Nancy Walsh

SAN DIEGO — Adding etanercept to standard immunosuppressive treatment in Wegener's granulomatosis does not increase efficacy and may increase the risks for developing solid tumors, according to Dr. John H. Stone.

Most patients with Wegener's granulomatosis achieve remission if treated with glucocorticoids and cyclophosphamide, but flares are common, adverse effects are troublesome, and no successful long-term maintenance regimen as yet exists. Moreover, the use of cyclophosphamide carries with it a risk of cancer induction, and patients with this vasculitis already are at elevated risk for malignancy.

The Wegener's Granulomatosis Etanercept Trial (WGET) was a randomized study comparing standard treatment plus the TNF-α inhibitor etanercept, 25 mg twice weekly, or placebo in 180 patients from eight centers.

Standard treatment in the trial consisted of glucocorticoids plus cyclophosphamide for patients with severe disease, and glucocorticoids plus methotrexate for those with limited disease.

Cyclophosphamide was given in doses of 2 mg/kg per day, adjusted for renal dysfunction. Patients who reached remission in 3–6 months could be switched to methotrexate or, if their creatinine was elevated, to azathioprine, Dr. Stone said.

Methotrexate was given in doses up to 25 mg/week, continued for 12 months after remission was achieved, and then tapered at a rate of 2.5 mg/month.

Azathioprine, used in only a small number of patients, was given in doses of 2 mg/kg per day. This was decreased by 25 mg/month after 12 months of remission.

“There were no differences at all in any of the major efficacy parameters, including sustained remission,” Dr. Stone said at the annual meeting of the American College of Rheumatology.

Only 49.4% of patients in the combined groups achieved and maintained disease remission throughout the trial, he said.

But there was one important difference between the etanercept and placebo groups: During the trial's 25-month follow-up period there were six solid malignancies, all in the etanercept group, said Dr. Stone of the Johns Hopkins Vasculitis Center, Baltimore, who chaired WGET.

There were two cases of colon cancer, one breast cancer, on renal cell carcinoma, one cholangiocarcinoma, and one recurrent liposarcoma. All six patients had received cyclophosphamide during the trial, and several had also been treated with this agent previously.

There were no differences between the two treatment groups in terms of gender, disease severity, or history of cancer, though patients in the etanercept group were 4–5 years older at baseline, and less likely to be newly diagnosed with Wegener's granulomatosis.

Data on age- and gender-specific incidence rates for invasive solid malignancies in the Surveillance, Epidemiology, and End Results (SEER) Program suggest that a total of 1.92 solid tumors could be expected in this cohort. The standardized incidence ratio in the trial therefore was 3.12, which was highly statistically significant, he said.

Three additional cancers were seen in the 6 months after the study (N. Engl. J. Med. 2005;352:351–61). One was prostate cancer in a 70-year-old man in the etanercept group; he had not received any cyclophosphamide during the trial. A second was in a patient initially randomized to placebo, who dropped out after a second severe flare. This patient was subsequently treated with infliximab for 14 months and was diagnosed with disseminated renal cell carcinoma.

The third was a cholangiocarcinoma in a patient in the placebo group who had not received any cyclophosphamide during the trial.

There were no differences between the groups in terms of the percentage of patients who had received cyclophosphamide before the trial, who had ever used daily cyclophosphamide, in the mean duration of daily cyclophosphamide therapy, or in the maximum daily cyclophosphamide dose.

“All of this does not prove an association between TNF inhibition, cyclophosphamide, and malignancy. But there is a biologic plausibility for this association—[the abbreviation] TNF stands for tumor necrosis factor,” Dr. Stone said.

Like infliximab and adalimumab, etanercept blocks this cytokine, which was shown in the 1970s to lyse tumors in vitro and in mice.

In discussing his findings, Dr. Stone noted that a strength of the study was the fact that the malignancy data were completely unbiased and were only detected at the end of the trial, when the database was unlocked.

Also important was the fact that the data were collected in the context of a clinical trial. “We know that postmarketing studies are very good at detecting rare events but not so good at detecting events that are common. Most of these cancers, such as those of the colon and breast, are common, so the likelihood of detecting them in any setting other than a clinical trial would be quite small,” he said.

The lack of efficacy and the heightened risk of malignancy seen in the trial also have potential implications for the use of other TNF blocking agents in Wegener's granulomatosis; in rheumatoid vasculitis, where patients might have received etanercept previously and now require cyclophosphamide; and in patients with systemic lupus erythematosus, many of whom have been previously treated with cyclophosphamide and now may be being given an anti-TNF drug, he said.

Ongoing follow-up from WGET, which was funded by the National Institutes of Health, the Food and Drug Administration Office of Orphan Products, and Amgen, is underway. Dr. Stone stated that he had no financial conflicts to disclose.

SAN DIEGO — Adding etanercept to standard immunosuppressive treatment in Wegener's granulomatosis does not increase efficacy and may increase the risks for developing solid tumors, according to Dr. John H. Stone.

Most patients with Wegener's granulomatosis achieve remission if treated with glucocorticoids and cyclophosphamide, but flares are common, adverse effects are troublesome, and no successful long-term maintenance regimen as yet exists. Moreover, the use of cyclophosphamide carries with it a risk of cancer induction, and patients with this vasculitis already are at elevated risk for malignancy.

The Wegener's Granulomatosis Etanercept Trial (WGET) was a randomized study comparing standard treatment plus the TNF-α inhibitor etanercept, 25 mg twice weekly, or placebo in 180 patients from eight centers.

Standard treatment in the trial consisted of glucocorticoids plus cyclophosphamide for patients with severe disease, and glucocorticoids plus methotrexate for those with limited disease.

Cyclophosphamide was given in doses of 2 mg/kg per day, adjusted for renal dysfunction. Patients who reached remission in 3–6 months could be switched to methotrexate or, if their creatinine was elevated, to azathioprine, Dr. Stone said.

Methotrexate was given in doses up to 25 mg/week, continued for 12 months after remission was achieved, and then tapered at a rate of 2.5 mg/month.

Azathioprine, used in only a small number of patients, was given in doses of 2 mg/kg per day. This was decreased by 25 mg/month after 12 months of remission.

“There were no differences at all in any of the major efficacy parameters, including sustained remission,” Dr. Stone said at the annual meeting of the American College of Rheumatology.

Only 49.4% of patients in the combined groups achieved and maintained disease remission throughout the trial, he said.

But there was one important difference between the etanercept and placebo groups: During the trial's 25-month follow-up period there were six solid malignancies, all in the etanercept group, said Dr. Stone of the Johns Hopkins Vasculitis Center, Baltimore, who chaired WGET.

There were two cases of colon cancer, one breast cancer, on renal cell carcinoma, one cholangiocarcinoma, and one recurrent liposarcoma. All six patients had received cyclophosphamide during the trial, and several had also been treated with this agent previously.

There were no differences between the two treatment groups in terms of gender, disease severity, or history of cancer, though patients in the etanercept group were 4–5 years older at baseline, and less likely to be newly diagnosed with Wegener's granulomatosis.

Data on age- and gender-specific incidence rates for invasive solid malignancies in the Surveillance, Epidemiology, and End Results (SEER) Program suggest that a total of 1.92 solid tumors could be expected in this cohort. The standardized incidence ratio in the trial therefore was 3.12, which was highly statistically significant, he said.

Three additional cancers were seen in the 6 months after the study (N. Engl. J. Med. 2005;352:351–61). One was prostate cancer in a 70-year-old man in the etanercept group; he had not received any cyclophosphamide during the trial. A second was in a patient initially randomized to placebo, who dropped out after a second severe flare. This patient was subsequently treated with infliximab for 14 months and was diagnosed with disseminated renal cell carcinoma.

The third was a cholangiocarcinoma in a patient in the placebo group who had not received any cyclophosphamide during the trial.

There were no differences between the groups in terms of the percentage of patients who had received cyclophosphamide before the trial, who had ever used daily cyclophosphamide, in the mean duration of daily cyclophosphamide therapy, or in the maximum daily cyclophosphamide dose.

“All of this does not prove an association between TNF inhibition, cyclophosphamide, and malignancy. But there is a biologic plausibility for this association—[the abbreviation] TNF stands for tumor necrosis factor,” Dr. Stone said.

Like infliximab and adalimumab, etanercept blocks this cytokine, which was shown in the 1970s to lyse tumors in vitro and in mice.

In discussing his findings, Dr. Stone noted that a strength of the study was the fact that the malignancy data were completely unbiased and were only detected at the end of the trial, when the database was unlocked.

Also important was the fact that the data were collected in the context of a clinical trial. “We know that postmarketing studies are very good at detecting rare events but not so good at detecting events that are common. Most of these cancers, such as those of the colon and breast, are common, so the likelihood of detecting them in any setting other than a clinical trial would be quite small,” he said.

The lack of efficacy and the heightened risk of malignancy seen in the trial also have potential implications for the use of other TNF blocking agents in Wegener's granulomatosis; in rheumatoid vasculitis, where patients might have received etanercept previously and now require cyclophosphamide; and in patients with systemic lupus erythematosus, many of whom have been previously treated with cyclophosphamide and now may be being given an anti-TNF drug, he said.

Ongoing follow-up from WGET, which was funded by the National Institutes of Health, the Food and Drug Administration Office of Orphan Products, and Amgen, is underway. Dr. Stone stated that he had no financial conflicts to disclose.

SAN DIEGO — Adding etanercept to standard immunosuppressive treatment in Wegener's granulomatosis does not increase efficacy and may increase the risks for developing solid tumors, according to Dr. John H. Stone.

Most patients with Wegener's granulomatosis achieve remission if treated with glucocorticoids and cyclophosphamide, but flares are common, adverse effects are troublesome, and no successful long-term maintenance regimen as yet exists. Moreover, the use of cyclophosphamide carries with it a risk of cancer induction, and patients with this vasculitis already are at elevated risk for malignancy.

