Nancy Walsh

SAN ANTONIO — The list of potential therapeutic targets in rheumatoid arthritis continues to expand, with preliminary evidence supporting the addition of the proinflammatory cytokine interleukin (IL)-15.

This signaling molecule, found in the synovium in those with rheumatoid arthritis (RA), appears early in the cascade of events that leads to inflammation, inducing the production of tumor necrosis factor (TNF)-α and recruiting inflammatory T cells.

A human monoclonal IgG antibody that binds to and inhibits IL-15 has been developed and is now undergoing clinical testing, Iain McInnes, M.D., said at the annual meeting of the American College of Rheumatology.

In an interim analysis of a proof-of-concept study of the antibody AMG 714, clinical effect was demonstrated at various doses in 110 patients with active RA, with the most pronounced benefit seen in the highest-dose group, he said.

Background methotrexate was permitted in stable doses of 25 mg/wk or less, but other disease-modifying drugs were not. None of the patients had previously received biologic response modifiers.

Stable limited doses of NSAIDs and corticosteroids were allowed.

Patients were randomized to receive placebo or AMG 714 in doses of 40 mg, 80 mg, 160 mg, or 280 mg, given by subcutaneous injection every 2 weeks for a 12-week period.

Among those patients in the highest dose group, 62% achieved an ACR 20 response, as did 26% in the placebo group; this between-group difference was statistically significant.

The response was maintained at week 14, though at that point, statistical significance was lost because of an increased placebo response, said Dr. McInnes, professor of experimental medicine and rheumatology at the Centre for Rheumatic Diseases, Glasgow, Scotland.

Approximately one-fourth of patients in the active treatment groups achieved an ACR 50 response, as did one patient in the placebo group. Some patients have achieved an ACR 70 response, but those data remain blinded, he said.

A 20% reduction in CRP was seen at weeks 4 and 14 in 29% and 39% of placebo patients, respectively, and in 70% and 63% of those in the high-dose AMG 714 group.

Worsening of RA was observed in 26% of placebo patients, compared with 5% of the high-dose treatment group.

Adverse events have been closely tracked in the study. “As this is the first time IL-15 is being targeted in humans, safety is our highest priority,” Dr. McInnes said.

Overall, the incidence of adverse events, such as infection, gastrointestinal complaints, and skin disorders, has been similar across the treatment and placebo groups. Approximately one-fourth of patients in the high-dose group have experienced transient injection-site reactions.

Two serious adverse events were reported. One was a case of deep venous thrombosis diagnosed 4 weeks after the last injection, and the other was sepsis following focal infection of a finger. Both resolved without sequelae, he said.

No deaths occurred during the trial.

“These are encouraging preliminary data,” he said in conclusion. An additional 70 patients now have entered the ongoing study.

Dr. McInnes disclosed a commercial relationship with Genmab A/S, the Copenhagen-based manufacturer of AMG 714.

SAN ANTONIO — The list of potential therapeutic targets in rheumatoid arthritis continues to expand, with preliminary evidence supporting the addition of the proinflammatory cytokine interleukin (IL)-15.

This signaling molecule, found in the synovium in those with rheumatoid arthritis (RA), appears early in the cascade of events that leads to inflammation, inducing the production of tumor necrosis factor (TNF)-α and recruiting inflammatory T cells.

A human monoclonal IgG antibody that binds to and inhibits IL-15 has been developed and is now undergoing clinical testing, Iain McInnes, M.D., said at the annual meeting of the American College of Rheumatology.

In an interim analysis of a proof-of-concept study of the antibody AMG 714, clinical effect was demonstrated at various doses in 110 patients with active RA, with the most pronounced benefit seen in the highest-dose group, he said.

Background methotrexate was permitted in stable doses of 25 mg/wk or less, but other disease-modifying drugs were not. None of the patients had previously received biologic response modifiers.

Stable limited doses of NSAIDs and corticosteroids were allowed.

Patients were randomized to receive placebo or AMG 714 in doses of 40 mg, 80 mg, 160 mg, or 280 mg, given by subcutaneous injection every 2 weeks for a 12-week period.

Among those patients in the highest dose group, 62% achieved an ACR 20 response, as did 26% in the placebo group; this between-group difference was statistically significant.

The response was maintained at week 14, though at that point, statistical significance was lost because of an increased placebo response, said Dr. McInnes, professor of experimental medicine and rheumatology at the Centre for Rheumatic Diseases, Glasgow, Scotland.

Approximately one-fourth of patients in the active treatment groups achieved an ACR 50 response, as did one patient in the placebo group. Some patients have achieved an ACR 70 response, but those data remain blinded, he said.

A 20% reduction in CRP was seen at weeks 4 and 14 in 29% and 39% of placebo patients, respectively, and in 70% and 63% of those in the high-dose AMG 714 group.

Worsening of RA was observed in 26% of placebo patients, compared with 5% of the high-dose treatment group.

Adverse events have been closely tracked in the study. “As this is the first time IL-15 is being targeted in humans, safety is our highest priority,” Dr. McInnes said.

Overall, the incidence of adverse events, such as infection, gastrointestinal complaints, and skin disorders, has been similar across the treatment and placebo groups. Approximately one-fourth of patients in the high-dose group have experienced transient injection-site reactions.

Two serious adverse events were reported. One was a case of deep venous thrombosis diagnosed 4 weeks after the last injection, and the other was sepsis following focal infection of a finger. Both resolved without sequelae, he said.

No deaths occurred during the trial.

“These are encouraging preliminary data,” he said in conclusion. An additional 70 patients now have entered the ongoing study.

Dr. McInnes disclosed a commercial relationship with Genmab A/S, the Copenhagen-based manufacturer of AMG 714.

SAN ANTONIO — The list of potential therapeutic targets in rheumatoid arthritis continues to expand, with preliminary evidence supporting the addition of the proinflammatory cytokine interleukin (IL)-15.

This signaling molecule, found in the synovium in those with rheumatoid arthritis (RA), appears early in the cascade of events that leads to inflammation, inducing the production of tumor necrosis factor (TNF)-α and recruiting inflammatory T cells.

A human monoclonal IgG antibody that binds to and inhibits IL-15 has been developed and is now undergoing clinical testing, Iain McInnes, M.D., said at the annual meeting of the American College of Rheumatology.

In an interim analysis of a proof-of-concept study of the antibody AMG 714, clinical effect was demonstrated at various doses in 110 patients with active RA, with the most pronounced benefit seen in the highest-dose group, he said.

Background methotrexate was permitted in stable doses of 25 mg/wk or less, but other disease-modifying drugs were not. None of the patients had previously received biologic response modifiers.

Stable limited doses of NSAIDs and corticosteroids were allowed.

Patients were randomized to receive placebo or AMG 714 in doses of 40 mg, 80 mg, 160 mg, or 280 mg, given by subcutaneous injection every 2 weeks for a 12-week period.

