Rheumatoid Arthritis

Patients with early-stage rheumatoid arthritis who are treated with methotrexate plus infliximab are more likely to remain employed or able to work than are patients treated with methotrexate alone, according to findings from another new analysis of the ASPIRE trial data.

Physical function deteriorates so rapidly in rheumatoid arthritis (RA) that 20% of employed patients have to quit their jobs within 2 years of disease onset, and approximately half of RA patients face work disability within 10 years, reported Dr. Josef S. Smolen of the Medical University of Vienna, and his colleagues in Europe and the United States (Arthritis Rheum. 2006;54:716–22).

Patients in the ASPIRE (Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset) trial—which compared methotrexate alone with methotrexate plus infliximab—were asked at each visit whether they were currently employed and if not, whether they felt well enough to work if a job were available.

The new analysis, which covered approximately 850 patients aged 65 years or younger, found that rapid disease control in early-stage RA reduced patients work disability and improved their employability, reported Dr. Smolen and colleagues.

While the actual employment rate did not differ significantly between the two treatment groups, the patients treated with both drugs were more likely to maintain their employability or to feel able to work throughout the 54-week study.

The proportion of patients whose status changed from employable at baseline to unemployable at week 54 was smaller in the methotrexate-plus-infliximab group than in the methotrexate-only group (8% vs. 14%, respectively). Similarly, the proportion of employed patients who lost more than 10 workdays was smaller in the combination group, when compared with the methotrexate-only group (10% vs. 17%, respectively), the investigators reported.

Patients with early-stage rheumatoid arthritis who are treated with methotrexate plus infliximab are more likely to remain employed or able to work than are patients treated with methotrexate alone, according to findings from another new analysis of the ASPIRE trial data.

Physical function deteriorates so rapidly in rheumatoid arthritis (RA) that 20% of employed patients have to quit their jobs within 2 years of disease onset, and approximately half of RA patients face work disability within 10 years, reported Dr. Josef S. Smolen of the Medical University of Vienna, and his colleagues in Europe and the United States (Arthritis Rheum. 2006;54:716–22).

Patients in the ASPIRE (Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset) trial—which compared methotrexate alone with methotrexate plus infliximab—were asked at each visit whether they were currently employed and if not, whether they felt well enough to work if a job were available.

The new analysis, which covered approximately 850 patients aged 65 years or younger, found that rapid disease control in early-stage RA reduced patients work disability and improved their employability, reported Dr. Smolen and colleagues.

While the actual employment rate did not differ significantly between the two treatment groups, the patients treated with both drugs were more likely to maintain their employability or to feel able to work throughout the 54-week study.

The proportion of patients whose status changed from employable at baseline to unemployable at week 54 was smaller in the methotrexate-plus-infliximab group than in the methotrexate-only group (8% vs. 14%, respectively). Similarly, the proportion of employed patients who lost more than 10 workdays was smaller in the combination group, when compared with the methotrexate-only group (10% vs. 17%, respectively), the investigators reported.

Patients with early-stage rheumatoid arthritis who are treated with methotrexate plus infliximab are more likely to remain employed or able to work than are patients treated with methotrexate alone, according to findings from another new analysis of the ASPIRE trial data.

Physical function deteriorates so rapidly in rheumatoid arthritis (RA) that 20% of employed patients have to quit their jobs within 2 years of disease onset, and approximately half of RA patients face work disability within 10 years, reported Dr. Josef S. Smolen of the Medical University of Vienna, and his colleagues in Europe and the United States (Arthritis Rheum. 2006;54:716–22).

Patients in the ASPIRE (Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset) trial—which compared methotrexate alone with methotrexate plus infliximab—were asked at each visit whether they were currently employed and if not, whether they felt well enough to work if a job were available.

The new analysis, which covered approximately 850 patients aged 65 years or younger, found that rapid disease control in early-stage RA reduced patients work disability and improved their employability, reported Dr. Smolen and colleagues.

While the actual employment rate did not differ significantly between the two treatment groups, the patients treated with both drugs were more likely to maintain their employability or to feel able to work throughout the 54-week study.

The proportion of patients whose status changed from employable at baseline to unemployable at week 54 was smaller in the methotrexate-plus-infliximab group than in the methotrexate-only group (8% vs. 14%, respectively). Similarly, the proportion of employed patients who lost more than 10 workdays was smaller in the combination group, when compared with the methotrexate-only group (10% vs. 17%, respectively), the investigators reported.

GLASGOW, SCOTLAND — Subclinical atherosclerosis is common among patients early in the course of inflammatory polyarthritis, even among those not considered to be otherwise at high risk for cardiovascular disease, Diane K. Bunn reported at the annual meeting of the British Society for Rheumatology.

Increased awareness of the excess mortality associated with rheumatoid and undifferentiated arthritis prompted institution of the Norfolk Arthritis Register, a primary-care-based inception cohort of patients with inflammatory polyarthritis, according to Ms. Bunn of Norfolk and Norwich (England) University Hospital.

The register now has enrolled 93 patients, 61 of whom are female. Median age of the cohort was 50 years, and median disease duration at presentation was 7 months. On recruitment, 56 (60%) were taking disease-modifying antirheumatic drugs, and 59 (63%) were taking nonsteroidal anti-inflammatory drugs. Among this latter group, 12 were being treated with coxibs and the remainder with NSAIDs.

Blood pressure was 140/90 or higher in 31 (33%), but only 7 were taking antihypertensive medication. Fasting cholesterol was 5.1 mmol or more in 44 (47%), yet only 3 (2 of whom were known diabetics) were taking a statin drug, she wrote in a poster session. Sixteen (17.2%) were smokers.

Cardiovascular risk, calculated using the Joint British Societies Cardiac Risk Assessor (www.bnf.org/BNF/extra/current/450024.htm

The finding that a large proportion of the cohort had subclinical atherosclerosis early in the course of their disease highlights the importance of considering cardiovascular risk right from the start in patients with inflammatory polyarthritis, she concluded.

GLASGOW, SCOTLAND — Subclinical atherosclerosis is common among patients early in the course of inflammatory polyarthritis, even among those not considered to be otherwise at high risk for cardiovascular disease, Diane K. Bunn reported at the annual meeting of the British Society for Rheumatology.

Increased awareness of the excess mortality associated with rheumatoid and undifferentiated arthritis prompted institution of the Norfolk Arthritis Register, a primary-care-based inception cohort of patients with inflammatory polyarthritis, according to Ms. Bunn of Norfolk and Norwich (England) University Hospital.

The register now has enrolled 93 patients, 61 of whom are female. Median age of the cohort was 50 years, and median disease duration at presentation was 7 months. On recruitment, 56 (60%) were taking disease-modifying antirheumatic drugs, and 59 (63%) were taking nonsteroidal anti-inflammatory drugs. Among this latter group, 12 were being treated with coxibs and the remainder with NSAIDs.

Blood pressure was 140/90 or higher in 31 (33%), but only 7 were taking antihypertensive medication. Fasting cholesterol was 5.1 mmol or more in 44 (47%), yet only 3 (2 of whom were known diabetics) were taking a statin drug, she wrote in a poster session. Sixteen (17.2%) were smokers.

Cardiovascular risk, calculated using the Joint British Societies Cardiac Risk Assessor (www.bnf.org/BNF/extra/current/450024.htm

The finding that a large proportion of the cohort had subclinical atherosclerosis early in the course of their disease highlights the importance of considering cardiovascular risk right from the start in patients with inflammatory polyarthritis, she concluded.

GLASGOW, SCOTLAND — Subclinical atherosclerosis is common among patients early in the course of inflammatory polyarthritis, even among those not considered to be otherwise at high risk for cardiovascular disease, Diane K. Bunn reported at the annual meeting of the British Society for Rheumatology.

Increased awareness of the excess mortality associated with rheumatoid and undifferentiated arthritis prompted institution of the Norfolk Arthritis Register, a primary-care-based inception cohort of patients with inflammatory polyarthritis, according to Ms. Bunn of Norfolk and Norwich (England) University Hospital.

The register now has enrolled 93 patients, 61 of whom are female. Median age of the cohort was 50 years, and median disease duration at presentation was 7 months. On recruitment, 56 (60%) were taking disease-modifying antirheumatic drugs, and 59 (63%) were taking nonsteroidal anti-inflammatory drugs. Among this latter group, 12 were being treated with coxibs and the remainder with NSAIDs.

Blood pressure was 140/90 or higher in 31 (33%), but only 7 were taking antihypertensive medication. Fasting cholesterol was 5.1 mmol or more in 44 (47%), yet only 3 (2 of whom were known diabetics) were taking a statin drug, she wrote in a poster session. Sixteen (17.2%) were smokers.

Cardiovascular risk, calculated using the Joint British Societies Cardiac Risk Assessor (www.bnf.org/BNF/extra/current/450024.htm

The finding that a large proportion of the cohort had subclinical atherosclerosis early in the course of their disease highlights the importance of considering cardiovascular risk right from the start in patients with inflammatory polyarthritis, she concluded.

SAN DIEGO — The overall sensitivity of MRI to detect chondral lesions found during arthroscopic knee surgery was only 45%, results from a study of 190 patients demonstrated.

The finding suggests that knee arthroscopists should be prepared to intraoperatively detect and treat chondral lesions that have been previously undiagnosed by MRI, Dr. Alex Vaisman said at a symposium sponsored by the International Cartilage Repair Society.

“Based on our results, we recommend that the instrumentation for different cartilage repair techniques should always be available [at] the time of an arthroscopic knee procedure,” said Dr. Vaisman, of the Universidad Del Desarrollo, Santiago, Chile.

The purpose of the study was to prospectively evaluate the incidence and morphologic characteristics of chondral lesions following arthroscopic knee surgery and to establish the correlation between microscopic and MRI findings.

Dr. Vaisman and his associates evaluated 190 consecutive knee procedures performed between March 2003 and February 2004 by two surgeons with 15 years of knee surgery experience.

Two musculoskeletal radiologists with 10 years of experience generated the MRI reports.

The time between MRI exam and knee surgery did not exceed 1 year. The MRI report of at least one chondral lesion found at arthroscopy was considered to be a positive correlation between both diagnostic instruments.

The average age of the 190 patients in the study was 35 years, and 116 were male. Most indications for arthroscopic surgery were for anterior cruciate ligament tears and meniscal tears.

On arthroscopy, Dr. Vaisman and fellow researchers found 115 chondral lesions in 82 patients. Most (72%) were single lesions located on the medial femoral condyle (32%) or the medial patella (23%). The average size of these lesions was 1.99 cm

There was no correlation between patient age and the number of lesions, but there was a direct correlation between patient age and the size of the lesion.

On MRI, chondral lesions were reported in 37 out of 82 patients, which translated into a sensitivity of 45% and a specificity of 100%.