The Wegener's Granulomatosis Etanercept Trial (WGET) was a randomized study comparing standard treatment plus the TNF-α inhibitor etanercept, 25 mg twice weekly, or placebo in 180 patients from eight centers.

Standard treatment in the trial consisted of glucocorticoids plus cyclophosphamide for patients with severe disease, and glucocorticoids plus methotrexate for those with limited disease.

Cyclophosphamide was given in doses of 2 mg/kg per day, adjusted for renal dysfunction. Patients who reached remission in 3–6 months could be switched to methotrexate or, if their creatinine was elevated, to azathioprine, Dr. Stone said.

Methotrexate was given in doses up to 25 mg/week, continued for 12 months after remission was achieved, and then tapered at a rate of 2.5 mg/month.

Azathioprine, used in only a small number of patients, was given in doses of 2 mg/kg per day. This was decreased by 25 mg/month after 12 months of remission.

“There were no differences at all in any of the major efficacy parameters, including sustained remission,” Dr. Stone said at the annual meeting of the American College of Rheumatology.

Only 49.4% of patients in the combined groups achieved and maintained disease remission throughout the trial, he said.

But there was one important difference between the etanercept and placebo groups: During the trial's 25-month follow-up period there were six solid malignancies, all in the etanercept group, said Dr. Stone of the Johns Hopkins Vasculitis Center, Baltimore, who chaired WGET.

There were two cases of colon cancer, one breast cancer, on renal cell carcinoma, one cholangiocarcinoma, and one recurrent liposarcoma. All six patients had received cyclophosphamide during the trial, and several had also been treated with this agent previously.

There were no differences between the two treatment groups in terms of gender, disease severity, or history of cancer, though patients in the etanercept group were 4–5 years older at baseline, and less likely to be newly diagnosed with Wegener's granulomatosis.

Data on age- and gender-specific incidence rates for invasive solid malignancies in the Surveillance, Epidemiology, and End Results (SEER) Program suggest that a total of 1.92 solid tumors could be expected in this cohort. The standardized incidence ratio in the trial therefore was 3.12, which was highly statistically significant, he said.

Three additional cancers were seen in the 6 months after the study (N. Engl. J. Med. 2005;352:351–61). One was prostate cancer in a 70-year-old man in the etanercept group; he had not received any cyclophosphamide during the trial. A second was in a patient initially randomized to placebo, who dropped out after a second severe flare. This patient was subsequently treated with infliximab for 14 months and was diagnosed with disseminated renal cell carcinoma.

The third was a cholangiocarcinoma in a patient in the placebo group who had not received any cyclophosphamide during the trial.

There were no differences between the groups in terms of the percentage of patients who had received cyclophosphamide before the trial, who had ever used daily cyclophosphamide, in the mean duration of daily cyclophosphamide therapy, or in the maximum daily cyclophosphamide dose.

“All of this does not prove an association between TNF inhibition, cyclophosphamide, and malignancy. But there is a biologic plausibility for this association—[the abbreviation] TNF stands for tumor necrosis factor,” Dr. Stone said.

Like infliximab and adalimumab, etanercept blocks this cytokine, which was shown in the 1970s to lyse tumors in vitro and in mice.

In discussing his findings, Dr. Stone noted that a strength of the study was the fact that the malignancy data were completely unbiased and were only detected at the end of the trial, when the database was unlocked.

Also important was the fact that the data were collected in the context of a clinical trial. “We know that postmarketing studies are very good at detecting rare events but not so good at detecting events that are common. Most of these cancers, such as those of the colon and breast, are common, so the likelihood of detecting them in any setting other than a clinical trial would be quite small,” he said.

The lack of efficacy and the heightened risk of malignancy seen in the trial also have potential implications for the use of other TNF blocking agents in Wegener's granulomatosis; in rheumatoid vasculitis, where patients might have received etanercept previously and now require cyclophosphamide; and in patients with systemic lupus erythematosus, many of whom have been previously treated with cyclophosphamide and now may be being given an anti-TNF drug, he said.

Ongoing follow-up from WGET, which was funded by the National Institutes of Health, the Food and Drug Administration Office of Orphan Products, and Amgen, is underway. Dr. Stone stated that he had no financial conflicts to disclose.

SAN DIEGO — A single infusion of pamidronate resulted in immunologic changes that, at least theoretically, could lead to a reduction in collagen production and fibrosis in scleroderma, Dr. Kenneth J. Warrington reported at the annual meeting of the American College of Rheumatology.

Immune activation plays a central role in the complex pathogenesis of scleroderma, with upregulation of certain profibrotic cytokines such as interleukin-4 (IL-4), IL-13, and transforming growth factor-β (TGF-β)

Pamidronate is an aminobisphosphonate that inhibits bone resorption and is indicated for the treatment of hypercalcemia associated with malignancy as well as for bone metastases and Paget's disease. In recent years it has come to light that this agent also has immunomodulatory properties, acting as a ligand for a subset of T cells that express the γΔ-T-cell receptor.

When this subclass of T cells is activated by pamidronate, an alteration in the cytokine pattern occurs. There is an increase in production of interferon-γ (IFN-γ, a cytokine that has antifibrotic properties. Upregulation of IFN-γ might alter the extracellular matrix deposition of collagen, said Dr. Warrington of the University of Tennessee, Memphis. “Therefore, administration of pamidronate could potentially restore the cytokine balance in scleroderma,” he said.

This hypothesis was tested in a small pilot study that included 19 patients, three-quarters of whom were women and whose mean disease duration was 11 years. They were given a single intravenous dose of 60 mg pamidronate and followed for 6 months, with cytokine production and lymphocyte activation being measured at 48 hours and at weeks 4, 8, 12, and 24 post infusion using enzyme-linked immunosorbent assay and flow cytometry.

At 48 hours there was a statistically significant increase in activated CD4 and CD8 lymphocytes; by week 4 the percentage of activated lymphocytes had returned to baseline levels. At weeks 4 and 8 a decrease in production of the profibrotic cytokine TGF-β was observed in vitro, along with an increase in the production of tumor necrosis factor-α (TNF-α, which regulates the transcription of type 1 collagen.

And with a specialized cytokine secretion assay it was noted that the γΔ-T-cell subset was indeed directly activated by pamidronate to produce IFN-γ. Cytokines from these T cells may then act indirectly on other cell subsets, inducing further activation downstream, Dr. Warrington said.

Safety was monitored throughout, and the drug was well tolerated. Four patients reported transient flulike symptoms at the 48-hour visit, a finding that has been reported previously with pamidronate. Clinical parameters overall were unchanged.

The findings of this study provide a basis for a follow-up study in which pamidronate would be infused repeatedly, with the goal of inducing sustained antifibrotic modulation of IFN-γ, TNF-α, and TGF-β, according to Dr. Warrington. This work was supported by grants from the Scleroderma Foundation and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

SAN DIEGO — A single infusion of pamidronate resulted in immunologic changes that, at least theoretically, could lead to a reduction in collagen production and fibrosis in scleroderma, Dr. Kenneth J. Warrington reported at the annual meeting of the American College of Rheumatology.

Immune activation plays a central role in the complex pathogenesis of scleroderma, with upregulation of certain profibrotic cytokines such as interleukin-4 (IL-4), IL-13, and transforming growth factor-β (TGF-β)

Pamidronate is an aminobisphosphonate that inhibits bone resorption and is indicated for the treatment of hypercalcemia associated with malignancy as well as for bone metastases and Paget's disease. In recent years it has come to light that this agent also has immunomodulatory properties, acting as a ligand for a subset of T cells that express the γΔ-T-cell receptor.

When this subclass of T cells is activated by pamidronate, an alteration in the cytokine pattern occurs. There is an increase in production of interferon-γ (IFN-γ, a cytokine that has antifibrotic properties. Upregulation of IFN-γ might alter the extracellular matrix deposition of collagen, said Dr. Warrington of the University of Tennessee, Memphis. “Therefore, administration of pamidronate could potentially restore the cytokine balance in scleroderma,” he said.

This hypothesis was tested in a small pilot study that included 19 patients, three-quarters of whom were women and whose mean disease duration was 11 years. They were given a single intravenous dose of 60 mg pamidronate and followed for 6 months, with cytokine production and lymphocyte activation being measured at 48 hours and at weeks 4, 8, 12, and 24 post infusion using enzyme-linked immunosorbent assay and flow cytometry.

At 48 hours there was a statistically significant increase in activated CD4 and CD8 lymphocytes; by week 4 the percentage of activated lymphocytes had returned to baseline levels. At weeks 4 and 8 a decrease in production of the profibrotic cytokine TGF-β was observed in vitro, along with an increase in the production of tumor necrosis factor-α (TNF-α, which regulates the transcription of type 1 collagen.

And with a specialized cytokine secretion assay it was noted that the γΔ-T-cell subset was indeed directly activated by pamidronate to produce IFN-γ. Cytokines from these T cells may then act indirectly on other cell subsets, inducing further activation downstream, Dr. Warrington said.

Safety was monitored throughout, and the drug was well tolerated. Four patients reported transient flulike symptoms at the 48-hour visit, a finding that has been reported previously with pamidronate. Clinical parameters overall were unchanged.

The findings of this study provide a basis for a follow-up study in which pamidronate would be infused repeatedly, with the goal of inducing sustained antifibrotic modulation of IFN-γ, TNF-α, and TGF-β, according to Dr. Warrington. This work was supported by grants from the Scleroderma Foundation and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

SAN DIEGO — A single infusion of pamidronate resulted in immunologic changes that, at least theoretically, could lead to a reduction in collagen production and fibrosis in scleroderma, Dr. Kenneth J. Warrington reported at the annual meeting of the American College of Rheumatology.

