everything, he said.

The challenge now is to identify those patients who will go on to develop aggressive disease before severe impairment sets in.

It's estimated that “20%-40% of patients with early disease aren't going to progress,” said Dr. Peterfy, who also is chief medical officer of Synarc, a San Francisco-based company that does MR imaging for clinical trials. Treating these patients empirically with biologics would be much too expensive and would entail an unacceptable level of unnecessary toxicity.

MRI can help identify those with aggressive disease because the technique allows direct visualization and assessment of synovitis and bone edema, which is a probable precursor of bone erosion.

“In early disease, MR identifies the aggressive phenotype much more sensitively than x-ray or any other test does so far,” Dr. Peterfy said.

The MRI atlas may help rheumatologists monitor treatment, adjust dosages, or change treatment regimens altogether. “That's the way I could see MR being used in the clinic,” Dr. Peterfy said.

Core Set of Basic MRI Sequences

It is suggested that future MRI studies that intend to assess inflammatory as well as destructive changes in rheumatoid arthritis joints should include the following:

▸ Imaging in two planes* with T1 weighted images before and after intravenous gadolinium contrast.**

▸ A T2 weighted fat saturated sequence or, if the latter is not available, a STIR (short tau inversion recovery) sequence.

*Can be acquired by obtaining a two-dimensional sequence in two planes, or a three-dimensional sequence with isometric voxels in one plane allowing reconstruction in other planes.

**Intravenous gadolinium injection is probably not essential if only destructive changes (bone erosions) are considered important.

Source: Ann. Rheum. Dis. 2005;64 (suppl. 1):i8-10

SNOWMASS, COLO. — Calcium crystals are likely to become a major target for future osteoarthritis therapies, Geraldine M. McCarthy, M.D., predicted at a symposium sponsored by the American College of Rheumatology.

Calcium crystals may actually be related to glucosamine's mechanism of action, said Dr. McCarthy, of the division of rheumatology at Mater Misericordiae Hospital and the Royal College of Surgeons, Dublin, Ireland.

Studies have shown that anywhere from 30% to 70% of patients with osteoarthritis of the knee have calcium crystals in their synovial fluid, Dr. McCarthy said at the meeting.

And yet because the crystals are extremely small, they're difficult to detect, making more precise estimates of their prevalence difficult to obtain.

Dr. McCarthy's interest in arthritis and the role of calcium crystals was spurred by her training at the University of Wisconsin, where Milwaukee shoulder syndrome was identified as the first osteoarthritis entity found to be associated with basic calcium phosphate crystals.

The idea is that these crystals “synergize with other pathogenic mediators of osteoarthritis, thus contributing to the degenerative process,” she said.

Calcium pyrophosphate dihydrate crystals in the synovium are believed to cause pseudogout and pseudo-rheumatoid arthritis.

Basic calcium phosphate crystals, by comparison, are believed to play a role in all osteoarthritis, Dr. McCarthy explained at the meeting.

Research into the role of basic calcium phosphate crystals has been hindered, however, by the size of the crystals. As small as calcium pyrophosphate dihydrate crystals are, basic calcium phosphate crystals are even smaller.

Basic calcium phosphate crystals clump as submicroscopic aggregates ranging in size from 1 μm to 50 μm in diameter.

A radiolabeled bisphosphonate that can detect the crystals has been available at the Medical College of Wisconsin, Milwaukee, but supply is dwindling, and at present no company has stepped up to manufacture more, Dr. McCarthy said.

Studies have shown that as people age basic calcium phosphate crystals tend to accumulate in the synovial fluid, synovial lining, and hyaline cartilage, and that the presence of these crystals correlates strongly with radiographic evidence of cartilage degeneration. In vitro experiments have shown that the crystals induce mitogenesis and increase production of prostaglandins and metalloproteinases.

The presence of crystals also is associated with the increased production and activation of cyclooxygenase-1 and -2.

Interestingly, COX-1 is not usually upregulated by disease processes, so this finding may explain why some osteoarthritis patients do not respond to selective COX-2 inhibitor therapy, Dr. McCarthy suggested.

The crystals appear to be actively generated by articular cartilage matrix vesicles.

