Nancy Walsh

EXETER, ENGLAND — The benefits of complementary therapies such as hypnotherapy are likely to be underestimated when they are evaluated using conventional clinical trial designs and outcome measures, according to Lesley M. Roberts, M.D., of the department of primary care, University of Birmingham (England).

Gut-directed hypnotherapy has proved effective in more than a dozen studies in the past 20 years. But a clinical trial in which 81 patients with irritable bowel syndrome (IBS) were randomized to hypnotherapy or usual care by a primary care physician found little difference between the approaches.

Was this a case of “right intervention, wrong outcome?” Dr. Roberts asked at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth.

“My background is in conventional medicine, so we chose conventional tools for the study—symptom scores and [an] IBS quality of life tool,” she said. Such disease-specific tools are allegedly more sensitive than generic tools for evaluating conventional therapies.

Patients in the study had gastroenterologist-confirmed IBS of 6 weeks' duration or longer and had failed at least one conventional treatment. They were evaluated at baseline and at 3, 6, and 12 months.

Both groups improved over the course of the trial. Symptom scores, pain, and diarrhea were significantly superior in the hypnotherapy group at 3 months, but the difference was not maintained over time. There were no between-group differences at any time point for constipation or quality of life.

“However, when we asked patients in the hypnotherapy group about their experiences, 81% reported definite improvement, 55% reported improvement greater than they had anticipated, and 91% would recommend gut-directed hypnotherapy to their friends,” Dr. Roberts said.

“So the question we had to ask was, did our study miss some important benefits? Patients were saying they felt better. The treatment was very helpful for mental well being, and it gave them control—all generic quality of life concerns. Yet we didn't pick up any quality of life benefit using the IBS-specific quality of life tool,” she said.

Perhaps complementary and alternative medicine research should reconsider its emphasis on the use of conventional methodology in clinical studies and should instead use more generic outcome measures such as the subjective assessment questionnaire used in the Manchester protocol, she said. “I think the benefit of hypnotherapy is that patients are better able to cope, not that they necessarily have fewer symptoms. They feel empowered,” Dr. Roberts said.

EXETER, ENGLAND — The benefits of complementary therapies such as hypnotherapy are likely to be underestimated when they are evaluated using conventional clinical trial designs and outcome measures, according to Lesley M. Roberts, M.D., of the department of primary care, University of Birmingham (England).

Gut-directed hypnotherapy has proved effective in more than a dozen studies in the past 20 years. But a clinical trial in which 81 patients with irritable bowel syndrome (IBS) were randomized to hypnotherapy or usual care by a primary care physician found little difference between the approaches.

Was this a case of “right intervention, wrong outcome?” Dr. Roberts asked at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth.

“My background is in conventional medicine, so we chose conventional tools for the study—symptom scores and [an] IBS quality of life tool,” she said. Such disease-specific tools are allegedly more sensitive than generic tools for evaluating conventional therapies.

Patients in the study had gastroenterologist-confirmed IBS of 6 weeks' duration or longer and had failed at least one conventional treatment. They were evaluated at baseline and at 3, 6, and 12 months.

Both groups improved over the course of the trial. Symptom scores, pain, and diarrhea were significantly superior in the hypnotherapy group at 3 months, but the difference was not maintained over time. There were no between-group differences at any time point for constipation or quality of life.

“However, when we asked patients in the hypnotherapy group about their experiences, 81% reported definite improvement, 55% reported improvement greater than they had anticipated, and 91% would recommend gut-directed hypnotherapy to their friends,” Dr. Roberts said.

“So the question we had to ask was, did our study miss some important benefits? Patients were saying they felt better. The treatment was very helpful for mental well being, and it gave them control—all generic quality of life concerns. Yet we didn't pick up any quality of life benefit using the IBS-specific quality of life tool,” she said.

Perhaps complementary and alternative medicine research should reconsider its emphasis on the use of conventional methodology in clinical studies and should instead use more generic outcome measures such as the subjective assessment questionnaire used in the Manchester protocol, she said. “I think the benefit of hypnotherapy is that patients are better able to cope, not that they necessarily have fewer symptoms. They feel empowered,” Dr. Roberts said.

EXETER, ENGLAND — The benefits of complementary therapies such as hypnotherapy are likely to be underestimated when they are evaluated using conventional clinical trial designs and outcome measures, according to Lesley M. Roberts, M.D., of the department of primary care, University of Birmingham (England).

Gut-directed hypnotherapy has proved effective in more than a dozen studies in the past 20 years. But a clinical trial in which 81 patients with irritable bowel syndrome (IBS) were randomized to hypnotherapy or usual care by a primary care physician found little difference between the approaches.

Was this a case of “right intervention, wrong outcome?” Dr. Roberts asked at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth.

“My background is in conventional medicine, so we chose conventional tools for the study—symptom scores and [an] IBS quality of life tool,” she said. Such disease-specific tools are allegedly more sensitive than generic tools for evaluating conventional therapies.

Patients in the study had gastroenterologist-confirmed IBS of 6 weeks' duration or longer and had failed at least one conventional treatment. They were evaluated at baseline and at 3, 6, and 12 months.

Both groups improved over the course of the trial. Symptom scores, pain, and diarrhea were significantly superior in the hypnotherapy group at 3 months, but the difference was not maintained over time. There were no between-group differences at any time point for constipation or quality of life.

“However, when we asked patients in the hypnotherapy group about their experiences, 81% reported definite improvement, 55% reported improvement greater than they had anticipated, and 91% would recommend gut-directed hypnotherapy to their friends,” Dr. Roberts said.

“So the question we had to ask was, did our study miss some important benefits? Patients were saying they felt better. The treatment was very helpful for mental well being, and it gave them control—all generic quality of life concerns. Yet we didn't pick up any quality of life benefit using the IBS-specific quality of life tool,” she said.

Perhaps complementary and alternative medicine research should reconsider its emphasis on the use of conventional methodology in clinical studies and should instead use more generic outcome measures such as the subjective assessment questionnaire used in the Manchester protocol, she said. “I think the benefit of hypnotherapy is that patients are better able to cope, not that they necessarily have fewer symptoms. They feel empowered,” Dr. Roberts said.

EXETER, ENGLAND — A proprietary formulation of St. John's wort was equivalent in efficacy to paroxetine for moderate to severe depression in a prospective, randomized, multicenter study, Stephan Klement, M.D., reported at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth.

A group of 101 German patients whose Hamilton Rating Scale for Depression (HAM-D) scores exceeded 22 points were randomized to receive standardized hypericum extract WS 5570 (Dr. Willmar Schwabe Pharmaceuticals, Karlsruhe, Germany) in an initial daily dose of 900 mg/day, or paroxetine (Paxil) in an initial dose of 20 mg/day.

Patients whose initial response was insufficient could increase the dose of hypericum extract to 1,800 mg/day or of paroxetine to 40 mg/day. Response was considered to be a reduction of 50% or greater on the HAM-D, and remission was defined as a HAM-D end point total score below 10, said Dr. Klement of Schwabe Pharmaceuticals.

In a preplanned interim analysis at 6 weeks, response rates were 60% in the hypericum group and 63% in the paroxetine group, while remission rates were 46.6% with hypericum and 42.9% with paroxetine. The rates in the two groups were comparable, he said in a poster session.

Adverse events when calculated as incidence densities were 0.039/day of exposure for hypericum and 0.056/day of exposure for paroxetine. This represents a 43.6% advantage for hypericum based on ratio.

These findings differ from those seen in another randomized trial that compared a different extract of St. John's wort (LI 160, Lichtwer Pharma, Berlin) with sertraline and placebo. In that study, performed in the United States by the Hypericum Depression Trial Study Group, neither sertraline nor the hypericum extract was significantly different from placebo in a group of 340 patients with major depression (JAMA 2002;287:1807–14).

“The major differences between the two trials can be attributed to different patient populations and the missing assay sensitivity in the [JAMA] trial,” Dr. Klement told FAMILY PRACTICE NEWS.

Patients in the American trials were recruited from tertiary care clinics, and patients who had not responded to adequate trials of two antidepressant trials were included. The depressive episode had already persisted for more than 2 years in roughly one-third of patients, and for between 6 months and 2 years in a further third. This suggests that many of the patients were chronically depressed and some may have been treatment resistant, Dr. Klement said.