Immune activation plays a central role in the complex pathogenesis of scleroderma, with upregulation of certain profibrotic cytokines such as interleukin-4 (IL-4), IL-13, and transforming growth factor-β (TGF-β)

Pamidronate is an aminobisphosphonate that inhibits bone resorption and is indicated for the treatment of hypercalcemia associated with malignancy as well as for bone metastases and Paget's disease. In recent years it has come to light that this agent also has immunomodulatory properties, acting as a ligand for a subset of T cells that express the γΔ-T-cell receptor.

When this subclass of T cells is activated by pamidronate, an alteration in the cytokine pattern occurs. There is an increase in production of interferon-γ (IFN-γ, a cytokine that has antifibrotic properties. Upregulation of IFN-γ might alter the extracellular matrix deposition of collagen, said Dr. Warrington of the University of Tennessee, Memphis. “Therefore, administration of pamidronate could potentially restore the cytokine balance in scleroderma,” he said.

This hypothesis was tested in a small pilot study that included 19 patients, three-quarters of whom were women and whose mean disease duration was 11 years. They were given a single intravenous dose of 60 mg pamidronate and followed for 6 months, with cytokine production and lymphocyte activation being measured at 48 hours and at weeks 4, 8, 12, and 24 post infusion using enzyme-linked immunosorbent assay and flow cytometry.

At 48 hours there was a statistically significant increase in activated CD4 and CD8 lymphocytes; by week 4 the percentage of activated lymphocytes had returned to baseline levels. At weeks 4 and 8 a decrease in production of the profibrotic cytokine TGF-β was observed in vitro, along with an increase in the production of tumor necrosis factor-α (TNF-α, which regulates the transcription of type 1 collagen.

And with a specialized cytokine secretion assay it was noted that the γΔ-T-cell subset was indeed directly activated by pamidronate to produce IFN-γ. Cytokines from these T cells may then act indirectly on other cell subsets, inducing further activation downstream, Dr. Warrington said.

Safety was monitored throughout, and the drug was well tolerated. Four patients reported transient flulike symptoms at the 48-hour visit, a finding that has been reported previously with pamidronate. Clinical parameters overall were unchanged.

The findings of this study provide a basis for a follow-up study in which pamidronate would be infused repeatedly, with the goal of inducing sustained antifibrotic modulation of IFN-γ, TNF-α, and TGF-β, according to Dr. Warrington. This work was supported by grants from the Scleroderma Foundation and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

SAN DIEGO — A second randomized clinical trial has confirmed that treatment with bosentan can help prevent the formation of digital ulcers in patients with scleroderma, Dr. James R. Seibold reported at the annual meeting of the American College of Rheumatology.

A total of 188 patients from 41 centers in North America and Europe were enrolled in the Randomized Placebo-Controlled Investigation of Digital Ulcers in Scleroderma (RAPIDS-2). All had scleroderma and at least one recent active digital ulcer, and their mean disease duration was 8.7 years.

At baseline, patients randomized to the placebo and bosentan groups had a mean of 3.6 and 3.7 digital ulcers, respectively.

By 24 weeks, a mean of 2.7 new ulcers were seen in the placebo group, compared with a mean of 1.9 in the active treatment group, Dr. Seibold said in a late-breaking poster session. This difference was statistically significant.

Statistically significant differences were already apparent by week 12, at which time the placebo group had a mean of 1.3 new digital ulcers, whereas the bosentan group had a mean of 0.8 new ulcers.

The effects were particularly marked in patients with more severe peripheral vascular injury, said Dr. Seibold, director of the University of Michigan Scleroderma Program, Ann Arbor.

Among patients who had more than 3 ulcers at baseline, those receiving placebo developed 4.4 new ulcers during the 24 weeks of the trial, while those receiving bosentan had 2.3 new ulcers, which was a statistically significant difference, he said.

“These data suggest that if a patient with scleroderma were to present at a physician's office with three digital ulcers, he or she would be likely to develop an additional four to five ulcers over the next 24 weeks, and the risk of that occurring would be reduced by nearly 50% on bosentan,” Dr. Seibold said in a discussion of the trial at a satellite symposium. Bosentan treatment did not, however, shorten the time to healing of active digital ulcers. In 6 months, only 50% of ulcers had healed despite treatment with topical and systemic antibiotics and adjustments to therapy for Raynaud's phenomenon. “These data are quite instructive in terms of getting a handle on how intractable this problem is. We are treating the untreatable,” he said.

The findings of this study are in agreement with those in RAPIDS-1, which evaluated bosentan in 122 patients with scleroderma for 16 weeks, and found a 48% reduction in the mean number of new ulcers (Arthritis Rheum. 2004;50:3985–93).

Serious adverse events were uncommon. As in RAPIDS-1, more patients in the active treatment group had elevations of liver enzymes greater than 3 times the upper limit of normal (10.5%) than in the placebo group (1.1%).

Bosentan (Tracleer) is a dual endothelin receptor antagonist. Endothelin-1 and its receptors, particularly the ETB receptor, are overexpressed in scleroderma, and the vasoconstrictive and pro-proliferative effects of endothelin-1 contribute to the vasculopathy associated with the disease. The RAPIDS data “support the contention that chronic endothelin receptor antagonism has an important effect on vascular integrity and function in systemic sclerosis,” he said.

Dr. Seibold disclosed that he has received research grants and consulting fees from Actelion Pharmaceuticals Ltd., the sponsor of the trial.

Bosentan blocks dual endothelin receptors, thereby preventing digital ulcers in patients with scleroderma. Courtesy Dr. James R. Seibold

SAN DIEGO — A second randomized clinical trial has confirmed that treatment with bosentan can help prevent the formation of digital ulcers in patients with scleroderma, Dr. James R. Seibold reported at the annual meeting of the American College of Rheumatology.

A total of 188 patients from 41 centers in North America and Europe were enrolled in the Randomized Placebo-Controlled Investigation of Digital Ulcers in Scleroderma (RAPIDS-2). All had scleroderma and at least one recent active digital ulcer, and their mean disease duration was 8.7 years.

At baseline, patients randomized to the placebo and bosentan groups had a mean of 3.6 and 3.7 digital ulcers, respectively.

By 24 weeks, a mean of 2.7 new ulcers were seen in the placebo group, compared with a mean of 1.9 in the active treatment group, Dr. Seibold said in a late-breaking poster session. This difference was statistically significant.

Statistically significant differences were already apparent by week 12, at which time the placebo group had a mean of 1.3 new digital ulcers, whereas the bosentan group had a mean of 0.8 new ulcers.

The effects were particularly marked in patients with more severe peripheral vascular injury, said Dr. Seibold, director of the University of Michigan Scleroderma Program, Ann Arbor.

Among patients who had more than 3 ulcers at baseline, those receiving placebo developed 4.4 new ulcers during the 24 weeks of the trial, while those receiving bosentan had 2.3 new ulcers, which was a statistically significant difference, he said.

“These data suggest that if a patient with scleroderma were to present at a physician's office with three digital ulcers, he or she would be likely to develop an additional four to five ulcers over the next 24 weeks, and the risk of that occurring would be reduced by nearly 50% on bosentan,” Dr. Seibold said in a discussion of the trial at a satellite symposium. Bosentan treatment did not, however, shorten the time to healing of active digital ulcers. In 6 months, only 50% of ulcers had healed despite treatment with topical and systemic antibiotics and adjustments to therapy for Raynaud's phenomenon. “These data are quite instructive in terms of getting a handle on how intractable this problem is. We are treating the untreatable,” he said.

The findings of this study are in agreement with those in RAPIDS-1, which evaluated bosentan in 122 patients with scleroderma for 16 weeks, and found a 48% reduction in the mean number of new ulcers (Arthritis Rheum. 2004;50:3985–93).

Serious adverse events were uncommon. As in RAPIDS-1, more patients in the active treatment group had elevations of liver enzymes greater than 3 times the upper limit of normal (10.5%) than in the placebo group (1.1%).

Bosentan (Tracleer) is a dual endothelin receptor antagonist. Endothelin-1 and its receptors, particularly the ETB receptor, are overexpressed in scleroderma, and the vasoconstrictive and pro-proliferative effects of endothelin-1 contribute to the vasculopathy associated with the disease. The RAPIDS data “support the contention that chronic endothelin receptor antagonism has an important effect on vascular integrity and function in systemic sclerosis,” he said.

Dr. Seibold disclosed that he has received research grants and consulting fees from Actelion Pharmaceuticals Ltd., the sponsor of the trial.

Bosentan blocks dual endothelin receptors, thereby preventing digital ulcers in patients with scleroderma. Courtesy Dr. James R. Seibold

SAN DIEGO — A second randomized clinical trial has confirmed that treatment with bosentan can help prevent the formation of digital ulcers in patients with scleroderma, Dr. James R. Seibold reported at the annual meeting of the American College of Rheumatology.

A total of 188 patients from 41 centers in North America and Europe were enrolled in the Randomized Placebo-Controlled Investigation of Digital Ulcers in Scleroderma (RAPIDS-2). All had scleroderma and at least one recent active digital ulcer, and their mean disease duration was 8.7 years.

At baseline, patients randomized to the placebo and bosentan groups had a mean of 3.6 and 3.7 digital ulcers, respectively.

By 24 weeks, a mean of 2.7 new ulcers were seen in the placebo group, compared with a mean of 1.9 in the active treatment group, Dr. Seibold said in a late-breaking poster session. This difference was statistically significant.

Statistically significant differences were already apparent by week 12, at which time the placebo group had a mean of 1.3 new digital ulcers, whereas the bosentan group had a mean of 0.8 new ulcers.

The effects were particularly marked in patients with more severe peripheral vascular injury, said Dr. Seibold, director of the University of Michigan Scleroderma Program, Ann Arbor.

Among patients who had more than 3 ulcers at baseline, those receiving placebo developed 4.4 new ulcers during the 24 weeks of the trial, while those receiving bosentan had 2.3 new ulcers, which was a statistically significant difference, he said.