When researchers analyzed MRI sensitivity by location of the defect, they observed that MRI was most accurate for patellar defects (53%), followed by femoral defects (43%) and tibial defects (16%).

When they analyzed the MRI sensitivity by the ICRS classification system, significant differences emerged.

For example, the MRI sensitivity for ICRS grade 1 lesions was 13%, compared with 53% for grade 2 lesions, 64% for grade 3 lesions, and 73% for grade 4 lesions.

MRI detected this medial femoral condyle osteonecrosis and lesion.

The same medial femoral chondral lesion is shown in arthroscopic view. Photos courtesy Dr. Alex Vaisman

SAN DIEGO — The overall sensitivity of MRI to detect chondral lesions found during arthroscopic knee surgery was only 45%, results from a study of 190 patients demonstrated.

The finding suggests that knee arthroscopists should be prepared to intraoperatively detect and treat chondral lesions that have been previously undiagnosed by MRI, Dr. Alex Vaisman said at a symposium sponsored by the International Cartilage Repair Society.

“Based on our results, we recommend that the instrumentation for different cartilage repair techniques should always be available [at] the time of an arthroscopic knee procedure,” said Dr. Vaisman, of the Universidad Del Desarrollo, Santiago, Chile.

The purpose of the study was to prospectively evaluate the incidence and morphologic characteristics of chondral lesions following arthroscopic knee surgery and to establish the correlation between microscopic and MRI findings.

Dr. Vaisman and his associates evaluated 190 consecutive knee procedures performed between March 2003 and February 2004 by two surgeons with 15 years of knee surgery experience.

Two musculoskeletal radiologists with 10 years of experience generated the MRI reports.

The time between MRI exam and knee surgery did not exceed 1 year. The MRI report of at least one chondral lesion found at arthroscopy was considered to be a positive correlation between both diagnostic instruments.

The average age of the 190 patients in the study was 35 years, and 116 were male. Most indications for arthroscopic surgery were for anterior cruciate ligament tears and meniscal tears.

On arthroscopy, Dr. Vaisman and fellow researchers found 115 chondral lesions in 82 patients. Most (72%) were single lesions located on the medial femoral condyle (32%) or the medial patella (23%). The average size of these lesions was 1.99 cm

There was no correlation between patient age and the number of lesions, but there was a direct correlation between patient age and the size of the lesion.

On MRI, chondral lesions were reported in 37 out of 82 patients, which translated into a sensitivity of 45% and a specificity of 100%.

When researchers analyzed MRI sensitivity by location of the defect, they observed that MRI was most accurate for patellar defects (53%), followed by femoral defects (43%) and tibial defects (16%).

When they analyzed the MRI sensitivity by the ICRS classification system, significant differences emerged.

For example, the MRI sensitivity for ICRS grade 1 lesions was 13%, compared with 53% for grade 2 lesions, 64% for grade 3 lesions, and 73% for grade 4 lesions.

MRI detected this medial femoral condyle osteonecrosis and lesion.

The same medial femoral chondral lesion is shown in arthroscopic view. Photos courtesy Dr. Alex Vaisman

SAN DIEGO — The overall sensitivity of MRI to detect chondral lesions found during arthroscopic knee surgery was only 45%, results from a study of 190 patients demonstrated.

The finding suggests that knee arthroscopists should be prepared to intraoperatively detect and treat chondral lesions that have been previously undiagnosed by MRI, Dr. Alex Vaisman said at a symposium sponsored by the International Cartilage Repair Society.

“Based on our results, we recommend that the instrumentation for different cartilage repair techniques should always be available [at] the time of an arthroscopic knee procedure,” said Dr. Vaisman, of the Universidad Del Desarrollo, Santiago, Chile.

The purpose of the study was to prospectively evaluate the incidence and morphologic characteristics of chondral lesions following arthroscopic knee surgery and to establish the correlation between microscopic and MRI findings.

Dr. Vaisman and his associates evaluated 190 consecutive knee procedures performed between March 2003 and February 2004 by two surgeons with 15 years of knee surgery experience.

Two musculoskeletal radiologists with 10 years of experience generated the MRI reports.

The time between MRI exam and knee surgery did not exceed 1 year. The MRI report of at least one chondral lesion found at arthroscopy was considered to be a positive correlation between both diagnostic instruments.

The average age of the 190 patients in the study was 35 years, and 116 were male. Most indications for arthroscopic surgery were for anterior cruciate ligament tears and meniscal tears.

On arthroscopy, Dr. Vaisman and fellow researchers found 115 chondral lesions in 82 patients. Most (72%) were single lesions located on the medial femoral condyle (32%) or the medial patella (23%). The average size of these lesions was 1.99 cm

There was no correlation between patient age and the number of lesions, but there was a direct correlation between patient age and the size of the lesion.

On MRI, chondral lesions were reported in 37 out of 82 patients, which translated into a sensitivity of 45% and a specificity of 100%.

When researchers analyzed MRI sensitivity by location of the defect, they observed that MRI was most accurate for patellar defects (53%), followed by femoral defects (43%) and tibial defects (16%).

When they analyzed the MRI sensitivity by the ICRS classification system, significant differences emerged.

For example, the MRI sensitivity for ICRS grade 1 lesions was 13%, compared with 53% for grade 2 lesions, 64% for grade 3 lesions, and 73% for grade 4 lesions.

MRI detected this medial femoral condyle osteonecrosis and lesion.

The same medial femoral chondral lesion is shown in arthroscopic view. Photos courtesy Dr. Alex Vaisman

CHICAGO — Highly cross-linked polyethylene bearing surfaces in total hip arthroplasties have passed their first long-term longitudinal trial with flying colors, according to a blue-ribbon poster presented at the annual meeting of the American College of Orthopaedic Surgeons.

“After a minimum of five years follow-up of patients all done at Massachusetts General Hospital, there were no signs of radiographic osteolysis either on the acetabular or femoral sides, and this is the earliest point where you might normally start to see that with conventional polyethylene,” Charles R. Bragdon, Ph.D., said in an interview.

Electron beam irradiated highly cross-linked polyethylene (HXLPE) is created by taking standard high-density polyethylene and irradiating it, which increases cross-linking and improves wear characteristics. The material then goes through “a melting step which allows the free radicals generated during radiation to extinguish themselves and form more cross-linking. With the free radicals gone, there's no long-term oxidation, so the properties you get do not change over time,” Dr. Bragdon said explained.

HXLPE has been used as total hip arthroplasty bearing surface for nearly 8 years, according to Dr. Bragdon and his colleagues at the Orthopaedic Biomechanics and Biomaterials Laboratory at Massachusetts General Hospital in Boston. Radiostereometric analysis (RSA) has shown little additional femoral head penetration after the early bedding-in period; however, such studies have been performed on relatively small groups of patients, the authors continued. Using standardized measures, the Boston group studied femoral head penetration in 77 primary total hip replacements in 70 patients with HXLPE liners, with either a 28-mm or 32-mm femoral head.

The average total femoral head penetration was calculated based on the total penetration from the initial postoperative film to the longest follow-up film.

“During the first year following surgery, there was about 100 microns of head penetration into the polyethylene,” Dr. Bragdon said. “Thereafter … [there was] no measurable wear of this material at 5 years,” he said. In addition, there was no significant difference in the average penetration rate or the steady state wear rates between the 28-mm and 32-mm groups.

“These results are encouraging for lysis in the long term because we've shown in the past that lysis and wear tend to go hand in hand; we think our study bodes well for 7–15 years' follow-up,” said Dr. Bragdon, adding that continued follow-up will be necessary to evaluate the material's clinical and radiographic durability.

Dr. Bragdon predicted that these more durable replacements will further reduce the average age of both knee and hip recipients. “Cross-linked polyethylene's introduction has been in hip arthroplasty, but now it's also being used in knees because knee components also suffer from wear and osteolysis.”

Osteolysis was seen on x-ray 7 years after placement of a conventional polyethylene liner for total hip arthroplasty (left). No osteolysis was seen 6 years later with a highly cross-linked polyethylene liner (right). Photos courtesy Dr. Meridith Greene

CHICAGO — Highly cross-linked polyethylene bearing surfaces in total hip arthroplasties have passed their first long-term longitudinal trial with flying colors, according to a blue-ribbon poster presented at the annual meeting of the American College of Orthopaedic Surgeons.

“After a minimum of five years follow-up of patients all done at Massachusetts General Hospital, there were no signs of radiographic osteolysis either on the acetabular or femoral sides, and this is the earliest point where you might normally start to see that with conventional polyethylene,” Charles R. Bragdon, Ph.D., said in an interview.

Electron beam irradiated highly cross-linked polyethylene (HXLPE) is created by taking standard high-density polyethylene and irradiating it, which increases cross-linking and improves wear characteristics. The material then goes through “a melting step which allows the free radicals generated during radiation to extinguish themselves and form more cross-linking. With the free radicals gone, there's no long-term oxidation, so the properties you get do not change over time,” Dr. Bragdon said explained.

HXLPE has been used as total hip arthroplasty bearing surface for nearly 8 years, according to Dr. Bragdon and his colleagues at the Orthopaedic Biomechanics and Biomaterials Laboratory at Massachusetts General Hospital in Boston. Radiostereometric analysis (RSA) has shown little additional femoral head penetration after the early bedding-in period; however, such studies have been performed on relatively small groups of patients, the authors continued. Using standardized measures, the Boston group studied femoral head penetration in 77 primary total hip replacements in 70 patients with HXLPE liners, with either a 28-mm or 32-mm femoral head.

The average total femoral head penetration was calculated based on the total penetration from the initial postoperative film to the longest follow-up film.

“During the first year following surgery, there was about 100 microns of head penetration into the polyethylene,” Dr. Bragdon said. “Thereafter … [there was] no measurable wear of this material at 5 years,” he said. In addition, there was no significant difference in the average penetration rate or the steady state wear rates between the 28-mm and 32-mm groups.

“These results are encouraging for lysis in the long term because we've shown in the past that lysis and wear tend to go hand in hand; we think our study bodes well for 7–15 years' follow-up,” said Dr. Bragdon, adding that continued follow-up will be necessary to evaluate the material's clinical and radiographic durability.

Dr. Bragdon predicted that these more durable replacements will further reduce the average age of both knee and hip recipients. “Cross-linked polyethylene's introduction has been in hip arthroplasty, but now it's also being used in knees because knee components also suffer from wear and osteolysis.”

Osteolysis was seen on x-ray 7 years after placement of a conventional polyethylene liner for total hip arthroplasty (left). No osteolysis was seen 6 years later with a highly cross-linked polyethylene liner (right). Photos courtesy Dr. Meridith Greene

CHICAGO — Highly cross-linked polyethylene bearing surfaces in total hip arthroplasties have passed their first long-term longitudinal trial with flying colors, according to a blue-ribbon poster presented at the annual meeting of the American College of Orthopaedic Surgeons.

