Patrice Wendling

NEW ORLEANS — Treatment with once-daily, high-dose valacyclovir caplets significantly decreases the duration and quantity of oral herpes simplex virus-1 shedding associated with recurrent herpes labialis, according to data from a randomized study.

Oral shedding, either associated with known outbreaks of herpes labialis or, perhaps more importantly, during asymptomatic periods, is the presumed mechanism for transmission of herpes simplex virus-1 (HSV-1), Stan C. Gilbert, M.D., said in a poster presentation at the annual meeting of the American Academy of Dermatology.

HSV-1 causes gingivostomatitis in infants and children and recurrent cold sores in most people. It also has become the primary cause of most genital herpes cases in young adults. Recurrent herpes labialis (RHL) is seen in up to 40% of HSV-1-seropositive adults.

Research has shown oral shedding associated with episodes of RHL lasting from 1 to 8 days. But the studies are rare and have relied mostly on viral cultures, according to Dr. Gilbert, of the University of Washington, Seattle.

Dr. Gilbert's study randomized 64 adults with a history of three or more RHL episodes a year to four 500-mg valacyclovir (Valtrex) caplets taken at the first sign of an outbreak or placebo. The dosing was repeated 12 hours later. PCR swabs were collected every 12 hours starting at the first sign of outbreak and continuing for 10 days.

Both groups had a history of cold sores for an average of 28 years and an average of four cold sores in the previous 12 months.

Patients receiving valacyclovir experienced fewer days on which shedding occurred than the placebo group (1.8 vs. 4 days). A comparison of the log HSV-1 DNA copies detected by PCR over time, using the average area under the curve (AUC), showed significantly less shedding from the treatment group than from the placebo group (mean AUC 1.1 vs. 2.2).

Dr. Gilbert is a member of the speakers' bureau for GlaxoSmithKline, which manufactures Valtrex and provided 50% of the funding for the study.

NEW ORLEANS — Treatment with once-daily, high-dose valacyclovir caplets significantly decreases the duration and quantity of oral herpes simplex virus-1 shedding associated with recurrent herpes labialis, according to data from a randomized study.

Oral shedding, either associated with known outbreaks of herpes labialis or, perhaps more importantly, during asymptomatic periods, is the presumed mechanism for transmission of herpes simplex virus-1 (HSV-1), Stan C. Gilbert, M.D., said in a poster presentation at the annual meeting of the American Academy of Dermatology.

HSV-1 causes gingivostomatitis in infants and children and recurrent cold sores in most people. It also has become the primary cause of most genital herpes cases in young adults. Recurrent herpes labialis (RHL) is seen in up to 40% of HSV-1-seropositive adults.

Research has shown oral shedding associated with episodes of RHL lasting from 1 to 8 days. But the studies are rare and have relied mostly on viral cultures, according to Dr. Gilbert, of the University of Washington, Seattle.

Dr. Gilbert's study randomized 64 adults with a history of three or more RHL episodes a year to four 500-mg valacyclovir (Valtrex) caplets taken at the first sign of an outbreak or placebo. The dosing was repeated 12 hours later. PCR swabs were collected every 12 hours starting at the first sign of outbreak and continuing for 10 days.

Both groups had a history of cold sores for an average of 28 years and an average of four cold sores in the previous 12 months.

Patients receiving valacyclovir experienced fewer days on which shedding occurred than the placebo group (1.8 vs. 4 days). A comparison of the log HSV-1 DNA copies detected by PCR over time, using the average area under the curve (AUC), showed significantly less shedding from the treatment group than from the placebo group (mean AUC 1.1 vs. 2.2).

Dr. Gilbert is a member of the speakers' bureau for GlaxoSmithKline, which manufactures Valtrex and provided 50% of the funding for the study.

NEW ORLEANS — Treatment with once-daily, high-dose valacyclovir caplets significantly decreases the duration and quantity of oral herpes simplex virus-1 shedding associated with recurrent herpes labialis, according to data from a randomized study.

Oral shedding, either associated with known outbreaks of herpes labialis or, perhaps more importantly, during asymptomatic periods, is the presumed mechanism for transmission of herpes simplex virus-1 (HSV-1), Stan C. Gilbert, M.D., said in a poster presentation at the annual meeting of the American Academy of Dermatology.

HSV-1 causes gingivostomatitis in infants and children and recurrent cold sores in most people. It also has become the primary cause of most genital herpes cases in young adults. Recurrent herpes labialis (RHL) is seen in up to 40% of HSV-1-seropositive adults.

Research has shown oral shedding associated with episodes of RHL lasting from 1 to 8 days. But the studies are rare and have relied mostly on viral cultures, according to Dr. Gilbert, of the University of Washington, Seattle.

Dr. Gilbert's study randomized 64 adults with a history of three or more RHL episodes a year to four 500-mg valacyclovir (Valtrex) caplets taken at the first sign of an outbreak or placebo. The dosing was repeated 12 hours later. PCR swabs were collected every 12 hours starting at the first sign of outbreak and continuing for 10 days.

Both groups had a history of cold sores for an average of 28 years and an average of four cold sores in the previous 12 months.

Patients receiving valacyclovir experienced fewer days on which shedding occurred than the placebo group (1.8 vs. 4 days). A comparison of the log HSV-1 DNA copies detected by PCR over time, using the average area under the curve (AUC), showed significantly less shedding from the treatment group than from the placebo group (mean AUC 1.1 vs. 2.2).

Dr. Gilbert is a member of the speakers' bureau for GlaxoSmithKline, which manufactures Valtrex and provided 50% of the funding for the study.

VIENNA — Successful Mohs micrographic surgery depends on two things: that the tumor is contiguous and that 100% of the surgical margins are examined histologically, Stuart J. Salasche, M.D., said at the 10th World Congress on Cancers of the Skin.

"Recurrences do happen, and if you're doing 1,000, 2,000 cases a year then even small percentages add up to numbers, and each number represents an individual patient who put [himself or herself] in your hands," Dr. Salasche said.

Some recurrences are caused by "housekeeping errors" such as inadequate slide preparation, mapping errors, and poor tissue samples, and can be reduced with repetition and good staff training, he said.

Large tumors in general, and particularly those on the ear or medial canthus of the eye, can be difficult to map, and should be marked carefully with scalpel hatch marks that correspond to color-coded maps for more accurate orientation.