Among those patients in the highest dose group, 62% achieved an ACR 20 response, as did 26% in the placebo group; this between-group difference was statistically significant.

The response was maintained at week 14, though at that point, statistical significance was lost because of an increased placebo response, said Dr. McInnes, professor of experimental medicine and rheumatology at the Centre for Rheumatic Diseases, Glasgow, Scotland.

Approximately one-fourth of patients in the active treatment groups achieved an ACR 50 response, as did one patient in the placebo group. Some patients have achieved an ACR 70 response, but those data remain blinded, he said.

A 20% reduction in CRP was seen at weeks 4 and 14 in 29% and 39% of placebo patients, respectively, and in 70% and 63% of those in the high-dose AMG 714 group.

Worsening of RA was observed in 26% of placebo patients, compared with 5% of the high-dose treatment group.

Adverse events have been closely tracked in the study. “As this is the first time IL-15 is being targeted in humans, safety is our highest priority,” Dr. McInnes said.

Overall, the incidence of adverse events, such as infection, gastrointestinal complaints, and skin disorders, has been similar across the treatment and placebo groups. Approximately one-fourth of patients in the high-dose group have experienced transient injection-site reactions.

Two serious adverse events were reported. One was a case of deep venous thrombosis diagnosed 4 weeks after the last injection, and the other was sepsis following focal infection of a finger. Both resolved without sequelae, he said.

No deaths occurred during the trial.

“These are encouraging preliminary data,” he said in conclusion. An additional 70 patients now have entered the ongoing study.

Dr. McInnes disclosed a commercial relationship with Genmab A/S, the Copenhagen-based manufacturer of AMG 714.

SAN ANTONIO — The safety and efficacy of etanercept have held up over time, with large cohorts of rheumatoid arthritis patients having been followed for as long as 7 years.

In a poster session at the annual meeting of the American College of Rheumatology, Michael E. Weinblatt, M.D., reported long-term efficacy results for two groups of American patients: 207 who at baseline had a history of having RA for 3 years or less and 644 who had long-standing disease that failed at least one disease-modifying antirheumatic drug.

The median length of exposure to etanercept in the early RA group was 5.5 years; in the long-standing RA group, it was 5.6 years. All patients had received dosages of 25 mg twice weekly by subcutaneous injection.

“Significant improvements in multiple measures of disease activity have been achieved with etanercept therapy,” he said. (See box.)

Concomitant medications were permitted during the extension studies, but most patients have been able to stop taking corticosteroids and methotrexate while receiving etanercept, said Dr. Weinblatt, professor of medicine, Harvard Medical School, Boston.

Patients who had received etanercept at any dose were included in the long-term safety analyses. Of this larger cohort, which included 558 early-disease patients and 884 long-standing disease patients, 323 (58%) and 391 (44%) of the early and long-standing disease patients, respectively, remain on the drug.

A total of 10% of the early disease group and 12% of the long-standing disease group discontinued the drug because of adverse effects.

There have been 28 deaths, including 4 from malignancy and 4 from cardiac disease, whereas 53 deaths were expected. There also have been 11 cases of sepsis but no cases of tuberculosis or opportunistic infections, Dr. Weinblatt said.

In a separate poster session, Larry W. Moreland, M.D., reported on a larger cohort of patients from North America and Europe who had been taking the drug. “Serious adverse events, infections, malignancies, and deaths do not increase over 7 years of treatment,” he said.

Analysis of data from that cohort of 2,054 patients, representing 7,382 patient-years of etanercept exposure, found that the rates of serious adverse events and serious infections were similar to those seen in control groups in previous trials. Rates of malignancies were similar to what was expected, with 67 observed and 61 expected.

A total of 42 patients died. “This death rate was lower than expected, as 53 deaths were expected in North America alone,” said Dr. Moreland, who holds the Anna Lois Waters Chair of Medicine in Rheumatology at the University of Alabama, Birmingham.

Of concern, however, are nine cases of lymphoma diagnosed in North America and one diagnosed in Europe. The incidence is higher than expected in the general population, and additional studies are needed to understand if this finding is related to etanercept or if it reflects the elevated risk of lymphoma inherent in patients with RA, Dr. Moreland said.

Both studies were funded by Immunex Corp., a subsidiary of Amgen Inc., and by Wyeth Research.

SAN ANTONIO — The safety and efficacy of etanercept have held up over time, with large cohorts of rheumatoid arthritis patients having been followed for as long as 7 years.

In a poster session at the annual meeting of the American College of Rheumatology, Michael E. Weinblatt, M.D., reported long-term efficacy results for two groups of American patients: 207 who at baseline had a history of having RA for 3 years or less and 644 who had long-standing disease that failed at least one disease-modifying antirheumatic drug.

The median length of exposure to etanercept in the early RA group was 5.5 years; in the long-standing RA group, it was 5.6 years. All patients had received dosages of 25 mg twice weekly by subcutaneous injection.

“Significant improvements in multiple measures of disease activity have been achieved with etanercept therapy,” he said. (See box.)

Concomitant medications were permitted during the extension studies, but most patients have been able to stop taking corticosteroids and methotrexate while receiving etanercept, said Dr. Weinblatt, professor of medicine, Harvard Medical School, Boston.

Patients who had received etanercept at any dose were included in the long-term safety analyses. Of this larger cohort, which included 558 early-disease patients and 884 long-standing disease patients, 323 (58%) and 391 (44%) of the early and long-standing disease patients, respectively, remain on the drug.

A total of 10% of the early disease group and 12% of the long-standing disease group discontinued the drug because of adverse effects.

There have been 28 deaths, including 4 from malignancy and 4 from cardiac disease, whereas 53 deaths were expected. There also have been 11 cases of sepsis but no cases of tuberculosis or opportunistic infections, Dr. Weinblatt said.

In a separate poster session, Larry W. Moreland, M.D., reported on a larger cohort of patients from North America and Europe who had been taking the drug. “Serious adverse events, infections, malignancies, and deaths do not increase over 7 years of treatment,” he said.

Analysis of data from that cohort of 2,054 patients, representing 7,382 patient-years of etanercept exposure, found that the rates of serious adverse events and serious infections were similar to those seen in control groups in previous trials. Rates of malignancies were similar to what was expected, with 67 observed and 61 expected.

A total of 42 patients died. “This death rate was lower than expected, as 53 deaths were expected in North America alone,” said Dr. Moreland, who holds the Anna Lois Waters Chair of Medicine in Rheumatology at the University of Alabama, Birmingham.

Of concern, however, are nine cases of lymphoma diagnosed in North America and one diagnosed in Europe. The incidence is higher than expected in the general population, and additional studies are needed to understand if this finding is related to etanercept or if it reflects the elevated risk of lymphoma inherent in patients with RA, Dr. Moreland said.