“These data suggest that if a patient with scleroderma were to present at a physician's office with three digital ulcers, he or she would be likely to develop an additional four to five ulcers over the next 24 weeks, and the risk of that occurring would be reduced by nearly 50% on bosentan,” Dr. Seibold said in a discussion of the trial at a satellite symposium. Bosentan treatment did not, however, shorten the time to healing of active digital ulcers. In 6 months, only 50% of ulcers had healed despite treatment with topical and systemic antibiotics and adjustments to therapy for Raynaud's phenomenon. “These data are quite instructive in terms of getting a handle on how intractable this problem is. We are treating the untreatable,” he said.

The findings of this study are in agreement with those in RAPIDS-1, which evaluated bosentan in 122 patients with scleroderma for 16 weeks, and found a 48% reduction in the mean number of new ulcers (Arthritis Rheum. 2004;50:3985–93).

Serious adverse events were uncommon. As in RAPIDS-1, more patients in the active treatment group had elevations of liver enzymes greater than 3 times the upper limit of normal (10.5%) than in the placebo group (1.1%).

Bosentan (Tracleer) is a dual endothelin receptor antagonist. Endothelin-1 and its receptors, particularly the ETB receptor, are overexpressed in scleroderma, and the vasoconstrictive and pro-proliferative effects of endothelin-1 contribute to the vasculopathy associated with the disease. The RAPIDS data “support the contention that chronic endothelin receptor antagonism has an important effect on vascular integrity and function in systemic sclerosis,” he said.

Dr. Seibold disclosed that he has received research grants and consulting fees from Actelion Pharmaceuticals Ltd., the sponsor of the trial.

Bosentan blocks dual endothelin receptors, thereby preventing digital ulcers in patients with scleroderma. Courtesy Dr. James R. Seibold

LONDON — Excimer laser treatment with minigrafting offers a new approach to repigmentation in vitiligo, according to Dr. Ludmila Nieuweboer-Krobotova of the Netherlands Institute for Pigment Disorders, University of Amsterdam.

The excimer laser has been used alone and in conjunction with topical therapies including tacrolimus and 8-methoxypsoralen. In the first preliminary study using this 308-nm laser with minigrafting in 20 patients with stable vitiligo, nine patients (45%) had 75%–99% repigmentation after 3 months, Dr. Nieuweboer-Krobotova reported in a poster session at the 14th Congress of the European Academy of Dermatology and Venereology.

Minigrafting was performed using 1.5-mm full-thickness punch grafts that were removed from a normally pigmented donor site. Grafted areas then were irradiated with the excimer laser twice weekly for 3 months.

The beginnings of repigmentation were visible after only 2 weeks, which is earlier than when narrowband UVB is used after minigrafting. At 3 months, three patients had 51%–74% repigmentation, four had 25%–50%, and four had 0%–24%.

LONDON — Excimer laser treatment with minigrafting offers a new approach to repigmentation in vitiligo, according to Dr. Ludmila Nieuweboer-Krobotova of the Netherlands Institute for Pigment Disorders, University of Amsterdam.

The excimer laser has been used alone and in conjunction with topical therapies including tacrolimus and 8-methoxypsoralen. In the first preliminary study using this 308-nm laser with minigrafting in 20 patients with stable vitiligo, nine patients (45%) had 75%–99% repigmentation after 3 months, Dr. Nieuweboer-Krobotova reported in a poster session at the 14th Congress of the European Academy of Dermatology and Venereology.

Minigrafting was performed using 1.5-mm full-thickness punch grafts that were removed from a normally pigmented donor site. Grafted areas then were irradiated with the excimer laser twice weekly for 3 months.

The beginnings of repigmentation were visible after only 2 weeks, which is earlier than when narrowband UVB is used after minigrafting. At 3 months, three patients had 51%–74% repigmentation, four had 25%–50%, and four had 0%–24%.

LONDON — Excimer laser treatment with minigrafting offers a new approach to repigmentation in vitiligo, according to Dr. Ludmila Nieuweboer-Krobotova of the Netherlands Institute for Pigment Disorders, University of Amsterdam.

The excimer laser has been used alone and in conjunction with topical therapies including tacrolimus and 8-methoxypsoralen. In the first preliminary study using this 308-nm laser with minigrafting in 20 patients with stable vitiligo, nine patients (45%) had 75%–99% repigmentation after 3 months, Dr. Nieuweboer-Krobotova reported in a poster session at the 14th Congress of the European Academy of Dermatology and Venereology.

Minigrafting was performed using 1.5-mm full-thickness punch grafts that were removed from a normally pigmented donor site. Grafted areas then were irradiated with the excimer laser twice weekly for 3 months.

The beginnings of repigmentation were visible after only 2 weeks, which is earlier than when narrowband UVB is used after minigrafting. At 3 months, three patients had 51%–74% repigmentation, four had 25%–50%, and four had 0%–24%.

WARSAW — Community-acquired methicillin-resistant Staphylococcus aureus infections in children are on the increase around the world, and while most cases involve the skin and soft tissue and are susceptible to clindamycin, severe invasive infections requiring treatment with vancomycin also are being reported, Sheldon L. Kaplan, M.D., said.

Infections are being seen in children who have no traditional risk factors, such as recent hospitalization, underlying illness, or frequent antibiotic exposure.

It appears that a number of different clones of S. aureus have acquired resistance genes, and most isolates contain a gene that codes for a toxin called Panton-Valentine leukocidin (PVL). This cytotoxin causes leukocyte destruction and tissue necrosis, and has been associated with particularly severe forms of infection including hemorrhagic pneumonia, Dr. Kaplan said at an international congress of the World Society for Pediatric Infectious Diseases.

“In our hospital at the moment, S. aureus is the most common cause of pneumonia with empyema, which used to be predominantly caused by pneumococcus,” he said.

It is not clear whether PVL is truly the causative factor in these highly virulent infections or is in some way participating in the ability of this organism to spread from person to person. What is clear is that mortality is high with S. aureus strains carrying the PVL gene: In one survey in France, the survival rate 48 hours after hospital admission was 63% among patients with PVL-positive infections, compared with 94% among those with PVL-negative infections (Lancet 2002;359:753–9).

Among other severe infections that have been seen are pyomyositis and myositis in association with osteomyelitis. “It's true that we're doing more MRI and that allows us to see these muscle infections, but I don't think we missed these infections prior to MRI. The organism just has more ability to invade muscle tissue,” said Dr. Kaplan, professor of pediatrics and infectious disease at Baylor College of Medicine, Houston.

Other infections that have been seen include extensive epidural abscesses, septic shock, and necrotizing fasciitis.

Almost all of the methicillin-resistant S. aureus (MRSA) isolates are susceptible to vancomycin, gentamicin, and trimethoprim-sulfamethoxazole. Rates of susceptibility to clindamycin vary somewhat, but in general are in the 92%–95% range. “In our area, clindamycin has been used quite a bit for community-acquired MRSA, and we are starting to see an increase in resistance, from 2% to 7%, so this is a warning,” Dr. Kaplan said. Once resistance rates reach 10%–15%, clindamycin would not be an appropriate drug to use for initial empiric treatment, he added.

When asked about possible reasons why some children develop fulminant, overwhelming infections with MRSA, Dr. Kaplan said it may be host related. “Is it related to polymorphisms in toll-like receptor 2, or some other immune factor? We can't explain it. Many have not had an obvious site of skin infection that preceded their invasive infection.”

CT scan of the lungs shows septic pulmonary emboli in a 14-year-old with severe staph sepsis and a DVT in the leg. Courtesy Dr. Sheldon L. Kaplan

WARSAW — Community-acquired methicillin-resistant Staphylococcus aureus infections in children are on the increase around the world, and while most cases involve the skin and soft tissue and are susceptible to clindamycin, severe invasive infections requiring treatment with vancomycin also are being reported, Sheldon L. Kaplan, M.D., said.

Infections are being seen in children who have no traditional risk factors, such as recent hospitalization, underlying illness, or frequent antibiotic exposure.

It appears that a number of different clones of S. aureus have acquired resistance genes, and most isolates contain a gene that codes for a toxin called Panton-Valentine leukocidin (PVL). This cytotoxin causes leukocyte destruction and tissue necrosis, and has been associated with particularly severe forms of infection including hemorrhagic pneumonia, Dr. Kaplan said at an international congress of the World Society for Pediatric Infectious Diseases.

“In our hospital at the moment, S. aureus is the most common cause of pneumonia with empyema, which used to be predominantly caused by pneumococcus,” he said.

It is not clear whether PVL is truly the causative factor in these highly virulent infections or is in some way participating in the ability of this organism to spread from person to person. What is clear is that mortality is high with S. aureus strains carrying the PVL gene: In one survey in France, the survival rate 48 hours after hospital admission was 63% among patients with PVL-positive infections, compared with 94% among those with PVL-negative infections (Lancet 2002;359:753–9).

Among other severe infections that have been seen are pyomyositis and myositis in association with osteomyelitis. “It's true that we're doing more MRI and that allows us to see these muscle infections, but I don't think we missed these infections prior to MRI. The organism just has more ability to invade muscle tissue,” said Dr. Kaplan, professor of pediatrics and infectious disease at Baylor College of Medicine, Houston.

Other infections that have been seen include extensive epidural abscesses, septic shock, and necrotizing fasciitis.

Almost all of the methicillin-resistant S. aureus (MRSA) isolates are susceptible to vancomycin, gentamicin, and trimethoprim-sulfamethoxazole. Rates of susceptibility to clindamycin vary somewhat, but in general are in the 92%–95% range. “In our area, clindamycin has been used quite a bit for community-acquired MRSA, and we are starting to see an increase in resistance, from 2% to 7%, so this is a warning,” Dr. Kaplan said. Once resistance rates reach 10%–15%, clindamycin would not be an appropriate drug to use for initial empiric treatment, he added.