“After a minimum of five years follow-up of patients all done at Massachusetts General Hospital, there were no signs of radiographic osteolysis either on the acetabular or femoral sides, and this is the earliest point where you might normally start to see that with conventional polyethylene,” Charles R. Bragdon, Ph.D., said in an interview.

Electron beam irradiated highly cross-linked polyethylene (HXLPE) is created by taking standard high-density polyethylene and irradiating it, which increases cross-linking and improves wear characteristics. The material then goes through “a melting step which allows the free radicals generated during radiation to extinguish themselves and form more cross-linking. With the free radicals gone, there's no long-term oxidation, so the properties you get do not change over time,” Dr. Bragdon said explained.

HXLPE has been used as total hip arthroplasty bearing surface for nearly 8 years, according to Dr. Bragdon and his colleagues at the Orthopaedic Biomechanics and Biomaterials Laboratory at Massachusetts General Hospital in Boston. Radiostereometric analysis (RSA) has shown little additional femoral head penetration after the early bedding-in period; however, such studies have been performed on relatively small groups of patients, the authors continued. Using standardized measures, the Boston group studied femoral head penetration in 77 primary total hip replacements in 70 patients with HXLPE liners, with either a 28-mm or 32-mm femoral head.

The average total femoral head penetration was calculated based on the total penetration from the initial postoperative film to the longest follow-up film.

“During the first year following surgery, there was about 100 microns of head penetration into the polyethylene,” Dr. Bragdon said. “Thereafter … [there was] no measurable wear of this material at 5 years,” he said. In addition, there was no significant difference in the average penetration rate or the steady state wear rates between the 28-mm and 32-mm groups.

“These results are encouraging for lysis in the long term because we've shown in the past that lysis and wear tend to go hand in hand; we think our study bodes well for 7–15 years' follow-up,” said Dr. Bragdon, adding that continued follow-up will be necessary to evaluate the material's clinical and radiographic durability.

Dr. Bragdon predicted that these more durable replacements will further reduce the average age of both knee and hip recipients. “Cross-linked polyethylene's introduction has been in hip arthroplasty, but now it's also being used in knees because knee components also suffer from wear and osteolysis.”

Osteolysis was seen on x-ray 7 years after placement of a conventional polyethylene liner for total hip arthroplasty (left). No osteolysis was seen 6 years later with a highly cross-linked polyethylene liner (right). Photos courtesy Dr. Meridith Greene

GLASGOW, SCOTLAND — Shoulder involvement is often overlooked in ankylosing spondylitis, despite patients' reports that upper body pain interferes with their daily activities, Dr. Charlotte E. Page reported in a poster session at the annual meeting of the British Society for Rheumatology.

Among a group of 31 ankylosing spondylitis (AS) patients attending a 2-week physiotherapy program who responded to questionnaires about their symptoms, 12 reported current shoulder pain, while 10 patients reported experiencing shoulder pain in the past, reported Dr. Page of the rheumatology department of University Hospital of Wales, Cardiff. The patients, aged 17–62 years, had a mean AS duration of 19 years.

Among patients with current shoulder pain, four reported bilateral symptoms, and nine indicated that their daily activities were affected. Among those with previous pain, three study patients reported that their shoulder involvement continued to interfere with their daily activities, noted Dr. Page.

The reported prevalence of shoulder pain among the general population is approximately 12%, and estimates among those with AS range from 7% to 33%, she noted. “Our prevalence of 39% is slightly higher, probably reflecting the type of patients who attend intensive physiotherapy programs.”

Only 10 of the 22 patients who had either current or past shoulder pain had undergone one or more radiologic investigations. Eight had been evaluated with plain radiographs, three with ultrasound, and three with MRI arthrograms.

Among the eight patients who had received one or more corticosteroid injections to the shoulder region, five reported still having shoulder pain and six reported still experiencing symptoms that interfered with daily activities. Among the seven who had received physiotherapy directed at their shoulder symptoms, five continued to experience pain.

Specific physiotherapy and corticosteroid injections had therefore been given to only 32% and 36% of patients, respectively, and had not alleviated the symptoms in the majority, she noted.

Moreover, a total of 26 patients reported peripheral joint involvement other than the shoulder. Despite this, only six patients received disease-modifying antirheumatic drugs or anti-tumor necrosis factor-α therapy, which suggests an underappreciation of the extent of AS patients' peripheral joint pain, according to Dr. Page.

Much of the shoulder involvement was rotator cuff tendonitis, which can be imaged and treated, Dr. Page said in an interview. Patients should be asked specifically about this, she said.

“We all know about their hip pain but we seem to forget about the top half” of the body, she said.

GLASGOW, SCOTLAND — Shoulder involvement is often overlooked in ankylosing spondylitis, despite patients' reports that upper body pain interferes with their daily activities, Dr. Charlotte E. Page reported in a poster session at the annual meeting of the British Society for Rheumatology.

Among a group of 31 ankylosing spondylitis (AS) patients attending a 2-week physiotherapy program who responded to questionnaires about their symptoms, 12 reported current shoulder pain, while 10 patients reported experiencing shoulder pain in the past, reported Dr. Page of the rheumatology department of University Hospital of Wales, Cardiff. The patients, aged 17–62 years, had a mean AS duration of 19 years.

Among patients with current shoulder pain, four reported bilateral symptoms, and nine indicated that their daily activities were affected. Among those with previous pain, three study patients reported that their shoulder involvement continued to interfere with their daily activities, noted Dr. Page.

The reported prevalence of shoulder pain among the general population is approximately 12%, and estimates among those with AS range from 7% to 33%, she noted. “Our prevalence of 39% is slightly higher, probably reflecting the type of patients who attend intensive physiotherapy programs.”

Only 10 of the 22 patients who had either current or past shoulder pain had undergone one or more radiologic investigations. Eight had been evaluated with plain radiographs, three with ultrasound, and three with MRI arthrograms.

Among the eight patients who had received one or more corticosteroid injections to the shoulder region, five reported still having shoulder pain and six reported still experiencing symptoms that interfered with daily activities. Among the seven who had received physiotherapy directed at their shoulder symptoms, five continued to experience pain.

Specific physiotherapy and corticosteroid injections had therefore been given to only 32% and 36% of patients, respectively, and had not alleviated the symptoms in the majority, she noted.

Moreover, a total of 26 patients reported peripheral joint involvement other than the shoulder. Despite this, only six patients received disease-modifying antirheumatic drugs or anti-tumor necrosis factor-α therapy, which suggests an underappreciation of the extent of AS patients' peripheral joint pain, according to Dr. Page.

Much of the shoulder involvement was rotator cuff tendonitis, which can be imaged and treated, Dr. Page said in an interview. Patients should be asked specifically about this, she said.

“We all know about their hip pain but we seem to forget about the top half” of the body, she said.

GLASGOW, SCOTLAND — Shoulder involvement is often overlooked in ankylosing spondylitis, despite patients' reports that upper body pain interferes with their daily activities, Dr. Charlotte E. Page reported in a poster session at the annual meeting of the British Society for Rheumatology.

Among a group of 31 ankylosing spondylitis (AS) patients attending a 2-week physiotherapy program who responded to questionnaires about their symptoms, 12 reported current shoulder pain, while 10 patients reported experiencing shoulder pain in the past, reported Dr. Page of the rheumatology department of University Hospital of Wales, Cardiff. The patients, aged 17–62 years, had a mean AS duration of 19 years.

Among patients with current shoulder pain, four reported bilateral symptoms, and nine indicated that their daily activities were affected. Among those with previous pain, three study patients reported that their shoulder involvement continued to interfere with their daily activities, noted Dr. Page.

The reported prevalence of shoulder pain among the general population is approximately 12%, and estimates among those with AS range from 7% to 33%, she noted. “Our prevalence of 39% is slightly higher, probably reflecting the type of patients who attend intensive physiotherapy programs.”

Only 10 of the 22 patients who had either current or past shoulder pain had undergone one or more radiologic investigations. Eight had been evaluated with plain radiographs, three with ultrasound, and three with MRI arthrograms.

Among the eight patients who had received one or more corticosteroid injections to the shoulder region, five reported still having shoulder pain and six reported still experiencing symptoms that interfered with daily activities. Among the seven who had received physiotherapy directed at their shoulder symptoms, five continued to experience pain.

Specific physiotherapy and corticosteroid injections had therefore been given to only 32% and 36% of patients, respectively, and had not alleviated the symptoms in the majority, she noted.

Moreover, a total of 26 patients reported peripheral joint involvement other than the shoulder. Despite this, only six patients received disease-modifying antirheumatic drugs or anti-tumor necrosis factor-α therapy, which suggests an underappreciation of the extent of AS patients' peripheral joint pain, according to Dr. Page.

Much of the shoulder involvement was rotator cuff tendonitis, which can be imaged and treated, Dr. Page said in an interview. Patients should be asked specifically about this, she said.

“We all know about their hip pain but we seem to forget about the top half” of the body, she said.

CHICAGO — Early treatment of ankylosing spondylitis may or may not prevent structural damage but it certainly improves quality of life and the ability to function, Dr. John Davis told a symposium of the American College of Rheumatology.

Dr. Davis pointed to four reasons for why ankylosing spondylitis (AS) is typically diagnosed about 8 years after disease onset: low awareness of the spondyloarthritis among nonrheumatologists; the erroneous belief among rheumatologists that AS is a “man's disease”; the difficulty in differentiating between mechanical and inflammatory back pain; and reliance on radiologic sacroiliitis, which is a late feature of AS.

Dr. Davis, who directs the Clinical Trials Center at the University of California, San Francisco, noted that the Spondylitis Association of America guidelines call for a thorough physical exam including x-rays, individual medical history, and any family history of AS, as well as blood work that includes a test for HLA-B27 antigen. Important signs of AS include pain that has persisted longer than 3 months, back pain, and stiffness that worsen with immobility but ease with physical activity, and a positive response to NSAIDs.

Research efforts are now focusing on three TNF inhibitors. Phase III trials of three biologics showed good responses that were maintained at over 2 years (etanercept and infliximab) and 24 weeks (adalimumab). All three drugs significantly outperformed placebo in phase III studies using the Assessment in AS (ASAS) International Working Group criteria and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The BASDAI form contains six visual analog scales (“none” to “very severe”) on fatigue, neck, back or hip pain, joint pain and swelling, tender areas, and morning stiffness. “If you use the BASDAI as an outcome measure you should expect about a 50% improvement in the BASDAI 50 in all the anti-TNF studies,” Dr. Davis explained, adding that physicians can print out the one-page form and have patients fill it out in their offices. The form is available at www.spondylitis.org/physician_resources/cme/basdai.pdf

In studies using the ASAS 5/6 Improvement Criteria, patient responses to tumor necrosis factor (TNF) inhibition approached 50%. Under this protocol, said Dr. Davis, patients had to have an improvement of at least 20% in four of five domains, including patient global, pain, function, inflammation, C-reactive protein, and/or spinal mobility. “Also, total spinal fusion is not a contraindication for using anti-TNF agents, as about 10% of patients who enrolled in the adalimumab study could have had total spinal fusion yet they responded to that drug,” he said, stressing that because anti-TNF therapy is lifelong, patients need to understand its risks and benefits.