“These crystals are not present in other destructive arthropathies,” Dr. McCarthy noted. But they are associated with Milwaukee shoulder syndrome, so it's likely that the crystals are also associated with joint destruction, she continued.

Further investigations are needed to identify therapeutic interventions and to determine why some individuals with basic calcium phosphate crystals have symptomatic degeneration while others do not, she said.

Calcium-chelating agents have been tried in the treatment of Milwaukee shoulder syndrome, but their use has caused severe arthritis flares.

In vitro experiments have shown that misoprostol can inhibit crystal formation, and glucosamine appears to directly inhibit the effects of the calcium crystals on mitogenesis and metalloproteinase production.

SNOWMASS, COLO. — Calcium crystals are likely to become a major target for future osteoarthritis therapies, Geraldine M. McCarthy, M.D., predicted at a symposium sponsored by the American College of Rheumatology.

Calcium crystals may actually be related to glucosamine's mechanism of action, said Dr. McCarthy, of the division of rheumatology at Mater Misericordiae Hospital and the Royal College of Surgeons, Dublin, Ireland.

Studies have shown that anywhere from 30% to 70% of patients with osteoarthritis of the knee have calcium crystals in their synovial fluid, Dr. McCarthy said at the meeting.

And yet because the crystals are extremely small, they're difficult to detect, making more precise estimates of their prevalence difficult to obtain.

Dr. McCarthy's interest in arthritis and the role of calcium crystals was spurred by her training at the University of Wisconsin, where Milwaukee shoulder syndrome was identified as the first osteoarthritis entity found to be associated with basic calcium phosphate crystals.

The idea is that these crystals “synergize with other pathogenic mediators of osteoarthritis, thus contributing to the degenerative process,” she said.

Calcium pyrophosphate dihydrate crystals in the synovium are believed to cause pseudogout and pseudo-rheumatoid arthritis.

Basic calcium phosphate crystals, by comparison, are believed to play a role in all osteoarthritis, Dr. McCarthy explained at the meeting.

Research into the role of basic calcium phosphate crystals has been hindered, however, by the size of the crystals. As small as calcium pyrophosphate dihydrate crystals are, basic calcium phosphate crystals are even smaller.

Basic calcium phosphate crystals clump as submicroscopic aggregates ranging in size from 1 μm to 50 μm in diameter.

A radiolabeled bisphosphonate that can detect the crystals has been available at the Medical College of Wisconsin, Milwaukee, but supply is dwindling, and at present no company has stepped up to manufacture more, Dr. McCarthy said.

Studies have shown that as people age basic calcium phosphate crystals tend to accumulate in the synovial fluid, synovial lining, and hyaline cartilage, and that the presence of these crystals correlates strongly with radiographic evidence of cartilage degeneration. In vitro experiments have shown that the crystals induce mitogenesis and increase production of prostaglandins and metalloproteinases.

The presence of crystals also is associated with the increased production and activation of cyclooxygenase-1 and -2.

Interestingly, COX-1 is not usually upregulated by disease processes, so this finding may explain why some osteoarthritis patients do not respond to selective COX-2 inhibitor therapy, Dr. McCarthy suggested.

The crystals appear to be actively generated by articular cartilage matrix vesicles.

“These crystals are not present in other destructive arthropathies,” Dr. McCarthy noted. But they are associated with Milwaukee shoulder syndrome, so it's likely that the crystals are also associated with joint destruction, she continued.

Further investigations are needed to identify therapeutic interventions and to determine why some individuals with basic calcium phosphate crystals have symptomatic degeneration while others do not, she said.

Calcium-chelating agents have been tried in the treatment of Milwaukee shoulder syndrome, but their use has caused severe arthritis flares.

In vitro experiments have shown that misoprostol can inhibit crystal formation, and glucosamine appears to directly inhibit the effects of the calcium crystals on mitogenesis and metalloproteinase production.

SNOWMASS, COLO. — Calcium crystals are likely to become a major target for future osteoarthritis therapies, Geraldine M. McCarthy, M.D., predicted at a symposium sponsored by the American College of Rheumatology.

Calcium crystals may actually be related to glucosamine's mechanism of action, said Dr. McCarthy, of the division of rheumatology at Mater Misericordiae Hospital and the Royal College of Surgeons, Dublin, Ireland.