In the German study, patients were limited to only one previous adequate antidepressant therapy trial, “probably limiting the number of treatment-resistant patients,” he said. The mean duration of the current depressive episode was significantly shorter in the German trial, suggesting that fewer patients were chronically depressed, and patients had sought care spontaneously in primary or secondary care settings.

The major drawback of the American study was its lack of assay sensitivity, Dr. Klement said. “Sertraline, a proven synthetic antidepressant, served as a positive control to check the sensitivity of the study. Neither St. John's wort extract nor sertraline differed significantly from placebo in the primary target criteria, which were reduction of the Hamilton depression total score and the number of patients showing complete remission.”

The trial therefore did not have the assay sensitivity to document an antidepressant drug effect and thus does not appear to be useful for estimating the therapeutic potential of either St. John's wort or sertraline, he said, adding that in the German study, “no placebo group was included as it would have been unethical to give placebo to patients suffering from severe depression.”

Expert Commentary

FAMILY PRACTICE NEWS asked David Spiegel, M.D., to comment on the new hypericum trial.

Dr. Spiegel, the Jack, Lulu, and Sam Willson Professor in the School of Medicine and associate chair of psychiatry and behavioral sciences, Stanford (Calif.) University, had this to say:

“This is an interesting study, well conducted but with the obvious drawbacks that it has no placebo control group. Also, it is always harder to prove statistically the absence of a difference (between hypericum and paroxetine) than the presence of a difference.

“The author is right that the JAMA study suffered because placebo patients actually did slightly better than those randomized to either hypericum or sertraline. Unfortunately, they used rather low doses of sertraline (50 or 100 mg) when one can prescribe up to 200 mg. Thus, neither treated group did especially well. They might have been treatment resistant, as the author suggests.

“This new study does provide suggestive, but not definitive, evidence that hypericum works as well for mild to moderate depression as paroxetine, but it does not rule out the possibility that this group of patients had transient depressive symptoms that are really responding to a placebo effect or the passage of time.”

EXETER, ENGLAND — A proprietary formulation of St. John's wort was equivalent in efficacy to paroxetine for moderate to severe depression in a prospective, randomized, multicenter study, Stephan Klement, M.D., reported at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth.

A group of 101 German patients whose Hamilton Rating Scale for Depression (HAM-D) scores exceeded 22 points were randomized to receive standardized hypericum extract WS 5570 (Dr. Willmar Schwabe Pharmaceuticals, Karlsruhe, Germany) in an initial daily dose of 900 mg/day, or paroxetine (Paxil) in an initial dose of 20 mg/day.

Patients whose initial response was insufficient could increase the dose of hypericum extract to 1,800 mg/day or of paroxetine to 40 mg/day. Response was considered to be a reduction of 50% or greater on the HAM-D, and remission was defined as a HAM-D end point total score below 10, said Dr. Klement of Schwabe Pharmaceuticals.

In a preplanned interim analysis at 6 weeks, response rates were 60% in the hypericum group and 63% in the paroxetine group, while remission rates were 46.6% with hypericum and 42.9% with paroxetine. The rates in the two groups were comparable, he said in a poster session.

Adverse events when calculated as incidence densities were 0.039/day of exposure for hypericum and 0.056/day of exposure for paroxetine. This represents a 43.6% advantage for hypericum based on ratio.

These findings differ from those seen in another randomized trial that compared a different extract of St. John's wort (LI 160, Lichtwer Pharma, Berlin) with sertraline and placebo. In that study, performed in the United States by the Hypericum Depression Trial Study Group, neither sertraline nor the hypericum extract was significantly different from placebo in a group of 340 patients with major depression (JAMA 2002;287:1807–14).

“The major differences between the two trials can be attributed to different patient populations and the missing assay sensitivity in the [JAMA] trial,” Dr. Klement told FAMILY PRACTICE NEWS.

Patients in the American trials were recruited from tertiary care clinics, and patients who had not responded to adequate trials of two antidepressant trials were included. The depressive episode had already persisted for more than 2 years in roughly one-third of patients, and for between 6 months and 2 years in a further third. This suggests that many of the patients were chronically depressed and some may have been treatment resistant, Dr. Klement said.

In the German study, patients were limited to only one previous adequate antidepressant therapy trial, “probably limiting the number of treatment-resistant patients,” he said. The mean duration of the current depressive episode was significantly shorter in the German trial, suggesting that fewer patients were chronically depressed, and patients had sought care spontaneously in primary or secondary care settings.

The major drawback of the American study was its lack of assay sensitivity, Dr. Klement said. “Sertraline, a proven synthetic antidepressant, served as a positive control to check the sensitivity of the study. Neither St. John's wort extract nor sertraline differed significantly from placebo in the primary target criteria, which were reduction of the Hamilton depression total score and the number of patients showing complete remission.”

The trial therefore did not have the assay sensitivity to document an antidepressant drug effect and thus does not appear to be useful for estimating the therapeutic potential of either St. John's wort or sertraline, he said, adding that in the German study, “no placebo group was included as it would have been unethical to give placebo to patients suffering from severe depression.”

Expert Commentary

FAMILY PRACTICE NEWS asked David Spiegel, M.D., to comment on the new hypericum trial.

Dr. Spiegel, the Jack, Lulu, and Sam Willson Professor in the School of Medicine and associate chair of psychiatry and behavioral sciences, Stanford (Calif.) University, had this to say:

“This is an interesting study, well conducted but with the obvious drawbacks that it has no placebo control group. Also, it is always harder to prove statistically the absence of a difference (between hypericum and paroxetine) than the presence of a difference.

“The author is right that the JAMA study suffered because placebo patients actually did slightly better than those randomized to either hypericum or sertraline. Unfortunately, they used rather low doses of sertraline (50 or 100 mg) when one can prescribe up to 200 mg. Thus, neither treated group did especially well. They might have been treatment resistant, as the author suggests.

“This new study does provide suggestive, but not definitive, evidence that hypericum works as well for mild to moderate depression as paroxetine, but it does not rule out the possibility that this group of patients had transient depressive symptoms that are really responding to a placebo effect or the passage of time.”

EXETER, ENGLAND — A proprietary formulation of St. John's wort was equivalent in efficacy to paroxetine for moderate to severe depression in a prospective, randomized, multicenter study, Stephan Klement, M.D., reported at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth.

A group of 101 German patients whose Hamilton Rating Scale for Depression (HAM-D) scores exceeded 22 points were randomized to receive standardized hypericum extract WS 5570 (Dr. Willmar Schwabe Pharmaceuticals, Karlsruhe, Germany) in an initial daily dose of 900 mg/day, or paroxetine (Paxil) in an initial dose of 20 mg/day.

Patients whose initial response was insufficient could increase the dose of hypericum extract to 1,800 mg/day or of paroxetine to 40 mg/day. Response was considered to be a reduction of 50% or greater on the HAM-D, and remission was defined as a HAM-D end point total score below 10, said Dr. Klement of Schwabe Pharmaceuticals.

In a preplanned interim analysis at 6 weeks, response rates were 60% in the hypericum group and 63% in the paroxetine group, while remission rates were 46.6% with hypericum and 42.9% with paroxetine. The rates in the two groups were comparable, he said in a poster session.

Adverse events when calculated as incidence densities were 0.039/day of exposure for hypericum and 0.056/day of exposure for paroxetine. This represents a 43.6% advantage for hypericum based on ratio.

These findings differ from those seen in another randomized trial that compared a different extract of St. John's wort (LI 160, Lichtwer Pharma, Berlin) with sertraline and placebo. In that study, performed in the United States by the Hypericum Depression Trial Study Group, neither sertraline nor the hypericum extract was significantly different from placebo in a group of 340 patients with major depression (JAMA 2002;287:1807–14).

“The major differences between the two trials can be attributed to different patient populations and the missing assay sensitivity in the [JAMA] trial,” Dr. Klement told FAMILY PRACTICE NEWS.

Patients in the American trials were recruited from tertiary care clinics, and patients who had not responded to adequate trials of two antidepressant trials were included. The depressive episode had already persisted for more than 2 years in roughly one-third of patients, and for between 6 months and 2 years in a further third. This suggests that many of the patients were chronically depressed and some may have been treatment resistant, Dr. Klement said.

In the German study, patients were limited to only one previous adequate antidepressant therapy trial, “probably limiting the number of treatment-resistant patients,” he said. The mean duration of the current depressive episode was significantly shorter in the German trial, suggesting that fewer patients were chronically depressed, and patients had sought care spontaneously in primary or secondary care settings.