International guidelines for treating patients with AS have been modified by the Spondyloarthritis Research and Treatment Network (SPARTAN) and are now in print (J. Rheumatol. 2006;33:978–82). “You can use the modified New York criteria or other evidence of spondyloarthropathy including inflammatory back pain, elevated acute phase reactants, rapid radiographic progression, spinal inflammation on imaging—including MRI—or, interestingly, ultrasound,” Dr. Davis explained, noting that French researchers found ultrasound to be especially useful in assessing enthesopathies.

“Your patient should have a BASDAI score of at least 4, and you as a physician should assign a moderate disease activity score on either a visual analog scale or the Likert scale. In general, there are three clinical presentations you need to keep in mind … the axial, peripheral arthritis excluding the hip, and the entheses. Pick out the predominant feature that you're going to treat and follow. All the manifestations should be treated with at least two courses of an NSAID, and those with significant arthritis or refractory enthesopathies should have failed either methotrexate or sulfasalazine at maximally tolerated doses for at least 3 months. For those with axial involvement, there's no requirement for nonbiologic disease-modifying antirheumatic drugs (DMARDs) and they should go directly to a biologic agent,” Dr. Davis said, adding that methotrexate and leflunomide have shown little evidence of efficacy in AS, while sulfasalizine has been shown to have effects mostly on peripheral manifestations. “Thalidomide and pamidronate interestingly have weak anti-TNF activity and have shown some clinical efficacy in small trials.”

Muscle relaxants can help, particularly when the patient is starting physical therapy. Corticosteroids injected into the sacroiliac joints alleviate refractory pain and topical corticosteroids are effective in treating acute anterior uveitis, Dr. Davis said.

After placing a patient on TNF blockade, expect a response (based on clinical trials and clinical experience) within 12 weeks. “And you want a change in your BASDAI score of at least 50% or two units, and a change in your physician global score of at least one.” Etanercept and infliximab have FDA approval, while approval of adalimumab is pending. Patients taking these medications should be screened for tuberculosis and consideration should be given to testing for hepatitis, especially in those from endemic areas, Dr. Davis said.

CHICAGO — Early treatment of ankylosing spondylitis may or may not prevent structural damage but it certainly improves quality of life and the ability to function, Dr. John Davis told a symposium of the American College of Rheumatology.

Dr. Davis pointed to four reasons for why ankylosing spondylitis (AS) is typically diagnosed about 8 years after disease onset: low awareness of the spondyloarthritis among nonrheumatologists; the erroneous belief among rheumatologists that AS is a “man's disease”; the difficulty in differentiating between mechanical and inflammatory back pain; and reliance on radiologic sacroiliitis, which is a late feature of AS.

Dr. Davis, who directs the Clinical Trials Center at the University of California, San Francisco, noted that the Spondylitis Association of America guidelines call for a thorough physical exam including x-rays, individual medical history, and any family history of AS, as well as blood work that includes a test for HLA-B27 antigen. Important signs of AS include pain that has persisted longer than 3 months, back pain, and stiffness that worsen with immobility but ease with physical activity, and a positive response to NSAIDs.

Research efforts are now focusing on three TNF inhibitors. Phase III trials of three biologics showed good responses that were maintained at over 2 years (etanercept and infliximab) and 24 weeks (adalimumab). All three drugs significantly outperformed placebo in phase III studies using the Assessment in AS (ASAS) International Working Group criteria and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The BASDAI form contains six visual analog scales (“none” to “very severe”) on fatigue, neck, back or hip pain, joint pain and swelling, tender areas, and morning stiffness. “If you use the BASDAI as an outcome measure you should expect about a 50% improvement in the BASDAI 50 in all the anti-TNF studies,” Dr. Davis explained, adding that physicians can print out the one-page form and have patients fill it out in their offices. The form is available at www.spondylitis.org/physician_resources/cme/basdai.pdf

In studies using the ASAS 5/6 Improvement Criteria, patient responses to tumor necrosis factor (TNF) inhibition approached 50%. Under this protocol, said Dr. Davis, patients had to have an improvement of at least 20% in four of five domains, including patient global, pain, function, inflammation, C-reactive protein, and/or spinal mobility. “Also, total spinal fusion is not a contraindication for using anti-TNF agents, as about 10% of patients who enrolled in the adalimumab study could have had total spinal fusion yet they responded to that drug,” he said, stressing that because anti-TNF therapy is lifelong, patients need to understand its risks and benefits.

International guidelines for treating patients with AS have been modified by the Spondyloarthritis Research and Treatment Network (SPARTAN) and are now in print (J. Rheumatol. 2006;33:978–82). “You can use the modified New York criteria or other evidence of spondyloarthropathy including inflammatory back pain, elevated acute phase reactants, rapid radiographic progression, spinal inflammation on imaging—including MRI—or, interestingly, ultrasound,” Dr. Davis explained, noting that French researchers found ultrasound to be especially useful in assessing enthesopathies.

“Your patient should have a BASDAI score of at least 4, and you as a physician should assign a moderate disease activity score on either a visual analog scale or the Likert scale. In general, there are three clinical presentations you need to keep in mind … the axial, peripheral arthritis excluding the hip, and the entheses. Pick out the predominant feature that you're going to treat and follow. All the manifestations should be treated with at least two courses of an NSAID, and those with significant arthritis or refractory enthesopathies should have failed either methotrexate or sulfasalazine at maximally tolerated doses for at least 3 months. For those with axial involvement, there's no requirement for nonbiologic disease-modifying antirheumatic drugs (DMARDs) and they should go directly to a biologic agent,” Dr. Davis said, adding that methotrexate and leflunomide have shown little evidence of efficacy in AS, while sulfasalizine has been shown to have effects mostly on peripheral manifestations. “Thalidomide and pamidronate interestingly have weak anti-TNF activity and have shown some clinical efficacy in small trials.”

Muscle relaxants can help, particularly when the patient is starting physical therapy. Corticosteroids injected into the sacroiliac joints alleviate refractory pain and topical corticosteroids are effective in treating acute anterior uveitis, Dr. Davis said.

After placing a patient on TNF blockade, expect a response (based on clinical trials and clinical experience) within 12 weeks. “And you want a change in your BASDAI score of at least 50% or two units, and a change in your physician global score of at least one.” Etanercept and infliximab have FDA approval, while approval of adalimumab is pending. Patients taking these medications should be screened for tuberculosis and consideration should be given to testing for hepatitis, especially in those from endemic areas, Dr. Davis said.

CHICAGO — Early treatment of ankylosing spondylitis may or may not prevent structural damage but it certainly improves quality of life and the ability to function, Dr. John Davis told a symposium of the American College of Rheumatology.

Dr. Davis pointed to four reasons for why ankylosing spondylitis (AS) is typically diagnosed about 8 years after disease onset: low awareness of the spondyloarthritis among nonrheumatologists; the erroneous belief among rheumatologists that AS is a “man's disease”; the difficulty in differentiating between mechanical and inflammatory back pain; and reliance on radiologic sacroiliitis, which is a late feature of AS.

Dr. Davis, who directs the Clinical Trials Center at the University of California, San Francisco, noted that the Spondylitis Association of America guidelines call for a thorough physical exam including x-rays, individual medical history, and any family history of AS, as well as blood work that includes a test for HLA-B27 antigen. Important signs of AS include pain that has persisted longer than 3 months, back pain, and stiffness that worsen with immobility but ease with physical activity, and a positive response to NSAIDs.

Research efforts are now focusing on three TNF inhibitors. Phase III trials of three biologics showed good responses that were maintained at over 2 years (etanercept and infliximab) and 24 weeks (adalimumab). All three drugs significantly outperformed placebo in phase III studies using the Assessment in AS (ASAS) International Working Group criteria and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The BASDAI form contains six visual analog scales (“none” to “very severe”) on fatigue, neck, back or hip pain, joint pain and swelling, tender areas, and morning stiffness. “If you use the BASDAI as an outcome measure you should expect about a 50% improvement in the BASDAI 50 in all the anti-TNF studies,” Dr. Davis explained, adding that physicians can print out the one-page form and have patients fill it out in their offices. The form is available at www.spondylitis.org/physician_resources/cme/basdai.pdf

In studies using the ASAS 5/6 Improvement Criteria, patient responses to tumor necrosis factor (TNF) inhibition approached 50%. Under this protocol, said Dr. Davis, patients had to have an improvement of at least 20% in four of five domains, including patient global, pain, function, inflammation, C-reactive protein, and/or spinal mobility. “Also, total spinal fusion is not a contraindication for using anti-TNF agents, as about 10% of patients who enrolled in the adalimumab study could have had total spinal fusion yet they responded to that drug,” he said, stressing that because anti-TNF therapy is lifelong, patients need to understand its risks and benefits.

International guidelines for treating patients with AS have been modified by the Spondyloarthritis Research and Treatment Network (SPARTAN) and are now in print (J. Rheumatol. 2006;33:978–82). “You can use the modified New York criteria or other evidence of spondyloarthropathy including inflammatory back pain, elevated acute phase reactants, rapid radiographic progression, spinal inflammation on imaging—including MRI—or, interestingly, ultrasound,” Dr. Davis explained, noting that French researchers found ultrasound to be especially useful in assessing enthesopathies.

“Your patient should have a BASDAI score of at least 4, and you as a physician should assign a moderate disease activity score on either a visual analog scale or the Likert scale. In general, there are three clinical presentations you need to keep in mind … the axial, peripheral arthritis excluding the hip, and the entheses. Pick out the predominant feature that you're going to treat and follow. All the manifestations should be treated with at least two courses of an NSAID, and those with significant arthritis or refractory enthesopathies should have failed either methotrexate or sulfasalazine at maximally tolerated doses for at least 3 months. For those with axial involvement, there's no requirement for nonbiologic disease-modifying antirheumatic drugs (DMARDs) and they should go directly to a biologic agent,” Dr. Davis said, adding that methotrexate and leflunomide have shown little evidence of efficacy in AS, while sulfasalizine has been shown to have effects mostly on peripheral manifestations. “Thalidomide and pamidronate interestingly have weak anti-TNF activity and have shown some clinical efficacy in small trials.”