Poor slide preparation can result in false negative margins because of missing epidermis or holes and folds in the tissue where tumor can exist.

False-negative margin situations are frequently caused by noncontiguous tumors. Common culprits are recurrent tumors where residual tumor was left in multiple foci of which only one became clinically apparent. This applies particularly in immunosuppressed patients, he said. Some tumors may inherently have skip areas such as those seen in sebaceous carcinoma and Merkel cell carcinoma.

"The ones that we see most often and cause us the most trouble are tumors that have already been operated on or previously treated," said Dr. Salasche of the Arizona Cancer Center at the University of Arizona in Tucson.

When evaluating recurrent tumors, consider the original treatment modality, the type of repair used, the time from original surgery to clinical recurrence, the aggressiveness of the tumor histology, and whether the area was covered with a graft, he said at the meeting, cosponsored by the Skin Cancer Foundation.

In the approach to a recurrence, all visual tumor and the entire scar should be resected, as if the scar were part of the original tumor. Pay particular attention to squamous cell carcinomas or lesions on the scalp, temple, or forehead, most notably in organ transplant patients, he said.

Inflammation can also mask tumors and is common in elderly populations with chronic lymphocytic leukemia. Tumor masked by the inflammation may go unrecognized by the surgeon, or result in the surgeon chasing the inflammation or subclinical extensions as they track along nerves for great distances, he said. Immunostaining is helpful in these cases.

Another problem is recognizing that basal cell carcinomas probably originate from stem cells that reside in the outer root sheath of the hair follicle, and result in subtle buds of tumor coming off the follicle that can be misread as hair follicles, he said.

VIENNA — Successful Mohs micrographic surgery depends on two things: that the tumor is contiguous and that 100% of the surgical margins are examined histologically, Stuart J. Salasche, M.D., said at the 10th World Congress on Cancers of the Skin.

"Recurrences do happen, and if you're doing 1,000, 2,000 cases a year then even small percentages add up to numbers, and each number represents an individual patient who put [himself or herself] in your hands," Dr. Salasche said.

Some recurrences are caused by "housekeeping errors" such as inadequate slide preparation, mapping errors, and poor tissue samples, and can be reduced with repetition and good staff training, he said.

Large tumors in general, and particularly those on the ear or medial canthus of the eye, can be difficult to map, and should be marked carefully with scalpel hatch marks that correspond to color-coded maps for more accurate orientation.

Poor slide preparation can result in false negative margins because of missing epidermis or holes and folds in the tissue where tumor can exist.

False-negative margin situations are frequently caused by noncontiguous tumors. Common culprits are recurrent tumors where residual tumor was left in multiple foci of which only one became clinically apparent. This applies particularly in immunosuppressed patients, he said. Some tumors may inherently have skip areas such as those seen in sebaceous carcinoma and Merkel cell carcinoma.

"The ones that we see most often and cause us the most trouble are tumors that have already been operated on or previously treated," said Dr. Salasche of the Arizona Cancer Center at the University of Arizona in Tucson.

When evaluating recurrent tumors, consider the original treatment modality, the type of repair used, the time from original surgery to clinical recurrence, the aggressiveness of the tumor histology, and whether the area was covered with a graft, he said at the meeting, cosponsored by the Skin Cancer Foundation.

In the approach to a recurrence, all visual tumor and the entire scar should be resected, as if the scar were part of the original tumor. Pay particular attention to squamous cell carcinomas or lesions on the scalp, temple, or forehead, most notably in organ transplant patients, he said.

Inflammation can also mask tumors and is common in elderly populations with chronic lymphocytic leukemia. Tumor masked by the inflammation may go unrecognized by the surgeon, or result in the surgeon chasing the inflammation or subclinical extensions as they track along nerves for great distances, he said. Immunostaining is helpful in these cases.

Another problem is recognizing that basal cell carcinomas probably originate from stem cells that reside in the outer root sheath of the hair follicle, and result in subtle buds of tumor coming off the follicle that can be misread as hair follicles, he said.

VIENNA — Successful Mohs micrographic surgery depends on two things: that the tumor is contiguous and that 100% of the surgical margins are examined histologically, Stuart J. Salasche, M.D., said at the 10th World Congress on Cancers of the Skin.

"Recurrences do happen, and if you're doing 1,000, 2,000 cases a year then even small percentages add up to numbers, and each number represents an individual patient who put [himself or herself] in your hands," Dr. Salasche said.

Some recurrences are caused by "housekeeping errors" such as inadequate slide preparation, mapping errors, and poor tissue samples, and can be reduced with repetition and good staff training, he said.

Large tumors in general, and particularly those on the ear or medial canthus of the eye, can be difficult to map, and should be marked carefully with scalpel hatch marks that correspond to color-coded maps for more accurate orientation.

Poor slide preparation can result in false negative margins because of missing epidermis or holes and folds in the tissue where tumor can exist.

False-negative margin situations are frequently caused by noncontiguous tumors. Common culprits are recurrent tumors where residual tumor was left in multiple foci of which only one became clinically apparent. This applies particularly in immunosuppressed patients, he said. Some tumors may inherently have skip areas such as those seen in sebaceous carcinoma and Merkel cell carcinoma.

"The ones that we see most often and cause us the most trouble are tumors that have already been operated on or previously treated," said Dr. Salasche of the Arizona Cancer Center at the University of Arizona in Tucson.

When evaluating recurrent tumors, consider the original treatment modality, the type of repair used, the time from original surgery to clinical recurrence, the aggressiveness of the tumor histology, and whether the area was covered with a graft, he said at the meeting, cosponsored by the Skin Cancer Foundation.

In the approach to a recurrence, all visual tumor and the entire scar should be resected, as if the scar were part of the original tumor. Pay particular attention to squamous cell carcinomas or lesions on the scalp, temple, or forehead, most notably in organ transplant patients, he said.

Inflammation can also mask tumors and is common in elderly populations with chronic lymphocytic leukemia. Tumor masked by the inflammation may go unrecognized by the surgeon, or result in the surgeon chasing the inflammation or subclinical extensions as they track along nerves for great distances, he said. Immunostaining is helpful in these cases.