Both studies were funded by Immunex Corp., a subsidiary of Amgen Inc., and by Wyeth Research.

SAN ANTONIO — The safety and efficacy of etanercept have held up over time, with large cohorts of rheumatoid arthritis patients having been followed for as long as 7 years.

In a poster session at the annual meeting of the American College of Rheumatology, Michael E. Weinblatt, M.D., reported long-term efficacy results for two groups of American patients: 207 who at baseline had a history of having RA for 3 years or less and 644 who had long-standing disease that failed at least one disease-modifying antirheumatic drug.

The median length of exposure to etanercept in the early RA group was 5.5 years; in the long-standing RA group, it was 5.6 years. All patients had received dosages of 25 mg twice weekly by subcutaneous injection.

“Significant improvements in multiple measures of disease activity have been achieved with etanercept therapy,” he said. (See box.)

Concomitant medications were permitted during the extension studies, but most patients have been able to stop taking corticosteroids and methotrexate while receiving etanercept, said Dr. Weinblatt, professor of medicine, Harvard Medical School, Boston.

Patients who had received etanercept at any dose were included in the long-term safety analyses. Of this larger cohort, which included 558 early-disease patients and 884 long-standing disease patients, 323 (58%) and 391 (44%) of the early and long-standing disease patients, respectively, remain on the drug.

A total of 10% of the early disease group and 12% of the long-standing disease group discontinued the drug because of adverse effects.

There have been 28 deaths, including 4 from malignancy and 4 from cardiac disease, whereas 53 deaths were expected. There also have been 11 cases of sepsis but no cases of tuberculosis or opportunistic infections, Dr. Weinblatt said.

In a separate poster session, Larry W. Moreland, M.D., reported on a larger cohort of patients from North America and Europe who had been taking the drug. “Serious adverse events, infections, malignancies, and deaths do not increase over 7 years of treatment,” he said.

Analysis of data from that cohort of 2,054 patients, representing 7,382 patient-years of etanercept exposure, found that the rates of serious adverse events and serious infections were similar to those seen in control groups in previous trials. Rates of malignancies were similar to what was expected, with 67 observed and 61 expected.

A total of 42 patients died. “This death rate was lower than expected, as 53 deaths were expected in North America alone,” said Dr. Moreland, who holds the Anna Lois Waters Chair of Medicine in Rheumatology at the University of Alabama, Birmingham.

Of concern, however, are nine cases of lymphoma diagnosed in North America and one diagnosed in Europe. The incidence is higher than expected in the general population, and additional studies are needed to understand if this finding is related to etanercept or if it reflects the elevated risk of lymphoma inherent in patients with RA, Dr. Moreland said.

Both studies were funded by Immunex Corp., a subsidiary of Amgen Inc., and by Wyeth Research.

NEW YORK — Simple trapeziectomy offers as much benefit as more complicated, combined procedures for osteoarthritis of the trapeziometacarpal joint, Timothy R.C. Davis, M.D., said at the annual meeting of the American Society for Surgery of the Hand.

Trapeziectomy has been widely performed for this condition since its use was first reported in 1949. It fell out of favor because it was perceived as having a protracted recovery, and there was a belief that the inevitable shortening of the thumb would weaken that digit.

Concerns about postoperative arthritis or instability that could lead to persistent pain led to modifications of the procedure, Dr. Davis said.

One approach was to do a tendon interposition after trapeziectomy, using the palmaris longus. A second alternative was to do the tendon interposition plus an additional ligament reconstruction, which is probably the most commonly used technique today, he said.

“But neither of these procedures has ever been demonstrated to produce better outcomes than simple excision of the trapezium,” said Dr. Davis, professor of orthopaedics and accident surgery at the University of Nottingham (England).

A series of 183 thumbs in 162 women whose painful basal thumb osteoarthritis had not responded to medical therapy were randomized to one of the three procedures.

Additional procedures such as carpal tunnel decompressions were performed as necessary. Following the surgery, each thumb was immobilized in a plaster of paris spica for 6 weeks.

Once the plaster was removed patients were encouraged to mobilize the thumb and were given physiotherapy as needed.

Subjective assessments included evaluation of pain, weakness, stiffness, and the ability to perform activities of daily living.

At 3 months about 50% of patients in all groups reported little or no pain, and by 1 year, 82% had reached this level of pain relief. “But the pain relief was not influenced by the type of operation—it was as if we had done the same operation in all the patients,” Dr. Davis said.

By 1 year, 68% reported no weakness or interference with activities of daily living.

Mean thumb key pinch strength, evaluated with a pinch meter, improved significantly across all groups from 3.5 kg preoperatively to 4.6 kg at 1 year, but again the improvement was not influenced by the type of surgery performed, he said.

“In the short term at least, we concluded that palmaris longus interposition or ligament reconstruction did not improve the outcome of simple trapeziectomy with the insertion of a Kirschner wire and did not speed up recovery from the operation,” Dr. Davis said.

Five-year follow-up is ongoing, but the results will have to wait until about 2007, he added.

NEW YORK — Simple trapeziectomy offers as much benefit as more complicated, combined procedures for osteoarthritis of the trapeziometacarpal joint, Timothy R.C. Davis, M.D., said at the annual meeting of the American Society for Surgery of the Hand.

Trapeziectomy has been widely performed for this condition since its use was first reported in 1949. It fell out of favor because it was perceived as having a protracted recovery, and there was a belief that the inevitable shortening of the thumb would weaken that digit.

Concerns about postoperative arthritis or instability that could lead to persistent pain led to modifications of the procedure, Dr. Davis said.

One approach was to do a tendon interposition after trapeziectomy, using the palmaris longus. A second alternative was to do the tendon interposition plus an additional ligament reconstruction, which is probably the most commonly used technique today, he said.

“But neither of these procedures has ever been demonstrated to produce better outcomes than simple excision of the trapezium,” said Dr. Davis, professor of orthopaedics and accident surgery at the University of Nottingham (England).

A series of 183 thumbs in 162 women whose painful basal thumb osteoarthritis had not responded to medical therapy were randomized to one of the three procedures.

Additional procedures such as carpal tunnel decompressions were performed as necessary. Following the surgery, each thumb was immobilized in a plaster of paris spica for 6 weeks.

Once the plaster was removed patients were encouraged to mobilize the thumb and were given physiotherapy as needed.

Subjective assessments included evaluation of pain, weakness, stiffness, and the ability to perform activities of daily living.

At 3 months about 50% of patients in all groups reported little or no pain, and by 1 year, 82% had reached this level of pain relief. “But the pain relief was not influenced by the type of operation—it was as if we had done the same operation in all the patients,” Dr. Davis said.

By 1 year, 68% reported no weakness or interference with activities of daily living.