The major drawback of the American study was its lack of assay sensitivity, Dr. Klement said. “Sertraline, a proven synthetic antidepressant, served as a positive control to check the sensitivity of the study. Neither St. John's wort extract nor sertraline differed significantly from placebo in the primary target criteria, which were reduction of the Hamilton depression total score and the number of patients showing complete remission.”

The trial therefore did not have the assay sensitivity to document an antidepressant drug effect and thus does not appear to be useful for estimating the therapeutic potential of either St. John's wort or sertraline, he said, adding that in the German study, “no placebo group was included as it would have been unethical to give placebo to patients suffering from severe depression.”

Expert Commentary

FAMILY PRACTICE NEWS asked David Spiegel, M.D., to comment on the new hypericum trial.

Dr. Spiegel, the Jack, Lulu, and Sam Willson Professor in the School of Medicine and associate chair of psychiatry and behavioral sciences, Stanford (Calif.) University, had this to say:

“This is an interesting study, well conducted but with the obvious drawbacks that it has no placebo control group. Also, it is always harder to prove statistically the absence of a difference (between hypericum and paroxetine) than the presence of a difference.

“The author is right that the JAMA study suffered because placebo patients actually did slightly better than those randomized to either hypericum or sertraline. Unfortunately, they used rather low doses of sertraline (50 or 100 mg) when one can prescribe up to 200 mg. Thus, neither treated group did especially well. They might have been treatment resistant, as the author suggests.

“This new study does provide suggestive, but not definitive, evidence that hypericum works as well for mild to moderate depression as paroxetine, but it does not rule out the possibility that this group of patients had transient depressive symptoms that are really responding to a placebo effect or the passage of time.”

BUDAPEST, HUNGARY — A 56-year-old man with a 7-year history of multiple small cutaneous tumors histologically identified as basal cell carcinomas presented with new skin-colored tumors on his forehead and back, K. Gaspar, M.D., said at an international symposium sponsored by the European Academy of Dermatology and Venereology.

Family history revealed that his brother, who was 2 years older, had undergone a hemicolectomy for adenocarcinoma several years earlier. The brother was called in for examination and was found to have a number of tiny, crust-covered tumors on his back and face that resembled sebaceous gland tumors.

Both of his sisters had had surgery for gynecologic cancers; one had died 2 years earlier of ovarian cancer. His mother also had died of an undetermined gynecologic cancer.

After excision, the patient's new tumors were found to be sebaceous adenomas, a result that raised the possibility that this patient and his family members had Muir-Torre syndrome, said Dr. Gaspar of the department of dermatology at Medical and Health Science Center, University of Debrecen (Hungary).

Muir-Torre syndrome is a rare genodermatosis that exhibits an autosomal dominant inheritance pattern. The syndrome, which is characterized by sebaceous lesions and visceral malignancies, is considered a phenotypical variant of hereditary nonpolyposis colorectal cancer. Both conditions are caused by inherited DNA mismatch repair defects, most commonly on the MSH2 and MLH1 genes.

Among the skin lesions characteristic of Muir-Torre syndrome are sebaceous adenomas, epitheliomas, and carcinomas. Adenomas appear as skin-colored or yellowish papules or nodules, sometimes with a central depression. Histologic evaluation in this case showed orthokeratotic, dilated follicles, numerous nucleoli, and a lack of sebum.

Sebaceous carcinoma appears as a poorly demarcated, asymmetrical, solid tumor with an irregular border. Histology showed that this lesion had deep penetrating tumor cell nests that obliterated the normal structure of the sebaceous gland.

This case illustrates the importance of a careful search for possibly asymptomatic abdominal tumors in the setting of multiple sebaceous tumors. Patients whose cutaneous tumor cells are genetically unstable (characterized by mutations of short DNA sequences known as microsatellites) also are at heightened risk for developing subsequent abdominal cancers. “Therefore, microsatellite screening can play a significant role in cancer prevention,” Dr. Gaspar said.

In more than half of cases the visceral malignancy is colorectal carcinoma. Genitourinary, hematologic, and head and neck sites also have been reported.

Vigilance is necessary, and repeated surgeries for both skin and visceral tumors can be expected. Family members also must be evaluated and followed. But with careful follow-up, the prognosis of Muir-Torre syndrome is good, with 10-year survival exceeding 50%, Dr. Gaspar said at the symposium, also sponsored by the Hungarian Dermatological Society.

At the patient's most recent follow-up examination, his tumor markers were normal, but radiographic evaluation revealed metastases to the paraaortic lymph nodes. He was started on a chemotherapeutic regimen that included irinotecan.

The patient's new tumors were found to be sebaceous adenomas, raising the possible diagnosis of Muir-Torre syndrome. Courtesy Dr. Istvan Juhasz

BUDAPEST, HUNGARY — A 56-year-old man with a 7-year history of multiple small cutaneous tumors histologically identified as basal cell carcinomas presented with new skin-colored tumors on his forehead and back, K. Gaspar, M.D., said at an international symposium sponsored by the European Academy of Dermatology and Venereology.

Family history revealed that his brother, who was 2 years older, had undergone a hemicolectomy for adenocarcinoma several years earlier. The brother was called in for examination and was found to have a number of tiny, crust-covered tumors on his back and face that resembled sebaceous gland tumors.

Both of his sisters had had surgery for gynecologic cancers; one had died 2 years earlier of ovarian cancer. His mother also had died of an undetermined gynecologic cancer.

After excision, the patient's new tumors were found to be sebaceous adenomas, a result that raised the possibility that this patient and his family members had Muir-Torre syndrome, said Dr. Gaspar of the department of dermatology at Medical and Health Science Center, University of Debrecen (Hungary).

Muir-Torre syndrome is a rare genodermatosis that exhibits an autosomal dominant inheritance pattern. The syndrome, which is characterized by sebaceous lesions and visceral malignancies, is considered a phenotypical variant of hereditary nonpolyposis colorectal cancer. Both conditions are caused by inherited DNA mismatch repair defects, most commonly on the MSH2 and MLH1 genes.

Among the skin lesions characteristic of Muir-Torre syndrome are sebaceous adenomas, epitheliomas, and carcinomas. Adenomas appear as skin-colored or yellowish papules or nodules, sometimes with a central depression. Histologic evaluation in this case showed orthokeratotic, dilated follicles, numerous nucleoli, and a lack of sebum.

Sebaceous carcinoma appears as a poorly demarcated, asymmetrical, solid tumor with an irregular border. Histology showed that this lesion had deep penetrating tumor cell nests that obliterated the normal structure of the sebaceous gland.

This case illustrates the importance of a careful search for possibly asymptomatic abdominal tumors in the setting of multiple sebaceous tumors. Patients whose cutaneous tumor cells are genetically unstable (characterized by mutations of short DNA sequences known as microsatellites) also are at heightened risk for developing subsequent abdominal cancers. “Therefore, microsatellite screening can play a significant role in cancer prevention,” Dr. Gaspar said.

In more than half of cases the visceral malignancy is colorectal carcinoma. Genitourinary, hematologic, and head and neck sites also have been reported.

Vigilance is necessary, and repeated surgeries for both skin and visceral tumors can be expected. Family members also must be evaluated and followed. But with careful follow-up, the prognosis of Muir-Torre syndrome is good, with 10-year survival exceeding 50%, Dr. Gaspar said at the symposium, also sponsored by the Hungarian Dermatological Society.

At the patient's most recent follow-up examination, his tumor markers were normal, but radiographic evaluation revealed metastases to the paraaortic lymph nodes. He was started on a chemotherapeutic regimen that included irinotecan.

The patient's new tumors were found to be sebaceous adenomas, raising the possible diagnosis of Muir-Torre syndrome. Courtesy Dr. Istvan Juhasz

BUDAPEST, HUNGARY — A 56-year-old man with a 7-year history of multiple small cutaneous tumors histologically identified as basal cell carcinomas presented with new skin-colored tumors on his forehead and back, K. Gaspar, M.D., said at an international symposium sponsored by the European Academy of Dermatology and Venereology.

Family history revealed that his brother, who was 2 years older, had undergone a hemicolectomy for adenocarcinoma several years earlier. The brother was called in for examination and was found to have a number of tiny, crust-covered tumors on his back and face that resembled sebaceous gland tumors.