Another problem is recognizing that basal cell carcinomas probably originate from stem cells that reside in the outer root sheath of the hair follicle, and result in subtle buds of tumor coming off the follicle that can be misread as hair follicles, he said.

VIENNA — For skin cancers on the nose, Mohs micrographic surgery is associated with low recurrence rates and spares a maximal amount of healthy tissue, Abel R. González, M.D., reported at the 10th World Congress on Cancers of the Skin.

"Some patients just want a healed wound, but others have a high aesthetic standard," said Dr. González of the Institute of Oncology Angel H. Roffo at the University of Buenos Aires. "They wish a nose restored to normal, no matter how much time or effort it takes" to accomplish the results.

Of the 2,648 Mohs surgeries performed between 1990 and 2004 at the Institute, 780 (29%) tumors were located on the nose. A review of 758 cases shows 322 (42%) of cases were managed with secondary-intention healing, 306 (40%) with flaps, 111 (15%) with grafts, and 19 (2%) with primary closure.

Secondary-intention healing is simple, complications are rare, and it saves time and cost associated with reconstruction, Dr. González said, at the meeting cosponsored by the Skin Cancer Foundation.

For procedures that require nasal reconstruction, skin quality is an important variable.

The upper two-thirds of the nose and the columella are covered by thin, nonsebaceous and slightly mobile skin. Here, local flaps rotate easily and are a good choice for small defects. Grafts blend well into the smooth and shiny surfaces of the dorsum and sidewalls, Dr. González said.

On the tip or ala, the skin is sebaceous and adherent to underlying tissues. Single lobe flaps rotate poorly, but bilobed or nasolabial flaps can overcome these problems. Grafts are a poor choice as they create a patch of shiny skin in the thick, pitted skin of the area, he said.

For superficial defects, a full-thickness skin graft can be performed. When using grafts, the preference is for delayed, full-thickness skin grafts because bleeding or exudation diminishes when a graft is delayed rather than performed immediately. This also results in a well-vascularized bed, which increases graft survival.

When bone or cartilage is exposed, a flap will be necessary.

When nasal support is missing, and a framework needs to be restored, a distant flap will prevent tension that could distort cartilage reconstruction. A distant flap also is needed when repairing defects larger than 1.5 cm.

Incisions placed strategically in the joins that separate the subunits of the nose—the tip, ala, paired sidewalls, dorsum, soft triangles, and columella—will be perceived as a normal fold or contour line.

If more than 50% of a subunit is lost, the guiding principle is that replacing the entire unit usually gives a better result than just patching the defect.

The forehead flap is an excellent option in nasal reconstruction because the forehead skin matches nasal skin almost exactly and has superb perfusion. The forehead flap should always be vertically oriented because of perfusion, and narrow, paramedian flaps allow easier rotation. It should never reconstruct the cheek.

The final defect after five stages of Mohs surgery is shown.

Photos courtesy Dr. Abel R. González

VIENNA — For skin cancers on the nose, Mohs micrographic surgery is associated with low recurrence rates and spares a maximal amount of healthy tissue, Abel R. González, M.D., reported at the 10th World Congress on Cancers of the Skin.

"Some patients just want a healed wound, but others have a high aesthetic standard," said Dr. González of the Institute of Oncology Angel H. Roffo at the University of Buenos Aires. "They wish a nose restored to normal, no matter how much time or effort it takes" to accomplish the results.

Of the 2,648 Mohs surgeries performed between 1990 and 2004 at the Institute, 780 (29%) tumors were located on the nose. A review of 758 cases shows 322 (42%) of cases were managed with secondary-intention healing, 306 (40%) with flaps, 111 (15%) with grafts, and 19 (2%) with primary closure.

Secondary-intention healing is simple, complications are rare, and it saves time and cost associated with reconstruction, Dr. González said, at the meeting cosponsored by the Skin Cancer Foundation.

For procedures that require nasal reconstruction, skin quality is an important variable.

The upper two-thirds of the nose and the columella are covered by thin, nonsebaceous and slightly mobile skin. Here, local flaps rotate easily and are a good choice for small defects. Grafts blend well into the smooth and shiny surfaces of the dorsum and sidewalls, Dr. González said.

On the tip or ala, the skin is sebaceous and adherent to underlying tissues. Single lobe flaps rotate poorly, but bilobed or nasolabial flaps can overcome these problems. Grafts are a poor choice as they create a patch of shiny skin in the thick, pitted skin of the area, he said.

For superficial defects, a full-thickness skin graft can be performed. When using grafts, the preference is for delayed, full-thickness skin grafts because bleeding or exudation diminishes when a graft is delayed rather than performed immediately. This also results in a well-vascularized bed, which increases graft survival.

When bone or cartilage is exposed, a flap will be necessary.

When nasal support is missing, and a framework needs to be restored, a distant flap will prevent tension that could distort cartilage reconstruction. A distant flap also is needed when repairing defects larger than 1.5 cm.

Incisions placed strategically in the joins that separate the subunits of the nose—the tip, ala, paired sidewalls, dorsum, soft triangles, and columella—will be perceived as a normal fold or contour line.

If more than 50% of a subunit is lost, the guiding principle is that replacing the entire unit usually gives a better result than just patching the defect.

The forehead flap is an excellent option in nasal reconstruction because the forehead skin matches nasal skin almost exactly and has superb perfusion. The forehead flap should always be vertically oriented because of perfusion, and narrow, paramedian flaps allow easier rotation. It should never reconstruct the cheek.

The final defect after five stages of Mohs surgery is shown.

Photos courtesy Dr. Abel R. González

VIENNA — For skin cancers on the nose, Mohs micrographic surgery is associated with low recurrence rates and spares a maximal amount of healthy tissue, Abel R. González, M.D., reported at the 10th World Congress on Cancers of the Skin.

"Some patients just want a healed wound, but others have a high aesthetic standard," said Dr. González of the Institute of Oncology Angel H. Roffo at the University of Buenos Aires. "They wish a nose restored to normal, no matter how much time or effort it takes" to accomplish the results.

Of the 2,648 Mohs surgeries performed between 1990 and 2004 at the Institute, 780 (29%) tumors were located on the nose. A review of 758 cases shows 322 (42%) of cases were managed with secondary-intention healing, 306 (40%) with flaps, 111 (15%) with grafts, and 19 (2%) with primary closure.