Muscle relaxants can help, particularly when the patient is starting physical therapy. Corticosteroids injected into the sacroiliac joints alleviate refractory pain and topical corticosteroids are effective in treating acute anterior uveitis, Dr. Davis said.

After placing a patient on TNF blockade, expect a response (based on clinical trials and clinical experience) within 12 weeks. “And you want a change in your BASDAI score of at least 50% or two units, and a change in your physician global score of at least one.” Etanercept and infliximab have FDA approval, while approval of adalimumab is pending. Patients taking these medications should be screened for tuberculosis and consideration should be given to testing for hepatitis, especially in those from endemic areas, Dr. Davis said.

SAN FRANCISCO — Ulcerated skin lesions in three patients with refractory pyoderma gangrenosum shrank and reepithelialized after 10–11 weekly treatments with granulocyte and monocyte adsorption apheresis, Dr. Mariko Seishima and her associates reported in a poster presentation at the annual meeting of the American Academy of Dermatology.

All three patients were being treated concurrently with prednisolone and cyclosporine, sulfasalazine, or cyclophosphamide, so it's difficult to sort out the exact benefit of granulocyte and monocyte adsorption apheresis (GCAP). It's significant, however, that the lesions had not healed with prior treatment with these medications and others, and clinicians were able to discontinue the drugs or reduce the dosages after GCAP, wrote Dr. Seishima and her associates at Ogaki (Japan) Municipal Hospital.

Pyoderma gangrenosum often is associated with other diseases, including Crohn's disease, ulcerative colitis, or rheumatoid arthritis. One of the three patients treated had rheumatoid arthritis. Recent studies of GCAP for ulcerative colitis have produced impressive results, the investigators noted.

Pyoderma gangrenosum is a chronic skin disorder characterized by intractable ulcers. Histology typically reveals dense cellular infiltration consisting of dominant neutrophils throughout the dermis. After the GCAP treatments, neutrophil counts and leukocyte counts decreased in all patients.

Dr. Seishima and her associates used the column design of GCAP to remove pathogenic granulocytes. The column is a device filled with 220 g of cellulose acetate beads, each 2 mm in diameter. The procedure draws peripheral blood from the cubital vein of one of the patient's arms, perfuses it through the column to remove pathogenic granulocytes, and returns the blood to the cubital vein of the opposite arm. The consecutive weekly sessions each lasted 60 minutes, with a flow rate of 30 mL/min.

No side effects were seen during 8 months of follow-up after completing the GCAP treatments.

For patients with pyoderma gangrenosum who do not respond to treatment with corticosteroids, sulfonamides, and immunosuppressive agents, GCAP may be a useful alternative, according to Dr. Seishima and her colleagues.

A double-blind clinical study is needed to confirm the effects of GCAP, they wrote. Future research also should examine GCAP alone or combined with drug therapy and try to identify the optimal frequency and number of treatments.

SAN FRANCISCO — Ulcerated skin lesions in three patients with refractory pyoderma gangrenosum shrank and reepithelialized after 10–11 weekly treatments with granulocyte and monocyte adsorption apheresis, Dr. Mariko Seishima and her associates reported in a poster presentation at the annual meeting of the American Academy of Dermatology.

All three patients were being treated concurrently with prednisolone and cyclosporine, sulfasalazine, or cyclophosphamide, so it's difficult to sort out the exact benefit of granulocyte and monocyte adsorption apheresis (GCAP). It's significant, however, that the lesions had not healed with prior treatment with these medications and others, and clinicians were able to discontinue the drugs or reduce the dosages after GCAP, wrote Dr. Seishima and her associates at Ogaki (Japan) Municipal Hospital.

Pyoderma gangrenosum often is associated with other diseases, including Crohn's disease, ulcerative colitis, or rheumatoid arthritis. One of the three patients treated had rheumatoid arthritis. Recent studies of GCAP for ulcerative colitis have produced impressive results, the investigators noted.

Pyoderma gangrenosum is a chronic skin disorder characterized by intractable ulcers. Histology typically reveals dense cellular infiltration consisting of dominant neutrophils throughout the dermis. After the GCAP treatments, neutrophil counts and leukocyte counts decreased in all patients.

Dr. Seishima and her associates used the column design of GCAP to remove pathogenic granulocytes. The column is a device filled with 220 g of cellulose acetate beads, each 2 mm in diameter. The procedure draws peripheral blood from the cubital vein of one of the patient's arms, perfuses it through the column to remove pathogenic granulocytes, and returns the blood to the cubital vein of the opposite arm. The consecutive weekly sessions each lasted 60 minutes, with a flow rate of 30 mL/min.

No side effects were seen during 8 months of follow-up after completing the GCAP treatments.

For patients with pyoderma gangrenosum who do not respond to treatment with corticosteroids, sulfonamides, and immunosuppressive agents, GCAP may be a useful alternative, according to Dr. Seishima and her colleagues.

A double-blind clinical study is needed to confirm the effects of GCAP, they wrote. Future research also should examine GCAP alone or combined with drug therapy and try to identify the optimal frequency and number of treatments.

SAN FRANCISCO — Ulcerated skin lesions in three patients with refractory pyoderma gangrenosum shrank and reepithelialized after 10–11 weekly treatments with granulocyte and monocyte adsorption apheresis, Dr. Mariko Seishima and her associates reported in a poster presentation at the annual meeting of the American Academy of Dermatology.

All three patients were being treated concurrently with prednisolone and cyclosporine, sulfasalazine, or cyclophosphamide, so it's difficult to sort out the exact benefit of granulocyte and monocyte adsorption apheresis (GCAP). It's significant, however, that the lesions had not healed with prior treatment with these medications and others, and clinicians were able to discontinue the drugs or reduce the dosages after GCAP, wrote Dr. Seishima and her associates at Ogaki (Japan) Municipal Hospital.

Pyoderma gangrenosum often is associated with other diseases, including Crohn's disease, ulcerative colitis, or rheumatoid arthritis. One of the three patients treated had rheumatoid arthritis. Recent studies of GCAP for ulcerative colitis have produced impressive results, the investigators noted.

Pyoderma gangrenosum is a chronic skin disorder characterized by intractable ulcers. Histology typically reveals dense cellular infiltration consisting of dominant neutrophils throughout the dermis. After the GCAP treatments, neutrophil counts and leukocyte counts decreased in all patients.

Dr. Seishima and her associates used the column design of GCAP to remove pathogenic granulocytes. The column is a device filled with 220 g of cellulose acetate beads, each 2 mm in diameter. The procedure draws peripheral blood from the cubital vein of one of the patient's arms, perfuses it through the column to remove pathogenic granulocytes, and returns the blood to the cubital vein of the opposite arm. The consecutive weekly sessions each lasted 60 minutes, with a flow rate of 30 mL/min.

No side effects were seen during 8 months of follow-up after completing the GCAP treatments.

For patients with pyoderma gangrenosum who do not respond to treatment with corticosteroids, sulfonamides, and immunosuppressive agents, GCAP may be a useful alternative, according to Dr. Seishima and her colleagues.

A double-blind clinical study is needed to confirm the effects of GCAP, they wrote. Future research also should examine GCAP alone or combined with drug therapy and try to identify the optimal frequency and number of treatments.

STOWE, VT. — Use of several agents prescribed for the management of arthritis and other diseases seen by rheumatologists can induce cutaneous reactions that require referral to a dermatologist, said Dr. Peter W. Heald at a dermatology conference sponsored by the University of Vermont.

Because these drug-aggravated conditions often present as known diseases but frequently have different underlying mechanisms and treatment responses, diagnosis and management can be problematic, according to Dr. Heald, professor of dermatology at Yale University, New Haven, Conn. Also, the condition the suspect drug is prescribed to treat may make it inadvisable to discontinue the medication. To help unmask some of the dermatologic impostors, Dr. Heald presented a series of clinical cases from his own practice along with management pearls gleaned from personal experience and recent literature.

Interferon-Induced Cytokine Psoriasis

Cytokine psoriasis—a subset of psoriasis with a unique clinical appearance and therapy profile—started appearing with some frequency around 1990, not coincidentally around the time treatment with interferon for hepatitis C became more common, Dr. Heald said. “Over the past decade, we've started seeing tons of patients who are 1–2 months into interferon therapy coming in with psoriasis that's just gone crazy. They have acute, irritated, oozing lesions, sometimes with pruritus and often associated with palmar lesions and acral dermatitis,” he said. Of interest, the psoriatic lesions are not local to the interferon injection sites, but rather are all over the body and, if the patient has or is prone to psoriatic arthritis, that will be induced or aggravated as well.

Although the exact underlying mechanism for this is not fully understood, psoriasis is thought to be an immune-mediated disease with a cytokine profile predominantly of the T helper cell, type 1 (TH1) subset. Presumably, interferon-α triggers psoriasis by activating dendritic cells and T cells involved in the pathogenesis of the condition, according to Dr. Heald. “I'm not a big believer in interferon inducing new cases;” it is more likely that interferon causes problems in people who are prone to psoriasis or who have a mild case, he said. “If you've got a condition where you've already got a TH1-mediated process going on in the skin, and you feed that interferon, it's going to cause problems.”

The plan for managing this type of psoriasis is to treat the patients while they are completing their course of interferon therapy. “The usual regimen is etanercept—I start them on 50 mg twice a week—with or without prednisone for rapid onset of relief,” Dr. Heald said. “In my experience, the response to etanercept for this type of psoriasis is even better than [it is for] regular psoriasis.” At the end of the interferon course, patients can be safely tapered off of the etanercept, he said.

An important consideration in the management of these patients, said Dr. Heald, is to involve the treating physician in the decision process. “Let them know that you are going to start treatment and that you're comfortable using the anti-tumor necrosis factor therapy.”

Antimalarial Psoriasis

“I recently saw a patient who started on an antimalarial medication to treat symmetric polyarthritis with psoriasis. Within 2 weeks of starting the drug, he began to develop what I call a 'fill in the gap' type of psoriasis, in which erythema develops in between preexisting plaques,” Dr. Heald said. “We've seen a bunch of these cases because for a while at our Veterans [Affairs] hospital a patient had to fail an antimalarial before getting approval for treatment with a biologic for psoriatic arthritis.” To manage this condition, “we stop the drug immediately and switch over to something that can treat both [psoriasis and psoriatic arthritis] and possibly a prednisone taper,” Dr. Heald said. “I don't think psoriasis patients should ever be put on antimalarials. Hydroxychloroquine inhibits epidermal transglutaminase activity, which leads to irregular keratinization and dermoepidermal detachment and cleft formation. In psoriatics, this leads to an erythrodermic form of the disease.”