When asked about possible reasons why some children develop fulminant, overwhelming infections with MRSA, Dr. Kaplan said it may be host related. “Is it related to polymorphisms in toll-like receptor 2, or some other immune factor? We can't explain it. Many have not had an obvious site of skin infection that preceded their invasive infection.”

CT scan of the lungs shows septic pulmonary emboli in a 14-year-old with severe staph sepsis and a DVT in the leg. Courtesy Dr. Sheldon L. Kaplan

WARSAW — Community-acquired methicillin-resistant Staphylococcus aureus infections in children are on the increase around the world, and while most cases involve the skin and soft tissue and are susceptible to clindamycin, severe invasive infections requiring treatment with vancomycin also are being reported, Sheldon L. Kaplan, M.D., said.

Infections are being seen in children who have no traditional risk factors, such as recent hospitalization, underlying illness, or frequent antibiotic exposure.

It appears that a number of different clones of S. aureus have acquired resistance genes, and most isolates contain a gene that codes for a toxin called Panton-Valentine leukocidin (PVL). This cytotoxin causes leukocyte destruction and tissue necrosis, and has been associated with particularly severe forms of infection including hemorrhagic pneumonia, Dr. Kaplan said at an international congress of the World Society for Pediatric Infectious Diseases.

“In our hospital at the moment, S. aureus is the most common cause of pneumonia with empyema, which used to be predominantly caused by pneumococcus,” he said.

It is not clear whether PVL is truly the causative factor in these highly virulent infections or is in some way participating in the ability of this organism to spread from person to person. What is clear is that mortality is high with S. aureus strains carrying the PVL gene: In one survey in France, the survival rate 48 hours after hospital admission was 63% among patients with PVL-positive infections, compared with 94% among those with PVL-negative infections (Lancet 2002;359:753–9).

Among other severe infections that have been seen are pyomyositis and myositis in association with osteomyelitis. “It's true that we're doing more MRI and that allows us to see these muscle infections, but I don't think we missed these infections prior to MRI. The organism just has more ability to invade muscle tissue,” said Dr. Kaplan, professor of pediatrics and infectious disease at Baylor College of Medicine, Houston.

Other infections that have been seen include extensive epidural abscesses, septic shock, and necrotizing fasciitis.

Almost all of the methicillin-resistant S. aureus (MRSA) isolates are susceptible to vancomycin, gentamicin, and trimethoprim-sulfamethoxazole. Rates of susceptibility to clindamycin vary somewhat, but in general are in the 92%–95% range. “In our area, clindamycin has been used quite a bit for community-acquired MRSA, and we are starting to see an increase in resistance, from 2% to 7%, so this is a warning,” Dr. Kaplan said. Once resistance rates reach 10%–15%, clindamycin would not be an appropriate drug to use for initial empiric treatment, he added.

When asked about possible reasons why some children develop fulminant, overwhelming infections with MRSA, Dr. Kaplan said it may be host related. “Is it related to polymorphisms in toll-like receptor 2, or some other immune factor? We can't explain it. Many have not had an obvious site of skin infection that preceded their invasive infection.”

CT scan of the lungs shows septic pulmonary emboli in a 14-year-old with severe staph sepsis and a DVT in the leg. Courtesy Dr. Sheldon L. Kaplan

WARSAW — Community-acquired methicillin resistant Staphylococcus aureus infections in children are on the increase around the world, and while most cases involve the skin and soft tissue and are susceptible to clindamycin, severe invasive infections requiring treatment with vancomycin also are being reported, Sheldon L. Kaplan, M.D., said.

Infections are being seen in children who have no traditional risk factors, such as recent hospitalization, underlying illness, or frequent exposure to antibiotics.

It appears that a number of different clones of S. aureus have acquired resistance genes, and most isolates contain a gene that codes for a toxin called Panton-Valentine leukocidin (PVL). This cytotoxin causes leukocyte destruction and tissue necrosis, and has been associated with particularly severe forms of infection including hemorrhagic pneumonia, Dr. Kaplan said at an international congress of the World Society for Pediatric Infectious Diseases.

“In our hospital at the moment, S. aureus is the most common cause of pneumonia with empyema, which used to be predominantly caused by pneumococcus,” he said.

It is not clear whether PVL is truly the causative factor in these highly virulent infections or is in some way participating in the ability of this organism to spread from person to person. What is clear is that mortality is high with S. aureus strains carrying the PVL gene: In one survey in France, the survival rate 48 hours after hospital admission was 63% among patients with PVL-positive infections, compared with 94% among those with PVL-negative infections (Lancet 2002; 359: 753–9).

Among other severe infections that have been seen are pyomyositis and myositis in association with osteomyelitis. “It's true that we're doing more MRI and that allows us to see these muscle infections, but I don't think we missed these infections prior to MRI. The organism just has more ability to invade muscle tissue,” said Dr. Kaplan, professor of pediatrics and infectious disease at Baylor College of Medicine, Houston.

Other infections that have been seen include extensive epidural abscesses, septic shock, and necrotizing fasciitis.

Almost all of the methicillin resistant Staphylococcus aureus (MRSA) isolates are susceptible to vancomycin, gentamicin, and trimethoprim-sulfamethoxazole. Rates of susceptibility to clindamycin vary somewhat, but in general are in the 92%–95% range.

“In our area, clindamycin has been used quite a bit for community-acquired MRSA, and we are starting to see an increase in resistance, from 2% to 7%, so this is a warning,” Dr. Kaplan said.

Once resistance rates reach 10%–15%, clindamycin would not be an appropriate drug to use for initial empiric treatment, he added.

When asked about possible reasons why some children develop fulminant, overwhelming infections with MRSA, Dr. Kaplan said it may be host related. “Is it related to polymorphisms in toll-like receptor 2, or some other immune factor? We can't explain it. Many have not had an obvious site of skin infection that preceded their invasive infection.”

CT scan of the lungs shows septic pulmonary emboli in a 14-year-old with severe staphylococcal sepsis. Courtesy Dr. Sheldon L. Kaplan

WARSAW — Community-acquired methicillin resistant Staphylococcus aureus infections in children are on the increase around the world, and while most cases involve the skin and soft tissue and are susceptible to clindamycin, severe invasive infections requiring treatment with vancomycin also are being reported, Sheldon L. Kaplan, M.D., said.

Infections are being seen in children who have no traditional risk factors, such as recent hospitalization, underlying illness, or frequent exposure to antibiotics.

It appears that a number of different clones of S. aureus have acquired resistance genes, and most isolates contain a gene that codes for a toxin called Panton-Valentine leukocidin (PVL). This cytotoxin causes leukocyte destruction and tissue necrosis, and has been associated with particularly severe forms of infection including hemorrhagic pneumonia, Dr. Kaplan said at an international congress of the World Society for Pediatric Infectious Diseases.

“In our hospital at the moment, S. aureus is the most common cause of pneumonia with empyema, which used to be predominantly caused by pneumococcus,” he said.

It is not clear whether PVL is truly the causative factor in these highly virulent infections or is in some way participating in the ability of this organism to spread from person to person. What is clear is that mortality is high with S. aureus strains carrying the PVL gene: In one survey in France, the survival rate 48 hours after hospital admission was 63% among patients with PVL-positive infections, compared with 94% among those with PVL-negative infections (Lancet 2002; 359: 753–9).

Among other severe infections that have been seen are pyomyositis and myositis in association with osteomyelitis. “It's true that we're doing more MRI and that allows us to see these muscle infections, but I don't think we missed these infections prior to MRI. The organism just has more ability to invade muscle tissue,” said Dr. Kaplan, professor of pediatrics and infectious disease at Baylor College of Medicine, Houston.

Other infections that have been seen include extensive epidural abscesses, septic shock, and necrotizing fasciitis.

Almost all of the methicillin resistant Staphylococcus aureus (MRSA) isolates are susceptible to vancomycin, gentamicin, and trimethoprim-sulfamethoxazole. Rates of susceptibility to clindamycin vary somewhat, but in general are in the 92%–95% range.

“In our area, clindamycin has been used quite a bit for community-acquired MRSA, and we are starting to see an increase in resistance, from 2% to 7%, so this is a warning,” Dr. Kaplan said.

Once resistance rates reach 10%–15%, clindamycin would not be an appropriate drug to use for initial empiric treatment, he added.

When asked about possible reasons why some children develop fulminant, overwhelming infections with MRSA, Dr. Kaplan said it may be host related. “Is it related to polymorphisms in toll-like receptor 2, or some other immune factor? We can't explain it. Many have not had an obvious site of skin infection that preceded their invasive infection.”

CT scan of the lungs shows septic pulmonary emboli in a 14-year-old with severe staphylococcal sepsis. Courtesy Dr. Sheldon L. Kaplan

WARSAW — Community-acquired methicillin resistant Staphylococcus aureus infections in children are on the increase around the world, and while most cases involve the skin and soft tissue and are susceptible to clindamycin, severe invasive infections requiring treatment with vancomycin also are being reported, Sheldon L. Kaplan, M.D., said.

Infections are being seen in children who have no traditional risk factors, such as recent hospitalization, underlying illness, or frequent exposure to antibiotics.

It appears that a number of different clones of S. aureus have acquired resistance genes, and most isolates contain a gene that codes for a toxin called Panton-Valentine leukocidin (PVL). This cytotoxin causes leukocyte destruction and tissue necrosis, and has been associated with particularly severe forms of infection including hemorrhagic pneumonia, Dr. Kaplan said at an international congress of the World Society for Pediatric Infectious Diseases.

“In our hospital at the moment, S. aureus is the most common cause of pneumonia with empyema, which used to be predominantly caused by pneumococcus,” he said.

It is not clear whether PVL is truly the causative factor in these highly virulent infections or is in some way participating in the ability of this organism to spread from person to person. What is clear is that mortality is high with S. aureus strains carrying the PVL gene: In one survey in France, the survival rate 48 hours after hospital admission was 63% among patients with PVL-positive infections, compared with 94% among those with PVL-negative infections (Lancet 2002; 359: 753–9).