Secondary-intention healing is simple, complications are rare, and it saves time and cost associated with reconstruction, Dr. González said, at the meeting cosponsored by the Skin Cancer Foundation.

For procedures that require nasal reconstruction, skin quality is an important variable.

The upper two-thirds of the nose and the columella are covered by thin, nonsebaceous and slightly mobile skin. Here, local flaps rotate easily and are a good choice for small defects. Grafts blend well into the smooth and shiny surfaces of the dorsum and sidewalls, Dr. González said.

On the tip or ala, the skin is sebaceous and adherent to underlying tissues. Single lobe flaps rotate poorly, but bilobed or nasolabial flaps can overcome these problems. Grafts are a poor choice as they create a patch of shiny skin in the thick, pitted skin of the area, he said.

For superficial defects, a full-thickness skin graft can be performed. When using grafts, the preference is for delayed, full-thickness skin grafts because bleeding or exudation diminishes when a graft is delayed rather than performed immediately. This also results in a well-vascularized bed, which increases graft survival.

When bone or cartilage is exposed, a flap will be necessary.

When nasal support is missing, and a framework needs to be restored, a distant flap will prevent tension that could distort cartilage reconstruction. A distant flap also is needed when repairing defects larger than 1.5 cm.

Incisions placed strategically in the joins that separate the subunits of the nose—the tip, ala, paired sidewalls, dorsum, soft triangles, and columella—will be perceived as a normal fold or contour line.

If more than 50% of a subunit is lost, the guiding principle is that replacing the entire unit usually gives a better result than just patching the defect.

The forehead flap is an excellent option in nasal reconstruction because the forehead skin matches nasal skin almost exactly and has superb perfusion. The forehead flap should always be vertically oriented because of perfusion, and narrow, paramedian flaps allow easier rotation. It should never reconstruct the cheek.

The final defect after five stages of Mohs surgery is shown.

Photos courtesy Dr. Abel R. González

Methotrexate was more effective than leflunomide in the treatment of polyarticular juvenile rheumatoid arthritis, although both drugs resulted in high rates of clinical improvement in a multinational, randomized, controlled trial.

A total of 94 children, aged 3–17 years, with polyarticular juvenile rheumatoid arthritis (JRA) were randomized to either leflunomide (Arava) or methotrexate (MTX) for 16 weeks, followed by a 32-week blinded extension phase (N. Engl. J. Med. 2005;352:1655–66).

The dose of leflunomide was based on three weight categories: Patients weighing less than 20 kg received 100 mg of leflunomide for 1 day, followed by a maintenance dose of 10 mg every other day; 20 kg to 40 kg patients received 100 mg for 2 days, followed by 10 mg/day; and those weighing more than 40 kg received 100 mg for 3 days, followed by 20 mg/day. The MTX dose was 0.5 g/kg per week, with a maximum of 25 mg per week. Concomitant treatment with nonsteroidal anti-inflammatory drugs and prednisone was allowed.

At week 16, the rate of American College of Rheumatology Pediatric 30% (ACR Pedi 30) responses was significantly higher in the methotrexate group than in the leflunomide group (89% vs. 68%).

There was not a significant difference between the leflunomide and methotrexate groups in the other primary outcome variable, the Percent Improvement Index (−44.41% vs. −52.87%).

In both groups, the improvements achieved at week 16 were maintained at week 48. The results compare favorably with previously published ACR Pedi 30 response rates of 48% with methotrexate, 44% with sulfasalazine, and 74% after 3 months of open-label etanercept, according to the authors.

“The higher-than-expected rates of responses in both treatment groups may in part be attributed to the early stage of disease (median duration 4 months) in this population…,” wrote lead author Earl Silverman, M.D., of the University of Toronto, a paid consultant for Sanofi-Aventis, which supported the study.

The most common adverse events in both groups included gastrointestinal symptoms, headache, and nasopharyngeal symptoms. ALT elevations were more frequent with MTX than with leflunomide during both phases of the study.

Methotrexate was more effective than leflunomide in the treatment of polyarticular juvenile rheumatoid arthritis, although both drugs resulted in high rates of clinical improvement in a multinational, randomized, controlled trial.

A total of 94 children, aged 3–17 years, with polyarticular juvenile rheumatoid arthritis (JRA) were randomized to either leflunomide (Arava) or methotrexate (MTX) for 16 weeks, followed by a 32-week blinded extension phase (N. Engl. J. Med. 2005;352:1655–66).

The dose of leflunomide was based on three weight categories: Patients weighing less than 20 kg received 100 mg of leflunomide for 1 day, followed by a maintenance dose of 10 mg every other day; 20 kg to 40 kg patients received 100 mg for 2 days, followed by 10 mg/day; and those weighing more than 40 kg received 100 mg for 3 days, followed by 20 mg/day. The MTX dose was 0.5 g/kg per week, with a maximum of 25 mg per week. Concomitant treatment with nonsteroidal anti-inflammatory drugs and prednisone was allowed.

At week 16, the rate of American College of Rheumatology Pediatric 30% (ACR Pedi 30) responses was significantly higher in the methotrexate group than in the leflunomide group (89% vs. 68%).

There was not a significant difference between the leflunomide and methotrexate groups in the other primary outcome variable, the Percent Improvement Index (−44.41% vs. −52.87%).

In both groups, the improvements achieved at week 16 were maintained at week 48. The results compare favorably with previously published ACR Pedi 30 response rates of 48% with methotrexate, 44% with sulfasalazine, and 74% after 3 months of open-label etanercept, according to the authors.

“The higher-than-expected rates of responses in both treatment groups may in part be attributed to the early stage of disease (median duration 4 months) in this population…,” wrote lead author Earl Silverman, M.D., of the University of Toronto, a paid consultant for Sanofi-Aventis, which supported the study.

The most common adverse events in both groups included gastrointestinal symptoms, headache, and nasopharyngeal symptoms. ALT elevations were more frequent with MTX than with leflunomide during both phases of the study.

Methotrexate was more effective than leflunomide in the treatment of polyarticular juvenile rheumatoid arthritis, although both drugs resulted in high rates of clinical improvement in a multinational, randomized, controlled trial.