Both of his sisters had had surgery for gynecologic cancers; one had died 2 years earlier of ovarian cancer. His mother also had died of an undetermined gynecologic cancer.

After excision, the patient's new tumors were found to be sebaceous adenomas, a result that raised the possibility that this patient and his family members had Muir-Torre syndrome, said Dr. Gaspar of the department of dermatology at Medical and Health Science Center, University of Debrecen (Hungary).

Muir-Torre syndrome is a rare genodermatosis that exhibits an autosomal dominant inheritance pattern. The syndrome, which is characterized by sebaceous lesions and visceral malignancies, is considered a phenotypical variant of hereditary nonpolyposis colorectal cancer. Both conditions are caused by inherited DNA mismatch repair defects, most commonly on the MSH2 and MLH1 genes.

Among the skin lesions characteristic of Muir-Torre syndrome are sebaceous adenomas, epitheliomas, and carcinomas. Adenomas appear as skin-colored or yellowish papules or nodules, sometimes with a central depression. Histologic evaluation in this case showed orthokeratotic, dilated follicles, numerous nucleoli, and a lack of sebum.

Sebaceous carcinoma appears as a poorly demarcated, asymmetrical, solid tumor with an irregular border. Histology showed that this lesion had deep penetrating tumor cell nests that obliterated the normal structure of the sebaceous gland.

This case illustrates the importance of a careful search for possibly asymptomatic abdominal tumors in the setting of multiple sebaceous tumors. Patients whose cutaneous tumor cells are genetically unstable (characterized by mutations of short DNA sequences known as microsatellites) also are at heightened risk for developing subsequent abdominal cancers. “Therefore, microsatellite screening can play a significant role in cancer prevention,” Dr. Gaspar said.

In more than half of cases the visceral malignancy is colorectal carcinoma. Genitourinary, hematologic, and head and neck sites also have been reported.

Vigilance is necessary, and repeated surgeries for both skin and visceral tumors can be expected. Family members also must be evaluated and followed. But with careful follow-up, the prognosis of Muir-Torre syndrome is good, with 10-year survival exceeding 50%, Dr. Gaspar said at the symposium, also sponsored by the Hungarian Dermatological Society.

At the patient's most recent follow-up examination, his tumor markers were normal, but radiographic evaluation revealed metastases to the paraaortic lymph nodes. He was started on a chemotherapeutic regimen that included irinotecan.

The patient's new tumors were found to be sebaceous adenomas, raising the possible diagnosis of Muir-Torre syndrome. Courtesy Dr. Istvan Juhasz

BUDAPEST, HUNGARY — The death of a patient with lupus from disseminated cryptococcosis illustrates the difficulty in finding the balance between therapeutic immunosuppression and treatment of a resulting infectious disease, Dr. Gabor Szabad said at an international symposium sponsored by the European Academy of Dermatology and Venereology.

The patient was a 36-year-old woman who had been diagnosed with systemic lupus erythematosus in 1989 when she began experiencing muscle weakness, fever, and arthropathy and also developed the characteristic facial butterfly rash. She was antinuclear antibody positive, and double-stranded DNA antibodies were present.

During the subsequent decade, she developed lupus nephritis, cerebral lupus, lower extremity ulceration, and Raynaud's phenomenon-associated gangrene that necessitated the amputation of two fingers, Dr. Szabad said.

Throughout these years, she was receiving continuous immunosuppressive therapy with prednisolone, cyclophosphamide, and azathioprine in varying doses.

In 2002, she presented with reddish-brown infiltrates across the gluteal area and yellowish nodules and papules on the left hand. She had an elevated sedimentation rate, marked lymphopenia, and mild renal insufficiency; a thoracic CT scan showed evidence of pneumonia, said Dr.Szabad of the department of dermatology and allergology, University of Szeged (Hungary).

Histopathologic investigation of the skin lesions revealed the presence of yeastlike organisms in the dermis. Buff-colored mucoid colonies characteristic of the genus Cryptococcus grew on culture and were positive on a cryptococcal antigen latex agglutination test.

Subsequent efforts to manipulate antimycotic, antibiotic, and immunosuppressive therapies resulted in a seesaw course. She died of acute respiratory distress syndrome on day 51.

Autopsy findings included mesangial glomerulonephritis, pulmonary cryptococcosis, and cryptococcal epidermolysis, Dr. Szabad said.

Most cases of disseminated cryptococcosis occur in patients who are immunocompromised because they have AIDS or received an organ transplant.

“Lupus patients also are susceptible to opportunistic infections such as this because of their prolonged immunosuppressive therapy, but the intrinsic immunologic abnormalities of systemic lupus erythematosus can also contribute to the susceptibility,” he said.

Most cases of serious cryptococcal infection in patients with lupus manifest as meningeal disease. The first reported case of cutaneous cryptococcosis in a patient with underlying lupus involved a 24-year-old woman who presented with cellulitis of the thigh and gluteus and who went on to develop nephrotic syndrome, arterial hypertension, and ultimately fatal acute renal insufficiency (Mycoses 2001;44:419–21).

BUDAPEST, HUNGARY — The death of a patient with lupus from disseminated cryptococcosis illustrates the difficulty in finding the balance between therapeutic immunosuppression and treatment of a resulting infectious disease, Dr. Gabor Szabad said at an international symposium sponsored by the European Academy of Dermatology and Venereology.

The patient was a 36-year-old woman who had been diagnosed with systemic lupus erythematosus in 1989 when she began experiencing muscle weakness, fever, and arthropathy and also developed the characteristic facial butterfly rash. She was antinuclear antibody positive, and double-stranded DNA antibodies were present.

During the subsequent decade, she developed lupus nephritis, cerebral lupus, lower extremity ulceration, and Raynaud's phenomenon-associated gangrene that necessitated the amputation of two fingers, Dr. Szabad said.

Throughout these years, she was receiving continuous immunosuppressive therapy with prednisolone, cyclophosphamide, and azathioprine in varying doses.

In 2002, she presented with reddish-brown infiltrates across the gluteal area and yellowish nodules and papules on the left hand. She had an elevated sedimentation rate, marked lymphopenia, and mild renal insufficiency; a thoracic CT scan showed evidence of pneumonia, said Dr.Szabad of the department of dermatology and allergology, University of Szeged (Hungary).

Histopathologic investigation of the skin lesions revealed the presence of yeastlike organisms in the dermis. Buff-colored mucoid colonies characteristic of the genus Cryptococcus grew on culture and were positive on a cryptococcal antigen latex agglutination test.

Subsequent efforts to manipulate antimycotic, antibiotic, and immunosuppressive therapies resulted in a seesaw course. She died of acute respiratory distress syndrome on day 51.

Autopsy findings included mesangial glomerulonephritis, pulmonary cryptococcosis, and cryptococcal epidermolysis, Dr. Szabad said.

Most cases of disseminated cryptococcosis occur in patients who are immunocompromised because they have AIDS or received an organ transplant.

“Lupus patients also are susceptible to opportunistic infections such as this because of their prolonged immunosuppressive therapy, but the intrinsic immunologic abnormalities of systemic lupus erythematosus can also contribute to the susceptibility,” he said.

Most cases of serious cryptococcal infection in patients with lupus manifest as meningeal disease. The first reported case of cutaneous cryptococcosis in a patient with underlying lupus involved a 24-year-old woman who presented with cellulitis of the thigh and gluteus and who went on to develop nephrotic syndrome, arterial hypertension, and ultimately fatal acute renal insufficiency (Mycoses 2001;44:419–21).

BUDAPEST, HUNGARY — The death of a patient with lupus from disseminated cryptococcosis illustrates the difficulty in finding the balance between therapeutic immunosuppression and treatment of a resulting infectious disease, Dr. Gabor Szabad said at an international symposium sponsored by the European Academy of Dermatology and Venereology.

The patient was a 36-year-old woman who had been diagnosed with systemic lupus erythematosus in 1989 when she began experiencing muscle weakness, fever, and arthropathy and also developed the characteristic facial butterfly rash. She was antinuclear antibody positive, and double-stranded DNA antibodies were present.

During the subsequent decade, she developed lupus nephritis, cerebral lupus, lower extremity ulceration, and Raynaud's phenomenon-associated gangrene that necessitated the amputation of two fingers, Dr. Szabad said.

Throughout these years, she was receiving continuous immunosuppressive therapy with prednisolone, cyclophosphamide, and azathioprine in varying doses.