Efalizumab-Interruption Psoriasis

Most dermatologists have legions of happy psoriasis patients thanks to the efficacy of biologics for continuous control of their conditions, “but there is one little side to this that has not been published enough: the possibility of psoriasis exacerbation when treatment is interrupted,” said Dr. Heald, who has had patients weeks and even months into successful therapy whose psoriasis returns with a vengeance following two or three missed doses. “One of my patients went on a trip and forgot his medication for 3 days. He experienced an unbelievably quick, abrupt aggravation with lots of very pruritic new lesions and oozing lesions.” It's unclear what's behind this, he said, but it's possible that with an interruption in therapy “all those cells go barreling back into the skin and create this abrupt syndrome.”

To manage the reaction, “I have sometimes tried getting prednisone or cyclosporine in there right away just to get immediate control because these patients get so bad so quickly, and then [I] start another form of therapy.”

Interferon: Pyoderma Gangrenosum

Although not common, the development of virulent pyoderma gangrenosum-type ulcers at the interferon injection sites of some patients receiving the drug for multiple sclerosis or hepatitis C, “appears to be the result of interferon aggravating one of the TH1 types of inflammatory processes that typically occurs within 3 months of starting the therapy,” Dr. Heald said. Biopsies of the affected areas may show neutrophil infiltrates of vasculitis.

“Because patients and their neurologists love the drug, they're not going to stop it, so they will want you to help manage them through it,” Dr. Heald said. This is particularly true for patients with multiple sclerosis. “Patients who are staying on interferon for MS can be taught how to do interlesional triamcinolone injections, which I've had the most success with.”

Vitiligo and Imiquimod

Topical imiquimod can induce local interferon-α release and vitiligo hypopigmentation. “In patients prone to vitiligo, the imiquimod triggers an immunomodulating event that may enhance a latent cell-mediated process,” Dr. Heald said. “In the patients I've treated with this condition, nobody has developed vitiligo all over. It's been localized to the area of imiquimod application.” Use one of the other topical immunomodulator drugs, he said.

Infliximab and Lupus Erythematosus

Four months on infliximab appears to bring out subclinical lupus in a small percentage of patients with preexisting antinuclear antibodies.

“I've had about a half-dozen patients who are on infliximab for rheumatoid arthritis coming in with a lupus-like syndrome of anular, flat, scaly skin lesions that tend to be mostly on the face and arms,” Dr. Heald said.

“The mechanism for the condition is a little bit murky, but what's clear is that in some systems with an ongoing autoimmune process, the anti-TNF action can exacerbate disease,” Dr. Heald said. “In these instances, you have to stop the drug. You can't treat through this.”

Alternative treatment options include methotrexate or thiopurines. “You want to stay away from the anti-TNF family in general,” he said, noting that once infliximab therapy is withdrawn, the skin lesions tend to clear in 2–3 months.

STOWE, VT. — Use of several agents prescribed for the management of arthritis and other diseases seen by rheumatologists can induce cutaneous reactions that require referral to a dermatologist, said Dr. Peter W. Heald at a dermatology conference sponsored by the University of Vermont.

Because these drug-aggravated conditions often present as known diseases but frequently have different underlying mechanisms and treatment responses, diagnosis and management can be problematic, according to Dr. Heald, professor of dermatology at Yale University, New Haven, Conn. Also, the condition the suspect drug is prescribed to treat may make it inadvisable to discontinue the medication. To help unmask some of the dermatologic impostors, Dr. Heald presented a series of clinical cases from his own practice along with management pearls gleaned from personal experience and recent literature.

Interferon-Induced Cytokine Psoriasis

Cytokine psoriasis—a subset of psoriasis with a unique clinical appearance and therapy profile—started appearing with some frequency around 1990, not coincidentally around the time treatment with interferon for hepatitis C became more common, Dr. Heald said. “Over the past decade, we've started seeing tons of patients who are 1–2 months into interferon therapy coming in with psoriasis that's just gone crazy. They have acute, irritated, oozing lesions, sometimes with pruritus and often associated with palmar lesions and acral dermatitis,” he said. Of interest, the psoriatic lesions are not local to the interferon injection sites, but rather are all over the body and, if the patient has or is prone to psoriatic arthritis, that will be induced or aggravated as well.

Although the exact underlying mechanism for this is not fully understood, psoriasis is thought to be an immune-mediated disease with a cytokine profile predominantly of the T helper cell, type 1 (TH1) subset. Presumably, interferon-α triggers psoriasis by activating dendritic cells and T cells involved in the pathogenesis of the condition, according to Dr. Heald. “I'm not a big believer in interferon inducing new cases;” it is more likely that interferon causes problems in people who are prone to psoriasis or who have a mild case, he said. “If you've got a condition where you've already got a TH1-mediated process going on in the skin, and you feed that interferon, it's going to cause problems.”

The plan for managing this type of psoriasis is to treat the patients while they are completing their course of interferon therapy. “The usual regimen is etanercept—I start them on 50 mg twice a week—with or without prednisone for rapid onset of relief,” Dr. Heald said. “In my experience, the response to etanercept for this type of psoriasis is even better than [it is for] regular psoriasis.” At the end of the interferon course, patients can be safely tapered off of the etanercept, he said.

An important consideration in the management of these patients, said Dr. Heald, is to involve the treating physician in the decision process. “Let them know that you are going to start treatment and that you're comfortable using the anti-tumor necrosis factor therapy.”

Antimalarial Psoriasis

“I recently saw a patient who started on an antimalarial medication to treat symmetric polyarthritis with psoriasis. Within 2 weeks of starting the drug, he began to develop what I call a 'fill in the gap' type of psoriasis, in which erythema develops in between preexisting plaques,” Dr. Heald said. “We've seen a bunch of these cases because for a while at our Veterans [Affairs] hospital a patient had to fail an antimalarial before getting approval for treatment with a biologic for psoriatic arthritis.” To manage this condition, “we stop the drug immediately and switch over to something that can treat both [psoriasis and psoriatic arthritis] and possibly a prednisone taper,” Dr. Heald said. “I don't think psoriasis patients should ever be put on antimalarials. Hydroxychloroquine inhibits epidermal transglutaminase activity, which leads to irregular keratinization and dermoepidermal detachment and cleft formation. In psoriatics, this leads to an erythrodermic form of the disease.”

Efalizumab-Interruption Psoriasis

Most dermatologists have legions of happy psoriasis patients thanks to the efficacy of biologics for continuous control of their conditions, “but there is one little side to this that has not been published enough: the possibility of psoriasis exacerbation when treatment is interrupted,” said Dr. Heald, who has had patients weeks and even months into successful therapy whose psoriasis returns with a vengeance following two or three missed doses. “One of my patients went on a trip and forgot his medication for 3 days. He experienced an unbelievably quick, abrupt aggravation with lots of very pruritic new lesions and oozing lesions.” It's unclear what's behind this, he said, but it's possible that with an interruption in therapy “all those cells go barreling back into the skin and create this abrupt syndrome.”

To manage the reaction, “I have sometimes tried getting prednisone or cyclosporine in there right away just to get immediate control because these patients get so bad so quickly, and then [I] start another form of therapy.”

Interferon: Pyoderma Gangrenosum

Although not common, the development of virulent pyoderma gangrenosum-type ulcers at the interferon injection sites of some patients receiving the drug for multiple sclerosis or hepatitis C, “appears to be the result of interferon aggravating one of the TH1 types of inflammatory processes that typically occurs within 3 months of starting the therapy,” Dr. Heald said. Biopsies of the affected areas may show neutrophil infiltrates of vasculitis.

“Because patients and their neurologists love the drug, they're not going to stop it, so they will want you to help manage them through it,” Dr. Heald said. This is particularly true for patients with multiple sclerosis. “Patients who are staying on interferon for MS can be taught how to do interlesional triamcinolone injections, which I've had the most success with.”

Vitiligo and Imiquimod

Topical imiquimod can induce local interferon-α release and vitiligo hypopigmentation. “In patients prone to vitiligo, the imiquimod triggers an immunomodulating event that may enhance a latent cell-mediated process,” Dr. Heald said. “In the patients I've treated with this condition, nobody has developed vitiligo all over. It's been localized to the area of imiquimod application.” Use one of the other topical immunomodulator drugs, he said.

Infliximab and Lupus Erythematosus

Four months on infliximab appears to bring out subclinical lupus in a small percentage of patients with preexisting antinuclear antibodies.

“I've had about a half-dozen patients who are on infliximab for rheumatoid arthritis coming in with a lupus-like syndrome of anular, flat, scaly skin lesions that tend to be mostly on the face and arms,” Dr. Heald said.

“The mechanism for the condition is a little bit murky, but what's clear is that in some systems with an ongoing autoimmune process, the anti-TNF action can exacerbate disease,” Dr. Heald said. “In these instances, you have to stop the drug. You can't treat through this.”

Alternative treatment options include methotrexate or thiopurines. “You want to stay away from the anti-TNF family in general,” he said, noting that once infliximab therapy is withdrawn, the skin lesions tend to clear in 2–3 months.

STOWE, VT. — Use of several agents prescribed for the management of arthritis and other diseases seen by rheumatologists can induce cutaneous reactions that require referral to a dermatologist, said Dr. Peter W. Heald at a dermatology conference sponsored by the University of Vermont.

Because these drug-aggravated conditions often present as known diseases but frequently have different underlying mechanisms and treatment responses, diagnosis and management can be problematic, according to Dr. Heald, professor of dermatology at Yale University, New Haven, Conn. Also, the condition the suspect drug is prescribed to treat may make it inadvisable to discontinue the medication. To help unmask some of the dermatologic impostors, Dr. Heald presented a series of clinical cases from his own practice along with management pearls gleaned from personal experience and recent literature.

Interferon-Induced Cytokine Psoriasis

Cytokine psoriasis—a subset of psoriasis with a unique clinical appearance and therapy profile—started appearing with some frequency around 1990, not coincidentally around the time treatment with interferon for hepatitis C became more common, Dr. Heald said. “Over the past decade, we've started seeing tons of patients who are 1–2 months into interferon therapy coming in with psoriasis that's just gone crazy. They have acute, irritated, oozing lesions, sometimes with pruritus and often associated with palmar lesions and acral dermatitis,” he said. Of interest, the psoriatic lesions are not local to the interferon injection sites, but rather are all over the body and, if the patient has or is prone to psoriatic arthritis, that will be induced or aggravated as well.

Although the exact underlying mechanism for this is not fully understood, psoriasis is thought to be an immune-mediated disease with a cytokine profile predominantly of the T helper cell, type 1 (TH1) subset. Presumably, interferon-α triggers psoriasis by activating dendritic cells and T cells involved in the pathogenesis of the condition, according to Dr. Heald. “I'm not a big believer in interferon inducing new cases;” it is more likely that interferon causes problems in people who are prone to psoriasis or who have a mild case, he said. “If you've got a condition where you've already got a TH1-mediated process going on in the skin, and you feed that interferon, it's going to cause problems.”