Among other severe infections that have been seen are pyomyositis and myositis in association with osteomyelitis. “It's true that we're doing more MRI and that allows us to see these muscle infections, but I don't think we missed these infections prior to MRI. The organism just has more ability to invade muscle tissue,” said Dr. Kaplan, professor of pediatrics and infectious disease at Baylor College of Medicine, Houston.

Other infections that have been seen include extensive epidural abscesses, septic shock, and necrotizing fasciitis.

Almost all of the methicillin resistant Staphylococcus aureus (MRSA) isolates are susceptible to vancomycin, gentamicin, and trimethoprim-sulfamethoxazole. Rates of susceptibility to clindamycin vary somewhat, but in general are in the 92%–95% range.

“In our area, clindamycin has been used quite a bit for community-acquired MRSA, and we are starting to see an increase in resistance, from 2% to 7%, so this is a warning,” Dr. Kaplan said.

Once resistance rates reach 10%–15%, clindamycin would not be an appropriate drug to use for initial empiric treatment, he added.

When asked about possible reasons why some children develop fulminant, overwhelming infections with MRSA, Dr. Kaplan said it may be host related. “Is it related to polymorphisms in toll-like receptor 2, or some other immune factor? We can't explain it. Many have not had an obvious site of skin infection that preceded their invasive infection.”

CT scan of the lungs shows septic pulmonary emboli in a 14-year-old with severe staphylococcal sepsis. Courtesy Dr. Sheldon L. Kaplan

ATLANTA — All children should receive hepatitis A vaccine beginning at age 12–23 months, and the vaccine should be integrated into the routine childhood immunization schedule, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices voted at its fall meeting.

In voting for inclusion in the routine childhood immunization schedule, the committee specified that all children in a single age cohort should be given the vaccine, and that those who are not vaccinated at 1–2 years can be vaccinated at subsequent visits during the preschool years.

ACIP's recommendation for nationwide use of the hepatitis A vaccine—which does not become official until approved and published by the CDC—reflects both the success of the vaccine and the limitations of current practice.

When it was licensed in 1995, the vaccine initially was recommended for use in areas with high rates of hepatitis A. Currently, it is being routinely given to children in 17 states, according to Beth Bell, M.D., of the CDC's division of viral hepatitis.

Overall rates of hepatitis A have been falling, primarily because of a precipitous decline in areas where the vaccine has been used. “The overall rate of 1.9 cases per 100,000 is certainly the lowest rate since we've been measuring,” she said.

But this policy of selective vaccination of children is no longer sustainable because, in an epidemiologic reversal, the highest rates of hepatitis A are now being seen in what were formerly considered low-incidence communities, according to committee member Tracy Lieu, M.D., of Harvard Pilgrim Health Care and Harvard Medical School, Boston.

“Our recommendation for vaccination in high-incidence states was an interim step, and our intention has always been to implement hepatitis A vaccination nationwide,” Dr. Lieu said.

Aside from the geographic shift in incidence rates, reasons why selective vaccinations can no longer be considered sustainable are that racial disparities exist and that without universal vaccination, models predict that the incidence of hepatitis A will once again increase. The highest rates now are among Hispanic children in areas not using the vaccine, Dr. Lieu said.

Recent approval of the vaccine for use among 1-year-olds provides a further impetus for change.

Currently, 5,000–7,000 cases of symptomatic hepatitis A cases are reported each year, and an estimated 20,000–30,000 cases occur nationwide.

Usage of the vaccine today prevents 81,000 cases annually. Nationwide use with vaccination at 1 year would prevent 180,000 cases of disease, according to Dr. Lieu. And while the $22 million annual direct costs of vaccination under the status quo would increase to $134 million, the cost-effectiveness ratio is still “very reasonable,” she said.

An additional question on epidemiology was raised by Jonathan Temte, M.D., who is liaison to ACIP from the American Academy of Family Physicians. “How many of the adult cases are due to transmission from children?”

“We have indirect evidence that a lot of adult cases are due to transmission from children,” said the CDC's Dr. Bell.

Those areas of the country where children have been immunized have seen enormous declines in cases among adults as well, Dr. Bell said. “And a large part of what I think of as a child-driven disease that affected both children and adults in communitywide outbreaks we don't see in that part of the country any more. There's little reason not to assume that we would see similar benefits by herd immunity in unvaccinated areas of the country.”

Two vaccines now are approved for use in children 1 year and older, Havrix (GlaxoSmithKline) and Vaqta (Merck). A minimum interval of 6 months between doses is recommended.

ATLANTA — All children should receive hepatitis A vaccine beginning at age 12–23 months, and the vaccine should be integrated into the routine childhood immunization schedule, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices voted at its fall meeting.

In voting for inclusion in the routine childhood immunization schedule, the committee specified that all children in a single age cohort should be given the vaccine, and that those who are not vaccinated at 1–2 years can be vaccinated at subsequent visits during the preschool years.

ACIP's recommendation for nationwide use of the hepatitis A vaccine—which does not become official until approved and published by the CDC—reflects both the success of the vaccine and the limitations of current practice.

When it was licensed in 1995, the vaccine initially was recommended for use in areas with high rates of hepatitis A. Currently, it is being routinely given to children in 17 states, according to Beth Bell, M.D., of the CDC's division of viral hepatitis.

Overall rates of hepatitis A have been falling, primarily because of a precipitous decline in areas where the vaccine has been used. “The overall rate of 1.9 cases per 100,000 is certainly the lowest rate since we've been measuring,” she said.

But this policy of selective vaccination of children is no longer sustainable because, in an epidemiologic reversal, the highest rates of hepatitis A are now being seen in what were formerly considered low-incidence communities, according to committee member Tracy Lieu, M.D., of Harvard Pilgrim Health Care and Harvard Medical School, Boston.

“Our recommendation for vaccination in high-incidence states was an interim step, and our intention has always been to implement hepatitis A vaccination nationwide,” Dr. Lieu said.

Aside from the geographic shift in incidence rates, reasons why selective vaccinations can no longer be considered sustainable are that racial disparities exist and that without universal vaccination, models predict that the incidence of hepatitis A will once again increase. The highest rates now are among Hispanic children in areas not using the vaccine, Dr. Lieu said.

Recent approval of the vaccine for use among 1-year-olds provides a further impetus for change.

Currently, 5,000–7,000 cases of symptomatic hepatitis A cases are reported each year, and an estimated 20,000–30,000 cases occur nationwide.

Usage of the vaccine today prevents 81,000 cases annually. Nationwide use with vaccination at 1 year would prevent 180,000 cases of disease, according to Dr. Lieu. And while the $22 million annual direct costs of vaccination under the status quo would increase to $134 million, the cost-effectiveness ratio is still “very reasonable,” she said.

An additional question on epidemiology was raised by Jonathan Temte, M.D., who is liaison to ACIP from the American Academy of Family Physicians. “How many of the adult cases are due to transmission from children?”

“We have indirect evidence that a lot of adult cases are due to transmission from children,” said the CDC's Dr. Bell.

Those areas of the country where children have been immunized have seen enormous declines in cases among adults as well, Dr. Bell said. “And a large part of what I think of as a child-driven disease that affected both children and adults in communitywide outbreaks we don't see in that part of the country any more. There's little reason not to assume that we would see similar benefits by herd immunity in unvaccinated areas of the country.”

Two vaccines now are approved for use in children 1 year and older, Havrix (GlaxoSmithKline) and Vaqta (Merck). A minimum interval of 6 months between doses is recommended.

ATLANTA — All children should receive hepatitis A vaccine beginning at age 12–23 months, and the vaccine should be integrated into the routine childhood immunization schedule, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices voted at its fall meeting.

In voting for inclusion in the routine childhood immunization schedule, the committee specified that all children in a single age cohort should be given the vaccine, and that those who are not vaccinated at 1–2 years can be vaccinated at subsequent visits during the preschool years.

ACIP's recommendation for nationwide use of the hepatitis A vaccine—which does not become official until approved and published by the CDC—reflects both the success of the vaccine and the limitations of current practice.

When it was licensed in 1995, the vaccine initially was recommended for use in areas with high rates of hepatitis A. Currently, it is being routinely given to children in 17 states, according to Beth Bell, M.D., of the CDC's division of viral hepatitis.

Overall rates of hepatitis A have been falling, primarily because of a precipitous decline in areas where the vaccine has been used. “The overall rate of 1.9 cases per 100,000 is certainly the lowest rate since we've been measuring,” she said.

But this policy of selective vaccination of children is no longer sustainable because, in an epidemiologic reversal, the highest rates of hepatitis A are now being seen in what were formerly considered low-incidence communities, according to committee member Tracy Lieu, M.D., of Harvard Pilgrim Health Care and Harvard Medical School, Boston.

“Our recommendation for vaccination in high-incidence states was an interim step, and our intention has always been to implement hepatitis A vaccination nationwide,” Dr. Lieu said.

Aside from the geographic shift in incidence rates, reasons why selective vaccinations can no longer be considered sustainable are that racial disparities exist and that without universal vaccination, models predict that the incidence of hepatitis A will once again increase. The highest rates now are among Hispanic children in areas not using the vaccine, Dr. Lieu said.

Recent approval of the vaccine for use among 1-year-olds provides a further impetus for change.

Currently, 5,000–7,000 cases of symptomatic hepatitis A cases are reported each year, and an estimated 20,000–30,000 cases occur nationwide.

Usage of the vaccine today prevents 81,000 cases annually. Nationwide use with vaccination at 1 year would prevent 180,000 cases of disease, according to Dr. Lieu. And while the $22 million annual direct costs of vaccination under the status quo would increase to $134 million, the cost-effectiveness ratio is still “very reasonable,” she said.

An additional question on epidemiology was raised by Jonathan Temte, M.D., who is liaison to ACIP from the American Academy of Family Physicians. “How many of the adult cases are due to transmission from children?”