Mean thumb key pinch strength, evaluated with a pinch meter, improved significantly across all groups from 3.5 kg preoperatively to 4.6 kg at 1 year, but again the improvement was not influenced by the type of surgery performed, he said.

“In the short term at least, we concluded that palmaris longus interposition or ligament reconstruction did not improve the outcome of simple trapeziectomy with the insertion of a Kirschner wire and did not speed up recovery from the operation,” Dr. Davis said.

Five-year follow-up is ongoing, but the results will have to wait until about 2007, he added.

NEW YORK — Simple trapeziectomy offers as much benefit as more complicated, combined procedures for osteoarthritis of the trapeziometacarpal joint, Timothy R.C. Davis, M.D., said at the annual meeting of the American Society for Surgery of the Hand.

Trapeziectomy has been widely performed for this condition since its use was first reported in 1949. It fell out of favor because it was perceived as having a protracted recovery, and there was a belief that the inevitable shortening of the thumb would weaken that digit.

Concerns about postoperative arthritis or instability that could lead to persistent pain led to modifications of the procedure, Dr. Davis said.

One approach was to do a tendon interposition after trapeziectomy, using the palmaris longus. A second alternative was to do the tendon interposition plus an additional ligament reconstruction, which is probably the most commonly used technique today, he said.

“But neither of these procedures has ever been demonstrated to produce better outcomes than simple excision of the trapezium,” said Dr. Davis, professor of orthopaedics and accident surgery at the University of Nottingham (England).

A series of 183 thumbs in 162 women whose painful basal thumb osteoarthritis had not responded to medical therapy were randomized to one of the three procedures.

Additional procedures such as carpal tunnel decompressions were performed as necessary. Following the surgery, each thumb was immobilized in a plaster of paris spica for 6 weeks.

Once the plaster was removed patients were encouraged to mobilize the thumb and were given physiotherapy as needed.

Subjective assessments included evaluation of pain, weakness, stiffness, and the ability to perform activities of daily living.

At 3 months about 50% of patients in all groups reported little or no pain, and by 1 year, 82% had reached this level of pain relief. “But the pain relief was not influenced by the type of operation—it was as if we had done the same operation in all the patients,” Dr. Davis said.

By 1 year, 68% reported no weakness or interference with activities of daily living.

Mean thumb key pinch strength, evaluated with a pinch meter, improved significantly across all groups from 3.5 kg preoperatively to 4.6 kg at 1 year, but again the improvement was not influenced by the type of surgery performed, he said.

“In the short term at least, we concluded that palmaris longus interposition or ligament reconstruction did not improve the outcome of simple trapeziectomy with the insertion of a Kirschner wire and did not speed up recovery from the operation,” Dr. Davis said.

Five-year follow-up is ongoing, but the results will have to wait until about 2007, he added.

BELFAST — In the burgeoning world of injectable cosmetic fillers, nothing is actually inert, Debjani Sahni, M.D., said at the annual meeting of the British Association of Dermatologists.

The new so-called biologically inert fillers have become increasingly popular, because bovine collagen is associated with allergic reactions in up to 3% of patients, Dr. Sahni said, and there is at least a theoretical risk of transmission of bovine spongiform encephalopathy.

“Manufacturers claim that these fillers are nonmigratory and that adverse reactions are rare, but we have seen three patients who developed disfiguring allergic reactions to inert injectable fillers,” said Dr. Sahni of the department of dermatology, Ealing Hospital, Southall, Middlesex, England.

The first patient was a 49-year-old woman who had received injections of Artecoll to the nasofacial sulcae. This filler contains polymethylmethacrylate microspheres. Although classified as inert, it also contains 3.5% bovine collagen, she said.

Within 3 weeks of receiving the injections, the patient developed marked inflammation at the injection sites. She required hospitalization and treatment with intravenous antibiotics and dexamethasone. Although the inflammation subsided, it never completely resolved, Dr. Sahni said.

A year later, the patient presented with an inflamed nodule in the right nasofacial sulcus, and a skin biopsy revealed sinus tracts extending to the deep dermis. Along the walls of these tracts a granulomatous reaction was visible, with multiple foreign body giant cells and distinctive spheres of uniform shape and size that under polarized light were negatively birefringent. “These features are typical of a granulomatous reaction to Artecoll, not to the bovine component of the filler,” she said.

The second patient was a 51-year-old woman who underwent lip augmentation, first with Restylane, a derivative of hyaluronic acid, and then Dermalive, which is hyaluronic acid plus hydroxyethylmetacrylate.

A year later, the patient presented with chronically sore, inflamed lips characterized by erythematous, nodular indurated areas. A skin biopsy demonstrated that much of the reticular dermis had been taken up by an inflammatory infiltrate. Histological features were typical of a granulomatous reation to Dermalive, Dr. Sahni said.

The third patient was a 71-year-old woman who had undergone multiple injections of bovine collagen, Restylane, and several other unidentified fillers. She had also undergone a permanent lip-line tattoo. She presented with a 4-month history of sore, indurated, inflamed lips. Histologic evaluation revealed a chronic inflammatory infiltrate and macrophages containing tattoo pigments.

She also had a granulomatous reaction, with florid foreign-body giant cells that were positively birefringent. A literature search suggested this reaction was typical for New-Fill, an inert filler consisting of polylactic acid.

These cases raise a number of issues, Dr. Sahni noted. “First, although classified as inert, these fillers clearly are able to stimulate a clinically evident granulomatous reaction. Second, none of the patients had been forewarned of the possibility of such a reaction, so informed consent was not adequate,” she said. There also had been no skin testing prior to the injections.

Inert fillers are classified as medical devices and not drugs and therefore do not undergo the same degree of scrutiny as drugs prior to release onto the market. Many fillers have not undergone prior animal testing or human trials and, in fact, are not required to do so, Dr. Sahni said.

“Physicians should be aware of the potential for adverse reactions to these fillers,” she said. “As they become more popular, we may see an increase in the frequency of granulomatous reactions. It is imperative that adequate informed consent be practiced so that patients can make an educated decision.

BELFAST — In the burgeoning world of injectable cosmetic fillers, nothing is actually inert, Debjani Sahni, M.D., said at the annual meeting of the British Association of Dermatologists.

The new so-called biologically inert fillers have become increasingly popular, because bovine collagen is associated with allergic reactions in up to 3% of patients, Dr. Sahni said, and there is at least a theoretical risk of transmission of bovine spongiform encephalopathy.

“Manufacturers claim that these fillers are nonmigratory and that adverse reactions are rare, but we have seen three patients who developed disfiguring allergic reactions to inert injectable fillers,” said Dr. Sahni of the department of dermatology, Ealing Hospital, Southall, Middlesex, England.

The first patient was a 49-year-old woman who had received injections of Artecoll to the nasofacial sulcae. This filler contains polymethylmethacrylate microspheres. Although classified as inert, it also contains 3.5% bovine collagen, she said.