The plan for managing this type of psoriasis is to treat the patients while they are completing their course of interferon therapy. “The usual regimen is etanercept—I start them on 50 mg twice a week—with or without prednisone for rapid onset of relief,” Dr. Heald said. “In my experience, the response to etanercept for this type of psoriasis is even better than [it is for] regular psoriasis.” At the end of the interferon course, patients can be safely tapered off of the etanercept, he said.

An important consideration in the management of these patients, said Dr. Heald, is to involve the treating physician in the decision process. “Let them know that you are going to start treatment and that you're comfortable using the anti-tumor necrosis factor therapy.”

Antimalarial Psoriasis

“I recently saw a patient who started on an antimalarial medication to treat symmetric polyarthritis with psoriasis. Within 2 weeks of starting the drug, he began to develop what I call a 'fill in the gap' type of psoriasis, in which erythema develops in between preexisting plaques,” Dr. Heald said. “We've seen a bunch of these cases because for a while at our Veterans [Affairs] hospital a patient had to fail an antimalarial before getting approval for treatment with a biologic for psoriatic arthritis.” To manage this condition, “we stop the drug immediately and switch over to something that can treat both [psoriasis and psoriatic arthritis] and possibly a prednisone taper,” Dr. Heald said. “I don't think psoriasis patients should ever be put on antimalarials. Hydroxychloroquine inhibits epidermal transglutaminase activity, which leads to irregular keratinization and dermoepidermal detachment and cleft formation. In psoriatics, this leads to an erythrodermic form of the disease.”

Efalizumab-Interruption Psoriasis

Most dermatologists have legions of happy psoriasis patients thanks to the efficacy of biologics for continuous control of their conditions, “but there is one little side to this that has not been published enough: the possibility of psoriasis exacerbation when treatment is interrupted,” said Dr. Heald, who has had patients weeks and even months into successful therapy whose psoriasis returns with a vengeance following two or three missed doses. “One of my patients went on a trip and forgot his medication for 3 days. He experienced an unbelievably quick, abrupt aggravation with lots of very pruritic new lesions and oozing lesions.” It's unclear what's behind this, he said, but it's possible that with an interruption in therapy “all those cells go barreling back into the skin and create this abrupt syndrome.”

To manage the reaction, “I have sometimes tried getting prednisone or cyclosporine in there right away just to get immediate control because these patients get so bad so quickly, and then [I] start another form of therapy.”

Interferon: Pyoderma Gangrenosum

Although not common, the development of virulent pyoderma gangrenosum-type ulcers at the interferon injection sites of some patients receiving the drug for multiple sclerosis or hepatitis C, “appears to be the result of interferon aggravating one of the TH1 types of inflammatory processes that typically occurs within 3 months of starting the therapy,” Dr. Heald said. Biopsies of the affected areas may show neutrophil infiltrates of vasculitis.

“Because patients and their neurologists love the drug, they're not going to stop it, so they will want you to help manage them through it,” Dr. Heald said. This is particularly true for patients with multiple sclerosis. “Patients who are staying on interferon for MS can be taught how to do interlesional triamcinolone injections, which I've had the most success with.”

Vitiligo and Imiquimod

Topical imiquimod can induce local interferon-α release and vitiligo hypopigmentation. “In patients prone to vitiligo, the imiquimod triggers an immunomodulating event that may enhance a latent cell-mediated process,” Dr. Heald said. “In the patients I've treated with this condition, nobody has developed vitiligo all over. It's been localized to the area of imiquimod application.” Use one of the other topical immunomodulator drugs, he said.

Infliximab and Lupus Erythematosus

Four months on infliximab appears to bring out subclinical lupus in a small percentage of patients with preexisting antinuclear antibodies.

“I've had about a half-dozen patients who are on infliximab for rheumatoid arthritis coming in with a lupus-like syndrome of anular, flat, scaly skin lesions that tend to be mostly on the face and arms,” Dr. Heald said.

“The mechanism for the condition is a little bit murky, but what's clear is that in some systems with an ongoing autoimmune process, the anti-TNF action can exacerbate disease,” Dr. Heald said. “In these instances, you have to stop the drug. You can't treat through this.”

Alternative treatment options include methotrexate or thiopurines. “You want to stay away from the anti-TNF family in general,” he said, noting that once infliximab therapy is withdrawn, the skin lesions tend to clear in 2–3 months.

Patients with early rheumatoid arthritis who are most likely to benefit from immediate introduction of infliximab plus high-dose methotrexate are those with high C-reactive protein levels, a high erythrocyte sedimentation rate, or persistent disease activity, as well as greater initial joint damage, according to a new analysis of trial data reported Dr. Josef S. Smolen, and his associates in Europe and the United States.

The 54-week trial showed that overall, combination therapy with methotrexate and infliximab provided greater clinical, radiographic, and functional benefits than treatment with methotrexate alone for patients with active, early-stage RA (Arthritis Rheum. 2006;54:702–10).

The new findings build on results from the ASPIRE study (Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset), the investigators reported.

Patients in the trial had RA for no longer than 3 years; the 1,049 patients were randomized to receive titrating doses of methotrexate up to 20 mg/wk plus placebo or infliximab at weeks 0, 2, and 6, and then every 8 weeks through week 46, Dr. Smolen, of the Medical University of Vienna, and his colleagues reported.

In the new analysis, the investigators looked for predictors of radiographic joint damage in order to identify subgroups of patients who would likely improve with methotrexate alone and those who would most benefit from the more expensive and potentially toxic combination therapy.

To do so, Dr. Smolen and his colleagues looked at the relationship between disease activity measures taken at baseline and at week 14, as well as those averaged over time, with changes in radiographic joint damage.

Radiographs were obtained within 4 weeks of the start of treatment and at weeks 30 and 54. Joint damage was assessed by changes in modified Sharp/van der Heijde scores (SHS).

The investigators found that methotrexate alone failed to prevent the progression of joint damage among patients with the highest C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and swollen joint counts, as well as the highest levels of joint damage at baseline.

Infliximab in combination with methotrexate, on the other hand, inhibited radiographic progression regardless of baseline and early disease activity or joint damage.

Patients in the highest baseline tertile of CRP (3 mg/dL or greater) and ESR (52 mm/hour or greater) who were treated only with methotrexate had mean increases in the SHS for joint damage of 5.62 and 5.89, respectively, from baseline to week 54. In patients who were treated with methotrexate plus infliximab, these changes were 0.73 and 1.12, respectively.

Also, patients receiving methotrexate alone who had persistently active disease—higher disease activity scores (DAS28)—at week 14 showed greater progression of joint damage from baseline to week 54 than those with lower DAS28 scores. Combination treatment led to significantly less joint damage regardless of disease activity at this time.

“This finding is of particular importance, since physicians generally prescribe [methotrexate] as initial [disease modifying-antirheumatic drug therapy] and then assess the adequacy of response [some] 3–6 months later,” the investigators said. The results “suggest that continuation of [methotrexate] alone in patients with a DAS28 of [greater than] 4.02 (or a simplified Disease Activity Index of [greater than] 23.8) at week 14 carries with it a significant risk of progressive joint damage.”

Overall, they said, the new analysis shows that “it is especially important to identify patients whose disease is rapidly advancing and who have the greatest potential to benefit from more intensive therapy.”

Patients with early rheumatoid arthritis who are most likely to benefit from immediate introduction of infliximab plus high-dose methotrexate are those with high C-reactive protein levels, a high erythrocyte sedimentation rate, or persistent disease activity, as well as greater initial joint damage, according to a new analysis of trial data reported Dr. Josef S. Smolen, and his associates in Europe and the United States.

The 54-week trial showed that overall, combination therapy with methotrexate and infliximab provided greater clinical, radiographic, and functional benefits than treatment with methotrexate alone for patients with active, early-stage RA (Arthritis Rheum. 2006;54:702–10).

The new findings build on results from the ASPIRE study (Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset), the investigators reported.

Patients in the trial had RA for no longer than 3 years; the 1,049 patients were randomized to receive titrating doses of methotrexate up to 20 mg/wk plus placebo or infliximab at weeks 0, 2, and 6, and then every 8 weeks through week 46, Dr. Smolen, of the Medical University of Vienna, and his colleagues reported.

In the new analysis, the investigators looked for predictors of radiographic joint damage in order to identify subgroups of patients who would likely improve with methotrexate alone and those who would most benefit from the more expensive and potentially toxic combination therapy.

To do so, Dr. Smolen and his colleagues looked at the relationship between disease activity measures taken at baseline and at week 14, as well as those averaged over time, with changes in radiographic joint damage.

Radiographs were obtained within 4 weeks of the start of treatment and at weeks 30 and 54. Joint damage was assessed by changes in modified Sharp/van der Heijde scores (SHS).

The investigators found that methotrexate alone failed to prevent the progression of joint damage among patients with the highest C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and swollen joint counts, as well as the highest levels of joint damage at baseline.

Infliximab in combination with methotrexate, on the other hand, inhibited radiographic progression regardless of baseline and early disease activity or joint damage.

Patients in the highest baseline tertile of CRP (3 mg/dL or greater) and ESR (52 mm/hour or greater) who were treated only with methotrexate had mean increases in the SHS for joint damage of 5.62 and 5.89, respectively, from baseline to week 54. In patients who were treated with methotrexate plus infliximab, these changes were 0.73 and 1.12, respectively.

Also, patients receiving methotrexate alone who had persistently active disease—higher disease activity scores (DAS28)—at week 14 showed greater progression of joint damage from baseline to week 54 than those with lower DAS28 scores. Combination treatment led to significantly less joint damage regardless of disease activity at this time.

“This finding is of particular importance, since physicians generally prescribe [methotrexate] as initial [disease modifying-antirheumatic drug therapy] and then assess the adequacy of response [some] 3–6 months later,” the investigators said. The results “suggest that continuation of [methotrexate] alone in patients with a DAS28 of [greater than] 4.02 (or a simplified Disease Activity Index of [greater than] 23.8) at week 14 carries with it a significant risk of progressive joint damage.”

Overall, they said, the new analysis shows that “it is especially important to identify patients whose disease is rapidly advancing and who have the greatest potential to benefit from more intensive therapy.”

Patients with early rheumatoid arthritis who are most likely to benefit from immediate introduction of infliximab plus high-dose methotrexate are those with high C-reactive protein levels, a high erythrocyte sedimentation rate, or persistent disease activity, as well as greater initial joint damage, according to a new analysis of trial data reported Dr. Josef S. Smolen, and his associates in Europe and the United States.