“We have indirect evidence that a lot of adult cases are due to transmission from children,” said the CDC's Dr. Bell.

Those areas of the country where children have been immunized have seen enormous declines in cases among adults as well, Dr. Bell said. “And a large part of what I think of as a child-driven disease that affected both children and adults in communitywide outbreaks we don't see in that part of the country any more. There's little reason not to assume that we would see similar benefits by herd immunity in unvaccinated areas of the country.”

Two vaccines now are approved for use in children 1 year and older, Havrix (GlaxoSmithKline) and Vaqta (Merck). A minimum interval of 6 months between doses is recommended.

LONDON — Borrelia burgdorferi from tick bites, the causative agent of Lyme disease in the United States, has been linked to cases of primary cutaneous B-cell lymphoma in certain areas of Europe, reported Rein Willemze, M.D.

“It is common dermatologic knowledge in Europe that B. burgdorferi infections can cause reactive B-cell proliferations in the skin,” Dr. Willemze said at the 14th Congress of the European Academy of Dermatology and Venereology. The lesions typically are located on the ear lobes and nipples, which are sites that attract ticks, and most often are marginal zone lymphomas.

Primary cutaneous marginal zone B-cell lymphomas are low-grade malignancies characterized by clonal proliferation of small neoplastic B cells with a Bcl-2+, Bcl-6-, CD10- phenotype, said Dr. Willemze of Leiden (the Netherlands) University Medical Center.

B. burgdorferi-associated cutaneous lymphomas have been reported in Austria and Scotland, though not in Asia or North America. “The most likely explanation is that different subspecies of B. burgdorferi are present in these parts of the world,” he said.

Systemic antibiotics, usually penicillin, cephalosporins, or tetracyclines, may be curative if lymphoma is associated with Borrelia infection, although the optimal regimen has not been established, said Dr. Willemze, who is in the Dutch Cutaneous Lymphoma Working Group.

The relationship between low-grade B-cell lymphomas and bacterial infections is not restricted to the skin. More recognized is the relationship between gastric mucosa-associated lymphoid tissue (MALT) lymphomas, which are similar to primary cutaneous B-cell lymphomas in the skin, and Helicobacter pylori infections.

LONDON — Borrelia burgdorferi from tick bites, the causative agent of Lyme disease in the United States, has been linked to cases of primary cutaneous B-cell lymphoma in certain areas of Europe, reported Rein Willemze, M.D.

“It is common dermatologic knowledge in Europe that B. burgdorferi infections can cause reactive B-cell proliferations in the skin,” Dr. Willemze said at the 14th Congress of the European Academy of Dermatology and Venereology. The lesions typically are located on the ear lobes and nipples, which are sites that attract ticks, and most often are marginal zone lymphomas.

Primary cutaneous marginal zone B-cell lymphomas are low-grade malignancies characterized by clonal proliferation of small neoplastic B cells with a Bcl-2+, Bcl-6-, CD10- phenotype, said Dr. Willemze of Leiden (the Netherlands) University Medical Center.

B. burgdorferi-associated cutaneous lymphomas have been reported in Austria and Scotland, though not in Asia or North America. “The most likely explanation is that different subspecies of B. burgdorferi are present in these parts of the world,” he said.

Systemic antibiotics, usually penicillin, cephalosporins, or tetracyclines, may be curative if lymphoma is associated with Borrelia infection, although the optimal regimen has not been established, said Dr. Willemze, who is in the Dutch Cutaneous Lymphoma Working Group.

The relationship between low-grade B-cell lymphomas and bacterial infections is not restricted to the skin. More recognized is the relationship between gastric mucosa-associated lymphoid tissue (MALT) lymphomas, which are similar to primary cutaneous B-cell lymphomas in the skin, and Helicobacter pylori infections.

LONDON — Borrelia burgdorferi from tick bites, the causative agent of Lyme disease in the United States, has been linked to cases of primary cutaneous B-cell lymphoma in certain areas of Europe, reported Rein Willemze, M.D.

“It is common dermatologic knowledge in Europe that B. burgdorferi infections can cause reactive B-cell proliferations in the skin,” Dr. Willemze said at the 14th Congress of the European Academy of Dermatology and Venereology. The lesions typically are located on the ear lobes and nipples, which are sites that attract ticks, and most often are marginal zone lymphomas.

Primary cutaneous marginal zone B-cell lymphomas are low-grade malignancies characterized by clonal proliferation of small neoplastic B cells with a Bcl-2+, Bcl-6-, CD10- phenotype, said Dr. Willemze of Leiden (the Netherlands) University Medical Center.

B. burgdorferi-associated cutaneous lymphomas have been reported in Austria and Scotland, though not in Asia or North America. “The most likely explanation is that different subspecies of B. burgdorferi are present in these parts of the world,” he said.

Systemic antibiotics, usually penicillin, cephalosporins, or tetracyclines, may be curative if lymphoma is associated with Borrelia infection, although the optimal regimen has not been established, said Dr. Willemze, who is in the Dutch Cutaneous Lymphoma Working Group.

The relationship between low-grade B-cell lymphomas and bacterial infections is not restricted to the skin. More recognized is the relationship between gastric mucosa-associated lymphoid tissue (MALT) lymphomas, which are similar to primary cutaneous B-cell lymphomas in the skin, and Helicobacter pylori infections.

VIENNA — Early rheumatoid nodules, pulmonary involvement, and malaise with weight loss are predictive of long-term poor outcomes in rheumatoid arthritis, Gouri Koduri, M.D., said at the annual European Congress of Rheumatology.

Although rheumatoid arthritis (RA) is primarily an articular disease, it also has myriad extraarticular manifestations, some of which are associated with increased morbidity and mortality. But there have been few reports on when in the course of disease these extraarticular features develop and what their impact is, she said.

These concerns are now being addressed in an ongoing inception cohort that includes 1,415 patients who have been enrolled since 1986 from nine centers in England.

Clinical and laboratory measures have been recorded at yearly intervals, and analyses of 10-year outcomes include function disability, joint damage, and causes of death.

The effects of other parameters such as age, sex, rheumatoid factor (RF) positivity, and smoking on the development of extraarticular manifestations also have been examined, said Dr. Koduri of St. Albans City Hospital, Hertfordshire (England) University.

A total of 576 (41%) patients have had at least one extraarticular feature. The most common were subcutaneous nodules, in 450 patients (34%). These developed within the first year after diagnosis in 11%, she said at the congress, sponsored by the European League Against Rheumatism.

Secondary Sjögren's syndrome developed in 140 (10%), pulmonary disease in 55 (4%), marked malaise and weight loss in 47 (3%), and vasculitis in 32 (2%).

Risk factors for mortality included pulmonary fibrosis, with an odds ratio of 6.93, and the presence of two or more extraarticular features at presentation or by 1 year after diagnosis, with an odds ratio of 4.3, she said.

Marked malaise with weight loss and rheumatoid nodules also were associated with increased risk of mortality, with odds ratios of 2.7 and 1.5, respectively.

Extraarticular manifestations were a primary or contributory cause of death in 24 patients, 23 with pulmonary fibrosis and 1 with vasculitis, Dr. Koduri said.

The presence of nodules within the first 2 years also was predictive of morbidities including erosive disease, with an odds ratio of 2.7, and poor physical function, with an odds ratio of 1.6.

Sjögren's syndrome was associated only with worse function.

VIENNA — Early rheumatoid nodules, pulmonary involvement, and malaise with weight loss are predictive of long-term poor outcomes in rheumatoid arthritis, Gouri Koduri, M.D., said at the annual European Congress of Rheumatology.

Although rheumatoid arthritis (RA) is primarily an articular disease, it also has myriad extraarticular manifestations, some of which are associated with increased morbidity and mortality. But there have been few reports on when in the course of disease these extraarticular features develop and what their impact is, she said.

These concerns are now being addressed in an ongoing inception cohort that includes 1,415 patients who have been enrolled since 1986 from nine centers in England.

Clinical and laboratory measures have been recorded at yearly intervals, and analyses of 10-year outcomes include function disability, joint damage, and causes of death.

The effects of other parameters such as age, sex, rheumatoid factor (RF) positivity, and smoking on the development of extraarticular manifestations also have been examined, said Dr. Koduri of St. Albans City Hospital, Hertfordshire (England) University.

A total of 576 (41%) patients have had at least one extraarticular feature. The most common were subcutaneous nodules, in 450 patients (34%). These developed within the first year after diagnosis in 11%, she said at the congress, sponsored by the European League Against Rheumatism.

Secondary Sjögren's syndrome developed in 140 (10%), pulmonary disease in 55 (4%), marked malaise and weight loss in 47 (3%), and vasculitis in 32 (2%).

Risk factors for mortality included pulmonary fibrosis, with an odds ratio of 6.93, and the presence of two or more extraarticular features at presentation or by 1 year after diagnosis, with an odds ratio of 4.3, she said.

Marked malaise with weight loss and rheumatoid nodules also were associated with increased risk of mortality, with odds ratios of 2.7 and 1.5, respectively.

Extraarticular manifestations were a primary or contributory cause of death in 24 patients, 23 with pulmonary fibrosis and 1 with vasculitis, Dr. Koduri said.

The presence of nodules within the first 2 years also was predictive of morbidities including erosive disease, with an odds ratio of 2.7, and poor physical function, with an odds ratio of 1.6.

Sjögren's syndrome was associated only with worse function.

VIENNA — Early rheumatoid nodules, pulmonary involvement, and malaise with weight loss are predictive of long-term poor outcomes in rheumatoid arthritis, Gouri Koduri, M.D., said at the annual European Congress of Rheumatology.

Although rheumatoid arthritis (RA) is primarily an articular disease, it also has myriad extraarticular manifestations, some of which are associated with increased morbidity and mortality. But there have been few reports on when in the course of disease these extraarticular features develop and what their impact is, she said.