A total of 94 children, aged 3–17 years, with polyarticular juvenile rheumatoid arthritis (JRA) were randomized to either leflunomide (Arava) or methotrexate (MTX) for 16 weeks, followed by a 32-week blinded extension phase (N. Engl. J. Med. 2005;352:1655–66).

The dose of leflunomide was based on three weight categories: Patients weighing less than 20 kg received 100 mg of leflunomide for 1 day, followed by a maintenance dose of 10 mg every other day; 20 kg to 40 kg patients received 100 mg for 2 days, followed by 10 mg/day; and those weighing more than 40 kg received 100 mg for 3 days, followed by 20 mg/day. The MTX dose was 0.5 g/kg per week, with a maximum of 25 mg per week. Concomitant treatment with nonsteroidal anti-inflammatory drugs and prednisone was allowed.

At week 16, the rate of American College of Rheumatology Pediatric 30% (ACR Pedi 30) responses was significantly higher in the methotrexate group than in the leflunomide group (89% vs. 68%).

There was not a significant difference between the leflunomide and methotrexate groups in the other primary outcome variable, the Percent Improvement Index (−44.41% vs. −52.87%).

In both groups, the improvements achieved at week 16 were maintained at week 48. The results compare favorably with previously published ACR Pedi 30 response rates of 48% with methotrexate, 44% with sulfasalazine, and 74% after 3 months of open-label etanercept, according to the authors.

“The higher-than-expected rates of responses in both treatment groups may in part be attributed to the early stage of disease (median duration 4 months) in this population…,” wrote lead author Earl Silverman, M.D., of the University of Toronto, a paid consultant for Sanofi-Aventis, which supported the study.

The most common adverse events in both groups included gastrointestinal symptoms, headache, and nasopharyngeal symptoms. ALT elevations were more frequent with MTX than with leflunomide during both phases of the study.

CHICAGO — Physicians should rule out leukemia when evaluating children with migratory arthritis, David D. Sherry, M.D., reported at a symposium sponsored by the American College of Rheumatology.

Acute lymphatic leukemia is the most common childhood systemic malignancy associated with musculoskeletal pain and/or arthritis, and its clinical features can often mimic those of juvenile idiopathic arthritis.

In about 50% of cases, the correct diagnosis is delayed.

Patients with leukemia may have very painful arthritis or arthralgia that is usually migratory or episodic. It can occur in one or more joints, including the hip or joints such as the talus-cuboid joint, which is rarely involved in juvenile arthritis, he said.

Other symptoms include low-grade fever and body aches that are accentuated by weight bearing.

“These kids have to be carried, and you don't carry kids with RA generally,” said Dr. Sherry, director of clinical rheumatology at the Children's Hospital of Philadelphia.

Systemic symptoms are present at or near onset of disease. But hematologic abnormalities may take time to develop. One early warning signal is an elevated erythrocyte sedimentation rate, which may be present without other inflammatory markers, he said.

In a case involving a 5-year-old boy, the white blood count was normal, but the erythrocyte sedimentation rate was 89 mm/hr—well above the normal range of 1 mm/hr to 13 mm/hr for males.

A plain radiograph of his swollen knee revealed a grey leukemic line. Metaphyseal bands may be present on x-ray, as well as osteopenia, cortical or periosteal lesions, and osteolytic reaction.

Physicians also should be watchful for leukemia in children with hip disease or Down syndrome, he said.

CHICAGO — Physicians should rule out leukemia when evaluating children with migratory arthritis, David D. Sherry, M.D., reported at a symposium sponsored by the American College of Rheumatology.

Acute lymphatic leukemia is the most common childhood systemic malignancy associated with musculoskeletal pain and/or arthritis, and its clinical features can often mimic those of juvenile idiopathic arthritis.

In about 50% of cases, the correct diagnosis is delayed.

Patients with leukemia may have very painful arthritis or arthralgia that is usually migratory or episodic. It can occur in one or more joints, including the hip or joints such as the talus-cuboid joint, which is rarely involved in juvenile arthritis, he said.

Other symptoms include low-grade fever and body aches that are accentuated by weight bearing.

“These kids have to be carried, and you don't carry kids with RA generally,” said Dr. Sherry, director of clinical rheumatology at the Children's Hospital of Philadelphia.

Systemic symptoms are present at or near onset of disease. But hematologic abnormalities may take time to develop. One early warning signal is an elevated erythrocyte sedimentation rate, which may be present without other inflammatory markers, he said.

In a case involving a 5-year-old boy, the white blood count was normal, but the erythrocyte sedimentation rate was 89 mm/hr—well above the normal range of 1 mm/hr to 13 mm/hr for males.

A plain radiograph of his swollen knee revealed a grey leukemic line. Metaphyseal bands may be present on x-ray, as well as osteopenia, cortical or periosteal lesions, and osteolytic reaction.

Physicians also should be watchful for leukemia in children with hip disease or Down syndrome, he said.

CHICAGO — Physicians should rule out leukemia when evaluating children with migratory arthritis, David D. Sherry, M.D., reported at a symposium sponsored by the American College of Rheumatology.

Acute lymphatic leukemia is the most common childhood systemic malignancy associated with musculoskeletal pain and/or arthritis, and its clinical features can often mimic those of juvenile idiopathic arthritis.

In about 50% of cases, the correct diagnosis is delayed.

Patients with leukemia may have very painful arthritis or arthralgia that is usually migratory or episodic. It can occur in one or more joints, including the hip or joints such as the talus-cuboid joint, which is rarely involved in juvenile arthritis, he said.

Other symptoms include low-grade fever and body aches that are accentuated by weight bearing.

“These kids have to be carried, and you don't carry kids with RA generally,” said Dr. Sherry, director of clinical rheumatology at the Children's Hospital of Philadelphia.

Systemic symptoms are present at or near onset of disease. But hematologic abnormalities may take time to develop. One early warning signal is an elevated erythrocyte sedimentation rate, which may be present without other inflammatory markers, he said.

In a case involving a 5-year-old boy, the white blood count was normal, but the erythrocyte sedimentation rate was 89 mm/hr—well above the normal range of 1 mm/hr to 13 mm/hr for males.

A plain radiograph of his swollen knee revealed a grey leukemic line. Metaphyseal bands may be present on x-ray, as well as osteopenia, cortical or periosteal lesions, and osteolytic reaction.