In 2002, she presented with reddish-brown infiltrates across the gluteal area and yellowish nodules and papules on the left hand. She had an elevated sedimentation rate, marked lymphopenia, and mild renal insufficiency; a thoracic CT scan showed evidence of pneumonia, said Dr.Szabad of the department of dermatology and allergology, University of Szeged (Hungary).

Histopathologic investigation of the skin lesions revealed the presence of yeastlike organisms in the dermis. Buff-colored mucoid colonies characteristic of the genus Cryptococcus grew on culture and were positive on a cryptococcal antigen latex agglutination test.

Subsequent efforts to manipulate antimycotic, antibiotic, and immunosuppressive therapies resulted in a seesaw course. She died of acute respiratory distress syndrome on day 51.

Autopsy findings included mesangial glomerulonephritis, pulmonary cryptococcosis, and cryptococcal epidermolysis, Dr. Szabad said.

Most cases of disseminated cryptococcosis occur in patients who are immunocompromised because they have AIDS or received an organ transplant.

“Lupus patients also are susceptible to opportunistic infections such as this because of their prolonged immunosuppressive therapy, but the intrinsic immunologic abnormalities of systemic lupus erythematosus can also contribute to the susceptibility,” he said.

Most cases of serious cryptococcal infection in patients with lupus manifest as meningeal disease. The first reported case of cutaneous cryptococcosis in a patient with underlying lupus involved a 24-year-old woman who presented with cellulitis of the thigh and gluteus and who went on to develop nephrotic syndrome, arterial hypertension, and ultimately fatal acute renal insufficiency (Mycoses 2001;44:419–21).

EXETER, ENGLAND — Data emerging from a large German research initiative sponsored by that country's insurance companies continue to support the use of acupuncture in the treatment of chronic pain conditions.

Two reports from the Acupuncture in Routine Care (ARC) study, presented at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth, demonstrated statistically significant and clinically relevant benefits for acupuncture when used in addition to routine care for headache and neck pain.

A total of 15,056 patients with migraine or tension-type headache were enrolled in the ARC headache study and randomly allocated to receive up to 15 acupuncture treatments during a 3-month period along with conventional treatment with analgesics, or to a control group receiving conventional treatment but no acupuncture. Patients who did not agree to randomization received acupuncture and were monitored as a third group, said Susanne Jena, M.D., of the Institute for Social Medicine, Charité Medical Center, Berlin.

Three-quarters of the patients were female, and their mean age was 44 years. Of the 3,182 who agreed to randomization, 1,613 were in the acupuncture group and 1,569 were in the control group.

After 3 months of treatment, the frequency of headache days per month decreased from 8.4 days to 4.7 days in the two acupuncture groups, a significantly greater reduction than in the control group (8.1 days per month before treatment and 7.5 days per month post treatment).

The data also were analyzed according to headache type. Patients with migraine had an average of 7 days per month with headache before treatment and 4 days per month with headache after treatment including acupuncture; those with tension type headache decreased from an average of 10 days per month with headache to 5 days per month, she said.

The improvements persisted for the subsequent 3 months, she said.

Among the control group, 70% of patients required concomitant treatment with analgesics, compared with 50% of patients in the acupuncture groups.

The second report, from the ARC neck pain study, found similar results among 13,846 patients with chronic neck pain. In this cohort, 68% of whom were women with a mean age of 53 years, 1,753 were randomized to receive acupuncture, 1,698 served as controls, and 10,395 who had declined randomization also received acupuncture.

After 3 months of treatment, improvements on the neck pain disability score were more pronounced in the acupuncture groups than in the control group, said Claudia Becker-Witt, M.D., also with Charité. Scores fell from 56.4 to 39.6 in the acupuncture groups and from 54.5 to 51.2 in the control group, a statistically significant difference.

In both studies, the acupuncture groups also experienced significantly greater improvements in quality of life.

About 8% -9% of patients in both studies experienced side effects from acupuncture; they were not life threatening.

Analyses of cost-effectiveness and overall health benefits are being done, Dr. Becker-Witt said.

EXETER, ENGLAND — Data emerging from a large German research initiative sponsored by that country's insurance companies continue to support the use of acupuncture in the treatment of chronic pain conditions.

Two reports from the Acupuncture in Routine Care (ARC) study, presented at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth, demonstrated statistically significant and clinically relevant benefits for acupuncture when used in addition to routine care for headache and neck pain.

A total of 15,056 patients with migraine or tension-type headache were enrolled in the ARC headache study and randomly allocated to receive up to 15 acupuncture treatments during a 3-month period along with conventional treatment with analgesics, or to a control group receiving conventional treatment but no acupuncture. Patients who did not agree to randomization received acupuncture and were monitored as a third group, said Susanne Jena, M.D., of the Institute for Social Medicine, Charité Medical Center, Berlin.

Three-quarters of the patients were female, and their mean age was 44 years. Of the 3,182 who agreed to randomization, 1,613 were in the acupuncture group and 1,569 were in the control group.

After 3 months of treatment, the frequency of headache days per month decreased from 8.4 days to 4.7 days in the two acupuncture groups, a significantly greater reduction than in the control group (8.1 days per month before treatment and 7.5 days per month post treatment).

The data also were analyzed according to headache type. Patients with migraine had an average of 7 days per month with headache before treatment and 4 days per month with headache after treatment including acupuncture; those with tension type headache decreased from an average of 10 days per month with headache to 5 days per month, she said.

The improvements persisted for the subsequent 3 months, she said.

Among the control group, 70% of patients required concomitant treatment with analgesics, compared with 50% of patients in the acupuncture groups.

The second report, from the ARC neck pain study, found similar results among 13,846 patients with chronic neck pain. In this cohort, 68% of whom were women with a mean age of 53 years, 1,753 were randomized to receive acupuncture, 1,698 served as controls, and 10,395 who had declined randomization also received acupuncture.

After 3 months of treatment, improvements on the neck pain disability score were more pronounced in the acupuncture groups than in the control group, said Claudia Becker-Witt, M.D., also with Charité. Scores fell from 56.4 to 39.6 in the acupuncture groups and from 54.5 to 51.2 in the control group, a statistically significant difference.

In both studies, the acupuncture groups also experienced significantly greater improvements in quality of life.

About 8% -9% of patients in both studies experienced side effects from acupuncture; they were not life threatening.

Analyses of cost-effectiveness and overall health benefits are being done, Dr. Becker-Witt said.

EXETER, ENGLAND — Data emerging from a large German research initiative sponsored by that country's insurance companies continue to support the use of acupuncture in the treatment of chronic pain conditions.

Two reports from the Acupuncture in Routine Care (ARC) study, presented at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth, demonstrated statistically significant and clinically relevant benefits for acupuncture when used in addition to routine care for headache and neck pain.

A total of 15,056 patients with migraine or tension-type headache were enrolled in the ARC headache study and randomly allocated to receive up to 15 acupuncture treatments during a 3-month period along with conventional treatment with analgesics, or to a control group receiving conventional treatment but no acupuncture. Patients who did not agree to randomization received acupuncture and were monitored as a third group, said Susanne Jena, M.D., of the Institute for Social Medicine, Charité Medical Center, Berlin.

Three-quarters of the patients were female, and their mean age was 44 years. Of the 3,182 who agreed to randomization, 1,613 were in the acupuncture group and 1,569 were in the control group.

After 3 months of treatment, the frequency of headache days per month decreased from 8.4 days to 4.7 days in the two acupuncture groups, a significantly greater reduction than in the control group (8.1 days per month before treatment and 7.5 days per month post treatment).

The data also were analyzed according to headache type. Patients with migraine had an average of 7 days per month with headache before treatment and 4 days per month with headache after treatment including acupuncture; those with tension type headache decreased from an average of 10 days per month with headache to 5 days per month, she said.

The improvements persisted for the subsequent 3 months, she said.

Among the control group, 70% of patients required concomitant treatment with analgesics, compared with 50% of patients in the acupuncture groups.

The second report, from the ARC neck pain study, found similar results among 13,846 patients with chronic neck pain. In this cohort, 68% of whom were women with a mean age of 53 years, 1,753 were randomized to receive acupuncture, 1,698 served as controls, and 10,395 who had declined randomization also received acupuncture.