Within 3 weeks of receiving the injections, the patient developed marked inflammation at the injection sites. She required hospitalization and treatment with intravenous antibiotics and dexamethasone. Although the inflammation subsided, it never completely resolved, Dr. Sahni said.

A year later, the patient presented with an inflamed nodule in the right nasofacial sulcus, and a skin biopsy revealed sinus tracts extending to the deep dermis. Along the walls of these tracts a granulomatous reaction was visible, with multiple foreign body giant cells and distinctive spheres of uniform shape and size that under polarized light were negatively birefringent. “These features are typical of a granulomatous reaction to Artecoll, not to the bovine component of the filler,” she said.

The second patient was a 51-year-old woman who underwent lip augmentation, first with Restylane, a derivative of hyaluronic acid, and then Dermalive, which is hyaluronic acid plus hydroxyethylmetacrylate.

A year later, the patient presented with chronically sore, inflamed lips characterized by erythematous, nodular indurated areas. A skin biopsy demonstrated that much of the reticular dermis had been taken up by an inflammatory infiltrate. Histological features were typical of a granulomatous reation to Dermalive, Dr. Sahni said.

The third patient was a 71-year-old woman who had undergone multiple injections of bovine collagen, Restylane, and several other unidentified fillers. She had also undergone a permanent lip-line tattoo. She presented with a 4-month history of sore, indurated, inflamed lips. Histologic evaluation revealed a chronic inflammatory infiltrate and macrophages containing tattoo pigments.

She also had a granulomatous reaction, with florid foreign-body giant cells that were positively birefringent. A literature search suggested this reaction was typical for New-Fill, an inert filler consisting of polylactic acid.

These cases raise a number of issues, Dr. Sahni noted. “First, although classified as inert, these fillers clearly are able to stimulate a clinically evident granulomatous reaction. Second, none of the patients had been forewarned of the possibility of such a reaction, so informed consent was not adequate,” she said. There also had been no skin testing prior to the injections.

Inert fillers are classified as medical devices and not drugs and therefore do not undergo the same degree of scrutiny as drugs prior to release onto the market. Many fillers have not undergone prior animal testing or human trials and, in fact, are not required to do so, Dr. Sahni said.

“Physicians should be aware of the potential for adverse reactions to these fillers,” she said. “As they become more popular, we may see an increase in the frequency of granulomatous reactions. It is imperative that adequate informed consent be practiced so that patients can make an educated decision.

BELFAST — In the burgeoning world of injectable cosmetic fillers, nothing is actually inert, Debjani Sahni, M.D., said at the annual meeting of the British Association of Dermatologists.

The new so-called biologically inert fillers have become increasingly popular, because bovine collagen is associated with allergic reactions in up to 3% of patients, Dr. Sahni said, and there is at least a theoretical risk of transmission of bovine spongiform encephalopathy.

“Manufacturers claim that these fillers are nonmigratory and that adverse reactions are rare, but we have seen three patients who developed disfiguring allergic reactions to inert injectable fillers,” said Dr. Sahni of the department of dermatology, Ealing Hospital, Southall, Middlesex, England.

The first patient was a 49-year-old woman who had received injections of Artecoll to the nasofacial sulcae. This filler contains polymethylmethacrylate microspheres. Although classified as inert, it also contains 3.5% bovine collagen, she said.

Within 3 weeks of receiving the injections, the patient developed marked inflammation at the injection sites. She required hospitalization and treatment with intravenous antibiotics and dexamethasone. Although the inflammation subsided, it never completely resolved, Dr. Sahni said.

A year later, the patient presented with an inflamed nodule in the right nasofacial sulcus, and a skin biopsy revealed sinus tracts extending to the deep dermis. Along the walls of these tracts a granulomatous reaction was visible, with multiple foreign body giant cells and distinctive spheres of uniform shape and size that under polarized light were negatively birefringent. “These features are typical of a granulomatous reaction to Artecoll, not to the bovine component of the filler,” she said.

The second patient was a 51-year-old woman who underwent lip augmentation, first with Restylane, a derivative of hyaluronic acid, and then Dermalive, which is hyaluronic acid plus hydroxyethylmetacrylate.

A year later, the patient presented with chronically sore, inflamed lips characterized by erythematous, nodular indurated areas. A skin biopsy demonstrated that much of the reticular dermis had been taken up by an inflammatory infiltrate. Histological features were typical of a granulomatous reation to Dermalive, Dr. Sahni said.

The third patient was a 71-year-old woman who had undergone multiple injections of bovine collagen, Restylane, and several other unidentified fillers. She had also undergone a permanent lip-line tattoo. She presented with a 4-month history of sore, indurated, inflamed lips. Histologic evaluation revealed a chronic inflammatory infiltrate and macrophages containing tattoo pigments.

She also had a granulomatous reaction, with florid foreign-body giant cells that were positively birefringent. A literature search suggested this reaction was typical for New-Fill, an inert filler consisting of polylactic acid.

These cases raise a number of issues, Dr. Sahni noted. “First, although classified as inert, these fillers clearly are able to stimulate a clinically evident granulomatous reaction. Second, none of the patients had been forewarned of the possibility of such a reaction, so informed consent was not adequate,” she said. There also had been no skin testing prior to the injections.

Inert fillers are classified as medical devices and not drugs and therefore do not undergo the same degree of scrutiny as drugs prior to release onto the market. Many fillers have not undergone prior animal testing or human trials and, in fact, are not required to do so, Dr. Sahni said.

“Physicians should be aware of the potential for adverse reactions to these fillers,” she said. “As they become more popular, we may see an increase in the frequency of granulomatous reactions. It is imperative that adequate informed consent be practiced so that patients can make an educated decision.

NEW YORK – A second-generation antipsychotic should be the first-line choice in early onset schizophrenia, Harvey N. Kranzler, M.D., said at the psychopharmacology update institute of the American Academy of Child and Adolescent Psychiatry.

The atypical antipsychotic agents cause significantly fewer extrapyramidal symptoms and less tardive dyskinesia than the older neuroleptics.

While little in the way of controlled data are available for any of these drugs in pediatric patients, the Treatment Recommendations for the Use of Antipsychotics for Aggressive Youth collaborative group has been formulating guidelines, particularly on dosing and titration.

“We're learning from clinical experience, and our mantra is start low and go slow,” said Dr. Kranzler of the collaborative group.

The second-generation agents risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), and ziprasidone (Geodon) all are serotonin-dopamine antagonists, but they differ in specific receptor activity with the result that they vary to some degree in side effect profiles. Because of those differences in receptor blockade, if one does not work another can be tried, which was generally not so with the older neuroleptics, said Dr. Kranzler, director of the division of child and adolescent psychiatry and professor of psychiatry at Albert Einstein College of Medicine, New York.