Physicians also should be watchful for leukemia in children with hip disease or Down syndrome, he said.

NEW ORLEANS — Psoriatic arthritis patients receiving etanercept reported sustained clinical benefits for up to 2 years, according to data from an open-label extension study.

Patients treated with the drug reported inhibition of disease as well as significant improvements in physical functioning and quality of life, Philip J. Mease, M.D., reported at the annual meeting of the American Academy of Dermatology.

After an initial 24-week blinded phase of the study and a maintenance phase of up to 24 weeks, during which patients were kept on their blinded drug, 169 patients received 25 mg of etanercept (Enbrel) twice weekly for an additional 48 weeks during the open-label extension phase.

Patient-reported outcomes included the physical and mental components of the Short-Form (SF-36) Health Survey and the Health Assessment Questionnaire-Disability Index (HAQ-DI). During the placebo-controlled phase, etanercept-treated patients had a mean improvement of 9.3 points on the SF-36 physical component summary scale; placebo patients improved only 0.7 on the scale.

In the open-label phase, patients originally randomized to etanercept maintained their improvements (mean 12.6 points), and patients switched to etanercept from placebo improved almost to the same level as those on continuous etanercept, said Dr. Mease, a rheumatologist at the Swedish Medical Center, the University of Washington, Seattle. Both groups had normal mental health at baseline and maintained it throughout the industry-sponsored trial.

In the placebo-controlled phase, the HAQ-DI improved from 1.1 to 0.5 in the etanercept group and from 1.1 to 1 in the placebo group. At 48 weeks, 40 (53%) of 75 patients originally randomized to etanercept had an HAQ-DI of zero, indicating no disability in performing activities of daily living. The mean HAQ-DI score at 48 weeks was 0.4 for patients continuously treated with etanercept and 0.6 for 70 patients switched from placebo to the drug.

NEW ORLEANS — Psoriatic arthritis patients receiving etanercept reported sustained clinical benefits for up to 2 years, according to data from an open-label extension study.

Patients treated with the drug reported inhibition of disease as well as significant improvements in physical functioning and quality of life, Philip J. Mease, M.D., reported at the annual meeting of the American Academy of Dermatology.

After an initial 24-week blinded phase of the study and a maintenance phase of up to 24 weeks, during which patients were kept on their blinded drug, 169 patients received 25 mg of etanercept (Enbrel) twice weekly for an additional 48 weeks during the open-label extension phase.

Patient-reported outcomes included the physical and mental components of the Short-Form (SF-36) Health Survey and the Health Assessment Questionnaire-Disability Index (HAQ-DI). During the placebo-controlled phase, etanercept-treated patients had a mean improvement of 9.3 points on the SF-36 physical component summary scale; placebo patients improved only 0.7 on the scale.

In the open-label phase, patients originally randomized to etanercept maintained their improvements (mean 12.6 points), and patients switched to etanercept from placebo improved almost to the same level as those on continuous etanercept, said Dr. Mease, a rheumatologist at the Swedish Medical Center, the University of Washington, Seattle. Both groups had normal mental health at baseline and maintained it throughout the industry-sponsored trial.

In the placebo-controlled phase, the HAQ-DI improved from 1.1 to 0.5 in the etanercept group and from 1.1 to 1 in the placebo group. At 48 weeks, 40 (53%) of 75 patients originally randomized to etanercept had an HAQ-DI of zero, indicating no disability in performing activities of daily living. The mean HAQ-DI score at 48 weeks was 0.4 for patients continuously treated with etanercept and 0.6 for 70 patients switched from placebo to the drug.

NEW ORLEANS — Psoriatic arthritis patients receiving etanercept reported sustained clinical benefits for up to 2 years, according to data from an open-label extension study.

Patients treated with the drug reported inhibition of disease as well as significant improvements in physical functioning and quality of life, Philip J. Mease, M.D., reported at the annual meeting of the American Academy of Dermatology.

After an initial 24-week blinded phase of the study and a maintenance phase of up to 24 weeks, during which patients were kept on their blinded drug, 169 patients received 25 mg of etanercept (Enbrel) twice weekly for an additional 48 weeks during the open-label extension phase.

Patient-reported outcomes included the physical and mental components of the Short-Form (SF-36) Health Survey and the Health Assessment Questionnaire-Disability Index (HAQ-DI). During the placebo-controlled phase, etanercept-treated patients had a mean improvement of 9.3 points on the SF-36 physical component summary scale; placebo patients improved only 0.7 on the scale.

In the open-label phase, patients originally randomized to etanercept maintained their improvements (mean 12.6 points), and patients switched to etanercept from placebo improved almost to the same level as those on continuous etanercept, said Dr. Mease, a rheumatologist at the Swedish Medical Center, the University of Washington, Seattle. Both groups had normal mental health at baseline and maintained it throughout the industry-sponsored trial.

In the placebo-controlled phase, the HAQ-DI improved from 1.1 to 0.5 in the etanercept group and from 1.1 to 1 in the placebo group. At 48 weeks, 40 (53%) of 75 patients originally randomized to etanercept had an HAQ-DI of zero, indicating no disability in performing activities of daily living. The mean HAQ-DI score at 48 weeks was 0.4 for patients continuously treated with etanercept and 0.6 for 70 patients switched from placebo to the drug.

Tumor necrosis factor agents do not increase the overall risk of cancer in patients with rheumatoid arthritis but may be associated with an increased risk of lymphomas, an analysis of data from the South Swedish Arthritis Treatment Group register suggests.

The study is the first to question whether use of anti-TNF-α agents increases the risk of lymphoma independently of disease severity.

Pierre Geborek, M.D., and colleagues at Lund (Sweden) University Hospital, identified 757 patients treated with etanercept (Enbrel) or infliximab (Remicade) from the register and 800 conservatively treated patients recruited from an outpatient clinic and private practices (Ann. Rheum. Dis. 2005;64:699–703).

Patients were followed from initiation of anti-TNF treatment (or July 1, 1997, for the comparison group) until death or Dec. 31, 2002.

In the anti-TNF group, there were 16 tumors (5 lymphomas) in 1,603 person-years at risk, compared with 69 tumors (2 lymphomas) in 3,948 person-years in the control group.