These concerns are now being addressed in an ongoing inception cohort that includes 1,415 patients who have been enrolled since 1986 from nine centers in England.

Clinical and laboratory measures have been recorded at yearly intervals, and analyses of 10-year outcomes include function disability, joint damage, and causes of death.

The effects of other parameters such as age, sex, rheumatoid factor (RF) positivity, and smoking on the development of extraarticular manifestations also have been examined, said Dr. Koduri of St. Albans City Hospital, Hertfordshire (England) University.

A total of 576 (41%) patients have had at least one extraarticular feature. The most common were subcutaneous nodules, in 450 patients (34%). These developed within the first year after diagnosis in 11%, she said at the congress, sponsored by the European League Against Rheumatism.

Secondary Sjögren's syndrome developed in 140 (10%), pulmonary disease in 55 (4%), marked malaise and weight loss in 47 (3%), and vasculitis in 32 (2%).

Risk factors for mortality included pulmonary fibrosis, with an odds ratio of 6.93, and the presence of two or more extraarticular features at presentation or by 1 year after diagnosis, with an odds ratio of 4.3, she said.

Marked malaise with weight loss and rheumatoid nodules also were associated with increased risk of mortality, with odds ratios of 2.7 and 1.5, respectively.

Extraarticular manifestations were a primary or contributory cause of death in 24 patients, 23 with pulmonary fibrosis and 1 with vasculitis, Dr. Koduri said.

The presence of nodules within the first 2 years also was predictive of morbidities including erosive disease, with an odds ratio of 2.7, and poor physical function, with an odds ratio of 1.6.

Sjögren's syndrome was associated only with worse function.

VIENNA — A new approach to forefoot reconstruction in patients with rheumatoid arthritis has shown superior results with regard to pain, deformity, and function, compared with conventional techniques, according to Takeshi Mitsuka, M.D., of the department of orthopedic surgery, Chiba Tokushukai Hospital, Funabashi, Japan.

Reconstruction of the lateral toes is done by means of a metatarsal oblique osteotomy. For the great toe, either a Swanson implant or a metatarsal osteotomy can be done, depending on the condition of the joint, and the result is the preservation of the function of the metatarsophalangeal joints, Dr. Mitsuka wrote in a poster presented at the annual European Congress of Rheumatology.

“I have been performing this procedure since 1998 for almost all rheumatoid [arthritis] patients with forefoot deformities. The outcome is better than with resection arthroplasty of the MTP [metatarsophalangeal] joints or arthrodesis of the big toe for stability and mobility of the joint, length of toe, gait, and cosmetic result,” he told FAMILY PRACTICE NEWS.

A total of 53 forefoot reconstructions in 31 patients have been done to date. Mean age at time of surgery was 60 years, and the mean duration of rheumatoid arthritis until time of operation was 18 years.

At their latest follow-up, patients were evaluated clinically using the American Orthopedic Foot and Ankle Society (AOFAS) score. Hallux valgus angle and intermetatarsal angle were examined radiologically.

Two patients died of causes unrelated to surgery, and in one foot the Swanson implant was removed 11 months after placement because of reactive synovitis.

Among the remaining 48 feet, with a mean follow-up of 40 months, the AOFAS score for the great toe improved from an average of 36 points preoperatively to 89 points (out of 100). For the lateral toes, the average score improved from 27 points to 87 points.

The hallux valgus angle improved from an average of 45 degrees preoperatively to 19 degrees at the latest evaluation, Dr. Mitsuka noted at the meeting, which was sponsored by the European League Against Rheumatism.

Intermetatarsal angle also improved, from an average of 16 degrees before surgery to 13 degrees.

Reconstruction of the great toe of 44 feet in 25 patients involved arthroplasty with a Swanson implant, and was done with a Mitchell's osteotomy in the remaining 9 feet in 6 patients.

In the lateral toes, an oblique osteotomy was performed at the metatarsal neck, starting proximally on the dorsum and proceeding distally and plantarward at an angle of 45 degrees. This was then resected at a width of 5–15 mm.

The metatarsal head subsequently was freed from its plantar aspect, and the dislocated base of the proximal phalanx was corrected.

The osteotomized bones were then transfixed longitudinally by Kirschner wires from the distal phalanx to the metatarsal base.

A 53-year-old RA patient with forefoot deformities is shown prior to surgery.

Reconstruction was performed by means of a metatarsal oblique osteotomy. Photos courtesy Dr. Takeshi Mitsuka

VIENNA — A new approach to forefoot reconstruction in patients with rheumatoid arthritis has shown superior results with regard to pain, deformity, and function, compared with conventional techniques, according to Takeshi Mitsuka, M.D., of the department of orthopedic surgery, Chiba Tokushukai Hospital, Funabashi, Japan.

Reconstruction of the lateral toes is done by means of a metatarsal oblique osteotomy. For the great toe, either a Swanson implant or a metatarsal osteotomy can be done, depending on the condition of the joint, and the result is the preservation of the function of the metatarsophalangeal joints, Dr. Mitsuka wrote in a poster presented at the annual European Congress of Rheumatology.

“I have been performing this procedure since 1998 for almost all rheumatoid [arthritis] patients with forefoot deformities. The outcome is better than with resection arthroplasty of the MTP [metatarsophalangeal] joints or arthrodesis of the big toe for stability and mobility of the joint, length of toe, gait, and cosmetic result,” he told FAMILY PRACTICE NEWS.

A total of 53 forefoot reconstructions in 31 patients have been done to date. Mean age at time of surgery was 60 years, and the mean duration of rheumatoid arthritis until time of operation was 18 years.

At their latest follow-up, patients were evaluated clinically using the American Orthopedic Foot and Ankle Society (AOFAS) score. Hallux valgus angle and intermetatarsal angle were examined radiologically.

Two patients died of causes unrelated to surgery, and in one foot the Swanson implant was removed 11 months after placement because of reactive synovitis.

Among the remaining 48 feet, with a mean follow-up of 40 months, the AOFAS score for the great toe improved from an average of 36 points preoperatively to 89 points (out of 100). For the lateral toes, the average score improved from 27 points to 87 points.

The hallux valgus angle improved from an average of 45 degrees preoperatively to 19 degrees at the latest evaluation, Dr. Mitsuka noted at the meeting, which was sponsored by the European League Against Rheumatism.

Intermetatarsal angle also improved, from an average of 16 degrees before surgery to 13 degrees.

Reconstruction of the great toe of 44 feet in 25 patients involved arthroplasty with a Swanson implant, and was done with a Mitchell's osteotomy in the remaining 9 feet in 6 patients.

In the lateral toes, an oblique osteotomy was performed at the metatarsal neck, starting proximally on the dorsum and proceeding distally and plantarward at an angle of 45 degrees. This was then resected at a width of 5–15 mm.

The metatarsal head subsequently was freed from its plantar aspect, and the dislocated base of the proximal phalanx was corrected.

The osteotomized bones were then transfixed longitudinally by Kirschner wires from the distal phalanx to the metatarsal base.

A 53-year-old RA patient with forefoot deformities is shown prior to surgery.

Reconstruction was performed by means of a metatarsal oblique osteotomy. Photos courtesy Dr. Takeshi Mitsuka

VIENNA — A new approach to forefoot reconstruction in patients with rheumatoid arthritis has shown superior results with regard to pain, deformity, and function, compared with conventional techniques, according to Takeshi Mitsuka, M.D., of the department of orthopedic surgery, Chiba Tokushukai Hospital, Funabashi, Japan.

Reconstruction of the lateral toes is done by means of a metatarsal oblique osteotomy. For the great toe, either a Swanson implant or a metatarsal osteotomy can be done, depending on the condition of the joint, and the result is the preservation of the function of the metatarsophalangeal joints, Dr. Mitsuka wrote in a poster presented at the annual European Congress of Rheumatology.

“I have been performing this procedure since 1998 for almost all rheumatoid [arthritis] patients with forefoot deformities. The outcome is better than with resection arthroplasty of the MTP [metatarsophalangeal] joints or arthrodesis of the big toe for stability and mobility of the joint, length of toe, gait, and cosmetic result,” he told FAMILY PRACTICE NEWS.

A total of 53 forefoot reconstructions in 31 patients have been done to date. Mean age at time of surgery was 60 years, and the mean duration of rheumatoid arthritis until time of operation was 18 years.

At their latest follow-up, patients were evaluated clinically using the American Orthopedic Foot and Ankle Society (AOFAS) score. Hallux valgus angle and intermetatarsal angle were examined radiologically.

Two patients died of causes unrelated to surgery, and in one foot the Swanson implant was removed 11 months after placement because of reactive synovitis.

Among the remaining 48 feet, with a mean follow-up of 40 months, the AOFAS score for the great toe improved from an average of 36 points preoperatively to 89 points (out of 100). For the lateral toes, the average score improved from 27 points to 87 points.

The hallux valgus angle improved from an average of 45 degrees preoperatively to 19 degrees at the latest evaluation, Dr. Mitsuka noted at the meeting, which was sponsored by the European League Against Rheumatism.

Intermetatarsal angle also improved, from an average of 16 degrees before surgery to 13 degrees.

Reconstruction of the great toe of 44 feet in 25 patients involved arthroplasty with a Swanson implant, and was done with a Mitchell's osteotomy in the remaining 9 feet in 6 patients.

In the lateral toes, an oblique osteotomy was performed at the metatarsal neck, starting proximally on the dorsum and proceeding distally and plantarward at an angle of 45 degrees. This was then resected at a width of 5–15 mm.

The metatarsal head subsequently was freed from its plantar aspect, and the dislocated base of the proximal phalanx was corrected.

The osteotomized bones were then transfixed longitudinally by Kirschner wires from the distal phalanx to the metatarsal base.

A 53-year-old RA patient with forefoot deformities is shown prior to surgery.

Reconstruction was performed by means of a metatarsal oblique osteotomy. Photos courtesy Dr. Takeshi Mitsuka