One drawback to those drugs is that because of the need for slow titration, it may take some time to achieve effect. “This sometimes presents problems when you have a very agitated or out-of-control youngster,” he said. In such a situation, treatment initiation can combine an atypical with an older antipsychotic such as haloperidol (Haldol) or chlorpromazine (Thorazine) to get a handle on the severe symptoms, he said. The traditional antipsychotic can then be titrated down.

The importance of improving pharmacotherapy for young patients with schizophrenia has been demonstrated by studies showing the poor prognosis when onset occurs before age 12, increased negative symptoms in adulthood when symptoms begin before age 15, and worse psychosocial impairment in patients whose illness begins before age 21.

Regarding the individual drugs, Dr. Kranzler offered advice based on clinical experience at his center:

▸ Risperidone. “At present, risperidone is often our first-line atypical, because it was the first one we had and we have more of a comfort level with it.” This agent also has the quickest onset of action of the second-generation drugs, similar to that of the traditional neuroleptics.

Risperidone should be used in the lowest dose possible, generally in the 0.25- to 2- mg/day range, according to Dr. Kranzler. Initially, this drug was typically given in doses of 3-6 mg/day in children, “but I don't go above 3 mg any more. If you're at 3 mg or above you might as well use Haldol–it's quicker, less expensive, and no different in side effect profile or receptor activity,” he said.

A common mistake is to give risperidone on a twice-daily or thrice-daily dosing schedule. “Once you've gotten through the titration period go to once a day dosing except for younger children,” he said. The main reasons are cost and compliance. “The economics of atypical antipsychotics are breaking the bank of the Medicaid and managed care systems, and it really is a great concern and we must be cognizant of this,” he said.

▸ Olanzapine. This agent showed efficacy in childhood onset schizophrenia in an open-label study, and, like risperidone, is now undergoing controlled studies.

And as with risperidone, clinicians should attempt to use as low a dose as possible and on a once-daily schedule. Higher dosages in the range of 15-30 mg/day might be required for optimal efficacy, however.

The cost of this agent is again a concern. In fact, some systems throughout the country are considering removing this drug from their formularies, Dr. Kranzler said.

▸ Quetiapine. Preliminary studies have also shown effectiveness for quetiapine in adolescents with psychosis, aggression, and affective symptoms. With this agent, t.i.d. or b.i.d. dosing is needed, with titration up to 800 mg/day if needed, he said.

“Quetiapine is the most frequently prescribed antipsychotic in the country today, because it is used by clinicians other than psychiatrists as a sleep medication at 25 mg. It is a low dose and it does work, but it is an antipsychotic medication with all its receptor activity,” he cautioned. It also is expensive, he said.

▸ Ziprasidone. This, too, is a very useful medication, but must be titrated very slowly because of its potential for activation, he said. It has some norepinephrine and serotonin uptake blocking activity, and may have beneficial antidepressant and antianxiety properties.

Prolongation of the QTc interval has been a concern with this drug, but “has not been a problem in our hands,” he said. ▸ Aripiprazole (Abilify). The atypical class of antipsychotics now includes a third-generation agent, aripiprazole. This drug is a dopamine-serotonin system stabilizer that has partial D2 agonist activity and modulates central serotonergic pathways. It improves executive functioning and negative symptoms, and may also affect depression and anxiety.

▸ Clozapine (Clozaril). Among the atypicals, clozapine exhibits the most complex receptor blockade activity, and because of its side effect profile is not considered a first-line antipsychotic. But it is very effective in treatment-resistant patients, Dr. Kranzler said. “You want to be comfortable using it, because it can save these kids' lives,” he said. In his center, 43 of 57 severely ill hospitalized patients were able to be discharged on clozapine. “They are not paragons of mental health but they are able to function in residences,” he said.

NEW YORK – A second-generation antipsychotic should be the first-line choice in early onset schizophrenia, Harvey N. Kranzler, M.D., said at the psychopharmacology update institute of the American Academy of Child and Adolescent Psychiatry.

The atypical antipsychotic agents cause significantly fewer extrapyramidal symptoms and less tardive dyskinesia than the older neuroleptics.

While little in the way of controlled data are available for any of these drugs in pediatric patients, the Treatment Recommendations for the Use of Antipsychotics for Aggressive Youth collaborative group has been formulating guidelines, particularly on dosing and titration.

“We're learning from clinical experience, and our mantra is start low and go slow,” said Dr. Kranzler of the collaborative group.

The second-generation agents risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), and ziprasidone (Geodon) all are serotonin-dopamine antagonists, but they differ in specific receptor activity with the result that they vary to some degree in side effect profiles. Because of those differences in receptor blockade, if one does not work another can be tried, which was generally not so with the older neuroleptics, said Dr. Kranzler, director of the division of child and adolescent psychiatry and professor of psychiatry at Albert Einstein College of Medicine, New York.

One drawback to those drugs is that because of the need for slow titration, it may take some time to achieve effect. “This sometimes presents problems when you have a very agitated or out-of-control youngster,” he said. In such a situation, treatment initiation can combine an atypical with an older antipsychotic such as haloperidol (Haldol) or chlorpromazine (Thorazine) to get a handle on the severe symptoms, he said. The traditional antipsychotic can then be titrated down.

The importance of improving pharmacotherapy for young patients with schizophrenia has been demonstrated by studies showing the poor prognosis when onset occurs before age 12, increased negative symptoms in adulthood when symptoms begin before age 15, and worse psychosocial impairment in patients whose illness begins before age 21.

Regarding the individual drugs, Dr. Kranzler offered advice based on clinical experience at his center:

▸ Risperidone. “At present, risperidone is often our first-line atypical, because it was the first one we had and we have more of a comfort level with it.” This agent also has the quickest onset of action of the second-generation drugs, similar to that of the traditional neuroleptics.

Risperidone should be used in the lowest dose possible, generally in the 0.25- to 2- mg/day range, according to Dr. Kranzler. Initially, this drug was typically given in doses of 3-6 mg/day in children, “but I don't go above 3 mg any more. If you're at 3 mg or above you might as well use Haldol–it's quicker, less expensive, and no different in side effect profile or receptor activity,” he said.

A common mistake is to give risperidone on a twice-daily or thrice-daily dosing schedule. “Once you've gotten through the titration period go to once a day dosing except for younger children,” he said. The main reasons are cost and compliance. “The economics of atypical antipsychotics are breaking the bank of the Medicaid and managed care systems, and it really is a great concern and we must be cognizant of this,” he said.

▸ Olanzapine. This agent showed efficacy in childhood onset schizophrenia in an open-label study, and, like risperidone, is now undergoing controlled studies.

And as with risperidone, clinicians should attempt to use as low a dose as possible and on a once-daily schedule. Higher dosages in the range of 15-30 mg/day might be required for optimal efficacy, however.