After 3 months of treatment, improvements on the neck pain disability score were more pronounced in the acupuncture groups than in the control group, said Claudia Becker-Witt, M.D., also with Charité. Scores fell from 56.4 to 39.6 in the acupuncture groups and from 54.5 to 51.2 in the control group, a statistically significant difference.

In both studies, the acupuncture groups also experienced significantly greater improvements in quality of life.

About 8% -9% of patients in both studies experienced side effects from acupuncture; they were not life threatening.

Analyses of cost-effectiveness and overall health benefits are being done, Dr. Becker-Witt said.

SAN ANTONIO — The clinical safety and efficacy of etanercept persist for more than 2 years in patients with active ankylosing spondylitis, according to the results of an open-label extension study.

Among 26 patients who entered the open, observational phase following a 12-week blinded study, 21 have continued with etanercept, 25 mg twice weekly, for an additional 102 weeks, Xenofon Baraliakos, M.D., said at the annual meeting of the American College of Rheumatology.

Response was evaluated according to a core set of end points proposed by the Assessments in Ankylosing Spondylitis (ASAS) working group. These included the Bath AS Disease Activity Index (BASDAI) and the ASAS 40, which represents a 40% improvement in several disease domains such as pain, function, and inflammation.

The primary end point was an improvement of 50% or more on the BASDAI, a 10-point visual analog scale that assesses fatigue, spinal pain, peripheral arthritis, enthesitis, and morning stiffness.

At 102 weeks, an intent-to-treat analysis of all 26 patients indicated that 54% maintained both a BASDAI 50% response and an ASAS 40. At week 54, the corresponding percentages were 58% and 62%, said Dr. Baraliakos, who is of the department of rheumatology, Benjamin Franklin Hospital, Free University Berlin.

An analysis that included only the 21 study completers also found that disease activity improved significantly, with a mean BASDAI score of 2.7 at week 102. The baseline BASDAI score in this group of patients had been 6.3, on a 0–10 scale, with 10 being the most severe, Dr. Baraliakos said in a poster session.

The mean C-reactive protein level at week 102 was 5 mg/dL, and the mean erythrocyte sedimentation rate was 9 mg/dL, which represented significant improvements over baseline levels, which had been 15.3 and 22.8, respectively. Similar improvements also were seen on the Bath AS functional and mobility indexes.

This study differed from previous investigations of etanercept in AS in that no concomitant corticosteroids or disease-modifying antirheumatic drugs (DMARDs) were permitted. In an earlier study, 40 patients were treated with the tumor necrosis factor-α blocking agent but were allowed to continue other medications (N. Engl. J. Med. 2002;346:1349–56).

In an interim analysis, the authors of this latest study noted that it was important to evaluate etanercept alone (Arthritis Rheum. 2003;48:1667–75).

SAN ANTONIO — The clinical safety and efficacy of etanercept persist for more than 2 years in patients with active ankylosing spondylitis, according to the results of an open-label extension study.

Among 26 patients who entered the open, observational phase following a 12-week blinded study, 21 have continued with etanercept, 25 mg twice weekly, for an additional 102 weeks, Xenofon Baraliakos, M.D., said at the annual meeting of the American College of Rheumatology.

Response was evaluated according to a core set of end points proposed by the Assessments in Ankylosing Spondylitis (ASAS) working group. These included the Bath AS Disease Activity Index (BASDAI) and the ASAS 40, which represents a 40% improvement in several disease domains such as pain, function, and inflammation.

The primary end point was an improvement of 50% or more on the BASDAI, a 10-point visual analog scale that assesses fatigue, spinal pain, peripheral arthritis, enthesitis, and morning stiffness.

At 102 weeks, an intent-to-treat analysis of all 26 patients indicated that 54% maintained both a BASDAI 50% response and an ASAS 40. At week 54, the corresponding percentages were 58% and 62%, said Dr. Baraliakos, who is of the department of rheumatology, Benjamin Franklin Hospital, Free University Berlin.

An analysis that included only the 21 study completers also found that disease activity improved significantly, with a mean BASDAI score of 2.7 at week 102. The baseline BASDAI score in this group of patients had been 6.3, on a 0–10 scale, with 10 being the most severe, Dr. Baraliakos said in a poster session.

The mean C-reactive protein level at week 102 was 5 mg/dL, and the mean erythrocyte sedimentation rate was 9 mg/dL, which represented significant improvements over baseline levels, which had been 15.3 and 22.8, respectively. Similar improvements also were seen on the Bath AS functional and mobility indexes.

This study differed from previous investigations of etanercept in AS in that no concomitant corticosteroids or disease-modifying antirheumatic drugs (DMARDs) were permitted. In an earlier study, 40 patients were treated with the tumor necrosis factor-α blocking agent but were allowed to continue other medications (N. Engl. J. Med. 2002;346:1349–56).

In an interim analysis, the authors of this latest study noted that it was important to evaluate etanercept alone (Arthritis Rheum. 2003;48:1667–75).

SAN ANTONIO — The clinical safety and efficacy of etanercept persist for more than 2 years in patients with active ankylosing spondylitis, according to the results of an open-label extension study.

Among 26 patients who entered the open, observational phase following a 12-week blinded study, 21 have continued with etanercept, 25 mg twice weekly, for an additional 102 weeks, Xenofon Baraliakos, M.D., said at the annual meeting of the American College of Rheumatology.

Response was evaluated according to a core set of end points proposed by the Assessments in Ankylosing Spondylitis (ASAS) working group. These included the Bath AS Disease Activity Index (BASDAI) and the ASAS 40, which represents a 40% improvement in several disease domains such as pain, function, and inflammation.

The primary end point was an improvement of 50% or more on the BASDAI, a 10-point visual analog scale that assesses fatigue, spinal pain, peripheral arthritis, enthesitis, and morning stiffness.

At 102 weeks, an intent-to-treat analysis of all 26 patients indicated that 54% maintained both a BASDAI 50% response and an ASAS 40. At week 54, the corresponding percentages were 58% and 62%, said Dr. Baraliakos, who is of the department of rheumatology, Benjamin Franklin Hospital, Free University Berlin.

An analysis that included only the 21 study completers also found that disease activity improved significantly, with a mean BASDAI score of 2.7 at week 102. The baseline BASDAI score in this group of patients had been 6.3, on a 0–10 scale, with 10 being the most severe, Dr. Baraliakos said in a poster session.

The mean C-reactive protein level at week 102 was 5 mg/dL, and the mean erythrocyte sedimentation rate was 9 mg/dL, which represented significant improvements over baseline levels, which had been 15.3 and 22.8, respectively. Similar improvements also were seen on the Bath AS functional and mobility indexes.

This study differed from previous investigations of etanercept in AS in that no concomitant corticosteroids or disease-modifying antirheumatic drugs (DMARDs) were permitted. In an earlier study, 40 patients were treated with the tumor necrosis factor-α blocking agent but were allowed to continue other medications (N. Engl. J. Med. 2002;346:1349–56).

In an interim analysis, the authors of this latest study noted that it was important to evaluate etanercept alone (Arthritis Rheum. 2003;48:1667–75).

SAN ANTONIO — Adding the selective costimulatory modulator abatacept to methotrexate in patients with rheumatoid arthritis who do not respond adequately to methotrexate alone resulted in “robust clinical efficacy” that persisted for 2 years, according to the findings of an extension study.

Among patients who completed 2 years of treatment, response rates were similar at 2 years to what they were at 1 year, Joel M. Kremer, M.D., said in a poster session at the annual meeting of the American College of Rheumatology. (See chart.)

In the initial double-blind phase of the trial, 115 participants whose mean age was 55.6 years and whose mean disease duration was 10 years were randomized to receive intravenous abatacept (10 mg/kg monthly) plus methotrexate in a stable dose of 10 to 30 mg/week for 1 year.

Those who completed the yearlong blinded phase were eligible to enroll in the long-term open trial, which used a fixed dose of abatacept (about 10 mg/kg) along with methotrexate.

A total of 84 patients entered the open phase and 75 completed the full 2 years. High rates of retention in the trial, along with improved ACR scores, demonstrated consistent and sustained clinical efficacy, said Dr. Kremer, director of research at the Center for Rheumatology, Albany, N.Y.

In addition to the standard American College of Rheumatology (ACR) 20, 50, and 70 responses, ACR 90 responses were assessed. This score was achieved by more than 13% of patients at year 1 and almost 15% at year 2.