The standardized incidence ratios in the anti-TNF group and the control group were 1.1 and 1.4 for all tumors and 11.5 and 1.3 for lymphomas, respectively.

The increased overall tumor incidence in the control group was mainly due to smoking-related lesions, according to the investigators.

The total cancer risk excluding lymphomas was 0.79 among patients treated with anti-TNF agents and 1.39 in the comparison group.

The unadjusted hazard ratio for lymphoma was 4.9 in anti-TNF-treated patients relative to the conventionally treated patients. The hazard ratio was 5.0 after adjusting for differences in baseline Health Assessment Questionnaire scores, which were used as a marker of severity.

The results for overall tumor standardized incidence ratios in the anti-TNF-treated patients, compared with controls, must be interpreted with caution because of the limited number of observations and the relatively short follow-up period, the investigators wrote.

The withholding of anti-TNF treatment in patients with a known previous cancer also may have contributed to the lower incidence of cancer in this group.

In an accompanying editorial, Jarrod Franklin and colleagues at Manchester (England) University noted the study failed to detect a raised incidence of lymphoma in the control group, despite detecting an increased risk of all-site cancers in this population.

This is surprising, they said; given that the results of several studies would suggest such patients would be at an increased risk of lymphoma.

They welcomed the investigation but agreed it is difficult to reach a “robust conclusion” on the question of anti-TNF-α agents, disease severity, and lymphoma risk.

“With increasing recruitment and follow-up of such cohorts, a more definitive answer should be available in the not too distant future,” they wrote.

Eric Ruderman, M.D., a rheumatologist with Northwestern University, Chicago, concurred. “It's important information, but the issue you have to take into consideration is that their denominators were fairly small to look at such a rare event,” he said in an interview. “One or two patients one way or the other may have made a significant difference.”

Tumor necrosis factor agents do not increase the overall risk of cancer in patients with rheumatoid arthritis but may be associated with an increased risk of lymphomas, an analysis of data from the South Swedish Arthritis Treatment Group register suggests.

The study is the first to question whether use of anti-TNF-α agents increases the risk of lymphoma independently of disease severity.

Pierre Geborek, M.D., and colleagues at Lund (Sweden) University Hospital, identified 757 patients treated with etanercept (Enbrel) or infliximab (Remicade) from the register and 800 conservatively treated patients recruited from an outpatient clinic and private practices (Ann. Rheum. Dis. 2005;64:699–703).

Patients were followed from initiation of anti-TNF treatment (or July 1, 1997, for the comparison group) until death or Dec. 31, 2002.

In the anti-TNF group, there were 16 tumors (5 lymphomas) in 1,603 person-years at risk, compared with 69 tumors (2 lymphomas) in 3,948 person-years in the control group.

The standardized incidence ratios in the anti-TNF group and the control group were 1.1 and 1.4 for all tumors and 11.5 and 1.3 for lymphomas, respectively.

The increased overall tumor incidence in the control group was mainly due to smoking-related lesions, according to the investigators.

The total cancer risk excluding lymphomas was 0.79 among patients treated with anti-TNF agents and 1.39 in the comparison group.

The unadjusted hazard ratio for lymphoma was 4.9 in anti-TNF-treated patients relative to the conventionally treated patients. The hazard ratio was 5.0 after adjusting for differences in baseline Health Assessment Questionnaire scores, which were used as a marker of severity.

The results for overall tumor standardized incidence ratios in the anti-TNF-treated patients, compared with controls, must be interpreted with caution because of the limited number of observations and the relatively short follow-up period, the investigators wrote.

The withholding of anti-TNF treatment in patients with a known previous cancer also may have contributed to the lower incidence of cancer in this group.

In an accompanying editorial, Jarrod Franklin and colleagues at Manchester (England) University noted the study failed to detect a raised incidence of lymphoma in the control group, despite detecting an increased risk of all-site cancers in this population.

This is surprising, they said; given that the results of several studies would suggest such patients would be at an increased risk of lymphoma.

They welcomed the investigation but agreed it is difficult to reach a “robust conclusion” on the question of anti-TNF-α agents, disease severity, and lymphoma risk.

“With increasing recruitment and follow-up of such cohorts, a more definitive answer should be available in the not too distant future,” they wrote.

Eric Ruderman, M.D., a rheumatologist with Northwestern University, Chicago, concurred. “It's important information, but the issue you have to take into consideration is that their denominators were fairly small to look at such a rare event,” he said in an interview. “One or two patients one way or the other may have made a significant difference.”

Tumor necrosis factor agents do not increase the overall risk of cancer in patients with rheumatoid arthritis but may be associated with an increased risk of lymphomas, an analysis of data from the South Swedish Arthritis Treatment Group register suggests.

The study is the first to question whether use of anti-TNF-α agents increases the risk of lymphoma independently of disease severity.

Pierre Geborek, M.D., and colleagues at Lund (Sweden) University Hospital, identified 757 patients treated with etanercept (Enbrel) or infliximab (Remicade) from the register and 800 conservatively treated patients recruited from an outpatient clinic and private practices (Ann. Rheum. Dis. 2005;64:699–703).

Patients were followed from initiation of anti-TNF treatment (or July 1, 1997, for the comparison group) until death or Dec. 31, 2002.

In the anti-TNF group, there were 16 tumors (5 lymphomas) in 1,603 person-years at risk, compared with 69 tumors (2 lymphomas) in 3,948 person-years in the control group.

The standardized incidence ratios in the anti-TNF group and the control group were 1.1 and 1.4 for all tumors and 11.5 and 1.3 for lymphomas, respectively.

The increased overall tumor incidence in the control group was mainly due to smoking-related lesions, according to the investigators.

The total cancer risk excluding lymphomas was 0.79 among patients treated with anti-TNF agents and 1.39 in the comparison group.

The unadjusted hazard ratio for lymphoma was 4.9 in anti-TNF-treated patients relative to the conventionally treated patients. The hazard ratio was 5.0 after adjusting for differences in baseline Health Assessment Questionnaire scores, which were used as a marker of severity.

The results for overall tumor standardized incidence ratios in the anti-TNF-treated patients, compared with controls, must be interpreted with caution because of the limited number of observations and the relatively short follow-up period, the investigators wrote.