The cost of this agent is again a concern. In fact, some systems throughout the country are considering removing this drug from their formularies, Dr. Kranzler said.

▸ Quetiapine. Preliminary studies have also shown effectiveness for quetiapine in adolescents with psychosis, aggression, and affective symptoms. With this agent, t.i.d. or b.i.d. dosing is needed, with titration up to 800 mg/day if needed, he said.

“Quetiapine is the most frequently prescribed antipsychotic in the country today, because it is used by clinicians other than psychiatrists as a sleep medication at 25 mg. It is a low dose and it does work, but it is an antipsychotic medication with all its receptor activity,” he cautioned. It also is expensive, he said.

▸ Ziprasidone. This, too, is a very useful medication, but must be titrated very slowly because of its potential for activation, he said. It has some norepinephrine and serotonin uptake blocking activity, and may have beneficial antidepressant and antianxiety properties.

Prolongation of the QTc interval has been a concern with this drug, but “has not been a problem in our hands,” he said. ▸ Aripiprazole (Abilify). The atypical class of antipsychotics now includes a third-generation agent, aripiprazole. This drug is a dopamine-serotonin system stabilizer that has partial D2 agonist activity and modulates central serotonergic pathways. It improves executive functioning and negative symptoms, and may also affect depression and anxiety.

▸ Clozapine (Clozaril). Among the atypicals, clozapine exhibits the most complex receptor blockade activity, and because of its side effect profile is not considered a first-line antipsychotic. But it is very effective in treatment-resistant patients, Dr. Kranzler said. “You want to be comfortable using it, because it can save these kids' lives,” he said. In his center, 43 of 57 severely ill hospitalized patients were able to be discharged on clozapine. “They are not paragons of mental health but they are able to function in residences,” he said.

NEW YORK – A second-generation antipsychotic should be the first-line choice in early onset schizophrenia, Harvey N. Kranzler, M.D., said at the psychopharmacology update institute of the American Academy of Child and Adolescent Psychiatry.

The atypical antipsychotic agents cause significantly fewer extrapyramidal symptoms and less tardive dyskinesia than the older neuroleptics.

While little in the way of controlled data are available for any of these drugs in pediatric patients, the Treatment Recommendations for the Use of Antipsychotics for Aggressive Youth collaborative group has been formulating guidelines, particularly on dosing and titration.

“We're learning from clinical experience, and our mantra is start low and go slow,” said Dr. Kranzler of the collaborative group.

The second-generation agents risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), and ziprasidone (Geodon) all are serotonin-dopamine antagonists, but they differ in specific receptor activity with the result that they vary to some degree in side effect profiles. Because of those differences in receptor blockade, if one does not work another can be tried, which was generally not so with the older neuroleptics, said Dr. Kranzler, director of the division of child and adolescent psychiatry and professor of psychiatry at Albert Einstein College of Medicine, New York.

One drawback to those drugs is that because of the need for slow titration, it may take some time to achieve effect. “This sometimes presents problems when you have a very agitated or out-of-control youngster,” he said. In such a situation, treatment initiation can combine an atypical with an older antipsychotic such as haloperidol (Haldol) or chlorpromazine (Thorazine) to get a handle on the severe symptoms, he said. The traditional antipsychotic can then be titrated down.

The importance of improving pharmacotherapy for young patients with schizophrenia has been demonstrated by studies showing the poor prognosis when onset occurs before age 12, increased negative symptoms in adulthood when symptoms begin before age 15, and worse psychosocial impairment in patients whose illness begins before age 21.

Regarding the individual drugs, Dr. Kranzler offered advice based on clinical experience at his center:

▸ Risperidone. “At present, risperidone is often our first-line atypical, because it was the first one we had and we have more of a comfort level with it.” This agent also has the quickest onset of action of the second-generation drugs, similar to that of the traditional neuroleptics.

Risperidone should be used in the lowest dose possible, generally in the 0.25- to 2- mg/day range, according to Dr. Kranzler. Initially, this drug was typically given in doses of 3-6 mg/day in children, “but I don't go above 3 mg any more. If you're at 3 mg or above you might as well use Haldol–it's quicker, less expensive, and no different in side effect profile or receptor activity,” he said.

A common mistake is to give risperidone on a twice-daily or thrice-daily dosing schedule. “Once you've gotten through the titration period go to once a day dosing except for younger children,” he said. The main reasons are cost and compliance. “The economics of atypical antipsychotics are breaking the bank of the Medicaid and managed care systems, and it really is a great concern and we must be cognizant of this,” he said.

▸ Olanzapine. This agent showed efficacy in childhood onset schizophrenia in an open-label study, and, like risperidone, is now undergoing controlled studies.

And as with risperidone, clinicians should attempt to use as low a dose as possible and on a once-daily schedule. Higher dosages in the range of 15-30 mg/day might be required for optimal efficacy, however.

The cost of this agent is again a concern. In fact, some systems throughout the country are considering removing this drug from their formularies, Dr. Kranzler said.

▸ Quetiapine. Preliminary studies have also shown effectiveness for quetiapine in adolescents with psychosis, aggression, and affective symptoms. With this agent, t.i.d. or b.i.d. dosing is needed, with titration up to 800 mg/day if needed, he said.

“Quetiapine is the most frequently prescribed antipsychotic in the country today, because it is used by clinicians other than psychiatrists as a sleep medication at 25 mg. It is a low dose and it does work, but it is an antipsychotic medication with all its receptor activity,” he cautioned. It also is expensive, he said.

▸ Ziprasidone. This, too, is a very useful medication, but must be titrated very slowly because of its potential for activation, he said. It has some norepinephrine and serotonin uptake blocking activity, and may have beneficial antidepressant and antianxiety properties.

Prolongation of the QTc interval has been a concern with this drug, but “has not been a problem in our hands,” he said. ▸ Aripiprazole (Abilify). The atypical class of antipsychotics now includes a third-generation agent, aripiprazole. This drug is a dopamine-serotonin system stabilizer that has partial D2 agonist activity and modulates central serotonergic pathways. It improves executive functioning and negative symptoms, and may also affect depression and anxiety.

▸ Clozapine (Clozaril). Among the atypicals, clozapine exhibits the most complex receptor blockade activity, and because of its side effect profile is not considered a first-line antipsychotic. But it is very effective in treatment-resistant patients, Dr. Kranzler said. “You want to be comfortable using it, because it can save these kids' lives,” he said. In his center, 43 of 57 severely ill hospitalized patients were able to be discharged on clozapine. “They are not paragons of mental health but they are able to function in residences,” he said.

NEW YORK — Digital sympathectomy appeared highly effective for pain relief in patients with severe, longstanding Raynaud's phenomenon associated with limited cutaneous systemic sclerosis, Andrew D. Thomas, M.D., said at the annual meeting of the American Society for Surgery of the Hand.