During the double-blind phase of the study, the most common adverse events were nasopharyngitis, headache, nausea, and cough. There were no new emerging safety issues during the long-term extension phase, he said.

Abatacept is the first in a new class of agents that inhibit the full activation of T cells. It blocks the engagement of the costimulatory molecule CD28, resulting in the inhibition of cytokines that activate inflammatory cells.

Dr. Kremer disclosed that he receives research grants and consulting fees from multiple sponsors, including Bristol-Myers Squibb Co., the manufacturer of abatacept.

SAN ANTONIO — Adding the selective costimulatory modulator abatacept to methotrexate in patients with rheumatoid arthritis who do not respond adequately to methotrexate alone resulted in “robust clinical efficacy” that persisted for 2 years, according to the findings of an extension study.

Among patients who completed 2 years of treatment, response rates were similar at 2 years to what they were at 1 year, Joel M. Kremer, M.D., said in a poster session at the annual meeting of the American College of Rheumatology. (See chart.)

In the initial double-blind phase of the trial, 115 participants whose mean age was 55.6 years and whose mean disease duration was 10 years were randomized to receive intravenous abatacept (10 mg/kg monthly) plus methotrexate in a stable dose of 10 to 30 mg/week for 1 year.

Those who completed the yearlong blinded phase were eligible to enroll in the long-term open trial, which used a fixed dose of abatacept (about 10 mg/kg) along with methotrexate.

A total of 84 patients entered the open phase and 75 completed the full 2 years. High rates of retention in the trial, along with improved ACR scores, demonstrated consistent and sustained clinical efficacy, said Dr. Kremer, director of research at the Center for Rheumatology, Albany, N.Y.

In addition to the standard American College of Rheumatology (ACR) 20, 50, and 70 responses, ACR 90 responses were assessed. This score was achieved by more than 13% of patients at year 1 and almost 15% at year 2.

During the double-blind phase of the study, the most common adverse events were nasopharyngitis, headache, nausea, and cough. There were no new emerging safety issues during the long-term extension phase, he said.

Abatacept is the first in a new class of agents that inhibit the full activation of T cells. It blocks the engagement of the costimulatory molecule CD28, resulting in the inhibition of cytokines that activate inflammatory cells.

Dr. Kremer disclosed that he receives research grants and consulting fees from multiple sponsors, including Bristol-Myers Squibb Co., the manufacturer of abatacept.

SAN ANTONIO — Adding the selective costimulatory modulator abatacept to methotrexate in patients with rheumatoid arthritis who do not respond adequately to methotrexate alone resulted in “robust clinical efficacy” that persisted for 2 years, according to the findings of an extension study.

Among patients who completed 2 years of treatment, response rates were similar at 2 years to what they were at 1 year, Joel M. Kremer, M.D., said in a poster session at the annual meeting of the American College of Rheumatology. (See chart.)

In the initial double-blind phase of the trial, 115 participants whose mean age was 55.6 years and whose mean disease duration was 10 years were randomized to receive intravenous abatacept (10 mg/kg monthly) plus methotrexate in a stable dose of 10 to 30 mg/week for 1 year.

Those who completed the yearlong blinded phase were eligible to enroll in the long-term open trial, which used a fixed dose of abatacept (about 10 mg/kg) along with methotrexate.

A total of 84 patients entered the open phase and 75 completed the full 2 years. High rates of retention in the trial, along with improved ACR scores, demonstrated consistent and sustained clinical efficacy, said Dr. Kremer, director of research at the Center for Rheumatology, Albany, N.Y.

In addition to the standard American College of Rheumatology (ACR) 20, 50, and 70 responses, ACR 90 responses were assessed. This score was achieved by more than 13% of patients at year 1 and almost 15% at year 2.

During the double-blind phase of the study, the most common adverse events were nasopharyngitis, headache, nausea, and cough. There were no new emerging safety issues during the long-term extension phase, he said.

Abatacept is the first in a new class of agents that inhibit the full activation of T cells. It blocks the engagement of the costimulatory molecule CD28, resulting in the inhibition of cytokines that activate inflammatory cells.

Dr. Kremer disclosed that he receives research grants and consulting fees from multiple sponsors, including Bristol-Myers Squibb Co., the manufacturer of abatacept.

NEW YORK — Injections of high molecular weight hyaluronan were as effective as corticosteroids in alleviating pain associated with arthritis of the trapeziometacarpal joint, Shalom Stahl, M.D., reported at the annual meeting of the American Society for Surgery of the Hand.

Trapeziometacarpal joint arthritis is a disabling condition that presents with pain at the base of the thumb, causing impairment of hand function. Early disease is usually treated conservatively with splints, rest, and nonsteroidal anti-inflammatory drugs.

Occasionally, intraarticular injections of corticosteroids also are given, but this treatment has unpredictable efficacy and the potential for adverse events, such as infection and subcutaneous fat degeneration, that can cause additional disability, Dr. Stahl said.

High molecular weight hyaluronan (Orthovisc) is indicated for the relief of pain in knee osteoarthritis.

It is intended to restore the viscoelastic properties of the joint lining in patients who are in the early stages of osteoarthritis, said Dr. Stahl of the hand surgery unit, Rambam Medical Center, Haifa, Israel.

A total of 52 patients with grade 2 trapeziometacarpal joint arthritis were prospectively randomized to injections of 40 mg methylprednisolone acetate or 15 mg hyaluronate.

Patients were evaluated for pain severity, pinch and grip strength, and function before injection and 1, 3, and 6 months later.

Both groups experienced similar degrees of pain reduction. In the corticosteroid group, pain evaluated on a visual analog scale fell from a mean of 4.5 to 2.8; in the hyaluronate group, it decreased from 4.2 to 2.3.

Grip strength improved significantly throughout the 6-month follow-up period in the corticosteroid group but only at the 6-month point in the hyaluronate group.

Pinch strength, considered a proxy for functional improvement, improved at 6 months in the hyaluronate group but not in the corticosteroid group.

“Additionally, a significant improvement in the three-point pinch, lateral pinch, and physical performance test has been observed in the Orthovisc group starting at 3 months' follow-up,” Dr. Stahl said.

“We believe that sodium hyaluronate actually works on the basic process of the degenerative arthritic changes, whereas the corticosteroid addresses only the inflammatory component,”Dr. Stahl said.

NEW YORK — Injections of high molecular weight hyaluronan were as effective as corticosteroids in alleviating pain associated with arthritis of the trapeziometacarpal joint, Shalom Stahl, M.D., reported at the annual meeting of the American Society for Surgery of the Hand.

Trapeziometacarpal joint arthritis is a disabling condition that presents with pain at the base of the thumb, causing impairment of hand function. Early disease is usually treated conservatively with splints, rest, and nonsteroidal anti-inflammatory drugs.

Occasionally, intraarticular injections of corticosteroids also are given, but this treatment has unpredictable efficacy and the potential for adverse events, such as infection and subcutaneous fat degeneration, that can cause additional disability, Dr. Stahl said.

High molecular weight hyaluronan (Orthovisc) is indicated for the relief of pain in knee osteoarthritis.

It is intended to restore the viscoelastic properties of the joint lining in patients who are in the early stages of osteoarthritis, said Dr. Stahl of the hand surgery unit, Rambam Medical Center, Haifa, Israel.

A total of 52 patients with grade 2 trapeziometacarpal joint arthritis were prospectively randomized to injections of 40 mg methylprednisolone acetate or 15 mg hyaluronate.

Patients were evaluated for pain severity, pinch and grip strength, and function before injection and 1, 3, and 6 months later.

Both groups experienced similar degrees of pain reduction. In the corticosteroid group, pain evaluated on a visual analog scale fell from a mean of 4.5 to 2.8; in the hyaluronate group, it decreased from 4.2 to 2.3.

Grip strength improved significantly throughout the 6-month follow-up period in the corticosteroid group but only at the 6-month point in the hyaluronate group.

Pinch strength, considered a proxy for functional improvement, improved at 6 months in the hyaluronate group but not in the corticosteroid group.

“Additionally, a significant improvement in the three-point pinch, lateral pinch, and physical performance test has been observed in the Orthovisc group starting at 3 months' follow-up,” Dr. Stahl said.

“We believe that sodium hyaluronate actually works on the basic process of the degenerative arthritic changes, whereas the corticosteroid addresses only the inflammatory component,”Dr. Stahl said.