Studies have shown that anywhere from 30% to 70% of patients with osteoarthritis of the knee have calcium crystals in their synovial fluid, Dr. McCarthy said at the meeting.

And yet because the crystals are extremely small, they're difficult to detect, making more precise estimates of their prevalence difficult to obtain.

Dr. McCarthy's interest in arthritis and the role of calcium crystals was spurred by her training at the University of Wisconsin, where Milwaukee shoulder syndrome was identified as the first osteoarthritis entity found to be associated with basic calcium phosphate crystals.

The idea is that these crystals “synergize with other pathogenic mediators of osteoarthritis, thus contributing to the degenerative process,” she said.

Calcium pyrophosphate dihydrate crystals in the synovium are believed to cause pseudogout and pseudo-rheumatoid arthritis.

Basic calcium phosphate crystals, by comparison, are believed to play a role in all osteoarthritis, Dr. McCarthy explained at the meeting.

Research into the role of basic calcium phosphate crystals has been hindered, however, by the size of the crystals. As small as calcium pyrophosphate dihydrate crystals are, basic calcium phosphate crystals are even smaller.

Basic calcium phosphate crystals clump as submicroscopic aggregates ranging in size from 1 μm to 50 μm in diameter.

A radiolabeled bisphosphonate that can detect the crystals has been available at the Medical College of Wisconsin, Milwaukee, but supply is dwindling, and at present no company has stepped up to manufacture more, Dr. McCarthy said.

Studies have shown that as people age basic calcium phosphate crystals tend to accumulate in the synovial fluid, synovial lining, and hyaline cartilage, and that the presence of these crystals correlates strongly with radiographic evidence of cartilage degeneration. In vitro experiments have shown that the crystals induce mitogenesis and increase production of prostaglandins and metalloproteinases.

The presence of crystals also is associated with the increased production and activation of cyclooxygenase-1 and -2.

Interestingly, COX-1 is not usually upregulated by disease processes, so this finding may explain why some osteoarthritis patients do not respond to selective COX-2 inhibitor therapy, Dr. McCarthy suggested.

The crystals appear to be actively generated by articular cartilage matrix vesicles.

“These crystals are not present in other destructive arthropathies,” Dr. McCarthy noted. But they are associated with Milwaukee shoulder syndrome, so it's likely that the crystals are also associated with joint destruction, she continued.

Further investigations are needed to identify therapeutic interventions and to determine why some individuals with basic calcium phosphate crystals have symptomatic degeneration while others do not, she said.

Calcium-chelating agents have been tried in the treatment of Milwaukee shoulder syndrome, but their use has caused severe arthritis flares.

In vitro experiments have shown that misoprostol can inhibit crystal formation, and glucosamine appears to directly inhibit the effects of the calcium crystals on mitogenesis and metalloproteinase production.

BUDAPEST, HUNGARY — While infliximab therapy for the treatment of rheumatoid arthritis lowers rheumatoid factor titers, the biologic appears to have little effect on another increasingly relevant marker of disease activity: anticyclic citrullinated peptide antibodies, Nathalie Bardin, M.D., said at the 4th International Congress on Autoimmunity.

“The long-term effect of infliximab therapy leads to a reduction in rheumatoid factor titers and the induction of IgG anti-double-stranded DNA [anti-dsDNA].” Yet there was no change in anticyclic citrullinated peptide (anti-CCP) levels,” said Dr. Bardin of Hôpital de la Conception, Marseille, France.

In a study of 33 rheumatoid arthritis (RA) patients, 20 treated with infliximab (Remicade), 13 untreated, and 20 controls with undetermined arthritis, the researchers measured levels of anti-CCP, anti-dsDNA antibodies, and IgM rheumatoid factor (RF).

Anti-CCP antibodies were identified in 70% of RA patients, regardless of treatment, but only 10% of those with undetermined arthritis. RF was found in 60% of RA patients but only 10% of the controls. The frequency of RF was 55% in treated patients compared with 69% in untreated patients.

Dr. Bardin also followed 16 RA patients over 2 years of infliximab therapy. No change in anti-CCP level was found, but there was a drop in RF titers, she said. “IgG anti-dsDNA was only detected in patients treated with infliximab.” Because of its high specificity and sensitivity, anti-CCP antibody testing is increasingly seen as an important marker of disease activity in RA patients.