Raynaud's phenomenon in the context of CREST syndrome, the symptoms of which can include calcinosis, esophageal dysmotility, sclerodactyly, and telangiectasia, is initially treated with calcium channel blockers.

Biofeedback, smoking cessation, and avoidance of cold also are central to management, Dr. Thomas said.

But if medical management fails, patients can face intractable fingertip pain and severe digital ulceration requiring amputation.

Studies have demonstrated that digital sympathectomy improves blood supply to the chronically ischemic hand. However, the long-term outcomes are unknown because of the infrequency with which it is performed and the diversity of conditions it is used to treat.

"We have attempted to clarify the effectiveness by analyzing the results from 17 patients, each with a firmly established diagnosis of CREST syndrome and painfully disabling Raynaud's phenomenon," said Dr. Thomas, a surgical resident at St. Luke's-Roosevelt Hospital, New York.

The patients underwent a total of 95 digital sympathectomies. Chronic ulceration was present in 22 digits, and 14 of the ulcers were 1 cm or greater. Bony exposure was present in five.

By way of standard microsurgical techniques, the digital artery was stripped of its sympathetic innervation and fibrotic adventitia for 2.5-3 cm distal to its origin from the common digital artery, he explained.

In 10 digits with major pulp loss, local flap resurfacing was performed to enhance wound healing, he said.

"All but one patient reported pain relief following the operation, and all 22 ulcerations healed after a period of meticulous local wound care," Dr. Thomas said at the meeting.

The time until healing ranged from 39 to 125 days based on the size and depth of the lesion. No amputations were necessary. Patient satisfaction was consistently high, he said.

Five patients developed recurrent ulcers after the initial healing, but these rehealed by secondary intention with meticulous outpatient care.

Follow-up ranged from 1.5 to 8 years.

"Despite the progressive nature of scleroderma, this study indicates that the efficacy of digital sympathectomy can persist for periods as long as 8 years after surgery," he said.

Of 17 patients who underwent the procedure, 16 reported pain relief after the operation. There were no amputations. Courtesy Dr. Andrew D. Thomas

NEW YORK — Digital sympathectomy appeared highly effective for pain relief in patients with severe, longstanding Raynaud's phenomenon associated with limited cutaneous systemic sclerosis, Andrew D. Thomas, M.D., said at the annual meeting of the American Society for Surgery of the Hand.

Raynaud's phenomenon in the context of CREST syndrome, the symptoms of which can include calcinosis, esophageal dysmotility, sclerodactyly, and telangiectasia, is initially treated with calcium channel blockers.

Biofeedback, smoking cessation, and avoidance of cold also are central to management, Dr. Thomas said.

But if medical management fails, patients can face intractable fingertip pain and severe digital ulceration requiring amputation.

Studies have demonstrated that digital sympathectomy improves blood supply to the chronically ischemic hand. However, the long-term outcomes are unknown because of the infrequency with which it is performed and the diversity of conditions it is used to treat.

"We have attempted to clarify the effectiveness by analyzing the results from 17 patients, each with a firmly established diagnosis of CREST syndrome and painfully disabling Raynaud's phenomenon," said Dr. Thomas, a surgical resident at St. Luke's-Roosevelt Hospital, New York.

The patients underwent a total of 95 digital sympathectomies. Chronic ulceration was present in 22 digits, and 14 of the ulcers were 1 cm or greater. Bony exposure was present in five.

By way of standard microsurgical techniques, the digital artery was stripped of its sympathetic innervation and fibrotic adventitia for 2.5-3 cm distal to its origin from the common digital artery, he explained.

In 10 digits with major pulp loss, local flap resurfacing was performed to enhance wound healing, he said.

"All but one patient reported pain relief following the operation, and all 22 ulcerations healed after a period of meticulous local wound care," Dr. Thomas said at the meeting.

The time until healing ranged from 39 to 125 days based on the size and depth of the lesion. No amputations were necessary. Patient satisfaction was consistently high, he said.

Five patients developed recurrent ulcers after the initial healing, but these rehealed by secondary intention with meticulous outpatient care.

Follow-up ranged from 1.5 to 8 years.

"Despite the progressive nature of scleroderma, this study indicates that the efficacy of digital sympathectomy can persist for periods as long as 8 years after surgery," he said.

Of 17 patients who underwent the procedure, 16 reported pain relief after the operation. There were no amputations. Courtesy Dr. Andrew D. Thomas

NEW YORK — Digital sympathectomy appeared highly effective for pain relief in patients with severe, longstanding Raynaud's phenomenon associated with limited cutaneous systemic sclerosis, Andrew D. Thomas, M.D., said at the annual meeting of the American Society for Surgery of the Hand.

Raynaud's phenomenon in the context of CREST syndrome, the symptoms of which can include calcinosis, esophageal dysmotility, sclerodactyly, and telangiectasia, is initially treated with calcium channel blockers.

Biofeedback, smoking cessation, and avoidance of cold also are central to management, Dr. Thomas said.

But if medical management fails, patients can face intractable fingertip pain and severe digital ulceration requiring amputation.

Studies have demonstrated that digital sympathectomy improves blood supply to the chronically ischemic hand. However, the long-term outcomes are unknown because of the infrequency with which it is performed and the diversity of conditions it is used to treat.

"We have attempted to clarify the effectiveness by analyzing the results from 17 patients, each with a firmly established diagnosis of CREST syndrome and painfully disabling Raynaud's phenomenon," said Dr. Thomas, a surgical resident at St. Luke's-Roosevelt Hospital, New York.

The patients underwent a total of 95 digital sympathectomies. Chronic ulceration was present in 22 digits, and 14 of the ulcers were 1 cm or greater. Bony exposure was present in five.

By way of standard microsurgical techniques, the digital artery was stripped of its sympathetic innervation and fibrotic adventitia for 2.5-3 cm distal to its origin from the common digital artery, he explained.

In 10 digits with major pulp loss, local flap resurfacing was performed to enhance wound healing, he said.

"All but one patient reported pain relief following the operation, and all 22 ulcerations healed after a period of meticulous local wound care," Dr. Thomas said at the meeting.

The time until healing ranged from 39 to 125 days based on the size and depth of the lesion. No amputations were necessary. Patient satisfaction was consistently high, he said.

Five patients developed recurrent ulcers after the initial healing, but these rehealed by secondary intention with meticulous outpatient care.

Follow-up ranged from 1.5 to 8 years.

"Despite the progressive nature of scleroderma, this study indicates that the efficacy of digital sympathectomy can persist for periods as long as 8 years after surgery," he said.

Of 17 patients who underwent the procedure, 16 reported pain relief after the operation. There were no amputations. Courtesy Dr. Andrew D. Thomas