NEW YORK — Injections of high molecular weight hyaluronan were as effective as corticosteroids in alleviating pain associated with arthritis of the trapeziometacarpal joint, Shalom Stahl, M.D., reported at the annual meeting of the American Society for Surgery of the Hand.

Trapeziometacarpal joint arthritis is a disabling condition that presents with pain at the base of the thumb, causing impairment of hand function. Early disease is usually treated conservatively with splints, rest, and nonsteroidal anti-inflammatory drugs.

Occasionally, intraarticular injections of corticosteroids also are given, but this treatment has unpredictable efficacy and the potential for adverse events, such as infection and subcutaneous fat degeneration, that can cause additional disability, Dr. Stahl said.

High molecular weight hyaluronan (Orthovisc) is indicated for the relief of pain in knee osteoarthritis.

It is intended to restore the viscoelastic properties of the joint lining in patients who are in the early stages of osteoarthritis, said Dr. Stahl of the hand surgery unit, Rambam Medical Center, Haifa, Israel.

A total of 52 patients with grade 2 trapeziometacarpal joint arthritis were prospectively randomized to injections of 40 mg methylprednisolone acetate or 15 mg hyaluronate.

Patients were evaluated for pain severity, pinch and grip strength, and function before injection and 1, 3, and 6 months later.

Both groups experienced similar degrees of pain reduction. In the corticosteroid group, pain evaluated on a visual analog scale fell from a mean of 4.5 to 2.8; in the hyaluronate group, it decreased from 4.2 to 2.3.

Grip strength improved significantly throughout the 6-month follow-up period in the corticosteroid group but only at the 6-month point in the hyaluronate group.

Pinch strength, considered a proxy for functional improvement, improved at 6 months in the hyaluronate group but not in the corticosteroid group.

“Additionally, a significant improvement in the three-point pinch, lateral pinch, and physical performance test has been observed in the Orthovisc group starting at 3 months' follow-up,” Dr. Stahl said.

“We believe that sodium hyaluronate actually works on the basic process of the degenerative arthritic changes, whereas the corticosteroid addresses only the inflammatory component,”Dr. Stahl said.

NEW YORK — Wrist fusion is an irreversible procedure resulting in total loss of radiocarpal movement, but for patients with advanced Kienböck's disease, it is the treatment of choice, Anant Tambe, M.B., said at the annual meeting of the American Society for Surgery of the Hand.

Kienböck's disease is an avascular necrosis of the lunate bone; its etiology is unknown. In its advanced stages 3 and 4, the condition is characterized by progressive carpal collapse, arthritis, and significant disability. Patients with this condition typically undergo either wrist fusion or one of several types of limited carpal fusion, but there is no published evidence showing that any procedure is optimal, said Dr. Tambe, who conducted the study at the Wrightington, Wigan, and Leigh NHS Trust, England.

All patients with Kienböck's disease in the United Kingdom are referred to Wrightington Hospital in Wigan and are entered into a registry, which currently consists of 223 patients, he said.

From this cohort, 18 were identified as having stage 3 or 4 disease and were retrospectively analyzed for outcome following surgery. Of these 18 patients, 6 had undergone wrist fusion and 12 had had limited carpal fusion.

The patients' average age was 39.6 years, and males predominated. The average follow-up was 61.8 months in the wrist fusion group and 66.8 months in the limited carpal fusion group.

Pain was rated on a visual analog scale. In the wrist fusion group, pain scores fell from a preoperative average of 8 to 3.3 following surgery, whereas in the carpal fusion group it decreased from a preoperative average of 8.9 to 7.2, Dr. Tambe said. The between-group difference was statistically significant.

On other measures, including the disability of arm, shoulder, and hand (DASH) score and the Short Form (SF)-12, which rates overall health status and grip strength, the limited carpal group fared slightly better. The differences were not statistically significant, however. Patient satisfaction was slightly higher in the wrist fusion group.

An important finding was that 4 of the 12 patients in the carpal fusion group had been advised to undergo wrist fusion. “At this time, three have undergone repeat surgery and one is awaiting surgery,” he commented.

An additional finding in the study was a predictable progressive pattern of arthritis, first with involvement of the midcarpal joints, then the radiolunate joint, then radioscaphoid involvement, and finally global arthritis, he said.

NEW YORK — Wrist fusion is an irreversible procedure resulting in total loss of radiocarpal movement, but for patients with advanced Kienböck's disease, it is the treatment of choice, Anant Tambe, M.B., said at the annual meeting of the American Society for Surgery of the Hand.

Kienböck's disease is an avascular necrosis of the lunate bone; its etiology is unknown. In its advanced stages 3 and 4, the condition is characterized by progressive carpal collapse, arthritis, and significant disability. Patients with this condition typically undergo either wrist fusion or one of several types of limited carpal fusion, but there is no published evidence showing that any procedure is optimal, said Dr. Tambe, who conducted the study at the Wrightington, Wigan, and Leigh NHS Trust, England.

All patients with Kienböck's disease in the United Kingdom are referred to Wrightington Hospital in Wigan and are entered into a registry, which currently consists of 223 patients, he said.

From this cohort, 18 were identified as having stage 3 or 4 disease and were retrospectively analyzed for outcome following surgery. Of these 18 patients, 6 had undergone wrist fusion and 12 had had limited carpal fusion.

The patients' average age was 39.6 years, and males predominated. The average follow-up was 61.8 months in the wrist fusion group and 66.8 months in the limited carpal fusion group.

Pain was rated on a visual analog scale. In the wrist fusion group, pain scores fell from a preoperative average of 8 to 3.3 following surgery, whereas in the carpal fusion group it decreased from a preoperative average of 8.9 to 7.2, Dr. Tambe said. The between-group difference was statistically significant.

On other measures, including the disability of arm, shoulder, and hand (DASH) score and the Short Form (SF)-12, which rates overall health status and grip strength, the limited carpal group fared slightly better. The differences were not statistically significant, however. Patient satisfaction was slightly higher in the wrist fusion group.

An important finding was that 4 of the 12 patients in the carpal fusion group had been advised to undergo wrist fusion. “At this time, three have undergone repeat surgery and one is awaiting surgery,” he commented.

An additional finding in the study was a predictable progressive pattern of arthritis, first with involvement of the midcarpal joints, then the radiolunate joint, then radioscaphoid involvement, and finally global arthritis, he said.

NEW YORK — Wrist fusion is an irreversible procedure resulting in total loss of radiocarpal movement, but for patients with advanced Kienböck's disease, it is the treatment of choice, Anant Tambe, M.B., said at the annual meeting of the American Society for Surgery of the Hand.

Kienböck's disease is an avascular necrosis of the lunate bone; its etiology is unknown. In its advanced stages 3 and 4, the condition is characterized by progressive carpal collapse, arthritis, and significant disability. Patients with this condition typically undergo either wrist fusion or one of several types of limited carpal fusion, but there is no published evidence showing that any procedure is optimal, said Dr. Tambe, who conducted the study at the Wrightington, Wigan, and Leigh NHS Trust, England.

All patients with Kienböck's disease in the United Kingdom are referred to Wrightington Hospital in Wigan and are entered into a registry, which currently consists of 223 patients, he said.

From this cohort, 18 were identified as having stage 3 or 4 disease and were retrospectively analyzed for outcome following surgery. Of these 18 patients, 6 had undergone wrist fusion and 12 had had limited carpal fusion.

The patients' average age was 39.6 years, and males predominated. The average follow-up was 61.8 months in the wrist fusion group and 66.8 months in the limited carpal fusion group.

Pain was rated on a visual analog scale. In the wrist fusion group, pain scores fell from a preoperative average of 8 to 3.3 following surgery, whereas in the carpal fusion group it decreased from a preoperative average of 8.9 to 7.2, Dr. Tambe said. The between-group difference was statistically significant.

On other measures, including the disability of arm, shoulder, and hand (DASH) score and the Short Form (SF)-12, which rates overall health status and grip strength, the limited carpal group fared slightly better. The differences were not statistically significant, however. Patient satisfaction was slightly higher in the wrist fusion group.

An important finding was that 4 of the 12 patients in the carpal fusion group had been advised to undergo wrist fusion. “At this time, three have undergone repeat surgery and one is awaiting surgery,” he commented.

An additional finding in the study was a predictable progressive pattern of arthritis, first with involvement of the midcarpal joints, then the radiolunate joint, then radioscaphoid involvement, and finally global arthritis, he said.