The 54-week trial showed that overall, combination therapy with methotrexate and infliximab provided greater clinical, radiographic, and functional benefits than treatment with methotrexate alone for patients with active, early-stage RA (Arthritis Rheum. 2006;54:702–10).

The new findings build on results from the ASPIRE study (Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset), the investigators reported.

Patients in the trial had RA for no longer than 3 years; the 1,049 patients were randomized to receive titrating doses of methotrexate up to 20 mg/wk plus placebo or infliximab at weeks 0, 2, and 6, and then every 8 weeks through week 46, Dr. Smolen, of the Medical University of Vienna, and his colleagues reported.

In the new analysis, the investigators looked for predictors of radiographic joint damage in order to identify subgroups of patients who would likely improve with methotrexate alone and those who would most benefit from the more expensive and potentially toxic combination therapy.

To do so, Dr. Smolen and his colleagues looked at the relationship between disease activity measures taken at baseline and at week 14, as well as those averaged over time, with changes in radiographic joint damage.

Radiographs were obtained within 4 weeks of the start of treatment and at weeks 30 and 54. Joint damage was assessed by changes in modified Sharp/van der Heijde scores (SHS).

The investigators found that methotrexate alone failed to prevent the progression of joint damage among patients with the highest C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and swollen joint counts, as well as the highest levels of joint damage at baseline.

Infliximab in combination with methotrexate, on the other hand, inhibited radiographic progression regardless of baseline and early disease activity or joint damage.

Patients in the highest baseline tertile of CRP (3 mg/dL or greater) and ESR (52 mm/hour or greater) who were treated only with methotrexate had mean increases in the SHS for joint damage of 5.62 and 5.89, respectively, from baseline to week 54. In patients who were treated with methotrexate plus infliximab, these changes were 0.73 and 1.12, respectively.

Also, patients receiving methotrexate alone who had persistently active disease—higher disease activity scores (DAS28)—at week 14 showed greater progression of joint damage from baseline to week 54 than those with lower DAS28 scores. Combination treatment led to significantly less joint damage regardless of disease activity at this time.

“This finding is of particular importance, since physicians generally prescribe [methotrexate] as initial [disease modifying-antirheumatic drug therapy] and then assess the adequacy of response [some] 3–6 months later,” the investigators said. The results “suggest that continuation of [methotrexate] alone in patients with a DAS28 of [greater than] 4.02 (or a simplified Disease Activity Index of [greater than] 23.8) at week 14 carries with it a significant risk of progressive joint damage.”

Overall, they said, the new analysis shows that “it is especially important to identify patients whose disease is rapidly advancing and who have the greatest potential to benefit from more intensive therapy.”

TUCSON, ARIZ. — A novel test for diagnosing carpal and cubital tunnel syndromes was at least as accurate as conventional tests, according to the findings of a prospective, case-control investigation.

During the so-called scratch-collapse test, patients perform a simple resistive motor task, such as pressing their extended arms against a clinician, who then lightly scratches the site of peripheral nerve compression. The patient then immediately attempts to repeat the motor task. If the test is positive, there is a brief loss of proximal postural stability, or “collapse,” in the arm, Dr. Christine Cheng explained at the annual meeting of the American Association for Hand Surgery.

“My first reaction was sort of like everyone else's—'This is crazy,'” she said in an interview. “But it does seem to bear out.”

The test was developed by San Diego orthopedic surgeon Dr. John Beck, based on observations of postural stimulation and muscle control in patients with Parkinson's disease.

The exact mechanism is not fully understood. But it is hypothesized that the test is detecting a short circuit or delay in the proximal muscles, said Dr. Cheng of Washington University, St. Louis.

She presented data from a prospective study in which 169 patients and 109 controls were evaluated for carpal and cubital tunnel syndromes using Tinel's sign, Phalen's test, elbow flexion, and the scratch-collapse test.

Electrodiagnostic studies were used to confirm the diagnosis of carpal tunnel in 119 patients and 175 hands, and cubital tunnel in 70 patients and 81 hands.

In the control group, testing was rarely positive, she said. In the 175 hands with carpal tunnel syndrome, 148 had a positive scratch-collapse test, 141 had a positive Tinel's sign, and 131 had a positive Phalen's test.

In the 81 hands with cubital tunnel syndrome, 64 had a positive scratch-collapse test, 64 had a positive Tinel's sign, and 56 had positive elbow flexion.

Sensitivity of the scratch-collapse test in subjects with carpal tunnel syndrome was 75%, compared with 37% for Tinel's sign and 47% for Phalen's test. Specificity was 62%, 75%, and 66%, respectively. Accuracy was 72%, 47%, and 54%.

Sensitivity of the scratch-collapse test in subjects with cubital tunnel syndrome was 83%, compared with 65% for Tinel's sign and 54% for elbow flexion. Specificity was 82%, 86%, and 81%, respectively. Accuracy was 82%, 77%, and 69%.

Dr. Cheng and her colleagues have been using the test for about 2 years, in conjunction with other testing, to establish a diagnosis of carpal tunnel in patients. Part of the problem in establishing this diagnosis is that it remains primarily clinical, she explained.

The sensitivity and specificity of clinical tests vary widely, electrodiagnostic studies still have significant false-positive and false-negative values, and predictive values depend on the prevalence of disease.

“For something as common and presumably simple as carpal tunnel syndrome, it's not all that easy to diagnose because there really isn't a gold standard that you can use,” she said.

TUCSON, ARIZ. — A novel test for diagnosing carpal and cubital tunnel syndromes was at least as accurate as conventional tests, according to the findings of a prospective, case-control investigation.

During the so-called scratch-collapse test, patients perform a simple resistive motor task, such as pressing their extended arms against a clinician, who then lightly scratches the site of peripheral nerve compression. The patient then immediately attempts to repeat the motor task. If the test is positive, there is a brief loss of proximal postural stability, or “collapse,” in the arm, Dr. Christine Cheng explained at the annual meeting of the American Association for Hand Surgery.

“My first reaction was sort of like everyone else's—'This is crazy,'” she said in an interview. “But it does seem to bear out.”

The test was developed by San Diego orthopedic surgeon Dr. John Beck, based on observations of postural stimulation and muscle control in patients with Parkinson's disease.

The exact mechanism is not fully understood. But it is hypothesized that the test is detecting a short circuit or delay in the proximal muscles, said Dr. Cheng of Washington University, St. Louis.

She presented data from a prospective study in which 169 patients and 109 controls were evaluated for carpal and cubital tunnel syndromes using Tinel's sign, Phalen's test, elbow flexion, and the scratch-collapse test.

Electrodiagnostic studies were used to confirm the diagnosis of carpal tunnel in 119 patients and 175 hands, and cubital tunnel in 70 patients and 81 hands.

In the control group, testing was rarely positive, she said. In the 175 hands with carpal tunnel syndrome, 148 had a positive scratch-collapse test, 141 had a positive Tinel's sign, and 131 had a positive Phalen's test.

In the 81 hands with cubital tunnel syndrome, 64 had a positive scratch-collapse test, 64 had a positive Tinel's sign, and 56 had positive elbow flexion.

Sensitivity of the scratch-collapse test in subjects with carpal tunnel syndrome was 75%, compared with 37% for Tinel's sign and 47% for Phalen's test. Specificity was 62%, 75%, and 66%, respectively. Accuracy was 72%, 47%, and 54%.

Sensitivity of the scratch-collapse test in subjects with cubital tunnel syndrome was 83%, compared with 65% for Tinel's sign and 54% for elbow flexion. Specificity was 82%, 86%, and 81%, respectively. Accuracy was 82%, 77%, and 69%.

Dr. Cheng and her colleagues have been using the test for about 2 years, in conjunction with other testing, to establish a diagnosis of carpal tunnel in patients. Part of the problem in establishing this diagnosis is that it remains primarily clinical, she explained.

The sensitivity and specificity of clinical tests vary widely, electrodiagnostic studies still have significant false-positive and false-negative values, and predictive values depend on the prevalence of disease.

“For something as common and presumably simple as carpal tunnel syndrome, it's not all that easy to diagnose because there really isn't a gold standard that you can use,” she said.

TUCSON, ARIZ. — A novel test for diagnosing carpal and cubital tunnel syndromes was at least as accurate as conventional tests, according to the findings of a prospective, case-control investigation.

During the so-called scratch-collapse test, patients perform a simple resistive motor task, such as pressing their extended arms against a clinician, who then lightly scratches the site of peripheral nerve compression. The patient then immediately attempts to repeat the motor task. If the test is positive, there is a brief loss of proximal postural stability, or “collapse,” in the arm, Dr. Christine Cheng explained at the annual meeting of the American Association for Hand Surgery.

“My first reaction was sort of like everyone else's—'This is crazy,'” she said in an interview. “But it does seem to bear out.”

The test was developed by San Diego orthopedic surgeon Dr. John Beck, based on observations of postural stimulation and muscle control in patients with Parkinson's disease.

The exact mechanism is not fully understood. But it is hypothesized that the test is detecting a short circuit or delay in the proximal muscles, said Dr. Cheng of Washington University, St. Louis.

She presented data from a prospective study in which 169 patients and 109 controls were evaluated for carpal and cubital tunnel syndromes using Tinel's sign, Phalen's test, elbow flexion, and the scratch-collapse test.

Electrodiagnostic studies were used to confirm the diagnosis of carpal tunnel in 119 patients and 175 hands, and cubital tunnel in 70 patients and 81 hands.

In the control group, testing was rarely positive, she said. In the 175 hands with carpal tunnel syndrome, 148 had a positive scratch-collapse test, 141 had a positive Tinel's sign, and 131 had a positive Phalen's test.

In the 81 hands with cubital tunnel syndrome, 64 had a positive scratch-collapse test, 64 had a positive Tinel's sign, and 56 had positive elbow flexion.

Sensitivity of the scratch-collapse test in subjects with carpal tunnel syndrome was 75%, compared with 37% for Tinel's sign and 47% for Phalen's test. Specificity was 62%, 75%, and 66%, respectively. Accuracy was 72%, 47%, and 54%.

Sensitivity of the scratch-collapse test in subjects with cubital tunnel syndrome was 83%, compared with 65% for Tinel's sign and 54% for elbow flexion. Specificity was 82%, 86%, and 81%, respectively. Accuracy was 82%, 77%, and 69%.

Dr. Cheng and her colleagues have been using the test for about 2 years, in conjunction with other testing, to establish a diagnosis of carpal tunnel in patients. Part of the problem in establishing this diagnosis is that it remains primarily clinical, she explained.

The sensitivity and specificity of clinical tests vary widely, electrodiagnostic studies still have significant false-positive and false-negative values, and predictive values depend on the prevalence of disease.

“For something as common and presumably simple as carpal tunnel syndrome, it's not all that easy to diagnose because there really isn't a gold standard that you can use,” she said.