In a study of 54 patients with early RA, 35 patients with established RA, 33 healthy donors, and 76 patients with non-RA autoimmune diseases, researchers at the University of Florence (Italy) confirmed that the presence of anti-CCP antibodies is specific to the diagnosis of RA and is also an indicator of bone lesions (Autoimmunity 2004;37:495-501).

BUDAPEST, HUNGARY — While infliximab therapy for the treatment of rheumatoid arthritis lowers rheumatoid factor titers, the biologic appears to have little effect on another increasingly relevant marker of disease activity: anticyclic citrullinated peptide antibodies, Nathalie Bardin, M.D., said at the 4th International Congress on Autoimmunity.

“The long-term effect of infliximab therapy leads to a reduction in rheumatoid factor titers and the induction of IgG anti-double-stranded DNA [anti-dsDNA].” Yet there was no change in anticyclic citrullinated peptide (anti-CCP) levels,” said Dr. Bardin of Hôpital de la Conception, Marseille, France.

In a study of 33 rheumatoid arthritis (RA) patients, 20 treated with infliximab (Remicade), 13 untreated, and 20 controls with undetermined arthritis, the researchers measured levels of anti-CCP, anti-dsDNA antibodies, and IgM rheumatoid factor (RF).

Anti-CCP antibodies were identified in 70% of RA patients, regardless of treatment, but only 10% of those with undetermined arthritis. RF was found in 60% of RA patients but only 10% of the controls. The frequency of RF was 55% in treated patients compared with 69% in untreated patients.

Dr. Bardin also followed 16 RA patients over 2 years of infliximab therapy. No change in anti-CCP level was found, but there was a drop in RF titers, she said. “IgG anti-dsDNA was only detected in patients treated with infliximab.” Because of its high specificity and sensitivity, anti-CCP antibody testing is increasingly seen as an important marker of disease activity in RA patients.

In a study of 54 patients with early RA, 35 patients with established RA, 33 healthy donors, and 76 patients with non-RA autoimmune diseases, researchers at the University of Florence (Italy) confirmed that the presence of anti-CCP antibodies is specific to the diagnosis of RA and is also an indicator of bone lesions (Autoimmunity 2004;37:495-501).

BUDAPEST, HUNGARY — While infliximab therapy for the treatment of rheumatoid arthritis lowers rheumatoid factor titers, the biologic appears to have little effect on another increasingly relevant marker of disease activity: anticyclic citrullinated peptide antibodies, Nathalie Bardin, M.D., said at the 4th International Congress on Autoimmunity.

“The long-term effect of infliximab therapy leads to a reduction in rheumatoid factor titers and the induction of IgG anti-double-stranded DNA [anti-dsDNA].” Yet there was no change in anticyclic citrullinated peptide (anti-CCP) levels,” said Dr. Bardin of Hôpital de la Conception, Marseille, France.

In a study of 33 rheumatoid arthritis (RA) patients, 20 treated with infliximab (Remicade), 13 untreated, and 20 controls with undetermined arthritis, the researchers measured levels of anti-CCP, anti-dsDNA antibodies, and IgM rheumatoid factor (RF).

Anti-CCP antibodies were identified in 70% of RA patients, regardless of treatment, but only 10% of those with undetermined arthritis. RF was found in 60% of RA patients but only 10% of the controls. The frequency of RF was 55% in treated patients compared with 69% in untreated patients.

Dr. Bardin also followed 16 RA patients over 2 years of infliximab therapy. No change in anti-CCP level was found, but there was a drop in RF titers, she said. “IgG anti-dsDNA was only detected in patients treated with infliximab.” Because of its high specificity and sensitivity, anti-CCP antibody testing is increasingly seen as an important marker of disease activity in RA patients.

In a study of 54 patients with early RA, 35 patients with established RA, 33 healthy donors, and 76 patients with non-RA autoimmune diseases, researchers at the University of Florence (Italy) confirmed that the presence of anti-CCP antibodies is specific to the diagnosis of RA and is also an indicator of bone lesions (Autoimmunity 2004;37:495-501).