The withholding of anti-TNF treatment in patients with a known previous cancer also may have contributed to the lower incidence of cancer in this group.

In an accompanying editorial, Jarrod Franklin and colleagues at Manchester (England) University noted the study failed to detect a raised incidence of lymphoma in the control group, despite detecting an increased risk of all-site cancers in this population.

This is surprising, they said; given that the results of several studies would suggest such patients would be at an increased risk of lymphoma.

They welcomed the investigation but agreed it is difficult to reach a “robust conclusion” on the question of anti-TNF-α agents, disease severity, and lymphoma risk.

“With increasing recruitment and follow-up of such cohorts, a more definitive answer should be available in the not too distant future,” they wrote.

Eric Ruderman, M.D., a rheumatologist with Northwestern University, Chicago, concurred. “It's important information, but the issue you have to take into consideration is that their denominators were fairly small to look at such a rare event,” he said in an interview. “One or two patients one way or the other may have made a significant difference.”

Eli Lilly & Co. has halted a trial of Xigris in pediatric patients with severe sepsis, because the drug failed to show efficacy over placebo, according to a Food and Drug Administration MedWatch report.

An interim analysis showed that Xigris (drotrecogin alfa [activated]) was “highly unlikely to show an improvement over placebo in the primary end point of composite time to complete organ failure resolution over 14 days.”

The mean time to resolution was 9.7 days in the Xigris group and 9.8 days in the placebo group.

An independent data monitoring committee also noted an increase in the rate of central nervous system bleeding in the Xigris group, officials at Eli Lilly & Co., which manufactures the drug, said in a statement. Over the 6-day infusion period, there were four intracranial hemorrhages among 201 Xigris-treated patients, compared with one among 198 placebo-treated patients.

Three of the four hemorrhages in the Xigris group occurred in patients aged 60 days or less. Over the 28-day study period, there were eight intracranial hemorrhages in the Xigris group, compared with five in the placebo group.

Mortality, the rate of serious adverse events, overall serious bleeding events, and major amputations appeared to be similar in the two groups of patients.

Xigris, a genetically engineered version of human activated protein C, is indicated only for adults with severe sepsis who are at high risk of death.

In March 2005, Lilly added a warning to the prescribing information for Xigris that it may not be appropriate for patients with single-organ dysfunction and recent surgery and should be administered only after careful consideration of the potential risks and benefits.

The warning was added after two studies indicated a small but clinically important increase in the rate of all-cause mortality among these patients treated with the agent, compared with those who received placebo. In the pediatric study, known as F1K-MC-EVBP, the 28-day all-cause mortality was 34 (17%) in the Xigris group vs. 36 (18%) in the placebo group. Data collection is ongoing in the pediatric study, and complete results are expected to be available in the latter part of 2005.

Eli Lilly & Co. has halted a trial of Xigris in pediatric patients with severe sepsis, because the drug failed to show efficacy over placebo, according to a Food and Drug Administration MedWatch report.

An interim analysis showed that Xigris (drotrecogin alfa [activated]) was “highly unlikely to show an improvement over placebo in the primary end point of composite time to complete organ failure resolution over 14 days.”

The mean time to resolution was 9.7 days in the Xigris group and 9.8 days in the placebo group.

An independent data monitoring committee also noted an increase in the rate of central nervous system bleeding in the Xigris group, officials at Eli Lilly & Co., which manufactures the drug, said in a statement. Over the 6-day infusion period, there were four intracranial hemorrhages among 201 Xigris-treated patients, compared with one among 198 placebo-treated patients.

Three of the four hemorrhages in the Xigris group occurred in patients aged 60 days or less. Over the 28-day study period, there were eight intracranial hemorrhages in the Xigris group, compared with five in the placebo group.

Mortality, the rate of serious adverse events, overall serious bleeding events, and major amputations appeared to be similar in the two groups of patients.

Xigris, a genetically engineered version of human activated protein C, is indicated only for adults with severe sepsis who are at high risk of death.

In March 2005, Lilly added a warning to the prescribing information for Xigris that it may not be appropriate for patients with single-organ dysfunction and recent surgery and should be administered only after careful consideration of the potential risks and benefits.

The warning was added after two studies indicated a small but clinically important increase in the rate of all-cause mortality among these patients treated with the agent, compared with those who received placebo. In the pediatric study, known as F1K-MC-EVBP, the 28-day all-cause mortality was 34 (17%) in the Xigris group vs. 36 (18%) in the placebo group. Data collection is ongoing in the pediatric study, and complete results are expected to be available in the latter part of 2005.

Eli Lilly & Co. has halted a trial of Xigris in pediatric patients with severe sepsis, because the drug failed to show efficacy over placebo, according to a Food and Drug Administration MedWatch report.

An interim analysis showed that Xigris (drotrecogin alfa [activated]) was “highly unlikely to show an improvement over placebo in the primary end point of composite time to complete organ failure resolution over 14 days.”

The mean time to resolution was 9.7 days in the Xigris group and 9.8 days in the placebo group.

An independent data monitoring committee also noted an increase in the rate of central nervous system bleeding in the Xigris group, officials at Eli Lilly & Co., which manufactures the drug, said in a statement. Over the 6-day infusion period, there were four intracranial hemorrhages among 201 Xigris-treated patients, compared with one among 198 placebo-treated patients.

Three of the four hemorrhages in the Xigris group occurred in patients aged 60 days or less. Over the 28-day study period, there were eight intracranial hemorrhages in the Xigris group, compared with five in the placebo group.

Mortality, the rate of serious adverse events, overall serious bleeding events, and major amputations appeared to be similar in the two groups of patients.

Xigris, a genetically engineered version of human activated protein C, is indicated only for adults with severe sepsis who are at high risk of death.

In March 2005, Lilly added a warning to the prescribing information for Xigris that it may not be appropriate for patients with single-organ dysfunction and recent surgery and should be administered only after careful consideration of the potential risks and benefits.

The warning was added after two studies indicated a small but clinically important increase in the rate of all-cause mortality among these patients treated with the agent, compared with those who received placebo. In the pediatric study, known as F1K-MC-EVBP, the 28-day all-cause mortality was 34 (17%) in the Xigris group vs. 36 (18%) in the placebo group. Data collection is ongoing in the pediatric study, and complete results are expected to be available in the latter part of 2005.